TUMOR GANAS PADA ANAK / CANCER IN CHILDREN

INTRODUCTION

At first, the incidence of colon and rectal malignancies are not taken into account prior to 1900. However, since economic progress and growing industry, this increased incidence of malignancy. At this time, colorectal cancer is the third leading cause of death of men and women from cancer in the United States.

The incidence of colorectal cancer in Indonesia is quite high, so the 2002 figures kematiannya.Pada colorectal cancer ranks second in cancer cases are found in men, whereas in women colorectal cancer ranks third of all cases kanker.Meskipun no definitive data, but of various reports in Indonesia there are increasing number of cases, data from the Ministry of Health found 1.8 per 100,000 population numbers. ^1.4

In most cases of cancer, there is geographic variation in incidence were found, reflecting differences in socioeconomic and population density, particularly between developed and developing countries. Similarly, between the West and Indonesia, there is a difference in the frequency of colorectal cancers are found. In Indonesia, the frequency of colorectal cancer were found comparable between men and women; numerous in the young person; and approximately 75% of cancers found in the rectosigmoid colon, whereas in Western countries the frequency of colorectal cancers are found in men than women; numerous in the older person; and of cancer that is found only about 50% are located in the rectosigmoid colon. ²

Location of colorectal cancer is most often found in colon colorectal cancer patients rektosigmoid.Keluhan depending on the size and location of the tumor. Complaints of colonic lesions erada on the right can be a feeling of fullness in abdominal, symptomatic anemia and bleeding, while complaints from lesions in the left colon may be changes in the pattern of defecation, bleeding, constipation until the obstruction.

The division is based on the classification stages of the Duke is a complete blood test, digital rectal, barium enema, sigmoidoscopy, colonoscopy. Therapy consisted of curative and paliatif.Pengobatan curative therapy is surgery. Palliative therapy with chemotherapy and radiation. ⁵

CHAPTER II

LITERATURE REVIEW

II. 1. Wilms tumor

Wilms tumor is a malignant tumor derived from embryonic kidney metanefros. . Wilms tumor is a malignant tumor of the kidney that is most in infants and children. Approximately 80% of these tumors occurring in children under 6 years, with a peak incidence at 2-4 years of age. Wilms tumor can also be found in Wilms neonatus.Tumor counted 6% of all malignant disease in children. The incidence of the disease is almost the same in every country, because there is no distinction of race, climate and environment, which is an estimated 8 per 1 million children under the age of 15 years. Comparison of the incidence of men and women almost equally. Location of the tumor is usually unilateral, more often on the left, could also bilateral (approximately 5%). ⁶

Figure 1. Wilm's Tumor

Wilms tumor is derived from the pathological proliferation of blastema metanefron due to the absence of normal stimulation of duct metanefron to produce tubules and glomeruli of the renal blastema baik.Perkembangan differentiate to form the structure of the kidney occurs at 8-34 weeks gestation. So that primitive blastema is expected that the ability to pave the way for the formation of Wilms tumor, whether as a germ or somatic mutations, it occurs at 8-34 weeks gestation. ^6,7,8

Approximately 1.5% of patients have relatives or other family members who also suffer from Wilms tumor. Nearly all cases of unilateral descent is not different with the case of bilateral tumors. Approximately 7-10% of cases of Wilms tumor inherited autosomal dominant. Genetic mechanisms associated with this disease, is not yet fully known. In patients with WAGR syndrome (Wilms tumor, aniridia, genital malformations and mental retadasi) showed the presence of cytogenetic deletion in chromosome 11, region p13. In some patients, found WT1 gene on the short arm of chromosome 11, region p13. WT1 gene expression specifically in the kidney and is known as a transcription factor that is thought to be responsible for the development of Wilms tumor. ⁷

Pathology

Wilms tumor is composed of a network of primitive blastema metanefrik. Besides, these tumors   often contain tissues that are not normally found in normal metanefron, eg bone tissue, cartilage and squamous epithelium. highly diverse histological picture is characteristic of a Wilms tumor. Classical picture of Wilms tumor is triphasic, including epithelial cells and stromal blastema. Based on histological and clinical correlations, Wilms tumor histopathological picture can be classified into three groups, namely low-risk tumors ( favorable ), moderate-risk tumors and high-risk tumors ( unfavorable ). ⁷

Stadium

The National Wilms Tumor Study (NWTS) divides 5 Wilms tumor stage, namely:

Stage I: Tumor confined to the kidney tissue without penetrating the capsule. These tumors can be in with a complete resection.

Stage II: Tumor penetrates the capsule and extends into the surrounding renal tissue and perirenal tissues, namely kidney, the renal hilum, the renal vein and para-aortal lymph nodes. Tumors can be resected completely still.

Stage III : The tumor spread to the abdominal cavity (perkontinuitatum), for example, to the liver, peritoneum and others.

Stage IV : The tumor hematogenous spread to the abdominal cavity, lungs, brain and bone.

Clinical manifestations

Hematuria (macroscopic) present in approximately 25% of cases, due to tumor infiltration into the system Calix. Hypertension was found in about 60% of cases, presumably due to suppression of tumor or hematoma on the blood vessels that supply blood to the kidneys, resulting in tissue ischemia which will stimulate the release of renin, or tumors themselves secrete renin. Other symptoms such as anemia, weight loss, urinary tract infections, fever, malaise and anorexia. match In some patients who are colicky abdominal pain, due to a blood clot in the urinary tract. Wilms tumors are not infrequently found with other congenital anomalies, such as aniridia, hemihypertrophy, urinary tract or genital anomalies and mental retardation. ^7.8

Diagnosis

Wilms tumor diagnosis based on:

·          Clinical symptoms

·          radiological examination (IVP and ultrasound), laboratory LDH 

·          confirmed by histopathological examination of tumor tissue

With IVP examination seemed distortion pielokalises system (changes shape pielokalises system) and once this examination is useful to determine kidney function. Ultrasound is non-invasive inspection can differentiate solid tumors with tumor-containing fluids. With ultrasound, Wilms tumor appears as a solid tumor in the kidney area. Results of laboratory tests essential that support for Wilms tumor is the concentration of lactic dehydrogenase (LDH) elevated and Vinyl mandelic acid (VMA) in the normal range. ⁷

 Therapy

Wilms tumor treatment modality consists of, operation (surgery), chemotherapy and radiotherapy. In stage I and II tumors with cell type favorable , surgery with dactinomycin and vincristine combination chemotherapy without radiation of the abdomen. With stage III tumor cell types favorable given surgical treatment with a combination daktinomisin, vincristine and doxorubicin with abdominal radiation. For stage IV tumors with cell type favorable , given the combination daktinomisin, vincristine and doxorubicin. Patients also received abdominal radiation and lungs when it is no spread to the lung tissue. In cases with stage II to IV anaplastic cell types ( unfavorable ) are given surgical treatment with a combination daktinomisin, vincristine and doxorubicin plus siklofospamid. In these patients also received abdominal radiation and lung. ^6,7,8

Prognosis

Several factors determine the prognosis, the tumor size, histopathologic picture, the age of the patient and the stage or degree of tumor dissemination. Those who have a good prognosis are patients who have tumor size was small, the high degree of cell differentiation in histopathologic, still early stage or no metastasis and patient age under two years.

II. II. RHABDOMIOSARKOMA

Rhabdomiosarkoma (RMS) This word comes from the Greek, (rhabdo, which means striated shapes, and myo meaning muscle). Rhabdomyosarcoma is a malignant tumor that originates from the soft tissue (soft tissue) of the body, including here is muscle tissue, tendons and connective tissue. Rhabdomyosarcoma is a malignancy that is often found in children anak.Respon treatment and prognosis of the disease is highly dependent on the location and histological features of the tumor itself. The rate was slightly higher incidence in boys and white children. These tumors can occur in any location but most frequently in the head and neck 40%, 20% genitorius tract, limb 20%, weight 10%.

Predisposition Factor

• Congenital abnormalities.
• Rare syndromes such as Beckwith-Wiedemann Syndrome and Recklinghausensyndrome.
• Abnormalities in the formation of tumor-derived (autosomal dominant, chromosome 17).
• Li-Fraumeni Syndrome
• Neurofibromatosis type 1 (NF 1)
• Costello syndrome.

Classification

Intergroup Rhabdomyosarcoma Study (IRS) made a classification of laboratory and surgery for rhabdomyosarcoma, namely:

a.       Group I:

Only local disease, regional lymph nodes are not involved, complete resectable

1)       Confined to muscle or organ original

2)       Infiltration out muscle or organ original

b.       Group II:

1)       widely resectable tumors with microscopic residual (lymph node negative)

2)       regional disease, complete resectable (positive or negative lymph nodes)

3)       Reginal disease involving lymph nodes can be resected widely but with microscopic residual

c.        Group III:

Incomplete resection or biopsy only with sufficiently large residual disease

d.       Group IV:

There has been a metastasis is diagnosed when

Staging TNM (tumor, nodes and metastases)

Tumors:

T0: no palpable tumor

T1: tumor <5 cm

T2: tumor> 5cm

T3: the tumor has invaded the bone, blood vessels and nerves

Nodules:

No: not found regional node involvement

N1: regional node involvement is found

Metastasis:

Mo: there are no distant metastases

M1: There is distant metastasis

Rhabdomyosarcoma Staging System:

Stage 1: the location of the orbit, and head or neck (not Parameningeal) extends to the urinary tract (bladder or prostate instead)

Stage 2: other locations, No or Nx

Satge 3: other locations, N1 if tumor <5 cm or No or Nx if tumor> 5 cm

Stage 4: any location and there are distant metastases

Based on histological examination, it can be determined the degree of severity (grading):

a.        G1: well differentiated (good)

b.       G2: moderately differentiated (moderate)

c.        G3: poorly differentiated (bad)

Determination of specific histiotipe need for therapy and prognosis. There are four types of known subhistologi namely:

a.        embryonal type

Embryonal rhabdomyosarcoma is the type most commonly found in children, approximately 60% of all cases rabdomiosarkoma.Tumor can occur anywhere, but most often on the genitourinary, head or leher.Pada histology histology of this type have a high variability, which illustrates some levels of muscle morphogenesis skeletal.Merupakan neoplasms with high differentiation consisting of rabdomioblas with eosinophilic cytoplasm. Desmin and actin were found in the muscles used for diagnosing rhabdomyosarcoma

b.       Alveolar Type

Alveolar tumors that cause approximately 15% of cases, is characterized by the chromosomal translocation T (2; 13). Tumor cells tend to grow in the nucleus (core), which often have a slit-like spaces that resemble alveolar alveoli.Tumor most often occurs in the body and limbs and have the worst prognosis.

c.        Botrioid type,

It is a variant form of embryonal tumor and stromal cells which are swollen protruding into the cavity of the body like a bunch of grapes, causing 6% of cases and most often appear in the vagina, uterus, bladder, nasopharyngeal and middle ear.

d.       pleomorphic type (adult form)

Pleomorphic type (adult form) is rare in children (1% of cases). Approximately 20% of patients are estimated to have undifferentiated sarcoma. This type is very rare in patients over 45 years the other three in 90% of cases occur before the age of 20 years. Pleomorphic variant has atypical tumor cells were large, some showing cytoplasm with corakan berlurik much typical for skeletal muscle differentiation.

Histopathologic Classification TNM After Unresectable

pT0: There is no tumor on histological examination.

PT1: Limited on the organ of origin. Excision perfect.

Pt2: The invasion into surrounding organs, excision perfect.

PT3: Invasion into surrounding organs, excision is not perfect.

         a. Remaining visible microscopically

         b. The rest can be seen as a macroscopic

         c. Tumor can not be resected.

Nopt 4

pN0: No lymph nodes affected

PN1: lymph nodes affected

pM0: No metastasis to distant sites

PM1: There is metastasis to distant sites

Stages

- Stage I (16% of cases)

Cancer is only found in the initial site of cancer arise On microscopic examination, there are no cancer cells in the tissue after the tumor is removed.

- Stage II (28% of cases)

Divided into II A, II B, and II C

1. IIA: Cancer can be lifted, but microscopically, there are remaining cancer cells in the tissue. No lymph nodes were affected.

2. IIB: The cancer is localized, it can be removed, ith or without lymph node involvement

3. C II: The cancer has spread to lymph nodes. Cancer and lymph nodes still can be removed surgically, but still terapat remaining cancer cells are microscopic.

- Stage III (36% of cases)

Cancers can be removed surgically, but still there are remaining cancer can be seen without mikroskop.Kanker has not spread to distant sites.

- Stage IV (20% of cases)

Cancer has spread to distant sites.

Other variants are basically small tumors primitive blue cell, poorly differentiated have a focal skeletal muscle differentiation (rabdomioblas with eosinophilic cytoplasm and corakan striated).

Differentiation rabdomioblastik may only appear with electron microscopic or immunohistochemical techniques (ribosome-myosin complex or positive imunoperoksidase to desmis / myoglobin). Variance alveolar characterized by translocation 2; 13 chromosomal).

Pathology

Rhabdomiosarkoma thought to arise from the same embryonic mesenchymal skeletal muscle denngan attack latitude. Definitive diagnostic test requires menggnakan histokimiawi with antibodies   against skeletal bibs (desmin) and electron microscopy to distinguish typical image. Histological typing of need for therapy and prognosis. Subhistologi there are four types are known. embryonal type, causing 60% of all cases with moderate prognosis. botrioid type, a variant form of embryonal tumor and stromal cells which are swollen protruding into the body cavity like a bunch of grapes, resulting in 6% of cases and most often appear in the vagina, uterus, bladder, nasopharynx, and middle ear. Alveolar tumors that cause approximately 15% of cases. Palling alveolar tumors often occur on the limbs of the body and have the worst prognosis. pleomorphic type is rare in childhood 1% of cases. approximately 20% of patients with undifferentiated sarcoma estimated possessed.

Clinical Manifestations

There are a wide variety of signs and symptoms in rabdomyosarkoma, we need to realize that people rhabdomyosarkoma especially children may get symptoms that differ from one another depending on the location of the tumor itself. Symptoms often do not appear before the tumor reaches a large size, if the tumor is located in the muscle tissue in the abdomen are the most common:

a. Rabdomyosarkoma mass of which can be seen and felt, can feel pain or not.

b. Bleeding in the nose, vagina, rectum, or mouth may occur if the tumor is located in this area.

c. Tingling, pain, and movement can occur when a tumor presses on a nerve affected area.

d. Protrusion and eyelid wilt, can indicate a tumor behind this area.

Risk group

Risk group  created by the merger between the  grouping system and staging systems . systems used to plan treatment. Divided into:

- Low risk: if one of the following criteria:

• Embryonal tumor of any size that are found on favorable sites . The tumor may be a tumor remaining after surgery that can be seen without mikorskop. The cancer may have spread to the lymph nodes.  Favorable site  are:

·          eye or eye area.

·          Head and neck (but not in the tissue that surrounds the brain and spinal cord).

·          The gall bladder and bile ducts.

·          Near the testes or vagina (but not the kidney, bladder, or prostate).

                        Embryonal tumor of any size that is not found on favorable sites . These tumors may be tumor remaining after surgery that can only be seen with a microscope. The cancer may have spread to the lymph nodes.

- Intermediate risk: if one of the following criteria:

• Embryonal tumor of any size that is not found on favorable sites . The tumor may be a tumor remaining after surgery that can be seen with or without a microscope. The cancer may have spread to nearby lymph nodes.
• Alveolar tumor of any size that are found in  favorable or  unfavorable site . The tumor may be a tumor remaining after surgery that can be seen with or without a microscope. The cancer may have spread to nearby lymph nodes.

- High risk: all types of rhabdomyosarcoma that may have spread to lymph nodes and has spread to great distances.

Diagnosis

Rhabdomyosarkoma diagnostic evaluation of symptoms in addition to the obvious, the diagnosis should also involve  standing  and classification of tumors, which is very useful useful in determining therapy in patients.  Standing  is a process to determine the extent to which the cancer has spread, and if it spreads, to which the deployment has occurred. There are various types of the system  standing  used in the determination of  standing  is that TMN system uses tumor ( T ), Nodes ( N ), and metastasis ( M ) to differentiate into various levels of disease ( Standing ).

