Keisha Leanne Bentley-Edwards, PhD

• Assistant Professor in Medicine
• Affiliate, Duke Global Health Institute
• Member of the Duke Cancer Institute

https://medicine.duke.edu/faculty/keisha-leanne-bentley-edwards-phd

This is particularly true or the younger patient wishing to preserve ertility and having the contralateral ovary le t in situ menstrual android 100 mg lady era sale. Grossly menopause urban dictionary purchase lady era american express, adult granulosa cell tumors are large and multicystic and o ten exceed 10 to 15 cm in diameter menopause urinary problems lady era 100 mg buy otc. For this reason menopause 52 years old buy discount lady era 100 mg online, more extensive dissection is typically required than or epithelial ovarian cancers or malignant germ cell tumors pregnancy vs period purchase cheap lady era line. During excision, inadvertent rupture and intraoperative bleeding rom the tumor itsel is also common. Alternatively, it can be cystic, with numerous locules lled with serosanguinous or gelatinous uid (Colombo, 2007). Microscopic examination shows predominately granulosa cells with pale, grooved, "cof ee bean" nuclei. The characteristic microscopic eature is the Call-Exner body-a rosette arrangement o cells around an eosinophilic uid space. Adult granulosa cell tumors are low-grade malignancies that typically demonstrate indolent growth. Ninety- ve percent are unilateral, and 70 to 90 percent are stage I at diagnosis (Table 36-6). The 5-year survival or patients with stage I disease is 90 to 95 percent (Colombo, 2007; Zhang, 2007). Attempts to grade these tumors using nuclear characteristics or mitotic activity counts have produced inconsistent results (Chen, 2003). They are typically unilateral and remain localized, retain hormone-secreting unctions, and in requently relapse. Recurrences tend to be late and usually develop in the abdomen or pelvis (Abu-Rustum, 2006). These tumors are ormed by cells believed to arise rom those surrounding the germinal cells within ovarian ollicles. There are two clinically and histologically distinct types: the adult orm, which makes up 95 percent o cases, and the juvenile type, accounting or 5 percent. With adult granulosa cell tumor, most women are diagnosed a ter age 30, and the average age approximates 55 years. Heavy, irregular menstrual bleeding and postmenopausal bleeding are common and re ect prolonged exposure o the endometrium to estrogen. Their elongated nuclei may have a longitudinal fold or groove that gives them a "coffee bean" appearance. Call-Exner bodies are rare, but o ten there is a theca cell component (Young, 1984). Similar to adult-type tumors, 95 percent o juvenile granulosa cell tumors are unilateral and stage I at diagnosis (Young, 1984). However, the juvenile type is more aggressive in advanced stages, and the time to relapse and death is much shorter. T ecomas are unique because they typically develop in postmenopausal women in their mid-60s and develop in requently be ore age 30. As a result, the primary signs and symptoms are abnormal vaginal bleeding or pelvic mass or both. Many women also present with concurrent endometrial hyperplasia or adenocarcinoma (Aboud, 1997). These tumors are composed o lipid-laden stromal cells that are occasionally luteinized. Hal o these luteinized thecomas are either hormonally inactive or androgenic with the potential or inducing masculinization. T ecomas are solid tumors whose cells resemble the theca cells that normally surround the ovarian ollicles (Chen, 2003). Because o this texture, these tumors appear sonographically as solid adnexal masses and may mimic extrauterine leiomyomas. Fortunately, ovarian thecomas are clinically benign, and surgical resection is curative. These solid, generally benign ovarian neoplasms arise rom the spindled stromal cells that orm collagen. They are round, oval, or lobulated solid tumors associated with ree uid or less commonly, with rank ascites and possess minimal to moderate vascularization (Paladini, 2009). Perhaps 1 percent o women present with Meigs syndrome, which is a triad o pleural ef usion, ascites, and a solid ovarian mass (Siddiqui, 1995). Pleural ef usions are usually rightsided, and these, as well as accompanying ascites, are typically transudative and resolve a ter tumor resection (Majzlin, 1964). Despite this association o ascites with benign bromas, when ascites and a pelvic mass coexist, evaluation is based on an assumption o malignancy. However, 10 percent will demonstrate increased cellularity and varying degrees o pleomorphism and mitotic activity that indicate a tumor better characterized as having low malignant potential. The average patient age is approximately 20 years, and 80 percent develop be ore Sources for survival figures are referenced within the text. The median time to recurrence is 5 to 6 years, but may be several decades (Abu-Rustum, 2006; East, 2005). Advantageously, these indolent tumors usually progress slowly therea ter, and the median length o survival a ter relapse is another 6 years. Advanced tumor stage and residual disease are poor prognostic actors (Al Badawi, 2002; Sehouli, 2004). Cellular atypia and mitotic count may help in determining the prognosis but are di cult to reproducibly quanti y (Miller, 2001). These rare neoplasms develop primarily in children and young adults, and approximately 90 percent are diagnosed be ore puberty (Colombo, 2007). The mean age at diagnosis is 13 years, but patient ages range rom newborn to 67 years (Young, 1984). Juvenile granulosa cell tumors are sometimes associated with Ollier disease or with Maf ucci syndrome, which is characterized by endochondromas and hemangiomas (Young, 1984; Yuan, 2004). In af ected emales, estrogen, progesterone, and testosterone levels may be elevated and lead to suppression o gonadotropins. Prepubertal girls typically display isosexual precocious puberty, which is characterized by breast enlargement and development o pubic hair, vaginal secretions, and other secondary sexual characteristics. These tumors in requently secrete androgens, but in such cases may induce virilization. Despite these endocrinologic signs, a delayed diagnosis o juvenile granulosa cell tumors in pre- and postpubertal girls is common and associated with a higher risk o peritoneal tumor spread (Kal a, 2005). For example, older patients usually seek medical attention or abdominal pain or swelling. Preoperative rupture with resulting hemoperitoneum may create acute abdominal symptoms in 5 to 10 percent o cases (Colombo, 2007). Juvenile granulosa cell tumors are grossly similar to