Книги по МРТ КТ на английском языке / Advanced Imaging of the Abdomen - Jovitas Skucas

Therapy

Resection

Currently surgical resection is the gold standard in treating BPH, most often using a transurethral approach. Post-resection MRI reveals degenerative changes near the prostate surface and shrinkage of the prostatic capsule. A dilated prostatic urethra is readily identified.

A complication of a radical retropubic prostatectomy is an inguinal hernia. Most of these hernias are indirect. Fistulas are uncommon; with surgery being close to the symphysis pubis, an occasional fistula leads to osteitis pubis.

Bladder hypertrophy due to obstruction by BPH is to a large extent reversible after surgical relief, except in those with irreversible degenerative changes.

Nonsurgical

The natural progression of BPH suggests that in many men an initial decision to prescribe no therapy is a viable option; symptoms in most men do not progress. In some, a-adrenergic- blocker therapy and 5a-reductase inhibitor therapy are helpful.

Although a number of nonsurgical techniques, such as laser therapy, microwave thermotherapy, and others have been tried, thermal ablation is currently the only viable alternative to surgery, achieving similar results. Balloon dilation has been disappointing.

Laser Therapy

Laser ablation thermotherapy leads to coagulation necrosis, with eventual reepithelialization. In theory, laser coagulation shrinks the prostate by inducing prostatic necrosis without injury to the urethra or surrounding tissues. Currently, results from US-guided laser-induced transurethral thermal therapy appear inferior to those obtained with transurethral resection. One disadvantage of laser therapy is that no tissue is obtained and it takes longer to attain symptomatic improvement compared to transurethral resection. Prostatic volume initially is not reduced, and postprocedure urinary retention is common. Laser therapy, however, is still a new technique, and further advances are to be expected.

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Few complications are encountered and symptoms eventually improve in most. Rarely, the loss of ejaculation, epididymitis, or an abscess develops. Urethral stricture is a late complication.

Magnetic resonance imaging detects prostate changes during and after laser-induced thermotherapy. Repetitive T2-weighted fast spin echo (FSE) MRI during coagulative laser thermotherapy revealed persistent hypointense regions, presumably representing coagulation necrosis. These regions increase in size during therapy. The prostate remains enlarged shortly after treatment, and contains poorly defined hypointense regions surrounding the urethra; with time, the prostate gland returns to its preoperative size.

Central coagulation necrosis is seen as a hypointense region surrounded by a hyperintense rim. The prostate increases in size, presumably due to edema; edema is evident in the surrounding tissues and the presacral space thickens. Subtracting postprocedure laserinduced lesion volume (obtained via MR planimetry) from preprocedure volume predicts prostatic volumes at late follow-up (13), although transitional zone volume was underestimated and peripheral zone volume was overestimated.

Microwave Ablation

Transurethral microwave thermotherapy is a potential outpatient procedure requiring little or no anesthesia. A temperature ≥60°C results in coagulation and tissue necrosis. Tissue vaporization ensues if the temperature is >100°C. Use of higher energy levels improves results but at the expense of increased morbidity.

Symptomatic improvement is achieved in about half of men treated with microwave thermotherapy. Imaging findings are inconstant. Magnetic resonance imaging detects prostatic urethral widening. Necrosis is an inconstant finding. Findings on voiding cystourethrography and retrograde urethrography before and after transurethral microwave therapy do not correlate with subjective improvement. The transition zone volume, obtained from pretreatment endorectal US, appears to relate to long-term microwave thermotherapy efficacy.

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Other Therapy

Self-expanding endourethral stents have been used to treat bladder outlet obstruction due to prostatic hyperplasia; still, urethral stents have had limited success, with some stents dislodge or become encrusted.

Preliminary results using an electrosurgical generator for transurethral prostatic electrovaporization are encouraging. Postoperative urine incontinence is a potential complication.

High-intensity focused ultrasound therapy is still experimental.

Infection/Inflammation

Prostatitis

Prostatitis can be either acute or chronic. At times a specific pathogen is detected; if not, the clinical symptoms are often ascribed to prostatodynia, a previously poorly defined condition. In this work prostatodynia is used to designate pelvic venous congestion and is discussed later (see Vascular Abnormalities).

Granulomatous prostatitis is a histologic diagnosis. Common causes are prior prostatic surgery and prostatic needle biopsy. Occasionally prostatic granulomas develop in a setting of prior bacillus Calmette-Guérin therapy.

