Gestational Trophoblastic Neoplasia Treatment & Management

  • Author: Enrique Hernandez, MD, FACOG, FACS; Chief Editor: Warner K Huh, MD   more...
 
Updated: Jan 30, 2012
 

Medical Care

Patients with gestational trophoblastic disease (GTD) do not require medical therapy. Because 20% of patients with hydatidiform mole develop malignant disease, such as persistent hydatidiform mole with or without metastasis, some have suggested the use of a prophylactic dose of methotrexate in noncompliant patients.[41, 42] However, observing patients with weekly serum hCG levels is preferable, and only patients with rising or plateauing titers, as occurs in patients with gestational trophoblastic neoplasia (GTN), should be treated with chemotherapy.[1]

Patients with nonmetastatic GTN or metastatic low-risk GTN are treated with single-agent chemotherapy.[43, 44, 45, 46, 47, 48] Many in the United States prefer methotrexate. However, actinomycin D can be used in patients with poor liver function. During treatment, the serum hCG levels are monitored every week. One additional course of chemotherapy is administered after a normal serum hCG level. After 3-4 normal serum hCG levels, the levels are observed once per month for 1 year. A switch from methotrexate to actinomycin D is made if the patient receiving methotrexate for nonmetastatic or metastatic low-risk GTN develops rising or plateauing serum hCG levels.

A randomized clinical trial comparing 30 mg/m2 methotrexate given weekly to patients with low-risk GTN versus 1.25 mg/m2 of actinomycin D given every other week showed a higher complete response rate with actinomycin D.[49]

Patients with high-risk metastatic GTN are subdivided into 2 groups: those with a WHO score of less than 7 and those with a score of 7 or higher and who are at high risk of therapy failure.

  • Patients with a WHO score of less than 7 can be treated with single-agent chemotherapy (methotrexate or actinomycin) because their chances of achieving a cure are high.[50] AT least 1 additional course of chemotherapy is administered after a normal serum hCG level is achieved.
  • Patients with WHO scores of 7 or higher
    • These patients are treated with a combination of etoposide, methotrexate, and actinomycin D administered in the first week of a 2-week cycle and cyclophosphamide and vincristine (Oncovin) administered in the second week.[51, 52, 53, 54] This is known as the EMA-CO regimen.
    • Some substitute cisplatin and etoposide for cyclophosphamide and vincristine during the second week. This is known as the EMA-CE regimen.[55] Some reserve the EMA-CE regimen for patients in whom EMA-CO fails.
    • At least 2 additional courses of EMA-CO or EMA-CE are administered after a normal serum hCG level.
    • Patients with metastasis to the brain receive whole brain irradiation (3000 cGy) in combination with chemotherapy.[56, 57, 58] Corticosteroids (dexamethasone) with systemic effect are administered to reduce brain edema. This is the most common approach in the United States.
    • Early neurosurgical intervention for solitary lesions or stereotactic radiotherapy for multiple lesions or solitary lesions in locations at high risk for surgical morbidity is used at the Charing Cross Hospital in the United Kingdom and has been reported by physicians from Duke University in North Carolina.[59] At Charing Cross, neurosurgery is followed by moderate- and high-dose intravenous methotrexate and intrathecal methotrexate. However, intrathecal methotrexate is not routinely used by others. A therapeutic level of methotrexate is achieved in the cerebrospinal fluid at doses of methotrexate >600 mg/m2 given intravenously to patients with brain metastases.[59]
    • In patients not receiving whole brain irradiation, the dose of methotrexate on day 1 of the EMA-CO or EMA-CE regimen is increased to 1000 mg/m2. Instead of 4 doses of folinic acid, 8 doses are given starting 24 hours after the methotrexate infusion. Patients with liver metastasis are considered for liver irradiation (2000 cGy).[60]
  • Patients with stage IV GTN are most often treated with multiagent chemotherapy, even when the WHO score is less than 7, which is uncommon.
  • After achieving 3-4 consecutive weekly normal serum hCG levels, patients with stage IV GTN are observed with monthly serum hCG levels for 2 years. If the levels begin to rise during follow-up, the patient is evaluated for possible intervening pregnancy, or persistent or recurrent disease.
Next

Surgical Care

  • A hysterectomy may be necessary in case of uncontrolled vaginal bleeding. Hysterectomy may reduce the total number of chemotherapy cycles needed to achieve remission.[37, 38]
  • Uterine or hypogastric artery ligation or embolization of feeding vessels may be needed to control hemorrhage. Hepatic artery embolization has been used successfully to control hemorrhage from hepatic metastases.[26]
  • A repeat D&C in the presence of persistent tissue on pelvic ultrasonography may reduce the number of chemotherapy cycles needed to achieve remission.[61]
  • Craniotomy may be needed to control bleeding and provide decompression.[59, 53]
  • Resection of solitary metastasis (eg, thoracotomy) or disease within the myometrium may help achieve a remission.[62, 63, 64]
Previous
Next

Consultations

A gynecologic oncologist experienced in managing GTN should be consulted.

