Michael August Blazing, MD

• Associate Professor of Medicine

https://medicine.duke.edu/faculty/michael-august-blazing-md

Iron therapy is usually ineffective; however medicine cabinet shelves discount seroquel 200mg with visa, surgical removal of tumors usually leads to physiologic correction of the anemia symptoms cervical cancer trusted 200mg seroquel. The incidence of an elevated erythrocyte sedimentation rate has been reported to be as high 75% treatment 1st line cheap 200mg seroquel free shipping. Ultrasound of renal masses plays a role in surveillance of cysts or active surveillance of solid masses in select patients medicine pill identification cheap seroquel express. Some investigators have shown sestamibi imaging to have some value in differentiating oncocytoma from renal cell carcinoma symptoms of colon cancer generic seroquel 300mg overnight delivery, but this remains experimental (Gorin et al symptoms thyroid problems generic seroquel 300mg otc, 2016). Cystic lesions are classified according to cyst wall thickness, septations, enhancement, nodularity, calcifications, and fluid density. Higher cyst classification correlates with increased likelihood of renal malignancy. For solid renal lesions, scoring systems can standardize the reporting of tumor size and complexity and are useful for standardized comparisons in research. Ultrasonography Ultrasound examination is a noninvasive, relatively inexpensive technique able to further delineate a renal mass. It is approximately 98% accurate in distinguishing simple cysts from solid lesions. Contrast-enhanced ultrasound using microbubbles, rather than a contrast agent, can better visualize renal parenchyma and blood flow within and around the tumor. This is useful in patients who may not receive contrast because of a severe allergy or chronic kidney disease (Bertolotto et al, 2018). Intraoperative ultrasonography is also often used to confirm the extent and number of masses in the kidney at the time of performing a partial nephrectomy. A: Ultrasound image of a simple renal cyst showing renal parenchyma (long arrows), cyst wall (arrowheads), and a strong posterior wall (short arrows). Right renal angiogram showing typical neovascularity (arrows) in a large lower pole renal cell cancer. According to the 2017 American Urological Association Guidelines for Localized Kidney Cancer, renal mass biopsy should be considered if a mass is concerning for metastatic, hematologic, infectious, or inflammatory etiology and should not be considered in otherwise young and healthy patients that would undergo intervention anyway or older, frail patients that are not planning to undergo intervention (Campbell et al, 2017). Other settings in which biopsy may be appropriate include establishing a diagnosis in patients who are not surgical candidates, selecting patients undergoing active surveillance for small renal masses, and evaluating radiographically indeterminate lesions. Biopsy should be considered primarily in those patients in whom the results would change management. Core biopsy is more sensitive and specific than fine-needle aspiration and is preferred. There have been no reported cases of tumor seeding in the contemporary literature. Approximately 8% of all patients undergoing renal mass biopsy experience a direct complication, such as benign hematomas (5%), significant pain (1%), pneumothorax (<1%), gross hematuria (<1%), and need for transfusion (rare) (Patel et al, 2016). Transaxial magnetic resonance image (T2) of a renal cell carcinoma (long arrows) with vena caval tumor thrombus (short arrows). Most patients present with a renal mass discovered after an evaluation of hematuria or pain or as an incidental finding during an imaging workup of an unrelated problem. Radionuclide Imaging Determination of metastases to bones is most accurate by radionuclide bone scan, although the study is nonspecific and requires confirmation with bone x-rays of identified abnormalities to verify the presence of the typical osteolytic lesions. A bone scan should be considered in patients with an elevated alkaline phosphatase and otherwise normal liver function tests. There is a very low incidence of bone metastasis with normal alkaline phosphatase and it is not routinely necessary (Henriksson et al, 1992). A renal abscess may be strongly suspected in a patient presenting with fever, flank pain, pyuria, and leukocytosis, and an early needle aspiration and culture should be performed. Other benign renal masses (in addition to those previously described) include granulomas and arteriovenous malformations. Pathology Renal cell carcinoma originates from the proximal renal tubular epithelium, as evidenced by electron microscopy and immunohistochemical analysis (Wilkerson et al, 2014; Mackay et al, 1987). These tumors occur with equal frequency in either kidney and are randomly distributed in the upper and lower poles. Grossly, the tumor is characteristically yellow to orange because of the abundance of lipids, particularly in the clear cell type. Benign renal tumors are papillary adenoma, renal oncocytoma, and metanephric adenoma. The cells present in the papillary (chromophilic) type contain less glycogen and lipids, and electron microscopy reveals that the granular cytoplasm contains many mitochondria and cytosomes. Collecting duct tumors tend to have irregular borders and a basophilic cytoplasm with extensive anaplasia and are likely to invade blood vessels and cause infarction of tissue. This latter cell type rarely occurs as a pure form and is most commonly a component of either the clear cell or papillary cell type (or both). Etiology Renal cell carcinoma is a heterogenous disease with multiple exposure-related and genetic etiologies, such as mutations along metabolic and hypoxia-related pathways. Acquired cystic disease of the kidneys is a well-recognized entity of multiple bilateral cysts in the native kidneys of uremic patients (Reichard et al, 198). Hereditary papillary renal carcinoma was described in 1994 and is characterized by a predisposition to develop multiple bilateral renal tumors with a papillary histologic appearance (Zbar et al, 1994). Succinate dehydrogenase, also part of the Krebs cycle, catalyzed the conversion of succinate to fumarate. However, liver, bone (osteolytic), ipsilateral adjacent lymph nodes and adrenal gland, brain, the contralateral kidney, and subcutaneous tissue are frequent sites of disease spread. Tumor Staging the ultimate goal of staging is to select appropriate therapy and obtain prognostic information. Appropriate studies for a complete clinical staging evaluation include history and Data from the American College of Surgeons. Thermal ablation can be considered as an effective nephronsparing approach in patients with significant comorbidities, obesity, a solitary kidney, or advanced age. Historically, the four-level Fuhrman grading system, based on nuclear size, irregularity, and nucleolar prominence, was used to grade renal cell carcinoma (Fuhrman et al, 1982). Of note, this grading system is applicable only to clear cell and papillary renal cell carcinoma, as it has not yet been validated in other histologic subtypes. Appropriate therapy depends almost entirely on the stage of tumor at presentation and therefore requires a thorough staging evaluation. Minimally invasive approaches (laparoscopic or robot-assisted laparoscopic partial nephrectomy, or laparoscopic radical nephrectomy) are preferred if technically feasible, because of the shorter patient recovery times compared to open approaches. The goal of partial nephrectomy is to achieve the removal of tumor with negative margins while minimizing ischemia time and preserving normal renal parenchyma. An open approach may be favored for large or complex masses, or in the case of solitary kidney. However, unless it