Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:The value of robotic surgery for gynecologic procedures has been critically evaluated over the past few years. Its drawbacks have been noted as larger port size, location of port placement, limited instrumentation, and cost. In this study, we describe a novel technique for robotic-assisted laparoscopic hysterectomy (RALH) with 3 important improvements: (1) more aesthetic triangular laparoscopic port configuration, (2) use of 5-mm robotic cannulas and instruments, and (3) improved access around the robotic arms for the bedside assistant with the use of pediatric-length laparoscopic instruments. METHODS:We reviewed a series of 44 women who underwent a novel RALH technique and concomitant procedures for benign hysterectomy between January 2008 and September 2011. RESULTS:The novel RALH technique and concomitant procedures were completed in all of the cases without conversion to larger ports, laparotomy, or video-assisted laparoscopy. Mean age was 49.9 years (SD 8.8, range 33-70), mean body mass index was 26.1 (SD 5.1, range 18.9-40.3), mean uterine weight was 168.2 g (SD 212.7, range 60-1405), mean estimated blood loss was 69.7 mL (SD 146.9, range 20-1000), and median length of stay was <1 day (SD 0.6, range 0-2.5). There were no major and 3 minor peri- and postoperative complications, including 2 urinary tract infections and 1 case of intravenous site thrombophlebitis. Mean follow-up time was 40.0 months (SD 13.6, range 15-59). CONCLUSION/CONCLUSIONS:Use of the triangular gynecology laparoscopic port placement and 5-mm robotic instruments for RALH is safe and feasible and does not impede the surgeon's ability to perform the procedures or affect patient outcomes.

Tumor-associated macrophages (TAMs) are derived from monocytes and recruited to the tumor microenvironment, where they play an important role in the progression of cancer. There is strong evidence for an inverse relationship between TAM density and clinical prognosis in solid tumors of the breast, prostate, ovary, and cervix. However, the role of TAMs in endometrial cancer is not well described. The objectives of this study were to determine whether macrophage distribution or density differed among normal endometrial tissue, hyperplasia, Type I, and II endometrial adenocarcinomas. In addition, we looked for a correlation among TAM density, known histopathologic prognostic indicators, and endometrial cancer progression. The pathologic specimens of women who underwent hysterectomy for benign disorders, endometrial hyperplasia, Type I, or Type II cancers were sectioned and stained with anti-CD68 antibody. The density of CD68 macrophages was quantified and stratified according to their epithelial or stromal location. Type I and II endometrial carcinomas had significantly higher macrophage density in both epithelial and stromal compartments than benign endometrium. In both benign and neoplastic specimens, the numbers of macrophages were significantly higher in the stroma compared with the epithelium. Although there were important trends in the density of TAMs with regard to several histopathologic prognostic indicators of endometrial cancer, none were statistically significant and the patients' cancer progression did not correlate significantly with the number of TAMs.

UNLABELLED:Catamenial migraine is a headache disorder occurring in reproductive-aged women relevant to menstrual cycles. Catamenial migraine is defined as attacks of migraine that occurs regularly in at least 2 of 3 consecutive menstrual cycles and occurs exclusively on day 1 to 2 of menstruation, but may range from 2 days before (defined as -2) to 3 days after (defined as +3 with the first day of menstruation as day +1). There are 2 subtypes: the pure menstrual migraine and menstrually related migraine. In pure menstrual migraine, there are no aura and no migraine occurring during any other time of the menstrual cycle. In contrast, menstrually related migraine also occurs in 2 of 3 consecutive menstrual cycles, mostly on days 1 and 2 of menstruation, but it may occur outside the menstrual cycle. Catamenial migraine significantly interferes with the quality of life and causes functional disability in most sufferers. The fluctuation of estrogen levels is believed to play a role in the pathogenesis of catamenial migraine. In this review, we discuss estrogen and its direct and indirect pathophysiologic roles in menstrual-related migraine headaches and the available treatment for women. TARGET AUDIENCE/BACKGROUND:Obstetricians and gynecologists, family physicians. LEARNING OBJECTIVES/OBJECTIVE:After completing this CME activity, physicians should be better able to discuss the pathophysiology of catamenial migraine, identify the risk factors for catamenial migraine among women, and list the prophylactic and abortive treatments for migraines.

Extranodal marginal zone B-cell lymphomas are uncommon. Most occur in the gastrointestinal tract. Marginal zone B-cell lymphomas of the female genital tract are rare, and few cases exist of marginal zone B-cell lymphomas of the uterus, cervix, and fallopian tubes. We report the first marginal zone B-cell lymphoma of the ovary, fallopian tube, and appendix arising in endometriosis.

Tubal factor infertility accounts for a large portion of female factor infertility. The most prevalent cause of tubal factor infertility is pelvic inflammatory disease and acute salpingitis. The diagnosis of tubal occlusion can be established by a combination of clinical suspicion based on patient history and diagnostic tests, such as hysterosalpingogram, sonohysterosalpingography, and laparoscopy with chromopertubation. Depending on several patient factors, tubal microsurgery or more commonly in vitro fertilization with its improving success rates are the recommended treatment options.