The history of the course of the disease, including a history of cancer in the family tendency (li-Fraumenn), a thorough physical examination to determine the location and size of the tumor and regional lymph nodes chills. Laboratory tests including complete blood necessary, liver and kidney function, serum electrolytes, calcium and possibly magnesium levels, uric acid and clotting function. Bone marrow aspiration is also necessary for the alleged RMS is recommended parameningeal.Pemeriksaan radiology x-rays and ultrasound scans toraks.CT area of ​​the primary tumor, if possible pmeriksaan MRI performed on tumor biopsies primer.Selanjutnya dilauakn of the primary tumor and lymph nodes suspected.

Diagnostic evaluation should describe the level of the primary tumor and metastatic disease level consisting of:

a. Physical examination

b. Blood cell count

c. Urinanalisis

d. Serum electrolytes: BUN, Creatine, SGOT, SGPT, LDH, and alkaline phospatase

e. Preview resonasi magnetic (MRI) and computer tomography (CT) challenged the main injury

f. CT Scan

g. Bone Scan

h. Or bone marrow biopsy

i. Biopsy of suspicious lymph

Management

The success of the rhabdomiosarkoma, management is requiring a multidisciplinary approach and the combined approach. The goal is

• Tumor control.
• Maintain the function of the affected part.
• Prevent metastases.

a.        surgery

most effective when the tumor occurs in the complex if not biopsy therapy, followed by chemotherapy and radiotherapy, followed by the remaining parts of the tumor.

Removal of the primary tumor is done with enough of the normal tissue. The approach to this surgery done on key areas where complete removal would not be functional impairment. Because the primary tumors arise in the path, head and neck and extremities and places tertentu.Kemoterapi Dangan or without radiotherapy should be entrusted to the upper control residual tumor is in a prime location.

Rules of the spleen in the division as part of a major surgery and approach the position of the tumor in an area where there is an involvement of the regional lymph nodes, surgery should be performed in this area include:

1) Extremity (15%)

2) genitourinary (20%)

3) perirectal (33%)

4) Paratesticular (40%)

b. Radio Therapy

Radiation therapy is recommended for patients on site, except for histopathological classification groups (complete lack of mokropik). Radiation dose is recommended based on the group klinis.Bila allow limitations should include 4-5 cm from the margin of normal tissue, metastasik location of radiation should be avoided if possible .

c. Stem cell transplantation

used to improve the system of blood vessels that have been damaged by cancer cells.

d. Other Therapies

Currently the new treatment being studied, using angiogenesis inhibitors  and  biological therapies .  Angiogenesis inhibitors  are substances that can prevent tumor growth by blocking the formation of new blood vessels that feed the tumor would.  Biological therapies  are therapies that improve the body's immune system, thus our body's immune system to fight cancer can also fight harmful side effects of chemotherapy and radiotherapy treatment.

e. Chemotherapy

All patients did not depend on their kinis grouping, receive combination chemotherapy, since its use resulted in a significant increase in the release of disease survival when added nursing and radiation.

 Prognosis

Among patients with resectable tumors, 80-90% gain disease-free survival time. Approximately 60% of patients with resected tumors were not totally Reginal also obtain disease-free survival in the long term. Patients with diffuse disease prognosis buruk.Hanya Approximately 505 have achieved remission and less than 50% of the experienced older kesembuhan.Anak have a worse prognosis than younger ones. rognosis depends on:

a. Staging of disease

b. The location of the tumor as well.

c. Presence or absence of metastases.

d. Tumor response to therapy.

e. Age and health conditions of the patient.

f. Patient tolerance to treatment, therapy procedures.

g. The discovery of the latest treatments.

To achieve a survival rate ( survival rate ) required high: Close cooperation with other disciplines

a. Appropriate clinical diagnosis

b. Appropriate treatment strategy, in which this issue depends on: the evaluation of post-surgical anatomical pathology, evaluation of the degree of malignancy, need / absence of adjuvant therapy (chemotherapy or radiotherapy).

II. III. Osteosarcoma

Osteosarcoma (osteogenic sarcoma) is a neoplastic cells produce osteoid spindleyang. Osteosarcoma is a primary malignant tumor of tulangyang characterized by the formation of immature bone or tissue osteoidoleh tumor cells.

Osteosarcoma is usually found in the long bones in manalempeng metaphysical growth (epiphyseal growth plate) is very active; ie padadistal femur, proximal tibia and fibula, proximal humerus and pelvis. To a person older than 50 years of age, osteosarcoma can occur due to degeneration ganasdari pagets disease, the prognosis is very bad.

Risk Factors

 The exact cause of osteosarcoma is unknown, but terdapatberbagai risk factors for osteosarcoma are:

a)       rapid bone growth          : rapid bone growth terlihatsebagai osteosarcoma predisposition, as it seemed that insidennyameningkat during adolescent growth. Location osteosarcoma palingsering the metaphysical, where this area is long daritulang growth area.

b)       Environmental factors        : the only environmental factor known adalahpaparan to radiation.

c)       Predisposisigenetik      : bone dysplasias, including Paget's disease, fibrousdysplasia, enchondromatosis, danhereditary multiple exostoses and retinoblastoma (germ-line form). The combination of RB gene mutations (germline retinoblastoma) and radiation therapy for osteosarcoma resikotinggi associated with Li-Fraumeni syndrome (germline p53mutation), and Rothmund-Thomson syndrome (autosomal recessive congenital yangberhubungan with bone defects, hair and bone dysplasias, hypogonadism, and cataracts ).

Clinical Symptoms

Symptoms usually been there for several weeks or months sebelumpasien diagnosed. The most common symptom is pain there, especially when nyeripada activity and mass or swelling. Not infrequently there is riwayattrauma, although the role of trauma in osteosarcoma is not jelas.Fraktur pathological extremely rare, except in telangiectatic osteosarcoma yanglebih common pathologic fracture.

Pain in the extremities can cause kekakuan.Riwayatpembengkakan be there or not, depending on the location and magnitude of systemic lesi.Gejala, such as fever or night sweats very jarang.Penyebarantumor the lung is very rare cause of respiratory symptoms and pulmonary involvement biasanyamenandakan wide.

The discovery of the physical examination is usually confined to a palpable utamatumor.Massa be there or not, can danhangat tenderness on palpation, although these symptoms are difficult to distinguish from osteomielitis.Pada inspection can be seen an increase in vascularity in kulit.Penurunan rangeof motion in the affected joints can be considered at the examination fisik.Lymphadenopathy is very rare.

Differential diagnosis

Some abnormalities that lead to formation of bone mass in seringsulit distinguished with osteosarcoma, both clinically and imaging denganpemeriksaan. The disorders include:

1. Ewings sarcoma

2. Osteomyelitis

3. Osteoblastoma

4. The Giant cell tumor

Examination Support

a.Laboratorium   Most laboratory tests are used berhubungandengan use of chemotherapy. It's important to know the function organsebelum chemotherapy and to monitor organ function setelahkemoterapi.Pemeriksaan blood for the benefit of the prognosis is lacticdehydrogenase (LDH) and alkaline phosphatase (ALP). Patients with an increase ALP values ​​at the time of diagnosis have a greater likelihood to have metastases at paru.Pada patients without metastases, yangmempunyai increase in LDH values ​​less able to heal when compared with patients who had normal LDH values.

Several laboratory tests are important include:

·          LDH

·          ALP (prognostic interest)

·          A complete blood count

·          Liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin.

·          Electrolytes: Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus.

·          Renal function tests: blood urea nitrogen (BUN), creatinine

Radiography

X-ray examination is the primary modality used to investigasi.Ketika suspected osteosarcoma, MRI is used to determine the distribution and spread of tumors to the bone in the soft tissues sensitf sekitarnya.CT less when compared to MRI for evaluation of tumor lokaldari but can be used to determine metastasis paru.Isotopic lungs bone scanning is generally used to detect tumor metastases or synchronous padatulang, but the whole body MRI scans can menggantikanbone.

. The X-ray

plain bibs are essential in the evaluation of the first lesitulang because the results can predict the diagnosis and determination of pemeriksaanlebih far right. Plain picture may vary, but kebanyakanmenunjukkan mixture of lytic areas and rarely sklerotik.Sangat lytic or sclerotic lesions hanyaberupa.

Looks aggressive lesions, can be moth eaten with no clear edge there ataukadangkala cortical multiple small holes. After chemotherapy, the surrounding bone may form around the edges with clear boundaries on tumor.Penyebaran often seen as a soft tissue mass with joints lunak.Dekat network, the spread is usually difficult to distinguish from efusi.Area like a cloud because of sclerosis due to the production of osteoid calcification can be seen malignadan the masses. Periosteal reaction is often terdapatketika the tumor has penetrated the cortex. A wide spectrum of changes may occur, including   Codman triangles and multilaminated, spiculated, and sunburst reaction, which all indicate an aggressive process.

Telangiectatic osteosarcoma generally reveals a lytic, with periosteal reaction and soft tissue mass. When the tumor boundary berbatastegas, can resemble aneurysmal bone cyst picture. Small-cell osteosarcoma   look identical to the image of conventional osteosarcoma, which mempunyaigambaran mixture of lytic and sclerotic. Low-grade intraosseous osteosarcoma may be lytic, sclerotic or mixed; mempunyaigambaran often benign with firm boundaries and no change danmassa periosteal soft tissue.

 Gnathic tumor can be either lytic, sclerotic or mixed and seringterjadi bone destruction, periosteal reaction and extension on the intracortical network lunak.osteosarkoma described as radiolucent and geographic overview, and contains an internal mineralization in the number of high degree kecil.Osteosarkoma has a picture with a soft tissue mass yangluas various degrees of mineralization that appears on the surface tulang.Osteosarkoma parosteal tumors typically a high density yangmuncul of extensive bone area. Not like the osteochondroma, osteosarkomaparosteal not involve the medullary cavity of bone.

CT Scan

CT may be useful locally when polosmembingungkan photo picture, especially in areas with complex anatomy (contohnyapada changes in the mandible and maxilla in osteosarcoma

gnathic and padapelvis associated with secondary osteosarcoma). Cross-sectional overview gives a clearer picture of the destruction of bone in the soft tissues surrounding danpenyebaran than polos.CT photo dapatmemperlihatkan matrix mineralization in small amounts that are not visible padagambaran polos.CT photo is especially helpful when changes periostealpada flat bones rarely difficult to diinterpretasikan.CT used for evaluation of tumors in the long bones, but is a modality that sangatberguna to determine metastasis to the lung.

CT is very useful in the evaluation of various variants of osteosarcoma. Padaosteosarkoma telangiectatic can show fluid levels, and if digunakanbersama contrast can differentiate aneurysmal bone lesions in cystdimana after contrast is given it will show an increase gambarannodular around the cystic spaces.

MRI

MRI is the modality for evaluating local spread daritumor because skill in the interpretation of bone marrow and network lunak.MRI is the most accurate imaging technique for staging of osteosarcoma menentuan and assist in surgical menentukanmanajemen tepat.Untuk goal of tumor stage, and tumor penilaianhubungan between compartments on the place of origin is penting.Tulang POINTS, joints and soft tissues of the compartment covered merupakanbagian fascia.

Intraosseous tumor spread and ekstraoseus must dinilai.Fitur yangpenting of intraosseous disease is the longitudinal distance yangmengandung bone tumors, epiphyseal involvement, and the presence Skip metastase.Keterlibatanepifisis by the tumor has been known to occur than expected, dansulit seen the picture plain. Epiphyseal involvement can be seen didiagnosaketika signal intensity similar to that seen in metafisisyang tumors associated with focal destruction of the growth plate.

 Skip metastases are synchronous focus of tumor secaraanatomis separate from the primary tumor but were still at secondary sama.Deposit bone on the other side of the bone is called transarticular skip metastases. Patients with more frequent mempunyaikecenderungan skip metasase presence of distant metastases and tumor-free survival interval yangrendah. Assessment of tumor spread involves determining ototmanakah ekstraoseus involved and the relationship of tumor to neurovascular structures sekitarnya.Hal dansendi is important to avoid yangmelebihi patients received resection of the joint compartments terlibat.Keterlibatan didiagnosaketika tumor tissue can be seen spreading to the bone subartikular dankartilago.

Bone scintigraphy

Osteosarcoma generally showed increased uptake on bone scan dariradioisotop using technetium-99m methylenediphosphonate (MDP). Bone scans are very useful for mengeksklusikanpenyakit multifocal. skip lesions and lung metastases can be detected, but the most consistent lesion skip if using MRI. Due to an increased uptake of radioisotope osteosarkomamenunjukkan the bone scan bersifatsensitif but not specific.

Angiography

Angiography is more invasive examination. Angiografidapat determined by a kind of diagnosis of osteosarcoma, such as the High-gradeosteosarcoma be found a very ekstensif.Selain neovascularization angiography was performed to evaluate the success of pengobatanpreoperative chemotheraphy, which occurs when the tumor had reduced or hilangnyavaskularisasi preoperative chemotherapy response indicates success.

Biopsy

Biopsy is to establish a definite diagnosis is not done properly osteosarkoma.Biopsi often causing misdiagnosis (misdiagnosis) which will further be fatal to the determination of many recent tindakan.Akhir recommended by percutaneous needle biopsy (biopsy percutaneousneedle) with various advantages such as: very minimal invasion, does not require surgery wound healing time, lower infection risk danbahkan no, and the occurrence of post-biopsy fractures can be prevented.

 On histopathologic picture will be found stroma or with high-grade sarcomatous malignant osteoblast cells, which will form osteoid tissue and bone. In the central part yangbanyak mineralization will occur, while the peripheral mineralization bit. Biasanyaanaplastik tumor cells, with nuclei and many mitotic pleomorphik. Sometimes in some places of the tumor will occur kondroblastik or fibroblastic differentiation between tumor tissue that form osteoid.

Management

Surgery

The main objective is the safety of resection pasien.Reseksi harussampai free boundary tumor.Semua patients with osteosarcoma should menjalanipembedahan if possible resection of the tumor prmer.Tipe of pembedahanyang required depends on several factors that must be evaluated on an individual pasiensecara.

Radical limit, defined as the removal seluruhkompartemen involved (bones, joints, muscles) are usually not necessary. Resulting from the combination of chemotherapy with resection look better if dibandingkandengan radical amputation without adjuvant therapy, the level of 5-year survival rates of 50-70% and by 20% in the treatment with only radikalamputasi.

Pathological fractures, with all the compartments contamination dapatmengeksklusikan limb salvage surgery therapeutic use, but if dapatdilakukan surgery with resection of the tumor-free limit limbsalvage surgery can be performed. In some cases amputation may merupakanpilihan therapy, but more than 80% of patients with osteosarcoma treated with surgery on eksrimitasdapat limb salvage and not membutuhkanamputasi. If possible, it can be done-salvageyang limb reconstruction should be selected based on individual consideration, as follows:

Autologous bone graft: this can be with or without vaskularisasi.Penolakan not appear on the graft type and a low infection rate. Padapasien having mempunyaipilihan immature growth plates are limited to a stable bone fixation (osteosynthesis).

Allografts          : graft healing and infection can be a problem, especially during chemotherapy. Can also arises graft rejection.

Prosthesis         : joint reconstruction using prosthesis can be solitary or expandable, but it requires huge cost. Durabilitasmerupakan own problems at implant placement for pasienremaja.

Rotationplasty : This technique is usually appropriate for patients with tumors in the distal femur yangberada and proximal tibia, especially when the size of large tumors so that surgery only alternative to amputation. During resection of tumors, blood vessels repaired by means of end-to-end   anastomosis to maintain the patency of the vessel darah.Kemudian distal part of the leg is rotated 180 º and put together denganbagian proximal resection. This rotation can make anklemenjadi joints knee joints were taken fungsional.Sebelum better decisions for your family and pasienmelihat videos of patients who have undergone the procedure.

Resection of pulmonary nodules         : metastatic nodules in the lungs dapatdisembuhkan in total with surgical resection. Lobar resection or pneumonectomy is usually required to obtain bebastumor limit. This procedure is done at the same time as the primary pembedahantumor. Although bilateral nodules that can direseksimelalui median sternotomy, but better surgical field jikamenggunakan lateral thoracotomy.Oleh therefore recommended to perform the bilateral thoracotomies for bilateral metastases (each performed separately for several weeks).

