Saturday, October 27, 2012

Basic urology: history taking and physical examination

Basic urology: history taking and physical examination  is a detailed book on history and examination and other useful related subjects as hematuria.
book by Prof.Dr. Atallah Ahmed Shaban
free link of the book from Mansura faculty of medicine,
many thanks for the great book
http://medfac.mans.edu.eg/english/dept/elearningunit/books/History%20Taking%20AND%20CLINICAL%20EXAMINATION.pdf

Friday, October 12, 2012

nice site for urology history and old photos

http://www.urologichistory.museum/

Saturday, October 6, 2012

Cancer Genetics

Mechanisms and Targets in CRPC


In general, resistance mechanisms can be divided into 6 groups.

(i) Increased Expression of Enzymes Involved in Steroidogenesis

Studies have suggested that, in CRPC patients, even castrate serum levels of androgen are still sufficient for AR activation and able to maintain cancer cells survival. Indeed, the intratumoral levels of testosterone in CRPC patients are equal of those found in noncastrate patients. The source of these androgens is thought to be derived from the synthesis of androgens directly in prostate cancer cells due to an upregulation of the enzymes and activation of the routes necessary for the synthesis of androgens such as testosterone and dihydrotestosterone. Also bone metastases contain intact enzyme pathways for conversion of adrenal androgens to testosterone and dihydrotestosterone. Montgomery and colleagues showed that there was marked reversal of the DHT : testosterone ratio in the metastatic tumor. These tumor cells express significantly lower levels of SRD5A2, which catalyses the conversion of testosterone to DHT, and higher levels of UGT2B15 and UGT2B17, which mediate the irreversible glucuronidation of DHT metabolites. Marked up regulation of CYP19A1, which mediates the aromatization of testosterone to estradiol, was also observed in the metastases samples.

(ii) Increased Expression of AR

The overexpression of AR have been involved in the progression of prostate cancer. The activated AR pathways observed in these CRPC patients has been postulated as a result of genetic phenomena that promotes increased sensitivity of AR. DNA amplifications are responsible for AR overexpression and for its activation in presence of low levels of ligand (androgens).

(iii) AR Gene Mutations and Altered Ligand Specificity

While the androgens are the main factors of tumor growth and AR signaling, the presence of AR mutations leads to its activation by nonandrogenic steroid molecules and antiandrogens. The majority AR mutations are point mutations in the AR ligand-binding domain, and initially this was considered relevant to explain why 10–30% of patients receiving antiandrogens treatment experience paradoxical PSA drop on cessation of treatment. However the AR mutations could occur in other regions such as the amino terminus or the DNA binding domain that confer oncogenic properties to the AR. At the present, the role of AR mutations in the anti-androgen withdrawal phenomena is called into questioned and a new explanation is offered since the discovery of alternative splicing of the AR. In fact, in recent reports it was shown that splice variants of AR with deletion of exons 5, 6, and 7 could result in AR capable to translocate to the nucleus without ligand binding.

(iv) Downstream Signaling Receptor for Androgens

One of the most important mechanisms in the development of castration resistance is the activation of different signal transduction pathways in CRPC cells. They could enhance the activity of the AR or its coactivators in the presence of low levels or even in the absence of androgen. These include other receptors such as epithelial growth factors, insulin growth factors, and tyrosine-kinase receptor.

(v) Bypass Pathways

The induction of bypass pathways independent of AR, is an important mechanism of castration resistance, that can overcame apoptosis induced by androgen-deprivation therapy. One such example of this is the up-regulation of antiapoptotic proteins, including the protein Bcl-2 gene.

(vi) Stem Cells

Prostatic cancer stem cells are rare and undifferentiated cells that do not express AR on their surface, being independent of androgens to survive. Currently it is thought that these cells can be responsible for maintaining tumor growth and development, because they are able to survive under androgen-deprivation therapy. The identification of these cells is possible based on the expression of surface protein (α1β1 integrin and CD133), which could allow new targets therapies.

