2. The prostate
2.1 Description and Structure
The prostate is an exocrine gland of the size of a walnut that lies at the base of the bladder. Its role is to secrete alkaline fluid that will be ejected hanging ejaculation with muscle fibers that are listed in this gland in the glandular tissue. The role of liquid is to protect sperm from the acidity of the vagina [1] .
From FUNCTIONAL ANATOMY OF THE PROSTATE: IMPLICATIONS FOR TREATMENT PLANNING
In the previous figure shows the prostate of a young man (A) and adult (B). There are several areas: AFS-anterior fibromuscular stroma, CZ-Zone Central Zone PZ-device-SV bladder seminal TZ-Transition zone. Over time the transition zone becomes dominant.
3. The epidemiology of prostate cancer
3.1. The incidence
Incidence is the number of new prostate cancer cells in a period of time. Prostate cancer is the most common cancer among men in the countries of Western Europe is North America. Below is a map of the incidence of prostate cancer in the world according Globocan 2002, a basis of give directed by IARC - International Agency for Research on Cancer. Every year we talk about 190 000 new spots of cancer of the prostate, with an incidence ranging from 19/100 000 inhabitants in Europe East and 55/100 000 inhabitants in Western Europe [2] .
Derived from Prostate Cancer, by Jacob Ramon, Denis L
In should be noted that these data are much influenced by the use in recent years, new diagnostic methods such as PSA (prostate specific antigen) that ensures that the initial stage cancers are found in developed countries - including U.S. whereas in other countries such cancers in the initial phase are not found and, obviously, are not reported. The impact is also dependent on age. Thus, for men under 45 years the incidence is 0.4/100 000. For 45 to 54 6 / 100, 000, 55 to 64 60/100 000 and finally 270 / 100 000 inhabitants over age 65.
3.2 The prevalence
Prevalence is the number of live cells, diagnosed. The data show that prostate cancer is the leading cancer as prevalence among men, lung cancer before. This number varies greatly in the countries of the continent such as 44/100 000 in Poland and 575 in Sweden. The average is 153 [2].
3.3 The survival
Survival in the case of prostate cancer is also significantly influenced the diagnostic method used. Because of that, there is a considerable difference between the United States and Europe, where the ratio of 81% to 56%, mainly due to the use of the PSA diagnostic method on a larger scale.
3.4 The mortality
Mortality has decreased especially in developed countries. The mortality rate has a very different world. China, Vietnam was a spleen of 1 / 100 000 inhabitants in Sweden as it was 27 dead and 100 000 [3] . A very interesting study done by IARC shows that between mortality and the environment is a link. If for UV radiation, cereals and sugar has a weak link for the diet rich in animal fats is high. So if you look at Table 1, we observe that for every single country the ratio between total fat and mortality is almost constant even though 8.8 are very different countries. Myanmar as an example to 10.6 total fat and 1.2 deaths. On the other hand Sweden 27.26 240 total fat and mortality.
4. Causes
The causes of the onset of prostate cancer are mostly not well known. Yet we can say that the appearance of barrels contribute risk factors and causal factors.
4.1. Risk factors
Among the risk factors we can list: diet (as we said earlier was due especially fat), obesity, smoking, vasectomy. By cons there are also factors that reduce the risk: alcohol, diabetes mellitus, tea, selenium, vitamin D and E, nonsteroidal anti-inflammatory drugs. The following table shows the dependence between mortality and diet and sun exposure.
4.2. The causal factors
Genetic and molecular aspects of prostate cancer is one of the major directions in research. There are several genes involved in the onset and development of prostate cancer. We fear list [4] :
- Genes can inhibit apoptosis, and subsequently the cells do not die, they breed, for example - BCL2
- Genes that encode the metabolism of androgens
- The loss of expression of genes that lead to tumor suppression: p27 , p53 , PTEN , GSTP1
From Janet Laura Colli, 2005, International comparisons of prostate cancer Mortality Rates With dietary practices and sunlight Levels Urologic Oncologic
4.3 The viral causes
As we have seen, there are several genes that are involved in the development of prostate cancer. One of these genes is a gene RNASEL antiviral. Was discovered in 2005 that a variant of this gene, called R462Q, may be associated with a new retrovirus, XMRV [5] .
