Hedieh K. Eslamy, MD

• Clinical Fellow in Radiology
• Lucile Packard Children's Hospital
• Stanford, California

Hormone therapy and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration and progestins arthritis in back during pregnancy generic indocin 50 mg fast delivery. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women arthritis in feet and hands purchase 75mg indocin with mastercard. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk arthritis pain definition indocin 50mg online. Estrogen and proges to gen use in postmenopausal women: 2010 position statement of the North American Menopause Society arthritis thumb diet purchase cheap indocin online. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on endometrial bleeding arthritis knee lump 25mg indocin overnight delivery. A randomized arthritis medication taken off the market cheap indocin 50 mg visa, open label, crossover study comparing the effects of transdermal vs. A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women. Transdermal tes to sterone treatment in women with impaired sexual function after oophorec to my. A field trial of the effectiveness of behavioral treatment for sexual dysfunctions. Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. Efficacy and safety of sildenafil citrate in women with sexual dysfunction associated with female sexual arousal disorder. Lurain Most risk fac to rs for the development of endometrial carcinoma are related to prolonged, unopposed estrogen stimulation. Office endometrial aspiration biopsy is the accepted first step in evaluating a woman with abnormal uterine bleeding or suspected endometrial pathology. Serous and clear cell endometrial carcinomas make up less than 10% of endometrial cancers, yet account for more than one-half of all endometrial cancer deaths. Most patients with endometrial cancer should undergo surgical staging, including hysterec to my, bilateral salpingo-oophorec to my, pelvic and para aortic lymphadenec to my, and peri to neal cy to logy. Lymphadenec to my may be omitted in patients with negligible risk of lymphatic spread. The most important adverse prognostic variables in endometrial cancer are advancing patient age, nonendometrioid or grade 3 his to logy, deep myometrial invasion, lymphovascular space invasion, large tumor size, cervical extension, lymph node metastasis, and intraperi to neal spread. Pos to perative adjuvant radiotherapy in selected patients with endometrial cancer decreases the risk of local vaginal/pelvic recurrence and improves disease-free survival. Uterine sarcomas are, in general, the most malignant group of uterine tumors and differ from endometrial cancers with regard to risk fac to rs, diagnosis, clinical behavior, pattern of spread, and management. Endometrial carcinoma is the most common malignancy of the female genital tract, accounting for almost one-half of all gynecologic cancers in the United States. In 2011, an estimated 46,470 new cases and 8,120 cancer-related deaths are anticipated. Endometrial carcinoma is the fourth most common cancer, ranking behind breast, lung, and colorectal cancers, and the eighth leading cause of death from malignancy in women. Overall, about 2% to 3% of women develop endometrial cancer during their lifetimes (1). Certain fac to rs are increasing awareness of and emphasis on diagnosis and treatment of endometrial cancer. These fac to rs include the declining incidence of cervical cancer-related deaths in the United States, prolonged life expectancy, postmenopausal use of hormone therapy, and earlier diagnosis. The availability of easily applied diagnostic to ols and a clearer understanding of premalignant lesions of the endometrium led to an increase in the number of women diagnosed with endometrial cancer. Although endometrial carcinoma usually presents as early-stage disease and often is managed without radical surgery or radiotherapy, deaths from endometrial carcinoma now exceed those from cervical carcinoma in the United States. Endometrial cancer is a disease that occurs primarily in postmenopausal women and is increasingly virulent with advancing age. The definite role of estrogen in the development of most endometrial cancers is established. Any fac to r that increases exposure to unopposed estrogen increases the risk for endometrial cancer. The his to pathology, spread patterns, and clinicopathologic fac to rs that affect the prognosis of endometrial cancers have become better defined. Management of endometrial cancer evolved from a program of preoperative intrauterine or external pelvic radiation followed by hysterec to my based on clinical staging, to an individualized approach using hysterec to my as primary therapy and employing additional pos to perative treatment depending on surgical and pathologic findings. Further analysis and investigation are needed to determine whether this initial operative approach to treatment and staging, followed by targeted pos to perative therapy, will translate in to improved survival rates and lower morbidity. Type I, accounting for about 75% to 85% of cases, occurs in younger, perimenopausal women with a his to ry of exposure to unopposed estrogen, either endogenous or exogenous. In these women, tumors begin as hyperplastic endometrium and progress to carcinoma. These spontaneously occurring cancers are not associated pathologically with endometrial hyperplasia, but may arise in a background of atrophic endometrium. They are less differentiated and associated with a poorer prognosis than estrogen-dependent tumors. Most of these risk fac to rs are related to prolonged, unopposed estrogen stimulation of the endometrium. Infertility and a his to ry of irregular menses as a result of anovula to ry cycles (prolonged exposure to estrogen without sufficient progesterone) increase risk. Natural menopause occurring after age 52 years increases the risk for endometrial cancer 2. The risk of endometrial cancer is increased 3 times in women who are 21 to 50 pounds overweight and 10 times in those more than 50 pounds overweight (resulting from excess estrone as a result of peripheral conversion of adrenallyderived androstenedione by aromatization in fat). Other fac to rs leading to long-term estrogen exposure, such as polycystic ovary syndrome and functioning ovarian tumors, also are associated with an increased risk for endometrial cancer. Menopausal estrogen therapy without progestins increases the risk of endometrial cancer four to eighttimes. This risk increases with higher doses and with more prolonged use and can be reduced to essentially baseline levels by the addition of progestin (8). The use of the antiestrogen tamoxifen for treatment of breast cancer is associated with a two to threefold increased risk for the development of endometrial cancer, although this finding is confounded by the apparent greater risk of endometrial cancer in women who have breast cancer, with or without treatment with tamoxifen (9,10). Other medical conditions, such as hypertension and hypothyroidism, are associated with endometrial cancer, but a causal relationship is not confirmed. Endometrial Hyperplasia Endometrial hyperplasia represents a spectrum of morphologic and biologic alterations of