eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Germinoma, Central Nervous System: Treatment & Medication

Author: Amani AlKofide, MBBS, Assistant Professor, Alfaisal University College of Medicine; Consultant, Department of Pediatric Hematology and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh
Contributor Information and Disclosures

Updated: Sep 2, 2009

Treatment

Medical Care

Radiation Therapy
 
In the past, patients with imaging findings typical of CNS germinoma were treated empirically with radiation therapy.2 This approach has largely been abandoned, since current stereotactic biopsy techniques permit histological diagnosis with minimal risk of morbidity. Identification of the histological elements of the tumor is important in determining the most appropriate therapeutic strategy, because the different histological types vary in their sensitivity to radiation.8,28,29 Germinomas are highly responsive to radiation therapy30,17,31 ; a complete response rate with a 5-year survival of more than 90% is seen with radiation therapy alone.2,32 NGGCTs are less radiosensitive than pure germinomas, with an overall 5-year survival of 30-50%.
 
Full-dose craniospinal radiation (CSI) was traditionally employed for patients with pure germinomas. Side effects of CSI may be significant, however. Studies comparing CSI with reduced-volume radiation, whether whole-brain or whole-ventricular, have shown no significant difference in the pattern of relapse in germinomas.33,8,16,34,35  
Therefore, CSI is no longer used for localized germinomas.33,36  
 
Trials to determine the best regimen for radiation therapy are ongoing.37,32 Currently, patients with localized or multifocal disease may receive 24 Gy to the whole-ventricular system and a 21-Gy boost to all measurable disease. Most experts advocate a boost to the primary tumor bed in order to prevent local recurrence; 45 Gy appears to be a satisfactory upper dose limit.38,39,40,41 Patients with disseminated disease may receive 24 Gy to the craniospinal axis.37,30,42

Studies of radiation therapy alone versus neoadjuvant chemotherapy followed by response-based radiotherapy are currently under way.33,15,30,43,35
 

Chemotherapy
 
In patients with germinomas, chemotherapy has been recently added to the treatment regimen in order to permit the use of a lower radiation dose, thereby reducing the long-term morbidity associated with radiation therapy while maintaining the excellent survival rates.32,5,8,29,43,39 .In patients with NGGCTs, the use of adjuvant chemotherapy with radiation therapy is intended to improve outcome, because even with surgery and CSI these patients have a poor prognosis.32,8,15,22,44 The increase in survival seen with combination therapy has made chemotherapy an integral part of treatment for NGGCTs.16,34,45,38
 
As with gonadal germ cell tumors, the agents that to date have shown the best activity against CNS GCTs are cisplatin, etoposide, vinblastine, bleomycin, and carboplatin.39
Ifosfamide and cyclophosphamide are also used.29

Patients with relapsed or progressive disease, especially those with NGGCTs, have a poor prognosis. High-dose chemotherapy followed by autologous stem cell transplant may be effective in this group of patients.46

Surgical Care

Currently the recommended practice is to acquire a tissue biopsy sample, with the exception of patients who have a characteristic elevation in tumor markers and in whom surgical intervention may lead to significant sequelae.5,17 {Ref27}38,39  

Surgical treatment of CNS GCTs varies according to the tumor type. Germinomas carry a relatively excellent prognosis and management has therefore focused on reducing morbidity. Partial and gross total resection of germinomas has no proven benefit and may lead to neurological or endocrinological deterioration. Therefore, most neurosurgeons limit surgical intervention to biopsy and instead treat these patients with radiation and chemotherapy.33,8,43  

Patients with choriocarcinoma have an increased tendency to hemorrhage; current recommendation is for early and radical surgery.
 
Patients with NGGCTs have poor long-term survival, and surgery for these patients is aimed at improving outcome. Reduction of tumor burden by partial resection is often an option when removal of all tumor tissue is impossible. Adjuvant radiation therapy and chemotherapy are often incorporated in the treatment plan.15,47,44
 
Patients presenting with obstructive hydrocephalus may require a ventriculoperitoneal shunt.
 
