Barbara A. Pockaj, MD

• Professor
• Department of Surgery
• Division of Surgical Oncology
• Mayo Clinic
• Phoenix, Arizona

Cytologies suspicious or squamous cell carcinoma or adenocarcinoma carry the highest risk o invasive cancer and are evaluated promptly condom causes erectile dysfunction order himcolin 30gm without a prescription. I initial evaluation ails to reveal invasive cancer erectile dysfunction drugs in canada purchase himcolin 30gm without prescription, a diagnostic excision procedure is indicated erectile dysfunction 2014 cheap himcolin online mastercard. Pregnant patients 21 years and older are screened and their abnormal cytologies managed according to guidelines or the general population erectile dysfunction johns hopkins buy discount himcolin 30 gm on line. Colposcopy and ectocervical biopsy are sa e and accurate during pregnancy (Economos erectile dysfunction doctor in atlanta order himcolin 30gm with amex, 1993) erectile dysfunction treatment mumbai order himcolin 30 gm with mastercard. Endocervical and endometrial sampling are not per ormed during pregnancy to avoid amnionic membrane rupture and in ection. This is because lesion progression is typically slow and lesion grade may change during delivery and puerperal remodeling (Yost, 1999). Although cervical conization is in requently per ormed during pregnancy, indications or this are discussed in Chapter 30 (p. These ndings include Trichomonas vaginalis, Candida species, Actinomyces species, herpes simplex virus, or shi t in ora consistent with bacterial vaginosis. Sensitivity is generally limited, and accuracy o diagnosis varies (Fitzhugh, 2008). For this reason, con rmatory tests or clinical correlation should dictate any actions related to these ndings. Other nonneoplastic ndings are reactive changes associated with in ammation or repair, radiation changes, atrophy, and posthysterectomy benign glandular cells. Because menstrual history and menopausal status are o ten unknown to the cytologist, benign endometrial cells are reported on cervical cytology or all women 45 years and older (Nayar, 2015). Premenopausal women do not require endometrial evaluation in the absence o abnormal bleeding. Colposcopy Preparation this outpatient procedure examines the lower anogenital tract with a binocular microscope a xed to a stand and requires skills that encompass colposcopic terminology, lesion identi cation and grading, and biopsy techniques. Its primary goal is to identi y invasive or preinvasive neoplastic lesions or directed biopsy and subsequent management. It remains the gold standard evaluation o patients with abnormal cervical cytology. However, its sensitivity, interobserver agreement, and reproducibility are less than previously thought. Sensitivity estimates range between 50 and 80 percent (American College o Obstetricians and Gynecologists, 2013; Ferris, 2005; Jeronimo, 2007). This highlights the need or urther evaluation or surveillance when initial colposcopy ails to reveal high-grade neoplasia. Benign surface vessels viewed through a colposcope using usual white light source. Use of a blue-green (red-free) light filter provides higher contrast and definition of vascular patterns. The colposcope contains a stereoscopic lens or digital imaging system that has magni cation settings ranging rom 3- to 20- old. However, it is not delayed in the patient with a visible lesion, abnormal bleeding, or poor appointment compliance. In cases o severe cervicitis or other pelvic in ection, treatment may be indicated be ore per orming biopsies or endocervical curettage. Notably, abnormal cervical discharge in the absence o an identi ed pathogen may be a cancer indicator. A Pap test per ormed at the time o colposcopy is o questionable value, may obscure colposcopic ndings, and should be per ormed on an individualized basis. Solutions may aid colposcopic examination and are applied by gently dabbing a saturated swab or sponge or by spray-bottle misting so as not to traumatize the cervical epithelium. Abnormal vessels, especially when viewed with green- ltered light, may be more prominent be ore acetic acid application. Acetic acid in a 3- to 5-percent solution is a mucolytic agent thought to exert its ef ect by reversibly clumping nuclear chromatin. This causes neoplastic lesions to assume a thicker density and hues o white depending on the degree o abnormal nuclear density. Applying acetic acid to abnormal epithelium results in the acetowhite change characteristic o neoplastic lesions and o some benign conditions. Dilute Lugol iodine solution stains mature squamous epithelial cells a dark purple-brown color in estrogenized women as a result o high cellular glycogen content. Due to incomplete cellular dif erentiation, dysplastic cells have lower glycogen content, ail to ully stain, and appear various shades o yellow. This solution is particularly use ul when abnormal tissue cannot be ound using acetic acid alone. It is also used to de ne the limits o the active Z, as immature squamous metaplasia does not stain as strongly as mature (ully dif erentiated) squamous epithelium. Lugol solution should not be used in patients allergic to iodine, radiographic contrast, or shell sh. Examination wo major components o colposcopic examination are general assessment and speci c colposcopic ndings. Several areas of acetowhite change adjacent to the squamocolumnar junction are apparent. Within a neoplastic lesion, the most severe disease tends to be at the proximal (cephalad or upper) limit o the lesion. A type 1 Z is entirely ectocervical and visible; a type 2 has an endocervical component that is ully visible; and a type 3 Z has an endocervical component that cannot be completely visualized. Against this normal colposcopic landscape, colposcopists discern abnormal tissue and choose or biopsy the sites most likely to harbor the most severe neoplasia. Several colposcopic grading systems quanti y lesion qualities to improve diagnostic accuracy (Coppleson, 1993; Reid, 1985). Best known, the Reid Colposcopic Index is based on our lesion eatures, which are margin, color, vascular pattern, and Lugol solution staining. Each category is scored rom 0 to 2, and the summation provides a numeric index that correlates with histology (Table 29-6). Blood vessels lie below this layer and there ore are not visible or are seen only as a ne capillary network. The mucin-secreting columnar epithelium appears red due to its thinness and the close proximity o blood vessels to the sur ace. Lesions with low-grade characteristics are labeled grade 1 (minor) lesions, whereas