the adult-type tumor and display variable solid and cystic components. They can attain signi cant size and have an average diameter o approximately 12 cm. Menstrual irregularities and pelvic pain are both requent symptoms (Marelli, 1998). Ascites is seldom encountered (unlike bromas), and sclerosing stromal tumors are hormonally inactive (unlike thecomas). Histologically, the presence o pseudolobulation o cellular areas separated by edematous connective tissue, increased vascularity, and prominent areas o sclerosis are distinguishing eatures. One quarter o patients present with estrogenic or androgenic mani estations, but most tumors are clinically non unctional. Sertoli cell tumors are typically unilateral, solid, and yellow and measure 4 to 12 cm in diameter. Derived rom the cell type that gives rise to the semini erous tubules, these tumor cells o ten organize into histologically characteristic tubules (Young, 2005). Sertoli cell tumors, however, may also mimic many di erent tumors, and immunostaining in these cases is invaluable to con rm the diagnosis. T eir incidence mirrors that o Sertoli cell tumors, and the average age is 25 years. Although Sertoli-Leydig cell tumors have been identi ed in children and postmenopausal emales, more than 90 percent develop during the reproductive years. As a result, rank virilization develops in one third o af ected women, and another 10 percent have clinical mani estations o androgen excess (Young, 1985). Accordingly, SertoliLeydig cell tumors are suspected preoperatively in a patient with a unilaterally palpable adnexal mass and with androgenic maniestations. For these women, an elevated serum testosteroneto-androstenedione ratio urther suggests the diagnosis. Although these hormonal ef ects requently develop, one hal o patients will have nonspeci c abdominal mass symptoms as their only presenting complaint. T yroid abnormalities also coexist with Sertoli-Leydig cell tumors at a requency that exceeds mere chance. These tumors tend to be large at the time o excision with an average diameter greater than 10 cm, but ranges rom 1 to 50 cm have been reported. This opened surgical specimen has a predominantly solid cut surface with focal cysts, variegated yellow-brown color, and foci of hemorrhage. The ve subtypes o dif erentiation (well, intermediate, poor, reti orm, and heterologous) have considerable overlap. Prognosis depends predominantly on the stage and degree o tumor dif erentiation in these malignant variants. For example, Young and Scully (1985) per ormed a clinicopathologic analysis o 207 cases and identi ed stage I disease in 97 percent. The 5-year survival rate or patients with stage I disease exceeds 90 percent (Zaloudek, 1984). Malignant eatures were observed in approximately 10 percent o tumors with intermediate dif erentiation and in 60 percent o poorly dif erentiated tumors. Reti orm and heterologous elements are seen only in intermediate or poorly dif erentiated Sertoli-Leydig cell tumors and typically are associated with poorer prognosis. These ill-de ned tumors are especially common during pregnancy due to alterations in their usual clinical and pathologic eatures (Young, 2005). The prognosis is similar to that o granulosa cell tumors and Sertoli-Leydig cell tumors o similar degrees o dif erentiation. Patients present at a mean age o 30 years and typically have menstrual irregularities or evidence o hormonal excess. The tumors are characterized by intermingled granulosa cells and tubules o Sertoli cells. Gynandroblastomas have low malignant potential, and only one death has been reported (Martin-Jimenez, 1994). These tumors are typically small, multi ocal, calci ed, bilateral, and diagnosed incidentally. These masses are usually larger, unilateral, and symptomatic and carry a clinical malignancy rate o 15 to 20 percent (Young, 1982). T us, operative goals are to establish a de nitive tissue diagnosis, determine the extent o disease, and also remove all grossly visible tumors in those in requent patients with advanced-stage disease. Endometrial sampling is per ormed, especially i ertility-sparing surgery is planned in women with granulosa cell tumors or thecomas. This is because many o these patients will have coexisting endometrial hyperplasia or adenocarcinoma that may af ect the decision or hysterectomy. When the diagnosis is not made until the nal pathology report is con rmed postoperatively, laparoscopic staging may be proposed to determine whether metastatic disease is present. T at said, only approximately 20 percent o cases have complete staging (Abu-Rustum, 2006; Brown, 2009). The average age at diagnosis is the mid-20s, but patients can present at virtually any age. These tumors are composed entirely or predominantly o cells that resemble steroid hormone-secreting cells and are categorized according to the histologic composition o these cells. Stromal luteomas are clinically benign tumors that by de nition lie completely within the ovarian stroma. Estrogenic ef ects are common, but occasional individuals have androgenic mani estations. Leydig cell tumors are also benign and typically are seen in postmenopausal women. They are distinguished microscopically by rectangular, crystal-like cytoplasmic inclusions, termed crystals o Reinke. Leydig cells secrete testosterone, and these tumors are usually associated with androgenic ef ects. Some o these cases may represent large stromal luteomas that have grown to reach the ovarian sur ace or Leydig-cell tumors in which Reinke crystals cannot be identi ed. There is some evidence immediate drop in elevated preoperative sex-steroid hormone indicating a prolonged survival in at least some women with levels. Physical mani estations o these elevated levels, however, newly diagnosed disease who received whole-abdominal radiopartially or completely resolve more gradually. Surveillance includes a general physical and pelvic examination, serum marker level testing, and imaging as clinically indicated. Women with one or more o these suspicious eatures are thought to be at higher risk o relapse and are considered or platinum-based chemotherapy (Schneider, 2003b). Ovarian Germ Cell and Sex Cord-Stromal Tumors primary postoperative treatment because it is generally better tolerated, more widely accessible, and easier to administer. In a Cali ornia population-based study o more than 4 million obstetric patients, one granulosa cell tumor was diagnosed among 202 women with an ovarian malignancy (Leiserowitz, 2006). Granulosa cell tumors are most common, but only 10 percent are diagnosed during pregnancy (Hasiakos, 2006).