In patients who have had an incomplete response to initial chemotherapy, second-look surgery may be performed to remove the residual tissue and permit its histological verification. The remaining tissue may contain malignant elements; however, it may consist of fibrosis, necrosis, or a mature teratoma — the so-called growing teratoma syndrome.38,39 . The growing teratoma syndrome is characterized by enlarging tumor mass during or after chemotherapy in the presence of normal or declining tumor markers. Surgical resection of the tumor is considered curative.28,48

Consultations

  • Endocrinology

Patients with CNS GCTs may have a range of endocrine dysfunctions, including diabetes insipidus, hypothyroidism, precocious or delayed puberty, sexual dysfunction, growth failure, adrenal crises, and panhypopituitarism. Proper monitoring of hormone levels and electrolytes is essential. Lifelong hormonal replacement may be required for most of these patients.

  • Ophthalmology

Disturbance in vision is a common presenting feature. Evaluation by an ophthalmologist will identify the visual deficit.

  • Audiometry

Audiogram studies should be performed, especially in patients expected to receive radiation therapy and ototoxic agents — specifically, cisplatin.


Medication

Chemotherapeutic agents (eg, cisplatin, bleomycin, etoposide, cyclophosphamide) are used to treat germinomas. They are discussed below along with desmopressin acetate, which is used for the treatment of diabetes insipidus.

Chemotherapeutic agents

These agents are chemical substances or drugs that treat neoplastic diseases by interfering with DNA synthesis49


Cisplatin (Platinol)

Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-links and denaturation of double helix.

Adult

20-120 mg/m2 IV q3-4wk

Pediatric

Not established

Increases toxicity of bleomycin and ethacrynic acid

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Pregnancy

D - Unsafe in pregnancy

Precautions

Administer adequate hydration before and for 24 h after dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, and nausea and vomiting may occur


Bleomycin (Blenoxane)

Glycopeptide antibiotic that inhibits DNA synthesis. For palliation in management of several neoplasms.

Adult

0.25-0.5 U/kg (10-20 U/m2) IV/IM/SC 1-2 times/wk; reconstitute 15-U vial with 1-5 mL of sterile water or isotonic saline for injection

Pediatric

Not established

May decrease plasma levels of digoxin and phenytoin; cisplatin may increase toxicity when administered systemically

Documented hypersensitivity; significant renal function impairment; compromised pulmonary function

Pregnancy

D - Unsafe in pregnancy

Precautions

Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment; may cause vasoocclusive phenomenon with distal necrosis of digits; permanent damage to nail matrix may occur


Etoposide, VP-16 (Toposar, VePesid)

Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 phase of cell cycle.

Adult

100 mg/m2 IV d 1-5

Pediatric

Not established

May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine has additive effects in cytotoxicity of tumor cells

Documented hypersensitivity; IT administration may cause death

Pregnancy

D - Unsafe in pregnancy

Precautions

Bleeding and severe myelosuppression may occur


Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Adult

50-100 mg/m2/d PO or 400-1000 mg/m2 PO in divided doses over 4-5 d; alternatively, 400-1800 mg/m2 (30-40 mg/kg) IV in divided doses over 2-5 d; may repeat at 2- to 4-wk intervals; alternatively, administer 10-15 mg/kg IV q7-10d or 3-5 mg/kg bid

Pediatric

Administer as in adults

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity

Documented hypersensitivity; severely depressed bone marrow function

Pregnancy

D - Unsafe in pregnancy

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis

Vasopressin analogs

These agents treat diabetes insipidus, a neuroendocrine abnormality associated with CNS germinomas.


