David J. Weitz, MD

• Chief, Ultrasound Imaging
• David Grant USAF Medical Center
• Travis AFB, California

Factors predictive of distant metastases in patients with breast cancer who have a pathologic complete response after neoadjuvant chemotherapy erectile dysfunction medicine by ranbaxy purchase himcolin 30gm with visa. While the histologic presence of invasive carcinoma invading dermal lymphatics is supportive of the diagnosis erectile dysfunction treatment implant video effective 30gm himcolin, it is not required erectile dysfunction age 18 30 gm himcolin fast delivery, nor is dermal lymphatic invasion without typical clinical findings sufficient for a diagnosis of inflammatory breast cancer impotence 24-year-old purchase himcolin 30 gm with visa. Confirmation of clinically detected metastatic disease by fine needle aspiration without excision biopsy is designated with an (f) suffix impotence quitting smoking 30 gm himcolin with amex, for example erectile dysfunction at age 21 purchase 30 gm himcolin mastercard, cN3a(f). Excisional biopsy of a lymph node or biopsy of a sentinel node, in the absence of assignment of a pT, is classified as a clinical N, for example, cN1. Information regarding the confirmation of the nodal status will be designated in sitespecific factors as clinical, fine needle aspiration, core biopsy, or sentinel lymph node biopsy. Pathologic classification (pN) is used for excision or sentinel lymph node biopsy only in conjunction with a pathologic T assignment. If the surgical procedure is not performed, the administered therapy no longer meets the definition of neoadjuvant therapy. Gynecologic Sites 377 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. Changes to the staging classification reflect a belief that tumor size independent of other factors (spread to adjacent structures, nodal metastases) is less important in predicting survival. For pN, histologic examination of regional lymphadenectomy specimens will ordinarily include six or more lymph nodes. The concept of sentinel lymph node mapping where only one or two key nodes are removed is currently being investigated. In most cases, a surgical assessment of regional lymph nodes (inguinal-femoral lymphadenectomy) is performed. The current revisions to staging adopted reflect a recognition that the number and size of lymph node metastases more accurately reflect prognosis. Vulva 379 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. The metastatic sites include any site beyond the area of the regional lymph nodes. Tumor involvement of pelvic lymph nodes, including internal iliac, external iliac, and common iliac lymph nodes, is considered distant metastasis. Cases should be classified as carcinoma of the vulva when the primary site of the growth is in the vulva. Tumors present on the vulva as secondary growths from either a genital or an extragenital site should be excluded. Stage should be assigned at the time of definitive surgical treatment or prior to radiation or chemotherapy if either of these is the initial mode of therapy. The stage cannot be changed on the basis of disease progression or recurrence or on the basis of response to initial radiation or chemotherapy that precedes primary tumor resection. Surgical-pathologic staging provides specific information about primary tumor size and lymph node status, which are the most important prognostic factors in vulvar cancer. Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis. Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Prognostic significance of lymph node variables in squamous cell carcinoma of the vulva. Extracapsular growth of lymph node metastases in squamous cell carcinoma of the vulva. The vagina is drained by lymphatics toward the pelvic nodes in its upper two-thirds and toward the inguinal nodes in its lower third. The most common sites of distant spread include the aortic lymph nodes, lungs, and skeleton. Cases should be classified as carcinoma of the vagina when the primary site of the growth is in the vagina. Tumors present in the vagina as secondary growths from either genital or extragenital sites should not be included. A growth that involves the cervix, including the external os, should always be assigned to carcinoma of the cervix. Tumor involving the vulva and extending to the vagina should be classified as carcinoma of the vulva. The results of biopsy or fine-needle aspiration of inguinal/femoral or other nodes may be included in Vagina 387 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. In addition to data used for clinical staging, information available from examination of the resected specimen, including pelvic and retroperitoneal lymph nodes, is to be used. On rectal examination, there is no cancer-free space between the tumor and pelvic wall. Approximately 10% of vaginal cancers are adenocarcinoma; melanoma and sarcoma occur rarely. A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Through the cervix runs the endocervical canal, which is the passageway connecting the vagina with the uterine cavity. The vaginal portion of the cervix, known as the exocervix, is covered by squamous epithelium. The squamocolumnar junction is usually located at the external cervical Cervix Uteri 395 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. Cancer of the cervix may originate from the squamous epithelium of the exocervix or the glandular epithelium of the canal. The cervix is drained by parametrial, cardinal, and uterosacral ligament routes into the following regional lymph nodes: Parametrial Obturator Internal iliac (hypogastric) External iliac Common iliac Sacral Presacral For pN, histologic examination of regional lymphadenectomy specimens will ordinarily include six or more lymph nodes. The following examinations are recommended for staging purposes: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton. Suspected involvement of the bladder mucosa or rectal mucosa must be confirmed by biopsy and histology. The results of these additional examinations or procedures may not be used to determine clinical staging because these techniques are not universally available. They may, however, be used to develop a treatment plan and may provide prognostic information. When nodal metastases are identified it is important to identify the extent of nodal involvement (pelvic lymph nodes and/or para-aortic lymph nodes) and the methodology by which the diagnosis was established (pathologic or radiologic). The most common sites of distant spread include the paraaortic and mediastinal nodes, lungs, peritoneal cavity, and skeleton. Mediastinal or supraclavicular node involvement is considered distant metastasis and is coded M1. These findings should not be allowed to change the clinical staging but should be recorded in the manner described for the pathologic staging of disease. Infrequently, hysterectomy is carried out in the presence of unsuspected invasive cervical carcinoma. Such cases cannot be clinically staged or included in therapeutic statistics; they should be reported separately. In addition to extent or stage of disease, prognostic factors include histology and tumor differentiation. Small cell, neuroendocrine, and clear cell lesions have a worse prognosis, as do poorly differentiated cancers. Because many patients with cervical cancer are treated by radiation and never undergo surgicalpathologic staging, clinical staging of all patients provides uniformity and is therefore preferred. The clinical stage must not be changed because of subsequent findings once treatment has started. When there is doubt about to which stage a particular cancer should be allocated, the lesser stage should be utilized. Careful clinical examination should be performed in all cases, preferably by an experienced examiner and with the patient under anesthesia. Vascular space involvement, venous or lymphatic, does not affect classification Measured stromal invasion 3. Cervix Uteri 397 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. A survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer. Tumor size, irradiation dose, and long-term outcome of carcinoma of uterine cervix. T3b lesions reflect regional extension of disease and include extension of the tumor through