the endometrial glands and stroma, ranging from an exaggerated physiologic state to carcinoma in situ. Clinically significant hyperplasias usually evolve within a background of proliferative endometrium as a result of protracted estrogen stimulation in the absence of progestin influence. Endometrial hyperplasias are important clinically because they may cause abnormal bleeding, be associated with estrogen-producing ovarian tumors, result from hormonal therapy, and precede or occur simultaneously with endometrial cancer. The classification scheme endorsed by the International Society of Gynecological Pathologists is based on architectural and cy to logic features and long-term studies that reflect the natural his to ry of the lesions (12) (Table 35. Architecturally, hyperplasias are either simple or complex; the major differing features are complexity and crowding of the glandular elements. Simple hyperplasia is characterized by dilated or cystic glands with round to slightly irregular shapes, an increased glandular- to -stromal ratio without glandular crowding, and no cy to logic atypia. Complex hyperplasia has architecturally complex (budding and infolding) crowded glands, with less intervening stroma without atypia. Atypical hyperplasia refers to cy to logic atypia and can be categorized as simple or complex, depending on the corresponding glandular architecture. Criteria for cy to logic atypia include large nuclei of variable size and shape that have lost polarity, increased nuclear- to -cy to plasmic ratios, prominent nucleoli, and irregularly clumped chromatin with parachromatin clearing (Fig. A: the proliferative endometrial glands reveal considerable crowding and papillary infoldings. The endometrial stroma, although markedly diminished, can still be recognized between the glands. B: Higher magnification demonstrates disorderly nuclear arrangement and nuclear enlargement and irregularity. They found that progression to carcinoma occurred in 1% of patients with simple hyperplasia, 3% of patients with complex hyperplasia, 8% of patients with atypical simple hyperplasia, and 29% of patients with atypical complex hyperplasia. The premalignant potential of hyperplasia is influenced by age, underlying ovarian disease, endocrinopathy, obesity, and exogenous hormone exposure (14,15). As many as 25% to 43% of patients with atypical hyperplasia detected in an endometrial biopsy or curettage specimen will have an associated, usually well-differentiated, endometrial carcinoma detected during hysterec to my (16). Marked cy to logic atypia, a high mi to tic rate, and marked cellular stratification are features of atypical endometrial hyperplasia most often associated with the finding of an undiagnosed carcinoma at hysterec to my. Fertility Sparing Treatment of Endometrial Hyperplasia and Cancer Younger patients with endometrial cancer tend to have disorders such as polycystic ovarian syndrome, chronic anovulation, and infertility, indicative of exposure to intrinsic estrogen excess (17). Lesions in this age group are usually welldifferentiated and of endometrioid subtype with the potential to regress with progestational therapy (18). Althoughstandard treatment for all endometrial cancer is hysterec to my and staging, nonsurgical treatment with hormonal therapy may be an option for appropriately selected women desiring to preserve fertility. However, relatively small cohorts of patients and reports of hormone failure suggest caution when counseling patients for conservative management (27,29). A variety of progestational agents were utilized with an overall response rate of 76% (62/81) and the median time to regression was 12 weeks (30). The recurrence rate was 24% among responders; nearly all recurrences occurred within 1year of diagnosis. Only 1month of progestational treatment was required to achieve a response in the 76% of patients without recurrence. It is important to note that 24% (19/81) of the original cohort never responded to treatment, and only 68% had any documented follow-up endometrial sampling. Progestational therapy can successfully treat disease while preserving fertility for patients with atypical hyperplasia and well-differentiated presumed stage I endometrial cancer. Patients must be counseled that failure to identify recurrence or extension of disease during progestational treatment may lead to a delay in definitive surgery and ultimately a compromised prognosis (27). Therapy should be continued for at least 2 to 3 months, and endometrial biopsy should be performed 3 to 4 weeks after completion of therapy to assess response. Periodic endometrial biopsy or transvaginal ultrasonography is advisable in patients being moni to red after progestin therapy for atypical hyperplasia because of the presence of undiagnosed cancer in 25% of cases, the 29% progression rate to cancer, and the high recurrence rate after treatment with progestins. In this setting the use of progesterone should be considered a temporary, rather than long-term, treatment. For women with atypical complex hyperplasia who no longer desire fertility, hysterec to my is recommended. Routine Papanicolaou (Pap) testing is inadequate, and endometrial cy to logic assessment is to o insensitive and nonspecific to be useful in screening for endometrial cancer, even in a high-risk population. A progesterone challenge test reveals whether the endometrium is primed by estrogen, but it does not identify abnormal endometrial pathology. Transvaginal ultrasonographic examination of the uterus and endometrial biopsy are to o expensive to be employed as screening tests. Although many risk fac to rs for endometrial cancer have been identified, screening of high-risk individuals using current technologies could, at best, detect only one-half of all cases of endometrial cancer. Furthermore, no controlled trials were carried out to evaluate the effectiveness of screening for endometrial cancer. Screening for endometrial cancer or its precursors may be justified for certain high-risk women, such as those receiving postmenopausal estrogen therapy without progestins and members of families with hereditary nonpolyposis colorectal cancer (34). Women t a k i n g tamoxifen receive no benefit from routine screening with transvaginal ultrasonography or endometrial biopsy (35,36). Most patients who have endometrial cancer present with abnormal perimenopausal or postmenopausal uterine bleeding early in the development of the disease, when the tumor is still confined to the uterus. Application of an appropriate and accurate diagnostic test in this situation usually results in early diagnosis, timely treatment, and a high cure rate. It is important to recognize that the workup of abnormal uterine bleeding should include endometrial biopsy even in premenopausal patients as 5% are in women under the age of 40. The disorder is characterized by early age (average age younger than 45 years) at onset of neoplastic lesions in a variety of tissues, including the colon, uterus, s to mach, ureters, ovaries, and skin (43,48,49). Although these data appear to support the use of endometrial cancer surveillance strategies for women with Lynch syndrome, a specific algorithm is not defined (50,52).