Ultrasonography reveals a complex pattern in prostatitis. At times prostatic nodules are present. In a normal gland Doppler US using a coronal plane reveals capsular and parenchymal arteries radiating symmetrically. These arteries become more prominent in acute prostatitis.

Ejaculatory duct calcifications develop in chronic prostatitis.

Early prostatic cancer and prostatitis are difficult to differentiate with current imaging. Of interest is that in some patients with prostatitis MR spectroscopy detects an elevated choline peak and reduced or no citrate, findings mimicking those of cancer (14).

prostate can be involved, and an abscess may or may not communicate with the urethra. Some prostatic abscesses result in bladder outlet obstruction.

A prostatic abscess is detected either by CT or endorectal US. Typically US reveals hypoechoic or anechoic regions with internal echoes, suggesting fluid-filled structures containing septations. Some mimic loculated cystic prostatic tumor.

Once diagnosed, a prostatic abscess can be drained using endorectal US guidance, and a perineal or transurethral drainage approach can be used.

Tuberculosis

Tuberculosis either is primarily genital in origin and involves the seminal vesicles, prostate, and adjacent structures, or these structures are involved by extension from the kidneys. An occasional tuberculous prostatitis is associated with intravesical carcinoma therapy with bacillus Calmette-Guérin.

Tuberculosis results in prostatic inflammation, enlargement, necrosis, or abscess. Cystography reveals prostatic enlargement simply as bladder base elevation. Urethrography identifies any urethral stricture or fistula to adjacent structures. Endorectal US reveals prostatic enlargement with multiple hypoechoic foci within the gland, usually anteriorly in the transition zone, representing necrotizing granulomas. Eventually these granulomas calcify.

In some men seminal vesicle and vas deferens calcifications are the only imaging abnormality. Vas deferens calcifications are either intramural or intraluminal in location, and the appearance mimics findings seen with diabetes mellitus.

Computed tomography reveals inflammation of the surrounding structures, including perivesical fat stranding.

Abscess

Predisposing factors for periprostatic or prostatic abscesses are diabetes mellitus, urethral catheterization or manipulation, and an immunocompromised status. Most abscesses are infected, with only an occasional sterile abscess encountered. Any portion of the

Other infections

The seminal vesicles dilate and calcify secondary to schistosomal involvement. At times the ejaculatory ducts also dilate. Schistosomiasis induces prostatic retention cyst formation and eventual prostatic enlargement and calcifications.

Ultrasonography detects hyperechoic prostatic foci. Seminal vesiculography outlines the dilated lumen and irregular border. After therapy the prostate decreases in size and the hyperechoic foci become less evident. Some investigators believe that calcifications also diminish.

In endemic regions the presence of typical calcifications is presumptive evidence for schistosomiasis.

Prostatic aspergillosis is rare in a immunocompetent patient. It is associated with recurrent urinary tract infections.

Brucellar prostatitis is rare even in brucel- losis-endemic regions, such as certain provinces of Spain. Ultrasonography is useful to follow therapy.

Malacoplakia

Prostatic malacoplakia is a granulomatous inflammatory disorder, presumably being a variant of chronic granulomatous prostatitis. Prostatic malacoplakia can form fistulas to adjacent structures. It often mimics a malignancy and some affected men have undergone a radical prostatectomy for suspected carcinoma.

Past urinary tract infections are a common precedent.

Ultrasonography revealed a hypoechoic peripheral zone tumor in three men with prostatic malacoplakia (15).

A biopsy should provide the diagnosis by detecting Michaelis-Gutmann bodies, although even a biopsy can be misdiagnosed as a carcinoma.

Tumors

Sclerosing Adenosis

Sclerosing adenosis usually develops in a setting of prostatic gland hyperplasia. Even histologically, this entity is difficult to differentiate from a well-differentiated adenocarcinoma.

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cysts. Müllerian duct cysts tend to project somewhat lateral to the midline, while utricle cysts are midline structures; müllerian duct cysts tend to be larger and extend further superiorly, while utricle cysts tend to be small. However, considerable overlap exists and these cysts cannot be readily differentiated from each other. A rare müllerian duct cyst is associated with prostatitis.

A dilated utricle is associated with hypospadias and testicular abnormalities. Some utricle cysts lead to dysuria. They vary in size. Urography and US simply detect a retrovesical cyst.

An occasional midline prostatic cyst is a cystadenoma or a simple cyst, but not all prostatic cysts are benign. A rare one is a prostatic cystic adenocarcinoma, often in a young man.