II. IV. Ewing's sarcoma

Ewing's sarcoma is a malignant tumor composed of round cells, small most common in the first three decades kehidupan.Sarkoma primeryang Ewing is the most frequent malignant tumor of the long bones, most of the most seringterkena diafisis.tulang is the pelvis and ribs. Ewing's sarcoma is a malignant neoplasm that is growing rapidly and the cells derived from bone primitivesumsum in young adults.

Ewing's sarcoma is a malignant with low cure rates despite good denganpembedahan ablative radiation with radiation therapy or tidak.Namun thus padadaerah primary and metastatic regions menggunakandoxorubicine combined with chemotherapy, cyclophosphamide, vincristine and dactynomycin reported to meningkatkankelangsungan life of patients with metastatic though. Indeed multimodalitasdiyakini therapy will increase the proportion of long-term disease-free survival of approximately 15% from 50% in menjadilebih 2-3 decades.

Incidence

These tumors are most often seen in children in their teens and most often adalahtulang-long bone. (5) In children, tumors of Ewing's sarcoma is the most common primary bone setelahosteosarkoma. Every year no less than 0.2 cases per 100,000 children in diagnosissebagai ewing sarcoma, and there are an estimated 160 new cases occurred in 1993.Di around the world, the incidence varies from region with high incidence, for example AmerikaSerikat and Europe to regions with low incidence, such as Africa and China. Ewingsering sarcoma also occurs in the second decade kehidupan.Jarang occurred at age 5 and sesudah30 years. The incidence is equal between men and women. Ewing's sarcoma usually not berhubungandengan congenital syndrome, but many associated with skeletal anomalies, for example: enchondroma, aneurysmal bone cyst and urogenital anomalies, eg hypospadias. (1)

There are several risk factors that affect the incidence of Ewing's sarcoma, namely: 1). Factor is age. The incidence of Ewing's sarcoma increased rapidly from near 0 at 5tahun age and peaked at age 10 -18 tahun.Sesudah age 20 years insidensinyamenurun back and approaching 0 at age 30 years.2). Factor kelamin.Resiko types of men is slightly higher than women , but after the age of 13 years the incidence between men and women almost sama.3). ras.Penyakit factor is rare in blacks. 4). Genetic factors, which are known include: a). History keluarga.Faktor risk in the first lineage adasindroma familia meningkat.Tidak not associated with sarcoma Ewing.b). Genetic anomalies, the presence of an anomaly on chromosome 22, translocation or hilangnyakromosom was detected in 85% of patients with sarcoma Ewing.c). History of disease bone, certain congenital anomalies of the skeletal system, namely aneurysm kistatulang and enchondroma increase the risk of Ewing's sarcoma, also genitourinaryseperti hypospadias anomalies and duplications are also associated with Ewing's sarcoma.

Clinical Manifestations

Clinical manifestations of Ewing's sarcoma can berupama sistemik.Manifestasi local or local manifestations include: pain and swelling in the area of ​​the femur or pelvis, although tulanglain may also be involved. Of bone and soft tissue around the tumor area and bisateraba frequent and visible erythema fluctuations originating from bleeding inside the tumor. Manifestasisistemik typically include: lethargy, weakness and weight loss and sometimes fever terjadiserta be found of the period which is the lung metastases. The duration of munculnyagejala be measured in weeks or months and often extends to patients yangmempunyai primary lesion on the bone axis. (1) Signs and symptoms are typical: pain, tenderness lump, fever (38-40 ° C), danleukositosis (20,000 to 40,000 leukosit/mm3).

Diagnosis

Panyakit history and complete physical examination should be performed on all patients yangdicurigai as Ewing's sarcoma. Special attention should be placed on the following matters: (7) general condition and nutritional status of the patient. Examination of lymph nodes, include: the number, consistency, tenderness and good distribution in the cervical area, supraclavicular, axilla should sertainguinal dicatat.Pada chest examination, may obtain evidence of pleural effusion lung danmetastase, eg a decrease or loss of breath sounds, presence of pleural friction noise padapemeriksaan lungs. Abdominal examination, the presence of hepato-splenomegaly, ascites and all massaabdomen should be described clearly. Examination of the pelvis, can be done palpasiuntuk aware of any mass, or pain when pressed areas. Examination of the extremities, skeletal examinations including tests covering space is needed. Systemsaraf thorough examination should be recorded with baik.Diagnosis at issue: it is very important clinically as soon as possible to remove the infected bone. At biopsy rate keganasansekitar essential to recognize tumor cells, the clarity of osteosarcoma. Approximately another tumor cells biased reticulum cell sarcoma that menyerupaiEwings and metastatic neuroblastoma.

Examination Support

Test and diagnostic procedures should be performed in all patients who dicurigaisarcoma Ewing: 1). Blood tests: a). Routine blood tests. b). Liver transaminases. c). Laktatdehidrogenase. Increased levels of this enzyme is associated with the presence or berkembangnyametastase.2). Radiological examination: a). X-rays. b). CT scans: In dicurigaineoplasma area (eg pelvis, extremities, head) and it is important to note the large and lokasimassa and relation to surrounding structures and the presence of pulmonary metastases. When adagejala neurologic, CT scan of the head should also dilakukan.3). Invasive tests: a). Bone marrow biopsy and aspiration. Samplesumsum aspiration and biopsy of bone at some distance from the tumor is done to rule out the presence metastase.b). Biopsy. Incision or with a needle biopsy on the tumor mass is very important to diagnose Ewing's Sarcoma. If there are components of soft tissue, biopsy in this area usually lebihdimungkinkan.

Diagnostic Radiology 

Radiological picture of Ewing's sarcoma: lesions appear infiltrative destructive nature yangberawal in the medulla; seen as an area in the photo - radiolucent area. Rapidly destroys the tumor cortex and looks reaction periosteal.Kadang periostealnya reaction times appear as lines that resemble multilayered onion skin and onion are known as peelappearance. This picture was once considered patognomonis for this tuimor, but ordinary dijumpaipada other bone lesions.

Management

In primary Ewing sarcoma.

Surgery is performed on the basis of:

(A). Indications.

Progress radiation therapy in order to decrease the role of control of Ewing's sarcoma Ewing's sarcoma treatment pembedahandalam therapy. At present surgical resection therapy (usually dilakukansetelah preoperative adjuvant chemotherapy) is recommended in pelvic lesions and tumors that dapatmenyebar into bone tissue, for example: the fibula, costa and tarsal bones. Furthermore amputasidiperlukan for pathologic fractures and tumors that can not be the primary infragenikulatum local ditanganisecara with radiation therapy.

(B). Approach

Surgical approach varies depending on the size, location and spread of tumors.

(C). Procedure:

1). BiopsiTeknik to perform a biopsy on bone tumors are identical with osteosarcoma.

2). Radical resection

If surgical treatment is indicated, removal of the tumor with accompanying network edge normalharus done, unless there is excessive functional deficits. For example, amputasiprimer with Therapy radasi adjuvanta).

Preoperative Radiotherapy: Because of the high rate of local control with radiation (alone and with chemotherapy), a widely used therapy initidak.

Postoperative radiation therapy   : After appropriate surgical resection for Ewing's sarcoma, treatment can be continued with radiation therapy, only if there is residual microscopic remains large and significant. (2) The spread of local and metastatic Ewing's sarcoma. Radiation therapy is often used for the treatment of metastases, particularly after chemotherapy sistemik.Radiasi bilateral pulmonary profilaksistelah attempted, but was less successful when compared with systemic chemotherapy dalammencegah pulmonary tumor metastases.

Morbidity and mortality

Complications after radiation therapy generally occurs varies with the location of the tumor and dose primer.Jika not more than 5000 cGy, complications and severe functional deficits sekunderyang malignancies occur less than 18% of patients. (9) Many types sitostatica very effective for Ewing's sarcoma eg vincristine , adriamycine, cyclophosphamide, isofosfamide, etoposide and actinomycine D. Sebelumdigunakannya adjuvant chemotherapy, long-term survival of Ewing's sarcoma patients is not banyak.Pada series of pre-chemotherapy study, of 374 patients treated with surgery and radisi, only 36 (9.6%) who survive for five years. (1) This primerSekarang Ewing's sarcoma, chemotherapy is given 3-5 cycles before radiation treatment and pembedahanpada primary tumor. This provides an accurate assessment of response to chemotherapy. (2) B. Adjuvant chemotherapy

Adjuvant chemotherapy

consists of: Preoperative Chemotherapy Chemotherapy initials (3-5 cycles) is now the standard in patients with indikasipembedahan.

2). Additional postoperative chemotherapy Chemotherapy may be combined with radiation therapy if complete resection is not bisadilakukan.

II. V. hepatocellular carcinoma

Hepatocellular carcinoma occurs most often in children before the age of 4 years. liver tumors in children can be benign or malignant (cancerous), and can be a primary or a metastasis from another organ. Primary liver tumors are rare in children, there are approximately 3% of all tumors in anak.Kira about 50-60% of liver tumors in children are malignant and more than 65% of them are malignant hepatoblastoma.Tumor that also often get in child is hepatocellular carcinoma.

Pathophysiology

Causes of liver tumors is still not jelas.Tumor found from birth generally benign, such as hamartoma, hemangioma, and hemangioendotelioma.Ada 2 types of malignant tumors are often found in children are hepatoblastoma and hepatocellular carcinoma. Hepatoblastoma are found under 3 years and is associated with a genetic disorder that is loss of heterozygosity on chromosome 11p15 that resulted in the disruption of tumor suppression genes. Hepatoblastoma is also commonly associated with the syndrome Beckwith-Weidemann  where an interruption in the gene  insulin-like growth factor-  I  with the clinical manifestation of  exophthalmos, gigantism, macroglossia,  microcephaly,  and viceromegaly . Hepatocellular carcinoma in children can be found from birth to age 19 years, usually related to infection with hepatitis B or C, tirosinemia hereditary chronic type, disease  glycogen storage , α1-antitrypsin deficiency, and biliary cirrhosis.

Clinical Manifestations

Clinical symptoms of liver tumors in children are varied and different in every patient because it depends on the size and type of tumor, sometimes the symptoms are also caused by metastatic tumors. Some of the symptoms that are common include:

• Future large abdominal, or stomach enlargement
• Right abdominal pain
• Decreased appetite, weight loss
• Gag
• Jaundice
• Hot
• Itching of the skin
• Anemia
• Back pain due to tumor suppression can also occur with the outbreak of the crisis of acute abdominal tumor and hemoperitonium (usually in hepatocellular carcinoma)

Diagnosis

In addition to history and physical examination are complete, some investigations are also needed in the diagnosis of liver tumors in children and metastasenya, include:

• Laboratory: Complete blood, blood chemistry, liver and kidney function tests, hepatitis B and C serology; α-fetoprotein/AFP (also for monitoring therapy)
• Liver biopsy for histopathological examination
• Radiology: Plain radiographs of the chest, ultrasound / ultrasound  Doppler , CT-scan/MRI addition to determining the diagnosis of liver tumors should also do the staging of the tumor, especially in the wild type. Staging is very useful in the treatment and determine prognosis. There are several methods of determining the stage of liver tumors in children, one of them is as follows: Stage I: the tumor can be surgically removed complete with Stage II: The tumor can be removed surgically but still leave some residual Stage III: The tumor can not be removed completely by surgery and obtained the spread on the surrounding lymph nodes Stage IV: The tumor has spread to other organs Recurrent tumors reappeared after treatment with either hearts or other organs

The differential diagnosis

• Liver abscess
• Neuroblastoma
• Wilm's tumor
• Cholestasis / cirrhosis of the liver

Management

Management of liver tumors in children depends on the type and stage of the tumor, and the age and physical condition of the patient. In benign tumors usually surgery to remove the tumor without treatment of malignant tumors lainnya.Pada required cooperation with pediatric surgeons and a pediatric oncologist. Treatment is usually a combination of:

• Surgery
• Chemotherapy
• Radiotherapy
• Liver transplantation

Treatment based on the type and stage of the tumor:

• Hepatoblastoma stage I and II: The removal of the tumor and chemotherapy followed 4 series using  cisplatin,  vincristine,  and  fluorouracil .
• Hepatocellular carcinoma stage I and II tumors followed by chemotherapy appointment  cisplatin  and or  doxorubicin
• Stage III and IV hepatoblastoma: Some alternative treatments that can be done

1. Chemotherapy to reduce the size of the tumor as possible followed removal of the tumor and chemotherapy is closed again
2. Tumor metastases in lung surgery
3. Chemotherapy
4. Radiotherapy followed by surgery
5. Injecting chemotherapy drugs directly into the liver vein
6. Chemotherapy and kemoembolisasi
7. Liver transplantation

• Hepatocellular carcinoma stage III and IV tumor size reduction by using chemotherapy  cisplatin  with  vincristine / fluorouracil  or  doxorubicin  followed removal of the tumor as possible
• Relapse

Re-treatment done by previous treatment In addition to treatment of the tumor should also be done with a supportive treatment to prevent and treat infections, medication side effects and complications, as well as provide comfort to the patient during the observation pengobatan.Perlu performed periodically to monitor response to treatment and side effects to be aware of long-term treatment.

II. VI. Neuroblastoma

            Neuroblastoma is a tumor neuroblastik of  neural crest cells  are primordial along the sympathetic nervous system. Neuroblastoma is a malignancy of the most common extracranial solid in childhood and the most common malignant tumors in patients younger than age 1 year. In addition, neuroblastoma represents 7% to 10% of all malignancies diagnosed in pediatric patients younger than 15 years and is responsible for approximately 15% of all pediatric cancer deaths. However, neuroblastoma is a heterogeneous disease. Tumors may regress spontaneously or mature, or can be very aggressive, malignant phenotype. The presentation of neuroblastoma depends on the anatomical location of the sympathetic nervous system in which the primary tumor and the status of developing metastases. Neuroblastoma is the most frequent tumor in the early decades of life, approximately 80% in children under 4 years of age ¹ .

            Local diseases associated with the sympathetic nervous system, reaching the base of the skull to the pelvis. The most common presentation was abdominal mass, with 35% of cases arising from adrenergic cells in the adrenal medulla, 35% in the paraspinal ganglia, 20% in the posterior mediastinum, and 5% in the pelvis and 5% dileher ² .

Epidemiology

            It is generally a solid tumor in children less than 4 years. The incidence of neuroblastoma 10.5 / million children under the age of 15 years. The average age shown is 23 months, with a peak 0-4 years. Generally occurring in males than females (1.2:1), no racial or geographic predilection. Is a familial disease ² .

E mbriologi

Adrenal gland develops from two different cells of origin. The adrenal cortex is formed from cells derived from the mesoderm while the adrenal medulla develops from neural crest cells. Neural crest cells formed from the ventrolateral migration of neuro-ectodermal cells derived from the neural tube about 3 weeks into development. Neural crest cells are divided into 2 groups of cells that give rise to sensory ganglia of the cranial and spinal nerves as well as migration to other positions in the body to cause the melanocytes and sympathetic ganglia. The adrenal cortex is formed first, usually during the week to 6 development. Week 7 of neural crest cells migrate from the sympathetic ganglia formed a mass on the medial side of cortical development. Over the next few months until the birth of the fetus, the cortex will grow and differentiate circle around the mass of neural crest cells. When they are surrounded, the cells differentiated into secretory cells of the adrenal medulla. At about the age of 1 year the end of the formation of the adrenal glands showed three layers of the adrenal cortex surrounds the mature cells of the adrenal medulla ³ .

P atologi

            Neuroblastoma is a tumor of the sympathetic nervous system embryonal. These tumors arise during fetal or early postnatal life of sympathetic cells (sympathogonia) derived from the  neural crest . Histologically, the picture of neuroblastoma are not specific, small blue round cell tumors with uniform cells, with dense hyperchromatic nuclei and minimal cytoplasm. According to the classification of the International Neuroblastoma Pathology Classification System (INPC), the tumor is classified well and less well, depending on the degree of differentiation of neuroblast, contains Schwannian stroma, mitosis-karyorrhexis index, and age at diagnosis ⁴ .