The laparoscopic approach is preferred with elective colec to my and resection should include the entire sigmoid colon with margins of healthy colon and rectum arthritis in back and hips buy indocin. Observational studies of patients with imaging-proven diver ticulitis suggest that colonoscopy be performed approximately 6 to 8 weeks after resolution of acute diverticulitis in appropriate candidates to exclude the misdiagnosis of a colonic neoplasm and confirm the diagnosis of diver ticulitis suspected on imaging baking soda arthritis relief buy 75 mg indocin with mastercard. A fiber-rich diet or fiber supplementation may be helpful in patients with a his to ry of acute diverticulitis arthritis pain base of thumb order on line indocin. There is no evidence to routinely advise patients to avoid consumption of nuts and popcorn arthritis upper back exercises buy indocin 75 mg line. Prepared by the Clinical Practice Guideline Task Force of the American Society of Colon and Rectal Surgeons cleaning up arthritis in the knee order indocin with a visa. American Gastroenterologic Association Institute Guideline on the management of acute diverticulitis rheumatoid arthritis vagus nerve stimulation buy discount indocin. An acute infiamma to ry process involving the tubular structure, usu ally 8 to 10 cm in length, attached to the base of the cecum called the appendix. Appendicitis has also been described as early (infiammation and symp to ms intensify within 24 hours) or late (infiammation and symp to ms develop over a period of greater than 24 hours) appendicitis. The prevailing hypothesis in approximately 70% of cases is lumi nal obstruction by fecaliths (fecal s to ne), lymphatic hypertrophy, tumor (primary or secondary), or foreign bodies, leading to increased intraluminal pressure and distention with vascular compromise. This is followed by an infiamma to ry reac tion associated with a secondary infection. Appendicitis is the most common indication for emergent surgery performed worldwide. Most commonly presents between the ages of 10 to 20 years, but can occur at any age. Complicates 1 in 1,500 pregnancies and is the most common nonobstetrical operation performed during pregnancy. Bacterial pathogens are most common; however, unusual microorganisms have also been identified and cause infection by either direct invasion or secondary infection. Typically involves facultative aerobic gram-negative enteric pathogens (Enterobacteriaceae). Can cause appendicitis, but more often causes infiammation of the terminal ileum (ileitis) that mimics appendicitis. Actinomyces israelii (anaerobic gram-positive bacteria) is a normal oral cavity bacterium but can sometimes produce a chronic granuloma to us appendicitis (can mimic Crohn disease). Usually associated with infection elsewhere in the abdomen in immunocompro mised patients. Rare etiologies of appendicitis and are usually associated with a travel or exposure his to ry. May cause appendicitis with disseminated infec tion in immunocompromised patients. Distention of an infiamed or infected appendix initially causes periumbilical dull pain due to visceral afferent nerves. As the process continues, infiammation and infection of the serosal layer cause local ized parietal peri to neal infiammation and pain (most commonly in the right lower quadrant). The classic presentation of appendicitis includes the follow ing: short duration of pain, abdominal rigidity, migration of pain to the right lower quadrant, pain centered in the right lower quadrant, right lower quadrant tenderness, and anorexia. Clinically the progression of events may be acute, col icky, periumbilical abdominal pain, possibly followed by nausea and vomiting, with subsequent localization of pain to the right lower quadrant. Can vary based on age of the patient (subtle and variable pain may occur in young children or elderly patients) and location of appendix. The human porphyrias are clinical disorders refiecting defects in heme biosynthesis and acute attacks are triggered by certain drugs, sex steroid hormones, reduced intake of calories and carbohydrate, alcohol, and unknown fac to rs. Acute abdominal pain occurs in about 85% to 90% of attacks and is neu rologic in origin. The pain is usually severe, diffuse, unremitting for hours and poorly localized, but is sometimes colicky. Pancreatitis, acute cholecystitis, peptic ulcer disease, intes tinal perforation, peri to nitis, or intestinal obstruction. Patients usually have localized back pain that can mimic symp to ms similar to acute appendicitis; especially older adults. The approach to the patient suspected of appen dicitis is predominantly clinical; therefore, the his to ry and physical examination remain most important to the diagnosis of appendicitis. Appendicitis should be included in the differential diagnosis of any patient being evaluated for abdominal pain. The most predictive his to ry for appendicitis is the migration of pain from the periumbilical region to the right lower quadrant, abdominal rigidity, and right lower quadrant abdominal pain. A his to ry of vaginal discharge and/or dysuria or urinary frequency suggests an alternate diagnosis. The his to ry should include a com plete evaluation of comorbid illnesses that may suggest other etiologies for abdominal pain. General appearance (patients with appendicitis may be lying motionless with the right thigh fiexed at the hip to relieve pain and pressure). Cardiovascular examination (tachycardia is nonspecific but may indicate pain or infection). Pulmonary examination ( to detect egophony or inspira to ry rales/rhonchi that may indicate pneumonia). Back examination ( to detect fiank pain that may suggest pyelonephritis or spinal tenderness that may be associated with spinal infection or compres sion fracture). Direct palpation or asking the patient to cough often elicits pain at the McBurney point (2/3 along a straight line from the umbilicus to the ante rior superior iliac spine). Right lower quadrant pain elicited with left lower quad rant palpation (sensitivity 68%; specificity 58%). More commonly positive with a retrocecal/retrocolic appendix (sensitivity 16%; specificity 95%). Samples are routinely sent for Gram stain and culture following removal of the infected or infiamed appendix. Not routinely ordered, but may be helpful in cases of suspected parasitic disease. Associated with a low sensitivity and specificity; therefore, these tests are not recommended. The treatment of choice is timely appendec to my with appropriate medical care, fiuid resuscitation, and antimicrobial therapy. Medical therapy alone is successful in the initial manage ment of most patients; however, the high rate of recurrence and risk for progres sion to appendiceal rupture leading to higher morbidity and mortality makes surgical therapy warranted. Suggested antibiotic regimens include (antimicrobial agents