Friday, October 5, 2012

Current and Emerging Treatments in the Management of Castration-Resistant Prostate Cancer

Prostate cancer is the second most common cause of death in American men, and a great majority of those men die with CRPC. There are currently four new agents approved in the USA for use in CRPC: cabazitaxel, AA (Abiraterone acetate), sipuleucel-T and denosumab. While the current first line treatments are docetaxel and sipuleucel-T, ongoing and future clinical trials of these new agents, different docetaxel regimens, and emerging and experimental agents aimed at novel targets will lead to changes in the current treatment algorithm outlined in this review.


Epothilones in prostate cancer


“ Although taxane-based regimens offer limited survival benefits, patients frequently relapse, and there are no standard regimens beyond progression.
“ Ixabepilone, sagopilone, and patupilone have demonstrated clinical activity and tolerability in phase II CRPC trials. ”
“ CONCLUSION: The epothilones have demonstrated efficacy in CRPC, and ongoing studies will help define their roles in this disease state, including optimal dosing, combination regimens, and clinical biomarkers of response.

Robotic-Assisted Partial Nephrectomy

What's New in Pediatric Urology


INFECTIONS

The presence of even a single episode of epididymitis in children has been considered an indication for evaluation to detect a renal or ureteral anomaly as its etiology. A study from Paris challenges this assumption with data from evaluation of 38 children seen over an 8-year period (Cappele et al., 2000.) They found that only 18% of evaluated children had renal anomalies such as reflux or renal malrotation, and only one child required surgery (for ureterocele.) The frequency of anomalies was lower than expected.

BLADDER ANOMALIES

A prospective placebo-controlled study of ultrasound therapy to the bladder was applied to 35 patients with primary nocturnal enuresis. Delivery of 0.8 W/cm2 was applied to the bladder 8 minutes a day for 10 days. Overall, 82% of children benefited from treatment and responses persisted for 12 months after therapy. There were no responses in placebo-treated controls (Kosar et al., 2000.) Further information on this treatment is needed in a larger trial. The role of bladder dysfunction in failure after renal transplantation was evaluated in a study from Paris in 66 boys with posterior urethral valves (Salomon et al., 2000.) In boys with symptomatic voiding dysfunction, mean serum creatinine increased after five years of followup. Closer followup of boys with symptomatic voiding problems after transplantation is warranted. A consensus survey of the Society for Fetal Urology members was reported on management of antenatally detected urological abnormalities. Only rare conditions were recommended for intervention. These may include oligohydramnios with suspected favorable renal function and the absence of life-threatening congenital anomalies. The presence of normal amniotic fluid was a contraindication to intervention regardless of the detected abnormality. However, early delivery of fetuses with severe genitourinary abnormalities, normal amniotic fluid and confirmed lung maturity is more commonly advocated now (Hernodon et al., 2000.) The group from Hopkins reported on long term outcome of epispadias repair in 93 males with epispadias alone or classic bladder exstrophy. A downward or horizontally-directed penis was obtained for 93% of boys. Early fistulas occurred for 23% of patients with 19% at 3 months. Urethral stricture occurred for 7 boys. These results were considered to be functionally and cosmetically excellent (Surer et al., 2000.) The voiding pattern of healthy preterm neonates was shown to involve a high frequency of interrupted voiding, suggesting the presence of immature detrusor-sphincter coordination. A high number of voids during sleep also indicated a more immature pattern than that seen in full term newborns (Sillen et al., 2000.) The group from Children's Hospital in Boston reported on 25 newborns with normal neurourological evaluation after surgical repair of myelodysplasia. Subsequent neurourological deterioration occurred for 32% of infants secondary to spinal cord tethering, especially during the first 6 years of life. Close followup and intervention of these children was recommended (Tarcan et al., 2001.)

REFLUX

A survey of American Association of Pediatrics, Section on Urology members on standard management of vesicoureteral reflux (Herndon et al., 2001.) Urine culture is routinely performed by 64-71% of respondents and yearly VCUG or radionuclide scan for followup by 99% of respondents with ultrasound by 77%. After reflux surgery, 91% of respondents perform VCUG and ultrasound. The overwhelming majority of practitioners agree on the timing and type of radiographic studies to be used to follow children with reflux. A low incidence (2%) of renal scars in children after ureteral reimplantation was noted in a prospective study from Australia (Webster et al., 2000.) These findings suggest that surgical correction of reflux may protect kidneys better than previously believed.