Treatment of Localized Disease Management options for small cT1a (<4-cm) localized renal cell carcinoma include active surveillance (for masses < 3 cm), surgical resection (partial or radical nephrectomy), and percutaneous thermal ablation. Treatment selection is driven by tumor size/stage, location, preservation of noninvolved renal parenchyma, preexisting patient comorbidity, surgical risk, and patient preference. For masses larger than 4 cm (cT1b and above), surgical resection is the standard of care. Active Surveillance Small renal masses, defined as being under 3 cm, are known to have a low growth rate and rare rate of metastatic spread. In patients with small renal masses that remain on active surveillance with long-term follow-up, the rate of growth is between 1 and 2 mm per year (Uzosike et al, 2018; McIntosh et al, 2018). At 5 years, approximately 1 in 5 patients can safely avoid intervention, and in a cohort of 457 patients followed for a median of 63 months, only one patient developed metastatic disease (McIntosh et al, 2018). Intervention is recommended in patients with a growth rate over 5 mm per year or absolute size greater than 3 cm (Campbell et al, 2017). Thermal Ablation Various thermal ablative options exist for treatment of small renal masses (<3 cm), including cryoablation, radiofrequency ablation, and microwave ablation (Shin et al, 2016). However, with improved imaging, stage migration and early detection, the benefit for routine lymphadenectomy in clinically node-negative patients became less clear. Only 4% were noted to have unsuspected lymph node metastasis, and there were no differences in overall survival, time to progression, and recurrence-free survival between the two groups (Blom et al, 2009; Leibovich and Blute, 2008). When deciding between radical and partial nephrectomy for resection of renal masses, the main goals are to maximize oncologic outcomes, protect renal function, and minimize surgical morbidity. The study suffered from low accrual and was terminated prematurely, and it was therefore underpowered. The trial was also critized as partial nephrectomies were performed by generally lower-volume surgeons, potentially biasing outcomes. In a comprehensive meta-analysis of 21 retrospective studies and over 11,000 patients, compared to those undergoing radical nephrectomy, patients undergoing partial nephrectomy are likely to be younger, have smaller masses, lower rates of tumor recurrence, lower cancer-specific mortality, and lower all-cause mortality (Mir et al, 2017). However, the size of negative margin is not significant, allowing for the resection of minimal normal renal parenchyma. The positive margin rates vary by approach; in a large retrospective analysis of administrative data the positive margin rates in partial nephrectomy are 4. The rate of recurrence was found to be approximately 2 times higher in patients with a positive surgical margin, but this was not associated with the site of recurrence (local or distant), and in stratified analyses a positive margin was associated with recurrence in high-risk tumors but not in low-risk tumors (Shah et al, 2016). The second goal of surgical resection is to protect renal function and spare noninvolved renal parenchyma when possible. During treatment, nephron loss can be due to the volume of resected normal renal parenchyma or ischemia induced during clamping of the renal artery. To minimize these impacts, surgeons opt for partial nephrectomy when technically feasible for appropriate masses with minimal additional normal renal parenchyma resected and to keep renal artery clamp times low. Traditionally, a cutoff of less than 30 minutes of ischemia time has been recommended, but a simple dichotomous cutoff is likely too simplistic (Mir et al, 2018). Partial nephrectomy with cold ischemia time (in open cases), or without arterial clamping, with superselective arterial clamping, and with early unclamping have been described. Partial nephrectomy is more technically complex and is associated with higher perioperative complication rates, including bleeding, and urine leak, and higher readmission rates (Van Poppel et al, 2011; Odisho et al, 2018). Preoperative renal artery embolization (angioinfarction) has been used in the past as a surgical adjunct to facilitate radical nephrectomy, but because there is no conclusive evidence that preoperative embolization actually decreases blood loss or facilitates surgery, its use should be limited to select patients with very large tumors in which the renal artery may be difficult to reach early in the procedure. Adjuvant Treatment for Localized Disease While the administration of systemic therapy after surgical resection plays an important role in many oncological settings, current data from randomized trials do not support its routine use in renal cell carcinoma. Despite some conflicting results, the evidence does not support adjuvant treatment for localized disease at this time. Coronal magnetic image (T1) of a large vena caval tumor thrombus (long arrows) in a patient with renal cell carcinoma. While the presence of tumor thrombus represents a combination of late diagnosis and more aggressive underlying tumor biology, once tumor is beyond the renal vein, the extent of thrombus does not appear to portend worse cancer-specific survival (Whitson et al, 2013; Wagner et al, 2009). The surgical approach to the removal of caval thrombi depends entirely on the level of cephalad extension. In general, these thrombi do not invade the wall of the cava and therefore can be removed without resection of the caval wall. For tumor thrombi that have reached the level of the right atrium, the use of cardiopulmonary bypass is typically required. Radical nephrectomy in these patients or in those with solitary kidneys obviously commits patients to long-term dialysis or renal transplantation and the morbidities of these conditions. Surgical alternatives to radical nephrectomy include open or laparoscopic/robotic partial nephrectomy, ex vivo partial nephrectomy, and enucleation of multiple lesions (Novick et al, 1980). Follow-up Care Surveillance of patients with localized renal cell carcinoma after definitive treatment consists of routine history and physical exams, laboratory evaluation, and imaging, with frequency on the basis of their disease stage and treatment. There are significant costs and radiation exposure associated with long-term surveillance, and some have proposed a more granular risk-based approach, which may inform future guidelines (Lobo et al, 2016; Stewart-Merrill et al, 2015). There has been a rapid growth in the understanding of kidney cancer biology, matched by a proliferation of systemic treatment options. Risk Stratification Selecting the most appropriate treatment of patients with metastatic renal cell carcinoma hinges on accurate risk stratification. Current risk stratification models rely on factors such as histology, patient performance status, and various common laboratory values, but molecular and genetic approaches to more accurately target therapy are under investigation (Graham et al, 2018). Patients are assigned one point each for hemoglobin below lower limit of normal, calcium >10 mg/dL, lactate dehydrogenase > 1. Median overall survival is 43 monhts in good risk, 23 months in intermediate risk, and 8 months in poor-risk patients (Heng et al, 2009, 2013). Because there was no randomized data to support cytoreductive nephrectomy in these patients, findings from the cytokine era were extrapolated forward. The benefit of cytoreductive nephrectomy in good-risk patients in the modern era remains unclear and currently enrolling trials may provide guidance. Metastasectomy-Patients presenting with a solitary or oligometastatic renal cell carcinoma may benefit from complete metastasectomy if technically feasible.