highergrade characteristics are grade 2 (major) ndings. O Reid index eatures, lesion margins and color are best assessed ollowing application o acetic acid. The color or degree o whiteness obtained, rapidity and duration o acetowhitening, and sharpness o lesion borders are observed. Grade 2 (major or high-grade) lesions demonstrate a more persistent, duller shade o white, whereas grade 1 (minor or low-grade) lesions are translucent or bright white and ade quickly. Generally, grade 1 lesions have eathery or irregular "geographic" margins, whereas grade 2 lesions have straighter, sharper outlines. Punctate and mosaic patterns are graded on the basis o vessel caliber, intercapillary distance, and the uni ormity o each o these. Fine punctation and mosaicism, which are created by narrow vessels and short, uni orm intercapillary distances, typi y low-grade (grade 1) lesions. A coarse pattern results rom wider and more variable vessel diameters and spacing and indicates high-grade (grade 2) abnormalities. Atypical vessels are irregular in caliber, shape, course, and arrangement and raise suspicion or invasive cancer. Biopsy Ectocervical Biopsy Under direct colposcopic visualization, suspicious lesions are biopsied using cervical biopsy orceps. T ickened Monsel solution (erric subsul ate) or a silver nitrate applicator are applied with pressure to the biopsy site, providing hemostasis i needed. Heavier bleeding is rare and can be controlled with direct pressure or brie vaginal packing. Negative endocervical curettage results add reassurance to this management (Schorge, 2003). Endocervical curettage is per ormed by introducing an endocervical curette 1 to 2 cm into the cervical canal. The length and circum erence o the canal is rmly curetted, care ully avoiding sampling o the ectocervix or the lower uterine segment. Endocervical scrapings admixed with cervical mucus are then removed using a ring orceps or cytobrush and included with the curettage specimen. Alternatively, vigorous brushing with a cytobrush may be used to obtain an endocervical tissue specimen. Endocervical brushing is more sensitive than curettage, but grading o any dysplasia present is more di cult. However, two studies have shown that colposcopically directed biopsy detects only 60 to 70 percent o high-grade disease. Disease detection rates increase with the addition o random biopsies o normal-appearing epithelium and with the total number o biopsies taken (Gage, 2006; Pretorius, 2004; Zuchna, 2010)). Goals are to diagnose occult invasive cancer, detect progression o minor abnormalities, and treat high-grade dysplasia to decrease cancer risk. Detection and prevention o invasive cervical cancer, a relatively rare outcome, must be balanced against the potential harms o excessive testing and overtreatment that include procedure-related morbidities, possible adverse reproductive outcomes, and psychologic stress. Special populations considered include women age 21 to 25 years and pregnant women. Immunosuppressed women are no longer considered a special population and can now be managed in accordance with general guidelines. From top to bottom: endocervical curette, endocervical speculum, and cervical biopsy forceps. Guidelines are complex and are applied on an individualized basis, as they cannot address all clinical scenarios or individual patient situations. In this context, "young women" re ers to those individuals or whom the possible risk to uture pregnancies rom treatment outweighs the risk o progression to malignancy, although either o these is di cult to quanti y. I these criteria are not met, excision is recommended and ablation is unacceptable. In women age 25 years or older with an adequate colposcopic examination, either a diagnostic excision or observation with cotesting at 12 and 24 months is acceptable. Exclusion o invasive cancer and removal o all af ected tissue are primary clinical goals. Lesions can be multi ocal, located deep within endocervical cle ts, and extend arther into the endocervical canal (Massad, 2013). Diagnostic excision is required to exclude invasive cancer with maximum certainty. Choice o excision modality should avor an intact specimen with the most interpretable margins. I used, loop excision should be large enough to obviate the need or a second, deeper pass and should minimize cautery arti act. I there is no invasive cancer in the excision specimen, simple hysterectomy is recommended in women who have completed childbearing. Individuals are counseled regarding the signi cant ongoing risk even with negative excision margins and endocervical sampling. Close, long-term surveillance is recommended until hysterectomy is per ormed (Massad, 2013). Either ablation or excision is acceptable and is chosen according to individual patient, cervical Z, and lesion characteristics. Early surveillance generally is either cytology or cotest once or twice at 1-year intervals. Return to routine screening or an additional cotest generally occurs 3 years later. These are always ollowed by excision unless invasive cancer is diagnosed during initial colposcopic examination and biopsy. Unlike ablation, excision provides a histologic specimen or evaluation o excised margins and urther assurance that invasive cancer is not present. No clear evidence shows any treatment technique to be superior, and surgical treatments have an approximate 90-percent success rate (Martin-Hirsch, 2013). Ablation In general, ablation o the Z is ef ective or noninvasive ectocervical disease. Be ore ablation, evidence o glandular neoplasia or invasive cancer is excluded with the greatest certainty possible. Cryosurgery is an ablative method that delivers a re rigerant gas, usually nitrous oxide, to a metal probe that reezes tissue on contact. Less evidence suggests subsequent adverse ef ects on pregnancy outcome with cryotherapy than with loop excision. I the cervical lesion extends onto the vagina, laser ablation may help customize removal o the entire lesion with avorable depth control. Laser ablation can also be augmented by laser or loop excision o central tissue or cases in which an ectocervical lesion extends into the endocervical canal or in which colposcopy is inadequate (American College o Obstetricians and Gynecologists, 2013). Excision Clinical scenarios with the highest risk o occult invasive cancer but without de nitive histologic con rmation are evaluated urther with an excision procedure. Diagnostic excision re ers to situations in which invasive cancer has not been excluded by the criteria needed be ore an ablation is per ormed.