Classification

   In 1984, Shimada and colleagues first developed the age-linked classification system based on morphology of the tumor neuroblastik are divided into groups according to tumor histology prognosis is good and not good histology. Shimada classification system based on

1. Mitosis karyorexis index (MKI)

2. Age children

3. Degrees differentiation

4.       Stroma rich  or  stroma-poor

Good prognosis include  infant, low MKI, rich stromal  tumors, well-differentiated tumors or tumors with a mixed degree of differentiation ⁵ . ICM was defined number of tumor cell mitosis or karyorrhexis neuroblastik per 5000 cells (low MKI <100 cells, intermediate cells 100-200, high> 200 cells)

Clinical symptoms

            Patients with neuroblastoma usually show symptoms and signs according to the primary location and extension of the disease, though often asymptomatic. Because 75% of neuroblastoma occur in the abdominal cavity (50% in the adrenal gland, 25% in the retroperitoneum), abdominal mass detected on physical examination, with complaints of abdominal pain. Other primary locations include mediatinum posterior (20%), cervical region (1%), and pelvis (4%). Respiratory distress or dysphagia may be a reflection of the thoracic region of the tumor. Changes in defecation and urination caused by compression of the spinal cord of paraspinal tumors. Tumors in the neck or upper chest can cause Horner syndrome (ptosis, miosis and anhidrosis), enophtalmus, and iris heterochromia. Acute cerebral ataxia observed, characterized dancing eye syndrome, opsoklonus, myoclonus and chaotic nystagmus. Two to three cases occurred in infants with primary tumor in the mediastinum. Other signs and symptoms result from the secretion of catecholamines and vasoactive intestinal polypeptide include diarrhea, weight loss, and hypertension. ^2.4

            The spread of neuroblastoma by age and stage shown in Table 3. More than 40% of patients with metastatic disease. In older patients, neuroblastoma have metastatic disease to the pattern of bone marrow, lymph nodes, and bone. Manifestation of metastases to bone (bone pain) or anemia (bone marrow infiltration). Brain, spinal cord, heart, lung is a rare location for metastasis. Metastasis is also associated with "raccoon eyes", the result of the spread of the retro-orbital venous plexux

Diagnosis

Laboratory

Lactate Dehydrogenase

Although not specific, serum lactate dehydrogenase (LDH) to determine the prognostic significance. High serum LDH values ​​marked proliferative activity or the extent of the tumor. Value LDH> 1500 IU / L is associated with a poor prognosis. LDH can be used to monitor disease activity or response to therapy. ⁴

Ferritin

A high value of serum ferritin (> 150 ng / mL) is also a picture of the rapid enlargement of tumor size or tumor. Increased serum ferritin is often at an advanced stage and indicates a poor prognosis. This value is often returned to normal during clinical remission. ⁴

Neuron Specific Enolase

Neurons are the specific Enolase (NSE) is a glycolytic enolase isoenzymes and contained within neurons in the central and peripheral nervous tissue. In neuroblastoma, NSE derived from tumor tissue and serum level values ​​are closely related to the clinical condition of the patient. Unfortunately a high value on NSE, are not always specific for neuroblastoma, and can also be found in patients with Wilms tumor, lymphoma, hepatoma. The top limit for serum NSE values ​​ranging from 14.6 ng / mL. NSE highest levels found in widespread neuroblastoma and metastatic, compared to the localized. Serum values ​​higher than 100ng/mL, usually associated with advanced stage that has a bad prognostic. ⁴

Catecholamines and their metabolites

When neuroblast cells derived from the neural crest is transformed into neoplastic, they are characterized by imperfect synthesis of catecholamines and their precursors, such as epinephrine (E), norepinephrine (NE), 3.4 dihydroxyphenilalanine (DOPA) and dopamine (DA) , and also metabolites such as vanillymaandellic acid (VMA), homovanillic acid (HVA), methoxydopamine (MDA), and methanephrine (MN), normethanephrine (NME) and 3 methoxytyramine (3MT). Neuroblastoma lack the enzyme phenylethanolamine N-methyltranferase, which converts noreepinefrin into epinephrine. Neuroblastoma cells do not have storage pockets catecholamines, like normal cells, so that these catecholamines are released into the circulation is rapidly degraded into VMA and HVA. VMA and HVA can be assessed from the urine, and both are very useful for the diagnosis and monitoring of disease activity. ¹

            Results of urinary catecholamine metabolites increased 90-95% in patients with neuroblastoma. Typically the value of 24-hour urine capacity assessed, but this time, the urine when using the assay sensitivity can also be used and have equal sensitivity. Normal values ​​for urinary VMA mmol/24 00:35 hours, while normal values ​​for HVA in urine was 0.40 mmol/24 hours.

Unfortunately, the catecholamines and their metabolites, it is impossible to detect the presence of a relapse during treatment of neuroblastoma patients who are being treated. In some cases the diagnosis of recurrence, these metabolites increased only 55%, when compared to the beginning of the presentation, more than 90% sensitivity. Therefore, the presence of this disease relapse or development, can not be detected reliably only with tumor markers alone.  ¹

Radiological examination

Radiography

Chest X-rays can be used to show a posterior mediastinal mass, usually in the thoracic neuroblastoma in children.

Ultrasonography

Although ultrasonography is the modality that is more often used in the initial assessment of suspected abdominal mass, less than the sensitivity and accuracy  of computed tomography  (CT) or magnetic resonance imaging (MRI) for the diagnosis of neuroblastoma. Other modalities typically used after screening with ultrasound to rule out diagnosis. Neuroblastoma ultrasound picture of a solid lesion, heterogeneous. ⁴

Computed Tomography (CT)

CT is commonly used used as a modality for the evaluation of neuroblastoma. It may show calcification in 85% of cases of neuroblastoma. Expansion of intraspinal tumor can be seen on CT with contrast. Overall, CT with contrast was reported by 82% accuracy in defining the extent of neuroblastoma. With an accuracy approaching 97% when performed by  bone scan . CT scan is a method that describes abdominal mass that can be done without anesthesia, which also showed evidence of local invasion, vascular wrap, lymphadenopathy, and calcification, which is highly suggestive of the diagnosis, particularly in relation to distinguishing between neuroblastoma and Wilms tumor. ⁴

Magnetic resonance imaging (MRI)

MRI is more sensitive imaging modality for the diagnosis and staging of neuroblastoma. MRI is more accurate than CT for the detection of stage 4 disease. Sensitivity of MRI was 83%, whereas 43% CT. MRI specificity of 97%, while 88% CT. MRI is the modality of choice to determine the involvement of the spinal cord. ⁴

Scintigraphy

Metaiodobenzylguanidine (MIBG) imaging is an option for evaluating the spread to the bone and bone marrow by neuroblastoma. Isotope 123 from I-metaiodobenzylguanidine ( ¹²³ I-MIBG) selectively taken catecholamine-secreting tumor cells (indicated more than 90%). ⁴

Bone Marrow Examination

Bone marrow biopsy is a routine and important method to detect the spread of bone marrow in neuroblastoma. Aspiration and biopsy should be performed, although it has a future diagnosis better.For gather accurate information, specimens taken from multiple locations recommended.

Tumor Staging

There are two primary systems used for staging of neuroblastoma. Evans classification used by the former Children's Cancer Group (CCG) and the classification of St. Jude Children's Research hospital used POG institutions. Evans covers the extent of tumor classification, according radiography. The staging classification Jude describe surgicopatologi, lymph node deployment. Both staging systems have prognostic value, they invented a system that is accepted, the International Neuroblastoma Staging System (INSS). Evaluation of the location of the primary tumor and metastatic dissemination depends on INSS inspection imaging (CT or MRI). ⁷

MIBG scanning is also in the initial evaluation recommendation to monitor therapeutic response.

Risk factors and therapy based on biological factors

            Treatment of neuroblastoma in children is not only based on the stage but also the basis of an appropriate risk clinical and biological variables. Biological factors that influence today is MYCN status, ploidy (for Infants), histopathological classification.

Group Risk

Risk groups	Prediction of survival of 3 years
Low Risk	> 90%
Moderate risk	70-90%
High risk	<30%

a.       groups a low risk

Ø Stage 1 (  localized resectable  neuroblastoma)

Ø Stage 2 <1 year

Ø Stage 4S

Adjuvant chemotherapy is usually not required for this group of patients except in cases in stage 4S disease cases life threatening.

b.       risk group was

Ø 3/4/4S disease state, age <1 year and good histological

Ø Stage 3, more than 1 year with  non-MYCN  and good histology.

                        Four chemotherapy agents (cyclophosphamide, doxorubicin, Carboplatin, Etoposide) given 4 or 8 cycles based on histology. Surgery performed after chemotherapy. If the disease recurs, radiotherapy may be considered.

c.        groups of high risk

Ø 2A/2B stage disease, age> 1 year and have MYCN amplification, histology was not good.

Ø Stadium 3/4/4S, age <1 year and MYCN amplification

Ø Stage 3 in children> 1 year with MYCN amplification or  non-MYCN amplified  and histology were not good.

Ø Stage 4 in children> 1 year

Multiagent induction chemotherapy for tumor remission, and increases the likelihood of resection. If the response is poor, second-line chemotherapy is used.

Treatment

The low risk group

All patients INSS Stage 1:

1. Surgery of the primary tumor with the observation of disease recurrence.  event free survival (EFS)  3 years by 94%,  overall survival (OS)  of 99%.

All patients with INSS stage 2A, 2B stage without MYCN amplification:

1. Surgery of the primary tumor without damage to vital organs. Observations obtained after surgery only patients with> 50% resection of the primary tumor.

2. For patients <50%: 4 cycles of chemotherapy with moderate doses using carboplantin, etoposide, cyclophosphamide, and doxorubicin. Agents and chemotherapy doses contained in the table below. COG protocol ANBL0531 lowered to 2 cycles of chemotherapy. During the 3-year 85% were symptomatic, overall  survival  99%

Patients with INSS stage 4S disease:

The majority of patients with INSS stage 4S entered the low-risk group with EFS 86% and OS 92%

1. Majority 4S tumors will regress spontaneously, although patients less than 2 months to have a high incidence of respiratory failure and liver dysfunction due to diffuse infiltration of the tumor to the liver.

2. No life-threatening complications, there is no indication of treatment.

3. Surgical resection of the primary tumor is usually not necessary, although biopsy of primary site or metastatic needed for the exact location of the biologic characteristics

4. Chemotherapy used in patients with life-threatening complications such as respiratory disorders and severe hepatic dysfunction. Research shows that brief ciclophosphamide low dose oral (5mg/kg/hari for 5 days every 2-3 weeks), or up to 4 cycles of chemotherapy untik moderate risk (cycles 1-4, Table 22-10) often induces remission.

Chemotherapy should be discontinued if remission is obtained before reaching 4 cycles of chemotherapy. Low-dose radiotherapy may also be used (150 cGy two to three times in two thirds of the anterior oblique lateral por liver through.

5. Patients with stage 4 S Biologic not infrequently be good candidates for more intensive treatment.

Moderate risk group   

Treatment

Surgery is indicated as described under the previous common treatment modality. The table below describes the various levels of response to induction chemotherapy of the Pediatric Oncology Group (POG), the Children's Cancer Group (COG), and the European Neuroblastoma Study Group (ENSG). Recently, COG, based on clinical INSS stage, age, and includes biological MYCN, Shimada histopathology, and ploidy, has developed a chemotherapy regimen that is designed to maintain or improve survival to minimize acute and long-term morbidity. This regimen using four of the most active agents in neuroblastoma (carboplatin, etoposide, cyclophosphamide, and doxorubicin).

Patients with moderate-risk neuroblastoma and favorable biology just get one of the four cycles of chemotherapy, and patients with unfavorable biology get two courses (eight cycles). Each cycle was given every 3 weeks. For details of chemotherapy, according to the scheme

Favorable Biology

For children aged <1 year, or weight ≤ 12 kg, the dose of chemotherapy administered milligrams per kilogram. Each of these 4 cycles administered at intervals of 3 weeks.

1. Carboplatin 560 mg / m ²  or 18 mg / kg IV over 1 hour to 1 day

2. Etoposide 120 mg / m ²  or 4 mg / kg IV over 2 hours a day for 3 days

3. Cyclophosphamide 1000 mg / m ²  or 33 mg / kg over 1 hour a day for 1 day

4. Doxorubicin 30 mg / m ²  or 1 mg / kg IV over 60 minutes per day for 1 day.

Variation of drug administered:

Treatment for moderate-risk patients

Unfavorable Biology

This patient received an additional 4 cycles of chemotherapy:

High-risk groups

Treatment

Surgery is performed under the indicated treatment modality, with the probability of long-term survival of patients group is less than 15%. As a whole Angaka survival increased to 43-50% with the comprehensive management of:

1. Induction chemotherapy

2. Consolidation high-dose therapy with autologous stem cell

3. Therapy for minimal residual disease:

a. Radiation to tumor sites

b. Agent nonsitotoksik

Induction chemo therapy

Due to the sensitive neuroblastoma chemotherapy, the goal of therapy is to reduce the induction to the maximum at the location of the primary tumor and metastasis. The duration of induction therapy protocols on each of approximately 4-5 months.

Consolidation therapy

The next phase is the consolidation therapy. The goal is to eliminate any tumor tersiasa with myeloablative cytotoxic agents and stem cell rescue. 3-year  survival rate in patients given myeloablative regimens followed by stem cell rescue is far superior (38-50%) with chemotherapy alone (15%). This is especially true for very high-risk patients such as age more than 1 year and MYCN amplification metastatic disease.

Operation Monitoring Post

Routine monitoring of the patient during the therapy completeness, detecting the risk of disease recurrence. Recommended list:

Risk factors for recurrence:

1. The local recurrence at the primary site:

a. Incomplete resection of the primary tumor. Tumor removal surgery on the primary tumor is important for the long-term prognosis.

2. Recurrence in bone marrow:

a. Bone marrow contains> 0.1%

b. Bone marrow involvement at the time of initial diagnosis

3. Recurrence in bone:

a. Bone involvement at the time of initial diagnosis. ⁶

CHAPTER III

CONCLUSION

The incidence of malignant tumors in children in Indonesia is quite high, and high mortality in men compared with 75% found in wanita.Sekitar rektosigmoid.Pemeriksaan digital rectal carcinoma is the determinant of the rectum. Risk factors for colorectal carcinoma is the degeneration of colonic polyps, genetic factors, lack of eating fibrous foods such as vegetables and fruits bsayur, and high consumption of animal fat.

Histological grade of carcinoma of the colon and rectum based on histological malignancy seen divided according to Dukes classification of colorectal carcinoma infiltrating hematogenous karsinoma.Penyebaran, limfogen and perkontinuitatum.

Clinical symptoms of colon carcinoma on the left is different from the left colon kanan.Karsinoma causing stenosis and obstruksi.Stenosis stool in the right colon carcinoma is rare and still be liquid stool so there is no first obstruksi.Gejala usually arise because of complications, namely bowel disorders physiology, obstruction, bleeding, or as a result of the left colon and rectum penyebaran.Karsinoma causes acute changes in bowel movements besar.Perdarahan rarely dialami.Nyeri the left colon is more real than kanan.Rasa diseased colon of the large intestine begins at the bottom left of the umbilicus, whereas from the gut right on the epigastrium.

Diagnosis is made based anammesis colorectal carcinoma, pemerikssan physical, digital rectal and colon with rektosigmoidiskopi or ganda.Komplikasi image contrast can occur in colorectal carcinoma is composed of obstruction and perforasi.Terapi curative and palliative therapy. Curative therapy is surgery n premises.Palliative therapy with chemotherapy and radiation

REFERENCES

1            Bowman LC, Hancock ML, Santana VM et al: Impact of intestified shemotheraphy on clinical outcomes in Infants and children with neuroblastoma: The St.. Jude Childern's Research Hospital experience, 1962 to 1988. J Clin Oncol 9: 1599, 1991.