5. Histological types
5.1 Adenocarcinoma
Adenocarcinoma accounts for about 95% of prostate cancers. There is talk of an adenocarcinoma when the malignancy is localized in the glandular epithelium.
5.2 The squamous cell cancer (SCC)
This type accounts for 0.5-1% of total prostate cancers. Besides the location for this type is the difference in negativity of the PSA test, the test of basic chemicals for screening prostate cancer.
5.3 The type you carcinoma signet ring
This guy is a rare but very aggressive. The ring shape is due to the fact that the cancer cell in a vacuole of mucin in the middle that pushes the nuclei.
6. The tumors' degree
The Gleason system is the most widespread classification system for prostate cancer tissue. Depending on the model of glandular and the difference between the cells was 5 degrees as shown in Figure 2. In practice, we evaluate the first 2 tumor model by giving them a grade for each (eg 3 for the first and 4 more met for the second) [2]. We did following the sum of these grades and you get what is called the Gleason score final. Prostatetectomie after the Gleason score is required.
7. Stages of prostate cancer
The Degree of Gleason system is the histology. But to have a complete picture of the risks of prostate cancer this classification is included in a comprehensive evaluation of states of prostate cancer. There are two systems that are usually used [2]:
1. Jewett System with stages A to D with sub-stages.
- A clinically undetectable in two stages with
- A1 bin differentiated tumor in a single nucleus
- A2 Cancer not well differentiated, with several development kernels
- B detectable tumor in the prostate
- B1 nonpalpable tumor, detectable PSA test
- B2 tumor with a single nodule in one lobe of the prostate
- B3 tumor with multiple nodules in which both lobes of the prostate
- C detectable tumor in the region surrounding the prostate gland with extension into the prostate, which may include channels seminal
- C1 tumor with extracapsular extension
- C2 tumor with extracapsular extension that produces blockage of the bladder or urethra
- Stage D metastatic
- D0 Located only in the prostate but with a high concentration of acid phosphatase
- D1 Located in regional lymph nodes
- Located in the D2 lymph nodes distal metastasis to visceral organs where dare
- D3 The same situation as the D2 stage but without improvement after adequate treatment
2. The TNM system
This system was proposed more complete of the International Union against Cancer.
· A primary tumors (T)
-Tx primary tumor can not be assessed
- T0 a primary tumor can not be observed mas
- T1 where inapparent tumor not visible by imaging
- T1a tumor found incidentally in less than 5% of the tissue observed
- T1b tumor incidentally found in more than 5% of the tissue observed
- T1c tumor was observed with the biopsy needle
- T2 tumor confined to the prostate
- T2a tumor in less than one half of one lobe
- T2b tumor in more than one half of one lobe
- T2c tumor in both lobs
T3-the tumor has rependue beyond the prostate capsule
- T3a extracapsular extension
- T3b tumor has invaded the seminal vesicles
T4 tumor has invaded adjacent structures other than seminal vesicles (bladder, rectum, etc.).
Pathological stages B
-PT2-limited to the prostate (no pathology pout T1)
PT2A-tumor in less than one half of one lobe
-PT2b tumor in more than one half of one lobe
PT2C-tumor in both lobes
PT3- extraprostatic extension
- Extracapsular extension pT3a
- PT3b tumor has invaded the seminal vesicles
-PT4 Invasion of bladder, rectum etc..