It is postulated that greater cortical density and thicker trabeculae compensate or ewer trabeculae in smaller bones icd 9 code for erectile dysfunction due to diabetes order himcolin with a mastercard. The Study o Osteoporotic Fractures erectile dysfunction caused by stroke discount himcolin 30gm with mastercard, or example erectile dysfunction treatment fort lauderdale buy discount himcolin 30 gm, identi ed that maternal emoral neck racture was a predictor or emoral neck racture in a population o elderly women (Cummings erectile dysfunction pills wiki cheap himcolin 30gm without prescription, 1995) erectile dysfunction drug stores buy himcolin 30 gm visa. Several genes have been associated with osteoporosis erectile dysfunction symptoms causes buy generic himcolin on line, but these discoveries have yet to translate into clinical application. Greater improvements in bone mass were also associated with increases in static balance. Exercise results in other general health bene ts that are not totally realized with pharmacological and nutritional interventions. T us, a history o alls or actors that increase all rates are included in a risk assessment (Table 21-7). Factors include those associated with general railty, such as reduced muscle strength, impaired balance, low body mass, and diminished visual acuity (Delaney, 2006). T erapy with glucocorticoids lasting more than 2 to 3 months is a major risk actor or bone loss and racture, particularly among postmenopausal women. The National Osteoporosis Foundation guidelines (2014) describe a chronic daily dose o prednisone that is 5 mg as the threshold or assessment and clinical intervention to prevent or treat glucocorticoid-induced osteoporosis. Fall Risk Factors Physiologic changes Prior falls Diminished balance Reduced muscle mass Comorbid conditions Arthritis Arrhythmia Alcohol abuse Gait disorders Balance disorders V isual impairment Cognitive impairment Orthostatic hypotension Environmental Poor lighting Unsafe footwear Telephone cords Cluttered hallways Loose rugs Slippery/damaged flooring No bathroom support bars Medications Narcotics Anticonvulsants Antiarrhythmic agents Psychiatric medications Antihypertensive agents ity. Un ortunately, Schnatz and associates (2011) ound that many women are not properly screened or treated or osteoporosis and that inappropriate screening may also lead to improper management o osteoporosis and its associated complications. During remodeling, osteoblasts synthesize several cytokines, peptides, and growth actors that are released into the circulation. Osteoclasts produce bone degradation products that are also released into the circulation and are eventually cleared via the kidney. These markers o bone ormation and resorption can estimate bone-remodeling rates and may help identi y ast bone losers. T at said, most prospective studies analyzing the relationship between bone remodeling and rates o bone loss have been shortterm and have been limited by the precision error o densitometry. Garnero and colleagues (1994) prospectively evaluated over 4 years the utility o bone markers to identi y ast bone losers in a large cohort o healthy menopausal women. Markers o bone resorption may also be use ul predictors o racture risk and bone loss. Elevation o these markers may be associated with an increased racture risk in elderly women, although data are not uni orm. However, biomarker measurements are currently limited by their high variability within individuals. Additional studies with racture endpoints are needed to con rm the useulness o these markers in individual patients. Biomarkers may also have value in predicting and monitoring response to potent antiresorptive therapy in clinical trials. Normalization o bone ormation and resorption marker levels ollowing therapy has been observed in prospective trials. However, with re nement o assay technology and better understanding o biological variability, it is likely that they will become a use ul adjunct in the uture or risk assessment and management. As expected, a sedentary li estyle correlated directly with an elevated risk or coronary events (McKechnie, 2001). This atherogenic lipid pro le associated with abdominal adiposity is at least partly mediated through interplay with insulin and estrogen. A strong correlation exists between the magnitude o the worsening in cardiovascular risk actors (lipid and lipoprotein changes, blood pressure, and insulin levels) and the amount o weight gained during M (Wing, 1991). Favorable lipoprotein pro les in young women are maintained in part by physiologic estrogen levels. A ter menopause and with the subsequent declines in estrogen levels, this avorable e ect on lipids is lost. A ter menopause, the risk o coronary heart disease doubles or women, and at approximately age 60, the atherogenic lipids reach levels higher than those in men. These counterbalancing risks primarily involve aspirin-related bleeding episodes such as hemorrhagic stroke and gastrointestinal bleeding (Lund, 2008). Be ore menopause, women have a much lower risk or cardiovascular events compared with men their same age. This becomes vitally important or women in M, when preventive measures can signi cantly improve both li e quality and quantity. Modi able elements are hypertension, dyslipidemia, obesity, diabetes/glucose intolerance, smoking, poor diet, and lack o physical activity. Since data question the widespread use o hormone treatment to avert this common problem, other strategies must be considered (Chap. Manson and colleagues (2002) determined that walking or vigorous exercise reduced the risk o cardiovascular events in postmenopausal Weight Gain and Fat Distribution Weight gain is a common complaint among women during M. Women aged 45 to 54 years had signi cantly greater increases in weight and in hip circum erence than those aged 55 to 65 years. These raise the likelihood o developing insulin resistance and subsequent diabetes mellitus and heart disease (Dallman, 2004; Wing, 1991). This stems rom associated alterations in cardiometabolic risks due to hormone-related declines in energy expenditure and at oxidation (Jull, 2014). In addition, data rom the Rosetta Study and the New Mexico Aging Process Study show that older adults have higher percentages o body at than younger adults at any age due to muscle mass loss with aging (Baumgartner, 1995). Numerous other actors underlie weight gain and include genetic actors, neuropeptides, and adrenergic nervous system activity (Milewicz, 1996). Although many women believe that noncontraceptive estrogen therapy causes weight gain, results rom clinical trials and epidemiologic studies indicate that the e ect o menopausal hormone therapy on body weight and girth, i any, is to blunt slightly the rate o age-related increases. Li estyle interventions to minimize gains in at mass and changes in body composition and body at distribution during M predominantly include exercise and healthy nutrition. Women exposed to a program o combined exercise and calorie-restricting dietary interventions or 54 weeks had improved body weight and reduced abdominal adiposity compared with usual activities in the control group (Simkin-Silverman, 2007). As well, signi cant reductions in waist circum erence and body at were maintained beyond 4 years. Hagner and coworkers (2009) ound that a Nordic walking program reduced weight gain during M. S C Breast Changes the breast undergoes change during M mainly because o hormonal withdrawal. In premenopausal women, estrogen and progesterone exert proli erative e ects on ductal