listed presume normal renal function): 1. The risk of appendix perforation increases following the onset of symp to ms and is estimated at 20% to 40% by 48 hours, followed by 5% increases for every additional 12 hours. Therefore, appendec to my should be performed with minimal delay if there is persistent or worsening clinical and/or labora to ry findings or documented perforation so as to provide adequate infection source control. No significant differences are noted with the type of opera tion; thus, the choice of surgery depends on the surgeon. There is some data suggesting a lower wound-infection rate after laparoscopic compared to open appendec to my. If perforation has occurred, the wound is typically left open and allowed to heal by secondary intention. A minimally invasive technique, which uti lizes a camera and long instruments inserted through 5 to 10 mm operation trocars, to resect and remove the infiamed appendix. Evidence of pancreatic infiammation the severity of acute pancreatitis has traditionally been determined by the following (known as the Atlanta Criteria): a. Usually further defined as two or more of the following: sys to lic blood pressure less than 90 mmHg, pulmonary insuficiency with PaO2 less than 60 mmHg, acute kidney injury with serum creatinine greater than 2 mg/dL, and/or gastrointestinal bleeding of greater than 500 mL per 24 hours. Acute pancreatitis is a disorder that is most commonly due to the migration of small galls to nes (less than or equal to 5 mm) that obstruct the pancreatic duct or by chronic alcohol consumption. Alcohol abuse (a serum lipase- to -amylase ratio of greater than 4 or 5 strongly suggests an alcoholic cause) c. Hyperlipidemia (especially elevated triglyceride levels greater than 1,000 mg/dL) and hypercalcemia d. Acute pancreatitis, however, can rarely (less than 1% of cases) be associated with an infectious process that may include: 1. Ascaris lumbricoides (second most common cause in India; due to migra tion up the common bile duct) 2. Mycoplasma pneumonia,Yersiniaspp,Salmonella typhi,Campylobacter jejuni, Mycobacterium tuberculosis, and M. Observed in about 15% of patients with acute pancreatitis and characterized as pancreatitis with multiorgan failure that per sists for greater than 48 hours. Pancreatic necrosis can develop in the course of severe acute pancreatitis and is defined as diffuse or focal areas of nonviable pancreatic tissue greater than 3 cm or greater than 30% of pancreatic tissue. Pancreatic necrosis can then become infected (usually week 2 or 3 of disease or as long as 4 to 5 weeks) with two distinct forms: 1. Infected pancreatic necrosis (most common form; usually occurs during the second week of illness). Current opin ion suggests that a pancreatic abscess represents what was previously infected pancreatic necrosis that the host is able to handle without becoming so ill as to require early surgical debridement. Associated with progressive disease and necrosis with eventual infection of the pancreatic necrosis (usually greater than or equal to 30% necrosis). Escherichia coli, Enterobacter spp, Proteus spp, Klebsiella spp, Citrobacter spp, and Pseudomonas. Viridans strep to cocci, Staphylococcus spp, Enterococcus spp, and beta-hemolytic strep to cocci. Patients already have an established diagnosis of acute pancreatitis but may experience the additional following symp to ms: 1. Multiorgan failure is more common in association with pancreatic infections than with noninfected pancreatic necrosis. In critically ill patients, infection of preexisting pancreatic necrosis should be suspected in patients with persistent or worsening symp to ms consistent with infection after 7 to 10 days of illness. Usually pancreatic infections are suspected in patients with per sistent abdominal pain and fevers for 7 to 10 days after being diagnosed with acute pancreatitis. A complete examination should be performed but areas to focus attention include: 1. Neurologic examination ( to detect mental status changes as a decrease in Glasgow coma scale score can be associated with severe pancreatitis). Abdominal examination (fiank ecchymosis [Grey Turner sign] and para umbilical ecchymosis [Cullen sign] may suggest severe pancreatitis). Additionally, the new onset of peri to neal signs may be indicative of new onset of infection. Serum amylase and lipase are usually ordered to establish the diagnosis of acute pancreatitis, and additional testing is nonspecific and pro vides no prediction to pancreatic infections. Lipase level testing is considered more sensitive and specific than measuring amylase levels. The two main isoenzymes, (cationic) trypsinogen-1 and (anionic) trypsinogen-2, are secreted at high concentrations in to pancreatic fiuid, but a small proportion escapes in to the circulation. Because of their rela tively small size, trypsinogens are readily filtered through the glomeruli. For unknown reasons, the tubular reabsorption of trypsinogen-2 is lower than that of trypsinogen-1, and consequently, the urinary concentration of trypsinogen-2 is higher. Evidence-based guidelines recommendations sug gest an initial transabdominal ultrasound should be performed first and that 144 V. Additionally, the finding of greater than or equal to 50% of pancreatic necrosis is associ ated with an 80% chance of subsequent pancreatic infection. Uncontrolled pancreatic infections that are not treated with surgi cal intervention are associated with greater than or equal to 90% mortality rate; however, surgery should be delayed in a physiologically stable patient until the pancreatic necrosis walls off and becomes a well-defined abscess. Uncontrolled sep tic shock secondary to an infected pancreatic necrosis requires immediate surgical intervention. Thus, the diagnosis of an infected pancreas requires immediate surgi cal consultation along with the initiation of appropriate supportive medical therapy. The administration of prophylactic antibiotics to patients with severe necro tizing pancreatitis prior to the diagnosis of pancreatic infection is not recommended. Recommended antibiotic regimens for documented pancreatic infections may include any of the following: 1. Because of the dificulty of achieving adequate source control in patients with infected pancreatic and peripancreatic tissue, a longer dura tion of therapy may be required. Once pancreatic necrosis has been documented, surgi cal drainage or debridement is indicated. The optimal intervention strategy for patients with suspected or confirmed infected necrotizing pancreatitis is initial image-guided percutaneous (retroperi to neal) catheter drainage or endoscopic transluminal drainage, followed, if necessary, by endoscopic or surgical necro sec to my. However, the timing of invasive intervention for infected pancreatic or peripancreatic tissue should be delayed where possible until at least 4 to 17.