TESTICULAR CONDITIONS

Men who had previously undergone prepubertal orchiopexy were studied with ultrasound as adults. Of 22 men, tunica albugineal calcification was seen in 32%, consistent with reaction from suture or persistence of a chromic suture, which is typically not absorbed in the region of the tunics. A subtunical hypoechoic area was seen in 14% of patients and only 54% had normal ultrasound studies (Ward et al., 2000.) Cystic testicular lesions are rare but may have multiple possible etiologies. Management with partial orchiectomy and frozen section histologic analysis is the recommended management, but a complete overview is available in this reference (Garrett et al., 2000.) Comparison of boys pretreated with hCG or GnRH prior to orchiopexy versus those who received no pretreatment was provided in a study from Denmark (Cortes et al., 2000.) They found a higher number of spermatogonia per tubule in the untreated patients, suggesting a possible detrimental effect of prior hormonal therapy. The use of orchidometer for assessment of testicular volume was provided in a study from Boston Children's (Diamond et al., 2000.) They found a strong linear relationship between orchidometer and ultrasound measurements, but they felt that orchidometer was not sufficiently accurate to determine growth impairment with sequential evaluations. Yearly ultrasound assessment was recommended for sequential analysis of relative testicular volume. A study from CHOP showed that in 723 patients, germ cell counts correlated with testicular volume. However, prediction of the cut point of <0.2 or >0.2 germ cells per tubule was not possible based on testicular volume measurements alone (Noh et al., 2000.)

TUMORS

The management of synchronous bilateral Wilms tumor was reported from CHOP (Cooper et al., 2000.) Preoperative chemotherapy followed by nephron-sparing surgery was recommended. Brachytherapy was recommended for treating local disease involving chemoresistant tumors. Those patients with diffuse anaplasia are not recommended to have nephron sparing surgery.

HYPOSPADIAS REPAIR

The complication rate of flaps and grafts for repair of proximal hypospadias was reported in a retrospective review of 142 patients from San Diego (Powell et al., 2000.) A higher complication rate occurred after free tubed grafts. Two-thirds of complications presented more than 1 year after surgery. Use of the dorsal inlay graft for 32 patients with coronal to penoscrotal hypospadias after chordee release was reported from Baylor (Kolon & Gonzales, 2000.) Glanuloplasty and in situ tubularization of the urethral plate was reported by Kass from Michigan for distal and midshaft hypospadias repair in 308 patients. They reported excellent overall cosmetic results with a complication rate of 9.7%, most of which occurred in mid shaft lesions (Kass & Chung, 2000.)

RECONSTRUCTION

The use of urinary diversion or stenting after dismembered pyeloplasty was evaluated by Austin et al.(2000) in a review of 137 pyeloplasties. They found that drainage with nephrostomy tube alone resulted in few complications and an open anastomosis in 100% of cases. Use of gastrocystoplasty for bladder reconstruction was reported by Leonard from Winnipeg in a series of 23 patients in a tertiary pediatric urology practice. They found that stomach may be used for augmentation in patients with cloacal exstrophy and/or metabolic acidosis. Histamine blockers and proton pump inhibitors are commonly required for hematuria-dysuria. The symptoms of this syndrome was disabling and resulted in another form of urinary reconstruction for 3 patients (Leonard et al., 2000.) The group from Hopkins reported decreased linear growth in 82% of exstrophy patients managed with intestinal bladder augmentation, compared to 33% of controls. Close followup of patients for subtle evidence of metabolic alterations was recommended (Gros et al., 2000)

Pediatric Urology / General Information



Pediatric Urology involves managment of genital and urinary problems that occur in children. A special emphasis on developmental problems affecting the kidneys, bladder, urethra or genital tract. Common conditions treated include hypospadias (urine passage ending short of the end of the penis), hydronephrosis (obstruction of urine flow from the kidneys), cryptorchidism (undescended testes), reflux (backup of urine from the bladder toward the kidneys), and intersex (incomplete or otherwise abnormal development of the genital organs.)