There ore menstrual discomfort lady era 100 mg overnight delivery, genetic abnormalities may adversely a ect this process women's health lose weight buy cheap lady era 100 mg line, as discussed later women's health group lafayette co cheap lady era. Several studies have demonstrated that pregnancy rates decline and time to conception lengthens as male age increases women's health center norman ok buy discount lady era online. Studies o semen parameters across age suggest that sperm concentration is maintained womens health 3 week diet purchase lady era without a prescription, however, sperm motility and morphology progressively worsen (Levitas, 2007). In short, although advancing male age may lower ertility, it is probably insigni cant compared with aging changes in women. For this test, the male is asked to re rain rom ejaculation or 2 to 3 days, and a specimen is collected by masturbation into a sterile cup. I masturbation is not an option, then a couple can use specially designed Silastic condoms without lubricants. Importantly, the sample should arrive in the laboratory within an hour o ejaculation to allow or optimal analysis. The sample undergoes lique action, or thinning o the seminal uid, due to enzymes rom the liquid contribution o the prostate gland. This process takes 5 to 20 minutes and allows more accurate evaluation o the sperm contained in the seminal uid. Semen Analysis Results the re erence values or the semen analysis are shown in Table 19-8. Second, semen analysis results, particularly morphologic interpretation, di er between laboratories. Note that the concept o "re erence" range is more appropriate than "normal" range. Although total motile sperm count correlates with ertility, not all males with "normal" semen parameters display normal ertility (Guzick, 2001). Evaluation of the Infertile Couple patients with semen analysis results outside the re erence range may achieve pregnancy. The lack o absolute predictive value or this test is likely due to the act that it does not provide in ormation regarding sperm unction, that is, the ultimate ability to ertilize an oocyte. Most semen analysis reports will indicate semen volume, pH, and presence or absence o ructose. Seminal uid is alkaline and is thought to protect sperm rom acidity in prostatic secretions and in the vagina. An acidic pH or lack o ructose is consistent with obstruction o the e erent ductal system (Daudin, 2000). O parameters, low semen volume o ten simply re ects incomplete specimen collection or short abstinence interval. However, it may indicate partial vas de erens obstruction or retrograde ejaculation. Partial or complete vas de erens obstruction may be caused by in ection, tumor, prior testicular or inguinal surgery, or trauma. Retrograde ejaculation ollows ailed closure o the bladder neck during ejaculation and allows seminal uid to ow backward into the bladder. Retrograde ejaculation is suspected in men with diabetes mellitus, spinal cord damage, or prior prostate or other retroperitoneal surgery that may have damaged nerves (Hershlag, 1991). A postejaculatory urinalysis can detect sperm in the bladder and con rm the diagnosis. I urine is properly alkalinized, these sperm are viable and can be retrieved to achieve pregnancy. Sperm counts may be normal, or males may have low sperm counts (oligospermia), or no sperm (azoospermia) (Sharlip, 2002). Oligospermia is de ned as a concentration less than 15 million sperm per milliliter, and counts below 5 million per milliliter are considered severe. Azoospermia may result rom out ow tract obstruction, termed obstructive azoospermia, such as that which occurs with congenital absence o the vas de erens, severe in ection, or vasectomy. Alternatively, this latter group may have viable sperm obtainable through either epididymal aspiration or testicular biopsy. As described later, endocrine and genetic evaluation is indicated or men with abnormal sperm counts. Sperm movement is also assessed, and decreased sperm motility is termed asthenospermia. Some laboratories will distinguish between rapid (grade 3 to 4), slow (grade 2), and nonprogressive (grade 0 to 1) movement. Total progressive motility is the percentage o sperm exhibiting orward movement (grades 2 to 4). Asthenospermia has been attributed to prolonged abstinence, antisperm antibodies, genital tract in ections, or varicocele. T us, when mixed with a hypoosmotic solution, living, nonmotile sperm with normal membrane unction swell and coil as uid is absorbed (Casper, 1996). Once identi ed, these viable sperm may be used or intracytoplasmic sperm injection. T eir criteria require care ul analysis o the shape and size o the sperm head, the relative size o the acrosome in proportion to the head, and characteristics o the tail, including length, coiling, or presence o two tails. Signi cantly decreased ertilization rates are seen when normal morphology o the sample alls below 4 percent. In this scenario, many andrologists consider empiric antibiotic treatment prior to obtaining a repeat semen analysis. A common protocol would include doxycycline at a dosage o 100 mg orally twice daily or 2 weeks. Alternative approaches include culture o any expressible discharge or o the semen sample. Unless a general obstetrician-gynecologist has developed a particular interest and expertise in the area o in ertility, persistent abnormal semen analysis ndings are an indication or re erral to an in ertility specialist. Although the partner may be re erred directly to a urologist, it may be more reasonable to re er the couple to a reproductive endocrinologist, as the emale will also require evaluation. In response to this observation, dietary supplementation with the antioxidants vitamin C and vitamin E has been proposed. These tests are currently hampered by a lack o consensus regarding appropriate threshold values and by con icting data regarding their ability to predict success ul pregnancy. As a result, currently evidence is insuf cient to recommend the routine use o these tests in in ertile couples. In act, replacement will decrease gonadotropin stimulation o remaining testicular unction through negative eedback at the hypothalamus and pituitary. Unless the couple has chosen to use donor sperm, androgen supplementation is de erred during ertility treatment. However, replacement will provide other bene ts, such as improved libido and sexual unction, maintenance o muscle mass and bone density, and a general sense o well-being. Additional hormonal testing may be included as part o an evaluation o the in ertile male. Elevated serum prolactin levels and thyroid dys unction a ect spermatogenesis and are the most likely endocrinopathies to be detected (Sharlip, 2002; Sigman, 1997). However, controversy exists regarding the negative ertility e ects o antisperm antibodies ound in semen. These antibodies may be particularly prevalent ollowing vasectomy, testicular torsion, testicular biopsy, or other clinical situations in which the blood-testis barrier is breached (urek, 1994). Moreover, signi cant side e ects, including aseptic necrosis o the hip, have been reported in treated patients. Current data suggest that antisperm antibody assay does not need to be a routine component o in ertility evaluation. These include the mannose uorescence assay, hemizona assay, sperm penetration assay, and acrosome reaction test. The predictive signi cance o these assays is questionable, as they are based on highly nonphysiologic conditions and results vary widely rom in ertility center to in ertility center. Genetic Testing of the Male Genetic abnormalities are a relatively common cause o abnormal semen characteristics (American Society or Reproductive Medicine, 2008a). Approximately 15 percent o azoospermic men and 5 percent o severely oligospermic men will have an abnormal karyotype. Although genetic abnormalities cannot be corrected, they may have implications or the health o the patient or their o spring. The lower limit in sperm concentration or such testing varies between practitioners but lies between 3 and 10 million sperm per milliliter. Kline elter syndrome is observed in approximately 1 in 500 men in the general population and accounts or 1 to 2 percent o male in ertility cases. Classically, these men are tall, undervirilized, and have gynecomastia and small, rm testes (De Braekeleer, 1991). As the phenotype varies widely, lack o these characteristics does not preclude chromosomal evaluation. Conversely, a clinician may strongly consider obtaining karyotype testing in any male with these characteristics. Autosomal abnormalities will also be ound in a subset o men with severe oligospermia. A patient with severely decreased sperm counts and a normal karyotype is o ered testing or microdeletion o the Y chromosome. In overview, abnormalities may be due to central de ects in hypothalamic-pituitary unction or due to de ects within the testes. Most urologists will de er testing unless a sperm concentration is below 10 million/mL. Although such treatment is requently success ul, at least 6 months may be required or detection o sperm production. In this patient group, it is important to determine, based on testosterone levels, whether testosterone replacement is indicated. Normal spermatogenesis requires high levels o intratesticular testosterone, which cannot be achieved with Evaluation of the Infertile Couple (Oates, 1994; Ratbi, 2007). Care ul genetic counseling and testing o the emale partner or carrier status is critical in these situations. Details will vary between practitioners and will be a ected by patient presentation. These couples are reminded that there is a relatively high incidence o couples having two abnormalities, one o which would be missed by this approach. These patients may be treated, but are strongly encouraged to complete the evaluation i they do not conceive within a ew months. Int J Fertil Womens Med 49:123, 2004 American Academy o Pediatrics and the American College o Obstetricians and Gynecologists: Guidelines or Perinatal Care, 7th Edition, Washington, 2012 American College o Obstetricians and Gynecologists: Carrier screening or ragile X syndrome. Fertil Steril 98(2):302, 2012a American Society or Reproductive Medicine: Diagnostic evaluation o the in ertile male: a committee opinion. Fertil Steril 98(2):294, 2012b American Society or Reproductive Medicine: E ectiveness and treatment or unexplained in ertility. Fertil Steril 86(5) Suppl 1:S111, 2006 American Society or Reproductive Medicine: Endometriosis and in ertility: a committee opinion. Fertil Steril 98(3):591, 2012c American Society or Reproductive Medicine: Evaluation o the azoospermic male. Fertil Steril 90 (Suppl 3):S74, 2008a American Society or Reproductive Medicine: Female age-related ertility decline. Fertil Steril 101(3):633, 2014a American Society or Reproductive Medicine: Myomas and reproductive unction. Fertil Steril 90(Suppl 3):S125, 2008b American Society or Reproductive Medicine: Obesity and reproduction: an educational bulletin. Fertil Steril 90 (Suppl 3):S21, 2008c American Society or Reproductive Medicine: Optimizing natural ertility: a committee opinion. Fertil Steril 100(3):631, 2013a American Society or Reproductive Medicine: Pathogenesis, consequences, and control o peritoneal adhesions in gynecologic surgery: a committee opinion. Fertil Steril 99(6):1550, 2013b American Society or Reproductive Medicine: Report on varicocele and in ertility: a committee opinion. Fertil Steril 102(6):1556, 2014b American Society or Reproductive Medicine: Smoking and in ertility: a committee opinion. Fertil Steril 98(6):1400, 2012d American Society or Reproductive Medicine: esting and interpreting measures o ovarian reserve: a committee opinion. Fertil Steril 98(6):1407, 2012e American Society or Reproductive Medicine: the clinical relevance o luteal phase de ciency: a committee opinion. Fertil Steril 99(3):673, 2013c American Society or Reproductive Medicine: Vaccination guidelines or emale in ertility patients: a committee opinion. Fertil Steril 99(2):337, 2013d Anderson J, Williamson R: Fertility a ter torsion o the spermatic cord. Br J Urol 65:225, 1990 Anguiano A, Oates R, Amos J, et al: Congenital bilateral absence o the vas de erens. Hum Reprod 13:1532, 1998 Baazeem A, Belzile E, Ciampi A, et al: Varicocele and male actor in ertility treatment: a new meta-analysis and review o the role o varicocele repair. Eur Urol 60(4):796, 2011 Balasch J, Fabregues F, Creus M, et al: the use ulness o endometrial biopsy or luteal phase evaluation in in ertility. Hum Reprod 7:973, 1992 Bates G, Garza D, Garza M: Clinical mani estations o hormonal changes in the menstrual cycle. Obstet Gynecol Clin North Am 17:299, 1990 Beard C, Benson R Jr, Kelalis P, et al: the incidence and outcome o mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc 52:3, 1977 S Ben-Arie A, Goldchmit C, Laviv Y, et al: the malignant potential o endometrial polyps. Louis, Mosby, 1997 Bracken M, Eskenazi B, Sachse K, et al: Association o cocaine use with sperm concentration, motility, and morphology. Fertil Steril 53:315, 1990 Buyalos R, Daneshmand S, Brzech a P: Basal estradiol and ollicle-stimulating hormone predict ecundity in women o advanced reproductive age undergoing ovulation induction therapy. Fertil Steril 68:272, 1997 Carson D, Lagow E, T athiah A, et al: Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening.