the myometrial wall of the uterus into the parametrium and/or extension/metastatic involvement of the vagina. The upper two-thirds of the uterus above the level of the internal cervical os is referred to as the uterine corpus. The oviducts (fallopian tubes) and the round ligaments enter the uterus at the upper and outer corners (cornu) of the pear-shaped organ. The portion of the uterus that is above a line connecting the tubo-uterine orifices is referred to as the uterine fundus. Tumor involvement of the cervical stroma is prognostically important and affects staging (T2). The location of the tumor must be carefully evaluated and recorded by the pathologist. The depth of tumor invasion into the myometrium is also of prognostic significance and should be included in the pathology report. Involvement of the ovaries by direct extension or metastases, or penetration of tumor to the uterine serosa is important to identify and classify the tumor as T3a. Malignant cells in peritoneal cytology samples have been documented in approximately 10% of cases of presumed uterine confined endometrial cancer cases. The regional lymph nodes are paired and each of the paired sites should be examined. The regional nodes are as follows: Obturator Internal iliac (hypogastric) External iliac Common iliac Para-aortic Presacral Parametrial For adequate evaluation of the regional lymph nodes, a representative evaluation of bilateral para-aortic and pelvic lymph nodes (including external iliac, internal iliac, and obturator nodes) should be documented in the operative and surgical pathology reports. Parametrial nodes are not commonly detected unless a radical hysterectomy is performed for cases with gross cervical stromal invasion. When there are insufficient surgical-pathologic findings, the clinical cT, cN, cM categories should be used on the basis of clinical evaluation. Intra-abdominal metastases to peritoneal surfaces or the omentum are seen particularly with serous and clear cell tumors. Palpation of regional nodes is well recognized to be much less accurate than pathologic evaluation of the nodes. Historically, the factors of grade of the tumor and depth of myometrial invasion have been recognized as important prognostic factors. In surgically staged patients, using multivariate analysis, these factors are surrogates for the probability of nodal metastasis. Preoperative endometrial biopsy does not accurately correlate with tumor grade and depth of myometrial invasion. The presence or absence of lymphovascular space involvement of the myometrium is important in most, but not all, series. When present, lymphovascular space involvement increases the probability of metastatic involvement of the regional lymph nodes. The presence or absence of lymphovascular space involvement should be recorded in the pathology report. The importance of tumor cells in peritoneal "washings" and the presence of metastatic foci in adnexal structures may have an adverse impact on prognosis, but they remain controversial and require further study. Serous papillary and clear cell adenocarcinomas have a higher incidence of extrauterine disease at detection than endometrioid adenocarcinomas. The risk of extrauterine disease does not correlate with the depth of myometrial invasion, because nodal or intraperitoneal mestastases can be found even when there is no myometrial invasion. In malignancies with squamous elements, the aggressiveness of the tumor seems to be related to the degree of differentiation of the glandular component rather than the squamous element. Clinicopathologic and immunohistochemical studies support classifying malignant mixed mesodermal tumors as high-grade (G3) malignancies of epithelial origin rather than as sarcomas with mixed epithelial and mesenchymal differentiation, as in earlier classification systems. If the surgeon feels that systematic regional lymph node sampling imposes an unfavorable riskto-benefit ratio, clinical assessment of the pertinent node groups (obturator, para-aortic groups, internal iliac, common iliac, and external iliac) should be performed and specifically annotated in the operative report and recorded as cN. Stage should be assigned at the time of definitive surgical treatment or prior to radiation or chemotherapy if those are the initial modes of therapy. The stage should not be changed on the basis of disease progression or recurrence or on the basis of response to initial radiation or chemotherapy that precedes primary tumor resections. Ideally, the depth of myometrial invasion (in millimeters) should be recorded, along with the thickness of the myometrium at that level (recorded as a percentage of myometrial invasion). The presence of carcinoma in the regional lymph nodes is a clinically critical prognostic variable. Multiple studies have confirmed the inaccuracy of clinical assessment of regional nodal metastasis in many anatomic sites. For this reason, surgical/pathologic assessment of the regional lymph nodes is strongly advocated for all patients with corpus uteri cancer. That distinction can best be made by histologic verification of clinically suspicious cervical involvement or histopathologic examination of the removed uterus. The pT, pN, and pM categories correspond to the T, N, and M categories and are used to designate cases where ade- 36 Corpus Uteri 405 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. It excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa) Uterine Carcinomas Carcinosarcomas should be staged as carcinoma. Notable nuclear atypia, which exceeds that which is routinely expected for the architectural grade, increases the tumor grade by 1. Serous, clear cell, and mixed mesodermal tumors are high risk and considered Grade 3. Adenocarcinomas with benign squamous elements (squamous metaplasia) are graded according to the nuclear grade of the glandular component.

For school-aged children and adults impotence due to diabetes buy himcolin 30 gm without a prescription, there are difficulties in learning academic skills involving reading erectile dysfunction 60 buy discount himcolin 30 gm on-line, writing erectile dysfunction keeping it up himcolin 30gm cheap, arithmetic erectile dysfunction pills comparison discount 30gm himcolin mastercard, time erectile dysfunction quad mix buy 30 gm himcolin fast delivery, or money erectile dysfunction drugs india cheap himcolin 30gm, with support needed in one or more areas to meet age-related expectations. There is a somewhat concrete approach to problems and solutions compared with age mates. For school-aged children, progress in reading, writing, mathematics, and understanding of time and money occurs slowly across the school years, and is markedly limited compared with that of peers. For adults, academic skill development is typically at an elementary level, and support is required for all use of academic skills in work and personal life. Ongoing assistance on a daily basis is needed to complete conceptual tasks of day-to-day life, and others may take over these responsibilities fully for the individual. Communication, conversation, and language are more concrete or immature than expected for age. There may be difficulties regulating emotion and behavior in age-appropriate fashion; these difficulties are noticed by peers in social situations. There is limited understanding of risk in social situations; social judgment is immature for age, and the person is at risk of being manipulated by others (gullibility). The individual shows marked differences from peers in social and communicative behavior across development. Spoken language is typically a primary tool for social communication, but is much less complex than that of peers. Capacity for relationships is evident in ties to family and friends, and the individual may have successful friendships across life and sometimes romantic relations in adulthood. Social judgment and decision-making abilities are limited, and caretakers must assist the person with life decisions. Friendships with typically developing peers are often affected by communication or social limitations. Significant social and communicative support is needed in work settings for success. The individual generally has little