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By L. Orknarok. Washington University in Saint Louis.

If one or able as the treatment is governed by the skills and more B-rules apply in the absence of an M-rule order clomiphene 25mg overnight delivery, the resources available in the hospital 50mg clomiphene otc. If both M-rules and B- key points for diagnosis and treatment in abdominal rules apply clomiphene 100mg line, the mass cannot be classified clomiphene 100 mg with mastercard. The most common gyneco- applies buy cheap clomiphene 25mg, the mass cannot be classified7. So women logical conditions are summarized in Table 9. Courtesy of Mirjam Figure 7 Hydrosalpinx at ultrasound. Courtesy of Esther Weemhoff Westen a complex ovarian mass would need further inves- tigation and attention. All emergencies must be managed simultane- ously with the initial assessment by appropriately trained staff. We will now describe the management of the following conditions, others can be found in the respective chapters as indicated in Tables 1 and 3: • Hematometra • Pyometra • Borderline ovarian tumors • Benign ovarian tumors and cysts. Courtesy of Mirjam Weemhoff Hematometra/pyometra This term describes a uterine cavity filled with either MINIMAL CARE/TREATMENT blood or pus and is related to a stenosis of the uterine Management strategies for each gynecological cervix. In young girls who never menstruated be- problem are based on patient factors and the nature fore, hematometra is caused by congenital anomalies of disease presentation. Some of these conditions of the uterus, vagina or hymen as described in need immediate attention and surgical, medical or Chapters 8 and 24. In women of reproductive age or multimodal treatment, e. Treatment not only consists 107 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS Table 7 Further investigations women. They tend to be confined to the ovary, but implants in the abdomen are described. They Chest X-ray, abdominal X-ray (dermoid cyst), intra- have different histological features: venous pyelograph (to look for hydronephrosis) or ultrasound of kidneys (establish the level of obstruction in • Mucinous borderline ovarian tumors are usually case of a hydro-ureter) restricted to one ovary. ECG as appropriate • Serous borderline ovarian tumors are in 25–50% bilateral, and 25–30% of the patients may have Culdocentesis and culdotomy (see Chapters 12 and 18) in some extra-ovarian disease so staging is appro- case of free fluid in Douglas’ pouch 8 priate. Frozen section diagnosis of a low malig- Cystoscopy and rectoscopy if available nant potential tumor of the ovary is changed to CT scan or MRI as appropriate and if available in the a final diagnosis of invasive cancer in approxi- hospital mately 10% of cases. Serous borderline tumors may have (invasive or non-invasive) implants. Explorative laparotomy Most patients present with an asymptomatic pel- vic/abdominal mass. On ultrasound the tumor is mostly multilocular with papillary formations but without ascites, but a non-suspicious cyst does Table 8 Key points in diagnosis and treatment of a not exclude borderline disease. Ca-125 may be swollen abdomen/abdominal mass (slightly) elevated. Look for signs of shock: pallor, low blood pressure and Therapy Surgical staging without pelvic and para- low volume rapid pulse aortal lymph node dissection as this does not influ- Lower abdominal/pelvic tenderness, rigidity, rebound or ence the prognosis9: obtain free fluid or wash the guarding and any mass arising from the pelvis abdomen for cytology, systematically examine Inspect the vulva for any bleeding the whole abdomen (see Chapter 28) and take a biopsy of any suspicious lesion, take biopsies of the Vaginal examination as appropriate +/- swabs peritoneal surface of Douglas’ pouch, the bladder Per rectal examination as appropriate peritoneum, the paracolic gutters and the right dia- phragm. Remove the omentum, the uterus, both Always a pregnancy test in any woman of reproductive age tubes and ovaries (see Chapter 19 for method). Consider a diag- patients who wish to spare their fertility a unilateral nostic peritoneal lavage in case of free fluid either by oophorectomy can be performed and the uterus culdocentesis or abdominal tapping depending on the and the healthy adnexa will not be removed. The most reliable prognostic indi- of dilatation of the cervical stenosis but always in cator for advanced stage tumors is the type of endometrial sampling (see Chapters 20 and 29) and peritoneal implant. Survival of patients with non- cervical examination to exclude malignancy. In cases invasive peritoneal implants is 95%, compared with of pyometra, the pus is most commonly sterile, so 66% for invasive implants, and lymph node involvement was associated with a 98% survival9. It is more important to produce There is no place for adjuvant chemotherapy in a specimen for histology. Treatment of hematometra/pyometra is a care- ful D&C under anesthesia and if possible under Benign ovarian cysts and tumors ultrasound guidance. Persistent or big ovarian cysts Borderline ovarian tumors Persistent or big ovarian cysts with sonographically These are ovarian tumors with low malignant suspicious features (see above) should be assessed by potential that occur mainly in premenopausal surgery (laparotomy or if available laparoscopy 108 Abdominal Masses in Gynecology Table 9 Common gynecological conditions associated with abdominal masses Gynecological condition Common symptoms associated with pelvic mass Uterine fibroids Reproductive age, abnormal uterine bleeding, secondary dysmenorrhea, frequent voiding, constipation, chronic pelvic or back pain, recurrent mis- carriage, infertility Advanced uterine cancer or sarcoma Postmenopausal bleeding, pressure