Stem cell transplant

Definition

A stem cell transplant is the infusion of healthy stem cells into your body. A stem cell transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy stem cells. A stem cell transplant can help your body make enough healthy white blood cells, red blood cells or platelets, and reduce your risk of life-threatening infections, anemia and bleeding.

Although the procedure to replenish your body's supply of healthy blood-forming cells is generally called a stem cell transplant, it's also known as a bone marrow transplant or an umbilical cord blood transplant, depending on the source of the stem cells. Stem cell transplants can use cells from your own body (autologous stem cell transplant), or they can use stem cells from donors (allogenic stem cell transplant).

Why it's done

Stem cell transplants are used to treat people whose stem cells have been damaged by disease or the treatment of a disease. Stem cell transplants can benefit people with a variety of both cancerous (malignant) and noncancerous (nonmalignant) diseases.

A stem cell transplant may help your body:

• Replace dysfunctional bone marrow. For instance, in aplastic anemia, a noncancerous condition, your bone marrow doesn't make enough new blood cells. A stem cell transplant procedure first destroys the dysfunctional marrow with powerful drugs or radiation, and then healthy stem cells are infused. If all goes well, the new stem cells migrate to the marrow and begin working normally.
• Destroy unhealthy bone marrow that may contain cancer cells. In the case of cancer, such as leukemia, a stem cell transplant procedure may first help rid the bone marrow of cancer cells. When healthy stem cells are then transplanted, normal cell production can resume. In addition, immune factors in the transplanted cells may help destroy any cancer cells that remain in your bone marrow.

Risks

A stem cell transplant poses many risks of complications, some potentially fatal. Although some people experience few problems with a transplant, others must endure frequent tests and repeated hospitalizations.

Complications that can arise with a stem cell transplant include:

• Graft-versus-host disease
• Stem cell (graft) failure
• Organ damage
• Cataracts
• Secondary cancers
• Death

Your doctor can explain your risk of complications from stem cell transplant. Together you can weigh the risks and benefits to decide whether stem cell transplant is right for you.

Graft-versus-host disease: A potential risk when stem cells come from donors
If you're undergoing a transplant that will use stem cells from a donor (allogenic stem cell transplant), you may be at risk of graft-versus-host disease. This condition occurs when a donor's transplanted stem cells attack your body. Graft-versus-host disease can be mild or severe. It can occur soon after your transplant or months to years later.

Graft-versus-host disease can cause skin rashes, abdominal pain, diarrhea, nausea and vomiting. Over time it can cause other complications and chronic illnesses. Your doctor will monitor you closely for signs and symptoms of graft-versus-host disease.

What they are and what they do

Researchers believe stem cells offer great promise for new medical treatments. Learn about stem cell types, current and possible uses, ethical issues and the state of research.

You've heard about stem cells in the news, and perhaps you've wondered if they might help you or a loved one with a serious disease. You may wonder what stem cells are, how they're being used to treat disease and injury, and why they're the subject of such vigorous debate.

Here are some answers to frequently asked questions about stem cells.

Why is there such an interest in stem cells?

Researchers hope stem cell studies can help to:

• Increase understanding of how diseases occur. By watching stem cells mature into cells that eventually become bones, heart muscle, nerve cells, and other organs and tissue, researchers and doctors may better understand how a variety of diseases and conditions develop.
• Generate healthy cells to replace diseased cells (regenerative medicine). Researchers hope they can train stem cells into becoming specific cells so that those specialized cells can be used to regenerate and repair diseased or damaged tissues in people. People who might benefit from stem cell therapies include those with spinal cord injuries, type 1 diabetes, Parkinson's disease, Alzheimer's disease, heart disease, stroke, rheumatoid arthritis, osteoarthritis and multiple sclerosis. Stem cells could also be grown to become new tissue for use in transplant medicine.
• Test new drugs for safety and effectiveness. Before using new drugs in people, researchers could use stem cells to test the safety and quality of investigational drugs. For instance, nerve cells could be generated in order to test a new drug for a nerve disease. Tests could show whether the new drug had any effect on the cells and whether the cells were harmed.

What are stem cells?

Stem cells: The body's master cells

Stem cells are the body's master cells. All other cells arise from stem cells, including blood cells, nerve cells and others.

Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated. Under the right conditions in the body or a laboratory, stem cells divide to form more cells, called daughter cells. These daughter cells either become new stem cells (self-renewal) or become specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle or bone. Stem cells are unique — no other cell in the body has the natural ability to generate new cell types.

Where do stem cells come from?

Researchers have discovered several sources of stem cells:

• Embryonic stem cells. These stem cells come from embryos that are four to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells. These are pluripotent (ploo-RIP-uh-tunt) stem cells, meaning they can divide into more stem cells or they can specialize and become any type of body cell. Because of this versatility, embryonic stem cells have the highest potential for use to regenerate or repair diseased tissue and organs in people.
• Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow. Adult stem cells are also found in children and in placentas and umbilical cords. Because of that, a more precise term is somatic stem cell, meaning "of the body." Until recently, it was believed that adult stem cells could only create similar types of cells. For instance, it was thought that stem cells residing in the bone marrow could give rise only to blood cells. However, emerging evidence suggests that adult stem cells may be more versatile than previously thought and able to create unrelated types of cells after all. For instance, bone marrow stem cells may be able to create muscle cells. This research has led to early-stage clinical trials to test usefulness and safety in people.
• Adult cells altered to have properties of embryonic stem cells (induced pluripotent stem cells). Scientists have successfully transformed regular adult cells into stem cells using a technique called nuclear reprogramming. By altering the genes in the adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells. This new technique may help researchers avoid the controversies that come with embryonic stem cells, and prevent immune system rejection of the new stem cells. But, it's not yet known if altering adult cells will cause adverse effects in humans. Researchers have been able to take regular connective tissue cells and reprogram them to become heart cells. The new heart cells were injected into mice with heart failure, where they improved heart function and survival time.
• Amniotic fluid stem cells. Researchers have also discovered stem cells in amniotic fluid. Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers have identified stem cells in samples of amniotic fluid drawn from pregnant women during a procedure called amniocentesis. During this test, a doctor inserts a long, thin needle into a pregnant woman's abdomen to collect amniotic fluid. The fluid can be tested for abnormalities, such as Down syndrome, and fetal maturity. The procedure is generally considered safe for the developing fetus and the mother. More study of amniotic fluid stem cells is needed to understand their potential.