Prostate Cancer / Treatment Options


Prostate cancer may be divided, based on its clinical presentation into localized or advanced disease. For men with clinical T1-T2 prostate cancer, curative therapy or observation are options. For men with advanced disease (T3 or above), hormonal therapy and other palliative treatments are the primary approaches for consideration. Men who have a less than 10 year life expectancy with localized disease, as well as men with less than 5 year life expectancy and asymptomatic advanced disease, expectant management is the optimal initial treatment. Management of localized prostate cancer is a controversial issue, in part because the natural history of localized prostate cancer has been only segmentally elucidated. At present, prostate cancer is the most common cancer diagnosed in men in the United States and the second most common cause of cancer death. The ratio of death rate to incidence suggests that between 20 and 50 percent of men with a clinical diagnosis of prostate cancer will die of the disease. In considering the management of localized prostate cancer, it is important to remember that men with latent, incidental microscopic tumors can only rarely have these cancers detected using today's screening tests of PSA and transrectal ultrasound-guided biopsies (Gardner et al., 1998). Preliminary studies that have evaluated a program of observation or watchful waiting rather than screening with a PSA-based approach suggest that the death rate from prostate cancer will decrease with screening. In addition, the small decrease in prostate cancer death rates associated with the increased screening by PSA (with a five- to seven-year lag period) suggests that earlier screening, detection and treatment of men with prostate cancer may have resulted in saving lives. However, little evidence is available at this point with well-performed randomized studies to confirm that treatment of localized prostate cancer will actually decrease death rates from this disease. In distinction, there is widespread acceptance that breast cancer is an important cause of death in women (Walsh, 1994).
Studies on the natural history of localized prostate cancer have suffered from selection biases, but they allow us some insight into what would occur if patients were not treated with curative intention for localized disease. Almost all of these studies indicate that men with metastatic disease had unrecognized advanced disease at least ten years prior to diagnosis. This is supported by the studies of Carter et al. (1992) where serum PSA levels were followed serially in a number of patients in the Baltimore Longitudinal Study of Aging. Therefore, patients who are candidates for curative local therapy should have a 10-year life expectancy.

RESULTS AFTER PROSTATECTOMY


Patients after radical prostatectomy should have an undetectable PSA level. Systemic PSA detection (>0.2 ng/mL) is indicative of recurrent local or systemic disease. The risk of biochemical recurrence is dependent on the local extent of tumor (organ confined vs. extracapsular penetration), invasion of seminal vesicles or lymph nodes and Gleason sum score.  However, Gleason score and extent of local disease in the prostatic specimen provides a far more accurate means of estimating the risk of disease recurrence (Pound et al. 1997).
Results for return of urinary control after prostatectomy vary greatly from surgeon to surgeon in different series, urinary control returns for 75-98% of patients postoperatively. Return of erectile function may take up to 12-18 months, and achievement of erections adequate for vaginal penetration and climax occur in 40-80% of men in selected series, based on the number of neurovascular bundles preserved, age of the patient, preoperative erectile function, and extent of tumor.

Thursday, October 4, 2012

BENIGN PROSTATIC HYPERPLASIA


A common, noncancerous tumor called benign prostatic hyperplasia (BPH) is characterized by uncontrolled growth in the deep, mucosal glands in the prostate and by proliferation of some of the nearby stroma cells. About 50% of men at age 50 and 80% of men at age 70 develop BPH.

Enlargement of the prostate and contraction of its smooth musculature constrict the prostatic urethra, making micturition difficult. BPH can lead to urinary retention, continual dribbling of urine, urinary tract infections, and the formation of kidney stones.

Diagnosis of BPH begins with inquiries about the patient’s urinary symptoms—whether he is hesitant to urinate, has a weak stream, must strain to urinate, feels that his bladder does not empty fully, has increased urinary frequency and urgency, and must urinate often at night.

Next, to determine whether the prostate is enlarged, the physician performs a digital rectal exam; a finger inserted into the anal canal can feel the prostate because it lies just anterior to the rectum (as shown in Figure 1).
FIGURE 1 Reproductive organs of the male, sagittal view. A portion of the pubis is shown in three-dimensional view to illustrate the position of the ductus deferens as it enters the pelvic cavity.

The physician may also order a blood test to check the levels of PSA (which are only mildly elevated in BPH; generally less so than in prostate cancer).