2            Dehner LP: Primitive neuroectodermal tumor and Ewing's sarcoma. Am J Pathol Sung 17:1, 1993.

3            Schwartz. 2000.Intisari Principles of Surgery, 6th Edition. EGC Book Medical Publishers. Jakarta.

4            Nelson. Child Health 2000.Ilmu edition 3 vols XV. Medicine Book Publishers. EGC. Jakarta. thing: 1759 - 1804

5            Sjamsuhidajat. R, Wim de Jong. , 2005. Edition Textbook of Surgery 2. Publisher Book of Medicine. EGC. Jakarta. Page: 658-667

6            http://medicastore.com/penyakit/949/Neuroblastoma.html

7            http://www.dokterbedahherryyudha.com/2012/07/intra-abdominal-tumor-in-children.html

8            http://www.dokterbedahherryyudha.com/2012/04/wilm-tumor-nephroblastoma.html

 INTRODUCTION

At first, the incidence of colon and rectal malignancies are not taken into account prior to 1900. However, since economic progress and growing industry, this increased incidence of malignancy. At this time, colorectal cancer is the third leading cause of death of men and women from cancer in the United States.

The incidence of colorectal cancer in Indonesia is quite high, so the 2002 figures kematiannya.Pada colorectal cancer ranks second in cancer cases are found in men, whereas in women colorectal cancer ranks third of all cases kanker.Meskipun no definitive data, but of various reports in Indonesia there are increasing number of cases, data from the Ministry of Health found 1.8 per 100,000 population numbers. ^1.4

In most cases of cancer, there is geographic variation in incidence were found, reflecting differences in socioeconomic and population density, particularly between developed and developing countries. Similarly, between the West and Indonesia, there is a difference in the frequency of colorectal cancers are found. In Indonesia, the frequency of colorectal cancer were found comparable between men and women; numerous in the young person; and approximately 75% of cancers found in the rectosigmoid colon, whereas in Western countries the frequency of colorectal cancers are found in men than women; numerous in the older person; and of cancer that is found only about 50% are located in the rectosigmoid colon. ²

Location of colorectal cancer is most often found in colon colorectal cancer patients rektosigmoid.Keluhan depending on the size and location of the tumor. Complaints of colonic lesions erada on the right can be a feeling of fullness in abdominal, symptomatic anemia and bleeding, while complaints from lesions in the left colon may be changes in the pattern of defecation, bleeding, constipation until the obstruction.

The division is based on the classification stages of the Duke is a complete blood test, digital rectal, barium enema, sigmoidoscopy, colonoscopy. Therapy consisted of curative and paliatif.Pengobatan curative therapy is surgery. Palliative therapy with chemotherapy and radiation. ⁵

CHAPTER II

LITERATURE REVIEW

II. 1. Wilms tumor

Wilms tumor is a malignant tumor derived from embryonic kidney metanefros. . Wilms tumor is a malignant tumor of the kidney that is most in infants and children. Approximately 80% of these tumors occurring in children under 6 years, with a peak incidence at 2-4 years of age. Wilms tumor can also be found in Wilms neonatus.Tumor counted 6% of all malignant disease in children. The incidence of the disease is almost the same in every country, because there is no distinction of race, climate and environment, which is an estimated 8 per 1 million children under the age of 15 years. Comparison of the incidence of men and women almost equally. Location of the tumor is usually unilateral, more often on the left, could also bilateral (approximately 5%). ⁶

Figure 1. Wilm's Tumor

Wilms tumor is derived from the pathological proliferation of blastema metanefron due to the absence of normal stimulation of duct metanefron to produce tubules and glomeruli of the renal blastema baik.Perkembangan differentiate to form the structure of the kidney occurs at 8-34 weeks gestation. So that primitive blastema is expected that the ability to pave the way for the formation of Wilms tumor, whether as a germ or somatic mutations, it occurs at 8-34 weeks gestation. ^6,7,8

Approximately 1.5% of patients have relatives or other family members who also suffer from Wilms tumor. Nearly all cases of unilateral descent is not different with the case of bilateral tumors. Approximately 7-10% of cases of Wilms tumor inherited autosomal dominant. Genetic mechanisms associated with this disease, is not yet fully known. In patients with WAGR syndrome (Wilms tumor, aniridia, genital malformations and mental retadasi) showed the presence of cytogenetic deletion in chromosome 11, region p13. In some patients, found WT1 gene on the short arm of chromosome 11, region p13. WT1 gene expression specifically in the kidney and is known as a transcription factor that is thought to be responsible for the development of Wilms tumor. ⁷

Pathology

Wilms tumor is composed of a network of primitive blastema metanefrik. Besides, these tumors   often contain tissues that are not normally found in normal metanefron, eg bone tissue, cartilage and squamous epithelium. highly diverse histological picture is characteristic of a Wilms tumor. Classical picture of Wilms tumor is triphasic, including epithelial cells and stromal blastema. Based on histological and clinical correlations, Wilms tumor histopathological picture can be classified into three groups, namely low-risk tumors ( favorable ), moderate-risk tumors and high-risk tumors ( unfavorable ). ⁷

Stadium

The National Wilms Tumor Study (NWTS) divides 5 Wilms tumor stage, namely:

Stage I: Tumor confined to the kidney tissue without penetrating the capsule. These tumors can be in with a complete resection.

Stage II: Tumor penetrates the capsule and extends into the surrounding renal tissue and perirenal tissues, namely kidney, the renal hilum, the renal vein and para-aortal lymph nodes. Tumors can be resected completely still.

Stage III : The tumor spread to the abdominal cavity (perkontinuitatum), for example, to the liver, peritoneum and others.

Stage IV : The tumor hematogenous spread to the abdominal cavity, lungs, brain and bone.

Clinical manifestations

Hematuria (macroscopic) present in approximately 25% of cases, due to tumor infiltration into the system Calix. Hypertension was found in about 60% of cases, presumably due to suppression of tumor or hematoma on the blood vessels that supply blood to the kidneys, resulting in tissue ischemia which will stimulate the release of renin, or tumors themselves secrete renin. Other symptoms such as anemia, weight loss, urinary tract infections, fever, malaise and anorexia. match In some patients who are colicky abdominal pain, due to a blood clot in the urinary tract. Wilms tumors are not infrequently found with other congenital anomalies, such as aniridia, hemihypertrophy, urinary tract or genital anomalies and mental retardation. ^7.8

Diagnosis

Wilms tumor diagnosis based on:

·          Clinical symptoms

·          radiological examination (IVP and ultrasound), laboratory LDH 

·          confirmed by histopathological examination of tumor tissue

With IVP examination seemed distortion pielokalises system (changes shape pielokalises system) and once this examination is useful to determine kidney function. Ultrasound is non-invasive inspection can differentiate solid tumors with tumor-containing fluids. With ultrasound, Wilms tumor appears as a solid tumor in the kidney area. Results of laboratory tests essential that support for Wilms tumor is the concentration of lactic dehydrogenase (LDH) elevated and Vinyl mandelic acid (VMA) in the normal range. ⁷

 Therapy

Wilms tumor treatment modality consists of, operation (surgery), chemotherapy and radiotherapy. In stage I and II tumors with cell type favorable , surgery with dactinomycin and vincristine combination chemotherapy without radiation of the abdomen. With stage III tumor cell types favorable given surgical treatment with a combination daktinomisin, vincristine and doxorubicin with abdominal radiation. For stage IV tumors with cell type favorable , given the combination daktinomisin, vincristine and doxorubicin. Patients also received abdominal radiation and lungs when it is no spread to the lung tissue. In cases with stage II to IV anaplastic cell types ( unfavorable ) are given surgical treatment with a combination daktinomisin, vincristine and doxorubicin plus siklofospamid. In these patients also received abdominal radiation and lung. ^6,7,8

Prognosis

Several factors determine the prognosis, the tumor size, histopathologic picture, the age of the patient and the stage or degree of tumor dissemination. Those who have a good prognosis are patients who have tumor size was small, the high degree of cell differentiation in histopathologic, still early stage or no metastasis and patient age under two years.

II. II. RHABDOMIOSARKOMA

Rhabdomiosarkoma (RMS) This word comes from the Greek, (rhabdo, which means striated shapes, and myo meaning muscle). Rhabdomyosarcoma is a malignant tumor that originates from the soft tissue (soft tissue) of the body, including here is muscle tissue, tendons and connective tissue. Rhabdomyosarcoma is a malignancy that is often found in children anak.Respon treatment and prognosis of the disease is highly dependent on the location and histological features of the tumor itself. The rate was slightly higher incidence in boys and white children. These tumors can occur in any location but most frequently in the head and neck 40%, 20% genitorius tract, limb 20%, weight 10%.

Predisposition Factor

• Congenital abnormalities.
• Rare syndromes such as Beckwith-Wiedemann Syndrome and Recklinghausensyndrome.
• Abnormalities in the formation of tumor-derived (autosomal dominant, chromosome 17).
• Li-Fraumeni Syndrome
• Neurofibromatosis type 1 (NF 1)
• Costello syndrome.

Classification

Intergroup Rhabdomyosarcoma Study (IRS) made a classification of laboratory and surgery for rhabdomyosarcoma, namely:

a.       Group I:

Only local disease, regional lymph nodes are not involved, complete resectable

1)       Confined to muscle or organ original

2)       Infiltration out muscle or organ original

b.       Group II:

1)       widely resectable tumors with microscopic residual (lymph node negative)

2)       regional disease, complete resectable (positive or negative lymph nodes)

3)       Reginal disease involving lymph nodes can be resected widely but with microscopic residual

c.        Group III:

Incomplete resection or biopsy only with sufficiently large residual disease

d.       Group IV:

There has been a metastasis is diagnosed when

Staging TNM (tumor, nodes and metastases)

Tumors:

T0: no palpable tumor

T1: tumor <5 cm

T2: tumor> 5cm

T3: the tumor has invaded the bone, blood vessels and nerves

Nodules:

No: not found regional node involvement

N1: regional node involvement is found

Metastasis:

Mo: there are no distant metastases

M1: There is distant metastasis

Rhabdomyosarcoma Staging System:

Stage 1: the location of the orbit, and head or neck (not Parameningeal) extends to the urinary tract (bladder or prostate instead)

Stage 2: other locations, No or Nx

Satge 3: other locations, N1 if tumor <5 cm or No or Nx if tumor> 5 cm

Stage 4: any location and there are distant metastases

Based on histological examination, it can be determined the degree of severity (grading):

a.        G1: well differentiated (good)

b.       G2: moderately differentiated (moderate)

c.        G3: poorly differentiated (bad)

Determination of specific histiotipe need for therapy and prognosis. There are four types of known subhistologi namely:

a.        embryonal type

Embryonal rhabdomyosarcoma is the type most commonly found in children, approximately 60% of all cases rabdomiosarkoma.Tumor can occur anywhere, but most often on the genitourinary, head or leher.Pada histology histology of this type have a high variability, which illustrates some levels of muscle morphogenesis skeletal.Merupakan neoplasms with high differentiation consisting of rabdomioblas with eosinophilic cytoplasm. Desmin and actin were found in the muscles used for diagnosing rhabdomyosarcoma

b.       Alveolar Type

Alveolar tumors that cause approximately 15% of cases, is characterized by the chromosomal translocation T (2; 13). Tumor cells tend to grow in the nucleus (core), which often have a slit-like spaces that resemble alveolar alveoli.Tumor most often occurs in the body and limbs and have the worst prognosis.

c.        Botrioid type,

It is a variant form of embryonal tumor and stromal cells which are swollen protruding into the cavity of the body like a bunch of grapes, causing 6% of cases and most often appear in the vagina, uterus, bladder, nasopharyngeal and middle ear.

d.       pleomorphic type (adult form)

Pleomorphic type (adult form) is rare in children (1% of cases). Approximately 20% of patients are estimated to have undifferentiated sarcoma. This type is very rare in patients over 45 years the other three in 90% of cases occur before the age of 20 years. Pleomorphic variant has atypical tumor cells were large, some showing cytoplasm with corakan berlurik much typical for skeletal muscle differentiation.

Histopathologic Classification TNM After Unresectable

pT0: There is no tumor on histological examination.

PT1: Limited on the organ of origin. Excision perfect.

Pt2: The invasion into surrounding organs, excision perfect.

PT3: Invasion into surrounding organs, excision is not perfect.

         a. Remaining visible microscopically

         b. The rest can be seen as a macroscopic

         c. Tumor can not be resected.

Nopt 4

pN0: No lymph nodes affected

PN1: lymph nodes affected

pM0: No metastasis to distant sites

PM1: There is metastasis to distant sites

Stages

- Stage I (16% of cases)

Cancer is only found in the initial site of cancer arise On microscopic examination, there are no cancer cells in the tissue after the tumor is removed.

- Stage II (28% of cases)

Divided into II A, II B, and II C

1. IIA: Cancer can be lifted, but microscopically, there are remaining cancer cells in the tissue. No lymph nodes were affected.

2. IIB: The cancer is localized, it can be removed, ith or without lymph node involvement

3. C II: The cancer has spread to lymph nodes. Cancer and lymph nodes still can be removed surgically, but still terapat remaining cancer cells are microscopic.

- Stage III (36% of cases)

Cancers can be removed surgically, but still there are remaining cancer can be seen without mikroskop.Kanker has not spread to distant sites.

- Stage IV (20% of cases)

Cancer has spread to distant sites.

Other variants are basically small tumors primitive blue cell, poorly differentiated have a focal skeletal muscle differentiation (rabdomioblas with eosinophilic cytoplasm and corakan striated).

Differentiation rabdomioblastik may only appear with electron microscopic or immunohistochemical techniques (ribosome-myosin complex or positive imunoperoksidase to desmis / myoglobin). Variance alveolar characterized by translocation 2; 13 chromosomal).

Pathology

Rhabdomiosarkoma thought to arise from the same embryonic mesenchymal skeletal muscle denngan attack latitude. Definitive diagnostic test requires menggnakan histokimiawi with antibodies   against skeletal bibs (desmin) and electron microscopy to distinguish typical image. Histological typing of need for therapy and prognosis. Subhistologi there are four types are known. embryonal type, causing 60% of all cases with moderate prognosis. botrioid type, a variant form of embryonal tumor and stromal cells which are swollen protruding into the body cavity like a bunch of grapes, resulting in 6% of cases and most often appear in the vagina, uterus, bladder, nasopharynx, and middle ear. Alveolar tumors that cause approximately 15% of cases. Palling alveolar tumors often occur on the limbs of the body and have the worst prognosis. pleomorphic type is rare in childhood 1% of cases. approximately 20% of patients with undifferentiated sarcoma estimated possessed.

Clinical Manifestations

There are a wide variety of signs and symptoms in rabdomyosarkoma, we need to realize that people rhabdomyosarkoma especially children may get symptoms that differ from one another depending on the location of the tumor itself. Symptoms often do not appear before the tumor reaches a large size, if the tumor is located in the muscle tissue in the abdomen are the most common:

a. Rabdomyosarkoma mass of which can be seen and felt, can feel pain or not.

b. Bleeding in the nose, vagina, rectum, or mouth may occur if the tumor is located in this area.

c. Tingling, pain, and movement can occur when a tumor presses on a nerve affected area.

d. Protrusion and eyelid wilt, can indicate a tumor behind this area.

Risk group

Risk group  created by the merger between the  grouping system and staging systems . systems used to plan treatment. Divided into:

- Low risk: if one of the following criteria:

• Embryonal tumor of any size that are found on favorable sites . The tumor may be a tumor remaining after surgery that can be seen without mikorskop. The cancer may have spread to the lymph nodes.  Favorable site  are:

·          eye or eye area.

·          Head and neck (but not in the tissue that surrounds the brain and spinal cord).

·          The gall bladder and bile ducts.

·          Near the testes or vagina (but not the kidney, bladder, or prostate).

                        Embryonal tumor of any size that is not found on favorable sites . These tumors may be tumor remaining after surgery that can only be seen with a microscope. The cancer may have spread to the lymph nodes.

- Intermediate risk: if one of the following criteria:

• Embryonal tumor of any size that is not found on favorable sites . The tumor may be a tumor remaining after surgery that can be seen with or without a microscope. The cancer may have spread to nearby lymph nodes.
• Alveolar tumor of any size that are found in  favorable or  unfavorable site . The tumor may be a tumor remaining after surgery that can be seen with or without a microscope. The cancer may have spread to nearby lymph nodes.

- High risk: all types of rhabdomyosarcoma that may have spread to lymph nodes and has spread to great distances.