understanding of written language or of concepts involving numbers, quantity, time, and money. Social Domain Spoken language is quite limited in terms of vocabulary and grammar. Speech may be single words or phrases, and may be supplemented through augmentative means. Relationships with family members and familiar others are a source of pleasure and help. The individual has very limited understanding of symbolic communication in speech or gesture. The individual expresses his or her own desires and emotions largely through nonverbal, nonsymbolic communication. The individual enjoys relationships with well-known family members, caretakers, and familiar others, and initiates and responds to social interactions through gestural and emotional cues. Profound Conceptual skills generally involve the physical world rather than symbolic processes. The individual may use objects in goal-directed fashion for self-care, work, and recreation. However, co-occurring motor and sensory impairments may prevent functional use of objects. Classification is based on physiologic and topographic characteristics as well as severity(Table9. Restricted repetitive patterns of behavior, interests, or activities Examples:Simplemotorstereotypies(handflapping,finger flicking),repetitiveuseofobjects(spinningcoins,lininguptoys), repetitivespeech(echolalia),resistancetochange,unusual sensoryresponses iii. Entitlesallchildrenwithqualifyingdisabilitiestoafree and appropriate public education inthe least restrictive environment. Surveillance for mental health issues should occur at all routine well-child visits from early childhood through adolescence,including historyofmoodsymptomsandanybehavioralissues. Commoncomorbidconditions:Disruptivebehaviordisorders,mood disorders,anxietydisorders Chapter 9 Development, Behavior, and Mental Health 251 2. Identifying infants and young children with developmental disorders in the medical home: an algorithm for developmental surveillance and screening. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Evidence report: genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. Draft Recommendation Statement: Autism Spectrum Disorder in Young Children: Screening. Naturalistic developmental behavioral interventions: empirically validated treatments for autism spectrum disorder. Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children- United States, 2003 and 2007. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003-2011. Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management, Wolraich M, Brown L, et al. Practice parameter for the assessment and treatment of children and adolescents with attentiondeficit/hyperactivity disorder. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. The use of medication in treating childhood and adolescent depression: information for physicians. Prepared by the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry. Clinical report-identification and management of eating disorders in children and adolescents. Practice parameter for the assessment and treatment of children and adolescents with substance use disorders. Effectiveness of motivational interviewing interventions for adolescent substance use behavior change: a meta-analytic review. However, serum K levels may be normal or elevated as a result of the shift of K to the extracellular compartment in the setting of acidosis. Collaboration from the Scottish Preterm Thyroid Group: Developmental trends in cord and postpartum serum thyroid hormones in preterm infants. Serum thyroid hormone levels in healthy children from birth to adulthood and in short children born small for gestational age. Hashimoto thyroiditis (diagnosis supported by presence of antithyroglobulin or antimicrosomal antibodies). Some infants may be relatively asymptomatic if the cause is other than absence of the thyroid gland. In this population, lower levels are associated with increased illness; however, the effect of replacement therapy remains controversial. The definition and consequences of vitamin D deficiency and insufficiency is an evolving field. Screening for congenital adrenal hyperplasia: adjustment of 17-hydroxyprogesterone cut-off values to both age and birth weight markedly improves the predictive value. To determine dose of a given steroid based on desired cortisol dose, divide desired hydrocortisone dose by corresponding number in the column. Signsandsymptoms(includingrapidweightgainwithcentral obesity,buffalohump,moonface,striae,thinningofskinandother Chapter 10 Endocrinology 273 membranes,hypertension)associatedwithelevatedcortisollevelsand overexposuretoglucocorticoids(eitherendogenousorexogenous). Abnormal Clinical evaluation suggests the possibility of a syndrome associated with an abnormal chromosome pattern. Chronic disease Clinical evaluation reveals evidence of chronic illness, short stature, or a decreased growth rate. Clinical findings in a neonate suspicious for ambiguous genitalia: (1) Anogenitalratio(distancebetweenanusandposteriorfourchette dividedbydistancebetweenanusandbaseofphallus)>0. Chapter 10 Endocrinology 287 (2) Hypoglycemiawithmidlinedefectsandmicropenisinamale suggesthypopituitarism,supportedbylowserumlevelsofgrowth hormoneandcortisolatthetimeofhypoglycemia. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. European Society for Pediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Developmental trends in cord and postpartum serum thyroid hormones in preterm infants. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics. American Academy of Pediatrics, Committee on Genetics, Sections on Endocrinology and Urology. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Standard of care or the health of transsexual, transgender, and gender- nonconforming people [Version 7]. Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline. Some basic principles should be followed whether providing enteral or parenteral fluids. Appropriate fluid management involves the calculation and administration of water volume and electrolyte concentration of: A. One should always strive to treat the underlying etiology of a fluid or electrolyte abnormality, rather than responding to scenarios or laboratory values in a rote manner. Metabolism creates two byproducts, heat and solute, that must be eliminated to maintain homeostasis. The amount of heat dissipated through insensible fluid losses and the amount of solute excreted in bodily fluids are directly related to caloric expenditure. The metabolic rate per kg body weight declines with age; an infant generates significantly more solute and heat per kg than a child or an adolescent. To accurately calculate maintenance needs, it is necessary to determine caloric expenditure. Maintenance Volume: Caloric Calculations There are three basic methods to calculate maintenance fluid volume needs: 1. Basal calorie method: Useful for all ages, types of body habitus, and clinical states a. In general, it overestimates fluid needs in neonates compared with the basal calorie method. For the purposes of fluid calculation, fluid lost via insensible losses through the skin and respiratory tract can be considered electrolytefree. Urine represents the primary source of electrolyte loss, with variability based on renal ability to dilute and concentrate. Cautions regarding hypotonic fluid administration: Although 3 mEq of Na+ per 100 mL of water should be sufficient to maintain basic sodium needs, there is overwhelming evidence that administration of hypotonic fluids to hospitalized children can lead to hyponatremia. These children may also have prior or ongoing losses of water and electrolytes that make them unsuitable candidates for mere "maintenance" fluid replacement. Their clinical context requires further volume and electrolyte deficit calculations, and appropriate adjustment of replacement fluids in their management (Tables 11. Clinical assessment: If weight loss is not known, clinical observation may be used (Table 11. For example, hyponatremia exaggerates instability, and hypernatremia maintains intravascular volume at the expense of intracellular volume. Solute Deficit: Hyponatremic Dehydration (Hyponatremic Hypovolemia) Although there is a vast differential for hyponatremia (see Section V.