Symptoms develop within 6 hours o trans usion and may include extreme respiratory distress pregnancy books cheap 100 mg lady era free shipping, rothy sputum breast cancer tattoos designs generic lady era 100 mg with amex, hypotension menopause insomnia treatment purchase lady era from india, ever menstruation uterine events order lady era overnight delivery, and tachycardia pregnancy 8 weeks 2 days lady era 100 mg with mastercard. Noncardiogenic pulmonary edema with di use bilateral pulmonary in ltrates on chest radiography is characteristic (oy, 2005). Platelets may be acquired rom a single individual during plateletpheresis and are termed single-donor platelets. Alternatively, platelets may be derived rom random units o whole blood and are re erred to as random-donor platelets. Fewer platelets are harvested rom a unit o whole blood compared with the amount removed during donor plateletpheresis. Speci cally, a single-donor platelet dose contains at least 3 × 1011 platelets in 250 to 300 mL o plasma, and this approximates the dose rom six random-donor platelet concentrates. Each concentrate trans used should raise the platelet count by 5 to 10 × 109/L, and the usual therapeutic dose is one platelet concentrate per 10 kg o body weight. Surgical patients with bleeding usually require platelet trans usion i the platelet count is less than 50 × 109/L and rarely require therapy i it is greater than 100 × 109/L (American Society o Anesthesiologists, 2015). One unit contains all coagulation actors, including 2 to 5 mg/mL o brinogen in 250 mL o volume. Fresh- rozen plasma is used commonly as rst-line hemostatic therapy in massive hemorrhage because it replaces multiple coagulation actors. Cryoprecipitate was developed and used originally or treatment o hemophilia A and von Willebrand disease. However, speci c actor concentrates are now available or these disorders, and thus, the clinical indications or cryoprecipitate are limited. Fresh- rozen plasma provides all coagulation actors and is avored in severe hemorrhage over cryoprecipitate. However, cryoprecipitate is an excellent source o brinogen and may be indicated i brinogen levels persist below 1. The dose o cryoprecipitate is usually 2 mL/kg o body weight, and each unit contains approximately 15 mL volume. The lower gastrointestinal and urinary tracts are closely related to the emale reproductive organs, and disease processes, anatomic distortion, and adverse operating conditions can increase their injury risk. Iatrogenic damage to the lower urinary tract is common, and up to 75 percent o ureter or bladder injuries sustained during gynecologic surgery occur during hysterectomy (Walters, 2007). Most injuries have no antecedent risk actors, but highrisk elements are ideally sought preoperatively. These include compromised visibility rom large pelvic masses, hemorrhage, pregnancy, obesity, inadequate incision, suboptimal retraction, and poor lighting. Additionally, scarring or anatomic distortion rom cervical and broad ligament leiomyomas, malignancy, endometriosis, pelvic organ prolapse, and prior pelvic in ection, surgery, or radiation are risks (Brandes, 2004; Francis, 2002). Patients who sustain surgical injury to the bladder or ureter su er signi cantly greater morbidity. In one case-control study, women with injury to the lower urinary tract during abdominal hysterectomy had signi cantly greater operative time, estimated blood loss, blood trans usion rates, ebrile morbidity, and postoperative stay length than their respective controls (Carley, 2002). In sum, depending on the procedure, the bladder may be at greater risk during: (1) initial abdominal entry when incising the anterior parietal peritoneum, (2) dissection within the space o Retzius, (3) vaginal epithelium dissection during anterior colporrhaphy, or (4) hysterectomy when dissecting in the vesicocervical space, entering the anterior vagina, or suturing the vaginal cu. With hysterectomy, bladder injury traditionally has been associated more o ten with the vaginal hysterectomy, but some data suggest that laparoscopic procedures pose the greatest risk (Francis, 2002; Frankman, 2010; Harris, 1997). During laparoscopy, the Foley bag may also distend with gas rom the pneumoperitoneum. For diagnosis, retrograde instillation o sterile milk through a catheter con rms injury and delineates its ull extent. This is superior to methylene blue and indigo carmine dyes, as in ant ormula does not stain surrounding tissues and is readily available. In addition, small de ects can be di cult to identi y and repair i the tissues surrounding the de ect become dye stained. Prior to repair, cystoscopy is indicated or any bladder base injury to assess ureteral patency. In addition, the ull extent o injury can be de ned, and the bladder can be evaluated or additional injuries or intravesical sutures. I bladder distension cannot be maintained during cystoscopy or i the patient is not in dorsal lithotomy, the ureteral ori ces can also be evaluated grossly through the cystotomy site. I the cystotomy is small, suprapubic teloscopy, which is described in Chapter 45, is also an option, or the cystotomy can be extended to allow evaluation. Repair during the primary surgery is pre erred and lowers risks o later vesicovaginal stula ormation. Principles o repair include injury delineation; wide mobilization o surrounding tissues; tension- ree, multilayered, watertight closure; and adequate postoperative bladder drainage (Utrie, 1998). Suture identi ed in the bladder is cut, as persistence can lead to cystitis, stone ormation, or both. Larger de ects may be closed in two or three layers with a running stitch using 3-0 absorbable or delayed-absorbable suture. The rst layer inverts the mucosa into the bladder, and subsequent layers reapproximate the bladder muscularis and serosa. In the area o the trigone, the ureters are typically stented rst, and the repair may be per ormed with interrupted sutures to avoid ureteral kinking (Popert, 2004). Postoperatively, continuous bladder drainage is continued or 7 to 10 days (Utrie, 1998). Urethral Injury the emale urethra is rarely injured during gynecologic surgery, but cystoscopy, urethral diverticulum repairs, antiincontinence operations, and possibly anterior colporrhaphy are at-risk procedures. Repair is completed with 3-0 or 4-0 absorbable suture in an interrupted ashion and in multiple layers, i possible. Similar to cystotomy, a Foley catheter is typically placed Bladder Injury Cystotomy is common and complicates approximately 0. Intravenous administration o indigo carmine or methylene blue can aid cystoscopic evaluation, with observation o blue-stained urine rom the ureteral ori ces. Un ortunately, normal-appearing ndings at cystoscopy do not guarantee ureteral integrity, as nonobstructive, partially obstructive, or late ureteral injuries may be unrecognized. Diagnosing injury shortly a ter surgery is challenging, as patient symptoms