symptoms, pelvic pain, rapid growth of uterine mass in sarcoma Endometriosis Reproductive age, chronic pelvic pain, secondary dysmenorrhea, dyspareunia, infertility Tubo-ovarian abscess, pyosalpinx, Reproductive age, chronic pelvic pain with aggravation, dyspareunia, often hydrosalpinx intermenstrual bleeding, spotting, abnormal vaginal discharge, infertility. A hydrosalpinx is most often symptomless Benign ovarian cysts or tumors Reproductive age, often symptomless, acute or chronic pelvic pain, pressure symptoms, sometimes irregular cycles, spotting Ovarian cancer Peak age postmenopausal, increased abdominal circumference, sometimes dyspnea, postmenopausal bleeding, pressure symptoms, obstipation or ileus by a skilled surgeon). Note however, that you mass you should not attempt this surgery unless you should not attempt doing a mini-laparotomy or are very experienced and able to repair a bowel or unskilled laparoscopy on an ovarian tumor with bladder lesion. If you are able to identify and suspicious sonographic features.

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HCV antibodies usually only become detectable one to five months after infection generic clomiphene 25 mg online. In one study purchase 25mg clomiphene mastercard, they were still lacking in 37% of patients 3 months after first detecting HCV RNA (Thomson 2009) cheap 25mg clomiphene with mastercard. Patients with HIV/HCV coinfection have significantly higher levels of HCV viremia than patients with HCV monoinfection (about 1 log) generic clomiphene 50 mg mastercard. Based on current knowledge the level of viremia does not have a prognostic value for the course of hepatitis C buy cheap clomiphene 50mg online. However, it should be noted that some patients might lose HCV RNA in parallel with progression of immune deficiency, but experience a flare up of hepatitis C together with clinical symptoms following immune reconstitution on ART (Kim 2006). Therefore, regular testing around the initiation of ART seems prudent. When considering the treatment of hepatitis C, genotyping is necessary before start- ing. Six genotypes with numerous subtypes are known, and are seen to have differ- ent regional distributions: genotypes 1 and 3 are predominantly found in Europe, whereas genotypes 4 and 5 are found in Africa, and genotype 6 in Asia. Genotypes 2 and 3 in particular have been associated with significantly better responses to inter- feron-containing therapy. Another marker associated with response to interferon-containing treatment is deter- mination of IL28B genotype. This is a T/C dimorphism close to a region coding for human interleukin 28B. Likelihood of response to interferon-containing, direct acting antiviral (DAA)-free treatment is about twofold higher in IL28B CC genotype than with the TT variant (Nattermann 2011). Spontaneous clearance in case of acute infection is better in CC genotype patients as well. Assessment of liver fibrosis is very important to assess liver disease stage. Among several non-invasive methods available the Fibroscan device is of special interest. This device measures liver stiffness directly correlated to the degree of fibrosis with a special technique (transient elastography). In persons treated with IFN-free regimens HCV RNA at 2–4 weeks and whenever needed in order to assess compliance and or breakthrough in patients experienced with oral DAAs. HCV RNA at week 4 (to evaluate rapid virological response (RVR) under IFN-based HCV regimens) and on all treatments at end-of-treatment and at week 12 and 24 after treatment cessation (to assess SVR). In patients receiving all-oral DAA therapy no association between viral load at any given timepoint on therapy and SVR has yet been found. CD4 cell count and HIV VL every 12 weeks TSH and non-organ specific autoantibodies every 12 weeks on IFN-based therapy 1 Low HCV RNA defined as <400,000-600,000 IU/mL when using PEG-IFN+RBV. There is no standard for converting the amount of HCV RNA reported in copies/mL to the amount reported in IU/mL. The conversion factor ranges from about one to five HCV RNA copies per IU/mL. Other causes of liver disease should be identified by blood tests and liver biopsy if needed. There are several histological classifications used. It distinguishes five stages of fibrosis (0 = no fibrosis, 1 = portal fibrosis without septa, 2 = some septa, 3 = significant septa without cirrhosis, 4 = cir- rhosis). Hepatitis activity is graded according to the intensity of necroinflammatory lesions (A0 = no activity, A1 = mild activity, A2 = moderate activity, A3 = severe activ- ity). As fibrosis progression is accelerated in HIV+ patients, monitoring of fibrosis in yearly intervals seems prudent. An increase of 2 or more stages in liver fibrosis after only 3 years was observed in 25% of all coinfected patients in one study (Sulkowski 2007). If there is clinical suspicion requiring the detection or exclusion of extrahepatic man- ifestations (vasculitis, glomerulonephritis, systemic cryoglobulinemia), appropriate investigations may be necessary (skin biopsy, urine tests, kidney biopsy, detection of serum cryoglobulins). The recommendations for diagnostic procedures in HCV/HIV-coinfected patients can be found in Table 1. For detailed information on TSH and autoantibody testing prior HIV and HBV/HCV Coinfections 457 to interferon-containing therapy please refer to the previous version of this book. As interferon-containing therapy is no longer recommended as first choice for treat- ment of chronic HCV following the licensing of various DAAs this chapter will only focus on DAA-based treatment of HCV coinfection. If HCV treatment is deferred, sonography of the liver should be performed every 6 months in cirrhotics in order to detect hepatocellular carcinoma (HCC).