G protein-coupled estrogen receptor 1 (GPER), also named GPR30, has been previously identified in the female reproductive system. In this study, GPER expression was found in the female rat myometrium by reverse transcriptase-polymerase chain reaction and immunocytochemistry. Using GPER-selective ligands, we assessed the effects of the GPER activation on resting membrane potential and cytosolic Ca(2+) concentration ([Ca(2+)](i)) in rat myometrial cells, as well as on contractility of rat uterine strips. G-1, a specific GPER agonist, induced a concentration-dependent depolarization and increase in [Ca(2+)](i) in myometrial cells. The depolarization was abolished in Na(+)-free saline. G-1-induced [Ca(2+)](i) increase was markedly decreased by nifedipine, a L-type Ca(2+) channel blocker, by Ca(2+)-free or Na(+)-free saline. Intracellular administration of G-1 produced a faster and transitory increase in [Ca(2+)](i), with a higher amplitude than that induced by extracellular application, supporting an intracellular localization of the functional GPER in myometrial cells. Depletion of internal Ca(2+) stores with thapsigargin produced a robust store-activated Ca(2+) entry; the Ca(2+) response to G-1 was similar to the constitutive Ca(2+) entry and did not seem to involve store-operated Ca(2+) entry. In rat uterine strips, administration of G-1 increased the frequency and amplitude of contractions and the area under the contractility curve. The effects of G-1 on membrane potential, [Ca(2+)](i), and uterine contractility were prevented by pretreatment with G-15, a GPER antagonist, further supporting the involvement of GPER in these responses. Taken together, our results indicate that GPER is expressed and functional in rat myometrium. GPER activation produces depolarization, elevates [Ca(2+)](i) and increases contractility in myometrial cells.

Endometriosis is a gynecological disease characterized by implantation of endometrial tissue outside of the uterus. Early familial aggregation and twin studies noted a higher risk of endometriosis among relatives. Studies on the roles of the environment, genetics and aberrant regulation in the endometrium and endometriotic lesions of women with endometriosis suggest that endometriosis arises from the interplay between genetic variants and environmental factors. Elucidating the hereditary component has proven difficult because multiple genes seem to produce a susceptibility to developing endometriosis. Molecular techniques, including linkage and genome-wide analysis, have identified candidate genes located near known loci related to development and regulation of the female reproductive tract. As new candidate genes are discovered and hereditary pathways identified using technologies such as genome-wide analysis, the possibility of prevention and treatment becomes more tangible for millions of women affected by endometriosis. Here, we discuss the advances of genetic research in endometriosis and describe technologies that have contributed to the current understanding of the genetic variability in endometriosis, variability that includes regulatory polymorphisms in key genes.

Distribution of neuronal nitric oxide synthase-immunoreactive (nNOS-IR) nerve fibers and somata in the rat epididymis and major pelvic ganglia was studied by immunohistochemical methods. In the epididymis, the supply of nNOS-IR fibers was highest in the cauda and became progressively fewer toward the caput. In the cauda and corpus, nNOS-IR fibers were distributed throughout the subepithelial tissues and around the epithelial. The pattern of distribution of vasoactive intestinal polypeptide (VIP)- and tyrosine hydroxylase (TH)-immunoreactive fibers in the epididymis was similar but the latter was generally more numerous in a given region as compared to that of nNOS-IR fibers. A population of neurons in the major pelvic ganglia were nNOS-IR-, TH- or VIP-IR. Double-labeling studies revealed that few neurons in the major pelvic ganglia contained both nNOS-IR and TH-IR. Whereas nNOS-IR and VIP-IR appeared to co-localize in the same population of the pelvic ganglion cells. Similarly, nNOS-IR fibers in the epididymis were mostly VIP-positive and TH-negative. Unilateral injection of the fluorescent tracer Fluorogold into the junction between the vas deferens and the cauda labeled a population of neurons in the right and left major pelvic ganglia, some of which were also nNOS-IR. A small number of dorsal root ganglion cells contained Fluorogold and very few expressed NOS-IR. It may be concluded that nNOS-IR nerve fibers in the rat epididymis arise mainly from neurons in the major pelvic ganglia the major of which express VIP-IR but not TH-IR. The extensive supply of nNOS-immunoreactive fibers around the epithelium and throughout the subepithelial tissues suggests that NO may be closely associated with smooth muscle contraction.

Immunoreactivity to pituitary adenylate cyclase activating polypeptide-38 was detected in numerous nerve fibres in layers I and II of the dorsal horn of the rat and some of these fibres extended into the deeper layers of all segments of the spinal cord. Immunoreactivity was also detected in the lateral funiculus projecting into the intermediolateral cell column of the lower cervical and thoracic segments and in the lateral pathway terminating in the intermediate gray area of the lower lumbar and sacral segments. Neurons in the lateral horn area were not immunoreactive nor were the ventral horn motoneurons. In the medulla, numerous immunoreactive fibres were observed in the spinal trigeminal tract and superficial layers of the caudal spinal trigeminal nucleus but few in the interpolar spinal trigeminal nucleus. A prominent immunoreactive nerve bundle emanated from the caudal spinal trigeminal nucleus and projected into the solitary tract. A dense network of immunoreactive neurons and fibres was present in the nucleus raphe obscurus, lateral reticular nucleus and parvocellular lateral reticular nucleus. Immunoreactive fibres could also be detected in the solitary tract and area postrema. Labelled somata were occasionally noted in various subnuclei of the nucleus of the solitary tract and nucleus raphe pallidus. In addition, a small number of positive neurons were detected in an area between the lateral reticular nucleus and inferior olive and near the ventral surface of the medulla (parapyramidal region). A few weakly-labelled cells were occasionally seen in the dorsal motor nucleus of vagus. A population of neurons in the trigeminal, nodose and dorsal root ganglia from all segments of the spinal cord displayed low to intense immunoreactivity. The presence of immunoreactivity in nodose and dorsal root ganglia, dorsal horn, spinal autonomic nuclei, solitary tract and in certain areas of the medulla suggests that this peptide may participate in a variety of sensory and autonomic functions.