Classification on lymph nodes
- Nx Regional lymph zone can not be assessed
- N0 no metastases in lymph nodes
- N1 metastasis in lymph nodes
Pathology of lymph nodes
- PNX regional nodes not assessed
- PN0 no regional nodes positive
- PN1 metastasis in lymph nodes
Distal metastasis
- Mx When distal metastasis can not be assessed
- M0 No metastases distal
- M1 distal metastasis
· M1a For non-regional lymph nodes
· M2b For ose
· M1c Other places with or without disease to dare
After the histological grade
- Gx histological grade can not be assessed
- Well differentiated G1 (Gleason2-4)
- G2 Moderately differentiated (Gleason 5-6)
- Low differential G3 (anaplasia) Gleason 7-10
All these criteria are all betting in the following table [2].
8. Diagnostic methods
8.1 The rectal exam by the finger DRE (DRE English - digital rectal examination )
This method was first used and it is still part of the diagnostic process of prostate cancer. The first time was when analyzed the sensitivity of this method and has been found that approximately 50% of cancers were being detected. Monitored for 5 years showed that 75% of men whose diagnosis was made solely by DRE have died [6] . In any case, this method remains valid not come first, as ongoing monitoring throughout the illness and in the special case of cancers not detected by PSA testing (around 1%).
8.2 The review of the Prostate Specific Antigen - ASP (ASP-English)
ASP is a protein produced by the prostate epithelium. It was first described in 1979 [6] and is located in chromosome 19. The concentration of PSA is an important indication about the presence of cancer. Thus, the first concentration threshold above which we consider that we should move to the next step in confirming the presence of cancer was made arbitrarily 4 ng / ml. There is an uncertainty range between 4 and 10 mg / ml. Production of ASP is not constant, it increases with age. For this, some authors have proposed a variation of this value called "cut-off value". The table below shows the dependence of age [7] .
An important aspect of the ASP, as with all diagnostic specificity is the sensitivity. The sensitivity is:
(NUMBERS OF TRUE POSITIVES)/(NUMBER OF TRUE POZITIVES + NUMBER OF FALSE NEGATIVES) x100
Specificity is:
(NUMBERS OF TRUE NEGATIVES)/(NUMBER OF TRUE NEGATIVES + NUMBER OF FALSE POZITIVES) x100
Several authors have sought to give an answer. In the meta-analysis [7] it was a centralization of 10 published studies, shown in the following table:
It is observed that the PSA test is a test with a relatively high sensitivity is a base specificity. That means that if the test is negative, due to high sensitivity, it has a small probability of false negative is you can stop aves investigation. By cons, if the test is positive, we continue the investigation but that does not mean that the patient has cancer. The advantage of this test is low cost. On the other hand, due to its small specificity many patients continue their investigations which become more expensive and there is also a source of great stress for the patient who was found positive. For this reason we tried to find methods to improve specificity.
a) the density of the ASP
Is obtained by dividing the concentration of ASP prostate volume. This method increases the specificity. The threshold value is much debated. A value of 0.15ng/ml 2 has been shown that leads to the non-detection of 47% of cancers. One of the problems is the calculation of the volume of the prostate.
b) The rate of change of the time in ASP
In this case is measured the increase in ASP in a year. An increase 0.75ng/ml year pushes the sensitivity to 90%. The major disadvantage of this method consists in the fact that, due to the relatively long interval between the measurements (1.7 to 2 years), a possible cancer can develop.
c) The spleen free ASP / ASP total
ASP is found in the circulation in 2 forms
- ASP bound in complexes such as α 1-antichymotrypsin .
- ASP Free
Their ratio of 25% gives a test with 95% sensitivity and 20% fewer biopsies.
d) The precursor pro ASP
This precursor has a greater associativity cancer that simple ASP test. And specificity of 23% of the test increases to 44% ASP in free association with ASP and ASP pro.
e) The concentration of urine produced by the marker gene PCA3
In Quebec DiagnoCure the firm has developed a test called uPM3, which measures the concentration of RNA not codified by the gene product pSA3. It is necessary to differentiate between gene name and the name of pSA3 uPM3 test which is a registered trademark [8] .