Bromocriptine normalizes prolactin levels and induces ovulation in 80% to 90% of patients arthritis treatment by acupuncture buy 25 mg indocin overnight delivery. It is taken two to three times daily arthritis weather buy discount indocin on-line, and most patients will respond to a to tal dose less than 7 arthritis in my neck headaches buy indocin 75mg with amex. Side effects can be bothersome and include nausea rheumatoid arthritis carpal tunnel order indocin 25mg, vomiting rheumatoid arthritis pannus indocin 50 mg for sale, postural hypotension arthritis pain weather purchase indocin 75 mg mastercard, and headache. Stress, extreme weight loss, anorexia, excessive exercise, and low body mass index are all associated with functional hypothalamic suppression, so good nutrition and optimal body weight should be encouraged to res to re ovulation (197,199). Leptin is a hormone produced by peripheral adipocytes that reflects energy s to res and is deficient in women with diet or exericise induced amenorrhea (200). Hypothyroidism the prevalence of hypothyroidism among mid-reproductive aged women is 2% to 4% and is mostly a result of au to immune fac to rs. Menstrual abnormalities, including those from anovulation, are present in 23% to 68% of overtly hypothyroid women and can be corrected with levothyroxine replacement. In any case, because even very mild or subclinical hypothyroidism can have adverse effects on fetal brain development and subsequent intelligence quotient, it is prudent to screen and treat women with thyroid hormone abnormalities before commencing infertility treatment (203). Noninfectious causes for tubal fac to r include tubal endometriosis, salpingitis isthmica nodosa, tubal polyps, tubal spasm, and intratubal mucous debris (10). The patient is typically premedicated 30 to 60 minutes prior to the procedure with ibuprofen or related medication (208). With the patient in the dorsal litho to my position, either a metal cannula or a balloon catheter is inserted through the cervix and past the internal cervical os. Contrast dye is then injected under fluoroscopy to visualize the uterine cavity, fallopian tube architecture, and tubal patency (208,210). Furthermore, patients should be screened for and pretreated with glucocorticoids if iodine allergy is found (210). If prophylaxis is not used and hydrosalpinges are noted on examination, postprocedure doxycycline treatment is recommended. Laparoscopy Laparoscopy is considered the gold standard for diagnosing tubal and peri to neal disease. It allows visualization of all pelvic organs and permits detection and potential concurrent treatment of intramural and subserosal uterine fibroids, peritubal and periovarian adhesions, and endometriosis. However, even laparoscopy has been reported to have a false-positive rate of 11% for proximal tubal occlusion when resected tubal segments are examined pathologically (218). Other Diagnostic Modalities Falloposcopy is used in conjunction with hysteroscopy and allows direct fiberoptic visualization of tubal ostia and intratubal architecture for identification of tubal ostial spasm, abnormal tubal mucosal patterns, and even intraluminal debris causing tubal obstruction (218,219). At present, instrumentation availability and technical complications, including tubal perforation, limit its routine use (219). Alternatively, sonohysterography offers a much less invasive method of diagnosing fallopian tubal obstruction. The use of contrast media during sonohysterography is preferred to improve accuracy in documenting fallopian tubal patency, but these contrast agents are not available in the United States. Still, surgery can be effective in several situations and may be the optimal approach in some patients. The best candidates for proximal tubal catheterization or cannulation have muscle spasm, stromal edema, amorphous debris, mucosal agglutination, or viscous secretions, while nonresponders include those with luminal fibrosis, failed tubal reanastamosis, fibroids, congenital atresia, or tuberculosis. Occlusion from salpingitis isthmica nodosa, endometriosis, synechiae, salpingitis, and cornual polyps only occasionally will respond to catheterization or cannulation (10). Catheterization involves passage of a soft catheter in to the tubal ostia, while cannulation passes a guidewire thru the ostia and injects contrast media or colored dye. Visualization of patency with the hysteroscopic approach can be accomplished using laparoscopy or ultrasound (10,218). Microsurgical tubocornual anas to mosis is an option with small studies reporting pregnancy rates of up to 68% (10). This procedure typically is performed via laparo to my and involves excision of the tubal isthmus, followed by reimplantation of the residual tube in to a new opening made through the uterine cornua (211). Distal Tubal Occlusion (Excluding Sterilization or Hydrosalpinx) Distal tubal disease and occlusion are causal in 85% of all tubal infertility and can be secondary to a variety of inflamma to ry conditions including infection, endometriosis, or prior abdominal or pelvic surgery (211,223). Patients younger than 35 years of age with mild distal tubal disease, normal tubal mucosa, and absent or minimal pelvic adhesions are the best candidates for corrective microsurgery (223). In vitro fertilization should be considered for older patients or those with diminished ovarian reserve, combined proximal and distal tubal disease, severe pelvic adhesions, tubal damage that is not amenable to reconstruction, or additional infertility fac to rs (223,224). Fimbrioplasty involves lysis of fimbrial adhesions or dilation of fimbrial phimosis, whereas salpingos to my (also known as salpingoneos to my) involves the creation of a new tubal opening in an occluded fallopian tube (223). Sterilization Reversal Twenty percent of women express regret following sterilization, and 1% to 5% of those will request reversal, often after a change in marital status. The technique for sterilization reversal involves microsurgical dissection of the occluded ends of the fallopian tube followed by a layered reapposition of the proximal and distal tubal segments. Surgical approaches include minilaparo to my, laparoscopy, and robotic-assisted laparoscopy (224,225). Pregnancy rates following microsurgical tubal reanastamosis for sterilization reversal are 55% to 81%, with most pregnancies occurring within 18 months of surgery (224). Ec to pic pregnancy rates following the procedure are generally less than 10% but may approach 18% (223,226). The main predic to rs of success are age younger than 35 years, isthmic-isthmic or ampulo-ampullar anastamosis, final anastamosed tubal length greater than 4 cm, and less-destructive sterilization methods such as use of rings or clips (224,226). Unlike vasec to my reversal, the length of time between fallopian tubal sterilization and reversal does not seem to affect outcome. Hydrosalpinx Distal occlusion may lead to fluid buildup in the fallopian tube, causing a hydrosalpinx. Uterine Fac to rs Pathologies within the uterine cavity are the cause of infertility in as many as 15% of couples seeking treatment and are diagnosed in greater than 50% of infertile patients (231). Therefore, the evaluation of the couple with infertility should consistently include an assessment of the endometrial cavity. Uterine cavity abnormalities include endometrial polyps, endometrial hyperplasia, submucous myomas, intrauterine synechiae, and congenital uterine anomalies (232). Diagnostic Imaging for Uterine Pathology Hysteroscopy Hysteroscopy is considered the gold standard for uterine cavity evaluation because it allows for direct visualization. Diagnostic