For men with low-risk prostate cancer medicine and health seroquel 200 mg without prescription, hypofractionated radiotherapy has been shown to be to conventional radiotherapy with respect to diseasefree survival and health-related quality-of-life measures in the bladder treatment pneumonia purchase 200 mg seroquel free shipping, bowel medicine pill identification discount seroquel 100mg without prescription, and sexual domains treatment 197 107 blood pressure discount seroquel online, with no differences in anxiety and depression (Bruner et al symptoms nausea dizziness buy seroquel cheap, 2019) medicine klonopin buy discount seroquel. Stereotactic body radiotherapy was recently shown to have low rates of severe toxicity and cancer recurrence in a pooled analysis of men with low- and intermediate-risk prostate cancer (Kishan et al, 2018). It should be reemphasized, however, that most men with low-risk disease should be managed with active surveillance rather than any form of radiation or surgery. Readers are referred to Chapter 26 for a more detailed discussion of radiation therapy in prostate cancer. Implants are permanent (usually iodine-125 or palladium-103) in that the seeds are placed in the prostate, and the radiation dose is delivered over time. Permanent implants have a lower dose rate, but a higher total dose delivered compared to temporary implants, which have a higher dose rate, but deliver a lower total dose. As opposed to external-beam radiation, androgen deprivation does not appear to improve the outcomes of men with intermediate disease who are treated with brachytherapy. Androgen deprivation is often used to shrink the prostate prior to brachytherapy to facilitate seed placement, although this does come at the price of additional side effects (Potters et al, 2001). Men with high-risk disease who choose brachytherapy receive external beam radiation and adjuvant androgen deprivation as described for those managed with external-beam techniques alone. Readers are referred to Chapter 26 for a more detailed discussion of brachytherapy in prostate cancer. Freezing of the prostate is carried out by using a multiprobe cryosurgical device. Doses of 72 cGy appear to result in improved biochemical outcomes compared with lower doses. Wholepelvis radiation, including regional lymph nodes, especially when combined with androgen deprivation, has demonstrated improved outcomes in those with intermediate and high-risk prostate cancer (Lawton et al, 2007), although this conclusion remains controversial among radiation oncologists (Lawton et al, 2007). In addition to the use of dose escalation and improved tumor targeting, several investigators have shown that the results of radiation therapy may be improved with the use of neoadjuvant, concurrent, and adjuvant androgen deprivation. Numerous randomized trials have revealed that androgen deprivation improves the outcome of radiation in those with intermediate- or high-risk disease. Although men who undergo surgery are more likely to suffer incontinence, men who undergo radiation are more likely to suffer obstructive or irritative voiding or bowel symptoms (urgency, frequency, diarrhea, hematuria, rectal bleeding, and tenesmus). Sexual side effects may be exacerbated with the concurrent use of androgen deprivation, especially if used long term (Wu et al, 2008). Long-term risks, such as urethral stricture, rectourinary fistula, and radiation cystitis, are uncommon but can be quite challenging to manage. There is a doubling of the risk of rectal cancer and bladder cancer starting 10 years after prostate radiation, although the absolute risks of these uncommon tumors remain low (Bhojani et al, 2010). Given the risk associated with radiation therapy, and concern regarding the efficacy of reduced radiation, there have been ongoing efforts to balance treatment efficacy with posttreatment quality of life and patient-reported outcomes. Therefore, actual tissue destruction occurs a few millimeters inside the iceball edge and cannot be monitored precisely by ultrasound imaging. Double freezing creates a larger tissue destruction area and theoretically brings the iceball edge and destruction zone edge closer together. An intraurethral warming device minimizes urethral freezing and subsequent sloughing, thus minimizing risk of severe urinary symptoms and/or retention. With modern (third-generation) cryoablation systems, severe complications such as rectourethral fistulas are much less common than they once were. However, erectile dysfunction is very common after cryotherapy, more so than after nerve-sparing surgery or radiation therapy, and for this reason cryotherapy has not been widely adopted for primary treatment. However, it is frequently effective for men with biopsy-confirmed locally persistent/recurrent disease after radiation and can serve as an appropriate modality for focal therapy. Focal therapy-Prostate cancer tends to be an infiltrative disease, with cancerous glands interspersed with normal ones, and it is frequently multifocal. Therefore, focal therapy- treating only the tumor while sparing the normal prostate and surrounding structures-is more challenging than for tumors that grow as discrete lesions such as renal cell carcinomas. Ultimately, widespread adoption of focal therapy awaits completing of ongoing prospective trials and validation of better imaging modalities currently under development that will identify-and ideally grade-prostate lesions with greater accuracy. However, this has since been modified to improve its specificity by defining failure as a rise of at least 2 ng/mL greater than the nadir level ("Phoenix" definition). It must be recognized that these definitions are neither intended nor able to allow comparisons between surgery and radiation patients, because the surgical definition will identify recurrence about 5 years earlier than the radiation definition (Nielsen et al, 2008). Biochemical failure may have a variable natural history after any kind of initial treatment and may signify localized disease, systemic disease, or a combination of the two. Cancer recurrence is more common in those with positive surgical margins, established extracapsular extension, seminal vesicle invasion, and high-grade disease. For men with high risk disease at time of radical prostatectomy, the Decipher test described above has been shown to identify a subset of men with very high risk of early cancer-specific mortality (Cooperberg et al, 2015). For such men at high risk of recurrence, early identification and salvage therapy can prolong survival and reduce the risk of progression to metastatic disease. Yet it is still unclear who may benefit from salvage treatment and who may die from other causes before metastatic disease can develop. For men with a biochemical recurrence after primary treatment, less than 20% will progress to metastatic disease at 15 years of follow-up (Boorjian et al, 2011). In the remaining subset of patients, overdetection of recurrence and overtreatment with salvage therapy will expose individuals to the risks and morbidity of salvage therapy with minimal benefits. By one count, 152 different definitions have been proposed: 53 after surgery and 99 after radiation therapy. A subcutaneous implant that releases leuprolide acetate at a constant rate for 1 year is also available. Such patients are not at increased risk of cancer recurrence, and repeat prostate biopsy should be deferred in such patients. Most patients who fail radiation therapy, irrespective of the site of recurrence, usually are managed with androgen deprivation. Those with documented local-only recurrence increasingly are candidates for salvage prostatectomy, cryosurgery, or additional radiation. However, morbidity can be high with these forms of treatment, as is risk of subsequent relapse. Initial endocrine therapy-Since death due to prostate cancer almost invariably reflects failure to control metastatic disease, decades of research have concentrated on efforts to improve control of distant disease. Most prostatic carcinomas are initially androgen-dependent, and the vast majority of men with metastatic prostate cancer respond initially to various forms of androgen deprivation. Although they are effective, their use is limited because of an increased risk of negative cardiovascular and thromboembolic effects. Transdermal estradiol preparations may avoid these risks and are under active investigation. Because of their rapid onset of action, ketoconazole or abiraterone should be considered in patients with advanced prostate cancer who present with spinal cord compression or disseminated intravascular coagulation. Although testosterone is the major circulating androgen, the adrenal gland secretes the androgens dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. Ketoconazole and abiraterone inhibit androgen biosynthesis throughout the body-in the testes and adrenals and within the tumor cells (de Bono et al, 2011). However, another study comparing the use of an antiandrogen with and without an orchiectomy failed to