One to three extremely painful ulcers erectile dysfunction treatment seattle himcolin 30gm free shipping, accompanied by tender inguinal lymphadenopathy erectile dysfunction from a young age 30 gm himcolin sale, are unlikely to be anything except chancroid impotence xanax purchase 30gm himcolin with mastercard. Recurrences more often result from reactivation of subclinical infection than reinfection by a sexual partner;therefore erectile dysfunction age 22 purchase himcolin 30 gm without prescription,examinationofsexualpartnersisnotabsolutelynecessary erectile dysfunction treatment uk himcolin 30 gm amex. However erectile dysfunction generic buy cheap himcolin 30gm, many partners may have external genital warts and may benefit from therapy and counseling concerningtransmissionofwarts. The warts tend to occur in areas most directly affectedbycoitus,namelytheposteriorfourchetteand lateralareasofthevulva. Minortraumaassociatedwithcoituscancause breaks in the vulvar skin, allowing direct contact betweentheviralparticlesfromaninfectedmanand the basal layer of the epidermis of his susceptible sexual partner. The goal of treatment is removal of the warts; it is not possible to eradicate the viral infection. Treatment is most successful in patients with small warts thathavebeenpresentforlessthan1year. Several factors increase the risk for cystitis, including sexual intercourse, the use of a diaphragm and a spermicide, delayed postcoital micturition, and a history of a recent urinary tract infection. Escherichia coli is present in the urine of 80% of young women with acute cystitisandStaphylococcus saprophyticus is present in an additional 5-15% of patients. The pathophysiology of cystitis in women involves the colonization of the vagina and urethra withcoliformbacteriafromtherectum. Forthisreason, the effects of an antimicrobial agent on the vaginal floraplayaroleintheeradicationofbacteriuria. High concentrations of trimethoprim and fluoroquinolone in vaginal secretions can eradicate E. Nitrofurantoin (macrocrystals, 100mg orally twice daily for 5 days) or trimethoprim-sulfamethoxazole (160/800mg orally twice daily for 3 days) are the optimal choices for empirical therapy for uncomplicated cystitis. In patients with typical symptoms, an abbreviated laboratory workup followed by empirical therapy is recommended. The diagnosis can be presumed if pyuriaisdetectedbymicroscopyorleukocyteesterase C H A P T E R 22 Infectious Diseases of the Female Reproductive and Urinary Tract 285 testing. Urine culture is not necessary, and a short course of antimicrobial therapy should be given. Recurrent cystitis should be documented by culture to rule out resistant microorganisms. Patientsmaybetreatedby oneofthreestrategies:(1)continuousprophylaxis,(2) postcoital prophylaxis, or (3) therapy initiated by the patientwhensymptomsarefirstnoted. Approximately 75% of infected women require augmentation of labor with oxytocin, and approximately 35% require cesarean delivery, usually because of arrest of progress in labor. Manyofthesemicroorganisms(especiallyanaerobicbacteria,themycoplasmas, and Gardnerella vaginalis) are associated with bacterialvaginosis. Maternal and fetal tachycardia are common with fever and add little additional information. Uterine tenderness is often obscured by conduction anesthesia, and foul-smelling amniotic fluid is rare. Maternal white blood cell counts increase with durationoflabor,butnoreliablebreakpointhasbeenestablishedtoreliablydistinguishfeverfrominfectiousand noninfectiouscauses. Physicalexaminationmayrevealthe presence of mucopurulent cervicitis or vulvovaginal herpetic lesions. A urine culture should be obtained inallwomenwithsuspectedpyelonephritis;bloodculturesshouldbeperformedinthosewhoarehospitalized,becauseresultsarepositivein15-20%ofcases. In theabsenceofnauseaandvomitingandsevereillness, outpatient oral therapy can be given safely. Pyelonephritis in a pregnant patient can cause premature labor and preterm delivery if not treated promptly. Outpatient treatment regimens include trimethoprim-sulfamethoxazole(160/800mgevery12hours for 14 days) or a quinolone. Inpatienttreatmentregimensinclude theuseofparenterallevofloxacin(750mgdaily),ceftriaxone(1to2gdaily),ampicillin(1gevery6hours), andgentamicin(especiallyifEnterococcusspeciesare suspected) or aztreonam (1g every 8 to 12 hours). Improved neonatal and maternal outcome is noted when antibiotic therapy is begun intrapartum rather than immediately postpartum. Delivery of the fetus and placenta removes the sites of infection, much like draininganabscess,makingthisinterventionasignificantpartoftherapy. This regimenis sufficienttotreatthemotherifthedeliveryisvaginalwith only one additional dose of the antibiotic regimen needed postpartum. If cesarean delivery is required, up to 15% of patients given only ampicillin and gentamicin will develop postpartum endometritis. Although delivery is essential for cure, no critical diagnosis-to-delivery interval has been identified. Accordingly, labor must be managed actively, but cesarean delivery should be performed only for acceptedobstetricindications. Thepathogenesisofthisinfectioninvolves inoculation of the amniotic fluid after membrane ruptureorduringlaborwithvaginalmicroorganisms. The myometrium, leaves of the broad ligament, and theperitonealcavityarethenexposedtothiscontaminatedfluidduringcesareansurgery. Risk factors for postcesarean endomyometritis include prolonged labor or rupture of the membranes, presence of bacterial vaginosis, frequent vaginal examinations, and use of internal fetal monitoring. When given before the skin incision rather than after cord clamping, the incidence of postcesarean endomyometritis and total infectious morbidities are decreased, without adversely affecting neonatal out- comes. It is characterized by early onset and rapid progression, with few localizing symptoms or physical signs. Other consistently associated findings are lower abdominal pain, uterine tenderness, and leukocytosis. These women may also exhibit a delayed postoperative return of bowel function due to an associated local peritonitis. Antimicrobial regimens used in the treatment of postcesarean endometritis should provide satisfactory coverage of penicillin-resistant anaerobic microorganisms. Parenteral therapy should be continued until the temperaturehasremainedlowerthan37. If fever persists despite apparently appropriate antimicrobial therapy,thedifferentialdiagnosisincludesawoundor pelvic abscess, refractory postpartum fever, and noninfectiousfever. Appropriate imaging studies, usually pelvic ultrasonographyorcomputedtomography,may confirm the presence of a wound or pelvic hematoma or abscess. Pelvic collections usually involve the space between theloweruterinesegmentandbladder. Risk factors include greater duration of pregnancy, technical difficulties with the procedure, and the unsuspected presence of sexually transmitted pathogens or bacterial vaginosis. Symptoms include fever, chills, abdominal pain, and vaginal bleeding, often withthepassageofplacentaltissue. Physical findings include an elevated temperature, tachycardia, tachypnea, and abdominal tenderness. Along with bacteremia, hypotension and frank shock mayoccur,andthepatientmaybeagitatedanddisoriented. Pelvicexaminationrevealsasanguinopurulent discharge and uterine tenderness, with or without adnexalandparametrialtenderness. It is important to inspect for cervical or vaginal lacerations, especially with a suspected illegal abortion. Transvaginal ultrasonography can assess the intrauterine cavity for the presenceofretainedproductsofconception,suggestingtheneedforuterinecurettage. Table 22-8 contains the firstline antibiotic regimen for women with suspected sepsis. Surgical removal of infected tissue is essential in all but the mildest of postabortal infections. Indications for laparotomy and possible hysterectomy include failure to respond to uterine evacuation and appropriate medical therapy, perforation and infection with suspected bowel injury, pelvic or adnexal abscess, and clostridial necrotizing myonecrosis (gas gangrene). Avoidance of unwanted pregnancies by making contraceptives widely available is the most important preventive measure (see Chapter 27). Fetal infection may occur and is most likely if maternal infection occurs in the third trimester. Chronic active hepatitis is associated with an