Clinically most prostatic cysts are asymptomatic,although an occasional larger one leads to bladder outlet obstruction or becomes infected.

Magnetic resonance reveals prostatic cysts similar to other fluid-filled structures; namely, they are hypointense on T1and hyperintense on T2-weighted images. Blood and other fluid modify these findings.

Prostatic cysts are amenable to transrectal puncture and drainage under US guidance. A müllerian duct cyst causing ejaculatory duct obstruction was drained transurethrally using US guidance (16).

Benign Neoplasm

Benign prostatic neoplasms are almost nonexistent, and most reported ones are anecdotal. No imaging features differentiate them from malignancies.

A schwannoma within the prostate ranges from a focal tumor to an enlarged prostate. Transrectal US identified one as a hypoechoic nodule in the periphery (17); specific diagnosis could be established only by biopsy.

Prostate involvement in neurofibromatosis is rare. Endorectal coil MR localizes and provides guidance for biopsy of suspicious tumors.

Prostatic and Müllerian Cysts

Prostatic cysts are uncommon. Embryologically, many of these cysts represent either an enlarged prostatic utricle or a cystic müllerian duct; both tend to be located close to the midline, which helps differentiate them from the more laterally located seminal vesicle and ejaculatory duct

Prostate Carcinoma

Primary

Clinical Aspects

General: In the West, prostatic cancer is the most commonly diagnosed cancer in men. For

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unknown reasons, the relative incidence appears to be increasing in both Europe and North America. Only part of this increase is explained by improved diagnosis. One factor influencing results is that the number of prostate T1a–b cancers has declined considerably, with the decline probably due to less frequent use of surgical prostatectomy for treating BPH. At least in the United States a rise and fall in prostate cancer detection rates occurred in the 1990s, believed by some to represent primarily a removal of previously undetected T2 cancers from the prostate cancer pool due to improved screening, leaving behind mostly undetected T1c cancers as a residual reservoir (18). Among men treated with a radical prostatectomy for clinical stages T1c to T2c from 1988 to 1996, T1c cancers increased from 10% in 1988 to 73% in 1996, cancers confined to the prostate increased from 40% to 75%, and transition zone cancers increased from 10% to 21% (18); on the other hand, seminal vesicle invasion decreased from 18% to 5%, positive surgical margins decreased from 30% to 14%, and the mean patient age decreased from 65 to 62 years.

Unlike many other cancers, prostate cancer has a wide spectrum of activity, and a number of these cancers do not result in serious morbidity and mortality. Especially welldifferentiated ones tend to be quiescent for considerable time, although the current concept is that prostatic cancers progress. Some investigators assume a simplistic division of prostatic cancers into indolent ones that are unlikely to progress and those that result in extensive morbidity and mortality. Probably a more realistic assumption is a continuous spectrum containing two peaks. Thus although prostate cancer is quite common in elderly men, it is difficult to predict in any one individual whether the cancer will progress or not. Extrapolating findings from an autopsy study of prostates containing a clinically undetected carcinoma, carcinomas remaining clinically insignificant throughout life tend to have long doubling time, while those that become clinically significant are likely to have doubling times of several years or less; thus knowledge of a tumor doubling time in an elderly patient could provide clinical guidance.

In men at a mean age of 64 years, the Association Française d’Urologie estimates a 43% histologic prevalence of prostate cancer and that it

takes about 12 years for a 0.5-cc cancer to reach a volume of 4cc, a size associated with the risk of distant metastases (19); without therapy, a localized cancer diagnosed before age of 65 years results in a survival of less than 30%. Complicating matters, even with therapy prostate cancer diagnosed before the age of 50 years is associated with <50% survival at 5 years; many of these men already have metastases at initial diagnosis.

Most prostatic carcinomas originate in the prostatic gland periphery. With growth, the tumor invades the surrounding structures, including the rectum. Thus occasionally an invasive prostatic carcinoma presents with rectal bleeding.

One patient with prostate cancer developed disseminated intravascular coagulopathy (20); the authors postulated the release of procoagulation substances during diagnostic or therapeutic procedures.

Etiology: A study combining data from several French urologic centers concluded that clusters in families (familial) account for 15% to 25% of prostate cancers and hereditary forms were evident in 5% to 10% (21). In addition to such an inherited trait, having an autosomal-dominant mode with variable penetrance, environmental factors also have a role,and in some of these men a purely environmental influence is evident.Carriers of a germline mutations in the BRCA1 gene on chromosome 17q appear at increased risk for prostate cancer. In general, a hereditary influence is more evident in those who develop prostate cancer at a younger age. No major pathologic differences exist between the hereditary and sporadic forms of cancer.