may be attributable to other causes. Renal damage may begin 24 hours a ter obstruction and can be irreversible in 1 to 6 weeks (Walter, 2002). Symptoms usually develop about 48 hours a ter surgery, and ever, abdominal pain, ank pain, and watery discharge may be among these. Prolonged skin or vaginal drainage suggests a urinary leak, and high creatinine levels in these uids are diagnostic o urine. Lack o contrast in the distal ureter on delayed C images con rms total obstruction (Armenakas, 1999). All o these imaging modalities can be used to diagnose injury in both the early and late postoperative periods. The primary layer inverts the bladder mucosa with running or interrupted sutures of 3-0 delayedabsorbable or absorbable suture. Second and possibly a third layer approximate the bladder muscularis to reinforce the incision closure. Ureteral Injury this is uncommon in benign gynecologic surgery, and the incidence approximates 0. For hysterectomy, the highest rate o ureteral injury is linked with laparoscopic hysterectomy, and the lowest with vaginal hysterectomy (Gilmour, 2006). Other associated procedures include operations or pelvic organ prolapse, incontinence, malignancy, or endometriosis (Patel, 2009; Utrie, 1998). Gynecologic ureteral injury typically occurs in the distal third and includes transection, ligation, kinking, and crushing (Brandes, 2004; Utrie, 1998). O these, the ureter more o ten is transected or kinked, and each accounts or approximately 40 percent o injuries. During hysterectomy, the most common trauma site is at the level o the uterine artery and accounts or 80 percent o injuries (Ibeanu, 2009). The ureter is also vulnerable near the pelvic brim during adnexectomy and at the distal uterosacral ligaments. Mechanisms o injury include clamping or suturing with the ureter poorly visualized. Ureteral stenting assists with intraoperative recognition but does not necessarily prevent injury. As with bladder injury, the best prevention is sound intraoperative technique and direct visualization o the peristalsing ureter. Treatment the best repair method depends on the location, extent, time rom surgery, and mechanism o injury. Expert assistance rom a urogynecologist, gynecologic oncologist, or urologist may be prudent. The ureter can be repaired by stenting, reimplantation, or end-to-end reanastomosis. For low-grade sheath injuries rom clamping or suturing, removal o the insult and stent placement Intraoperative Considerations may be su cient. For incomplete obstruction or injury identied postoperatively, stenting alone can resolve injuries in up to 80 percent o cases. For more extensive injury, either reimplantation or reanastomosis is per ormed (Utrie, 1998). Reimplantation, namely, ureteroneocystotomy, is pre erred or injuries within 6 cm o the bladder. Uncommonly with this, i the ureter is short, a psoas hitch, that is, mobilizing the bladder and attaching it to the psoas muscle tendon, may be necessary to bridge the gap and relieve tension on the repair. In this procedure, the bladder ipsilateral to the injury is mobilized, and a pedicle o anterior bladder wall is ashioned into a tube to bridge to the ureter. For injuries greater than 7 cm rom the bladder, ureteral reanastomosis, that is, ureteroureterostomy, is pre erred. Rarely, transureteroureterostomy is needed or a more proximal injury or one in which the bladder cannot be mobilized. With this procedure, the injured ureter is tunneled across and connected to the healthy ureter. Little evidence guides the decision or reoperation in the early postoperative period. Intraoperatively, tissues are in their best condition, and the likelihood or success ul repair is great. However, most iatrogenic injuries are recognized a ter a delay and tend to be complex (Brandes, 2004). In general, reexploration within the rst ew days appears to be well tolerated, leads to good outcomes, and is not technically di cult (Preston, 2000; Stanhope, 1991). Firm recommendations regarding reoperation beyond this early postoperative period are lacking, but reexploration 2 to 3 weeks a ter initial surgery is di cult due to in ammation, brosis, adhesions, hematoma, and distorted anatomy (Brandes, 2004). For delayed diagnoses, retrograde stenting is unsuccess ul in 50 to 95 percent o cases and recommended only or certain low-grade injuries (Brandes, 2004). Occasionally, an antegrade stent can be placed percutaneously, which will avoid the need or laparotomy, provided there is no ureteral leak or stricture. More extensive damage, such as complete transection, cannot be easily stented and is more appropriately repaired by de nitive surgery. Using a decision analysis model, one study estimated that routine cystoscopy was cost-e ective when ureteral injury rates were above 1. Cystoscopy is currently indicated or urogynecologic procedures, but there are no strict recommendations or other routine gynecologic procedures, including hysterectomy (American College o Obstetricians and Gynecologists, 2013; Patel, 2009). Some have elected selective cystoscopy, or cystoscopy restricted to patients with risk actors or when intraoperative events make injury more likely. A traumatic breach during dissection is the most common, particularly i the bowel wall is abnormally xed by adhesions (Mathevet, 2001; Maxwell, 2004). Additional risks include reduced organ mobility rom Crohn disease or diverticulitis, laparoscopic trocar or Veress needle insertion, diathermy use, and anterior abdominal wall entry during laparotomy. For the gynecologic surgeon, prevention and injury recognition help avoid serious postoperative sequelae. Strict adherence to surgical principles with sharp dissection or adhesions, gentle tissue handling, adequate exposure, light retraction, and sparing use o diathermy near hollow organs is key. Entering through prior abdominal incisions, dissection proceeds methodically in layers. Alternatively, a separate incision or extension o the existing one to an area that has not been previously opened can be considered. A ter any extensive pelvic dissection, the bowel is systematically inspected along its entire length to detect serosal de ects and unrecognized per oration. At suspected sites, the bowel is scrutinized or mucosal eversion and content leakage. Management o enterotomy depends on the site and size o injury, surgeon skill, degree o blood supply compromise, and time o recognition. With the small intestines, serosal de ects may be either le t alone or rein orced with small-gauge absorbable suture (Maxwell, 2004). Short small-intestine enterotomies may be repaired in layers using ne absorbable suture. During repair, rubber-shod clamps are placed across the intestinal lumen on either side o the wound to prevent content spill. Large-bowel injuries increase the risk o ecal peritonitis, sepsis, and poor wound healing. Serosal de ects and small lacerations may be managed similarly to those o the small intestine.

