Overview of the Prostate

The Prostate

Embryology

• Prostate first appears in the 3^rd  month of fetal growth from the urogenital sinus. Its growth is dependent on DHT, not testosterone.
• Five epithelial buds form in a paired manner on the posterior side of the urogenital sinus on both sides of the verumontanum and they then invade the mesenchyme to form the prostate.
• The top parts of the buds for the inner zone of the prostate and appear to be of mesodermal origin, whereas the lower buds form the outer zone of the prostate and appear to be of endodermal origin.
• The inner zone gives rise to BPH tissue whereas the outer zone contains the primary origin of cancer.

Benign Enlargement of the Prostate

• In the adult, the prostate can be divided into zones. The central zone (CZ) is what enlarges in BPH (Benign Prostatic Hyperplasia) and the peripheral zone (PZ) is what changes in prostate cancer. On digital rectal exam (DRE), prostate cancer can be felt as hard gritty nodules.
• Histologically speaking, the prostate contains glandular epithelium. It is a bilayer. This epithelium secretes PSA. There is also a fibromuscular stroma which is pretty vascular. In BPH, there is hyperplasia (not hypertrophy) of both the amount of glands and the amount of stroma. The adjacent picture shows normal prostate in section.

  
   

  • Histological evidence of BPH is seen in 90% of men above 90 years old and is symptomatic (nocturia, dysuria etc.) in 50% of those with clinically detectable enlargement.

  
   

• The image above is an example of a section which depicts BPH. Note proliferation within the glands makes the epithelium fold on itself forming papillary projections which eventually crowd each other to form nodules. The stroma is also overgrown (not seen well in this picture.
   

• BPH is an androgen driven process.
  • Testosterone is converted to DHT by the enzyme 5-alpha-reductase in the stromal cells only. The DHT then induces growth of both glandular (the DHT diffuses out of the stromal cell and into the epithelial cells) and stromal elements.
• An enlarged prostate effectively cuts off the prostatic urethra, leading to difficulty urinating. Some complications are:
  • Cystitis and bladder hypertrophy (the bladder needs to get stronger to push urine through the constricted prostatic urethra)
  • Stone formation
  • Reflux of urine leading to hydronephrosis, pyelonephritis

• Treatment
  • Medical Treatment
    • Alpha-adrenergic blockers (terazosin, doxazosin, tamsulosin, and alfuzosin). By blocking alpha receptors, these drugs relax smooth muscles of prostate and bladder neck. They work rapidly and in a dose dependent matter
    • 5 alpha reductase inhibitors (ex. Finasteride). They lower serum (stop hair loss bc DHT is what kills follicles) and intraprostate DHT levels (stops BPH). Basically, they reduce prostate volume with a maximal effect at around 6 months. The max reduction is about 20%.
  • If medical treatment doesn’t get the job done, we do minimally invasive procedures such as
    • Intraprostatic stent: basically hold the prostatic urethra open
    • Transurethra needle ablation and transurethral microwave therapy
      • Induce necrosis of the enlarged area, and thereby make prostate smaller
      • Caveat: by inducing necrosis, the prostate gets inflamed, which actually makes it bigger. Once the inflammation goes down, then you have resolved your problem.
    • Laser ablation
      • Ablates tissue and avoids inflammation. Downside: requires lots of time. My guess its probably expensive too.
      • [insert cool video here]
    • TURP (Transurethral resection of prostate)
      • This is the GOLD STANDARD for treatment of invasive BPH. It accounts for over 90% of prostatectomies performed for BPH.
      • Chance of improvement – 88%. The magnitude or reduction in symptoms score was 85%, which is much better than which minimally invasive procedures.
    • Transurethral vaporization of prostate
    • Transurethral incision of the prostate
    • When do you do a prostatectomy? If a patient has:
      • acute urinary retention. I.e. the BPH is so bad that no urine gets out and as a result they could be azotemic.
      • Recurrrent or persistent UTIs
      • Significant symptoms from bladder outlet obstruction not responsive to medical therapy
      • Recurrent gross hematuria of prostatic origin
      • Pathophysiologic changes of the kidneys, ureters, or bladder secondary to prostatic obstruction.
    • When do you do a open simple prostatectomy?
      • When obstructive tissue weights more than 75 g
      • If sizable bladder diverticulae need to be removed
      • Large bladder calculi that cant be removed any other way
      • A man who can’t be positioned for TURP, i.e. someone with ankylosis of the hip or other orthopedic conditions
      • Med with recurrent or complex uretheral conditions such as urethral stricture or previous hypospadias repair, to avoid the urethral trauma associated with TURP.
      • If one is comorbid with an inguinal hernia, both the prostatectomy and hernia repair can be done through the same lower abdominal incision.
      • Contraindications:
        • Small fibrous gland
        • Prostate cancer
        • Previous prostatectomy
        • Pelvic surgery that may obliterate access to the prostate gland

Prostate Cancer

• Prostate cancer is the most common carcinoma in men. It is the second leading cause of cancer death in American men (2^nd to lung cancer). Risk factors for prostate cancer are currently under investigation.
• How is prostate cancer detected?
  • Digital rectal exam (DRE) (this procedure is vital to have in your clinical ARSEnal)
    • 50-60% of the time when you feel a hard nodule on DRE, it’s a localized cancer
  • Elevated PSA (> 4 ng/mL)
    • Normal PSA (0-4 ng/ml)
    • Confirmed pathologically 2/3 of the time
    • 90% of the time, with positive DRE and elevated PSA, there is localized cancer
    • Note that prostate cancer can develop even when PSA levels are low. PSA has low specificity for prostate cancer. Patients with BPH also can have very high PSA levels.
• What are complications?
  • Metastasis to spine, lung, femur etc.
  • If you ever see osteoblastic deposits in the lumbar spine of an older man then this patient most likely has metastatic prostate cancer.
• Prostate cancer is better felt than seen!

• Histologically, prostate cancer can be recognized. Normal organization involves glands with wide lumen and a bilayered epithelium. In prostate cancer, you see small back to back glands with tiny lumen, and ONLY 1 LAYER OF CELLS IN THE EPITHELIUM. The basal layer has been lost.

• As prostate cancer progresses, you see a decrease in glandular organization and an increased prominence of nucleoli (my guess is that the cancer cells are highly involved in protein synthesis). The picture below shows high grade cancer. Notice the loss of glands and abnormality of cells. If you get out a magnifying glass, you can see prominent nucleoli (which become more prominent as the cancer progresses).

• But wait? So is there any precancerous stage to this terrible prostate cancer. You better believe it. It is called Prostatic intraepithelial neoplasia
  • 1/3 pts with this will progress to prostate cancer in a 10 year period.
  • 80% of patients with prostate cancer had this in-situ stage.
  • Histologically, you see epithelial proliferation, but the basal layer is intact. I.e. the epithelium has more than two layers.

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