Applying familial cancer data to clinical practice, the Association Française d’Urologie estimates that, compared to the general population, a family history (first-degree relative) of prostate cancer is associated with a twoto threefold increased risk of prostatic cancer (19); such a familial association thus defines a highrisk group for screening.

Schistosomiasis is associated with bladder, rectal, and renal cancers. No definite association with prostate cancer is established, although prostate cancer is occasionally reported in young men with schistosomiasis.

Although adenomatous hyperplasia appears intermediate between BPH and a welldifferentiated carcinoma, suggesting that it is a

possible precursor for carcinomas arising in the transition zone, BPH is not considered to be a precursor to prostatic cancer. Likewise, in spite of some earlier reports, no definite association exists between prior vasectomy and prostate cancer.

Screening: Screening for prostatic cancer is controversial. In the United States and some European countries routine physical examination of men at risk (generally considered to be those over age 50 years) include a digital rectal examination and determination of serum prostate-specific antigen (PSA) level. In some countries PSA testing is not routinely performed, the reasoning being that its use in screening results in overdiagnosis and overtreatment. Also, some believe that no firm evidence exists that early diagnosis decreases mortality. In addition, because of the prolonged time course of prostatic cancer growth in some men, whether cure in the higher surgical risk group really represents the best option is also questioned. Some physicians believe that PSA testing is not usually indicated in men over about 70 years unless digital examination suggests prostatic disease; another viewpoint is that in those with a life expectancy greater than of 10 to 15 years an elevated PSA level is an indication for US and biopsy. Nevertheless, in countries with extensive screening, evidence suggests that an earlier diagnosis has an impact on this cancer, and the number of men seen with advanced disease decreases.

In the United States, the recommended frequency for PSA screening for prostate cancer is every year, although an optimal interval has not been established. A Rotterdam study, in which 4133 men, aged 55 to 75 years, underwent PSA screening initially, again 4 years later in over half the subjects, and, when indicated, a needle biopsy was performed, found that initially 36% of the cancers detected had a Gleason score of 7 or higher but only 16% of those detected 4 years later had such an elevated score (22); initially 25% of the cancers detected had adverse prognostic features, but only 6% of those detected 4 years later did, and the authors concluded that most large prostate cancers are detected by PSA screening and, among these men, a screening interval of 4 years appears to be short enough to prevent large tumors from developing.

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A serum PSA level of up to 4 nanograms per milliliter is commonly assumed to be within the normal range, although this level is arbitrary, and a number of men with a lower PSA level have developed prostatic cancer. Of interest is that many of these tumors are also not detected by endorectal US and digital rectal examination.

The production of PSA is influenced by androgen levels, and those taking drugs for androgen suppression have low PSA levels even in the presence of a prostatic carcinoma. False serum positive PSA levels are uncommon when using a monoclonal assay. The PSA levels are elevated in some men with urinary tract infection but decline as infection clears; this marker thus appears useful in following infection progression. The PSA level is also increased with some nonprostatic neoplasms, including some lymphomas.

A digital rectal screening examination detects two thirds to three quarters of prostatic cancers. In general, the sensitivity of the PSA assay is higher than either digital rectal examination or endorectal US. When combining serum PSA levels and digital rectal examinations for screening, some cancers are detected because of an elevated PSA level only. A high proportion of these men will have a nonpalpable prostate cancer, and endorectal US is appropriate in this population.

About 40% to 50% of hypoechoic foci identified by endorectal US are cancerous. These percentages can be improved; thus a majority of hypoechoic foci in men with a PSA >10ng/mL are positive for cancer, but in those with a PSA £4ng/mL only a small minority are positive.

What is the effect of instituting PSA screening and sextant biopsies on prostate cancer detection? From serum stored in Göteborg, Sweden, in 1980, PSA was analyzed for 658 men born in 1913 with no previously known prostate cancer (23); among those found to have a PSA level of >3ng/mL, the mean time from increased PSA to an eventual clinical diagnosis of prostate cancer was 7 years. Thus screening 67-year-old men should lead to cancer detection and treatment a mean of 7 years before clinical symptoms develop.