Why is there a controversy about using embryonic stem cells?

Embryonic stem cells are obtained from early-stage embryos — a group of cells that forms when a woman's egg is fertilized with a man's sperm. Extracting stem cells from embryos raises significant ethical questions.

Where do these embryos come from?

The embryos being used in embryonic stem cell research come from eggs that were fertilized at in vitro fertilization clinics but never implanted in a woman's uterus because they were no longer wanted or needed. The excess embryos were frozen and later voluntarily donated for research purposes. The stem cells can live and grow in special solutions in test tubes or petri dishes in laboratories.

Why can't researchers use adult stem cells instead?

While research into adult stem cells is promising and moving forward rapidly, adult stem cells may not be as versatile and durable as embryonic stem cells are. Adult stem cells may not be able to be manipulated to produce all cell types, which limits how they can be used to treat diseases, and they don't seem to have the same ability to multiply that embryonic stem cells do. They're also more likely to contain abnormalities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication. However, researchers have found that adult stem cells are more adaptable than was initially suspected. There have been significant advances in work with adult stem cells, and more studies are under way.

What are stem cell lines and why do researchers want to use them?

A stem cell line is a group of cells that all descend from a single original stem cell. Cells in a stem cell line keep growing but don't differentiate into specialized cells. Ideally, they remain free of genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers. That way, researchers don't have to get stem cells from an embryo itself.

What is stem cell therapy (regenerative medicine) and how does it work?

Stem cell therapy, also known as regenerative medicine, is the replacement of diseased, dysfunctional or injured cells with stem cells or their derivatives. It's somewhat similar to the organ transplant process but uses cells instead of organs.

Researchers grow stem cells in the lab. These stem cells are manipulated to make them specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells. This manipulation may involve changing the material in which the stem cells are grown or even injecting genes into the cells. The specialized cells could then be implanted into a person. For example, if the person had heart disease, the cells could be injected into the heart muscle. The healthy, transplanted heart cells could then contribute to repairing defective heart muscle. In fact, researchers have already shown that adult bone marrow cells guided to become heart-like cells can repair heart tissue in mice, and much more research is ongoing.

Have stem cells already been used to treat diseases?

Yes, stem cell transplants, also known as bone marrow transplants, have been performed in the United States since the late 1960s. These transplants use adult stem cells.

Adult stem cells are being tested in other applications, including a number of degenerative diseases, such as heart failure. Stem cells from umbilical cord blood have been successfully used in clinical trials to treat cancer and blood-related diseases.

The Food and Drug Administration has approved an initial safety study using an embryonic stem cell therapy for the treatment of serious spinal cord injuries.

What are the potential problems with using embryonic stem cells in humans?

To be useful in people, researchers must be certain that stem cells will differentiate into the specific cell types desired. Researchers, for instance, don't want to transplant a stem cell into a person hoping it'll become a heart cell only to learn that it's become a bone cell, with potentially dangerous consequences. Researchers have found ways to direct stem cells to become specific types of cells, and research into this area has advanced significantly.

Embryonic stem cells could also grow irregularly — something that's been reported in animal experiments — or travel to a part of the body where they're not intended to go. They also might trigger an immune response in which the recipient's body attacks the stem cells as foreign invaders, or simply fail to function normally, with unknown consequences. Researchers are working on ways to avoid these possible complications.

What is therapeutic cloning and what benefits might it offer?

Therapeutic cloning is a technique to create versatile stem cells independent of fertilized eggs. In this technique, the nucleus, which contains the genetic material, is removed from an unfertilized egg. The nucleus is also removed from a somatic cell of a donor. This donor nucleus is then injected into the egg, replacing the nucleus that was removed, a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This creates a line of stem cells that is genetically identical to the donor's — in essence, a clone. This technique is also called somatic cell nuclear transfer.

Some researchers believe that stem cells derived from therapeutic cloning may offer benefits over those from fertilized eggs because they're less likely to be rejected once transplanted back into the donor, and they may allow researchers to see exactly how a disease develops.

Has therapeutic cloning in people been successful?

No. Researchers haven't been able to successfully perform therapeutic cloning with humans, despite success in a number of other species.

What does the future hold for stem cell therapy?

Researchers say the field has promise. Stem cell transplants using adult stem cells continue to be refined and improved. And researchers are discovering that adult stem cells may be somewhat more versatile than originally thought, which means they may be able to treat a wider variety of diseases. Studies using embryonic stem cells or embryonic-like stem cells to regenerate tissue and organs in people are just getting started. Researchers are enthusiastic about the potential for regenerative medicine treatments.

How you prepare

Pretransplant tests and procedures
Once donor stem cells become available, you undergo many tests and procedures to assess your health and the status of your condition, and to ensure that you're physically prepared for the transplant.

In addition, an intravenous (IV) catheter is typically surgically implanted, usually in your chest near your neck. This is often called a central line, and it usually remains in place for the duration of your treatment. It's through the central line that the transplanted stem cells will be infused. The central line is also used to collect blood samples, give chemotherapy, provide blood transfusions and even supply nutrition when necessary.

The conditioning process
After you complete your pretransplant tests and procedures, you begin a process known as conditioning. During conditioning, you undergo chemotherapy and possibly radiation in order to:

• Destroy cancer cells
• Suppress your immune system so that your body doesn't reject the transplanted stem cells

The type of conditioning process you undergo depends on a number of factors, including your disease, overall health and the type of transplant planned — whether you get stem cells donated from someone else (allogenic transplant) or whether the stem cells come from your own body (autologous transplant).

In some cases, the conditioning process involves high doses of chemotherapy and total body irradiation (TBI). In other cases, the conditioning process may include only high doses of chemotherapy and no radiation at all. The type of conditioning you undergo depends on your unique circumstances.

Side effects of the conditioning process can include:

• Nausea and vomiting
• Diarrhea
• Hair loss
• Mouth sores or ulcers
• Infections, such as pneumonia
• Bleeding
• Infertility or sterility
• Anemia
• Fatigue
• Cataracts
• Organ failure, such as heart, liver or lung failure
• Secondary cancers

You may be able to take medications or other measures to reduce such side effects.

