Osteosarcoma
309888
224244188
2008-07-07T23:37:24Z
Sfmammamia
3859960
[[WP:UNDO|Undid]] revision 224233368 by [[Special:Contributions/75.69.178.18|75.69.178.18]] ([[User talk:75.69.178.18|talk]]) rv unexplained deletions of external links
{{Infobox_Disease
| Name = Osteosarcoma
| Image =
| Caption =
| DiseasesDB = 9392
| ICD10 = {{ICD10|C|40||c|40}}-{{ICD10|C|41||c|40}}
| ICD9 = {{ICD9|170}}
| ICDO = {{ICDO|9180|3}}
| OMIM = 259500
| MedlinePlus = 001650
| eMedicineSubj = ped
| eMedicineTopic = 1684
| eMedicine_mult = {{eMedicine2|orthoped|531}} {{eMedicine2|radio|504}} {{eMedicine2|radio|505}}
| MeshID =
}}
'''Osteosarcoma''' is the most common type of malignant [[bone cancer]], accounting for 35% of primary bone malignancies. There is a preference for the [[metaphysis|metaphyseal]] region of tubular long [[bone]]s. 50% of cases occur around the [[knee]]. It is a malignant connective (soft) tissue tumor whose neoplastic cells present [[osteoblast]]ic differentiation and form tumoral bone.
==Prevalence==
[[Image:TerryFoxToronto19800712.JPG|right|thumb|200px|[[Terry Fox]] (1958-1981) began a run across Canada to raise money for cancer research. He developed osteogenic sarcoma as a teenager and had a leg amputated. Today the [[Terry Fox Run]] continues to raise money for cancer research. Through the money raised by the fundraising runs major improvements were made in the treatment of the cancer. Today amputations are rare.]]
Osteogenic Sarcoma is the 6th leading [[cancer]] in children under age 15. Osteogenic Sarcoma affects 400 children under age 20 and 500 adults (most between the ages of 15-30) every year in the [[United States|USA]]. Approximately 1/3 of the 900 will die each year, or about 300 a year. A second peak in incidence occurs in the elderly, usually associated with an underlying bone pathology such as [[Paget's disease of bone|Paget's disease]], [[medullary infarct]], or prior [[irradiation]]. Although about 90% of patients are able to have limb-salvage surgery, complications, such as infection, prosthetic loosening and non-union, or local tumor recurrence may cause the need for further surgery or amputation.
== Pathology ==
The tumor may be localized at the end of the long bones. Most often it affects the upper end of [[tibia]] or [[humerus]], or lower end of [[femur]]. The tumor is solid, hard, irregular ("fir-tree" or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating in right angles. These right angles form what is known as [[Codman's triangle]]. Surrounding tissues are infiltrated.
Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumour. Tumor cells are very [[pleomorphic]] ([[anaplastic]]), some are giant, numerous atypical [[mitoses]]. These cells produce [[osteoid]] describing irregular [[trabeculae]] (amorphous, [[eosinophilic]]/pink) with or without central calcification ([[hematoxylin]]ophilic/blue, granular) - tumor bone. Tumor cells are included in the [[osteoid]] matrix. Depending on the features of the tumour cells present (whether they resemble bone cells, cartilage cells or fibroblast cells), the tumour can be subclassified.
==Causes==
The causes of osteosarcoma are not known. Questions remain about whether [[radium]], or [[fluoride]], in drinking water can act as "[[Natural environment|environmental]] triggers" for increasing the incidence of the disease.{{Fact|date=March 2008}}
A low [[selenium]] or [[Vitamin D|Vitamin D3]] level or a high level of [[inflammation]], as measured by interleukin-6, interleukin-8, or Nf-kB, Tumor Necrosis Factor Alpha may have a significant role as tumor suppressors and tumor initiators respectively.{{Fact|date=March 2008}}
Recent studies show that an increased level of c-Fos can lead to osteosarcoma. The study that showed this result was done on transgenic mice in which the Fluid Sheer Stress (FSS) was increased to increase the number of osteoblast. Since c-Fos is ubiquitous in its over expression it can not only increase the osteoblast resulting in the symptoms osteosarcoma. Therefore it is recently believed that a biological effect that may cause osteosarcoma is an error in the molecular pathway that controls c-Fos, causing an overexpression with no other counter stimuli to stop over production.{{Fact|date=March 2008}}
==Symptoms==
Many patients first complain of pain that may be worse at night, and may have been occurring for some time. If the tumor is large, it can appear as a swelling. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture).
==Diagnosis==
Family [[physicians]] and [[orthopedists]] rarely see a [[malignant]] bone tumor (most bone tumors are [[benign]]). Thus, many patients are initially misdiagnosed with [[cysts]] or muscle problems, and some are sent straight to [[physical therapy]] without an [[x-ray]].
The route to [[osteosarcoma]] diagnosis usually begins with an [[x-ray]], continues with a combination of scans ([[CT scan]], [[PET scan]], bone scan, [[MRI]]) and ends with a surgical [[biopsy]]. Films are suggestive, but bone [[biopsy]] is the only definitive method to determine whether a tumor is [[malignant]] or [[benign]].