In summary, in asymptomatic men a screening digital rectal examination together with a

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serum PSA level detects more prostate cancer and at an earlier stage than a digital rectal examination alone. Currently endorectal US is not sufficiently sensitive and specific to be used for routine screening for prostate cancer. Nevertheless, a basic question remains: Are the additional cancers detected with a screening program mostly latent ones of limited future significance or do they represent those that will progress and, if untreated, metastasize?

A number of PSA-related tests have been investigated: serum PSA level, age-adjusted PSA level, PSA density, PSA velocity and a ratio of free-to-total PSA. In blood, PSA is either free or bound to proteins. PSA associated with prostate cancer tends to be more protein-bound and thus the ratio of free-to-bound PSA appears of some value in estimating cancer risk. A PSA agecorrected level is often used in screening programs. The rationale is that it will detect younger patients with potentially curable prostate cancer and identify those older patients not requiring additional tests.

The ratio of free to total PSA varies with prostate volume, but this ratio is of limited use in differentiating benign from malignant disease. It appears to have a role with a serum total PSA level between 4 and 10ng/mL, and some authors suggest the use of this ratio in men with a total PSA level between these levels as an indicator of whether to biopsy or not, yet the cutoff ratio used influences the resultant sensitivity and specificity. The specificity can be improved, but at decreased sensitivity (i.e., fewer cancers detected). Currently this ratio is not commonly employed as an initial guide about whether to biopsy.

Serum PSA levels increase with prostate volume. Thus rather than relying on an absolute serum value, a PSA density value appears useful, defined as serum PSA level divided by prostatic gland volume as measured by rectal US and expressed in nanograms per milliliter per milliliter of tissue. Theoretically, PSA density compensates for the gradual increase in PSA level due to gland growth with age. A PSA density value is most useful in men with a normal digital rectal examination and a PSA level between 4 and 10ng/mL, although some authors deem such density measurements unreliable. In men with a PSA level >10ng/mL, the PSA density is of even less significance.

A variant of the above is to use the PSA value adjusted for prostate transitional zone volume. This PSA transition zone density is obtained by dividing the PSA value by the transition zone volume. A change in PSA blood level over time is known as PSA velocity and is expressed as a PSA increase per year. Although men with BPH also have an increase in PSA level with age, those with cancer have a more logarithmic increase. The PSA velocity is of less use in patients with an elevated PSA level and negative biopsy.

Pathologic Study

Adenocarcinoma accounts for about 95% of all prostatic malignancies. Mucinous adenocarcinomas of the prostate are uncommon, and their prognosis is worse than that of a more typical adenocarcinoma. A rare papillary cystadenocarcinoma has been reported; cyst aspiration yields a very high PSA level. An adenoid cystic carcinoma is a variant of a prostatic adenocarcinoma; some of these are associated with a normal PSA level even in the face of spread.

Of the rest, transitional cell carcinoma predominates, followed by an occasional squamous cell carcinoma, small cell carcinoma, sarcoma, and metastasis to the prostate. Primary squamous cell carcinomas and sarcomatoid carcinoma have developed in previously treated adenocarcinomas, although a sarcomatoid carcinoma can originate de novo (24). A rare prostatic carcinoma contains endometrioid features; both PSA and CEA levels tend to be elevated. These are rather aggressive cancers. A curiosity is one malignancy metastasizing to another malignancy. Thus prostate carcinomas have metastasized to renal cell carcinomas.

Occasionally a biopsy reveals prostatic intraepithelial neoplasia without an adenocarcinoma. This neoplasia, considered a precursor of prostate cancer, is subdivided into high grade and low grade; high-grade intraepithelial neoplasia is believed to be premalignant and a strong predictor of later cancer, while the lowgrade variety tends to behave like BPH and is associated with a low risk of carcinoma. Abnormal growth factor receptors and general genetic instability are associated findings with prostatic intraepithelial neoplasia. A biopsy finding of

high-grade intraepithelial neoplasia without evidence of a carcinoma generally should be followed by additional biopsies. One should also keep in mind that some prostatic intraepithelial neoplasias are difficult to differentiate from cancers based on cytologic material.

A finding of neuroendocrine tumor cells is not uncommon in prostate cancers and presumably reflects different stem cell evolution. In distinction to androgen-responsive prostate cancer cells, these neuroendocrine tumor cells lack androgen receptors and are androgen insensitive.