demonstrate a survival difference between the two arms (Eisenberger et al, 1998). A meta-analysis of monotherapy and complete androgen blockade for the treatment of men with advanced prostate carcinoma suggested that there might be a small survival advantage to complete androgen blockade. This advantage must be balanced against an increased risk of side effects and costs among those on combined therapy (Lukka et al, 2006), often for a number of years. The timing of initial endocrine therapy in prostate cancer has been an area of intensive debate for many years. Data from the Veterans Administration Cooperative Studies from the 1960s did not demonstrate a clear survival advantage for early intervention with androgen ablation therapy in patients with advanced prostate cancer. Intermittent therapy, compared with continuous therapy, may be associated with improved quality of life as serum testosterone levels may normalize during periods of therapy (Hussain et al, 2013). Androgen deprivation is not without significant side effects, including hot flashes, anemia, loss of libido and sexual function, loss of bone mineral density, increased weight and body fat, and cognitive changes. In addition, increases in total cholesterol, low- and high-density lipoproteins, and serum triglycerides have been reported. Men on androgen deprivation should be monitored for such side effects as treatment for most is readily available. Many men diagnosed with prostate cancer suffer from low bone mineral density, which can be exacerbated with androgen deprivation therapy. Ultimately, most prostate cancers will adapt to survive without androgens, at which point they are denoted "castrate-resistant. Moreover, the costs of expensive novel treatments accumulate very quickly, and there is a clear need for much better personalization of treatment based on biomarkers and other predictors of response currently in development. Readers are referred to Chapter 25 for a detailed discussion of the therapy for hormone-refractory prostate cancer. Evaluation and management of prostate cancer has evolved dramatically over the past decade. A growing consensus supports active surveillance for most men with low-risk disease and an aggressive, often multimodal, strategy for those with highrisk disease. Bach-Gansmo T et al: Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine (18F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate cancer. Bader P et al: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Bhojani N et al: the rate of secondary malignancies after radical prostatectomy versus external beam radiation therapy for localized prostate cancer: A population-based study on 17,845 patients. Bill-Axelson A et al: Radical prostatectomy or watchful waiting in prostate cancer-29-year follow-up. Cullen J et al: A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Draisma G et al: Lead time and overdiagnosis in prostate-specific antigen screening: Importance of methods and context. Erho N et al: Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. Etzioni R et al: Overdiagnosis due to prostate-specific antigen screening: Lessons from U. Ficarra V et al: Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Ficarra V et al: Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomy. Hussain M et al: Intermittent versus continuous androgen deprivation in prostate cancer. Lughezzani G et al: Head-to-head comparison of the three most commonly used preoperative models for prediction of biochemical recurrence after radical prostatectomy. Lukka H et al: Maximal androgen blockade for the treatment of metastatic prostate cancer-a systematic review. McKiernan J et al: A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. Okudaira H et al: Accumulation of trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid in prostate cancer due to androgeninduced expression of amino acid transporters. Palvolgyi R et al: Bone scan overuse in staging of prostate cancer: An analysis of a Veterans Affairs cohort. Klotz L et al: Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. Loeb S et al: Uptake of active surveillance for very-low-risk prostate cancer in Sweden. Tewari A et al: Positive surgical margin and perioperative complication rates of primary surgical treatments for prostate cancer: A systematic review and meta-analysis comparing retropubic, laparoscopic, and robotic prostatectomy. Thompson I et al: Guideline for the management of clinically localized prostate cancer: 2007 update. Van Neste L et al: Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Vickers A et al: Cancer control and functional outcomes after radical prostatectomy as markers of surgical quality: Analysis of heterogeneity between surgeons at a single cancer center. Xia J et al: Overdetection of recurrence after radical prostatectomy: Estimates based on patient and tumor characteristics. Yoshii Y et al: Acetate/acetyl-CoA metabolism associated with cancer fatty acid synthesis: Overview and application.

If chromatin is neither lost nor gained medications metabolized by cyp2d6 cheap seroquel 100mg with mastercard, the exchange is called a balanced reciprocal translocation 7 medications that cause incontinence order generic seroquel line. The loss or gain of chromatin material results in partial monosomy or trisomy for a segment of the chromosome treatment 3 degree heart block order seroquel amex, which is designated an unbalanced rearrangement medicine prices 100mg seroquel fast delivery. Another type of translocation involving breakage and reunion near the centromeric regions of two acrocentric chromosomes is known as a robertsonian translocation medications made easy discount 50mg seroquel with visa. Effectively this is a fusion between two whole chromosomes rather than an exchange of material medicine quotes best purchase seroquel, as in a reciprocal translocation. These translocations are among the most common balanced structural rearrangements seen in the general population, with a frequency of 0. In hematologic neoplasias specific structural rearrangements are associated with distinct subtypes of leukemia that have characteristic morphologic and clinical features. Cytogenetic analysis of malignant cells can help determine the diagnosis and often the prognosis of a hematologic malignancy, assist the oncologist in the selection of appropriate therapy, and aid in monitoring the effects of therapy. Bone marrow is the tissue most frequently used to study the cytogenetics of a hematologic malignancy. Unstimulated peripheral blood and bone marrow trephine biopsy samples also may be analyzed. Cytogenetic analysis of cancers involving other organ systems may be performed using solid tissue obtained during surgery or by needle biopsy. Chromosomal defects in cancer include a wide range of numeric abnormalities and structural rearrangements, as discussed earlier (Table 30. Cancer results from multiple and sequential genetic mutations occurring in a somatic cell. At some juncture a critical mutation occurs, and the cell becomes self-perpetuating or clonal. The primary aberration, or stemline, of a clone is a cytogenetic abnormality that is frequently observed as the sole abnormality associated with the cancer. The secondary aberration, or sideline, includes abnormalities additional to the primary aberration. A sideline of this clone would include secondary abnormalities, such as trisomy for chromosome 8, written as 18,t(9;22)(q34;q11. Leukemia Leukemias are clonal proliferations of malignant leukocytes that arise initially in the bone marrow before disseminating to the peripheral blood, lymph nodes, and other organs. They are broadly classified by the type of blood cell giving rise to the clonal proliferation (lymphoid or myeloid) and by the clinical course of the disease (acute or chronic). The two red and two green signals represent the genes on the normal chromosomes 9 and 22. This signaling can be blocked by imatinib mesylate or another tyrosine kinase inhibitor. At diagnosis the characteristic karyotype is the presence of the Philadelphia chromosome in all cells analyzed. A complete cytogenetic response is defined as a bone marrow karyotype with only normal cells. The therapeutic response is often monitored using peripheral blood instead of a bone marrow aspirate. As a result chromosomal analysis of a specimen of unstimulated peripheral blood may be unsuccessful because of the absence of dividing cells. The t(4;11) translocation is the one most commonly found in infants with acute lymphoblastic leukemia. Solid Tumors Just as recurring structural and numeric chromosome defects have been observed in the hematologic malignancies, a wide range of nonrandom abnormalities have also been found in solid tumors. Most of these abnormalities confer a proliferative advantage on the malignant cell and serve as useful prognostic indicators. Chromosomal microarrays, like standard cytogenetic analysis, look at the entire genome but with higher levels of resolution (base pair or kilobase level) determined by the number and composition of targets on the array. Attached to the backbone of deoxyribose are adenine (A), guanine (G), cytosine (C), and thymine (T). Which of the following compounds is used to halt mitosis in metaphase for chromosome analyses Which of the following types of mutations would likely not be detectable with cytogenetic banding techniques Loss of genetic material from a chromosome that does not appear on any other chromosome d. That is diploid but has a balanced deletion and duplication of whole chromosomes d. Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions. Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Phytohemagglutinin: an initiator of mitosis in culture of normal human leukocytes. Chemical differentiation with fluorescent alkylating agents in Vicia faba metaphase chromosomes. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Philadelphia chromosome positive acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French-American-British Cooperative Group. Criteria for the diagnosis of acute leukemia of megakaryocytic lineage (M7): a report of the French-American-British Cooperative Group. Detection of fusion transcripts generated by the inversion 16 chromosome in acute myelogenous leukemia. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/ College of American Pathologists clinical practice guideline update. Consensus statement: chromosomal microarray is the first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. American College of Medical Genetics recommendations for the design and performance expectations for clinical genomic copy number microarrays intended for use in the postnatal setting for detection of constitutional abnormalities. Characterize the diagnostic criteria used for acute myeloid and acute lymphoblastic leukemias. Compare and contrast acute lymphoblastic and myeloid leukemias by morphology, presenting signs and symptoms, laboratory findings, and prognosis. Discuss the cell staining patterns for the following tests: myeloperoxidase, Sudan black B, and esterases. She had been in good health except for the usual communicable diseases of childhood. Rodak, Woodlyne Roquiz, and Pranav Gandhi, whose work in prior editions provided the foundation for this chapter. For most cases of acute leukemia, the causes directly related to the development of the malignancy are unknown. The exceptions that exist are certain toxins that can induce genetic changes leading to a malignant phenotype. Environmental exposures known to lead to hematopoietic malignancies include radiation and exposure to organic solvents, such as benzene. Rarely, leukemias can be seen in patients with known familial cancer predisposition syndromes. Regardless of the mechanism of initial genetic damage, the development of leukemia is currently believed to be a stepwise progression of mutations or "multiple hits" involving mutations in genes that give cells a proliferative advantage, in addition to mutations that hinder differentiation. The use of cytochemical stains continues to be a useful adjunct for differentiation of hematopoietic diseases, especially acute leukemias. In addition to morphologic and cytochemical stains, techniques commonly used to diagnose hematopoietic malignancies include flow cytometry and genetic/molecular studies. Findings of these techniques are discussed throughout the chapter in relation to specific leukemias. Hematologists and pathologists are now moving toward more precise classification of many of the leukocyte neoplasms based on recurring chromosomal and genetic lesions found in many patients. These lesions are related to disruptions of oncogenes, tumor suppressor genes, and other regulatory elements that control proliferation, maturation, apoptosis, and other vital cell functions. Chromosomal translocations are the strongest predictor of adverse treatment outcomes for children and adults. Peripheral blood lymphoblast counts greater than 20 to 30 3 109/L, hepatosplenomegaly, and lymphadenopathy all are associated with a worse outcome. The effects of other variables previously associated with a poorer prognosis, such as sex and ethnic group, have been eliminated when patients have been given equal access to treatment in trials carried out at a single institution. Although 50% to 70% of patients with T-lymphoblastic leukemia/lymphoma have abnormal gene rearrangements, none of the abnormalities is clearly associated with specific biologic features. The degree of differentiation of B-lineage lymphoblasts often correlates with genetics and plays an important role in treatment decisions. Conversely, hypodiploidy (less than 46 chromosomes) conveys a poor prognosis in both children and adults. Anemia, thrombocytopenia, and neutropenia give rise to the clinical findings of pallor, fatigue, fever, bruising, and bleeding. In addition, disseminated intravascular coagulation and other bleeding abnormalities can be significant. Common abnormalities in laboratory test results include hyperuricemia (caused by increased cellular turnover), hyperphosphatemia (due to cell lysis), and hypocalcemia (the latter two are also involved in progressive bone destruction). Tumor lysis syndrome is a group of metabolic complications that can occur in patients with malignancy, most notably lymphomas and leukemias, with and without treatment of the malignancy. These complications are caused by the breakdown products of dying cancer cells, which in turn cause acute uric acid nephropathy and renal failure. Tumor lysis syndrome is characterized by hyperkalemia, hyperphosphatemia, hyperuricemia and hyperuricosuria, and hypocalcemia. Aggressive prophylactic measures to prevent or reduce the clinical manifestations of tumor lysis syndrome are critical. Imatinib, which has shown success in treating chronic myeloid leukemia, has improved survival (Chapter 32). Prognosis is generally favorable but may be negatively affected if unfavorable additional abnormalities, such as monosomy 7, occur. This disorder is characterized by a differentiation block at the promyelocytic stage. The abnormal promyelocytes are considered to be comparable to blasts for the purpose of diagnosis. Detection of the 15;17 translocation is sufficient for diagnosis regardless of blast count. When promyelocytes release primary granule contents, their procoagulant activity initiates disseminated intravascular coagulation; however, thromboembolic events may occur at presentation and during treatment. Typically this disease occurs in children and may be associated with gingival and skin involvement and/or disseminated intravascular coagulation. There must be morphologic criteria for multilineage dysplasia, defined as greater than 50% dysplasia in at least two cell lineages. Erythrocyte precursors have vacuoles, karyorrhexis, megaloblastoid features, and ring sideroblasts. Generally these disorders occur following treatment for a prior malignancy, but they have also been associated with intensive treatment of patients with nonmalignant disorders requiring cytotoxic therapy. Blasts lack myeloid morphologic features and yield negative results with myeloperoxidase and Sudan black B staining. The cells yield negative results with the cytochemical stains myeloperoxidase and Sudan black B. At least 3% of blasts give positive results with myeloperoxidase or Sudan black B stains. Blasts constitute 90% of the nonerythroid cells; there is less than 10% maturation of the granulocytic series beyond the promyelocyte stage. Monocytic cells comprise at least 20% of all marrow cells, with monoblasts and promonocytes present. Blasts constitute 20% or more of the nucleated cells of the bone marrow, and there is maturation beyond the promyelocyte stage in more than 10% of the nonerythroid cells. Monocytic cells (monoblasts and promonocytes) constitute at least 20% of all marrow cells, as do neutrophils and their precursors. The monoblasts are large with abundant cytoplasm containing small granules and pseudopodia. In these leukemias, which are divided into monoblastic and monocytic based on the degree of maturity of the monocytic cells present in the marrow and peripheral blood, more than 80% of the marrow cells are of monocytic origin. Extramedullary involvement, including cutaneous and gingival infiltration, and bleeding disorders are common. Erythroid precursors showing dysplastic features, including multinucleation and megaloblastic asynchrony. Diagnosis requires the presence of at least 20% blasts, of which at least 50% must be of megakaryocyte origin. Megakaryoblast diameters vary from that of a small lymphocyte to three times their size. However, older techniques, such as cytochemical stains, still retain their importance. An advantage of cytochemical stains is that they are relatively inexpensive and can be performed by laboratories throughout the world, including in areas where resources and access to advanced techniques are limited. Myeloid Sarcoma Myeloid sarcoma refers to extramedullary proliferation of blasts of one or more myeloid lineages that disrupts tissue architecture. Tissue architecture must be effaced for the neoplasm to qualify for this diagnosis.