Previous
Next

Diet

No restrictions

Previous
Next

Activity

No restrictions

Previous
Proceed to Medication
 
 
Contributor Information and Disclosures
Author

Enrique Hernandez, MD, FACOG, FACS  Chairman, Department of Obstetrics and Gynecology, Director of Gynecologic Oncology, Abraham Roth Professor of Obstetrics, Gynecology and Reproductive Science, Professor of Pathology, Temple University Hospital, Temple University School of Medicine

Enrique Hernandez, MD, FACOG, FACS is a member of the following medical societies: Alpha Omega Alpha, American Cancer Society, American College of Obstetricians and Gynecologists, American College of Surgeons, American Gynecological and Obstetrical Society, American Medical Association, American Society for Colposcopy and Cervical Pathology, Association of Professors of Gynecology and Obstetrics, Johns Hopkins Medical and Surgical Association, Pennsylvania Medical Society, Philadelphia County Medical Society, and Society of Gynecologist Oncologists

Disclosure: GSK Honoraria Speaking and teaching

Specialty Editor Board

Robert C Shepard, MD, FACP  Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Warner K Huh, MD  Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, American Society of Clinical Oncology, Massachusetts Medical Society, and Society of Gynecologist Oncologists

Disclosure: MERCK Consulting fee Consulting; ROCHE PHARMA/DIAGNOSTICS Consulting fee Consulting; INTUITIVE SURGICAL Proctor Fee Consulting; Qiagen Consulting fee Consulting

References

  1. Smith HO, Kohorn E, Cole LA. Choriocarcinoma and gestational trophoblastic disease. Obstet Gynecol Clin North Am. Dec 2005;32(4):661-84. [Medline].

  2. Soper JT. Gestational trophoblastic disease. Obstet Gynecol. Jul 2006;108(1):176-87. [Medline].

  3. Agarwal R, Teoh S, Short D, et al. Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study. Lancet. Jan 14 2012;379(9811):130-5. [Medline].

  4. Yuen BH, Cannon W. Molar pregnancy in British Columbia: estimated incidence and postevacuation regression patterns of the beta subunit of human chorionic gonadotropin. Am J Obstet Gynecol. Feb 1 1981;139(3):316-9. [Medline].

  5. Goto S, Yamada A, Ishizuka T, et al. Development of postmolar trophoblastic disease after partial molar pregnancy. Gynecol Oncol. Feb 1993;48(2):165-70. [Medline].

  6. Hancock BW, Tidy JA. Current management of molar pregnancy. J Reprod Med. May 2002;47(5):347-54. [Medline].

  7. Watson EJ, Hernandez E, Miyazawa K. Partial hydatidiform moles: a review. Obstet Gynecol Surv. Sep 1987;42(9):540-4. [Medline].

  8. Cheung AN, Khoo US, Lai CY, et al. Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis. Cancer. Apr 1 2004;100(7):1411-7. [Medline].

  9. Menczer J, Girtler O, Zajdel L, et al. Metastatic trophoblastic disease following partial hydatidiform mole: case report and literature review. Gynecol Oncol. Aug 1999;74(2):304-7. [Medline].

  10. Lurain JR, Sand PK, Brewer JI. Choriocarcinoma associated with ectopic pregnancy. Obstet Gynecol. Aug 1986;68(2):286-7. [Medline].

  11. Baergen RN, Rutgers JL, Young RH, et al. Placental site trophoblastic tumor: A study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol Oncol. Mar 2006;100(3):511-20. [Medline].

  12. Tsuji Y, Tsubamoto H, Hori M, et al. Case of PSTT treated with chemotherapy followed by open uterine tumor resection to preserve fertility. Gynecol Oncol. Dec 2002;87(3):303-7. [Medline].

  13. Nigam S, Singhal N, Kumar Gupta S, et al. Placental site trophoblastic tumor in a postmenopausal female--a case report. Gynecol Oncol. May 2004;93(2):550-3. [Medline].

  14. Hassadia A, Gillespie A, Tidy J, et al. Placental site trophoblastic tumour: clinical features and management. Gynecol Oncol. Dec 2005;99(3):603-7. [Medline].