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Some adverse effects such as lipid elevations were less pronounced with saquinavir buy 25 mg clomiphene mastercard, as was diarrhea cheap 50 mg clomiphene with visa. However cheap 50 mg clomiphene with mastercard, discontinuation rates due to adverse events were comparable between arms 100mg clomiphene sale. During recent years buy generic clomiphene 50 mg, several warning letters were published, regarding QT prolongation and the need for ECG monitoring with saquinavir. Treatment naïve patients should be started on a reduced dose of 500 mg BID for the first seven days, before increasing to the standard dose of 1000 mg BID (always in conjunction with ritonavir 100 mg BID). In addition to baseline, the ECG should now be performed after approximately 10 days of treatment. Thus, it is difficult find any reason for starting saquinavir. Tipranavir (TPV, Aptivus) is the first non-peptidic PI licensed in Europe in July 2005 for treatment-experienced patients. As oral bioavailability is only moderate, double the standard ritonavir boosting (McCallister 2004) is necessary, so 2 x 200 mg (BID) has to be used. The plasma levels can also be increased by a high fat meal. Tipranavir shows good efficacy against PI-resistant viruses (Larder 2000). However, efficacy is not limitless – with a combination of the above mutations, sensitivity declines significantly (Baxter 2006). RESIST-1 (USA) and RESIST-2 (Europe) were two Phase III studies on 1,483 intensively pretreated but viremic patients with at least one primary PI mutation. All patients received either tipranavir/r or a comparison PI/r, each combined with an optimized background therapy. After 48 weeks, virologic and immunologic response to tipranavir was better than with the comparison PI (Hicks 2006). A significant problem with tipranavir, apart from dyslipidemia (grade 3-4 increase in triglycerides: 22% vs 13% for the comparison PI), is an increase in transaminases which is sometimes substantial (grade 3–4: 7% versus 1%) and requires careful mon- itoring. In treatment-naïve patients, tipranavir/r was less effective than lopinavir/r, mainly due to more adverse events leading to discontinuation (Cooper 2006). In addition, some unfavorable interactions also occur. Plasma levels of many PIs fall significantly, so that double PI therapy with tipranavir is not recommended. As the levels of AZT, abacavir and etravirine also drop, these combinations are not recom- mendable either. Tipranavir remains an important option in extensively treated patients harboring PI-resistant viruses. A study that directly compared tipranavir/r to darunavir/r was halted due to slow accrual. Cross-trial comparisons between these drugs should be discouraged as patient populations in the RESIST (tipranavir/r) studies differed con- siderably from those of the POWER (darunavir/r) trials. Metabolic effects of darunavir/ritonavir versus atazanavir/ritonavir in treat- ment-naive, HIV-1-infected subjects over 48 weeks. A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study. Ananworanich J, Hirschel B, Sirivichayakul S, et al. Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir. Blockade of HERG channels by HIV protease inhibitors. Baxter J, Schapiro J, Boucher C, Kohlbrenner V, Hall D, Scherer J, Mayers D. Genotypic changes in HIV-1 protease associated with reduced susceptibility and virologic response to the protease inhibitor tipranavir. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. Overview of antiretroviral agents 97 Carey D, Amin J, Boyd M, Petoumenos K, Emery S. Lipid profiles in HIV-infected adults receiving atazanavir and atazanavir/ritonavir: systematic review and meta-analysis of randomized controlled trials. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experi- enced patients with HIV-1 infection in POWER 1 and 2.

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