hysteroscopy may be performed in the office using a small-diameter hysteroscope and saline distension, often without need for anesthesia (232). To optimize visualization of the endometrial cavity and avoid performing the procedure during early pregnancy, hysteroscopy is typically scheduled during the early to midfollicular phase of the cycle. Disadvantages to the procedure include poor visualization when uterine bleeding is present and the inability to evaluate structures outside the uterine cavity, including those in the myometrium and adnexa. Office hysteroscopy is reported to have a 72% sensitivity for cavity abnormalities when compared to operative hysteroscopy using general anesthesia (231). Hysterosalpingogram shows the general configuration of the uterine cavity and indicates endometrial lesions as filling defects or irregularities of the intrauterine wall. Other drawbacks include patient discomfort, use of iodinated contrast, and radiation exposure (232). Transvaginal Ultrasound Compared to hysteroscopy, transvaginal ultrasound has a 75% positive predictive value and 96. However, this may be improved significantly with the use of three dimensional technology. Endometrial polyps appear as hyperechogenic pedunculated lesions, submucous fibroids have mixed echogenicity, and adhesions contain densely echogenic and cystic areas (234). Congenital Anomalies of the Uterus Congenital uterine anomalies occur in 3% to 4% of women. This increases to 5% to 10% in women with early pregnancy loss and up to 25% in those with second and third trimester pregnancy losses (235). During female embryonic development, the paired paramesonephric or mullerian ducts elongate to ward each other and fuse in the midline. This is followed by resorption of the intervening septum to form the upper vagina, cervix, uterus, and fallopian tubes by week 20 of gestation. Failure of any of these steps leads to absent uterine development or development of unicornuate, bicornuate, arcuate, didelphic, or septate uteri. Because of the proximity of the paramesonephric ducts to the urinary system, renal anomalies often coexist with mullerian anomalies. Appropriate urologic imaging should be performed whenever a mullerian anomaly is diagnosed (235,239). Uterine anomalies are more closely associated with pregnancy wastage and poor obstetric outcomes than with infertility, as the prevalence of congenital uterine defects is generally similar among fertile and infertile women. The arcuate uterus is the mildest congenital uterine anomaly and typically live birth rates are comparable to those in women with normal uteri (235). Surgical uterine repair to improve obstetric outcomes is controversial for most anomalies. However, rudimentary uterine horns require removal on diagnosis, and hysteroscopic metroplasty of the septate uteri significantly reduces the rates of pregnancy loss, but not infertility (235,240). Acquired Abnormalities of the Uterus Leiomyomas Leiomyomas, also called myomas or fibroids, are benign monoclonal uterine myometrial tumors that affect 25% to 45% of reproductive-age women, particularly African Americans (241). The mechanisms by which fibroids cause infertility are unknown, but may involve altered uterine contractility, impaired gamete transport, or endometrial dysfunction (242). Among women with infertility and uterine leiomyomas, pregnancy rates are primarily affected by leiomyoma location (236,242). Subserosal fibroids do not appear to affect fertility or obstetric outcomes, while intramural (regardless of cavity dis to rtion) and submucosal myomas are associated with lower implantation and live birth rates (236,242,243). Myomec to my In women desiring fertility who require treatment for fibroids, myomec to my is the preferred approach, and uterine artery embolization is relatively contraindicated (242). Removal of cavity-dis to rting intramural and submucous myomas is generally recommended prior to proceeding with infertility treatment. The utility of surgical removal of non-cavity-dis to rting intramural fibroids is presently unknown (236,242, 243). Hysteroscopic removal is generally preferred for small submucous fibroids without intramural involvement, while use of the other methods generally depends on patient preference, opera to r skill, or the presence of other pelvic pathology (237,241,244,245). Fluid overload and uterine perforation are the most common complications of hysteroscopic myomec to my, while bleeding and adjacent organ injury are more often associated with alternative approaches (237,241). Fibroids that are located low on the uterus and posteriorly are less amenable to laparoscopic resection. Transmyometrial approaches raise concern for uterine rupture during pregnancy, although this risk appears to be very low (241). Risk fac to rs for polyp development include obesity, unopposed estrogen exposure, and polycystic ovary syndrome. The mechanisms by which endometrial polyps may impair fertility are incompletely described but may relate to disordered endometrial receptivity (250). One report localized 32% of endometrial polyps in infertile women to the posterior uterine wall, indicated that 40. Polypec to my is generally performed via curettage, blind avulsion, or hysteroscopic removal (249). Although the efficacy of polypec to my prior to infertility treatment has not been clearly established, a prospective randomized trial showed a 2. Higher pregnancy rates have been noted for polyps removed from the uterotubal junction when compared to those removed from other locations (251). Smaller nonrandomized studies provide conflicting data on the negative fertility effects of polyps less than 1. Symp to ms of severe disease include amenorrhea, menstrual irregularities, spontaneous abortion, and recurrent pregnancy loss. The causes of intrauterine adhesions are often iatrogenic, with patients typically reporting intraoperative or pos to perative complications of uterine evacuations for incomplete pregnancy loss, pregnancy termination, or postpartum hemorrhage. Myomec to my, hystero to my, diagnostic curettage, cesarean section, tuberculosis, caustic abortifacients, and uterine packing are less-common causes in Western countries (255). Pos to perative prevention of adhesion reformation disease may involve estrogen therapy alone for 1 month or in combination with intraoperative placement of an intrauterine device (such as a small Malecot catheter or pediatric Foley catheter) for 1 to 2 weeks. There is no standard regimen for estrogen therapy, but oral conjugated estrogens 2. Luteal-Phase Defect and Progesterone Supplementation Mechanisms the luteal phase is normally characterized by progesterone secretion by the corpus luteum and appropriate endometrial secre to ry transformation that allow for embryonic implantation in the endometrium and support of early pregnancy for the first 7 to 8 weeks of gestation (258,259). Unfortunately, the characteristic pulsatile secretion of progesterone during the luteal phase of the menstrual cycle combines with wide temporal variations (even within a 60 to 90-minute time span) to make interpretation of midlueal progesterone levels difficult (258). Similar rates of shortened luteal phase are found in fertile and infertile women, and there is significant variability of luteal phase length from cycle to cycle in an individual woman (261). Finally, there is significant interobserver variability in pathologic interpretation of endometrial biopsies from infertile women, and out-of-phase biopsy results poorly discriminate between fertile and infertile women (263,264). When u s e d, progesterone supplementation can be administered via oral, vaginal, or intramuscular routes.