and glandular structures, respectively. At menopause, withdrawal o estrogen and progesterone leads to a relative reduction in breast proli eration. A signi cant reduction in the volume and tissue density is seen during mammography as these areas become replaced with adipose tissue. Mammography is advisable or women older than age 40, and breast imaging is ully discussed in Chapter 12 (p. Hollander and associates (2001) studied late reproductive-aged women and ound that women with a greater incidence o hot ushes were more likely to report poor sleep than were women with ewer vasomotor symptoms. As with most menopausal symptoms, severity and prevalence seem to peak during late M, when women have prolonged amenorrhea. Even women with ew vasomotor symptoms may experience insomnia and associated menopause-related mood symptoms (Erlik, 1982; Woodward, 1994). As women age, they are more likely to experience lighter sleep and are awakened more easily by pain, sound, or bodily urges. Health issues and other chronic conditions experienced by women or by their spouse or bedmate are likely to urther disrupt sleep. Arthritis, carpal tunnel syndrome, chronic lung disease, heartburn, and certain medications that are known to disrupt sleep may dramatically lower the quality and quantity o rest ul sleep. Nocturia, urinary requency, and urgency, all o which are more common in menopausal women, are other notable actors. Loud snoring can ollow partial upper airway obstruction that ranges in severity rom upper airway resistance to obstructive sleep apnea (Gislason, 1993). Disturbed sleep can lead to atigue, irritability, depressive symptoms, cognitive dys unction, and impaired daily unctioning. Importantly, although atigue may stem rom night sweats and poor sleep, other common potential etiologies, such as anemia or thyroid disease, among Dermatologic Changes Skin changes that may develop during M include hyperpigmentation (age spots), wrinkles, and itching. These are caused in part by skin aging, which results rom the synergistic e ects o intrinsic aging and photo-aging (Guinot, 2005). Hormonal aging o the skin is also thought to be responsible or many dermal changes. These include a reduced thickness due to lower collagen content, diminished sebaceous gland secretion, loss o elasticity, and decreased blood supply (Wines, 2001). Although the e ect o hormone de ciency on skin aging has been widely studied, distinguishing its contribution rom those o intrinsic aging, photo-aging, and other environmental insults is dif cult. Dental Changes Dental problems may also develop as estrogen levels wane in late M. The buccal epithelium atrophies due to estrogen deprivation, resulting in decreased saliva and sensation. A bad taste in the mouth, increased incidence o cavities, and tooth loss also may occur (Krall, 1994). Oral alveolar bone loss is strongly positively correlated with osteoporosis and can lead to tooth loss. Fatigue Prevention Instructions Obtain adequate sleep every night Exercise regularly to reduce stress Avoid long work hours and maintain your personal schedule If stress is environmental, take vacations, switch jobs, or approach your company or family to help resolve sources of stress Limit intake of alcohol, drugs, and nicotine Eat a healthy, well-balanced diet Drink adequate amounts water (8 to 10 glasses) during the early part of the day Consider seeing a specialist in menopausal medicine alcohol consumption, and male gender, which would imply lack o estrogen. In all these examples, treatment o underlying health conditions is the main ocus to improve patient sleep. At times, short-term use o pharmacologic sleep aids is indicated, and these are listed in able 1-16 (p. Although no direct e ect o lowered estrogen levels on memory and cognition has been determined, many investigators suspect a relationship between the two. Cognitive unctioning was assessed in a cohort study o reproductive-aged and postmenopausal women not using hormone replacement therapy. Premenopausal women in their 40s were less likely to exhibit cognitive decline compared with postmenopausal patients in the same decade o li. These researchers concluded that deterioration o some orms o cognitive unction is accelerated a ter menopause (Halbreich, 1995). In another study, Henderson and coworkers (2013) studied 643 healthy postmenopausal women not using hormone therapy who were recruited as early (< 6 years a ter menopause) and late (> 10 years a ter menopause) groups. Cognitive outcomes were standardized composite measures o verbal memory, executive unctions, and global cognition. Results or early and late groups did not di er signi cantly, although progesterone concentrations were signi cantly positively associated with verbal memory and global cognition in early group women. Factors accelerating cerebral degenerative changes represent potentially modi able risks or cognitive decline (Kuller, 2003; Meyer, 1999). Investigators have studied putative risk actors and have correlated them with measures o cerebral atrophy, computed tomography (C) densitometry, and cognitive testing among neurologically and cognitively normal, aging volunteers. The World Health Organization has consistently ranked depression as a leading cause o disability in women. A prior depressive episode (particularly i related to reproductive events) remains the strongest predictor o mood symptoms or depression during midli. Vasomotor symptoms, anxiety, and other healthrelated issues also modulate depression risks (Soares, 2014). Contemporary ndings have dispelled myths that natural menopause itsel is associated with depressed mood (Ballinger, 1990; Busch, 1994). However, an increased risk o depressive symptoms during M has been repeatedly observed in population-based studies. In the Penn Ovarian Aging Study, the risk was nearly three times higher in women in M compared with premenopausal women. Moreover, women with no history o depression were two and a hal times more likely to report depressed mood during M than during the premenopausal period (Freeman, 2004). Other cohort studies report similar ndings (Bromberger, 2011; Cohen, 2006; Dennerstein, 2004; Woods, 2008). Moreover, there are a high percentage o subjects with recurrent depression during M (Freeman, 2007). T us, a screen or depression is prudent or women in this transition, and tools are described in Chapter 13 (p. It has been suggested that the hormonal uctuations during early M are responsible, in part, or this a ective instability. Similarly, surgical menopause induces mood changes because o the rapid hormonal loss at this time. Soares (2005) hypothesizes that a major component o the reported emotional distress during M may be causally related to high and erratic estradiol levels. For example, Ballinger and colleagues (1990) showed that increases in stress hormones (and probably symptoms that are stress related) are physiologically linked with high estrogen levels. They also reported that women with abnormal psychometric test scores early a ter menopause had higher estradiol levels than women with lower scores. Spinelli and associates (2005) showed that estrogen levels are correlated with the intensity o menopausal symptoms. A randomized, placebo-controlled menopause treatment study evaluated administered standard doses o conjugated equine estrogen (0. Importantly, the M is a complex sociocultural as well as a hormonal event, and psychosocial actors may contribute to mood and cognitive symptoms. Lock (1991) suggests that part o the stress reported by Western women is clearly culture-speci c.

