Laboratory, imaging and endoscopic examinations in urology

Laboratory investigations

Dipstick urine testing: although it is readily available and often used, dipstick testing of urine is an inaccurate investigation. The presence of white cells and nitrites is a rough guide to the presence of infection, although the absence of nitrites in the urine normally is enough to rule out an infection and the need for urine microscopy.
Urine sediment: many laboratories now use an automated method to identify red and white cells in the urine. The numbers of each that can be considered normal are considerably higher than the numbers regarded as normal when urine microscopy is used. These values must be recognised, particularly for red cells, to prevent inappropriate referrals. Microscopic haematuria may be intermittent, but the presence of blood cells in the urine should normally prompt referral for further investigation, and it is considered unnecessary to confirm the presence of red cells by urine microscopy.
Urine culture: culture of a midstream specimen of urine is the only way to identify patients whose symptoms truly result from infection.
Urine cytology: although some automation is used for the analysis of urine cytology, the final arbiter is microscopy - the accuracy of which depends on the expertise of the cytopathologist. Malignant cells are often found in urine of patients with urothelial cancer (mostly high grade bladder cancer).
Biochemistry: Renal function is measured better by serum creatinine than by blood urea, the latter being influenced by the degree of hydration and rate of metabolism. The extent of reserve renal function means there must be a loss of two thirds of overall renal function before levels of serum creatinine increase. Measurements of sodium, potassium, and chloride electrolytes are the other baseline biochemical tests of relevance. Prostate-specific antigen (PSA) is a protein produced by normal, as well as malignant cells of the prostate gland. The PSA test measures the level of PSA in the blood. Prostate-specific antigen is organ specific but not cancer specific; therefore, it may be elevated in benign prostatic hypertrophy (BPH), prostatitis and other non-malignant conditions. There are no agreed standards for defining PSA thresholds. It is a continuous parameter, with higher levels indicating greater likelihood of PCa. Many men may harbour PCa despite having low serum PSA. Normal PSA levels by age are in Tab. 1.

Tab. 1. Normal PSA levels by age
Age Normal PSA (years) (ng/ml) 40-50 0-2.5 50-60 2.5-3.5 60-70 3.5-4.5 70-80 4.5-5.5 Alfa fetoprotein (AFP) is a protein that the liver produces when the cells are growing and dividing.

AFP is normally high in unborn babies. Testing of AFP as tumor marker can help diagnose and monitor treatment of cancers that cause high AFP levels (liver, ovarian, or testicular cancer). Beta subunit of Human chorionic gonadotropin (β-HCG) is a hormone produced in the body during pregnancy. Higher than normal level may indicate in men testicular cancer (in women also choriocarcinoma of the uterus, hydatidiform mole of the uterus and ovarian cancer). β-HCG is also used as a marker postoperatively to monitor residual tumor and the effectiveness of therapy. Lactic dehydrogenase (LDH) is an important enzyme of the anaerobic pathway. Elevated LDH is an indicator of possible tumor burden- metastatic involvement of liver and lung and about 60% of nonseminomatous germ cell tumors but also tissue damage.

Imaging
Ultrasound examinations are used in the investigation of renal, ureteric, bladder, prostatic, and scrotal pathology. They may be regarded as an extension of physical examination. The person who undertakes the examination has the advantage of seeing the images in real time, whereas the doctor has only a few still images. The report thus is of prime importance. Limitations of ultrasonography vary in different situations. In the kidney, ultrasound is enough to identify renal parenchymal cysts, but it may fail to distinguish between parapelvic cysts and hydronephrosis. Ultrasound is a way of screening for renal stones, but assessment of the size of a stone using ultrasound is not very accurate. Renal pelvis and ureteric dilatation can be identified, but the cause is much more difficult to define. A stone at the lower end of the ureter may be identified by using the full bladder as an acoustic window. The bladder is seen easily on transabdominal ultrasound, and volume measurement of residual urine is simple and accurate. Intravesical pathology, such as tumours and stones, can be seen best when the bladder is full.