Diagnosis

Rhabdomyosarkoma diagnostic evaluation of symptoms in addition to the obvious, the diagnosis should also involve  standing  and classification of tumors, which is very useful useful in determining therapy in patients.  Standing  is a process to determine the extent to which the cancer has spread, and if it spreads, to which the deployment has occurred. There are various types of the system  standing  used in the determination of  standing  is that TMN system uses tumor ( T ), Nodes ( N ), and metastasis ( M ) to differentiate into various levels of disease ( Standing ).

The history of the course of the disease, including a history of cancer in the family tendency (li-Fraumenn), a thorough physical examination to determine the location and size of the tumor and regional lymph nodes chills. Laboratory tests including complete blood necessary, liver and kidney function, serum electrolytes, calcium and possibly magnesium levels, uric acid and clotting function. Bone marrow aspiration is also necessary for the alleged RMS is recommended parameningeal.Pemeriksaan radiology x-rays and ultrasound scans toraks.CT area of ​​the primary tumor, if possible pmeriksaan MRI performed on tumor biopsies primer.Selanjutnya dilauakn of the primary tumor and lymph nodes suspected.

Diagnostic evaluation should describe the level of the primary tumor and metastatic disease level consisting of:

a. Physical examination

b. Blood cell count

c. Urinanalisis

d. Serum electrolytes: BUN, Creatine, SGOT, SGPT, LDH, and alkaline phospatase

e. Preview resonasi magnetic (MRI) and computer tomography (CT) challenged the main injury

f. CT Scan

g. Bone Scan

h. Or bone marrow biopsy

i. Biopsy of suspicious lymph

Management

The success of the rhabdomiosarkoma, management is requiring a multidisciplinary approach and the combined approach. The goal is

• Tumor control.
• Maintain the function of the affected part.
• Prevent metastases.

a.        surgery

most effective when the tumor occurs in the complex if not biopsy therapy, followed by chemotherapy and radiotherapy, followed by the remaining parts of the tumor.

Removal of the primary tumor is done with enough of the normal tissue. The approach to this surgery done on key areas where complete removal would not be functional impairment. Because the primary tumors arise in the path, head and neck and extremities and places tertentu.Kemoterapi Dangan or without radiotherapy should be entrusted to the upper control residual tumor is in a prime location.

Rules of the spleen in the division as part of a major surgery and approach the position of the tumor in an area where there is an involvement of the regional lymph nodes, surgery should be performed in this area include:

1) Extremity (15%)

2) genitourinary (20%)

3) perirectal (33%)

4) Paratesticular (40%)

b. Radio Therapy

Radiation therapy is recommended for patients on site, except for histopathological classification groups (complete lack of mokropik). Radiation dose is recommended based on the group klinis.Bila allow limitations should include 4-5 cm from the margin of normal tissue, metastasik location of radiation should be avoided if possible .

c. Stem cell transplantation

used to improve the system of blood vessels that have been damaged by cancer cells.

d. Other Therapies

Currently the new treatment being studied, using angiogenesis inhibitors  and  biological therapies .  Angiogenesis inhibitors  are substances that can prevent tumor growth by blocking the formation of new blood vessels that feed the tumor would.  Biological therapies  are therapies that improve the body's immune system, thus our body's immune system to fight cancer can also fight harmful side effects of chemotherapy and radiotherapy treatment.

e. Chemotherapy

All patients did not depend on their kinis grouping, receive combination chemotherapy, since its use resulted in a significant increase in the release of disease survival when added nursing and radiation.

 Prognosis

Among patients with resectable tumors, 80-90% gain disease-free survival time. Approximately 60% of patients with resected tumors were not totally Reginal also obtain disease-free survival in the long term. Patients with diffuse disease prognosis buruk.Hanya Approximately 505 have achieved remission and less than 50% of the experienced older kesembuhan.Anak have a worse prognosis than younger ones. rognosis depends on:

a. Staging of disease

b. The location of the tumor as well.

c. Presence or absence of metastases.

d. Tumor response to therapy.

e. Age and health conditions of the patient.

f. Patient tolerance to treatment, therapy procedures.

g. The discovery of the latest treatments.

To achieve a survival rate ( survival rate ) required high: Close cooperation with other disciplines

a. Appropriate clinical diagnosis

b. Appropriate treatment strategy, in which this issue depends on: the evaluation of post-surgical anatomical pathology, evaluation of the degree of malignancy, need / absence of adjuvant therapy (chemotherapy or radiotherapy).

II. III. Osteosarcoma

Osteosarcoma (osteogenic sarcoma) is a neoplastic cells produce osteoid spindleyang. Osteosarcoma is a primary malignant tumor of tulangyang characterized by the formation of immature bone or tissue osteoidoleh tumor cells.

Osteosarcoma is usually found in the long bones in manalempeng metaphysical growth (epiphyseal growth plate) is very active; ie padadistal femur, proximal tibia and fibula, proximal humerus and pelvis. To a person older than 50 years of age, osteosarcoma can occur due to degeneration ganasdari pagets disease, the prognosis is very bad.

Risk Factors

 The exact cause of osteosarcoma is unknown, but terdapatberbagai risk factors for osteosarcoma are:

a)       rapid bone growth          : rapid bone growth terlihatsebagai osteosarcoma predisposition, as it seemed that insidennyameningkat during adolescent growth. Location osteosarcoma palingsering the metaphysical, where this area is long daritulang growth area.

b)       Environmental factors        : the only environmental factor known adalahpaparan to radiation.

c)       Predisposisigenetik      : bone dysplasias, including Paget's disease, fibrousdysplasia, enchondromatosis, danhereditary multiple exostoses and retinoblastoma (germ-line form). The combination of RB gene mutations (germline retinoblastoma) and radiation therapy for osteosarcoma resikotinggi associated with Li-Fraumeni syndrome (germline p53mutation), and Rothmund-Thomson syndrome (autosomal recessive congenital yangberhubungan with bone defects, hair and bone dysplasias, hypogonadism, and cataracts ).

Clinical Symptoms

Symptoms usually been there for several weeks or months sebelumpasien diagnosed. The most common symptom is pain there, especially when nyeripada activity and mass or swelling. Not infrequently there is riwayattrauma, although the role of trauma in osteosarcoma is not jelas.Fraktur pathological extremely rare, except in telangiectatic osteosarcoma yanglebih common pathologic fracture.

Pain in the extremities can cause kekakuan.Riwayatpembengkakan be there or not, depending on the location and magnitude of systemic lesi.Gejala, such as fever or night sweats very jarang.Penyebarantumor the lung is very rare cause of respiratory symptoms and pulmonary involvement biasanyamenandakan wide.

The discovery of the physical examination is usually confined to a palpable utamatumor.Massa be there or not, can danhangat tenderness on palpation, although these symptoms are difficult to distinguish from osteomielitis.Pada inspection can be seen an increase in vascularity in kulit.Penurunan rangeof motion in the affected joints can be considered at the examination fisik.Lymphadenopathy is very rare.

Differential diagnosis

Some abnormalities that lead to formation of bone mass in seringsulit distinguished with osteosarcoma, both clinically and imaging denganpemeriksaan. The disorders include:

1. Ewings sarcoma

2. Osteomyelitis

3. Osteoblastoma

4. The Giant cell tumor

Examination Support

a.Laboratorium   Most laboratory tests are used berhubungandengan use of chemotherapy. It's important to know the function organsebelum chemotherapy and to monitor organ function setelahkemoterapi.Pemeriksaan blood for the benefit of the prognosis is lacticdehydrogenase (LDH) and alkaline phosphatase (ALP). Patients with an increase ALP values ​​at the time of diagnosis have a greater likelihood to have metastases at paru.Pada patients without metastases, yangmempunyai increase in LDH values ​​less able to heal when compared with patients who had normal LDH values.

Several laboratory tests are important include:

·          LDH

·          ALP (prognostic interest)

·          A complete blood count

·          Liver function tests: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, and albumin.

·          Electrolytes: Sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus.

·          Renal function tests: blood urea nitrogen (BUN), creatinine

Radiography

X-ray examination is the primary modality used to investigasi.Ketika suspected osteosarcoma, MRI is used to determine the distribution and spread of tumors to the bone in the soft tissues sensitf sekitarnya.CT less when compared to MRI for evaluation of tumor lokaldari but can be used to determine metastasis paru.Isotopic lungs bone scanning is generally used to detect tumor metastases or synchronous padatulang, but the whole body MRI scans can menggantikanbone.

. The X-ray

plain bibs are essential in the evaluation of the first lesitulang because the results can predict the diagnosis and determination of pemeriksaanlebih far right. Plain picture may vary, but kebanyakanmenunjukkan mixture of lytic areas and rarely sklerotik.Sangat lytic or sclerotic lesions hanyaberupa.

Looks aggressive lesions, can be moth eaten with no clear edge there ataukadangkala cortical multiple small holes. After chemotherapy, the surrounding bone may form around the edges with clear boundaries on tumor.Penyebaran often seen as a soft tissue mass with joints lunak.Dekat network, the spread is usually difficult to distinguish from efusi.Area like a cloud because of sclerosis due to the production of osteoid calcification can be seen malignadan the masses. Periosteal reaction is often terdapatketika the tumor has penetrated the cortex. A wide spectrum of changes may occur, including   Codman triangles and multilaminated, spiculated, and sunburst reaction, which all indicate an aggressive process.

Telangiectatic osteosarcoma generally reveals a lytic, with periosteal reaction and soft tissue mass. When the tumor boundary berbatastegas, can resemble aneurysmal bone cyst picture. Small-cell osteosarcoma   look identical to the image of conventional osteosarcoma, which mempunyaigambaran mixture of lytic and sclerotic. Low-grade intraosseous osteosarcoma may be lytic, sclerotic or mixed; mempunyaigambaran often benign with firm boundaries and no change danmassa periosteal soft tissue.

 Gnathic tumor can be either lytic, sclerotic or mixed and seringterjadi bone destruction, periosteal reaction and extension on the intracortical network lunak.osteosarkoma described as radiolucent and geographic overview, and contains an internal mineralization in the number of high degree kecil.Osteosarkoma has a picture with a soft tissue mass yangluas various degrees of mineralization that appears on the surface tulang.Osteosarkoma parosteal tumors typically a high density yangmuncul of extensive bone area. Not like the osteochondroma, osteosarkomaparosteal not involve the medullary cavity of bone.

CT Scan

CT may be useful locally when polosmembingungkan photo picture, especially in areas with complex anatomy (contohnyapada changes in the mandible and maxilla in osteosarcoma

gnathic and padapelvis associated with secondary osteosarcoma). Cross-sectional overview gives a clearer picture of the destruction of bone in the soft tissues surrounding danpenyebaran than polos.CT photo dapatmemperlihatkan matrix mineralization in small amounts that are not visible padagambaran polos.CT photo is especially helpful when changes periostealpada flat bones rarely difficult to diinterpretasikan.CT used for evaluation of tumors in the long bones, but is a modality that sangatberguna to determine metastasis to the lung.

CT is very useful in the evaluation of various variants of osteosarcoma. Padaosteosarkoma telangiectatic can show fluid levels, and if digunakanbersama contrast can differentiate aneurysmal bone lesions in cystdimana after contrast is given it will show an increase gambarannodular around the cystic spaces.

MRI

MRI is the modality for evaluating local spread daritumor because skill in the interpretation of bone marrow and network lunak.MRI is the most accurate imaging technique for staging of osteosarcoma menentuan and assist in surgical menentukanmanajemen tepat.Untuk goal of tumor stage, and tumor penilaianhubungan between compartments on the place of origin is penting.Tulang POINTS, joints and soft tissues of the compartment covered merupakanbagian fascia.

Intraosseous tumor spread and ekstraoseus must dinilai.Fitur yangpenting of intraosseous disease is the longitudinal distance yangmengandung bone tumors, epiphyseal involvement, and the presence Skip metastase.Keterlibatanepifisis by the tumor has been known to occur than expected, dansulit seen the picture plain. Epiphyseal involvement can be seen didiagnosaketika signal intensity similar to that seen in metafisisyang tumors associated with focal destruction of the growth plate.

 Skip metastases are synchronous focus of tumor secaraanatomis separate from the primary tumor but were still at secondary sama.Deposit bone on the other side of the bone is called transarticular skip metastases. Patients with more frequent mempunyaikecenderungan skip metasase presence of distant metastases and tumor-free survival interval yangrendah. Assessment of tumor spread involves determining ototmanakah ekstraoseus involved and the relationship of tumor to neurovascular structures sekitarnya.Hal dansendi is important to avoid yangmelebihi patients received resection of the joint compartments terlibat.Keterlibatan didiagnosaketika tumor tissue can be seen spreading to the bone subartikular dankartilago.

Bone scintigraphy

Osteosarcoma generally showed increased uptake on bone scan dariradioisotop using technetium-99m methylenediphosphonate (MDP). Bone scans are very useful for mengeksklusikanpenyakit multifocal. skip lesions and lung metastases can be detected, but the most consistent lesion skip if using MRI. Due to an increased uptake of radioisotope osteosarkomamenunjukkan the bone scan bersifatsensitif but not specific.

Angiography

Angiography is more invasive examination. Angiografidapat determined by a kind of diagnosis of osteosarcoma, such as the High-gradeosteosarcoma be found a very ekstensif.Selain neovascularization angiography was performed to evaluate the success of pengobatanpreoperative chemotheraphy, which occurs when the tumor had reduced or hilangnyavaskularisasi preoperative chemotherapy response indicates success.

Biopsy

Biopsy is to establish a definite diagnosis is not done properly osteosarkoma.Biopsi often causing misdiagnosis (misdiagnosis) which will further be fatal to the determination of many recent tindakan.Akhir recommended by percutaneous needle biopsy (biopsy percutaneousneedle) with various advantages such as: very minimal invasion, does not require surgery wound healing time, lower infection risk danbahkan no, and the occurrence of post-biopsy fractures can be prevented.

 On histopathologic picture will be found stroma or with high-grade sarcomatous malignant osteoblast cells, which will form osteoid tissue and bone. In the central part yangbanyak mineralization will occur, while the peripheral mineralization bit. Biasanyaanaplastik tumor cells, with nuclei and many mitotic pleomorphik. Sometimes in some places of the tumor will occur kondroblastik or fibroblastic differentiation between tumor tissue that form osteoid.

Management

Surgery

The main objective is the safety of resection pasien.Reseksi harussampai free boundary tumor.Semua patients with osteosarcoma should menjalanipembedahan if possible resection of the tumor prmer.Tipe of pembedahanyang required depends on several factors that must be evaluated on an individual pasiensecara.

Radical limit, defined as the removal seluruhkompartemen involved (bones, joints, muscles) are usually not necessary. Resulting from the combination of chemotherapy with resection look better if dibandingkandengan radical amputation without adjuvant therapy, the level of 5-year survival rates of 50-70% and by 20% in the treatment with only radikalamputasi.

Pathological fractures, with all the compartments contamination dapatmengeksklusikan limb salvage surgery therapeutic use, but if dapatdilakukan surgery with resection of the tumor-free limit limbsalvage surgery can be performed. In some cases amputation may merupakanpilihan therapy, but more than 80% of patients with osteosarcoma treated with surgery on eksrimitasdapat limb salvage and not membutuhkanamputasi. If possible, it can be done-salvageyang limb reconstruction should be selected based on individual consideration, as follows:

Autologous bone graft: this can be with or without vaskularisasi.Penolakan not appear on the graft type and a low infection rate. Padapasien having mempunyaipilihan immature growth plates are limited to a stable bone fixation (osteosynthesis).

Allografts          : graft healing and infection can be a problem, especially during chemotherapy. Can also arises graft rejection.

Prosthesis         : joint reconstruction using prosthesis can be solitary or expandable, but it requires huge cost. Durabilitasmerupakan own problems at implant placement for pasienremaja.

Rotationplasty : This technique is usually appropriate for patients with tumors in the distal femur yangberada and proximal tibia, especially when the size of large tumors so that surgery only alternative to amputation. During resection of tumors, blood vessels repaired by means of end-to-end   anastomosis to maintain the patency of the vessel darah.Kemudian distal part of the leg is rotated 180 º and put together denganbagian proximal resection. This rotation can make anklemenjadi joints knee joints were taken fungsional.Sebelum better decisions for your family and pasienmelihat videos of patients who have undergone the procedure.