increased risk of prematurity, low birth weight, and neonatal death. Maternalprognosisisverypoorifthe disease is complicated by cirrhosis, varices, or liver failure. Household members and sexual contacts should be tested and offered vaccination if they are susceptible. Transmission to the infant is believed to occur by direct contact during delivery. Therefore the newborn should be givenhepatitisimmuneglobulinandhepatitisvaccine soonafterdelivery,whichwillreducetheriskofinfectiontolessthan10%. The Centers for Disease Control and Prevention has also recommended that all children receive vaccination againsthepatitisB. Treatment during pregnancy, however, has not been adequately studied and all treatment (for pregnant and nonpregnant women) is evolving. C H A P T E R 22 Infectious Diseases of the Female Reproductive and Urinary Tract 289 Toxoplasmosis Toxoplasmosis is caused by an obligate intracellular protozoanorganismToxoplasma gondii. Householdcats may play a role in contaminating soil, which is then transferred to a litter box in the house. The infection is usually without symptoms in the mother, but when symptoms do occur they involve fever, rash, and fatigue. This infection can result in an enlarged placenta and fetal hepatomegalyandascites. Routine screening is not recommended because of the relatively rare occurrence with the following preventive activities encouraged: avoidanceofraworundercookedmeatoreggs;washing fruitsandvegetables;avoidanceofcatlitterwhenpregnant; and keeping household cats away from outside (potentiallycontaminated)soil. Pregnant women who are affected are usually exposed to children with the infection. The highest rate of transmission is in the third trimester but the severity of fetal effects is highest in the first trimester. The "blueberry muffin baby" has been described withtheappearancecausedbynumerouspetechiaeon the skin. Ganciclovir and valacyclovir have been used in nonpregnant women and in neonates after birth. Gravidas with a history of genital herpes should receive antiviral prophylaxis during the third trimester. The neonatal effects may be severe and are due to exposure to the virus in utero or during delivery. The complications of disseminated neonatal disease are seizures, tremors, poor feeding, and bulging fontanelles. Up to 30% of newborns may die, with more than 50% having neurological damage despite antiviraltherapy. Vaccination has reduced the rate of infection in pregnant women with a reported incidence of <0. Rubella spreads by respiratory droplets, and has an incubation period of 2 to 3 weeks. The symptoms are malaise and myalgia in the presence of a nonpruritic, maculopapular, reddishrash. Deafness,retinopathies, and central nervous system and cardiac malformations are the most common teratogenic manifestations. The transmission is via contaminated urine, blood, saliva, semen, or cervical secretions. As the pregnancy advances, the frequency of infection increasesandtheseverityoffetalinfectiondecreases. Repeat testing is recommended in the third trimester (at 28 to 32 weeks) and again at deliveryinwomenwhoareathighriskforsyphilis,or thosewhohadapositivescreeningtestinthefirsttrimester. In those patients with a history of penicillinallergy, a penicillin skin test to check that a genuine allergy exists should be offered. If the penicillin skin test is negative, treatment with penicillin should proceed. Patients who have a positive penicillin skin test should be desensitized and treated with penicillin, becausetherisksassociatedwithsyphilisduringpregnancy outweigh the risks of inpatient treatment of a penicillinallergy. Defectsof vaginalsupportincludeanteriorvaginalprolapse(cystocele), posterior vaginal prolapse (rectocele and enterocele), and apical uterine prolapse. Surgicalprocedures include anterior and posterior repairs (colporrhaphy)usingexistingnaturaltissueandsyntheticmesh materials, vaginal vault suspension (colpopexy) for apical vaginal prolapse, and complete vaginal closure procedures (colpocleisis) for some women who no longerdesirecoitalfunction. Itisestimated thatasmanyas50%ofwomenhavesomeurinaryincontinence at some time during their lives. Overflowincontinenceandurinaryfistulasmayalsobe causes of involuntary passing of urine. An accurate knowledge of the anatomy of the female pelvic floor enables the student to understand pelvic organ prolapse and its management. This new certification process recognizes the importance of disorders of the female pelvic floor and the increased knowledge and skills necessary to evaluate andtreatthesedisorders. Normal Pelvic Anatomy and Supports Thebonypelvisactslikeabasket,supportingthemuscular attachments, pelvic organs, vessels, and nerves contained within it.

Ki-67 expression and patients survival in lung cancer: Systematic review of the literature with meta-analysis erectile dysfunction injections cost buy 30gm himcolin mastercard. Pathologic stage I non-small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: Clinicopathologic characteristics and prognosis erectile dysfunction doctors in maine himcolin 30 gm lowest price. The role of microvessel density on the survival of patients with lung cancer: A systematic review of the literature with meta-anslysis erectile dysfunction kidney disease cheap himcolin 30 gm free shipping. Prognostic significance of p53 alterations in patients with non-small cell lung cancer: A meta-analysis erectile dysfunction drugs from himalaya himcolin 30gm sale. Survival impact of epidermal growth factor receptor overexpression in patients with non-small cell lung cancer: A meta-analysis buy erectile dysfunction injections purchase himcolin 30gm without a prescription. Role of p53 as a prognostic factor for survival in lung cancer: A systematic review of the literature with a meta-analysis impotence with lisinopril generic himcolin 30 gm on line. World Health Organization Classification of tumours: Pathology and genetics of tumours of the lung, pleura, thymus and heart. Proposals for changes in the Mountain and Dresler mediastinal and pulmonary lymph node map. In a few patients, however, multiple cytopathologic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and is not an exudate. The most common risk factor for malignant mesotheliomas is previous exposure to asbestos. The latency period between the asbestos exposure and the development of malignant mesothelioma is generally 20 years or more. Although peritoneal mesotheliomas are thought to occur in individuals who have had more extensive exposure than those with pleural mesothelioma, there is no clearly documented relationship between the amount of asbestos exposure and the subsequent development of this neoplasm. However, this impression was probably related to the fact that most mesotheliomas are diagnosed when they are already at an advanced stage. Recent data indicate that the clinical and biological behavior of mesotheliomas is variable and that most mesotheliomas grow relatively slowly. However, their morphology ranges from a pure epithelial appearance to an entirely sarcomatoid or even desmoplastic one. Distinguishing the pleomorphic histology of mesotheliomas from that of other neoplasms can be difficult, especially for the pure epithelial mesotheliomas that may closely resemble metastatic adenocarcinoma. Therefore, confirmation of the histological diagnosis by immunohistochemistry and/or electron microscopy is essential. During the past 30 years, many staging systems have been proposed for malignant pleural mesothelioma. This system has been validated by several surgical reports, but will likely require revision in the future as further data in larger numbers of patients become available. The mesothelium covers the external surface of the lungs and the inside of the chest wall. It is usually composed of flat tightly connected cells no more than one layer thick. For pN, histologic examination of a mediastinal lymphadenectomy or lymph node sampling specimen will ordinarily include regional nodes taken from the ipsilateral N1 and N2 nodal stations. In addition, mesotheliomas often metastasize to lymph nodes not involved by lung cancers, most commonly the internal mammary and peridiaphragmatic nodes. Contralateral mediastinal and supraclavicular nodes may be available if a mediastinoscopy or node biopsy is also performed. Patient age, gender, symptoms (absence or presence of chest pain), and history of asbestos exposure are also cited in various studies as potential prognostic factors. Further analysis of these various factors in a large multicenter database is needed to determine their true prognostic validity. Advanced malignant pleural mesotheliomas often metastasize widely to uncommon sites, including retroperitoneal lymph nodes, the brain, and spine, or even to organs such as the thyroid or prostate. However, the most frequent sites of metastatic disease are the peritoneum, contralateral pleura, and lung. In some cases, complete N classification may not be possible, especially if technical unresectable tumor (T4) is found at thoracotomy which prevents access to both N1 and N2 lymph nodes. Desmoplastic In general, the pure epithelioid tumors are associated with a better prognosis than the biphasic or sarcomatoid tumors. Despite their bland histological appearance, desmoplastic tumors appear to have the worst prognosis. Symptoms and patientreported well being: Do they predict survival in malignant pleural mesothelioma Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. The pattern of lymph node involvement influences outcome after extrapleural pneumonectomy for malignant mesothelioma. Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center. The impact of lymph node station on survival in 348 patients with surgically resected malignant pleural mesothelioma: Implications for revision of the American Joint Committee on Cancer staging system. Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. If a grading system is not specified, generally the following system is used: 26 Pleural Mesothelioma 273 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. The importance of surgical staging in the treatment of malignant pleural mesothelioma. Important prognostic factors in patients with malignant pleural mesothelioma, managed surgically. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results of 183 patients. Job Name: - /381449t 27 Bone (Primary malignant lymphoma and multiple myeloma are not included. Data from these three histologies analyzed at multiple institutions, predominantly influence this staging system. Staging of bone sarcomas is the process whereby patients are evaluated with regard to histology, as well as the local and distant extent of disease. Bone sarcomas are staged based on grade, size, and the presence and location of metastases. Site groups for bone sarcoma: Extremity Pelvis Spine the radiograph remains the mainstay in determining whether a lesion of bone requires staging and usually is the modality that permits reliable prediction of the probable histology of a lesion of bone. To improve conspicuity in locations such as the pelvis or vertebrae, these sequences could be augmented by fat-suppressed pulse sequences. The decision to use intravenous contrast should be based upon medical appropriateness. Technetium scintigraphy is the examination of choice for evaluating the entire skeleton to determine whether there are multiple bony lesions. Reports indicate usefulness in detecting extrapulmonary metastases, evaluating response to chemotherapy, and determining local recurrence adjacent to prosthetic implants. A metastatic site includes any site beyond the regional lymph nodes of the primary site. Extra pulmonary metastases occur infrequently, and may include secondary bone metastases, for example. Biopsy of the tumor completes the staging process, and the location of the biopsy must be carefully planned to allow for eventual en bloc resection of the entire biopsy tract together with a malignant neoplasm. Imaging the tumor after biopsy may compromise the accuracy of the staging process. The pathologic diagnosis is based on the microscopic examination of tissue, correlated with imaging studies. Because regional lymph node involvement from bone tumors is rare, the pathologic stage grouping includes any of the following combinations: pT pG pN pM, or pT pG cN cM, or cT cN pM. Based upon published outcomes data, the current staging system accommodates a two-tiered system (low vs. Clinical staging includes all relevant data prior to primary definitive therapy, including physical examination, imaging, and biopsy. This divided into lesions of maximum dimension 8 cm or less (T1), and lesions greater than 8 cm (T2). T3 has been redefined to include only high-grade tumors, discontinuous, within the same bone. Job Name: - /381449t primary lesions or lesions that were previously treated and have subsequently recurred. Patients who have an anatomically resectable primary tumor have a better prognosis than those with a non-resectable tumor, and tumors of the spine and pelvis tend to have a poorer prognosis. Osteosarcoma patients with a tumor 9 cm or less in greatest dimension have a better prognosis than those with a tumor greater than 9 cm. Those patients with a "good" response, >90% tumor necrosis, have a better prognosis than those with less necrosis. As with soft tissue sarcomas, investigation has been undertaken to identify molecular markers that are useful both as prognostic tools as well as in directing treatment. For practical purposes, prognostically relevant molecular aberrations are considered in terms of gene translocations, expression of multidrug resistance genes, expression of growth factor receptors, and mutations in cell cycle regulators. In contrast, a study concluded that no prognostic value was attributed to different fusion genes when evaluated for event-free and overall survival by univariate analysis. Further investigation showed that P-glycoprotein-positivity at diagnosis emerged as the single factor significantly associated with an unfavorable outcome from survival and multivariate analyses and this association was strong enough to be useful in stratifying patients in whom alternative treatments were being considered. They noted that there was a correlation with histologic response to neoadjuvant chemotherapy and event-free survival. Overall event-free survival has been correlated to P53 alteration in osteosarcoma as well. A variety of other markers have been described as relevant to the prognosis of osteosarcoma. Overexpression of parathyroid hormone Type 1 has been shown to confer an aggressive phenotype in osteosarcoma. Nuclear survivin expression/localization has been associated with prolonged survival. Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis. Finally, telomerase expression in osteosarcoma is associated with decreased progression free survival and overall survival. Investigation to identify molecular markers in chondrosarcoma has progressed at a slower pace. Intramedullary high grade Osteoblastic Chondroblastic Fibroblastic Mixed Small cell Other (telangiectatic, epithelioid, chondromyxoid fibroma-like, chondroblastoma-like, osteoblastomalike, giant cell rich) b. Intramedullary Conventional (hyaline/myxoid) Clear cell Dedifferentiated Mesenchymal b. Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas. Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. Osteosarcoma of the pelvis: oncologist results of 40 patients registered by the Netherlands committee on bone tumours. Peripheral chondrosarcoma progression is accompanied by decreased Indian hedgehog signaling. Ki-67: a proliferative marker that may predict pulmonary metastases and mortality of primary osteosarcoma. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant cooperative osteosarcoma study group protocols. Chemotherapy response in an important predictor of local recurrence in Ewing sarcoma. Osteosarcoma of the spine: experience of the cooperative osteosarcoma study group. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur: a long-term oncological, functional, and quality-of-life study. Pathologic fracture in osteosarcoma: prognostic importance and treatment implications. Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities. Relationship between surgical margins and local recurrence in sarcomas of the spine. Uozaki H, Ishida T, Kakiuchi C, Horiuchi H, Gotoh T, Iijima T, Imamura T, Machinami R. Expression of heat shock proteins in osteosarcoma and its relationship to prognosis. Evaluation of Her-2/neu gene status in osteosarcoma by fluorescence in situ hybridization and multiplex and monoplex polymerase chain reactions. Over-expression of parathyroid hormone type 1 receptor confers an aggressive phenotype in osteosarcoma.