Transrectal ultrasonography of the prostate has transformed the understanding of prostatic anatomy and pathology. Volume of enlarged prostate can be measured precisely. Biopsies of the prostate and placement of radioactive seeds in brachytherapy are always undertaken with ultrasound imaging. Scrotal ultrasound can help to diagnose testicular tumor, epididymis, absces, varicocele and hydrocele. Radiological investigations are in Tab. 2.

Tab. 2. Radiological investigations
• Plain abdominal x ray • Intravenous urogram • Urethrogram • Retrograde uretero(pyelo)gram • Antegrade pyelo(uretero)gram • Computed tomography • Magnetic resonance imaging • Isotope renogram • Isotopic glomerular filtration rate • Isotope bone scan • PET/CT scan

The methods of radiological investigation are used in different situations. Intravenous urography (combined with renal ultrasonography) was the investigation of choice for patients with painless haematuria. Now is replaced by CT urography. Non-contrast computed tomography of abdomen is standard for diagnosis in renal colic. Contrast enhanced computed tomography is the investigation of choice for identifying renal masses and retroperitoneal processes. CT urography is investigation for detecting urotelial cancer in upper urinary tract, ureteral stenosis, trauma etc. Magnetic resonance imaging has been adopted as the investigation of choice in the staging of prostate and bladder cancer and lymph nodes. In patients with elevated PSA levels is multiparametric MRI of the prostate the first step in examination and detection of changes of the structure, which can help to navigate the biopsy (fusion biopsy). The same investigation can be helpful if used on bone settings to interpret areas of increased isotope uptake on a bones scan. Dynamic isotope renography that uses mercaptoacetylglycine (MAG3) as the radiopharmaceutical is the most accurate method of identifying upper urinary tract obstruction and also shows differential renal function. The most accurate measurement of glomerular filtration rate is obtained by using an ethylenediamine tetra-acetic acid (EDTA) clearance technique. Isotope bone scans are used in uro-oncology to identify bony metastatic disease (isotope Technetium 99). A positron emission tomography (PET) scan is an imaging test that can help reveal the metabolic or biochemical function of your tissues and organs. The PET scan uses a radioactive drug called a tracer to show both typical and atypical metabolic activity. A PET scan can often detect the atypical metabolism of the tracer in diseases before the disease shows up on other imaging tests, such as computerized tomography (CT) and magnetic resonance imaging (MRI). Positron emission tomography/computed tomography (PET/CT) is integration of PET and CT scan, which can help to localise precisely atypical metabolic activity. There are different modalities of PET/CT depending on type of tracer and carrier. 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT) has emerged as a powerful imaging tool for the detection of various cancers. In Urology is already recommended in the European Association of Urology guidelines for the follow up of seminomas. 68Ga-PSMA PET/CT is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen (PSMA) expression. Is very helpful in diagnostics of the metastatic disease. Endoscopic examinations Cystoscopy is a procedure which enable to look inside the bladder using a thin camera. A cystoscope is inserted into the urethra and passed into the bladder to allow to see inside. Small surgical instruments can also be passed down the cystoscope to treat some bladder problems at the same time. Urodynamics Urodynamic investigations of the upper urinary tract are not often performed. Assessment of the function of the lower urinary tract can be made by a number of investigations, which are listed in Tab. 3.

Tab. 3. Urodynamic investigations • Uroflowmetry (measurement of urinary flow rate during voiding) • Filling cystometry (assessment of bladder capacity, size of the residual urine volume and measurement of bladder pressures with a inserted special urethral catheter during bladder filling) • Voiding cystometry (bladder pressure and urinary flow assessment during voiding with inserted special urethral and rectal catheters). • Profilometry

Courses

• Surgery 5 (Trauma Surgery, Urology) [ChK/S-GM5/18]