In up to one third o cases pregnancy yoga classes discount lady era 100 mg on line, extrauterine extension is present menopause urinary frequency lady era 100 mg purchase visa, o ten appearing as "worm-like" plugs o tumor within the vessels o the broad ligament and adnexa menstrual 10 days generic 100 mg lady era visa. At operation menopause 7 keto dhea buy 100 mg lady era otc, this may resemble intravenous leiomyomatosis or a broad ligament leiomyoma breast cancer yard decorations buy lady era from india, both described in Chapter 9 (p. B High grade Undifferentiated Sarcoma Compared with endometrial stromal sarcomas, these tumors tend to be larger and more polypoid, o ten lling the uterine cavity. Instead o an in ltrating pattern, high-grade undi erentiated sarcomas displace the myometrium more destructively, leading to prominent hemorrhage and necrosis. These tumors lack speci c di erentiation and bear no histologic resemblance to endometrial stroma (Hendrickson, 2003; Zaloudek, 2011). C Carcinosarcoma Accumulating clinical and pathologic evidence suggests that carcinosarcomas actually represent endometrial carcinomas that have undergone clonal evolution, resulting in the acquisition o sarcomatous eatures. In this low-power view that involved the corpus and cervix, irregular tongues of tumor (asterisks) are seen dissecting into the cervical stroma. The tumor cells are spindled and relatively bland, similar to normal endometrial proliferative phase stroma. Photograph of the surgical specimen after it has been bisected and remains joined at the fundus. In addition, metastases usually show carcinomatous elements, with or without sarcomatous di erentiation. However, by convention, carcinosarcomas are usually grouped with uterine sarcomas, accounting or 2 to 3 percent o all uterine malignancies. Grossly, the tumor is sessile or polypoid, bulky, necrotic, and o ten hemorrhagic. On occasion, a large tumor protrudes through the external cervical os and lls the vaginal vault. In this carcinosarcoma with cartilaginous differentiation, malignant glands are present at the periphery (arrows). Centrally is a focus of malignant cartilage (asterisk), with its characteristic lacunae embedded within a bluish chondroid matrix. The malignant epithelial element is typically an adenocarcinoma o endometrioid type, but serous, clear cell, mucinous, squamous cell, and undi erentiated carcinoma are also common. Mesenchymal components can be homologous, usually resembling endometrial stromal sarcomas or brosarcomas. Alternatively, heterologous mesenchymal di erentiation can be ound in association with areas o endometrial stromal or undi erentiated sarcomas. Most commonly, rhabdomyosarcoma or chondrosarcoma compose these cases o heterologous mesenchymal di erentiation. Carcinosarcoma is a biphasic malignant neoplasm composed of both carcinomatous and sarcomatous elements. In this example, malignant endometrioid-type glands are present within an atypical spindled stroma. Immunohistochemical stain for cytokeratin marks the epithelial component but not the stromal component. Conversely, an immunohistochemical stain for vimentin (a mesenchymal marker) stains the sarcomatous component. These adenosarcomas are designated as having "sarcomatous overgrowth," and patients have a poor prognosis, similar to that o carcinosarcomas (Krivak, 2001; McCluggage, 2003). Leiomyosarcomas, high-grade undi erentiated sarcomas, and carcinosarcomas are consistently characterized by an aggressive growth pattern and rapid disease progression despite treatment. In contrast, endometrial stromal sarcomas and adenosarcomas have an indolent growth pattern with long diseaseree intervals. Lung metastases are particularly common, and more than hal o patients will have distant spread i diagnosed with recurrent disease. The opposite is true or carcinosarcomas, in which one third o patients with clinically stage I tumors will have nodal metastases (Park, 2010). T us, comprehensive pelvic and paraaortic lymphadenectomy is particularly important (emkin, 2007). Extraabdominal spread is less common, and most recurrences are ound in the pelvis or abdomen. Adenosarcoma this rare, biphasic neoplasm is characterized by a benign epithelial component and a sarcomatous mesenchymal component. Grossly, adenosarcomas grow as exophytic polypoid masses that extend into the uterine cavity. Microscopically, isolated glands are dispersed throughout the mesenchymal component and are o ten dilated or compressed into thin slits. In general, these are considered low-grade tumors with mild atypia and relatively ew mitotic gures. However, beginning in 2009, only carcinosarcomas share the same staging criteria as endometrial carcinomas (able 33-9, p. Normal endometrial glands are surrounded by a cellular stroma consisting of a low-grade sarcoma. In general, laparotomy is per ormed due to the typical eatures o sarcomas, which include uterine enlargement, parametrial extension, and tumor metastasis. Laparoscopic or vaginal approaches have not yet been shown to yield equivalent outcomes. For instance, peritoneal washings may be easily obtained upon opening the abdomen but are not part o the staging system and have limited value (Kanbour, 1989). Exploration is particularly important to assess the abdomen or unresectable or widely metastatic disease that might indicate a need to abort the procedure. As in endometrial carcinomas, some evidence shows bene t rom aggressive cytoreductive surgery (Dinh, 2004; Leath, 2007; T omas, 2009). With uterine leiomyosarcoma, all patients should undergo a hysterectomy, i easible. A modi ed radical or radical procedure may be occasionally required i there is parametrial in ltration. In the absence o other gross disease, ewer than 5 percent will have ovarian or nodal metastases. In addition, lymph node dissection is reserved or patients with clinically suspicious nodes (Kapp, 2008; Leitao, 2003; Major, 1993). Endometrial stromal tumors and adenosarcomas are also best treated by hysterectomy. Preservation o the ovaries is generally accepted or endometrial stromal sarcomas or adenosarcomas in the absence o extrauterine disease (Chan, Uterine Sarcoma 2008; Li, 2005; Shah, 2008). Although nodal metastases are most o ten identi ed in patients with obvious extrauterine disease, they do occur in 5 to 10 percent o patients with no evidence or intraabdominal spread (Dos Santos, 2011; Go, 1993; Signorelli, 2010). Lymph node metastases will be ound in up to one third o patients with clinical stage I disease, and thus, comprehensive lymphadenectomy should be per ormed as or poorly di erentiated endometrial cancers (Major, 1993; Nemani, 2008; Park, 2010; emkin, 2007). Because this component may be serous or clear cell, extended surgical staging with in racolic omentectomy and random peritoneal biopsies is also advisable (Greer, 2015). Although a reduced rate o pelvic relapse or those with carcinosarcomas was noted, no bene t was gained or those