  15. Berkowitz BJ, Jones JG, Merkatz IR, et al. Ovarian conservation in placental site trophoblastic tumor. Gynecol Oncol. May 1990;37(2):239-43. [Medline].

  16. Zhao J, Xiang Y, Wan XR, et al. Clinical and pathologic characteristics and prognosis of placental site trophoblastic tumor. J Reprod Med. Dec 2006;51(12):939-44. [Medline].

  17. Papadopoulos AJ, Foskett M, Seckl MJ, et al. Twenty-five years' clinical experience with placental site trophoblastic tumors. J Reprod Med. Jun 2002;47(6):460-4. [Medline].

  18. Grimes DA. Epidemiology of gestational trophoblastic disease. Am J Obstet Gynecol. Oct 1 1984;150(3):309-18. [Medline].

  19. McDonald TW, Ruffolo EH. Modern management of gestational trophoblastic disease. Obstet Gynecol Surv. Feb 1983;38(2):67-83. [Medline].

  20. Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med. Mar 1994;39(3):155-62. [Medline].

  21. Chakrabarti BK, Mondal NR, Chatterjee T. Gestational trophoblastic tumor at a tertiary level cancer center: a retrospective study. J Reprod Med. Nov 2006;51(11):875-8. [Medline].

  22. Soper JT, Evans AC, Conaway MR, et al. Evaluation of prognostic factors and staging in gestational trophoblastic tumor. Obstet Gynecol. Dec 1994;84(6):969-73. [Medline].

  23. Mutch DG, Soper JT, Babcock CJ, et al. Recurrent gestational trophoblastic disease. Experience of the Southeastern Regional Trophoblastic Disease Center. Cancer. Sep 1 1990;66(5):978-82. [Medline].

  24. Smith HO, Qualls CR, Prairie BA, et al. Trends in gestational choriocarcinoma: a 27-year perspective. Obstet Gynecol. Nov 2003;102(5 Pt 1):978-87. [Medline].

  25. Yingna S, Yang X, Xiuyu Y, et al. Clinical characteristics and treatment of gestational trophoblastic tumor with vaginal metastasis. Gynecol Oncol. Mar 2002;84(3):416-9. [Medline].

  26. Grumbine FC, Rosenshein NB, Brereton HD, et al. Management of liver metastasis from gestational trophoblastic neoplasia. Am J Obstet Gynecol. Aug 15 1980;137(8):959-61. [Medline].

  27. Soper JT, Mutch DG, Chin N, et al. Renal metastases of gestational trophoblastic disease: a report of eight cases. Obstet Gynecol. Nov 1988;72(5):796-8. [Medline].

  28. Fulop V, Mok SC, Berkowitz RS. Molecular biology of gestational trophoblastic neoplasia: a review. J Reprod Med. Jun 2004;49(6):415-22. [Medline].

  29. Fong PY, Xue WC, Ngan HY, et al. Mcl-1 expression in gestational trophoblastic disease correlates with clinical outcome: a differential expression study. Cancer. Jan 15 2005;103(2):268-76. [Medline].

  30. Kim SJ, Park SE, Lee C, et al. Altered imprinting, promoter usage, and expression of insulin-like growth factor-II gene in gestational trophoblastic diseases. Gynecol Oncol. Mar 2003;88(3):411-8. [Medline].

  31. Olsen TG, Barnes AA, King JA. Elevated HCG outside of pregnancy--diagnostic considerations and laboratory evaluation. Obstet Gynecol Surv. Oct 2007;62(10):669-74; quiz 691. [Medline].

  32. Olsen TG, Hubert PR, Nycum LR. Falsely elevated human chorionic gonadotropin leading to unnecessary therapy. Obstet Gynecol. Nov 2001;98(5 Pt 1):843-5. [Medline].

  33. Khanlian SA, Cole LA. Management of gestational trophoblastic disease and other cases with low serum levels of human chorionic gonadotropin. J Reprod Med. Oct 2006;51(10):812-8. [Medline].

  34. Ngan HY, Chan FL, Au VW, et al. Clinical outcome of micrometastasis in the lung in stage IA persistent gestational trophoblastic disease. Gynecol Oncol. Aug 1998;70(2):192-4. [Medline].

  35. Gamer EI, Garrett A, Goldstein DP, et al. Significance of chest computed tomography findings in the evaluation and treatment of persistent gestational trophoblastic neoplasia. J Reprod Med. Jun 2004;49(6):411-4. [Medline].

  36. Kohorn EI. Negotiating a staging and risk factor scoring system for gestational trophoblastic neoplasia. A progress report. J Reprod Med. Jun 2002;47(6):445-50. [Medline].