With vaginal cancer impotence in men symptoms and average age discount himcolin 30gm with mastercard, local extension and lymphatic invasion are common patterns o spread erectile dysfunction natural remedies diabetes buy himcolin 30gm amex. The lymphatic channels that drain the vagina orm extensive erectile dysfunction treatment exercise purchase himcolin us, complex erectile dysfunction protocol real reviews buy himcolin without a prescription, and variable anastomoses erectile dysfunction see urologist cheap himcolin master card. As a result impotence at 18 generic 30gm himcolin fast delivery, any node in the pelvis, groin, or anorectal area may drain any part o the vagina. O these, the external, internal, and common iliac lymph nodes are the primary sites o vaginal lymphatic drainage. T us, pelvic lymphadenectomy, which samples these nodal groups, is commonly per ormed during primary surgical excision o proximally located vaginal cancers. Invasive tumor is composed of irregular nests of malignant squamous cells with keratin pearls (arrow) and intercellular bridges. It is possible that use o this vaccine will decrease invasive vaginal cancer rates in the uture. Diagnosis Vaginal bleeding is the most common complaint associated with vaginal cancer, although pelvic pain and vaginal discharge also may be noted. Less requently, lesions involving the anterior vaginal wall may lead to dysuria, hematuria, or urgency. Moreover, o those with cancers, women who have had a prior hysterectomy are signi cantly more likely to have lesions in the upper vagina (70 percent) than those without prior hysterectomy (36 percent) (Chyle, 1996). During pelvic evaluation in all women, the vagina is inspected as the speculum is inserted or removed. I a gross lesion is ound, vaginal cancer usually can be diagnosed by punch biopsy in the of ce. An Emmett hook, one type o skin hook, may be use ul to elevate and stabilize vaginal tissue during biopsy. Bimanual examination assists in determining the tumor size, and rectovaginal examination is especially important or posterior wall lesions. Once cancer is diagnosed, no speci c laboratory testing other than that used generally or preoperative preparation such as complete blood count and serum chemistry panel is required. Chest radiography aids the search or metastatic disease (Table 32-1 and Table 32-2). I needed, general anesthesia can permit a more detailed pelvic examination or accurate staging. Proctosigmoidoscopy to a depth o at least 15 cm can detect local bowel invasion, whereas cystourethroscopy assists identi cation o bladder or urethral involvement. Advances in radiation technology and earlier diagnosis are largely responsible or the improved 5-year survival rate, which now ranges rom 45 to 68 percent or all stages (Ghia, 2011; Hellman, 2006). Other actors associated with poor prognosis include larger tumor size, adenocarcinoma cell type, and older age (Hellman, 2006; jalma, 2001; ran, 2007). There ore, therapy is individualized and based on actors such as tumor type, stage, location, and size. Surgery includes radical vaginectomy, radical hysterectomy (or women with an intact uterus), and pelvic lymphadenectomy or most tumors located in the upper third o the vaginal vault. However, concurrent chemotherapy with cisplatin can be considered to bene t those with locally advanced vaginal cancer because o its proven ef cacy in cervical cancer treatment. In a small series o vaginal cancer cases, adjuvant chemotherapy provided a 10- to 33-percent decline in the total radiation dose delivered (Dalrymple, 2004). Although not intending to show an improved survival rate with chemoradiation, the authors ound that local control o tumor growth and survival rates were comparable with those who had received higher radiation doses alone. Smaller total radiation doses may lead to lower rates o vaginal stenosis and stula ormation. Despite this increased use, the authors did not observe any survival advantage among those vaginal cancer patients who received chemoradiation compared with radiation alone (Ghia, 2011). Further, brachytherapy alone has been used success ully to treat selected small stage I lesions (Nori, 1983; Perez, 1999; Reddy, 1991). Radiation is generally recommended i negative margins cannot be achieved surgically due to tumor location or size or to patient comorbidities that preclude surgery. External beam radiation generally is given rst, and depending on tumor response, brachytherapy is tailored to remaining disease. As discussed subsequently, adjuvant chemotherapy is o ten administered during radiation therapy. Chemotherapy In general, chemotherapy alone is ine ective to treat vaginal cancer, although data are limited. Five o 16 patients with squamous cell carcinoma had stable disease, and 10 had cancer progression. Based on this trial, single-agent cisplatin is considered to have insigni cant activity at that dose and schedule (T igpen, 1986). Concurrent chemotherapy with cisplatin as a radiation sensitizer is generally also recommended. Radiation Therapy Radiation to the primary tumor usually involves pelvic external beam with or without brachytherapy, and o ten concurrent platinum-based sensitizing chemotherapy depending on the stage and other actors described above. Additionally, groin radiation is e ective in patients with palpable nodal metastases. The addition o bevacizumab to these chemotherapy combinations improved overall survival length by approximately 4 months in women with metastatic cervical cancer (ewari, 2014). C 698 Gynecologic Oncology Moreover, elective irradiation may be delivered to clinically negative inguinal lymph nodes i the distal third o the vagina is involved. In a retrospective review, Perez and colleagues (1999) ound that o 100 women who did not receive groin radiation, i disease was con ned to the upper two thirds o the vagina, then none developed groin metastases. However, 10 percent o patients with lower-third primary tumors and 5 percent with tumors involving the entire length o the vagina developed inguinal node metastases. Primary vaginal adenocarcinoma in general is more aggressive than squamous cell carcinoma. In one series o 30 patients, it was associated with local and metastatic relapse rates that were more than double those or squamous cell carcinoma (Chyle, 1996). Despite this, an estimated 1 to 4 million women used this synthetic estrogen and approximately 0. The median age at diagnosis o vaginal clear cell carcinoma in the United States is 19 years. However, in the Netherlands, a bimodal distribution o vaginal clear cell carcinoma has been observed-the rst peak occurring with a mean age o 26 years and the second at 71 years. The 5-year survival rate or 219 women with stage I vaginal clear cell adenocarcinoma was 92 percent and was equivalent regardless o therapy mode (Senekjian, 1987). T us, patients are typically examined every 3 months or the rst 2 years and then every 6 months until 5 years o surveillance is completed (Pingley, 2000; Rubin, 1985). A