'Mini' stem cell transplants
A less intense conditioning process is available through what's known as a mini stem cell transplant. It's also called a reduced-intensity conditioning transplant or a nonmyeloablative transplant.

Reduced-intensity conditioning doesn't try to kill all of the cancer cells that may be in your body. Instead, it relies on the donor's immune system cells to fight your cancer cells.

A less intense conditioning regimen may seem attractive because it may pose fewer life-threatening complications. But this kind of transplant isn't appropriate for all situations. Mini stem cell transplants are typically used only for people who can't endure the harsher conditioning regimen, such as people in poorer health, and for people whose disease isn't rapidly progressing.

What you can expect

During your stem cell transplant
Stem cell transplantation involves infusing, or injecting, donor stem cells through your central line. This usually takes one to five hours. The transplanted stem cells make their way to your bone marrow cavities, where they begin creating new bone marrow and stem cells. It can take a few weeks, though, for your blood counts to begin recovering.

Bone marrow or blood stem cells that have been frozen and thawed contain a preservative that protects the cells. Just before the transplant, you may receive medications to reduce the side effects the preservative can cause. These side effects include:

• Nausea
• Fever
• Chills
• Hives

Not everyone experiences side effects from the preservative, and for some people those side effects are minimal.

After your stem cell transplant
After your stem cell transplant, you may stay in the hospital until your blood counts recover or you may return home but remain under close medical care. Some people who have inpatient transplants are able to leave the hospital within three to five weeks, but others may face much longer hospitalizations. Some transplant facilities require transplant recipients to remain nearby to allow close monitoring.

In the days and weeks after your stem cell transplant, you may have many of the same kinds of tests and procedures to monitor your condition that you had before the transplant. You may also need supplemental nutrition to compensate for nausea and diarrhea.

To combat various complications, you may need to take numerous medications. You may also need periodic transfusions of red blood cells and platelets until your bone marrow begins producing enough of those cells on its own.

Results

It usually takes about a year for your blood cells and immune system to recover to normal levels after a stem cell transplant. In general, recovery from a stem cell transplant that uses your own harvested stem cells is quicker than from one that uses donor stem cells.

A stem cell transplant can cure some diseases and put others into remission. Most people who have a stem cell transplant expect the procedure to extend their life, and it often does.

Some people sail through stem cell transplantation with few side effects and complications. Others experience numerous problems, both short and long term. The severity of side effects and the success of the transplant vary from person to person.

Most people who have a stem cell transplant and don't have a relapse of their diseases go on to enjoy a good quality of life. Many are able to return to work or school and resume their normal activities.

VIDEO :

Bone marrow is the spongy tissue inside some bones. Its job is to produce blood cells. If your bone marrow isn't functioning properly because of cancer or another disease, you may receive a stem cell transplant. To prepare for a stem cell transplant, you receive chemotherapy to kill the diseased cells and malfunctioning bone marrow. Then, transplanted blood stem cells are put into your bloodstream. The transplanted stem cells find their way to your marrow, where — ideally — they begin producing new, healthy blood cells.

Diseases of the Nails

chronic mucocutaneous candidiasis

Diseases of the nails can cause significant social, psychological, and physical damage to an affected individual. These disorders may be isolated to the nail unit itself or be part of a larger systemic disease that may present first, or only, in the nail unit. The image shown is of an individual with chronic mucocutaneous candidiasis.

The nail unit is composed of the nail plate, the nailbed, the hyponychium, the nail matrix, the nail folds, the cuticle, the anchoring portion of the nailbed, and the distal phalangeal bones. The nail plate is the largest component of the nail unit. The nail matrix gives rise to the nail plate. Any defect to the matrix results in onychodystrophy of the growing nail plate. The proximal nail matrix forms the dorsal portion of the nail plate, whereas the distal matrix forms the ventral part of the nail plate. Clinical disease may vary depending on the location and the severity of inflammation of the affected nail unit.

Onychomycosis

Onychomycosis is a fungal infection involving any component of the nail unit. It may cause pain, discomfort, and disfigurement that can lead to physical and occupational limitations. Trichophyton rubrum and T mentagrophytes are responsible for 90% of all cases of onychomycosis. Most commonly the fungus spreads from the plantar skin and invades the nailbed via the hyponychium. Onychomycosis is typically asymptomatic. Patients tend to request help for cosmetic reasons but occasionally complain of pain, discomfort, and loss of dexterity. Treatment involves topical or oral antifungals depending on the location and extent of infection.

Clubbing

Clubbing is a clinical finding characterized by bulbous fusiform enlargement of the distal portion of a digit in which the angle between the proximal nail fold and the nail plate decreases to less than 160°. The exact pathophysiologic mechanism is unknown. Primary clubbing is caused by pachydermoperiostosis, familial clubbing, and hypertrophic osteoarthropathy. Causes of secondary clubbing include disorders of the lungs (such as lung cancer, interstitial lung disease, cystic fibrosis), heart (including cyanotic congenital heart disease), gastrointestinal tract (such as inflammatory bowel disease, liver cirrhosis, achalasia), and skin (as exemplified by palmoplantar keratoderma), as well as many malignancies, such as thyroid cancer, chronic myeloid leukemia, and other miscellaneous conditions, including acromegaly and pregnancy. There is no specific treatment for clubbing. If the underlying disease process or condition is treated, then the clubbing may improve or resolve.

Paronychia

Paronychia is a soft-tissue infection of the crease between the nail and the nail fold (shown). It is the most commonly encountered hand infection, often seen in individuals whose occupation requires frequent contact with water, such as bartenders. Patients typically describe pain and tenderness. Acute paronychia typically develops after minor trauma and can lead to infection, with Staphylococcus aureus as the organism most commonly implicated in infection. Chronic paronychia develops after exposure to moist environments and lasts 6 weeks or longer, with Candida albicans as the most common etiologic agent. On examination, the affected area may appear erythematous and swollen with pus in advanced cases and nail changes in chronic ones. Acute paronychia is treated with warm soaks and oral antibiotics. Chronic paronychia is treated by keeping the lesion dry and by the application of topical antifungals. Surgical intervention may be required in acute or chronic paronychia cases that are refractory to therapy or in which an abscess develops.