with leiomyosarcomas and no signi cant increase in survival rates or either group. Un ortunately, the number o patients with endometrial stromal sarcoma was too small to permit analysis (Reed, 2008). Pelvic radiation does not prevent distant recurrences and has yet to be shown to improve survival rates (Nemani, 2008). In many circumstances, vaginal brachytherapy may be an alternative, especially i paired with systemic chemotherapy (Greer, 2015). Although no survival advantage was demonstrated, the observed di erences avored the use o combination chemotherapy in uture trials (Wol son, 2007). T us, because the recurrence rate or the clinically aggressive types is excessive, enrollment in an experimental clinical trial should be care ully considered, i available. In practice, many patients receive postoperative radiation with or without chemotherapy. A ter surgery, menopausal symptoms such as hot f ushes may be treated as appropriate or uterine leiomyosarcomas, highgrade undi erentiated sarcomas, and adenosarcomas. However, although it is considered sa e to preserve the ovaries in a premenopausal woman with endometrial stromal sarcoma, the use o estrogen replacement therapy has been associated with disease progression and is avoided (Chu, 2003; Pink, 2006). Surgically treated patients with uterine sarcoma should have a physical examination every 3 months or the rst 2 years and then at 6- to 12-month intervals therea ter. Depending on the type o sarcoma, a chest radiograph or C imaging is per ormed every 6 to 12 months or 2 years, then annually. Adjuvant Chemotherapy There is no proven survival bene t or using adjuvant chemotherapy in patients with stage I uterine sarcoma (Omura, 1985). However, because most patients will recur distantly, adjuvant systemic treatment is requently used. In high-grade undi erentiated sarcomas and carcinosarcomas, chemotherapy regimens used or more advanced disease may be considered. Fertility sparing Management Rarely, young patients may desire to delay de nitive hysterectomy a ter a ertility-sparing "myomectomy" demonstrates sarcomatous eatures on the nal pathology report (Lissoni, 1998; Yan, 2010). Although expectant management ollowing tumor resection can result in success ul pregnancies in select patients, it is risky not to per orm a hysterectomy, and eventually all such women should undergo hysterectomy (Lissoni, 1998). Most patients, even those with negative margins, should be counseled regarding de nitive surgery and ovarian preservation during surgery or clinical stage I uterine leiomyosarcomas or endometrial stromal sarcomas. Egg retrieval, assisted reproductive technologies, and pregnancy surrogacy would still be possible. Adjuvant Radiation Approximately hal o patients with stage I disease who are observed without adjuvant therapy will relapse (Leath, 2009). Due to the rarity o these tumors and limited data to support a consistent approach, the use o postoperative therapy is usually individualized. Neoadjuvant chemotherapy can be considered or patients whose disease is considered unresectable or who are medically un t or surgery. For recurrent disease, secondary cytoreductive surgery may be easible in some circumstances (Giuntoli, 2007). Palliative radiation may also have a role, depending on the site and distribution o the tumor. In general, uterine sarcomas have a propensity or relapse at distant sites, and chemotherapy is more use ul. Since current treatment options have only modest e cacy, patients are encouraged to enroll in experimental clinical trials. Leiomyosarcoma Doxorubicin is considered the most active single agent (Miller, 2000; Omura, 1983). However, treatment with the combination o gemcitabine and docetaxel currently has the highest proven response rate (36 percent) (Hensley, 2008). Five-year survival rates o 30 to 50 percent have been reported ollowing pulmonary resection or lung metastases. Local and regional recurrences may also be amenable to surgical resection (Giuntoli, 2007). In a study o 141 women ollowed or a median o 3 years, 74 percent died o disease progression. Other poor prognostic actors across all subtypes include older age, A rican-American race, and lack o primary surgery (Chan, 2008; Kapp, 2008; Nemani, 2008). Leiomyosarcomas have the worst prognosis and are ollowed by carcinosarcoma and the group o endometrial stromal tumors (Livi, 2003). Endometrial stromal sarcomas and uterine adenosarcomas without sarcomatous overgrowth are the two notable exceptions. Patients with these tumors tend to have a good prognosis due to their indolent growth (Pautier, 2000; Verschraegen, 1998). Endometrial Stromal Tumors Surgical resection may be easible or some patients with recurrent endometrial stromal sarcoma, but hormonal therapy is particularly use ul. Progestins such as megestrol acetate and medroxyprogesterone acetate are most commonly used either postoperatively or advanced-stage disease or or relapses (Reich, 2006). Advanced disease or recurrences o these rare tumors are also typically not amenable to surgical resection, although palliative radiation may have some utility. Systemic chemotherapy is usually the only option, and i os amide is the only cytotoxic drug with proven activity (Sutton, 1996). Gynecol Oncol 93(1): 204, 2004 Burke C, Hickey K: reatment o endometrial stromal sarcoma with a gonadotropin-releasing hormone analogue. Results rom a 10-year experience (1990-1999) at the Massachusetts General Hospital. Br J Cancer 108(3):727, 2013 Carcinosarcoma I os amide is the most active single agent or carcinosarcoma. Cancer Res 60(1):114, 2000 Galaal K, van der Heijden E, God rey K, et al: Adjuvant radiotherapy and/or chemotherapy a ter surgery or uterine carcinosarcoma. Gynecol Oncol 91(1):209, 2003 Leunen M, Breugelmans M, De Sutter P, et al: Low-grade endometrial stromal sarcoma treated with the aromatase inhibitor letrozole. Obstet Gynecol 106(6):1304, 2005 Lieng M, Berner E, Busund B: Risk o morcellation o uterine leiomyosarcomas in laparoscopic supracervical hysterectomy and laparoscopic myomectomy, a retrospective trial including 4791 women. Abstract presented at American Congress o Obstetricians and Gynecologists Annual Clinic and Scienti c Meeting. San Francisco, 2-6 May 2015 Lissoni A, Cormio G, Bonazzi C, et al: Fertility-sparing surgery in uterine leiomyosarcoma. Obstet Gynecol 83(1):118, 1994 Livi L, Paiar F, Shah N, et al: Uterine sarcoma: twenty-seven years o experience. Nucl Med Commun 33(2):185, 2012 Signorelli M, Fruscio R, Dell-Anna, et al: Lymphadenectomy in uterine lowgrade endometrial stromal sarcoma: an analysis o 19 cases and a literature review. Oncol Rep 5 (4):939, 1998 Wada H, Enomoto, Fujita M, et al: Molecular evidence that most but not all carcinosarcomas o the uterus are combination tumors. Gynecol Oncol 107:177, 2007 Yan L, ian Y, Zhao X: Success ul pregnancy a ter ertility-preserving surgery or endometrial stromal sarcoma.

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