Desmopressin acetate (DDAVP, Stimate)

Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

Adult

2-4 mcg IV/SC divided bid

Pediatric

<3 months: Not established
3 months to 12 years: 5-30 mcg/d intranasally qd or divided bid
>12 years: Administer as in adults

Demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects

Documented hypersensitivity; platelet-type von Willebrand disease

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Avoid overhydration if patient is to benefit from its hemostatic effects

More on Germinoma, Central Nervous System

Overview: Germinoma, Central Nervous System
Differential Diagnoses & Workup: Germinoma, Central Nervous System
Treatment & Medication: Germinoma, Central Nervous System
Follow-up: Germinoma, Central Nervous System
Multimedia: Germinoma, Central Nervous System
References
[ CLOSE WINDOW ]

References

  1. Villano JL, Propp JM, Porter KR, Stewart AK, Valyi-Nagy T, Li X. Malignant pineal germ-cell tumors: an analysis of cases from three tumor registries. Neuro Oncol. Apr 2008;10(2):121-30. [Medline].

  2. Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg. Aug 1985;63(2):155-67. [Medline].

  3. Keene D, Johnston D, Strother D, Fryer C, Carret AS, Crooks B. Epidemiological survey of central nervous system germ cell tumors in Canadian children. J Neurooncol. May 2007;82(3):289-95. [Medline].

  4. Bentley AJ, Parkinson MC, Harding BN, Bains RM, Lantos PL. A comparative morphological and immunohistochemical study of testicular seminomas and intracranial germinomas. Histopathology. Nov 1990;17(5):443-9. [Medline].

  5. Echevarría ME, Fangusaro J, Goldman S. Pediatric central nervous system germ cell tumors: a review. Oncologist. Jun 2008;13(6):690-9. [Medline].

  6. Rosenblum MK. CNS germ cell tumors: WHO Classification of Tumors of Central Nervous System ed 4. 4.

  7. Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA. CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology. May 15 2007;68(20):1668-73. [Medline].

  8. Finlay J, da Silva NS, Lavey R, Bouffet E, Kellie SJ, Shaw E, et al. The management of patients with primary central nervous system (CNS) germinoma: current controversies requiring resolution. Pediatr Blood Cancer. Aug 2008;51(2):313-6. [Medline].

  9. Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W. Comparative genomic hybridization in pineal germ cell tumors. J Neuropathol Exp Neurol. Sep 2000;59(9):815-21. [Medline].

  10. Schneider DT, Zahn S, Sievers S. Molecular genetic analysis of central nervous system germ cell tumors with comparative genomic hybridization. Mod Pathol. Jun 2006;19(6):864-73.

  11. Palmer RD, Foster NA, Vowler SL, Roberts I, Thornton CM, Hale JP. Malignant germ cell tumours of childhood: new associations of genomic imbalance. Br J Cancer. Feb 26 2007;96(4):667-76. [Medline].

  12. Sato K, Takeuchi H, Kubota T. Pathology of intracranial germ cell tumors. Prog Neurol Surg. 2009;23:59-75. [Medline].

  13. Kamakura Y, Hasegawa M, Minamoto T, Yamashita J, Fujisawa H. C-kit gene mutation: common and widely distributed in intracranial germinomas. J Neurosurg. Mar 2006;104(3 Suppl):173-80. [Medline].

  14. Sakuma Y, Sakurai S, Oguni S, Satoh M, Hironaka M, Saito K. c-kit gene mutations in intracranial germinomas. Cancer Sci. Sep 2004;95(9):716-20. [Medline].

  15. Frank Saran. Pineal Tumors: Germinomas and Non-germinomatous Germ Cell Tumor. In: Clinical Endocrine Oncology Second Edition. 2008 pp 310-317.

  16. Matsutani M,. Combined chemotherapy and radiation therapy for CNS germ cell tumors--the Japanese experience. J Neurooncol. Sep 2001;54(3):311-6. [Medline].

  17. Kaur H, Singh D, Peereboom DM. Primary central nervous system germ cell tumors. Curr Treat Options Oncol. Dec 2003;4(6):491-8. [Medline].