Melanonychia

Melanonychia is a brown or black pigmentation of the nail plate. It most often occurs because of increased production of melanin by melanocytes in the nail matrix. It is more common in darkly pigmented individuals and may be found in almost 100% of African Americans over the age of 50 years. There are 2 types of melanonychia: diffuse and longitudinal. Distinction depends upon the extent of discoloration. It may be caused by a number of different conditions, including melanocytic hyperplasia in melanoma (shown), lentigo, melanocytic nevi, physiologic causes (including darker skin tone and pregnancy), local factors (such as trauma, carpal tunnel, and ultraviolet light), systemic diseases (including hyperthyroidism, Addison's disease, systemic lupus erythematosus, and vitamin B₁₂ deficiency), and dermatologic disorders (such as psoriasis vulgaris, progressive systemic sclerosis, and lupus erythematosus), or iatrogenically by medication, especially chemotherapeutic agents and antibiotics. Patients are typically asymptomatic; treatment is aimed at correction of the underlying process.

Distal onycholysis

Distal onycholysis refers to spontaneous separation of the nail plate starting at the distal free margin and progressing proximally. Local irritation is the most common insult, such as excessive filing or chemical overexposure in manicures. Onycholysis has also been associated with a number of other systemic disorders, specifically systemic lupus erythematosus, hyperthyroidism, iron-deficiency anemia, primary dermatologic diseases (such as atopic dermatitis and psoriasis vulgaris), or neoplasms (including squamous cell carcinoma and lung carcinoma), as well as medications (especially fluoroquinolones and doxycycline), infections, or congenital etiologies. Patients do not typically report any pain or discomfort unless there is a superimposed infection. Treatment involves controlling or eliminating any risk factors and clipping off the unattached nail to prevent additional prying off and to allow for normal replacement of nail growth.

Subungual hematomas

Subungual hematomas are common nailbed injuries caused by blunt or sharp trauma to the nail. The rich vascular supply in the nailbed makes it prone to bleeding. Patients with minor hematomas are typically asymptomatic. Large hematomas may produce enough throbbing pain for patients to seek medical attention. Treatment involves trephination, in which a hole is drilled or burned through the nail body to release pressure, or nail removal.

Onychocryptosis

Onychocryptosis refers to an ingrown toenail, typically found in the big toe. Extrinsic compression of a toenail, typically from tight footwear, places constant pressure on the nail wall. If the nail is cut inappropriately short and the nail fold is irritated or penetrated, then colonization of bacteria or fungi may occur. Inflammation, edema, erythema, and pain are common findings; an abscess or cellulitis may develop. Treatment for early inflammation focuses on avoiding compressive footwear, dislodging the embedded nail plate, and education on proper nail care, including trimming the nail with squared corners. Treatment for more advanced cases involves partial or complete toenail removal. Antibiotic therapy is typically not required except for those who are diabetic, immunocompromised, or who show significant evidence of cellulitis.

Nail-patella syndrome

Nail-patella syndrome is an autosomal dominant condition characterized by nail dysplasia (shown), patellar aplasia-hypoplasia, elbow arthrodysplasia, and iliac horns. The nails may be absent, hypoplastic, or dystrophic with ridges, pits, and/or triangular lunulae. The anomalies are typically symmetric with the thumbs most severely affected and decreased severity progressing towards the fifth digit. Anomalies are evident at birth. Patients may also suffer from proteinuria, glaucoma, attention-deficit/hyperactivity disorder, recurrent dislocations, and irritable bowel syndrome. Treatment is aimed at pain management, physical therapy, and controlling renal failure. No specific therapy is available for the nail anomalies.

Psoriatic nail disease

Psoriatic nail disease is deformation of the nail unit of unclear etiology. It typically occurs in patients with clinically evident psoriasis and rarely is the only cutaneous finding. The clinical manifestations are protean and depend upon the portion of the nail unit affected. Findings may include pitting, Beau's lines (transverse lines in the nail caused by intermittent growth arrest), salmon patches, subungual hyperkeratosis, onycholysis, nail plate crumbling, splinter hemorrhages, and a spotted lunula. Diagnosis is made on clinical findings or by a nail biopsy. Treatment focuses on the functional and psychosocial aspects of the disease, as no curative treatment is available. Options include corticosteroids, psoralen plus ultraviolet light (PUVA), chemotherapeutic agents, and avulsion therapy.

Kanker Payudara

DEFINISI

Kanker Payudara adalah tumor ganas yang tumbuh di dalam jaringan payudara.

Kanker bisa mulai tumbuh di dalam kelenjar susu, saluran susu, jaringan lemak maupun jaringan ikat pada payudara.

Terdapat beberapa jenis kanker payudara:

1. Karsinoma in situ
   Karsinoma in situ artinya adalah kanker yang masih berada pada tempatnya, merupakan kanker dini yang belum menyebar atau menyusup keluar dari tempat asalnya.
2. Karsinoma duktal
   Karsinoma duktal berasal dari sel-sel yang melapisi saluran yang menuju ke puting susu.
   Sekitar 90% kanker payudara merupakan karsinoma duktal.
   Kanker ini bisa terjadi sebelum maupun sesudah masa menopause.
   Kadang kanker ini dapat diraba dan pada pemeriksaan mammogram, kanker ini tampak sebagai bintik-bintik kecil dari endapan kalsium (mikrokalsifikasi).
   Kanker ini biasanya terbatas pada daerah tertentu di payudara dan bisa diangkat secara keseluruhan melalui pembedahan.
   Sekitar 25-35% penderita karsinoma duktal akan menderita kanker invasif (biasanya pada payudara yang sama).
3. Karsinoma lobuler
   Karsinoma lobuler mulai tumbuh di dalam kelenjar susu, biasanya terjadi setelah menopause.
   Kanker ini tidak dapat diraba dan tidak terlihat pada mammogram, tetapi biasanya ditemukan secara tidak sengaja pada mammografi yang dilakukan untuk keperluan lain.
   Sekitar 25-30% penderita karsinoma lobuler pada akhirnya akan menderita kanker invasif (pada payudara yang sama atau payudara lainnya atau pada kedua payudara).
4. Kanker invasif
   Kanker invasif adalah kanker yang telah menyebar dan merusak jaringan lainnya, bisa terlokalisir (terbatas pada payudara) maupun metastatik (menyebar ke bagian tubuh lainnya).
   Sekitar 80% kanker payudara invasif adalah kanker duktal dan 10% adalah kanker lobuler.
5. Karsinoma meduler
   Kanker ini berasal dari kelenjar susu.
6. Karsinoma tubuler
   Kanker ini berasal dari kelenjar susu.