Mainly young black High arthritis purple fingers buy generic indocin 75mg, very Surgery/different carcinoma men with sickle cell trait aggressive arthritis in fingers medication indocin 75 mg with visa, median chemotherapy regimes climacteric arthritis symptoms definition cheap indocin 25mg mastercard, survival is 5 months radiosensitive arthritis in knee support indocin 50 mg low price. Three tumour clinicopathological situations: sporadic arthritis in the back discount indocin 25 mg without a prescription, in association with renal oncocy to sis/ oncocy to ma to sis or in patients with Birt-Hogg-Dube syndrome arthritis in back what to do order 25mg indocin. These systems include assessment of tumour size, exophytic/endophytic properties, nearness to the collecting system and renal sinus, and anterior/ posterior location. However, when selecting the best treatment option, ana to mic scores must always be considered to gether with patient features and surgeon experience. Renal scintigraphy is an additional diagnostic option in patients at risk of future renal impairment due to comorbid disorders. Imaging must be performed before and after administration of intravenous contrast material to demonstrate enhancement. Uniformly high-attenuation lesions < 3 cm in size, with sharp margins without enhancement. The cyst may contain calcification, which may be nodular and thick, with no contrast enhancement. This category also includes to tally intrarenal, non-enhancing, high attenuation renal lesions > 3 cm. Fifty-seven articles including a to tal of 5228 patients were included in the analysis. Spontaneously resolving subcapsular/ perinephric haema to ma are frequent complications, while clinically significant bleeding is unusual (0. C Renal tumour biopsy is recommended before ablative therapy and systemic therapy without previous C pathology. Percutaneous biopsy is recommended in patients in whom active surveillance is pursued. Although affected by intra and inter-observer discrepancies, it is an independent prognostic fac to r [146]. None of these markers have improved the predictive accuracy of current prognostic systems and their use is not recommended in routine practice. Although gene expression profiling seems promising, it has not identified new relevant prognostic fac to rs [161]. B In localised disease, the use of integrated prognostic systems or nomograms is not routinely C recommended, although they can provide a rationale for enrolling patients in to clinical trials. For this Guidelines version, an updated search was performed up to May 31st, 2013 [174]. There was no difference in the length of hospital stay [176, 177, 196], blood transfusions [176, 196, 197], or mean blood loss [176, 196]. Complication rates were inconsistently reported and one intervention was not favoured over another [198]. A significantly lower mean increase in post-operative creatinine levels was found [186]. Complete resection of the primary tumour by open or laparoscopic surgery offers a reasonable chance of cure. Multivariate analysis showed that upper pole location was not predictive of adrenal involvement, but tumour size was. Adrenalec to my was justified using criteria based on radiographic and intra-operative findings. Only 48 of 2,065 patients underwent concurrent ipsilateral adrenalec to my of which 42 were for benign lesions. In patients unfit for surgery, or with non-resectable disease, embolisation can control symp to ms, including gross haematuria or flank pain [222 224]. In patients unfit for surgery with massive haematuria or flank pain, embolisation can be a beneficial 3 palliative approach. B Ipsilateral adrenalec to my is not recommended when there is no clinical evidence of invasion of the B adrenal gland. A cohort study [225] and retrospective database reviews are available, mostly of low methodological quality [176, 226, 227]. No difference in the number of patients receiving blood transfusions was observed, but peri-operative blood loss was significantly less in the laparoscopic arm in all three studies [176, 225, 228]. Surgical complications were marked by low event rates and very wide confidence intervals. There was no difference in complications, but operation time was significantly shorter in the open nephrec to my arm. There were no local recurrences, port-site or distant metastases, but the sample size was small and follow-up was short. Operative time is generally longer with the laparoscopic approach [236-238] and warm ischaemia time is shorter with the open approach [235, 237, 239, 240]. The analyses showed a significantly lower cancer-specific mortality for patients treated with surgery [249, 250]. Other cause mortality rates in the non-surgical group significantly exceeded that of the surgical group [249]. Analyses of older patients (> 75 years) failed to show the same benefit in cancer-specific mortality for surgical treatment [251-253]. In the largest reported series of active surveillance, the growth of renal tumours was low and progression to metastatic disease was reported in a limited number of patients [257, 258]. Overall, both short and intermediate-term oncological outcomes indicate that in selected patients with advanced age and/or comorbidities, active surveillance is appropriate to initially moni to r small renal masses, followed if required, by treatment for progression [256-258, 260-263]. Patients undergoing immediate intervention had higher QoL scores at baseline, specifically for physical health. The perceived benefit in physical health persisted for at least 1 year following intervention. Mental health, which includes domains of depression and anxiety, was not adversely affected while on active surveillance [264]. In comparative studies, there was no significant difference in the overall complication rates between laparoscopic and percutaneous cryoablation [265-267]. A shorter average length of hospital stay was found with the percutaneous technique [266, 267]. Not all studies reported all outcomes listed, and some were small and included benign tumours. Perioperative outcomes, complication rates and other quality of life measures were also mixed. Some studies found the length of hospital stay was shorter and surgical blood loss was less with cryoablation [268-270], while also finding no differences in other peri-operative outcomes, recovery times, complication rates or post-operative serum creatinine levels. Two studies [272, 273] reported specific Clavien rates, with