Prostate carcinomas are graded using either the Gleason or World Health Organization (WHO) grading systems (with nucleolar subgrading). In the United States the Gleason grading system is more widely used. At least for relatively advanced primary tumors the Gleason grading system appears superior in predicting prognosis than the WHO grading system (25).

In the Gleason system the tumor glandular pattern is evaluated and the two most common patterns graded from 1 to 5. These primary and secondary patterns are then combined to obtain a Gleason score. A score of 2 signifies a well-differentiated tumor and 10 is a highly malignant one. In general, a biopsy Gleason score correlates with resected prostate specimen Gleason score. Paired biopsies and prostatectomy specimens from clinically localized prostate cancers revealed exact score agreement in 57% and a difference of ±1 unit in 92% of the paired samples and predicted tumor stage (26); with minimal tumor size on a biopsy, however, the Gleason score does not predict tumor stage.

A less often used grading system is based on an estimate of mean nuclear volume, developed by Gunderson and Jensen. In some hands this system is prognostically superior to the Gleason system.

Cytometry of the DNA is useful in some patients. Thus a finding of a constant diploid and tetraploid pattern with DNA cytometry identifies those who are at little or no significant risk of tumor progression even without therapy (27); men with a DNA tetraploid histogram may deteriorate with hormonal therapy. A DNA aneuploid pattern suggests that a cancer may not respond to hormonal therapy.

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A xanthoma is a localized collection of cholesterol-filled histiocytes. Most are idiopathic, although some develop in a setting of hyperlipidemia. Their importance is that occasionally a xanthoma biopsy suggests a carcinoma; confusing the issue, xanthomas have been reported adjacent to foci of adenocarcinoma. A foamy gland carcinoma contains xanthomatous cytoplasm but lacks the nuclear enlargement and prominent nucleoli associated with a carcinoma.

Detection

Currently the most common initiator for a search for prostate carcinoma is a screening finding of an elevated PSA level. Examinations used in prostate cancer detection include digital rectal examination, endorectal US, MRI, and US-guided transrectal biopsy. Each of these procedures has its limitations. In general, the detection rate for prostate carcinoma increases when these procedures are used in combination.

Computed Tomography: Nonhelical CT detects an enlarged gland but cannot distinguish between BPH and a neoplasm. Carcinoma is suggested only by an irregular contour outline. Helical CT, on the other hand, identified cancer in 88% of patients as peripheral zone regions of contrast enhancement (28); transitional zone cancers, on the other hand, appear similar to benign nodules.

Ultrasonography: Most peripheral zone carcinomas are hypoechoic, a nonspecific finding because a number of benign conditions are also hypoechoic. If a tumor is hypoechoic and also palpable, the probability of carcinoma is about 75%. Hyperechoic prostatic cancers are less common. They tend to be large when first detected. The least common are isoechoic ones. Common US criteria used to suggest a prostate cancer are the presence of a peripheral zone hypoechoic nodule, peripheral zone inhomogeneity, and loss of zonal architecture.

Adenocarcinomas originating in the transition zone are usually not detected with US.

Endorectal US provides more information than a transabdominal approach. Nevertheless, to put US in perspective, based on data from sextant biopsies, in one study overall agreement

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between gray-scale and Doppler US findings and biopsy results were minimally superior to chance, and the authors concluded that sextant biopsies are still necessary (29). A number of controlled studies suggest that gray-scale US detects about half or less of prostatic cancers. One study found that endorectal gray-scale US detected less than half of 190 subsequently found cancers (30); targeted biopsies detected 57% of these cancers, with the rest detected by sextant biopsies, and the authors concluded that targeted biopsies should be accompanied by sextant biopsies. Although sensitivity and specificity obtained with US is disappointing, US has an established role in biopsy guidance and a potential future role in evaluating tumor blood supply and possibly assessing temperature distribution during some therapeutic heat applications.

Preliminary studies suggest that contrastenhanced US aids cancer detection. Using biopsy sites showing prostate cancers as a gold standard, gray-scale and Doppler US sensitivity of cancer detection increased from 38% precontrast to 65% postcontrast, but the specificity was unchanged (31). Endorectal US and color Doppler US achieved a 78% sensitivity in detecting proven prostate carcinomas (32); use of a contrast agent (Levovist) improved the sensitivity significantly to 93%. Of interest is that post-Levovist, most of the cancers appeared avascular within a strongly enhancing peripheral gland.