  18. Matsutani M. Pineal germ cell tumors. Prog Neurol Surg. 2009;23:76-85. [Medline].

  19. Sugiyama K, Yamasaki F, Kurisu K, Kenjo M. Quality of life of extremely long-time germinoma survivors mainly treated with radiotherapy. Prog Neurol Surg. 2009;23:130-9. [Medline].

  20. Sutton LN, Radcliffe J, Goldwein JW, Phillips P, Janss AJ, Packer RJ, et al. Quality of life of adult survivors of germinomas treated with craniospinal irradiation. Neurosurgery. Dec 1999;45(6):1292-7; discussion 1297-8. [Medline].

  21. Yoshida J, Sugita K, Kobayashi T, Takakura K, Shitara N, Matsutani M, et al. Prognosis of intracranial germ cell tumours: effectiveness of chemotherapy with cisplatin and etoposide (CDDP and VP-16). Acta Neurochir (Wien). 1993;120(3-4):111-7. [Medline].

  22. Jubran RF, Finlay J. Central nervous system germ cell tumors: controversies in diagnosis and treatment. Oncology (Williston Park). May 2005;19(6):705-11; discussion 711-2, 715-7, 721. [Medline].

  23. Sonoda Y, Kumabe T, Sugiyama S, Kanamori M, Yamashita Y, Saito R. Germ cell tumors in the basal ganglia: problems of early diagnosis and treatment. J Neurosurg Pediatr. Aug 2008;2(2):118-24. [Medline].

  24. Kim A, Ji L, Balmaceda C, Diez B, Kellie SJ, Dunkel IJ. The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors. Pediatr Blood Cancer. Dec 2008;51(6):768-73. [Medline].

  25. Calaminus G, Bamberg M, Harms D, Jürgens H, Kortmann RD, Sörensen N, et al. AFP/beta-HCG secreting CNS germ cell tumors: long-term outcome with respect to initial symptoms and primary tumor resection. Results of the cooperative trial MAKEI 89. Neuropediatrics. Apr 2005;36(2):71-7. [Medline].

  26. Shibamoto Y, Oda Y, Yamashita J, et al. The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma. Int J Radiat Oncol Biol Phys. Jul 30 1994;29(5):1089-94. [Medline].

  27. Shinoda J, Sakai N, Yano H, Hattori T, Ohkuma A, Sakaguchi H. Prognostic factors and therapeutic problems of primary intracranial choriocarcinoma/germ-cell tumors with high levels of HCG. J Neurooncol. Jan 2004;66(1-2):225-40. [Medline].

  28. Friedman JA, Lynch JJ, Buckner JC, Scheithauer BW, Raffel C. Management of malignant pineal germ cell tumors with residual mature teratoma. Neurosurgery. Mar 2001;48(3):518-22; discussion 522-3. [Medline].

  29. Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, et al. Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer. Aug 2004;43(2):126-33. [Medline].

  30. Haas-Kogan DA, Missett BT, Wara WM, Donaldson SS, Lamborn KR, Prados MD, et al. Radiation therapy for intracranial germ cell tumors. Int J Radiat Oncol Biol Phys. Jun 1 2003;56(2):511-8. [Medline].

  31. Matsatani M. Clinical Management of Primary Central Nervous System Germ Cell Tumors. Semin Oncol. 2004;31:676-683.

  32. Blakeley JO, Grossman SA. Management of pineal region tumors. Curr Treat Options Oncol. Nov 2006;7(6):505-16. [Medline].

  33. Cho J, Choi JU, Kim DS, Suh CO. Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma. Radiother Oncol. Apr 2009;91(1):75-9. [Medline].

  34. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O. Combined treatment with chemotherapy and radiation therapy for intracranial germ cell tumors. Childs Nerv Syst. Jan-Feb 1998;14(1-2):59-62. [Medline].

  35. Roberge D, Kun LE, Freeman CR. Intracranial germinoma: on whole-ventricular irradiation. Pediatr Blood Cancer. Apr 2005;44(4):358-62. [Medline].