Pap smear and pelvic examination with care ul attention to the inguinal and scalene nodes are per ormed. Recurrent Disease Disease recurrence should be con rmed by biopsy i urther treatment is planned. T erapeutic options in women with central pelvic recurrence who have had prior pelvic radiation are limited. There ore, clinicians are alert to the triad o sciatic pain, leg edema, and hydronephrosis, which suggests pelvic sidewall disease. These women are not surgical candidates but can be managed with chemoradiation or with chemotherapy alone or women previously irradiated. In a review o 301 patients, 5-year survival was 20 percent or local recurrence and 4 percent or metastatic disease recurrence (Chyle, 1996). Histologic types include clear cell, endometrioid, mucinous, and serous carcinoma, and these may arise in endometriosis oci, in areas o vaginal adenosis, in periurethral glands, or in wolf an duct remnants. Adenosis in the vagina is de ned by subepithelial glandular structures lined by mucinous columnar cells that resemble endocervical cells (Sandberg, 1965). Clinically, adenosis appears as red granular spots or patches and does not stain ollowing Lugol solution application. More commonly, vaginal adenocarcinoma is metastatic disease, typically rom a lesion higher in the genital tract. Disease is requently metastatic rom the endometrium, although it also may originate rom the cervix or ovary (Saitoh, 2005). In addition, adenocarcinoma metastases rom the breast, pancreas, kidney, and colon also have been identi ed in the vagina. This rare tumor develops almost exclusively in girls younger than 5 years, although vaginal and cervical sarcoma botryoides have been reported in emales aged 15 to 20 years (Copeland, 1985). In in ants and children, sarcoma botryoides usually is ound in the vagina; in reproductiveaged women, within the cervix; and a ter menopause, within the uterus. Its name, derived rom the Greek word botrys, which means "bunch o grapes," describes its appearance. The most common site is the vulva (70 percent), ollowed by the vagina (21 percent) and the cervix (9 percent) (Miner, 2004). The most requent presenting symptoms include vaginal bleeding, discharge, and vaginal mass. Vaginal melanoma is o ten detected late, and this may be largely responsible or poor treatment outcomes. With a reported 5-year survival rate ranging rom 10 to 20 percent, the prognosis is among the worst o vaginal malignancies (Ragnarsson-Olding, 1993; Weinstock, 1994; Xia, 2014). Cutaneous melanomas at other body sites are staged by microstaging systems, including the Chung, the Clark, and the Breslow systems, which use criteria such depth o invasion, tumor size, and tumor thickness (Chap. However, Clark levels are not applicable to vaginal melanoma because the typical microscopic skin landmarks used are not present. Although some advocate radical surgery, including exenteration, growing evidence shows that wide local excision has similar survival rates and less morbidity (Buchanan, 1998; Xia, 2014). Although this distinctive appearance may guide diagnosis, the classic histologic nding o this tumor is the rhabdomyoblast. Embryonal rhabdomyosarcomas have a poor prognosis, but sarcoma botryoides is the easiest to treat and has the best chance o cure. It has gradually shi ted away rom radical pelvic exenteration surgery and toward primary chemotherapy plus adjuvant conservative surgery to excise residual tumor (Andrassy, 1995, 1999; Hays, 1981, 1985). However, it makes up no more than 1 percent o vaginal malignancies, and only 140 cases have been described in the literature to date (Ahram, 2006; Khosla, 2014; Suh, 2008). Because o the small number o these tumors, their epidemiology has not been widely studied, and ew risk actors have been identi ed. However, patients previously treated with pelvic radiotherapy or cervical cancer appear to be at risk. A ected women most o ten complain o an asymptomatic vaginal mass, but other symptoms mirror those o their squamous cell counterpart. Any wall o the vagina may be a ected, but most tumors develop posteriorly (Ahram, 2006). However, some clinicians recommend adjuvant radiation or those with high-grade tumor or local recurrence (Curtin, 1995). One study demonstrated a survival bene t to the wide local excision approach (Frumovitz, 2010). However, because o their size or location, many vaginal melanomas are not amenable to this less radical approach. However, radiation therapy in one series was ound to provide local tumor control in women who had surgically unresectable disease (Miner, 2004). Ipilimumab is a monoclonal antibody that promotes -cell activation, which in turn produces antitumor e ects. Its use in patients with metastatic melanoma improves overall survival rates (Hodi, 2010). Int J Gynecol Cancer 21:378, 2011 Gupta D, Malpica A, Deavers M, et al: Vaginal melanoma: a clinicopathologic and immunohistochemical study o 26 cases. Am J Surg Pathol 26: 1450, 2002 Hanselaar A, van Loosbroek M, Schuurbiers O, et al: Clear cell adenocarcinoma o the vagina and cervix: an update o the central Netherlands registry showing twin age incidence peaks. J Pediatr Surg 20:718, 1985 Hellman K, Lundell M, Sil versward C, et al: Clinical and histopathologic actors related to prognosis in primary squamous cell carcinoma o the vagina. Am Soc Clin Oncol Educ Book 2014:e277, 2014 Melnick S, Cole P, Anderson D, et al: Rates and risks o diethylstilbestrolrelated clear-cell adenocarcinoma o the vagina and cervix: an update. N Engl J Med 316:514, 1987 Miner J, Delgado R, Zeisler J, et al: Primary vaginal melanoma: a critical analysis o therapy. Int J Gynecol Cancer 16:884, 2006 Alemany L, Saunier M, inoco L, et al: Large contribution o human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples. Gynecol Oncol 20:346, 1985 Saitoh M, Hayasaka, Ohmichi M, et al: Primary mucinous adenocarcinoma o the vagina: possibility o di erentiating rom metastatic adenocarcinomas. Gynecol Oncol 81:360, 2001 ran P, Su Z, Lee P, et al: Prognostic actors or outcomes and complications or primary squamous cell carcinoma o the vagina treated with radiation. Am J Obstet Gynecol 171:1225, 1994 Xia L, Han D, Yang W, et al: Primary malignant melanoma o the vagina. Risks speci cally or type I cancers are associated with an excess-estrogen environment. Excessive adipose tissue increases peripheral aromatization o androstenedione to estrone. In premenopausal women, elevated estrone levels trigger abnormal eedback in the hypothalamic-pituitary-ovarian axis. In the absence o ovulation, the endometrium is exposed to virtually continuous estrogen stimulation without subsequent progestational e ect and without menstrual withdrawal bleeding. Fortunately, the malignant potential o continuously administered estrogen was recognized more than three decades ago (Smith, 1975). Currently, it is rare to encounter a woman with a uterus who has taken unopposed estrogen or years. Menstrual and reproductive in uences are commonly associated with endometrial cancer.