Women with known urinary stone disease do not have an increased risk of stones during pregnancy medications used for anxiety discount seroquel 200 mg without prescription. The fetus demands special considerations regarding the potential dangers of radiation exposure (especially during the first trimester) 340b medications purchase seroquel 100mg amex, medications treatment 6th nerve palsy buy seroquel 100 mg amex, anesthesia treatment venous stasis order seroquel mastercard, and surgical intervention medicine garden purchase seroquel 50 mg free shipping. Initial investigations can be undertaken with renal ultrasonography and limited abdominal x-rays with appropriate shielding medicine ketorolac order generic seroquel canada. Treatment requires balancing the safety of the fetus with the health of the mother. Scout abdominal radiograph demon- strating renal calculus in a renal transplant in the right iliac fossa. Note native renal vasculature with marked calcifications secondary to malignant diabetes mellitus. Standard lithotripters have focal lengths of <15 cm between the energy source and the F2 target, frequently making treatment of obese patients challenging. Standard Amplatz nephrostomy sheaths may not be long enough to enter the collecting system. Such sheaths may need to be advanced well below the skin, or specialized long sheaths with long nephroscopes may be required. Positioning a patient in a modified supine fashion will allow for a combined percutaneous and retrograde access to the collecting system. Risks of anesthesia are increased, and special highpressure respirators may be required if patients are placed in a prone position for a percutaneous procedure. Careful positioning for open procedures helps to reduce the likelihood of crush injuries and associated rhabdomyolysis. Calculi on the concave side in a patient with severe scoliosis may eliminate percutaneous puncture access between the rib and the posterosuperior iliac spine. Retrograde manipulations may need to be performed with flexible endoscopes due to marked contractures, making conventional dorsal lithotomy positioning impossible. Many such patients have undergone supravesical urinary diversion so that retrograde access may be limited. A full metabolic evaluation is even more important because these social and physical restrictions may be difficult or impossible to remedy. Medullary Sponge Kidney Medullary sponge kidney is a common condition characterized by tubular ectasia associated with parenchymal cysts and clefts that predispose to nephrolithiasis in 50% of affected patients. It is most often an asymptomatic condition; however, it may present with renal colic, hematuria, or urinary tract infection. Patients with type I renal tubular acidosis present with persistent acidemia with a low serum bicarbonate value unexplained by hyperventilation or known renal failure. The diagnosis should be suspected in those with a known family history, severe hypocitraturia (<50 mg/24 hours), nephrocalcinosis, medullary sponge kidney, or a fasting urine pH of >6. Scout abdominal radiograph demon- strating a right renal calculus (arrow) in a patient with severe kyphoscoliosis. This disease can be acquired as an adult or inherited with an autosomal dominant pattern. The dose can be given before bedtime in the evening; the patient is instructed to fast until a second morning voided urine sample and a serum bicarbonate level are obtained. A normal person responds by eliminating the acid load in the urine, resulting in a urinary pH of <5. Those who do not respond in this fashion can be assumed to have type I renal tubular acidosis. In addition, the diagnosis should be challenged in those with normal citrate values. Treatment is centered on base replacement with potassium citrate or potassium bicarbonate solutions. Associated Tumors Squamous cell carcinoma of the upper urinary tract is uncommon but has been associated with calculi. Unlike most issues with the pediatric age group, urinary stone disease has pathophysiologic cascades and treatment algorithms that are similar to those found in adults. Children born prematurely and given furosemide while in the neonatal intensive care unit are at increased risk of developing urinary stone disease. More commonly, percutaneous access and, more recently, laparoscopic means are used with success. Dilation of the caliceal neck, direct cauterization or sclerosis of the caliceal epithelium, or direct cauterization and sclerosis of the caliceal epithelium can help reduce stone recurrence rates. Renal Malformations Anatomic renal variants such as ectopic kidneys, including the horseshoe and pelvic kidney, predispose to renal calculi due to impaired urinary drainage. Pain symptoms appear to be no different from those reported in patients with normally positioned kidneys. Large stone burdens should be approached percutaneously as in normally positioned kidneys. Severe outlet obstruction should be corrected with laparoscopic or open surgery, and concurrent calculi can be removed at the same setting. Aberrant vasculature should be appreciated before percutaneous, laparoscopic, and open procedures are undertaken. Caliceal diverticuli are usually asymptomatic, but patients may complain of flank pain or recurrent urinary tract infections. Frequently, many small calculi, rather than a solitary stone, are found in these obstructed cavities. When intervention was required in the past, treatment was with nephrectomy, heminephrectomy, or open surgical unroofing. Differential Diagnosis Urinary stones can mimic other retroperitoneal and peritoneal pathologic states. Urine samples should be fresh; they should be centrifuged and examined immediately for optimum results. Cystine and struvite crystals are always abnormal and require further investigation. Socioeconomic factors-Renal stones are more common in affluent, industrialized countries. Immigrants from less industrialized nations gradually increase their stone incidence and eventually match that of the indigenous population. As per capita income increases, the average diet changes, with an increase in saturated and unsaturated fatty acids; an increase in animal protein and sugar; and a decrease in dietary fiber, vegetable protein, and unrefined carbohydrates. This fact has been documented during war years when diets containing minimal fat and protein resulted in a decreased incidence of stones. High sodium intake is associated with increased urinary sodium, calcium, and pH and a decreased excretion of citrate; this increases the likelihood of calcium salt crystallization because the urinary saturation of monosodium urate and calcium phosphate (brushite) is increased. Physicians and other white-collar workers have an increased incidence of stones compared with manual laborers. This finding may be related to differences in diet but also may be related to physical activity; physical activity may agitate urine and dislodge crystal aggregates. Individuals exposed to high temperatures may develop higher concentrations of solutes owing to dehydration, which may have an impact on the incidence of stones. Climate-Individuals living in hot climates are prone to dehydration, which results in an increased incidence of urinary stones, especially uric acid calculi. Although heat may cause a higher fluid intake, sweat loss results in lowered voided volumes. Hot climates usually expose people to more ultraviolet light, increasing vitamin D3 production. Increased calcium and oxalate excretion have been correlated with increased exposure time to sunlight. Scout abdominal radiograph demon- strating horseshoe kidney with lateral ureteral deviation and double-J ureteral stent. The nature of the pain should be evaluated, including its onset; character; potential radiation; activities that exacerbate or ease the pain; associated nausea, vomiting, or gross hematuria; and a history of similar pain. Patients with previous stones frequently have had similar types of pain in the past, but not always. Stone formers, especially those with calcium oxalate stones, frequently excrete more calcium oxalate crystals, and those crystals are larger than normal (>12 m). The rate of stone formation is proportional to the percentage of large crystals and crystal aggregates. Family history-A family history of urinary stones is associated with an increased incidence of renal calculi. A patient with stones is twice as likely as a stone-free cohort to have at least one first-degree relative with renal stones (30% vs 15%). Those with a family history of stones have an increased incidence of multiple and early recurrences. Spouses of patients with calcium oxalate stones have an increased incidence of stones; this may be related to environmental or