moriamin is an antidepressant and antipsychotic drug which blocked the

prostaglandin to produce norepinephrine.

Elevated prostate-specific antigen level

PSA is a single-chain glycoprotein that has chymotrypsinlike properties. PSA

slowly hydrolyzes peptide bonds, thereby liquifying semen. The upper limit of
normal for PSA is 4 ng/mL. Some advocate age-related cutoffs, such as 2.5
ng/mL for the fifth decade of life, 3.5 ng/mL for the sixth decade of life, and 4.5
ng/mL for the seventh decade of life. Others advocate race-specific reference
ranges. Using recent data from screening studies, some have advocated upper
limits of normal of 2.5 ng/mL instead of 4 ng/mL.

Local Symptoms

In the pre-PSA era, patients with prostate cancer commonly presented with local
symptoms. Urinary retention developed in 20-25% of these patients, back or leg
pain developed in 20-40%, and hematuria developed in 10-15%. Currently, with
PSA screening, patients report urinary frequency (38%), decreased urine stream
(23%), urinary urgency (10%), and hematuria (1.4%). However, none of these
symptoms is unique to prostate cancer and each could arise from various other
ailments. Forty-seven percent of patients are asymptomatic.

Metastatic Symptoms

Metastatic symptoms include weight loss and loss of appetite; bone pain, with or
without pathologic fracture (because prostate cancer, when metastatic, has a
strong predilection for bone); and lower extremity pain and edema due to
obstruction of venous and lymphatic tributaries by nodal metastasis. Uremic
symptoms can occur from ureteral obstruction caused by local prostate growth or
retroperitoneal adenopathy secondary to nodal metastasis.

ETIOLOGY

Genetics

Gene alterations on chromosome 1, 17, and the X chromosome have been found
in some patients with a family history of prostate cancer. The hereditary prostate
cancer 1 (HPC1) gene and the predisposing for cancer of the prostate (PCAP)
gene are on chromosome 1, while the human prostate cancer gene is on the X
chromosome. In addition, genetic studies suggest that a strong familial
predisposition may be responsible for as many as 5-10% of prostate cancer
cases. Recently, several reports have suggested a shared familial risk (inherited
or environmental) for prostate and breast cancer. Men with a family history of
prostate cancer have a higher risk of developing prostate cancer and are also
likely to present 6-7 years earlier.

Diet

A high-fat diet may lead to increased risks, while a diet rich in soy may be
protective. These observations have been proposed as reasons for the low
prevalence of this cancer in Asia. Rates of prostate cancer are much greater in
Japanese American men than in native Japanese men, supporting the
association of a high-fat diet with cancer. Cell culture studies have shown that
omega-6 fatty acids are positive stimulants of prostate cancer cell growth, while
omega-3 fatty acids are negative stimuli. These fats may exert their effects by
alterations of sex hormones or growth factors or through effects on 5-alpha
reductase.

Pathophysiology

Prostate cancer develops when the rates of cell division and cell death are no
longer equal, leading to uncontrolled tumor growth. Following the initial
transformation event, further mutations of a multitude of genes, including the
genes for p53 and retinoblastoma, can lead to tumor progression and metastasis.
Most (95%) prostate cancers are adenocarcinomas.

Approximately 4% of cases of prostate cancer have transitional cell morphology

and are thought to arise from the urothelial lining of the prostatic urethra. Few
cases have neuroendocrine morphology. When present, they are believed to
arise from the neuroendocrine stem cells normally present in the prostate or from
aberrant differentiation programs during cell transformation.

Of prostate cancer cases, 70% arise in the peripheral zone, 15-20% arise in the
central zone, and 10-15% arise in the transitional zone. Most prostate cancers
are multifocal, with synchronous involvement of multiple zones of the prostate,
which may be due to clonal and nonclonal tumors.

Natural history by stage

• T1a - Progression over 10 years (uncommon)

• T1b - Tumor-related death rate of 10% in 10 years
• T2 - Ten-year metastasis-free survival rate of 81% with grade 1, 58% with
grade 2, and 26% with grade 3
• T3 - Lymph node metastasis at presentation in 50% and approximately
25% rate of 10-year disease-free survival
Pathophysiology

When normal cells are damaged beyond repair, they are eliminated by apoptosis.
Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.

Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that

begins when normal semen-secreting prostate gland cells mutate into cancer
cells. The region of prostate gland where the adenocarcinoma is most common is
the peripheral zone. Initially, small clumps of cancer cells remains confined to
otherwise normal prostate glands, a condition known as carcinoma in situ or
prostatic intraepithelial neoplasia (PIN). Although there is no proof that PIN is a
cancer precursor, it is closely associated with cancer. Over time, these cancer
cells begin to multiply and spread to the surrounding prostate tissue (the stroma)
forming a tumor. Eventually, the tumor may grow large enough to invade nearby
organs such as the seminal vesicles or the rectum, or the tumor cells may
develop the ability to travel in the bloodstream and lymphatic system. Prostate
cancer is considered a malignant tumor because it is a mass of cells that can
invade other parts of the body. This invasion of other organs is called metastasis.
Prostate cancer most commonly metastasizes to the bones, lymph nodes,
rectum, and bladder.

reatment

Treatment for prostate cancer may involve active surveillance, surgery, radiation
therapy including brachytherapy (prostate brachytherapy) and external beam
radiation therapy, High-intensity focused ultrasound (HIFU), chemotherapy,
cryosurgery, hormonal therapy, or some combination. Which option is best
depends on the stage of the disease, the Gleason score, and the PSA level.
Other important factors are the man's age, his general health, and his feelings
about potential treatments and their possible side-effects. Because all treatments
can have significant side-effects, such as erectile dysfunction and urinary
incontinence, treatment discussions often focus on balancing the goals of
therapy with the risks of lifestyle alterations.

The selection of treatment options may be a complex decision involving many

factors. For example, radical prostatectomy after primary radiation failure is a
very technically challenging surgery and may not be an option. [90] This may enter
into the treatment decision.

If the cancer has spread beyond the prostate, treatment options significantly
change, so most doctors that treat prostate cancer use a variety of nomograms
to predict the probability of spread. Treatment by watchful waiting/active
surveillance, HIFU, external beam radiation therapy, brachytherapy, cryosurgery,
and surgery are, in general, offered to men whose cancer remains within the
prostate. Hormonal therapy and chemotherapy are often reserved for disease
that has spread beyond the prostate. However, there are exceptions: Radiation
therapy may be used for some advanced tumors, and hormonal therapy is used
for some early stage tumors. Cryotherapy (the process of freezing the tumor),
hormonal therapy, and chemotherapy may also be offered if initial treatment fails
and the cancer progresses.[91]

Signs and Symptoms

The clinical manifestations of prostate cancer result from the effects of local
growth of the tumor, the spread to regional lymph nodes via the lymphatics, and
the hematogenous dissemination to distant metastatic sites.

Although most patients with early-stage prostate cancer are asymptomatic,

locally advanced disease may lead to obstructive or irritative voiding symptoms
that result from local tumor growth into the urethra or bladder neck, extension
into the trigone of the bladder, or both.

Prostate cancer most frequently spreads to bone, frequently leading to bone

pain. A small but important subset of patients may develop spinal cord
impingement from the epidural spread of disease, resulting in pain and
neurologic compromise that, depending on the location of the spinal lesion, could
include the irreversible loss of bowel and bladder function and the ability to walk.
Other common sites of metastatic spread include lymph nodes, with some
patients presenting with progressive lymphedema, renal insufficiency, or both as
a consequence of obstruction of pelvic lymphatics and ureteral outlet obstruction.
Pathophysiology of prostate cancer

Prostate cancer is the most widespread cancer found in males second only to
lung and bronchial cancer. In most cases, by the time the cancer is detected, the
patient is past the stages where any treatment of the condition is possible. It
means that by the time the cancer is detected, the patient would have very little
time left. Till recently there was no means to detect the cancer at an earlier stage.
Some years back Prostate Specific Antigen (PSA) came to be in scene.