PENYEBAB

Penyebabnya tidak diketahui, tetapi ada beberapa faktor resiko yang menyebabkan seorang wanita menjadi lebih mungkin menderita kanker payudara.
Beberapa faktor resiko tersebut adalah:

1. Usia.
   Sekitar 60% kanker payudara terjadi pada usia diatas 60 tahun. Resiko terbesar ditemukan pada wanita berusia diatas 75 tahun.
2. Pernah menderita kanker payudara.
   Wanita yang pernah menderita kanker in situ atau kanker invasif memiliki resiko tertinggi untuk menderita kanker payudara.
   Setelah payudara yang terkena diangkat, maka resiko terjadinya kanker pada payudara yang sehat meningkat sebesar 0,5-1%/tahun.
3. Riwayat keluarga yang menderita kanker payudara.
   Wanita yang ibu, saudara perempuan atau anaknya menderita kanker, memiliki resiko 3 kali lebih besar untuk menderita kanker payudara.
4. Faktor genetik dan hormonal.
   Telah ditemukan 2 varian gen yang tampaknya berperan dalam terjadinya kanker payudara, yaitu BRCA1 dan BRCA2. Jika seorang wanita memiliki salah satu dari gen tersebut, maka kemungkinan menderita kanker payudara sangat besar.
   Gen lainnya yang juga diduga berperan dalam terjadinya kanker payudara adalah p53, BARD1, BRCA3 dan Noey2.
   Kenyataan ini menimbulkan dugaan bahwa kanker payudara disebabkan oleh pertumbuhan sel-sel yang secara genetik mengalami kerusakan.
   Faktor hormonal juga penting karena hormon memicu pertumbuhan sel. Kadar hormon yang tinggi selama masa reproduktif wanita, terutama jika tidak diselingi oleh perubahan hormonal karena kehamilan, tampaknya meningkatkan peluang tumbuhnya sel-sel yang secara genetik telah mengalami kerusakan dan menyebabkan kanker.
5. Pernah menderita penyakit payudara non-kanker.
   Resiko menderita kanker payudara agak lebih tinggi pada wanita yang pernah menderita penyakit payudara non-kanker yang menyebabkan bertambahnya jumlah saluarn air susu dan terjadinya kelainan struktur jaringan payudara (hiperplasia atipik).
6. Menarche (menstruasi pertama) sebelum usia 12 tahun, menopause setelah usia 55 tahun, kehamilan pertama setelah usia 30 tahun atau belum pernah hamil.
   Semakin dini menarche, semakin besar resiko menderita kanker payudara. Resiko menderita kanker payudara adalah 2-4 kali lebih besar pada wanita yang mengalami menarche sebelum usia 12 tahun.
   Demikian pula halnya dengan menopause ataupun kehamilan pertama. Semakin lambat menopause dan kehamilan pertama, semakin besar resiko menderita kanker payudara
7. Pemakaian pil KB atau terapi sulih estrogen.
   Pil KB bisa sedikit meningkatkan resiko terjadinya kanker payudara, yang tergantung kepada usia, lamanya pemakaian dan faktor lainnya. Belum diketahui berapa lama efek pil akan tetap ada setelah pemakaian pil dihentikan.
   Terapi sulih estrogen yang dijalani selama lebih dari 5 tahun tampaknya juga sedikit meningkatkan resiko kanker payudara dan resikonya meningkat jika pemakaiannya lebih lama.
8. Obesitas pasca menopause.
   Obesitas sebagai faktor resiko kanker payudara masih diperdebatkan. Beberapa penelitian menyebutkan obesitas sebagai faktor resiko kanker payudara kemungkinan karena tingginya kadar estrogen pada wanita yang obes.
9. Pemakaian alkohol.
   Pemakaian alkoloh lebih dari 1-2 gelas/hari bisa meningkatkan resiko terjadinya kanker payudara.
10. Bahan kimia.
    Beberapa penelitian telah menyebutkan pemaparan bahan kimia yang menyerupai estrogen (yang terdapat di dalam pestisida dan produk industri lainnya) mungkin meningkatkan resiko terjadinya kanker payudara.
11. DES (dietilstilbestrol).
    Wanita yang mengkonsumsi DES untuk mencegah keguguran memiliki resiko tinggi menderita kanker payudara.
12. Penyinaran.
    Pemaparan terhadap penyinaran (terutama penyinaran pada dada), pada masa kanak-kanak bisa meningkatkan resiko terjadinya kanker payudara.
13. Faktor resiko lainnya.
    Beberapa penelitian menunjukkan bahwa kanker rahim, ovarium dan kanker usus besar serta adanya riwayat kanker dalam keluarga bisa meningkatkan resiko terjadinya kanker payudara.

GEJALA

Gejala awal berupa sebuah benjolan yang biasanya dirasakan berbeda dari jaringan payudara di sekitarnya, tidak menimbulkan nyeri dan biasanya memiliki pinggiran yang tidak teratur.

Pada stadium awal, jika didorong oleh jari tangan, benjolan bisa digerakkan dengan mudah di bawah kulit.
Pada stadium lanjut, benjolan biasanya melekat pada dinding dada atau kulit di sekitarnya.

Pada kanker stadium lanjut, bisa terbentuk benjolan yang membengkak atau borok di kulit payudara. Kadang kulit diatas benjolan mengkerut dan tampak seperti kulit jeruk.

Gejala lainnya yang mungkin ditemukan:
- Benjolan atau massa di ketiak
- Perubahan ukuran atau bentuk payudara
- Keluar cairan yang abnormal dari puting susu (biasanya berdarah atau berwarna kuning sampai hijau, mungkin juga bernanah)
- Perubahan pada warna atau tekstur kulit pada payudara, puting susu maupun areola (daerah berwana coklat tua di sekeliling puting susu)
- Payudara tampak kemerahan
- Kulit di sekitar puting susu bersisik
- Puting susu tertarik ke dalam atau terasa gatal
- Nyeri payudara atau pembengkakan salah satu payudara .