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The ve subtypes o dif erentiation (well erectile dysfunction treatment garlic order himcolin 30 gm fast delivery, intermediate erectile dysfunction gel order himcolin on line amex, poor cheap erectile dysfunction pills uk order himcolin 30gm with mastercard, reti orm erectile dysfunction reasons best buy for himcolin, and heterologous) have considerable overlap erectile dysfunction doctor in dubai discount himcolin 30gm without prescription. Prognosis depends predominantly on the stage and degree o tumor dif erentiation in these malignant variants erectile dysfunction treatment vacuum pump buy 30gm himcolin with visa. 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). Secondary surgical debulking is strongly considered due to the indolent growth pattern, the typically long disease- ree interval a ter initial treatment, and the inherent insensitivity to chemotherapy (Crew, 2005; Powell, 2001). Platinum-based combination chemotherapy is the primary treatment chosen or recurrent disease with or without surgical debulking (Uygun, 2003). There is no standard treatment or women who have progressive disease despite aggressive surgery and platinum-based chemotherapy. Hormonal therapy is minimally toxic, but the clinical experience with this approach is extremely limited (Hardy, 2005). Further insights into its unction and downstream ef ects may identi y molecular alterations in these tumors that can be targeted (Kobel, 2009). Gynecol Oncol 99:764, 2005 Aoki Y, Kase H, Fujita K, et al: Dysgerminoma with a slightly elevated alphaetoprotein level diagnosed as a mixed germ cell tumor a ter recurrence. Gynecol Oncol 93:381, 2004 Billmire D, Vinocur C, Rescorla F, et al: Outcome and staging evaluation in malignant germ cell tumors o the ovary in children and adolescents: an intergroup study. O the clinical actors af ecting prognosis, surgical stage and residual disease are the most important (Lee, 2008; Zanagnolo, 2004). They concluded that age younger than 50 years was also an independent predictor o an improved survival rate. Am J Surg Pathol 28:1341, 2004 Cicin I, Saip P, Guney N, et al: Yolk sac tumours o the ovary: evaluation o clinicopathological eatures and prognostic actors. Eur J Obstet Gynecol Reprod Biol 146:210, 2009 Colombo N, Parma G, Zanagnolo V, et al: Management o ovarian stromal cell tumors. J Clin Oncol 25:2944, 2007 Corakci A, Ozeren S, Ozkan S, et al: Pure nongestational choriocarcinoma o ovary. Gynecol Oncol 95:695, 2004 Dos Santos L, Mok E, Iasonos A, et al: Squamous cell carcinoma arising in mature cystic teratoma o the ovary: a case series and review o the literature. Gynecol Oncol 83:400, 2001 East N, Alobaid A, Go n F, et al: Granulosa cell tumour: a recurrence 40 years a ter initial diagnosis. J Obstet Gynaecol Can 27:363, 2005 Elit L, Bocking A, Kenyon C, et al: An endodermal sinus tumor diagnosed in pregnancy: case report and review o the literature. Gynecol Oncol 72:131, 1999 Horbelt D, Delmore J, Meisel R, et al: Mixed germ cell malignancy o the ovary concurrent with pregnancy. Cancer Res 69:9160, 2009 Kollmannsberger C, Nichols C, Bokemeyer C: Recent advances in management o patients with platinum-re ractory testicular germ cell tumors. Gynecol Oncol 110:125, 2008 Kurihara S, Hirakawa, Amada S, et al: Inhibin-producing ovarian granulosa cell tumor as a cause o secondary amenorrhea: case report and review o the literature. Gynecol Oncol 37:417, 1990 Leblanc E, Querleu D, Narducci F, et al: Laparoscopic restaging o early stage invasive adnexal tumors: a 10-year experience. Chin Med J (Engl) 115:1496, 2002 Li J, Yang W, Wu X: Prognostic actors and role o salvage surgery in chemore ractory ovarian germ cell malignancies: a study in Chinese patients. Gynecol Oncol 105:769, 2007 Liu Q, Ding X, Yang J, et al: the signi cance o comprehensive staging surgery in malignant ovarian germ cell tumors. J Int Coll Surg 42:625, 1964 Malmstrom H, Hogberg, Risberg B, et al: Granulosa cell tumors o the ovary: prognostic actors and outcome. Gynecol Oncol 52:50, 1994 Marelli G, Carinelli S, Mariani A, et al: Sclerosing stromal tumor o the ovary: report o eight cases and review o the literature. J Clin Oncol 17:2137, 1999 Martin-Jimenez A, Condom-Munro E, Valls-Porcel M, et al: [Gynandroblastoma o the ovary: review o the literature. J Gynecol Obstet Biol Reprod (Paris) 23:391, 1994 McKenna M, Kenny B, Dorman G, et al: Combined adult granulosa cell tumor and mucinous cystadenoma o the ovary: granulosa cell tumor with heterologous mucinous elements. Gynecol Oncol 55:217, 1994 Murugaesu N, Schmid P, Dancey G, et al: Malignant ovarian germ cell tumors: identi cation o novel prognostic markers and long-term outcome a ter multimodality treatment. J Clin Oncol 24:4862, 2006 Nawa A, Obata N, Kikkawa F, et al: Prognostic actors o patients with yolk sac tumors o the ovary. Int J Gynecol Pathol 13:283, 1994 Okada I, Nakagawa S, akemura Y, et al: Ovarian thecoma associated