  37. Hammond CB, Weed JC Jr, Currie JL. The role of operation in the current therapy of gestational trophoblastic disease. Am J Obstet Gynecol. Apr 1 1980;136(7):844-58. [Medline].

  38. Suzuka K, Matsui H, Iitsuka Y, et al. Adjuvant hysterectomy in low-risk gestational trophoblastic disease. Obstet Gynecol. Mar 2001;97(3):431-4. [Medline].

  39. Fukunaga M. Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles. Hum Pathol. Dec 2002;33(12):1188-92. [Medline].

  40. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology Committee. Int J Gynaecol Obstet. Jun 2002;77(3):285-7. [Medline].

  41. Kashimura Y, Kashimura M, Sugimori H, et al. Prophylactic chemotherapy for hydatidiform mole. Five to 15 years follow-up. Cancer. Aug 1 1986;58(3):624-9. [Medline].

  42. Massad LS, Abu-Rustum NR, Lee SS, et al. Poor compliance with postmolar surveillance and treatment protocols by indigent women. Obstet Gynecol. Dec 2000;96(6):940-4. [Medline].

  43. Soper JT, Clarke-Pearson DL, Berchuck A, et al. 5-day methotrexate for women with metastatic gestational trophoblastic disease. Gynecol Oncol. Jul 1994;54(1):76-9. [Medline].

  44. Foulmann K, Guastalla JP, Caminet N, et al. What is the best protocol of single-agent methotrexate chemotherapy in nonmetastatic or low-risk metastatic gestational trophoblastic tumors? A review of the evidence. Gynecol Oncol. Jul 2006;102(1):103-10. [Medline].

  45. Roberts JP, Lurain JR. Treatment of low-risk metastatic gestational trophoblastic tumors with single-agent chemotherapy. Am J Obstet Gynecol. Jun 1996;174(6):1917-23; discussion 1923-4. [Medline].

  46. Matsui H, Suzuka K, Yamazawa K, et al. Relapse rate of patients with low-risk gestational trophoblastic tumor initially treated with single-agent chemotherapy. Gynecol Oncol. Mar 2005;96(3):616-20. [Medline].

  47. Kohorn EI. Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy resistance?. Gynecol Oncol. Apr 2002;85(1):36-9. [Medline].

  48. Homesley HD, Blessing JA, Schlaerth J, et al. Rapid escalation of weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease: a Gynecologic Oncology Group study. Gynecol Oncol. Dec 1990;39(3):305-8. [Medline].

  49. Osborne R, Filiaci V, Schink J, et al. A randomized phase III trial comparing weekly parenteral methotrexate and "pulsed" dactinomycin as primary management for low-risk gestational trophoblastic neoplasia: A Gynecologic Oncology Group study. Gynecol Oncol. 2008;108:S2-S3.

  50. Ngan HY, Odicino F, Maisonneuve P, Creasman WT, Beller U, Quinn MA, et al. Gestational trophoblastic neoplasia. FIGO 6th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. Nov 2006;95 Suppl 1:S193-203. [Medline].

  51. Lurain JR. Advances in management of high-risk gestational trophoblastic tumors. J Reprod Med. Jun 2002;47(6):451-9. [Medline].

  52. Lurain JR, Singh DK, Schink JC. Primary treatment of metastatic high-risk gestational trophoblastic neoplasia with EMA-CO chemotherapy. J Reprod Med. Oct 2006;51(10):767-72. [Medline].

  53. Lehman E, Gershenson DM, Burke TW, et al. Salvage surgery for chemorefractory gestational trophoblastic disease. J Clin Oncol. Dec 1994;12(12):2737-42. [Medline].

  54. Escobar PF, Lurain JR, Singh DK, et al. Treatment of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy. Gynecol Oncol. Dec 2003;91(3):552-7. [Medline].

  55. Xiang Y, Sun Z, Wan X, et al. EMA/EP chemotherapy for chemorefractory gestational trophoblastic tumor. J Reprod Med. Jun 2004;49(6):443-6. [Medline].

  56. Yordan EL Jr, Schlaerth J, Gaddis O, et al. Radiation therapy in the management of gestational choriocarcinoma metastatic to the central nervous system. Obstet Gynecol. Apr 1987;69(4):627-30. [Medline].

  57. Cagayan MS, Lu-Lasala LR. Management of gestational trophoblastic neoplasia with metastasis to the central nervous system: A 12-year review at the Philippine General Hospital. J Reprod Med. Oct 2006;51(10):785-92. [Medline].