dietary factors. Large studies of identical twins have found that >50% of stones have a significant genetic component. A significant association between urinary stones and cardiovascular disease has been confirmed in many studies. Medications-A thorough history of medications taken may provide valuable insight into the cause of urinary calculi. The antihypertensive medication triamterene is found as a component of several medications, including Dyazide, and has been associated with urinary calculi with increasing frequency. Long-term use of antacids containing silica has been associated with the development of silicate stones. The long-term effect of sodium- and calcium-containing medications on the development of renal calculi is not known. Protease inhibitors in immunocompromised patients are associated with radiolucent calculi. Intestinal ileus may be associated with renal colic or other intraperitoneal or retroperitoneal processes. Bladder palpation should be performed because urinary retention may present with pain similar to that due to renal colic. Incarcerated inguinal hernias, epididymitis, orchitis, and female pelvic pathologic states may mimic urinary stone disease. It images other peritoneal and retroperitoneal structures and helps when the diagnosis is uncertain. Prone positioning will help differentiate impacted ureterovesical junction calculi from stones that have already passed into the urinary bladder. An inadequate bowel preparation, associated ileus and swallowed air, and lack of available technicians may result in a less than ideal study when obtained during acute renal colic. Physical Examination A detailed physical examination is an essential component of the evaluation of any patient suspected of having a urinary calculus. The patient presenting with acute renal colic typically is in severe pain, often attempting to find relief in multiple, frequently bizarre, positions. This fact helps differentiate patients with this condition from those with peritonitis, who are afraid to move. Systemic components of renal colic may be obvious, with tachycardia, sweating, and nausea often prominent. An abdominal mass may be palpable in patients with longstanding obstructive urinary calculi and severe hydronephrosis. Fever, hypotension, and cutaneous vasodilation may be apparent in patients with urosepsis. In such instances, there is an urgent need for decompression of the obstructed urinary tract, massive intravenous fluid resuscitation, and intravenous antibiotics. Abdominal tumors, abdominal aortic aneurysms, herniated lumbar disks, and pregnancy may mimic renal colic. The distal ureter is easily visualized through the acoustic window of a full bladder. Retrograde pyelography-Retrograde pyelography occasionally is required to delineate upper tract anatomy and localize small or radiolucent offending calculi. Bulb ureterograms frequently leak contrast material back into the bladder, resulting in a suboptimal study. Intermittent fluoroscopic images direct appropriate injection volumes and help reduce the likelihood of pyelolymphatic, pyelosinus, and pyelovenous reflux. Magnetic resonance imaging-Magnetic resonance imaging is a poor study to document urinary stone disease. Nuclear scintigraphy-Nuclear scintigraphic imaging of stones has recently been appreciated. Differential radioactive uptake dependent on stone composition appreciated during in vitro studies cannot be appreciated on in vivo studies. Nuclear scintigraphy cannot delineate upper-tract anatomy in sufficient detail to help direct a therapeutic plan. Scout abdominal radiograph demon- strating large extraosseous calcification that represents a uterine fibroid. Acute forniceal rupture is not uncommonly associated with a highly obstructive ureteral calculus (typically of a small distal ureteral stone). It may result in dramatic radiographs but is of no clinical significance, and no specific intervention is required. The rupture may be precipitated by the osmotic diuresis of the intravenous contrast agent.

Transurethral resection and drainage may be required if transrectal drainage is inadequate and is recommended when the abscess is larger than 1 cm medicine over the counter purchase discount seroquel line. When properly diagnosed and treated symptoms 6 days post embryo transfer buy 300 mg seroquel free shipping, most cases of prostatic abscess resolve without significant sequelae (Weinberger et al symptoms of colon cancer order seroquel discount, 1988) treatment 12mm kidney stone seroquel 200mg sale. Presentation and Findings Patients with granulomatous prostatitis often present acutely medicine januvia buy generic seroquel 100mg on line, with fever treatment uveitis discount 300mg seroquel free shipping, chills, hematuria, and obstructive/irritative voiding symptoms. Patients with eosinophilic granulomatous prostatitis are severely ill and have high fevers. Digital rectal examination in patients with granulomatous prostatitis demonstrates a hard, indurated, and fixed prostate, which is difficult to distinguish from prostate carcinoma. Serum blood analysis typically demonstrates leukocytosis; marked eosinophilia is often seen in patients with eosinophilic granulomatous prostatitis. Management Some patients respond to antibiotic therapy, corticosteroids, and temporary bladder drainage. Those with eosinophilic granulomatous prostatitis respond dramatically to corticosteroids (Ohkawa et al, 2001). Transurethral resection of the prostate may be required in patients who do not respond A. Presentation and Findings Patients with urethritis may be completely asymptomatic (up to 75% of patients) or present with urethral discharge and dysuria. Transrectal ultrasonography demonstrates hypoechoic lesions (black and white arrows) in the prostate consistent with abscesses. Radiologic Imaging Retrograde urethrography is indicated only in patients with recurrent infection and obstructive voiding symptoms. Most patients with uncomplicated urethritis do not require any radiologic imaging. Sexual partners of the affected patients should be treated, and protective sexual practices (such as using condoms) are recommended. Most cases of epididymitis/orchitis in men younger than 35 years are due to sexually transmitted organisms (N. Children rarely have a positive urine culture, and other causes of epididymitis/orchitis in young children are due to a postinfectious inflammatory reaction to pathogens such as Mycoplasma pneumoniae, enteroviruses, and adenoviruses. In addition, congenital abnormalities or functional voiding problems may lead to urinary reflux into the ejaculatory ducts, leading to a predilection for chemical epididymitis, which often follows a more benign course (Raveenthiran and Sam, 2011). Therefore, epididymitis/orchitis can be of infectious etiology or chemical/irritative in nature. In addition, bed rest, scrotal elevation, and the use of nonsteroidal anti-inflammatory agents are helpful in reducing the duration of the symptoms. In patients with epididymitis/orchitis caused by sexually transmitted organisms, treatment of their sexual partners is recommended to prevent reinfection. For patients with sepsis or severe infection, hospitalization and parenteral antibiotic therapy may be needed. Occasionally, patients with chronic, relapsing epididymitis and scrotal pain may require epididymectomy/orchiectomy for relief of their symptoms. Presentation and Findings Patients with epididymitis/orchitis present with gradually worsening, severe scrotal pain that may radiate to the groin or flank. Scrotal enlargement due to the inflammation of the epididymis/testis or a reactive hydrocele may develop rapidly. Other symptoms of urethritis, cystitis, or prostatitis may be present before or concurrent with the onset of scrotal pain. On physical examination, an enlarged and red scrotum is present, and it is often difficult to distinguish the epididymis from the testis during the acute infection. Renal length increases by approximately 1 cm during normal pregnancy as a result of increased vascular and interstitial volume (Waltzer, 1981). Typically, there is significant ureteral dilation with resultant urinary stasis during the second and third trimesters of gestation. This hydroureter is attributed to the smooth-muscle-relaxing effects of progesterone and the mechanical compression of the ureters by the uterus at the level of the pelvic brim (Waltzer, 1981). Because of these changes in the urinary tract during normal pregnancy, bacteriuria is a clinically relevant finding in pregnant women. When left untreated, pyelonephritis during pregnancy is associated with a high rate of infant prematurity and its associated perinatal mortality (Locksmith and Duff, 2001; McGregor and French, 1998; Schieve