Most malignant tumors are associated with angiogenesis and increased blood velocity through these vessels. Although color Doppler US detects such increased velocity, small neoplasms are missed. Also, some infiltrating cancers are isovascular and isoechoic. Some studies suggest a positive correlation between tumor blood supply and Gleason score. One should keep in mind that some benign lesions also have increased flow.

Magnetic Resonance Imaging: Of all imaging modalities, MRI shows the greatest potential in detecting prostatic carcinomas. It is performed with either a body coil or, preferably, an endorectal coil. Compared to histopathological results in consecutive patients with prostate cancer, endorectal coil MRI cancer detection rate for tumors <5mm was only 5% but increased to 89% for tumors >10mm (33). MRI

using endorectal and pelvic phased-array coils detects more prostate cancers than digital rectal examination or endorectal US; predicted tumor volume obtained from MRI correlates with resected tumor volume.

On T2-weighted images a prostatic carcinoma typically is hypointense relative to the higher intensity normal peripheral zone. Nevertheless, a hypointense peripheral zone is not pathognomonic for a prostatic cancer; prostatitis, benign prostatic hyperplasia, or an infarct can have a similar appearance. A wedge shape and diffuse extension without mass in a hypointense peripheral zone suggest benignity, while a large size is associated with malignancy (34). Cancers in the central and transitional zones are difficult to identify with MRI; when large, they tend to disrupt the normal gland architecture. On gadolinium enhanced images the normal prostate enhances more in the central zone than peripheral zone; a carcinoma, on the other hand, ranges from enhancing more than the normal peripheral zone, to about the same enhancement and occasionally even less than peripheral zone and gadolinium-enhanced images do not appear reliable in MR imaging of prostatic carcinoma. Overlap also exists with hyperplasia. Dynamic contrast enhanced images may, however, provide better tumor definition by outlining tumor margins more clearly than with unenhanced images. Currently gadolinium is not routinely employed in evaluating prostatic carcinomas.

Dynamic contrast-enhanced images, on the other hand, may provide better tumor definition by outlining tumor margins more clearly than with unenhanced images. Currently gadolinium is not routinely employed in evaluating prostatic carcinomas.

1H–MR spectroscopy reveals a correlation between water T2-relaxation time and tissue citrate concentration. Endorectal 1H–MR spectroscopy detects metabolic differences between normal prostatic tissue, benign disease, and cancer, and thus potentially can differentiate benign from malignant disease. Significantly higher choline levels and significantly lower citrate levels are found in cancer tissue compared with BPH and normal tissue. Men with cancer have a significantly lower citrate-to- choline ratio than those with BPH. A present limitation in differentiating tumors is MR

spatial resolution. MR spectroscopy appears to be useful in a setting of negative biopsy and a rising PSA level. Also, with extensive postbiopsy distortion, such as hemorrhage, adding MR spectroscopic imaging to MR imaging improves prostate cancer detection rates; cancer is identified at MR spectroscopic imaging by an elevated metabolite ratio above normal.

Adding 3D proton MR spectroscopic imaging to MRI improves prostate cancer detection and localization compared to the use of MRI alone (35).

Scintigraphy: Attempts have been made to differentiate BPH and prostate cancer with 2- [18F]-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET), but results are unreliable. Regions of high tumor uptake blend with radioactivity in urine and measures should be taken to eliminate the latter. Likewise, PET is not as sensitive as bone scintigraphy in detecting bone metastases. On the other hand, prostate cancers have an increased uptake of choline, which is needed for phosphatidylcholine synthesis, a cell membrane phospholipid. Positron emission tomography after IV carbon-11-choline in men with prostate cancer reveals marked tumor uptake and negligible urine radioactivity. Occasionally a positive choline scan detects a tumor in the face of a negative PET-FDG scan (36).

Radioimmunoscintigraphy using Tc-99m- labeled monoclonal antibody (CYT-351) against a membrane antigen in men with suspected prostatic malignancy shows potential in imaging both the primary site and metastatic foci.

Biopsy: Six sextant core needle biopsies represent the current standard in detecting stage T1c and T2 prostate cancer. Ultrasonography guidance using an endorectal approach and an automated biopsy gun are some of the refinements available. More extensive biopsies are obtained from sonographically detected hypoechoic regions. Combining the two techniques yields a higher positive rate than with either one alone. Using a sextant biopsy pattern, cancer detection rates appear higher if the prostate is small; a greater sampling error is probably introduced with a large prostate, and thus more samples are needed with a large gland. The positive yield of systematic sixsector biopsy decreases when the prostate gland volume is enlarged. In men with a clinical sus-

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picion of prostate cancer, a correlation exists between serum PSA level and a likelihood of obtaining a positive biopsy.