Resection of pulmonary nodules         : metastatic nodules in the lungs dapatdisembuhkan in total with surgical resection. Lobar resection or pneumonectomy is usually required to obtain bebastumor limit. This procedure is done at the same time as the primary pembedahantumor. Although bilateral nodules that can direseksimelalui median sternotomy, but better surgical field jikamenggunakan lateral thoracotomy.Oleh therefore recommended to perform the bilateral thoracotomies for bilateral metastases (each performed separately for several weeks).

II. IV. Ewing's sarcoma

Ewing's sarcoma is a malignant tumor composed of round cells, small most common in the first three decades kehidupan.Sarkoma primeryang Ewing is the most frequent malignant tumor of the long bones, most of the most seringterkena diafisis.tulang is the pelvis and ribs. Ewing's sarcoma is a malignant neoplasm that is growing rapidly and the cells derived from bone primitivesumsum in young adults.

Ewing's sarcoma is a malignant with low cure rates despite good denganpembedahan ablative radiation with radiation therapy or tidak.Namun thus padadaerah primary and metastatic regions menggunakandoxorubicine combined with chemotherapy, cyclophosphamide, vincristine and dactynomycin reported to meningkatkankelangsungan life of patients with metastatic though. Indeed multimodalitasdiyakini therapy will increase the proportion of long-term disease-free survival of approximately 15% from 50% in menjadilebih 2-3 decades.

Incidence

These tumors are most often seen in children in their teens and most often adalahtulang-long bone. (5) In children, tumors of Ewing's sarcoma is the most common primary bone setelahosteosarkoma. Every year no less than 0.2 cases per 100,000 children in diagnosissebagai ewing sarcoma, and there are an estimated 160 new cases occurred in 1993.Di around the world, the incidence varies from region with high incidence, for example AmerikaSerikat and Europe to regions with low incidence, such as Africa and China. Ewingsering sarcoma also occurs in the second decade kehidupan.Jarang occurred at age 5 and sesudah30 years. The incidence is equal between men and women. Ewing's sarcoma usually not berhubungandengan congenital syndrome, but many associated with skeletal anomalies, for example: enchondroma, aneurysmal bone cyst and urogenital anomalies, eg hypospadias. (1)

There are several risk factors that affect the incidence of Ewing's sarcoma, namely: 1). Factor is age. The incidence of Ewing's sarcoma increased rapidly from near 0 at 5tahun age and peaked at age 10 -18 tahun.Sesudah age 20 years insidensinyamenurun back and approaching 0 at age 30 years.2). Factor kelamin.Resiko types of men is slightly higher than women , but after the age of 13 years the incidence between men and women almost sama.3). ras.Penyakit factor is rare in blacks. 4). Genetic factors, which are known include: a). History keluarga.Faktor risk in the first lineage adasindroma familia meningkat.Tidak not associated with sarcoma Ewing.b). Genetic anomalies, the presence of an anomaly on chromosome 22, translocation or hilangnyakromosom was detected in 85% of patients with sarcoma Ewing.c). History of disease bone, certain congenital anomalies of the skeletal system, namely aneurysm kistatulang and enchondroma increase the risk of Ewing's sarcoma, also genitourinaryseperti hypospadias anomalies and duplications are also associated with Ewing's sarcoma.

Clinical Manifestations

Clinical manifestations of Ewing's sarcoma can berupama sistemik.Manifestasi local or local manifestations include: pain and swelling in the area of ​​the femur or pelvis, although tulanglain may also be involved. Of bone and soft tissue around the tumor area and bisateraba frequent and visible erythema fluctuations originating from bleeding inside the tumor. Manifestasisistemik typically include: lethargy, weakness and weight loss and sometimes fever terjadiserta be found of the period which is the lung metastases. The duration of munculnyagejala be measured in weeks or months and often extends to patients yangmempunyai primary lesion on the bone axis. (1) Signs and symptoms are typical: pain, tenderness lump, fever (38-40 ° C), danleukositosis (20,000 to 40,000 leukosit/mm3).

Diagnosis

Panyakit history and complete physical examination should be performed on all patients yangdicurigai as Ewing's sarcoma. Special attention should be placed on the following matters: (7) general condition and nutritional status of the patient. Examination of lymph nodes, include: the number, consistency, tenderness and good distribution in the cervical area, supraclavicular, axilla should sertainguinal dicatat.Pada chest examination, may obtain evidence of pleural effusion lung danmetastase, eg a decrease or loss of breath sounds, presence of pleural friction noise padapemeriksaan lungs. Abdominal examination, the presence of hepato-splenomegaly, ascites and all massaabdomen should be described clearly. Examination of the pelvis, can be done palpasiuntuk aware of any mass, or pain when pressed areas. Examination of the extremities, skeletal examinations including tests covering space is needed. Systemsaraf thorough examination should be recorded with baik.Diagnosis at issue: it is very important clinically as soon as possible to remove the infected bone. At biopsy rate keganasansekitar essential to recognize tumor cells, the clarity of osteosarcoma. Approximately another tumor cells biased reticulum cell sarcoma that menyerupaiEwings and metastatic neuroblastoma.

Examination Support

Test and diagnostic procedures should be performed in all patients who dicurigaisarcoma Ewing: 1). Blood tests: a). Routine blood tests. b). Liver transaminases. c). Laktatdehidrogenase. Increased levels of this enzyme is associated with the presence or berkembangnyametastase.2). Radiological examination: a). X-rays. b). CT scans: In dicurigaineoplasma area (eg pelvis, extremities, head) and it is important to note the large and lokasimassa and relation to surrounding structures and the presence of pulmonary metastases. When adagejala neurologic, CT scan of the head should also dilakukan.3). Invasive tests: a). Bone marrow biopsy and aspiration. Samplesumsum aspiration and biopsy of bone at some distance from the tumor is done to rule out the presence metastase.b). Biopsy. Incision or with a needle biopsy on the tumor mass is very important to diagnose Ewing's Sarcoma. If there are components of soft tissue, biopsy in this area usually lebihdimungkinkan.

Diagnostic Radiology 

Radiological picture of Ewing's sarcoma: lesions appear infiltrative destructive nature yangberawal in the medulla; seen as an area in the photo - radiolucent area. Rapidly destroys the tumor cortex and looks reaction periosteal.Kadang periostealnya reaction times appear as lines that resemble multilayered onion skin and onion are known as peelappearance. This picture was once considered patognomonis for this tuimor, but ordinary dijumpaipada other bone lesions.

Management

In primary Ewing sarcoma.

Surgery is performed on the basis of:

(A). Indications.

Progress radiation therapy in order to decrease the role of control of Ewing's sarcoma Ewing's sarcoma treatment pembedahandalam therapy. At present surgical resection therapy (usually dilakukansetelah preoperative adjuvant chemotherapy) is recommended in pelvic lesions and tumors that dapatmenyebar into bone tissue, for example: the fibula, costa and tarsal bones. Furthermore amputasidiperlukan for pathologic fractures and tumors that can not be the primary infragenikulatum local ditanganisecara with radiation therapy.

(B). Approach

Surgical approach varies depending on the size, location and spread of tumors.

(C). Procedure:

1). BiopsiTeknik to perform a biopsy on bone tumors are identical with osteosarcoma.

2). Radical resection

If surgical treatment is indicated, removal of the tumor with accompanying network edge normalharus done, unless there is excessive functional deficits. For example, amputasiprimer with Therapy radasi adjuvanta).

Preoperative Radiotherapy: Because of the high rate of local control with radiation (alone and with chemotherapy), a widely used therapy initidak.

Postoperative radiation therapy   : After appropriate surgical resection for Ewing's sarcoma, treatment can be continued with radiation therapy, only if there is residual microscopic remains large and significant. (2) The spread of local and metastatic Ewing's sarcoma. Radiation therapy is often used for the treatment of metastases, particularly after chemotherapy sistemik.Radiasi bilateral pulmonary profilaksistelah attempted, but was less successful when compared with systemic chemotherapy dalammencegah pulmonary tumor metastases.

Morbidity and mortality

Complications after radiation therapy generally occurs varies with the location of the tumor and dose primer.Jika not more than 5000 cGy, complications and severe functional deficits sekunderyang malignancies occur less than 18% of patients. (9) Many types sitostatica very effective for Ewing's sarcoma eg vincristine , adriamycine, cyclophosphamide, isofosfamide, etoposide and actinomycine D. Sebelumdigunakannya adjuvant chemotherapy, long-term survival of Ewing's sarcoma patients is not banyak.Pada series of pre-chemotherapy study, of 374 patients treated with surgery and radisi, only 36 (9.6%) who survive for five years. (1) This primerSekarang Ewing's sarcoma, chemotherapy is given 3-5 cycles before radiation treatment and pembedahanpada primary tumor. This provides an accurate assessment of response to chemotherapy. (2) B. Adjuvant chemotherapy

Adjuvant chemotherapy

consists of: Preoperative Chemotherapy Chemotherapy initials (3-5 cycles) is now the standard in patients with indikasipembedahan.

2). Additional postoperative chemotherapy Chemotherapy may be combined with radiation therapy if complete resection is not bisadilakukan.

II. V. hepatocellular carcinoma

Hepatocellular carcinoma occurs most often in children before the age of 4 years. liver tumors in children can be benign or malignant (cancerous), and can be a primary or a metastasis from another organ. Primary liver tumors are rare in children, there are approximately 3% of all tumors in anak.Kira about 50-60% of liver tumors in children are malignant and more than 65% of them are malignant hepatoblastoma.Tumor that also often get in child is hepatocellular carcinoma.

Pathophysiology

Causes of liver tumors is still not jelas.Tumor found from birth generally benign, such as hamartoma, hemangioma, and hemangioendotelioma.Ada 2 types of malignant tumors are often found in children are hepatoblastoma and hepatocellular carcinoma. Hepatoblastoma are found under 3 years and is associated with a genetic disorder that is loss of heterozygosity on chromosome 11p15 that resulted in the disruption of tumor suppression genes. Hepatoblastoma is also commonly associated with the syndrome Beckwith-Weidemann  where an interruption in the gene  insulin-like growth factor-  I  with the clinical manifestation of  exophthalmos, gigantism, macroglossia,  microcephaly,  and viceromegaly . Hepatocellular carcinoma in children can be found from birth to age 19 years, usually related to infection with hepatitis B or C, tirosinemia hereditary chronic type, disease  glycogen storage , α1-antitrypsin deficiency, and biliary cirrhosis.

Clinical Manifestations

Clinical symptoms of liver tumors in children are varied and different in every patient because it depends on the size and type of tumor, sometimes the symptoms are also caused by metastatic tumors. Some of the symptoms that are common include:

• Future large abdominal, or stomach enlargement
• Right abdominal pain
• Decreased appetite, weight loss
• Gag
• Jaundice
• Hot
• Itching of the skin
• Anemia
• Back pain due to tumor suppression can also occur with the outbreak of the crisis of acute abdominal tumor and hemoperitonium (usually in hepatocellular carcinoma)

Diagnosis

In addition to history and physical examination are complete, some investigations are also needed in the diagnosis of liver tumors in children and metastasenya, include:

• Laboratory: Complete blood, blood chemistry, liver and kidney function tests, hepatitis B and C serology; α-fetoprotein/AFP (also for monitoring therapy)
• Liver biopsy for histopathological examination
• Radiology: Plain radiographs of the chest, ultrasound / ultrasound  Doppler , CT-scan/MRI addition to determining the diagnosis of liver tumors should also do the staging of the tumor, especially in the wild type. Staging is very useful in the treatment and determine prognosis. There are several methods of determining the stage of liver tumors in children, one of them is as follows: Stage I: the tumor can be surgically removed complete with Stage II: The tumor can be removed surgically but still leave some residual Stage III: The tumor can not be removed completely by surgery and obtained the spread on the surrounding lymph nodes Stage IV: The tumor has spread to other organs Recurrent tumors reappeared after treatment with either hearts or other organs

The differential diagnosis

• Liver abscess
• Neuroblastoma
• Wilm's tumor
• Cholestasis / cirrhosis of the liver

Management

Management of liver tumors in children depends on the type and stage of the tumor, and the age and physical condition of the patient. In benign tumors usually surgery to remove the tumor without treatment of malignant tumors lainnya.Pada required cooperation with pediatric surgeons and a pediatric oncologist. Treatment is usually a combination of:

• Surgery
• Chemotherapy
• Radiotherapy
• Liver transplantation

Treatment based on the type and stage of the tumor:

• Hepatoblastoma stage I and II: The removal of the tumor and chemotherapy followed 4 series using  cisplatin,  vincristine,  and  fluorouracil .
• Hepatocellular carcinoma stage I and II tumors followed by chemotherapy appointment  cisplatin  and or  doxorubicin
• Stage III and IV hepatoblastoma: Some alternative treatments that can be done

1. Chemotherapy to reduce the size of the tumor as possible followed removal of the tumor and chemotherapy is closed again
2. Tumor metastases in lung surgery
3. Chemotherapy
4. Radiotherapy followed by surgery
5. Injecting chemotherapy drugs directly into the liver vein
6. Chemotherapy and kemoembolisasi
7. Liver transplantation

• Hepatocellular carcinoma stage III and IV tumor size reduction by using chemotherapy  cisplatin  with  vincristine / fluorouracil  or  doxorubicin  followed removal of the tumor as possible
• Relapse

Re-treatment done by previous treatment In addition to treatment of the tumor should also be done with a supportive treatment to prevent and treat infections, medication side effects and complications, as well as provide comfort to the patient during the observation pengobatan.Perlu performed periodically to monitor response to treatment and side effects to be aware of long-term treatment.

II. VI. Neuroblastoma

            Neuroblastoma is a tumor neuroblastik of  neural crest cells  are primordial along the sympathetic nervous system. Neuroblastoma is a malignancy of the most common extracranial solid in childhood and the most common malignant tumors in patients younger than age 1 year. In addition, neuroblastoma represents 7% to 10% of all malignancies diagnosed in pediatric patients younger than 15 years and is responsible for approximately 15% of all pediatric cancer deaths. However, neuroblastoma is a heterogeneous disease. Tumors may regress spontaneously or mature, or can be very aggressive, malignant phenotype. The presentation of neuroblastoma depends on the anatomical location of the sympathetic nervous system in which the primary tumor and the status of developing metastases. Neuroblastoma is the most frequent tumor in the early decades of life, approximately 80% in children under 4 years of age ¹ .

            Local diseases associated with the sympathetic nervous system, reaching the base of the skull to the pelvis. The most common presentation was abdominal mass, with 35% of cases arising from adrenergic cells in the adrenal medulla, 35% in the paraspinal ganglia, 20% in the posterior mediastinum, and 5% in the pelvis and 5% dileher ² .

Epidemiology

            It is generally a solid tumor in children less than 4 years. The incidence of neuroblastoma 10.5 / million children under the age of 15 years. The average age shown is 23 months, with a peak 0-4 years. Generally occurring in males than females (1.2:1), no racial or geographic predilection. Is a familial disease ² .

E mbriologi

Adrenal gland develops from two different cells of origin. The adrenal cortex is formed from cells derived from the mesoderm while the adrenal medulla develops from neural crest cells. Neural crest cells formed from the ventrolateral migration of neuro-ectodermal cells derived from the neural tube about 3 weeks into development. Neural crest cells are divided into 2 groups of cells that give rise to sensory ganglia of the cranial and spinal nerves as well as migration to other positions in the body to cause the melanocytes and sympathetic ganglia. The adrenal cortex is formed first, usually during the week to 6 development. Week 7 of neural crest cells migrate from the sympathetic ganglia formed a mass on the medial side of cortical development. Over the next few months until the birth of the fetus, the cortex will grow and differentiate circle around the mass of neural crest cells. When they are surrounded, the cells differentiated into secretory cells of the adrenal medulla. At about the age of 1 year the end of the formation of the adrenal glands showed three layers of the adrenal cortex surrounds the mature cells of the adrenal medulla ³ .

P atologi

            Neuroblastoma is a tumor of the sympathetic nervous system embryonal. These tumors arise during fetal or early postnatal life of sympathetic cells (sympathogonia) derived from the  neural crest . Histologically, the picture of neuroblastoma are not specific, small blue round cell tumors with uniform cells, with dense hyperchromatic nuclei and minimal cytoplasm. According to the classification of the International Neuroblastoma Pathology Classification System (INPC), the tumor is classified well and less well, depending on the degree of differentiation of neuroblast, contains Schwannian stroma, mitosis-karyorrhexis index, and age at diagnosis ⁴ .