et al, 1994). It remains unclear whether treated pyelonephritis during pregnancy has any effect on the developing fetus (Gilstrap and Ramin, 2001). Radiologic Imaging Frequently, it is difficult to distinguish epididymitis from acute testicular torsion from the history and physical examination alone (Petrack and Hafeez, 1992). The presence of blood flow in the testis on Doppler ultrasonography or uptake of the tracers into the center of the testis on radionuclide scanning rules out torsion. On scrotal ultrasonography, patients with epididymitis/orchitis commonly have an enlarged epididymis or testis with increased blood flow. Postpubertal children who are diagnosed with epididymitis should be educated about sexually transmitted diseases and safe sexual practices. Aminoglycosides Fluoroquinolones Penicillins Cephalosporins -Lactamase inhibitors Monobactams Fosfomycin trometamol B. Prostatitis Consequently, it is recommended that women be screened for asymptomatic bacteriuria during pregnancy to prevent the development of pyelonephritis. A voided urine specimen should be obtained at the first prenatal visit and during the third trimester. Pregnant women who are found to have bacteriuria should be treated with penicillins, oral cephalosporins (Christensen, 2000; Wing et al, 1999), or fosfomycin trometamol (Minassian et al, 1998). Of note, nitrofurantoin can be utilized in the first and second trimesters of pregnancy but should be avoided in the third trimester secondary to hemolytic risks. Repeat urine culture to document eradication of bacteriuria is necessary in all patients. Patients with acute bacterial pyelonephritis should be treated with parenteral cephalosporins, penicillins with -lactamase inhibitors, or monobactams (Rubin et al, 1992). Periodic surveillance urine culture is recommended because many of these women will have recurrent episodes of pyelonephritis. The kidneys are first infected and the infection spreads to the lower urinary tract. No relationship between specific uropathogen prevalence and diabetes status has been found; however, diabetic patients with asymptomatic bacteriuria are more likely to be infected by Klebsiella and Enterococcus than by E. One important exception is that staphylococcal infection is not uncommon in diabetic patients and can lead to urinary tract sepsis. This should be considered especially when a diabetic patient presents with a renal carbuncle. Asymptomatic Bacteriuria in Catheterized Patients Patients with indwelling Foley catheters or suprapubic cystotomy tubes and those performing clean intermittent catheterization present a unique challenge. Most of these patients will have a positive urine culture or urinalysis when sampled, but the question remains when to treat the patient. Bacteriuria is established secondary to biofilm formation and bacteria that ascend into the bladder and establishes presence within 72 hours of catheter placement. The Infectious Disease Society of America guidelines have proposed strategies to reduce antibiotic resistance and do not recommend antimicrobial treatment in asymptomatic bacteriuria patients with indwelling catheters. In spinal cord patients who may not be sensate, other symptoms that must be relied on include leakage around the catheter or between catheterizations, foul-smelling urine, suprapubic pressure, increasing muscle spasticity, fever, and costovertebral angle tenderness (Nicolle, 2012). There is a two- to fivefold increase in the incidence of acute pyelonephritis in diabetic patients compared with nondiabetic patients. Complications such as emphysematous pyelonephritis and renal and perirenal abscesses are more frequently seen in the diabetic patients (Williams and Schaeffer, 2004). Asymptomatic bacteriuria occurs in diabetic women more commonly than in nondiabetics. Autonomic neuropathy resulting in dysfunctional voiding and urinary retention can prevent bacterial clearance through micturition and thereby promote bacterial growth. Defects in the local urinary cytokine secretions and an increased adherence of the microorganisms to the uroepithelial cells are also potential mechanisms that may contribute to the increased prevalence of both asymptomatic and symptomatic bacteriuria in these patients (Hoepelman et al, 2003; Nicolle, 2005). Chowdhury P et al: Minireview: Functions of the renal tract epithelium in coordinating the innate immune response to infection. Connell I et al: Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. Copp H, Yiee J, Smith A, et al: Use of urine testing in outpatients treated for urinary tract infection. Costelloe C et al: Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: Systematic review and meta-analysis. Dixon L et al: Chlamydia trachomatis infection and non-gonococcal urethritis in homosexual and heterosexual men in Edinburgh. Ernst E, Diekema D, BootsMiller B, et al: Are United States hospitals following national guidelines for the analysis and presentation of cumulative antimicrobial susceptibility data Al-Orifi F et al: Urine culture from bag specimens in young children: Are the risks too high Bjorksten B, Kaijser B: Interaction of human serum and neutrophils with Escherichia coli strains: Differences between strains isolated from urine of patients with pyelonephritis or asymptomatic bacteriuria. Blanco M et al: Virulence factors and O groups of Escherichia coli isolates from patients with acute pyelonephritis, cystitis and asymptomatic bacteriuria. Bortolussi R et al: Capsular K1 polysaccharide of Escherichia coli: Relationship to virulence in newborn rats and resistance to phagocytosis. Flores-Mireles A, Walker J, Caparon M, Hultgren S: Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Foxman B et al: Urinary tract infection among women aged 40 to 65: Behavioral and sexual risk factors. Franz M, Horl W: Common errors in diagnosis and management of urinary tract infection: Clinical management. Fudaba H, Ooba H, Abe T, Kamida T, Wakabayashi Y, Nagatomi H, et al: An adult case of cerebral malakoplakia successfully cured by treatment with antibiotics, bethanechol and ascorbic acid. Ghiro L et al: Retrospective study of children with acute pyelonephritis: Evaluation of bacterial etiology, antimicrobial susceptibility, drug management and imaging studies. Gupta K et al: Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women. Hoberman A et al: Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Hoberman A, Charron M, Hickey R, et al: Imaging studies after a first febrile urinary tract infection in young children. Hughes C et al: Hemolysin production as a virulence marker in symptomatic and asymptomatic urinary tract infections caused by Escherichia coli. Johnson L et al: Emergence of fluoroquinolone resistance in outpatient urinary Escherichia coli isolates. Kallenius G et al: Occurrence of P-fimbriated Escherichia coli in urinary tract infections. Kanamaru S, Kurazono H, Terai A, Monden K, Kumon H, Mizunoe Y, et al: Increased biofilm formation in Escherichia coli isolated from acute prostatitis. Nagy V, Kubej D: Acute bacterial prostatitis in humans: current microbiological spectrum, sensitivity to antibiotics and clinical findings. Karaca Y et al: Co-trimoxazole and quinolone resistance in Escherichia coli isolated from urinary tract infections over the last 100 years. Leport C et al: Bacterial prostatitis in patients infected with the human immunodeficiency virus. Likitnukul S et al: Epididymitis in children and adolescents: A 20-year retrospective study. Lomberg H et al: Influence of blood group on the availability of receptors for attachment of uropathogenic Escherichia coli. Marcus N et al: Non-Escherichia coli versus Escherichia coli communityacquired urinary tract infections in children hospitalized in a tertiary center: Relative frequency, risk factors, antimicrobial resistance and outcome. Ofek I et al: Role of bacterial lectins in urinary tract infections: Molecular mechanisms for diversification of bacterial surface lectins. Ohkawa M et al: Non-specific eosinophilic granulomatous prostatitis responded favorably to an antimicrobial agent and a hydrocortisone. Orskov I et al: O, K, H and fimbrial antigens in Escherichia coli serotypes associated with pyelonephritis and cystitis. Osset J et al: Assessment of the capacity of Lactobacillus to inhibit the growth of uropathogens and block their adhesion to vaginal epithelial cells. Pak J et al: Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. Pallet A, Hand K: Complicated urinary tract infections: Practical solutions for the treatment of multiresistant Gram-negative bacteria. Rajesh A, Jakanani G, Mayer N, et al: Computed tomography findings in xanthogranulomatous pyelonephritis.

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