8.3 The Ultrasound graphics and transrectal biopsy (TRUS)
Ultrasound at 7.5 MHz was used initially as an independent method for imaging the prostate using a probe of 2.5 cm that is introduced into the rectum. The sensitivity is the specificity was low. Less than 20% of hypo echo have been proven as having come from cancer, and on the other hand, 50% of cancers were not detected. For these reasons TRUS was partly abandoned as an independent method of imaging the prostate. It remains for advanced stages, cysts, abscesses calculate the volume of the prostate. Yet his ability to guide us was chosen to help the biopsy.
In biopsy, using the needles are taken probes, usually 10 to 12. Indications for biopsy were: abnormal DRE, ASP or high growth, previous biopsies have shown a prostatic intraepithelial neoplasia (PIN - PIN English) or atypical small acinar proliferations (ASB APAS-English).
If the biopsy is not concluded and resumed. Repeated biopsies may increase the cancer cells detected with 15%.
Another variant of the biopsy is the biopsy saturated. In this case instead of 12 probes were taken 20 probes. Biopsy saturated gives good results especially in cases when it is used as repeat biopsy.
The biopsy may have complications. We can enumerate: urinary tract infections, sepsis occasional (less than 1% of cases). Any bleeding can be faecal, urinary or hemospermia. In the latter case the term may be up to 6 weeks.
The biopsy is contraindicated in the case that the patient take wafarine.
This type of biopsy is done on local anesthesia.
8.4 The transperineal biopsy and biopsy with template
For people with large rectal problems, transrectal biopsy is replaced by transperineal biopsy. This time the biopsy is done on a regional anesthesia over large or very general. It is usually 24 probes in different positions [9] as in Fig.
This type of biopsy is more effective than TRUS findings in the spleen of cancer. In addition, after perineal biopsy, because of greater cleanliness, the remakes of the patient is more rapid, complications are rare. This biopsy is the other side more expensive because of the anesthesia more complex.
9. Treatment
Treatment of prostate cancer is, like all cancers, depends on the stage of cancer and results analysis. Thus, the stages can be grouped into 3 groups and for each there is a specific approach that requires one or more of the chosen include: watchful waiting (WW - watchful waiting), surgery, radiotherapy, hormone therapy, chemotherapy.
9.1 The non-advanced stage localized
This stage is characterized under the previous classifications, T1 and T2, Nx N0, M0.
9.1.1. Watchful waiting (WW)
This expectation represents the first option in the case of fabrics with good or moderate differentiation. During this waiting is making clinical examinations and biochemical analysis (ASP).
9.1.2. Surgery
Radical prostatectomy (removal of the prostate is full of canals is of seminal lymph nodes) became the primary method of treatment. 25 years before the surgery had a high morbidity. Significant improvements have been made with regard to urinary incontinence and preservation of sexual function. Among the surgical methods remain the standard retro pubic prostatectomy. Node dissection climate is made in the case of ASP> = 10 ng / ml, stage T2, Gleason score> 6. After prostatectomy it is possible that the disease remains. For this reason, before the operation, was developed neoadjuvant hormone therapy. Note that this procedure preoperatively remains controversial because there are studies showing that hormonal treatment has no influence in the spleen of patient survival.
9.1.2.1. Surgical changes
The first Radical Prostatectomy Retro Pubic (PRR) was made in 1947 by Milin. The operation was associated with a large blood loss, incontinence, impotence and prolonged convalescence [10] . Walch in 1980 structured the surgical method PRR through better understanding of anatomy and physiology of the prostate, especially on the veins and nerves, a fact which has led to better results after surgery. 1991 is the year of the first Prostatectomy Laparoscopiyque made by Schusler (LRP). This method can be done in under four variants: transperitoneal antegrade , retrograde transperitoneal, extraperitoneal retrograde extraperitoneal ante grade. Transperitoneal techniques are the first choice of many clinics due to space more degree work.