in the rst trimester o pregnancy. Am J Surg Pathol 29:143, 2005 Oliva E, Andrada E, Pezzica E, et al: Ovarian carcinomas with choriocarcinomatous dif erentiation. Ultrasound Obstet Gynecol 15:365, 2000 Paladini D, esta A, Van Holsbeke C, et al: Imaging in gynecological disease (5): clinical and ultrasound characteristics in broma and brothecoma o the ovary. Ultrasound Obstet Gynecol 34:188, 2009 Palenzuela G, Martin E, Meunier A, et al: Comprehensive staging allows or excellent outcome in patients with localized malignant germ cell tumor o the ovary. Ann Surg 248:836, 2008 Pavlakis K, Messini I, Vrekoussis, et al: Intraoperative assessment o epithelial and non-epithelial ovarian tumors: a 7-year review. Am J Surg Pathol 20:823, 1996 Piura B, Nemet D, Yanai-Inbar I, et al: Granulosa cell tumor o the ovary: a study o 18 cases. N Engl J Med 360:2719, 2009 Sharony R, Aviram R, Fishman A, et al: Granulosa cell tumors o the ovary: do they have any unique ultrasonographic and color Doppler ow eatures Int J Gynecol Cancer 23(2):249, 2013 Shimizu Y, Komiyama S, Kobayashi, et al: Success ul management o endodermal sinus tumor o the ovary associated with pregnancy. Obstet Gynecol 87:737, 1996 Suita S, Shono K, ajiri, et al: Malignant germ cell tumors: clinical characteristics, treatment, and outcome. A report rom the study group or Pediatric Solid Malignant umors in the Kyushu Area, Japan. J Pediatr Surg 37:1703, 2002 akemori M, Nishimura R, Yamasaki M, et al: Ovarian mixed germ cell tumor composed o polyembryoma and immature teratoma. Gynecol Oncol 69:260, 1998 alukdar S, Kumar S, Bhatla N, et al: Neo-adjuvant chemotherapy in the treatment o advanced malignant germ cell tumors o ovary. Gynecol Oncol 132(1):28, 2014 angir J, Zelterman D, Ma W, et al: Reproductive unction a ter conservative surgery and chemotherapy or malignant germ cell tumors o the ovary. Obstet Gynecol 101:251, 2003 eilum G: Classi cation o endodermal sinus tumour (mesoblastoma vitellinum) and so-called "embryonal carcinoma" o the ovary. Mod Pathol 18 (Suppl 2):S61, 2005 Uygun K, Aydiner A, Saip P, et al: Clinical parameters and treatment results in recurrent granulosa cell tumor o the ovary. Chin Med J 117:1592, 2004 Zagame L, Pautier P, Duvillard P, et al: Growing teratoma syndrome a ter ovarian germ cell tumors. Am J Surg Pathol 8:405, 1984 Zanagnolo V, Pasinetti B, Sartori E: Clinical review o 63 cases o sex cord stromal tumors. Eur J Gynaecol Oncol 25:431, 2004 Zanetta G, Bonazzi C, Cantu M, et al: Survival and reproductive unction a ter treatment o malignant germ cell ovarian tumors. The outlook or preservation o ertility and or success ul subsequent pregnancy outcomes is equally bright (Vargas, 2014; Wong, 2014). Although historically higher incidence rates have been reported in parts o Asia, some o this disparity may re ect discrepancies between population-based and hospital-based data collection (Chong, 1999; Kim, 2004; Matsui, 2003). Improved socioeconomic conditions and dietary changes may be partly responsible as well. T at said, certain Southeast Asian populations as well as Hispanics and Native Americans living in the United States do have increased incidences (Drake, 2006; Smith, 2003; T am, 2003). This association is much greater or complete moles, whereas the risk o partial molar pregnancy varies relatively little with age. Moreover, compared with the risk in those aged 15 years or younger, the degree o risk is much greater or women 45 years (1 percent) or older (17 percent at age 50) (Savage, 2010; Sebire, 2002a). One explanation relates to ova rom older women having higher rates o abnormal ertilization. Similarly, older paternal age has been associated with increased risk (La Vecchia, 1984; Parazzini, 1986). For example, previous spontaneous abortion at least doubles the risk o molar pregnancy (Parazzini, 1991). The requency in a subsequent conception is approximately 1 percent, and most cases mirror the same type o mole as the preceding pregnancy (Garrett, 2008; Sebire, 2003). Furthermore, ollowing two episodes o molar pregnancy, 23 percent o later conceptions result in another molar gestation (Berkowitz, 1998). These tumors require ormal staging and typically respond avorably to chemotherapy. These moles classically have swollen enlarged villi, some of which show cistern formation, that is, central cavitation within the large villi (black asterisks). Complete moles also typically show trophoblastic proliferation (yellow asterisk), which may be focal or widespread. Normal term placenta showing smaller, nonedematous villi and absence of trophoblastic proliferation. Many o these associations, however, are weak and could be explained by con ounding actors other than causality (Parazzini, 2002). Some epidemiologic characteristics di er markedly between complete and partial moles. For example, vitamin A de ciency and low dietary intake o carotene are associated only with an increased risk o complete moles (Berkowitz, 1985, 1995; Parazzini, 1988).