  36. Shikama N, Ogawa K, Tanaka S. Lack of benefit of spinal irradiation in the primary treatment of intracranial germinoma: a multiinstitutional, retrospective review of 180 patients. Cancer. Jul 1 2005;104(1):126-34.

  37. Aoyama H. Radiation therapy for intracranial germ cell tumors. Prog Neurol Surg. 2009;23:96-105. [Medline].

  38. Sawamura Y. Strategy of combined treatment of germ cell tumors. Prog Neurol Surg. 2009;23:86-95. [Medline].

  39. Shibamoto Y. Management of central nervous system germinoma: proposal for a modern strategy. Prog Neurol Surg. 2009;23:119-29. [Medline].

  40. Shim KW, Kim TG, Suh CO, Cho JH, Yoo CJ, Choi JU, et al. Treatment failure in intracranial primary germinomas. Childs Nerv Syst. Oct 2007;23(10):1155-61. [Medline].

  41. Yasuda K, Taguchi H, Sawamura Y, Ikeda J, Aoyama H, Fujieda K, et al. Low-dose craniospinal irradiation and ifosfamide, cisplatin and etoposide for non-metastatic embryonal tumors in the central nervous system. Jpn J Clin Oncol. Jul 2008;38(7):486-92. [Medline].

  42. Schoenfeld GO, Amdur RJ, Schmalfuss IM, Morris CG, Keole SR, Mendenhall WM, et al. Low-dose prophylactic craniospinal radiotherapy for intracranial germinoma. Int J Radiat Oncol Biol Phys. Jun 1 2006;65(2):481-5. [Medline].

  43. Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M. Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children's Oncology Group. Pediatr Blood Cancer. Mar 2007;48(3):285-91. [Medline].

  44. Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, et al. Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol. J Clin Oncol. Mar 1 2004;22(5):846-53. [Medline].

  45. Ogawa K, Toita T, Nakamura K, Uno T, Onishi H, Itami J. Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients. Cancer. Jul 15 2003;98(2):369-76. [Medline].

  46. Modak S, Gardner S, Dunkel IJ, Balmaceda C, Rosenblum MK, Miller DC, et al. Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors. J Clin Oncol. May 15 2004;22(10):1934-43. [Medline].

  47. Janmohamed S, Grossman AB, Metcalfe K, Lowe DG, Wood DF, Chew SL, et al. Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen. Clin Endocrinol (Oxf). Oct 2002;57(4):487-500. [Medline].

  48. Peltier J, Vinchon M, Baroncini M, Kerdraon O, Dhellemmes P. Bifocal mixed germ-cell tumor with growing teratoma syndrome and metachronous mature metastases: case report. J Neurooncol. Oct 2008;90(1):111-5. [Medline].

  49. Skeel RT. Handbook of Cancer Chemotherapy. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:. 85, 91, 93, 105.

  50. Nakamura H, Takeshima H, Makino K, Kuratsu J. Evaluation of residual tissues after adjuvant therapy in germ cell tumors. Pediatr Neurosurg. 2007;43(2):82-91. [Medline].

  51. Ogino H, Shibamoto Y, Takanaka T, Suzuki K, Ishihara S, Yamada T. CNS germinoma with elevated serum human chorionic gonadotropin level: clinical characteristics and treatment outcome. Int J Radiat Oncol Biol Phys. Jul 1 2005;62(3):803-8. [Medline].

  52. Robertson Patricia. intracranial nongerminoma germ cell tumors. Available at www.medlink.com.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Intracranial germ cell tumors, germinoma, nongerminomatous germ cell tumor, germ cell tumor, teratoma, pineal lesions, suprasellar lesions, gonadotrophines, tumor markers, alpha-fetoprotein (AFP),  beta-human chorionic gonadotrophins (β-hCG) , primordial germ cells, Klinefelter syndrome, syncytiotrophoblasts
 
 

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Amani AlKofide, MBBS, Assistant Professor, Alfaisal University College of Medicine; Consultant, Department of Pediatric Hematology and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh
Amani AlKofide, MBBS is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

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

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
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.