Nine years later, in 2000, the robotic prostatectomy approach was made by Abbou. From surgical point of view the method does not differ from the method laparoscopiyque. Six small incisions are made to gain access to the prostate. Robotic technology in the standard robot system Da Vinci, Intuitive Surgical Inc.., Sunnyvale, CA, which was sold over 1000 copies worldwide. Using the robotic approach is still under debate because of the high price of the device - 1.2 million dollars for the standard and it can reach 1.4 million with special accessories. The maintenance cost is approximately $ 100 000 per year. The company that sells the product marketing has focused on the learning curve smaller robotic technology.
The incisions in the techniques
The Da Vinci robotic system
LRP and RALP
The following table shows a comparison of three techniques of oncologic point of view, the surgical results and cost.
9.1.3. External radiation
This method is an alternative to prostatectomy. There are not many conclusive studies that make the comparison between radical prostatectomy and external radiation. However, some preliminary articles show that both therapies have the same survival rate after 10-15 years of treatment. The cancellation is made with a conventional dose of 65-70 Gy is often a persistence of the tumor. New techniques have been developed. One such technique is x-ray consistent 3D (3D-CRT). This method allows to evaluate the dose administered to each 3D pixel. It results in increasing the dose to 80-86 Gray. Another alternative that leads to still larger doses of radiation therapy with intensity modulated (IMRT intensity modulated radiotherapy). It may be that radiotherapy ale a recurrence of the disease. There are several ways to continue treatment after radiation therapy: Prostatectomy (called palliative surgery in this case), the hormonal treatment. The new techniques are still in a stage of evaluation are cryosurgery and ultrasound with much focus. (Hi-FU, high Focused Ultrasound)
9.1.4. Brachytherapy
Brachytherapy is the treatment with internal radiation. Procédée by a grain of radioactive isotope (usually palladium 125 or iodine 103) is inseminated into the body. This treatment is recommended in cases not advanced ASP <10, Gleason <= 6.
9.2. The advanced local
This stage is characterized under the previous classifications, T3 and T4, Nx N1 M0.
9.2.1. Radiotherapy plus hormone therapy
This combination is considered the treatment of choice in the case of locally advanced cancer of the prostate. Today stage T3 cancer has an incidence of less than 40% of total malignant tumors of the prostate.
9.2.2. Surgery more hormone
Once past the tumor beyond the prostate capsule (as defined in stage T3) the role of surgery is still under debate. But as in statistics is shown that 15% of patients who received a diagnosis of cancer stage T3 had a lower stage, these patients are best felt after prostatectomy. In a study of 98 patients who underwent prostatectomy, hormonal treatment has been found that leads to an improvement in survival at 5 years.
9.2.3. Surgery plus radiotherapy
Several studies have shown that this combination has led to a smaller return of cancer compared to treatment with only radiotherapy. Yet survival remains the same.
9.3. Advanced stages
This stage is characterized under the previous classifications: Tx, Nx, M +
9.3.1. Hormonal therapy
Hormonal therapy consists of androgen ablation. For 60 years, and Huggins and Hodges noted the role of ablation in the case of metastasis. Removal may be surgical (castration) by the administration of female hormones or chemical by the administration of cyproterone acetate as hormone androgen. This therapy is effective but not curative. There are two variants of the ablation. The first has as its target only the testicles. The second part of the idea that it is not only the testes that secrete androgens for growth, but they are also the major adrenal. The second is called Maximum androgen blockade or combined androgen blockade.
9.3.2. Chemotherapy
Years in the early 80's chemotherapy led to a positive response of only 6.5-9.7%. In tests with 90 Years of extramustine and vinblastine was obtained a positive response from 20% to 48% of number of patients. Yet the survival time has not increased, and for this reason, chemotherapy has been seen as a palliative treatment but active.
In a more recent study in 770 patients who received docetaxel alone or in combination with estramustine phosphate has been found that chemotherapy is effective also in the duration of survival has increased with 2.5 -3 months. This is the first time when chemotherapy shows such a positive result. Quality of life was also improved.