Treatment for BPH begins with drugs that inhibit the production or action of testosterone, which the tumor cells depend on, or drugs that relax the prostate’s smooth muscle. If such treatment does not increase ease of urination, the prostate is either removed in a surgical procedure called transurethral prostatectomy or destroyed by heat from a microwave device or an electrode inserted into the urethra.


Wednesday, October 3, 2012

Urology Board Review: Pearls of Wisdom, Third Edition

Atlas of Colonoscopy

Percutaneous Nephrostomy (Indications+ Relative Contraindications)


Indications
1. Urinary tract obstruction
(a) Malignancy (commonly cervical, prostatic, metastatic pelvic adenopathy, urothelial)
(b) Stone
(c) Ureteric or anastomotic stricture
(d) Pyonephrosis
(e) Assessment of functional recovery of obstructed kidney
2. Urinary diversion
(a) Ureteral injury
(b) Vesical fistula
(c) Hemorrhagic cystitis
3. Access for subsequent interventional or endoscopic procedures
(a) Removal of renal or ureteral calculi
(b) Antegrade ureteral stenting
(c) Dilatation of ureteral or anastomotic stricture
(d) Endopyelotomy
(e) Deliver medications (fungal ball, urothelial tumors, stone dissolution)
(f) Ureteral occlusion for refractory leak
(g) Biopsy of urothelial lesion
(h) Foreign body retrieval

Relative Contraindications
1. Uncontrolled coagulopathy
(a) INR > 1.3
(b) aPTT > 1.5 times normal
(c) Platelet count < 50–100 × 109/L
2. Anticoagulant therapy (aspirin, heparin, warfarin)
3. Uncontrolled hypertension
4. Terminal illness, imminent death

Prostate biopsy ( transrectal US-guided and Transgluteal CT-guided prostate biopsy) part 4


CT-guided transgluteal prostate biopsy
 The patient needs to fast for 6 h before the procedure.
 Antibiotic prophylaxis is not routinely used.
 Intravenous conscious sedation is used with midazolam and fentanyl. Oxygen saturation,
blood pressure, and heart rate and rhythm are monitored throughout the procedure.
 The patient is placed prone on the CT table.
 Lidocaine infiltration of the skin and soft tissues is performed. Peri-prostatic lidocaine
is not necessary in this scenario.
 Under CT guidance and using a transgluteal approach, two 17-gauge coaxial systems
are advanced to the near surface of the peripheral zone of the prostate on each side. The
17-gauge needle is manipulated to guide the core caudally, cranially, medially and laterally
in the prostate and biopsies are taken at the apex, midway between the apex and
base and at the base. Twelve 18-gauge cores are obtained.
 A post-procedure CT is performed to rule out any immediate complication.

Immediate Post-Procure Care CT-guided Transgluteal Prostate Biopsy
 The patient may be discharged 3 h after the procedure, if stable.

Complications
 Infections: Febrile urinary tract infection, bacteremia or acute prostatitis. Rare cases of
fatal septicemia have been reported. Treatment is achieved with oral or intravenous antibiotics depending on the severity of the infection.
 Bleeding: Rectal bleeding, hematuria or hematospermia. Usually bleeding is self-limiting
and should resolve within 1 week. More significant rectal bleeding may require
anoscopic intervention.
 Acute urinary retention has been described, especially in patients with significant BPH.

Alternative Procedures/Future Directions
 Contrast-enhanced transrectal ultrasound: Infusion of intravenous microbubble ultrasound
contrast agents can amplify flow signals within the microvasculature of prostate
tumors, thus making them more conspicuous and allowing for more accurate biopsy
sampling of the prostate.


Key pointsey Points
›› Antibiotic prophylaxis is needed for transrectal US-guided prostate biopsy.
›› Extended biopsy schemes should be performed with five peripheral and one
central core on either side of the prostate, with additional cores for any
hypoechoic lesions detected.
›› Transgluteal CT-guided prostate biopsy can be performed in patients lacking a
rectum.
›› Most common complications include infections and bleeding (rectal, hematuria,
hematospermia).
 IInterventional Radiology Procedures in Biopsy and Drainage,
DOI: 10.1007/978-1-84800-899-1_12, © Springer-Verlag London Limited 2011

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