Pada stadium lanjut bisa timbul nyeri tulang, penurunan berat badan, pembengkakan lengan atau ulserasi kulit.


Penyaringan

Kanker pada stadium awal jarang menimbulkan gejala, karena itu sangat penting untuk melakukan penyaringan.
Beberapa prosedur yang digunakan untuk penyaringan kanker payudara:

1. SADARI (Pemeriksaan Payudara Sendiri).
   Jika SADARI dilakukan secara rutin, seorang wanita akan dapat menemukan benjolan pada stadium dini.
   Sebaiknya SADARI dilakukan pada waktu yang sama setiap bulan. Bagi wanita yang masih mengalami menstruasi, waktu yang paling tepat untuk melakukan SADARI adalah 7-10 hari sesudah hari 1 menstruasi. Bagi wanita pasca menopause, SADARI bisa dilakukan kapan saja, tetapi secara rutin dilakuka setiap bulan (misalnya setiap awal bulan).
2. Mammogram.
   Pada mammogram digunakan sinar X dosis rendah untuk menemukan daerah yang abnormal pada payudara.
   Para ahli menganjurkan kepada setiap wanita yang berusia diatas 40 tahun untuk melakukan mammogram secara rutin setiap 1-2 tahun. Dan pada usia 50 tahun keatas mammogarm dilakukan sekali/tahun.
3. USG payudara.
   USG digunakan untuk membedakan kista (kantung berisi cairan) dengan benjolan padat.
4. Termografi.
   Pada termografi digunakan suhu untuk menemukan kelainan pada payudara.

SADARI

(Pemeriksaan Payudara Sendiri)

1. Berdiri di depan cermin, perhatikan payudara. Dalam keadaan normal, ukuran payudara kiri dan kanan sedikit berbeda. Perhatikan perubahan perbedaan ukuran antara payudara kiri dan kanan dan perubahan pada puting susu (misalnya tertarik ke dalam) atau keluarnya cairan dari puting susu. Perhatikan apakah kulit pada puting susu berkerut.
2. Masih berdiri di depan cermin, kedua telapak tangan diletakkan di belakang kepala dan kedua tangan ditarik ke belakang. Dengan posisi seperti ini maka akan lebih mudah untuk menemukan perubahan kecil akibat kanker. Perhatikan perubahan bentuk dan kontur payudara, terutama pada payudara bagian bawah.
3. Kedua tangan di letakkan di pinggang dan badan agak condong ke arah cermin, tekan bahu dan sikut ke arah depan. Perhatikan perubahan ukuran dan kontur payudara.
4. Angkat lengan kiri. Dengan menggunakan 3 atau 4 jari tangan kanan, telusuri payudara kiri. Gerakkan jari-jari tangan secara memutar (membentuk lingkaran kecil) di sekeliling payudara, mulai dari tepi luar payudara lalu bergerak ke arah dalam sampai ke puting susu. Tekan secara perlahan, rasakan setiap benjolan atau massa di bawah kulit.
   Lakukan hal yang sama terhadap payudara kanan dengan cara mengangkat lengan kanan dan memeriksanya dengan tangan kiri.
   Perhatikan juga daerah antara kedua payudara dan ketiak.
5. Tekan puting susu secara perlahan dan perhatikan apakah keluar cairan dari puting susu.
   Lakukan hal ini secara bergantian pada payudara kiri dan kanan.
6. Berbaring terlentang dengan bantal yang diletakkan di bawah bahu kiri dan lengan kiri ditarik ke atas. Telusuri payudara kiri dengan menggunakan jari-jari tangan kanan. Dengan posisi seperti ini, payudara akan mendatar dan memudahkan pemeriksaan.
   Lakukan hal yang sama terhadap payudara kanan dengan meletakkan bantal di bawah bahu kanan dan mengangkat lengan kanan, dan penelusuran payudara dilakukan oleh jari-jari tangan kiri.

Pemeriksaan no. 4 dan 5 akan lebih mudah dilakukan ketika mandi karena dalam keadaan basah tangan lebih mudah digerakkan dan kulit lebih licin.

DIAGNOSA

Diagnosis ditegakkan berdasarkan gejala, hasil pemeriksaan fisik dan hasil pemeriksaan berikut:

- Biopsi (pengambilan contoh jaringan payudara untuk diperiksa dengan mikroskop)

- Rontgen dada

- Pemeriksaan darah untuk menilai fungsi hati dan penyebaran kanker

- Skening tulang (dilakukan jika tumornya besar atau ditemukan pembesaran kelenjar getah bening)

- Mammogram

- USG payudara.


Staging

(Penentuan Stadium Kanker)

Penentuan stadium kanker penting sebagai panduan pengobatan, follow-up dan menentukan prognosis.
Staging kanker payudara (American Joint Committee on Cancer):
- Stadium 0 : Kanker in situ dimana sel-sel kanker berada pada tempatnya di dalam jaringan payudara yang normal
- Stadium I : Tumor dengan garis tengah kurang dari 2 cm dan belum menyebar keluar payudara
- Stadium IIA : Tumor dengan garis tengah 2-5 cm dan belum menyebar ke kelenjar getah bening ketiak atau tumor dengan garis tengah kurang dari 2 cm tetapi sudah menyebar ke kelenjar getah bening ketiak
- Stadium IIB : Tumor dengan garis tengah lebih besar dari 5 cm dan belum menyebar ke kelenjar getah bening ketiak atau tumor dengan garis tengah 2-5 cm tetapi sudah menyebar ke kelenjar getah bening ketiak
- Stadium IIIA : Tumor dengan garis tengah kurang dari 5 cm dan sudah menyebar ke kelenjar getah bening ketiak disertai perlengketan satu sama lain atau perlengketah ke struktur lainnya; atau tumor dengan garis tengah lebih dari 5 cm dan sudah menyebar ke kelenjar getah bening ketiak
- Stadium IIIB : Tumor telah menyusup keluar payudara, yaitu ke dalam kulit payudara atau ke dinding dada atau telah menyebar ke kelenjar getah bening di dalam dinding dada dan tulang dada
- Stadium IV : Tumor telah menyebar keluar daerah payudara dan dinding dada, misalnya ke hati, tulang atau paru-paru.