9.3.3. Palliative radiotherapy
Systemic treatment often does not give results. It may be that in some places still a pain, especially in bone or brain. One goal of treatment in cases of prostate cancer with metastasis in the vertebrae is to avoid paraplegia or, in the case of metastasis in the cervical area quadriplegia. To avoid that, we made a local radiation therapy has been found effective in the case of 80% of patients. The dose is 30 to 40 Gy administered in a period of 2 weeks.
In the case of patients with pain not well localized instead of radiation therapy (external radiation source) should be used by radiation radioisotopes (source of internal radiation). For that we made with intravenous radioisotope strontium, samarium and rhenium .
10. Quality of life after treatment
10.1. The result after surgery
The choice of treatment should be done well so that the benefits of surgery are not less than the disadvantages.
10.1.2. The urinary control
After prostatetectomie there is a risk of urinary unconsciousness. The rate varies from those who assess. Thus in the case of evaluation by the surgery rate is 5-10%. If the assessment is made by patients through a questionnaire, the rate rises to 19 to 31%. Several factors contribute to urinary control after surgery: age, surgical technique, preservation of the length of the urethra, preservation of innervation. Of these the latter two seem to have the greatest importance.
10.1.2. The sexual functions.
Recovery of erection is 11-58% in the case of a cut nerve. In the case where both nerves are spared the recovery rate rises to 68-82%. Recovery is dependent on the age of the patient and the surgeon's experience.
10.2. The effects of radiotherapy
After radiotherapy can have side effects on the urinary route: hematuria (blood in urine), laburnum, narrowing of the urethra. The incidence is 7%. On the way digestive manifestations may be inflammation of the rectum (proctitis), diarrhea, traces of blood. The incidence rate is 3.5%.
The demonstrations lasted for a secondary event following the procedure and the dose. Thus in the case of normal radiotherapy - dose of 64 Gy - the duration is 3 to 6 months. Sexual function have a slower recovery of more than a year. If the dose was 70Gy augment the effects of toxicity occur at 3 years.
The modern method of radiotherapy gives an incidence of blood in stool, after 5 years, 17% in the case of 3D radiotherapy and 2% in the case of radiotherapy with modulated intensity.
Conclusions
Prostate cancer is the cancer with the highest incidence among men in several countries. The effort is now made to find a method of diagnosis with greater specificity.
The discovery of a new virus can lead to a vaccine for prophylaxis. Surgery is the gold standard for local fields with high hopes. If the cancer has extended extracapsular choice is a combination of treatments.
BIBLIOGRAPHY
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[1] Karla Baur, Robert Crooks, 2008, Our Sexuality , p. 119
[2] Sergio Bracard, Ottavio of Cobelli, Carlo Greco, Tommaso Prayer, 2005, Cancer of the Prostate , - Galetti ogy / Hematology ,
[3] Janet Laura Colli, Albert Colli, 2005, International comparisons of prostate cancer Mortality Rates With dietary practices and sunlight Levels ,
[4] Hossein Jadvar, 2009, Molecular Imaging of Prostate Cancer: A Concise Synopsis
[5] Anatoly Urisman, 2006, Identification of a Novel Gamma retroviruses in Prostate Tumors of Patients Homozygous for R462Q Variant RNASEL Department of Biochemistry and Biophysics, University of California San Francisco
[6] Nigel Borley, Mark R. FENELEY, 2008, Prostate cancer: diagnosis and staging
[7] Philip Harvey, 2009, A Systematic Review of the Diagnostic Accuracy of prostate specific antigen
[8] Stephen J. Freedland, 2005, Detecting Prostate Cancer With Molecular Markers: uPM3. REVIEWS IN UROLOGY
[9] AV Taira1, Merrick GS, 2010, Performance of transperineal template-guided mapping biopsy in Detecting Prostate Cancer In The initial and repeat biopsy setting
[10] Rodrigo Frota, 2008, C
Comparison of Radical Prostatectomy Techniques: Open, Laparoscopic and Robotic Assisted