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In determining the management of the primary cancer erectile dysfunction medications comparison generic 30gm himcolin overnight delivery, the following two factorsaretakenintoaccount: 1 erectile dysfunction treatment germany cheap himcolin 30gm on line. Theconditionoftheremainderofthevulva For patients whose tumor is unifocal and the remainder of the vulva is normal impotence from prostate surgery 30 gm himcolin, radical local excision with surgical margins of at least 1 cm is the treatment of choice drugs for erectile dysfunction ppt buy discount himcolin 30 gm online. Diagnosis and Staging Any pigmented lesion on the vulva erectile dysfunction at age 30 safe himcolin 30gm, unless it has been known to be present for a long time impotence psychological treatment generic himcolin 30 gm visa, should be excised for histologic diagnosis. The prognosis correlates more closely with the depth of penetration into the dermis. Those lesions that penetrate to a depth of 1 mm or less from the granular layer of the epidermis rarely metastasize. They commonly present as a rolled-edged "rodent" ulcer, although nodules and macules may occur. Many histologic types have been reported, including leiomyosarcomas, fibrosarcomas, neurofibrosarcomas, liposarcomas, rhabdomyosarcomas, angiosarcomas, and epithelioid sarcomas. Leiomyosarcomas are the most common, and recurrences are mostlikelywithlesionsthatarelargerthan5cm,have infiltratingmargins,andhave5ormoremitoticfigures per10high-powerfields. Management Forlesionsinvadinglessthan1mm,radicallocalexcision alone, with margins of at least 1cm, is adequate therapy. For lesions with 1mm or greater invasion, radical local excision of the primary tumor is usually combined with at least ipsilateral inguinofemoral lymphadenectomy. Most lesions occur in the upper third of the vagina, and the patients are usuallyasymptomatic. Prognosis the overall 5-year survival rate for vulvar melanomas isapproximately30%. The lesions, which are cauliflower-like in nature, may occur in the cervix, vulva, or vagina. Invasion occurs with a broad "pushing" front, and unlessthebaseofthelesionissubmittedforhistologic examination,thesetumorsmaybedifficulttodifferentiate from a condyloma acuminatum or squamous papilloma. Metastasis to regional lymph nodes is rare, butthetumorsarelocallyaggressiveandpronetolocal recurrenceunlesswidesurgicalmarginsareobtained. Diagnosis the diagnosis is usually considered because of an abnormal Papanicolaou smearinawomanwhoeither hashadahysterectomyorhasnodemonstrablecervical abnormality. Definitive diagnosis requires vaginal biopsy, which should be directed by colposcopy or Lugoliodinestaining. In postmenopausal patients, a 4-week course of topical estrogen before colposcopy is indicated to enhance the colposcopic features and eliminate those patients with Papanicolaou smear abnormalities caused by inflammatory atypia. Ahistoryofpreceding inflammation of the Bartholin gland is present in about10%ofpatients,andmalignanciesmaybemistaken for benign cysts or abscesses. Current management consists of hemivulvectomy and ipsilateral inguinofemoral lymphadenectomy. Postoperative vulvar irradiation appears to decrease the local recurrence rate for patients with large lesions. Extensive C H A P T E R 40 Vulvar and Vaginal Cancer 455 diseasemayrequiretotalvaginectomyandcreationof aneovaginausingasplit-thicknessskingraft. Up to 30% of patients with primary vaginal cancer have a history of in situ or invasive cervical cancer that was treated at least 5 years earlier. During a physical examination, ulcerative, exophytic, and infiltrative growthpatternsmaybeseen. Brachytherapy is then given, either with intracavitary vaginalapplicatorsorbyusinginterstitialtechniques. When the lower third of the vagina is involved, the groin nodes should either be included in the treatment field or surgically removed. Radical hysterectomy, partial vaginectomy, and pelvic lymphadenectomy may be performed for early lesions in the posterior fornix. Pelvic exenteration with creation of a neovagina may berequiredformedicallyfitpatientsinwhomacentral recurrencedevelopsfollowingirradiation. Patterns of Spread Vaginalcancerspreadsbydirectinvasionaswellasby lymphatic and hematogenous dissemination. Direct tumor spread may result in involvement of the bladder, urethra, or rectum or in progressive lateral extension to the pelvic side wall. Thelymphaticdrainagefromtheuppervaginaistotheobturator,hypogastric, and external iliac nodes, whereas the lower third of the vagina drains primarily to the inguinofemoral nodes. In practice, all patients should haveatleastachest,pelvic,andabdominalcomputed tomographicscanormagneticresonanceimagingscan to detect evidence of metastatic spread, including bulkypelvicorparaaorticlymphnodes. Management Chemoradiation is the main method of treatment for primary vaginal cancer. Radical surgery has been the traditional treatment, but comparable local control and overall survival may be obtained with conservative tumor resection and postoperative radiation therapy. Inadults,leiomyosarcomas are most common, whereas in infants and children, sarcoma botryoides predominates. Treatment consists of conservative surgical resection followed by adjuvant chemotherapy, with or without radiation therapy. Vaginal adenosis (vaginal columnar epithelium) is the most common anomaly and is present in about 30% of exposed females. Thistissuebehaves similarlytothecolumnarepitheliumofthecervixand is replaced initially by immature metaplastic squamousepithelium. Withprogressivesquamousmaturation, complete resolution of this anomaly usually occurs. Structural changes of the cervix and vagina occur in about 25% of exposed females. Possible changes include a transverse vaginal septum, cervical collar, cockscomb (a raised ridge, usually on the anterior cervix), or cervical hypoplasia. In addition to these changes in the lower genital tract, upper genital tract anomalies occur in at least half of the patientsandmaybeassociatedwithexposurelaterinpregnancy. The most common abnormalities are a T-shaped uterus and a small uterine cavity (<2. Exposed individuals have an increased risk of miscarriage, premature delivery, or ectopicpregnancy,butmostareabletodeliveraviable infantsuccessfully. TypeIendometrialcancersarecausedby unopposedestrogenicstimulation,areendometrioidin histologic type, and generally have a good prognosis. The commonest presenting symptom of patients with endometrial cancer is postmenopausal bleeding. A transvaginalultrasoundwillrevealanendometrialstripe that is wider than 4mm, and an endometrial biopsy doneintheofficewillusuallyallowhistologicdiagnosis. If the office biopsy is negative