The biopsy of suspected [[osteosarcoma]] should be performed by a qualified [[orthopedic]] [[oncologist]]. The [[American Cancer Society]] states: "Probably in no other [[cancer]] is it as important to perform this procedure properly. An improperly performed [[biopsy]] may make it difficult to save the affected limb from [[amputation]]."
==Treatment==
Patients with osteosarcoma are best managed by a [[medical oncologist]] when possible (or amputation in some cases) and an [[orthopedic oncologist]] experienced in managing [[sarcomas]]. Current standard treatment is to use [[neoadjuvant]] [[chemotherapy]] ([[chemotherapy]] given before [[surgery]]) followed by surgical resection. The percentage of tumor cell [[necrosis]] (cell death) seen in the tumor after surgery gives an idea of the prognosis and also lets the oncologist know if the [[chemotherapy]] regime should be altered after surgery.
Standard therapy is a combination of limb-salvage [[orthopedic surgery]] when possible (or amputation in some cases) and a combination of high dose [[methotrexate]] with [[leucovorin]] rescue, intra-arterial [[cisplatin]], [[adriamycin]], [[ifosfamide]] with [[mesna]], [[BCD]], [[etoposide]], [[muramyl tri-peptite]] (MTP). Rotationplasty is also another surgical technigue that may be used.
Ifosfamide can be used as an adjuvant treatment if the [[necrosis]] rate is low.
3-year event free survival ranges from 50% to 75%. and 5-year survival ranges from
60% to 85+% in some studies. Overall, 60-65% treated 5-years ago will be alive today. These survival rates are overall averages and vary greatly depending on the individual necrosis rate.
Osteosarcoma has one of the lowest survival rates for pediatric cancer despite chemotherapy's success in osteosarcoma of 6 chemotherapies, [[interferon-alpha]], [[interleukin-2]], and being the prototype of solid tumors in cancer.
Fluids are given for [[hydration]].
Drugs like [[Kytril]] and [[Zofran]] help with [[nausea]] and [[vomiting]].
[[Neupogen]], [[epogen]], [[Neulasta]] help with [[white blood cell]] counts and [[neutrophil]] counts.
Blood transfusion helps with [[anemia]].
==Prognosis==
*Prognosis is separated into three groups.
* '''Stage I''' osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.
* '''Stage IIb''' prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.) size of the tumor mass (in cm.), and the degree of necrosis from neoadjuvant chemotherapy (chemotherapy prior to surgery). Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive <ref>http://www.osteosarcomasupport.org/cxcr4_metastases.pdf</ref>, or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases, (more than 12 months-24 months), a smaller number of metastases (and their resectability). It is better to have fewer metastases than longer time to metastases. Those with a longer length of time(>24months) and few nodules (2 or fewer) have the best prognosis with a 2-year survival after the metastases of 50% 5-year of 40% and 10 year 20%. If metastases are both local and regional, the prognosis is worse.
* Initial Presentation of '''stage III''' osteosarcoma with lung metastates depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall prognosis is 30% or greater depending.
==Canine Osteosarcoma==
[[Image:Canine osteosarcoma.JPG|thumb|[[X-ray]] of osteosarcoma of the distal femur in a dog]]
===Risk factors===
Osteosarcoma is the most common bone tumor in dogs and typically afflicts middle-age large and giant breed dogs such as [[Irish Wolfhound]]s, [[Greyhound]]s, [[German Shepherd Dog|German Shepherd]]s, [[Rottweiler]]s, and [[Great Dane]]s. It has a ten times greater [[incidence (epidemiology)|incidence]] in dogs than humans.<ref name=Withrow>{{cite web|author=Withrow, S.J.|year=2003|title=Limb Sparing Trials and Canine Osteosarcoma|work=Genes, Dogs and Cancer: 3rd Annual Canine Cancer Conference, 2003|url=http://www.ivis.org/proceedings/Keystone/2003/withrow/chapter_frm.asp?LA=1| accessdate=2006-06-16}}</ref> A [[heredity|hereditary]] base has been shown in St. Bernard dogs.<ref name=Bech-Nielsen>{{cite journal|author=Bech-Nielsen, S., Haskins, M. E. et al.|year=1978|title=Frequency of osteosarcoma among first-degree relatives of St. Bernard dogs|journal=J Natl Cancer Inst 60(2):349-53}}</ref> [[neutering|Spayed/neutered]] dogs have twice the risk of intact ones to develop osteosarcoma.<ref name=Ru>{{cite journal|author=Ru, B., Terracini, G. et al.|year=1998|title=Host related risk factors for canine osteosarcoma|journal=Vet J 156(1):31-9|volume=156|pages=31|doi=10.1016/S1090-0233(98)80059-2}}</ref> Infestation with the parasite [[Spirocerca lupi]] can cause osteosarcoma of the [[esophagus]].<ref name=Ranen>{{cite journal|author=Ranen E, Lavy E et al.|year=2004|title=Spirocercosis-associated esophageal sarcomas in dogs. A retrospective study of 17 cases (1997-2003)|journal=Vet Parasitol 119(2-3):209-21|volume=119|pages=209|doi=10.1016/j.vetpar.2003.10.023}}</ref>
===Clinical presentation===
The most commonly affected bones are the proximal [[humerus]], the distal [[radius (bone)|radius]], the distal [[femur]], and the [[tibia]],<ref name=Morrison_1998>{{cite book|author=Morrison, Wallace B.|title=Cancer in Dogs and Cats|edition=1st ed.|publisher=Williams and Wilkins|year=1998|id=ISBN 0-683-06105-4}}</ref> following the basic premise "far from the elbow, close to the knee". Other sites include the ribs, the [[mandible]], the spine, and the pelvis. Rarely, osteosarcoma may arise from soft-tissues (extraskeletal osteosarcoma). [[Metastasis]] of tumors involving the limb bones is very common, usually to the lungs. The tumor causes a great deal of pain, and can even lead to fracture of the affected bone.