Aspiration cytology rather than core biopsy is also feasible, although aspiration cytology detects somewhat fewer cancers than a needle biopsy and appears to be an inadequate screening modality for occult carcinomas in a setting of a normal digital rectal examination and normal acid phosphatase level. An advantage of a core needle biopsy is that with sufficient carcinoma tissue in the biopsy, grading is similar to that obtained from prostatectomy tissue, because most prostatic cancers tend to be highly malignant.

Prostatic cancer detection is improved if instead of six biopsies, additional US-guided transrectal prostatic biopsies are obtained. Thus 10 instead of six biopsies increases cancer detection several percentages, with a greatest improvement found in those with a small cancer. An increased number of biopsies should be balanced, however, against an increased risk for complications.

Although some studies suggest that USguided transrectal biopsy results are similar to those obtained with finger-guided transperineal biopsy (37), most authors consider the transperineal approach to be less reliable and use it when a transrectal approach is contraindicated. Biopsy sensitivity is superior when using US guidance versus digital rectal guidance, and, in fact, often a primary use of endorectal US is in directing a biopsy needle into suspicious regions.

Instead of endorectal US, endourethral US guidance is an alternative for transperineal prostate biopsies; this approach provides biopsy guidance for those men who had a previous rectal resection.

Endorectal MR is potentially useful both to identify tumor sites and as a guide for prostatic biopsy, replacing US.

Few major but frequent minor complications are encountered after transrectal prostatic biopsy. The most common complication is persistent hematuria; infectious complications are rare. Postbiopsy hemorrhage affects MR spectroscopy by hiding metabolic peaks and this test should be performed prior to biopsy or at least a month later.

What should be suggested in a setting of an elevated PSA level or an abnormal digital rectal

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examination but negative transrectal US-guided biopsies? Several studies suggest that among this subset of men a repeat biopsy within 6 weeks to 6 months will be positive in 10% to 50%. The chance of a second biopsy being positive increases if the serum PSA level is >10 ng/mL or if premalignant changes are detected on the initial biopsy. A negative sextant biopsy thus does not exclude a tumor and is of limited prognostic value. Also, prior hormone therapy influences biopsy results; some men who undergo hormone therapy have sparse tumor cells.

Staging

Whether a cancer is confined to the prostate or extends beyond the prostatic capsule is of obvious importance because it influences whether a prostatectomy or nonsurgical therapy is considered. A cancer growing beyond the prostate most often is in the posterolateral portion of the gland. At times a sharp beak extending from the prostate at this location is identified, representing tumor penetration through the capsule. The capsule itself is not identified. A bulging prostate capsule is suggestive but not diagnostic of extension beyond the capsule.

Table 13.2 outlines the tumor, node, metastasis (TNM) clinical staging system. Although a biopsy specimen Gleason score and digital rectal examination are relatively reliable in predicting tumor stage, the initial serum PSA level has evolved to be of greatest prognostic significance. It not only correlates directly with the probability of extracapsular tumor spread, but also is a predictor of treatment failure.

Prostate-Specific Antigen Level: In some institutions prostate cancer staging consists of a digital rectal examination, measurement of serum tumor markers, and a radionuclide bone scan,with CT or MRI performed only as needed. Others do not obtain bone scans and skeletal radiography in the routine staging of prostatic carcinoma, believing that these studies are useful primarily with clinical suspicion of bone involvement or if the PSA level is elevated (bone metastases are discussed later; see Distal Spread).

Prostate volume can be calculated from US data and density of serum PSA relative to total

Table 13.2. Tumor, node, metastasis (TNM) staging (clinical) of prostate tumors

G: Gleason score

Gx Grade cannot be assessed

G1 Well-differentiated tumor (Gleason 2–4)

G2 Moderately differentiated (Gleason 5–6)

G3–4 Poorly differentiated/undifferentiated (Gleason 7–10)

Source: From the AJCC Cancer Staging Manual, 6th edition (2002), published by Springer-Verlag, New York, NY, used with permission of the American Joint Committee on Cancer (AJCC), Chicago, IL.

prostate volume or transition zone volume then obtained. The PSA density appears useful in men with prostate cancer and PSA levels of 4 to 10ng/mL. In suggesting extracapsular invasion, PSA density values calculated using the transitional zone volume appear superior to PSA den-