or shows endometrial hyperplasia,hysteroscopyanduterinecurettagewillbe necessarytodefinitivelyexcludeendometrialcancer. Totalhysterectomyandbilateralsalpingo-oophorectomy isthebasictreatmentforstageIendometrialcancer,and this is usually performed by laparoscopic or robotic surgery. Formalsurgicalstaging, including at least pelvic lymphadenectomy, should be performed in high-risk patients, including those with serous,clearcell,orgrade3histology,outer-halfmyometrialinvasion,orcervicalextension. Ifthepatienthasanadvanced grade1or2tumorwithpositiveestrogenorprogesterone receptors, good responses and prolonged survival may be seen with the use of high-dose progestins or tamoxifen. ItisthefourthmostcommonmalignancyfoundinAmericanwomenafterbreast,colorectal,andlungcancers,anditispredominantlyadisease of affluent, obese, postmenopausal women of low parity. Any factor that increases exposure to unopposed estrogen increases the risk for type I endometrial cancer. If the proliferative effects of estrogen are not counteractedbyaprogestin,endometrialhyperplasia andpossiblyadenocarcinomacanresult. Obesity results in an increased extraovarian aromatization of androstenedione to estrone. Androstenedioneissecretedbytheadrenalglands,whereas the increased peripheral conversion occurs predominantlyinfatdepots,aswellasintheliver,kidneys,and skeletal muscles. Granulosa-theca cell tumors of the ovary produce estrogen, and up to 15% of patients with these tumors have an associated endometrial cancer. Unopposed estrogenic stimulation from anovulatory cycles occurs in patients who have polycystic ovarian syndrome(Stein-Leventhalsyndrome)and in patients with a late menopause. The addition of progestin in a cyclic fashion for 10 to 14 days of themonthorinacontinuousfashiondailythroughout the month eliminates this increased risk. Women taking tamoxifen for breast cancer have a two- to threefold increased risk of endometrial cancer. Young womenwhouseoralcontraceptiveshavebeenshown to have a lower incidence of subsequent endometrial cancer. The most common conditions associated with postmenopausal bleeding arelistedinTable41-2. Signs A general physical examination may reveal obesity, hypertension, and the stigmata of diabetes mellitus. Evidenceofmetastaticdiseaseisunusualatinitialpresentation, but the chest should be examined for any effusionandtheabdomencarefullypalpatedandpercussedtoexcludeascites,hepatomegaly,orevidenceof upperabdominalmasses. Thevaginaandcervixarealsousually normal, but they should be inspected and palpated carefullyforevidenceofinvolvement. A patulous cervical os or a firm, expanded cervix may indicate extension of disease from the corpus to the cervix. Theuterusmaybeofnormalsizeorenlarged,depending on the extent of the disease and the presence or absence of other uterine conditions, such as adenomyosis or fibroids. The adnexa should be palpated carefullyforevidenceofextrauterinemetastasesoran ovarianneoplasm. A granulosa cell tumor or an endometrioid ovarian carcinoma may occasionally coexist with endometrial cancer. Screening of Asymptomatic Women Population screening for endometrial cancer is not feasible, because there is no simple method of cancer detection available. Only about 50% of women with endometrial cancer will have malignant cells on a Papanicolaou smear. Since the 1990s, transvaginal ultrasonography has increasingly been used for endometrial evaluation. Tamoxifen produces a confusing ultrasonic image, which leads to frequent false-positive reports. C H A P T E R 41 Uterine Corpus Cancer 459 Diagnosis Any woman who presents with postmenopausal bleeding should undergo transvaginal ultrasonography. If the endometrial biopsy is negative for cancer or reveals endometrial hyperplasia, a hysteroscopy and fractional dilation and curettage should be performed with the patient under general anesthesia. Specimens from the endometrium and endocervix should be submitted separately for histologic evaluation to determine whether the tumor has extendedtotheendocervix. In a premenopausal patient with high-risk factors and abnormal uterine bleeding, the endometrium must be sampled. If there are no high-risk factors present,failuretorespondtomedicalmanagementor asuspicioustransvaginalultrasoundisalsoanindicationforhysteroscopyanduterinecurettage. Preoperative Investigations Inadditiontoathoroughphysicalexamination,blood studiesshouldincludeacompletebloodcount;determinations of hepatic enzymes, serum electrolytes, bloodureanitrogen,andserumcreatinine;andacoagulation profile. Magnetic resonance imaging is useful for differentiating superficial from deep myometrial invasion or detection of cervical involvement. Invasive adenocarcinoma of the endometrium demonstrates proliferative glandular formation with minimal or no intervening stroma. Tumor grade is determined by both the degree of abnormality of the glandulararchitectureandthedegreeofnuclearatypia. A lesion that is well differentiated (grade 1) forms a glandular pattern similar to normal endometrial glands (Figure 41-1). A moderately well-differentiated lesion(grade2)hasglandularstructuresadmixedwith papillary, and occasionally solid, areas of tumor. In a poorly differentiated lesion (grade 3), the glandular structures have become predominantly solid with a relative paucity of identifiable endometrial glands (Figure41-2). Pattern of Spread Endometrialcancerspreadsby(1)directextension,(2) exfoliationofcellsthatareshedthroughthefallopian tubes, (3) lymphatic dissemination, and (4) hematogenousdissemination. The most common route of spread is direct extension of the tumor to adjacent structures. The tumor may invade through the myometrium and eventually Pathologic Features About 75% of endometrial cancers are pure adenocarcinomas. When squamous elements are present, thetumoriscalledanadenocarcinoma with squamous differentiation. Note the back-to-back glands with minimal intervening stroma and the gland-within-gland pattern. The uterus has been opened to reveal an exophytic carcinoma on the posterior wall of the corpus. Hematogenous dissemination is less common,but itresultsinparenchymalmetastases,particularlyinthe lungsorliver,orboth. This is usually performed by laparoscopic or robotic surgery, although some cases will still require openlaparotomy. Retroperitoneal spaces should be opened and evaluated, and any enlarged pelvic or paraaortic lymph nodes should be resected. Formal surgical staging, including at least pelvic lymphadenectomy, should be performed on high-risk patients, including those with serous, clear cell, or grade 3 histology; outer-half myometrial invasion; or cervical extension. Although uncommon, progressive growth may eventually involve the vagina, parametrium,rectum,orbladder.