===Treatment and prognosis===
Amputation of the leg is the initial treatment, although this alone will not prevent metastasis. [[Chemotherapy]] combined with amputation improves the survival time, but most dogs still die within a year.<ref name=Morrison_1998/> There are surgical techniques designed to save the leg (limb-sparing procedures), but they do not improve the prognosis. One key difference between osteosarcoma in dogs and humans is that the cancer is far more likely to spread to the lungs in dogs.
Some current studies indicate that [[osteoclast]] inhibitors such as alendronate and pamidronate may have beneficial effects on the quality of life by reducing osteolysis, thus reducing the degree of pain as well as the risk of [[pathological fracture]]s.<ref name=Tomlin>{{cite journal|author=Tomlin, J. L., Sturgeon, C. et al.|year=2000|title=Use of the bisphosphonate drug alendronate for palliative management of osteosarcoma in two dogs|journal=Vet Rec 147(5):129-32}}</ref>
==Osteosarcoma in cats==
Osteosarcoma is also the most common bone tumor in the cat, although not as frequently encountered, and most typically affects the rear legs. The cancer is less aggressive in cats than in dogs, and therefore amputation alone can lead to a significant survival time.<ref name=Morrison_1998/>
==References==
<references/>
==External links==
*[http://www.osteosarcomasupport.org Support and information website for osteosarcoma patients]
*[http://www.cancer.umn.edu/osteosarcoma Genetic Epidemiology of Osteosarcoma Study at the University of Minnesota]
*[http://www.aafp.org/afp/20020315/1123.html Osteosarcoma: A Multidisciplinary Approach to Diagnosis and Treatment]
*http://www.mayoclinic.org/osteosarcoma/index.html
*[http://cancer.gov/cancertopics/pdq/treatment/osteosarcoma/healthprofessional Treatment Information from U.S. National Cancer Institute]
* [http://www.liddyshriversarcomainitiative.org/Newsletters/V02N01/Osteosarcoma/osteosarcoma.htm Osteosarcoma by Peter Buecker, MD and Mark Gebhardt, MD]
*[http://www.petcancercenter.org/Cancer_Types_Bone.html ''Osteosarcoma in Pets'' from Pet Cancer Center]
*[http://www.annalssurgicaloncology.org/cgi/content/full/10/5/498 Superior Survival Seen with Osteosarcoma 2004]
'''Media'''<br>
*{{cite book |author=James, H. |title=Promises in the Dark |publisher=Bantam Books |location=New York |year=1979 |pages= |isbn=0-553-13453-1 |oclc= |doi=}} Story of a young girl's osteosarcoma fight and its effect on her relationship with her boyfriend
*{{cite book |author=Trottier, Maxine |title=Terry Fox: A Story of Hope |publisher=Scholastic Canada |location=Markham, Ont |year=2005 |pages= |isbn=0-439-94888-6 |oclc= |doi=}} About Terry Fox and his quest to raise $25 million for cancer research by running across Canada on his prosthetic leg. Also ''The Terry Fox Story'', a 1983 movie.
*{{cite book |author=Belshaw, Sheila M. |title=Fly With a Miracle |publisher=Denor Press |location= |year=2001 |pages= |isbn=0 9526056 7 8 |oclc= |doi=}} The story of a family's journey through teenage osteosarcoma and its aftermath.
{{Soft tissue tumors and sarcomas}}
[[Category:Dog diseases]]
[[Category:Orthopedics]]
[[Category:Types of cancer]]
[[de:Osteosarkom]]
[[es:Osteosarcoma]]
[[fr:Ostéosarcome]]
[[hr:Osteosarkom]]
[[it:Osteosarcoma]]
[[nl:Osteosarcoom]]
[[ja:骨肉腫]]
[[pl:Kostniakomięsak]]
[[pt:Osteossarcoma]]
[[tr:Osteosarkom]]
[[ur:عظمی لحمومہ]]