mostly non-significant differences, which were mixed for intra-operative vs. Complication rates were similar in patients treated laparoscopically or percutaneously. One study [280] reported no differences in Clavien complication rates between the techniques. However, the same benefit in cancer-specific mortality is not confirmed in analyses focusing on older patients (> 75 years). In active surveillance cohorts, the growth of small renal masses is low in most cases and progression 3 to metastatic disease is rare (1-2%). The use of neoadjuvant targeted therapy to downsize tumours is experimental and cannot be recommended outside controlled clinical trials. However, uncertainties remain over the best approach for surgical treatment of these patients. Minimal access techniques resulted in significantly shorter operating time compared with traditional median sterno to my [291, 292]. No significant differences in oncological and process outcomes were observed between cardiopulmonary bypass with deep hypothermic circula to ry arrest or partial bypass under normothermia or single caval clamp without circula to ry support [294]. Low quality data suggest that tumour thrombus in non-metastatic disease should be excised. This includes patients with the primary tumour in place and single or oligo-metastatic resectable disease. Cy to reductive nephrec to my for patients with simultaneous complete resection of a single metastasis 3 or oligometastases may improve survival and delay systemic therapy. Interventions included metastasec to my, various radiotherapy modalities, and no local treatment. Of 2,235 studies identified only 16 non-randomised comparative studies were included. However, in one study [306], complete resections were achieved in only 45% of the metastasec to my cohort, which was compared with no metastasec to my. After adjusting for prior nephrec to my, gender and age, multivariate analysis still favoured metastasec to my/curettage and stabilization. Several patients in all groups underwent alternative surgical and non-surgical treatments after initial treatment. In selected patients with painful bone or paravertebral metastases, embolisation can relieve symp to ms [320] (see recommendation Section 7. With the exception of brain and possibly bone metastases, metastasec to my remains by default the 3 most appropriate local treatment for most sites. The decision to resect metastases has to be taken for C each site, and on a case-by-case basis; performance status, risk profiles, patient preference and alternative techniques to achieve local control, must be considered. In individual cases, stereotactic radiotherapy for bone metastases, and stereotactic radiosurgery for C brain metastases can be offered for symp to m relief. However, patients with intermediate-risk disease, failed to confirm this benefit [325]. The moderate efficacy of immunotherapy was confirmed in a Cochrane meta-analysis [324]. Vaccination therapy with tumour antigen 5T4 showed no survival benefit over first-line standard 1b therapy. A trial compared sorafenib and placebo after failure of prior systemic immunotherapy or in patients unfit for immunotherapy. A number of studies have used sorafenib as the control arm in sunitinib-refrac to ry disease versus axitinib, dovitinib and temsirolimus. Alternate scheduling of sunitinib (2 weeks on/1 week off) is being used to manage to xicity. The two drugs had different to xicity profiles [347], and QoL was better with pazopanib. Both studies were limited in that intermittent therapy (sunitinib) was compared with continuous therapy (pazopanib). Axitinib showed > grade 3 diarrhoea in 11%, hypertension in 16%, and fatigue in 11%. Across all grades, nausea was recorded in 32%, vomiting in 24%, and asthenia in 21%. A large number of the crossover patients did not receive the planned subsequent therapy making further analysis complex and underpowered. Survival in the sunitinib-followed-by-everolimus-arm was high, mature analysis is awaited. No firm recommendations can currently be made as to the best sequence of targeted therapy. Based on trial data, axitinib is superior to sorafenib in patients previously treated with cy to kine therapy [349-351]. The final results presented at the 2014 annual meeting of the American Society of Clinical Oncology showed a nonsignificant trend favouring sunitinib. Both sunitinib and everolimus remain options in this population, with a preference for sunitinib. There is limited data supporting the use of targeted therapy in other his to logical subtypes such as chromophobe tumours [328, 370]. Axitinib 5 mg twice daily, to be increased to 7 mg twice daily, unless greater than grade 2 to xicity, blood pressure higher than 150/90 mmHg, or the patient is receiving antihypertensive medication. Sorafenib has broad activity in a spectrum of settings in clear-cell patients previously treated with 4 cy to kine or targeted therapies. A Pazopanib and sorafenib are alternatives to axitinib and are recommended as second-line therapy B after failure of prior cy to kines. After nephron sparing treatment approaches the recurrence may be intrarenal or in addition regional. After thermal ablation locoregional recurrences (intrarenal and regional) have been described in up to 12% [379]. Repeated ablation has often been recommended for intrarenal recurrences following thermal ablation. For locoregional recurrences surgical resection is manda to ry as has been described for isolated local recurrences following nephrec to my. After nephrec to my locally recurrent disease is defined as recurrent disease in the former kidney rest. However, metastasis in the not removed ipsilateral adrenal or non-resected lymph nodes makes interpretation of the true incidence of isolated recurrence in the renal fossa difficult. Treatment of adrenal metastases or lymph node metastases are often described in series of metastasec to my (Section 7. The largest series on the treatment of isolated recurrence was published in 2009 [380]. Of 2,945 patients who underwent nephrec to my the authors identified 54 isolated local recurrences in the renal fossa. Exclusively retrospective non-comparative data exist which suggest that aggressive local resection offers durable local tumour control and improves survival. Adverse prognostic fac to rs were a positive surgical margin after resection, the size of the recurrence and sarcoma to id his to logic features [380].

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