Selain stadium kanker, terdapat faktor lain yang mempengaruhi jenis pengobatan dan prognosis:

- Jenis sel kanker

- Gambaran kanker

- Respon kanker terhadap hormon
Kanker yang memiliki reseptor estrogen tumbuh secara lebih lambat dan lebih sering ditemukan pada wanita pasca menopause.

- Ada atau tidaknya gen penyebab kanker payudara.

PENGOBATAN

Biasanya pengobatan dimulai setelah dilakukan penilaian secara menyeluruh terhadap kondisi penderita, yaitu sekitar 1 minggu atau lebih setelah biopsi.
Pengobatannya terdiri dari pembedahan, terapi penyinaran, kemoterapi dan obat penghambat hormon.

Terapi penyinaran digunakan membunuh sel-sel kanker di tempat pengangkatan tumor dan daerah sekitarnya, termasuk kelenjar getah bening.
Kemoterapi (kombinasi obat-obatan untuk membunuh sel-sel yang berkembanganbiak dengan cepat atau menekan perkembangbiakannya) dan obat-obat penghambat hormon (obat yang mempengaruhi kerja hormon yang menyokong pertumbuhan sel kanker) digunakan untuk menekan pertumbuhan sel kanker di seluruh tubuh.


Pengobatan untuk kanker payudara yang terlokalisir

Untuk kanker yang terbatas pada payudara, pengobatannya hampir selalu meliputi pembedahan (yang dilakukan segera setelah diagnosis ditegakkan) untuk mengangkat sebanyak mungkin tumor.
Terdapat sejumlah pilihan pembedahan, pilihan utama adalah mastektomi (pengangkatan seluruh payudara) atau pembedahan breast-conserving (hanya mengangkat tumor dan jaringan normal di sekitarnya).

Pembedahan breast-conserving

1. Lumpektomi : pengangkatan tumor dan sejumlah kecil jaringan normal di sekitarnya
2. Eksisi luas atau mastektomi parsial : pengangkatan tumor dan jaringan normal di sekitarnya yang lebih banyak
3. Kuadrantektomi : pengangkatan seperempat bagian payudara.

Pengangkatan tumor dan beberapa jaringan normal di sekitarnya memberikan peluang terbaik untuk mencegah kambuhnya kanker.
Keuntungan utama dari pembedahan breast-conserving ditambah terapi penyinaran adalah kosmetik.
Biasanya efek samping dari penyinaran tidak menimbulkan nyeri dan berlangsung tidak lama. Kulit tampak merah atau melepuh.

Mastektomi

1. Mastektomi simplek : seluruh jaringan payudara diangkat tetapi otot dibawah payudara dibiarkan utuh dan disisakan kulit yang cukup untuk menutup luka bekas operasi. Rekonstruksi payudara lebih mudah dilakukan jika otot dada dan jaringan lain dibawah payudara dibiarkan utuh.
   Prosedur ini biasanya digunakan untuk mengobati kanker invasif yang telah menyebar luar ke dalam saluran air susu, karena jika dilakukan pembedahan breast-conserving, kanker sering kambuh.
2. Mastektomi simplek ditambah diseksi kelenjar getah bening atau modifikasi mastektomi radikal : seluruh jaringan payudara diangkat dengan menyisakan otot dan kulit, disertai pengangkatan kelenjar getah bening ketiak.
3. Mastektomi radikal : seluruh payudara, otot dada dan jaringan lainnya diangkat.

Terapi penyinaran yang dilakukan setelah pembedahan, akan sangat mengurangi resiko kambuhnya kanker pada dinding dada atau pada kelenjar getah bening di sekitarnya.

Ukuran tumor dan adanya sel-sel tumor di dalam kelenjar getah bening mempengaruhi pemakaian kemoterapi dan obat penghambat hormon.
Beberapa ahli percaya bahwa tumor yang garis tengahnya lebih kecil dari 1,3 cm bisa diatasi dengan pembedahan saja. Jika garis tengah tumor lebih besar dari 5 cm, setelah pembedahan biasanya diberikan kemoterapi. Jika garis tengah tumor lebih besar dari 7,6 cm, kemoterapi biasanya diberikan sebelum pembedahan.

Penderita karsinoma lobuler in situ bisa tetap berada dalam pengawasan ketat dan tidak menjalani pengobatan atau segera menjalani mastektomi bilateral (pengangkatan kedua payudara).
Hanya 25% karsinoma lobuler yang berkembang menjadi kanker invasif sehingga banyak penderita yang memilih untuk tidak menjalani pengobatan.
Jika penderita memilih untuk menjalani pengobatan, maka dilakukan mastektomi bilateral karena kanker tidak selalu tumbuh pada payudara yang sama dengan karsinoma lobuler.
Jika penderita menginginkan pengobatan selain mastektomi, maka diberikan obat penghambat hormon yaitu tamoxifen.

Setelah menjalani mastektomi simplek, kebanyakan penderita karsinoma duktal in situ tidak pernah mengalami kekambuhan.
Banyak juga penderita yang menjalani lumpektomi, kadang dikombinasi dengan terapi penyinaran.

Kanker payudara inflamatoir adalah kanker yang sangat serius meskipun jarang terjadi. Payudara tampak seperti terinfeksi, teraba hangat, merah dan membengkak.
Pengobatannya terdiri dari kemoterapi dan terapi penyinaran.

Rekonstrusi payudara

Untuk rekonstruksi payudara bisa digunakan implan silikon atau salin maupun jaringan yang diambil dari bagian tubuh lainnya.
Rekonstruksi bisa dilakukan bersamaan dengan mastektomi atau bisa juga dilakukan di kemudian hari.

Akhir-akhir ini keamanan pemakaian silikon telah dipertanyakan. Silikon kadang merembes dari kantongnya sehingga implan menjadi keras, menimbulkan nyeri dan bentuknya berubah. Selain itu, silikon kadang masuk ke dalam laliran darah.