  58. Schechter NR, Mychalczak B, Jones W, et al. Prognosis of patients treated with whole-brain radiation therapy for metastatic gestational trophoblastic disease. Gynecol Oncol. Feb 1998;68(2):183-92. [Medline].

  59. Soper JT, Spillman M, Sampson JH, et al. High-risk gestational trophoblastic neoplasia with brain metastases: individualized multidisciplinary therapy in the management of four patients. Gynecol Oncol. Mar 2007;104(3):691-4. [Medline].

  60. Barnard DE, Woodward KT, Yancy SG, et al. Hepatic metastases of choriocarcinoma: a report of 15 patients. Gynecol Oncol. Sep 1986;25(1):73-83. [Medline].

  61. van Trommel NE, Massuger LF, Verheijen RH, et al. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey. Gynecol Oncol. Oct 2005;99(1):6-13. [Medline].

  62. Rojas-Espaillat L, Houck KL, Hernandez E, et al. Fertility-sparing surgery for persistent gestational trophoblastic neoplasia in the myometrium: a case report. J Reprod Med. May 2007;52(5):431-4. [Medline].

  63. Jones WB, Romain K, Erlandson RA, et al. Thoracotomy in the management of gestational choriocarcinoma. A clinicopathologic study. Cancer. Oct 1 1993;72(7):2175-81. [Medline].

  64. Carlson N, Winter WE 3rd, Krivak TC, et al. Successful management of metastatic placental site trophoblastic tumor with multiple pulmonary resections. Gynecol Oncol. Oct 2002;87(1):146-9. [Medline].

  65. Rustin GJ, Newlands ES, Lutz JM, et al. Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors. J Clin Oncol. Oct 1996;14(10):2769-73. [Medline].

  66. Matsui H, Iitsuka Y, Suzuka K, et al. Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor. Gynecol Oncol. Feb 2003;88(2):104-7. [Medline].

  67. Woolas RP, Bower M, Newlands ES, et al. Influence of chemotherapy for gestational trophoblastic disease on subsequent pregnancy outcome. Br J Obstet Gynaecol. Sep 1998;105(9):1032-5. [Medline].

  68. Lok CA, van der Houwen C, ten Kate-Booij MJ, et al. Pregnancy after EMA/CO for gestational trophoblastic disease: a report from The Netherlands. BJOG. Jun 2003;110(6):560-6. [Medline].

  69. Matsui H, Iitsuka Y, Suzuka K, et al. Salvage chemotherapy for high-risk gestational trophoblastic tumor. J Reprod Med. Jun 2004;49(6):438-42. [Medline].

  70. Knox S, Brooks SE, Wong-You-Cheong J, et al. Choriocarcinoma and epithelial trophoblastic tumor: successful treatment of relapse with hysterectomy and high-dose chemotherapy with peripheral stem cell support: a case report. Gynecol Oncol. Apr 2002;85(1):204-8. [Medline].

 
Previous
Next
 
Histologic section of a complete hydatidiform mole stained with hematoxylin and eosin. Villi of different sizes are present. The large villous in the center exhibits marked edema with a fluid-filled central cavity known as cisterna. Marked proliferation of the trophoblasts is observed. The syncytiotrophoblasts stain purple, while the cytotrophoblasts have a clear cytoplasm and bizarre nuclei. No fetal blood vessels are in the mesenchyme of the villi.
In this microphotograph of a choriocarcinoma metastatic to the brain, the neuropil is seen on the right and the biphasic (2 cell populations) choriocarcinoma is seen to the left with hemorrhage at the left border of the photograph (H&E stain).
Table. Prognostic Scoring Index
Prognostic FactorPoints
Age ≥40 y1
Antecedent pregnancy terminated in abortion1
Antecedent full-term pregnancy2
Interval of 4-7 mo between antecedent pregnancy and start of chemotherapy1
Interval of 7-12 mo between antecedent pregnancy and start of chemotherapy2
Interval of more than 12 mo between antecedent pregnancy and start of chemotherapy4
Beta-hCG level in serum is 1,000 to < 10,000 mIU/mL1
Beta-hCG level in serum is 10,000 to < 100,000 mIU/mL2
Beta-hCG level in serum is ³100,000 mIU/mL4
Largest tumor is 3 cm to < 5 cm1
Largest tumor is ³5 cm2
Site of metastases is spleen or kidney1
Site of metastases is gastrointestinal tract2
Site of metastases is brain or liver4
Number of metastases is 1-41
Number of metastases is 5-82
Number of metastases is >84
Prior chemotherapy with single drug2
Prior chemotherapy with multiple drugs4
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.