Classification

   In 1984, Shimada and colleagues first developed the age-linked classification system based on morphology of the tumor neuroblastik are divided into groups according to tumor histology prognosis is good and not good histology. Shimada classification system based on

1. Mitosis karyorexis index (MKI)

2. Age children

3. Degrees differentiation

4.       Stroma rich  or  stroma-poor

Good prognosis include  infant, low MKI, rich stromal  tumors, well-differentiated tumors or tumors with a mixed degree of differentiation ⁵ . ICM was defined number of tumor cell mitosis or karyorrhexis neuroblastik per 5000 cells (low MKI <100 cells, intermediate cells 100-200, high> 200 cells)

Clinical symptoms

            Patients with neuroblastoma usually show symptoms and signs according to the primary location and extension of the disease, though often asymptomatic. Because 75% of neuroblastoma occur in the abdominal cavity (50% in the adrenal gland, 25% in the retroperitoneum), abdominal mass detected on physical examination, with complaints of abdominal pain. Other primary locations include mediatinum posterior (20%), cervical region (1%), and pelvis (4%). Respiratory distress or dysphagia may be a reflection of the thoracic region of the tumor. Changes in defecation and urination caused by compression of the spinal cord of paraspinal tumors. Tumors in the neck or upper chest can cause Horner syndrome (ptosis, miosis and anhidrosis), enophtalmus, and iris heterochromia. Acute cerebral ataxia observed, characterized dancing eye syndrome, opsoklonus, myoclonus and chaotic nystagmus. Two to three cases occurred in infants with primary tumor in the mediastinum. Other signs and symptoms result from the secretion of catecholamines and vasoactive intestinal polypeptide include diarrhea, weight loss, and hypertension. ^2.4

            The spread of neuroblastoma by age and stage shown in Table 3. More than 40% of patients with metastatic disease. In older patients, neuroblastoma have metastatic disease to the pattern of bone marrow, lymph nodes, and bone. Manifestation of metastases to bone (bone pain) or anemia (bone marrow infiltration). Brain, spinal cord, heart, lung is a rare location for metastasis. Metastasis is also associated with "raccoon eyes", the result of the spread of the retro-orbital venous plexux

Diagnosis

Laboratory

Lactate Dehydrogenase

Although not specific, serum lactate dehydrogenase (LDH) to determine the prognostic significance. High serum LDH values ​​marked proliferative activity or the extent of the tumor. Value LDH> 1500 IU / L is associated with a poor prognosis. LDH can be used to monitor disease activity or response to therapy. ⁴

Ferritin

A high value of serum ferritin (> 150 ng / mL) is also a picture of the rapid enlargement of tumor size or tumor. Increased serum ferritin is often at an advanced stage and indicates a poor prognosis. This value is often returned to normal during clinical remission. ⁴

Neuron Specific Enolase

Neurons are the specific Enolase (NSE) is a glycolytic enolase isoenzymes and contained within neurons in the central and peripheral nervous tissue. In neuroblastoma, NSE derived from tumor tissue and serum level values ​​are closely related to the clinical condition of the patient. Unfortunately a high value on NSE, are not always specific for neuroblastoma, and can also be found in patients with Wilms tumor, lymphoma, hepatoma. The top limit for serum NSE values ​​ranging from 14.6 ng / mL. NSE highest levels found in widespread neuroblastoma and metastatic, compared to the localized. Serum values ​​higher than 100ng/mL, usually associated with advanced stage that has a bad prognostic. ⁴

Catecholamines and their metabolites

When neuroblast cells derived from the neural crest is transformed into neoplastic, they are characterized by imperfect synthesis of catecholamines and their precursors, such as epinephrine (E), norepinephrine (NE), 3.4 dihydroxyphenilalanine (DOPA) and dopamine (DA) , and also metabolites such as vanillymaandellic acid (VMA), homovanillic acid (HVA), methoxydopamine (MDA), and methanephrine (MN), normethanephrine (NME) and 3 methoxytyramine (3MT). Neuroblastoma lack the enzyme phenylethanolamine N-methyltranferase, which converts noreepinefrin into epinephrine. Neuroblastoma cells do not have storage pockets catecholamines, like normal cells, so that these catecholamines are released into the circulation is rapidly degraded into VMA and HVA. VMA and HVA can be assessed from the urine, and both are very useful for the diagnosis and monitoring of disease activity. ¹

            Results of urinary catecholamine metabolites increased 90-95% in patients with neuroblastoma. Typically the value of 24-hour urine capacity assessed, but this time, the urine when using the assay sensitivity can also be used and have equal sensitivity. Normal values ​​for urinary VMA mmol/24 00:35 hours, while normal values ​​for HVA in urine was 0.40 mmol/24 hours.

Unfortunately, the catecholamines and their metabolites, it is impossible to detect the presence of a relapse during treatment of neuroblastoma patients who are being treated. In some cases the diagnosis of recurrence, these metabolites increased only 55%, when compared to the beginning of the presentation, more than 90% sensitivity. Therefore, the presence of this disease relapse or development, can not be detected reliably only with tumor markers alone.  ¹

Radiological examination

Radiography

Chest X-rays can be used to show a posterior mediastinal mass, usually in the thoracic neuroblastoma in children.

Ultrasonography

Although ultrasonography is the modality that is more often used in the initial assessment of suspected abdominal mass, less than the sensitivity and accuracy  of computed tomography  (CT) or magnetic resonance imaging (MRI) for the diagnosis of neuroblastoma. Other modalities typically used after screening with ultrasound to rule out diagnosis. Neuroblastoma ultrasound picture of a solid lesion, heterogeneous. ⁴

Computed Tomography (CT)

CT is commonly used used as a modality for the evaluation of neuroblastoma. It may show calcification in 85% of cases of neuroblastoma. Expansion of intraspinal tumor can be seen on CT with contrast. Overall, CT with contrast was reported by 82% accuracy in defining the extent of neuroblastoma. With an accuracy approaching 97% when performed by  bone scan . CT scan is a method that describes abdominal mass that can be done without anesthesia, which also showed evidence of local invasion, vascular wrap, lymphadenopathy, and calcification, which is highly suggestive of the diagnosis, particularly in relation to distinguishing between neuroblastoma and Wilms tumor. ⁴

Magnetic resonance imaging (MRI)

MRI is more sensitive imaging modality for the diagnosis and staging of neuroblastoma. MRI is more accurate than CT for the detection of stage 4 disease. Sensitivity of MRI was 83%, whereas 43% CT. MRI specificity of 97%, while 88% CT. MRI is the modality of choice to determine the involvement of the spinal cord. ⁴

Scintigraphy

Metaiodobenzylguanidine (MIBG) imaging is an option for evaluating the spread to the bone and bone marrow by neuroblastoma. Isotope 123 from I-metaiodobenzylguanidine ( ¹²³ I-MIBG) selectively taken catecholamine-secreting tumor cells (indicated more than 90%). ⁴

Bone Marrow Examination

Bone marrow biopsy is a routine and important method to detect the spread of bone marrow in neuroblastoma. Aspiration and biopsy should be performed, although it has a future diagnosis better.For gather accurate information, specimens taken from multiple locations recommended.

Tumor Staging

There are two primary systems used for staging of neuroblastoma. Evans classification used by the former Children's Cancer Group (CCG) and the classification of St. Jude Children's Research hospital used POG institutions. Evans covers the extent of tumor classification, according radiography. The staging classification Jude describe surgicopatologi, lymph node deployment. Both staging systems have prognostic value, they invented a system that is accepted, the International Neuroblastoma Staging System (INSS). Evaluation of the location of the primary tumor and metastatic dissemination depends on INSS inspection imaging (CT or MRI). ⁷

MIBG scanning is also in the initial evaluation recommendation to monitor therapeutic response.

Risk factors and therapy based on biological factors

            Treatment of neuroblastoma in children is not only based on the stage but also the basis of an appropriate risk clinical and biological variables. Biological factors that influence today is MYCN status, ploidy (for Infants), histopathological classification.

Group Risk

Risk groups	Prediction of survival of 3 years
Low Risk	> 90%
Moderate risk	70-90%
High risk	<30%

a.       groups a low risk

Ø Stage 1 (  localized resectable  neuroblastoma)

Ø Stage 2 <1 year

Ø Stage 4S

Adjuvant chemotherapy is usually not required for this group of patients except in cases in stage 4S disease cases life threatening.

b.       risk group was

Ø 3/4/4S disease state, age <1 year and good histological

Ø Stage 3, more than 1 year with  non-MYCN  and good histology.

                        Four chemotherapy agents (cyclophosphamide, doxorubicin, Carboplatin, Etoposide) given 4 or 8 cycles based on histology. Surgery performed after chemotherapy. If the disease recurs, radiotherapy may be considered.

c.        groups of high risk

Ø 2A/2B stage disease, age> 1 year and have MYCN amplification, histology was not good.

Ø Stadium 3/4/4S, age <1 year and MYCN amplification

Ø Stage 3 in children> 1 year with MYCN amplification or  non-MYCN amplified  and histology were not good.

Ø Stage 4 in children> 1 year

Multiagent induction chemotherapy for tumor remission, and increases the likelihood of resection. If the response is poor, second-line chemotherapy is used.

Treatment

The low risk group

All patients INSS Stage 1:

1. Surgery of the primary tumor with the observation of disease recurrence.  event free survival (EFS)  3 years by 94%,  overall survival (OS)  of 99%.

All patients with INSS stage 2A, 2B stage without MYCN amplification:

1. Surgery of the primary tumor without damage to vital organs. Observations obtained after surgery only patients with> 50% resection of the primary tumor.

2. For patients <50%: 4 cycles of chemotherapy with moderate doses using carboplantin, etoposide, cyclophosphamide, and doxorubicin. Agents and chemotherapy doses contained in the table below. COG protocol ANBL0531 lowered to 2 cycles of chemotherapy. During the 3-year 85% were symptomatic, overall  survival  99%

Patients with INSS stage 4S disease:

The majority of patients with INSS stage 4S entered the low-risk group with EFS 86% and OS 92%

1. Majority 4S tumors will regress spontaneously, although patients less than 2 months to have a high incidence of respiratory failure and liver dysfunction due to diffuse infiltration of the tumor to the liver.

2. No life-threatening complications, there is no indication of treatment.

3. Surgical resection of the primary tumor is usually not necessary, although biopsy of primary site or metastatic needed for the exact location of the biologic characteristics

4. Chemotherapy used in patients with life-threatening complications such as respiratory disorders and severe hepatic dysfunction. Research shows that brief ciclophosphamide low dose oral (5mg/kg/hari for 5 days every 2-3 weeks), or up to 4 cycles of chemotherapy untik moderate risk (cycles 1-4, Table 22-10) often induces remission.

Chemotherapy should be discontinued if remission is obtained before reaching 4 cycles of chemotherapy. Low-dose radiotherapy may also be used (150 cGy two to three times in two thirds of the anterior oblique lateral por liver through.

5. Patients with stage 4 S Biologic not infrequently be good candidates for more intensive treatment.

Moderate risk group   

Treatment

Surgery is indicated as described under the previous common treatment modality. The table below describes the various levels of response to induction chemotherapy of the Pediatric Oncology Group (POG), the Children's Cancer Group (COG), and the European Neuroblastoma Study Group (ENSG). Recently, COG, based on clinical INSS stage, age, and includes biological MYCN, Shimada histopathology, and ploidy, has developed a chemotherapy regimen that is designed to maintain or improve survival to minimize acute and long-term morbidity. This regimen using four of the most active agents in neuroblastoma (carboplatin, etoposide, cyclophosphamide, and doxorubicin).

Patients with moderate-risk neuroblastoma and favorable biology just get one of the four cycles of chemotherapy, and patients with unfavorable biology get two courses (eight cycles). Each cycle was given every 3 weeks. For details of chemotherapy, according to the scheme

Favorable Biology

For children aged <1 year, or weight ≤ 12 kg, the dose of chemotherapy administered milligrams per kilogram. Each of these 4 cycles administered at intervals of 3 weeks.

1. Carboplatin 560 mg / m ²  or 18 mg / kg IV over 1 hour to 1 day

2. Etoposide 120 mg / m ²  or 4 mg / kg IV over 2 hours a day for 3 days

3. Cyclophosphamide 1000 mg / m ²  or 33 mg / kg over 1 hour a day for 1 day

4. Doxorubicin 30 mg / m ²  or 1 mg / kg IV over 60 minutes per day for 1 day.

Variation of drug administered:

Treatment for moderate-risk patients

Unfavorable Biology

This patient received an additional 4 cycles of chemotherapy:

High-risk groups

Treatment

Surgery is performed under the indicated treatment modality, with the probability of long-term survival of patients group is less than 15%. As a whole Angaka survival increased to 43-50% with the comprehensive management of:

1. Induction chemotherapy

2. Consolidation high-dose therapy with autologous stem cell

3. Therapy for minimal residual disease:

a. Radiation to tumor sites

b. Agent nonsitotoksik

Induction chemo therapy

Due to the sensitive neuroblastoma chemotherapy, the goal of therapy is to reduce the induction to the maximum at the location of the primary tumor and metastasis. The duration of induction therapy protocols on each of approximately 4-5 months.

Consolidation therapy

The next phase is the consolidation therapy. The goal is to eliminate any tumor tersiasa with myeloablative cytotoxic agents and stem cell rescue. 3-year  survival rate in patients given myeloablative regimens followed by stem cell rescue is far superior (38-50%) with chemotherapy alone (15%). This is especially true for very high-risk patients such as age more than 1 year and MYCN amplification metastatic disease.

Operation Monitoring Post

Routine monitoring of the patient during the therapy completeness, detecting the risk of disease recurrence. Recommended list:

Risk factors for recurrence:

1. The local recurrence at the primary site:

a. Incomplete resection of the primary tumor. Tumor removal surgery on the primary tumor is important for the long-term prognosis.

2. Recurrence in bone marrow:

a. Bone marrow contains> 0.1%

b. Bone marrow involvement at the time of initial diagnosis

3. Recurrence in bone:

a. Bone involvement at the time of initial diagnosis. ⁶

CHAPTER III

CONCLUSION

The incidence of malignant tumors in children in Indonesia is quite high, and high mortality in men compared with 75% found in wanita.Sekitar rektosigmoid.Pemeriksaan digital rectal carcinoma is the determinant of the rectum. Risk factors for colorectal carcinoma is the degeneration of colonic polyps, genetic factors, lack of eating fibrous foods such as vegetables and fruits bsayur, and high consumption of animal fat.

Histological grade of carcinoma of the colon and rectum based on histological malignancy seen divided according to Dukes classification of colorectal carcinoma infiltrating hematogenous karsinoma.Penyebaran, limfogen and perkontinuitatum.

Clinical symptoms of colon carcinoma on the left is different from the left colon kanan.Karsinoma causing stenosis and obstruksi.Stenosis stool in the right colon carcinoma is rare and still be liquid stool so there is no first obstruksi.Gejala usually arise because of complications, namely bowel disorders physiology, obstruction, bleeding, or as a result of the left colon and rectum penyebaran.Karsinoma causes acute changes in bowel movements besar.Perdarahan rarely dialami.Nyeri the left colon is more real than kanan.Rasa diseased colon of the large intestine begins at the bottom left of the umbilicus, whereas from the gut right on the epigastrium.

Diagnosis is made based anammesis colorectal carcinoma, pemerikssan physical, digital rectal and colon with rektosigmoidiskopi or ganda.Komplikasi image contrast can occur in colorectal carcinoma is composed of obstruction and perforasi.Terapi curative and palliative therapy. Curative therapy is surgery n premises.Palliative therapy with chemotherapy and radiation

REFERENCES

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2            Dehner LP: Primitive neuroectodermal tumor and Ewing's sarcoma. Am J Pathol Sung 17:1, 1993.

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7            http://www.dokterbedahherryyudha.com/2012/07/intra-abdominal-tumor-in-children.html

8            http://www.dokterbedahherryyudha.com/2012/04/wilm-tumor-nephroblastoma.