Kemoterapi & Obat Penghambat Hormon

Kemoterapi dan obat penghambat hormon seringkali diberikan segera setelah pembedahan dan dilanjutkan selama beberapa bulan atau tahun.
Pengobatan ini menunda kembalinya kanker dan memperpanjang angka harapan hidup penderita.
Pemberian beberapa jenis kemoterapi lebih efektif dibandingkan dengan kemoterapi tunggal. Tetapi tanpa pembedahan maupun penyinaran, obat-obat tersebut tidak dapat menyembuhkan kanker payudara.

Efek samping dari kemoterapi bisa berupa mual, lelah, muntah, luka terbuka di mulut yang menimbulkan nyeri atau kerontokan rambut yang sifatnya sementara.
Pada saat ini muntah relatif jarang terjadi karena adanya obat ondansetron. Tanpa ondansetron, penderita akan muntah sebanyak 1-6 kali selama 1-3 hari setelah kemoterapi. Berat dan lamanya muntah bervariasi, tergantung kepada jenis kemoterapi yang digunakan dan penderita.
Selama beberapa bulan, penderita juga menjadi lebih peka terhadap infeksi dan perdarahan.
Tetapi pada akhirnya efek samping tersebut akan menghilang.

Tamoxifen adalah obat penghambat hormon yang bisa diberikan sebagai terapi lanjutan setelah pembedahan.
Tamoxifen secara kimia berhubungan dengan esrogen dan memiliki beberapa efek yang sama dengan terapisulih hormon (misalnya mengurangi resiko terjadinya osteoporosis dan penyakit jantung serta meningkatkan resiko terjadinya kanker rahim). Tetapi tamoxifen tidak mengurangi hot flashes ataupun merubah kekeringan vagina akibat menopause.


Pengobatan kanker payudara yang telah menyebar

Kanker payudara bisa menyebar ke berbagai bagian tubuh. Bagian tubuh yang paling sering diserang adalah paru-paru, hati, tulang, kelenjar getah bening, otak dan kulit.
Kanker muncul pada bagian tubuh tersebut dalam waktu bertahun-tahun atau bahkan berpuluh-puluh tahun setelah kanker terdiagnosis dan diobati.

Penderita kanker payudara yang telah menyebar tetapi tidak menunjukkan gejala biasanya tidak akan memperoleh keuntungan dari pengobatan. Akibatnya pengobatan seringkali ditunda sampai timbul gejala (misalnya nyeri) atau kanker mulai memburuk.
Jika penderita merasakan nyeri, diberikan obat penghambat hormon atau kemoterapi untuk menekan pertumbuhan sel kanker di seluruh tubuh.
Tetapi jika kanker hanya ditemukan di tulang, maka dilakukan terapi penyinaran. Terapi penyinaran merupakan pengobatan yang paling efektif untuk kanker tulang dan kanker yang telah menyebar ke otak.

Obat penghambat hormon lebih sering diberikan kepada:
- kanker yang didukung oleh estrogen
- penderita yang tidak menunjukkan tanda-tanda kanker selama lebih dari 2 tahun setelah terdiagnosis - kanker yang tidak terlalu mengancam jiwa penderita.
Obat tersebut sangat efektif jika diberikan kepada penderita yang berusia 40 tahun dan masih mengalami menstruasi serta menghasilkan estrogen dalam jumlah besar atau kepada penderita yang 5 tahun lalu mengalami menopause.

Tamoxifen memiliki sedikit efek samping sehingga merupakan obat pilihan pertama.
Selain itu, untuk menghentikan pembentukan estrogen bisa dilakukan pembedahan untuk mengangkat ovarium (indung telur) atau terapi penyinaran untuk menghancurkan ovarium.

Jika kanker mulai menyebar kembali berbulan-bulan atau bertahun-tahun setelah pemberian obat penghambat hormon, maka digunakan obat penghambat hormon yang lain.
Aminoglutetimid adalah obat penghambat hormon yang banyak digunakan untuk mengatasi rasa nyeri akibat kanker di dalam tulang. Hydrocortisone (suatu hormon steroid) biasanya diberikan pada saat yang bersamaan, karena aminoglutetimid menekan pembentukan hydrocortisone alami oleh tubuh.

Kemoterapi yang paling efektif adalah cyclophosphamide, doxorubicin, paclitaxel, dosetaxel, vinorelbin dan mitomycin C. Obat-obat ini seringkali digunakan sebagai tambahan pada pemberian obat penghambat hormon.

PROGNOSIS

Stadium klinis dari kanker payudara merupakan indikator terbaik untuk menentukan prognosis penyakit ini.
Angka kelangsungan hidup 5 tahun pada penderita kanker payudara yang telah menjalani pengobatan yang sesuai mendekati:
- 95% untuk stadium 0
- 88% untuk stadium I
- 66% untuk stadium II
- 36% untuk stadium III
- 7% untuk stadium IV.

PENCEGAHAN

Banyak faktor resiko yang tidak dapat dikendalikan.
Beberapa ahli diet dan ahli kanker percaya bahwa perubahan diet dan gaya hidup secara umum bisa mengurangi angka kejadian kanker.

Diusahakan untuk melakukan diagnosis dini karena kanker payudara lebih mudah diobati dan bisa disembhan jika masih pada stadium dini.
SADARI, pemeriksan payudara secara klinis dan mammogram sebagai prosedur penyaringan merupakan 3 alat untuk mendeteksi kanker secara dini.

Penelitian terakhir telah menyebutkan 2 macam obat yang terbukti bisa mengurangi resiko kanker payudara, yaitu tamoksifen dan raloksifen. Keduanya adalah anti estrogen di dalam jaringan payudara.
Tamoksifen telah banyak digunakan untuk mencegah kekambuhan pada penderita yang telah menjalani pengobatan untuk kanker payudara.
Obat ini bisa digunakan pada wanita yang memiliki resiko sangat tinggi.

Mastektomi pencegahan adalah pembedahan untuk mengangkat salah satu atau kedua payudara dan merupakan pilihan untuk mencegah kanker payudara pada wanita yang memiliki resiko sangat tinggi (misalnya wanita yang salah satu payudaranya telah diangkat karena kanker, wanita yang memiliki riwayat keluarga yang menderita kanker payudara dan wanita yang memiliki gen p53, BRCA1 atauk BRCA 2).

- Mammogram