Skip to main content
SpringerLink
Log in

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review

  • Review
  • Published:
Neurosurgical Review Aims and scope Submit manuscript

Abstract

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Van Beuken-Van Everdingen D, Hochstenbach MHJ, Joosten LMJ, Tjan-Heijnen EAJ, Janssen VCG (2016) DJA. Update on Prevalence of Pain in patients with Cancer: systematic review and Meta-analysis. 51, Journal of Pain and Symptom Management

  2. Els C, Jackson TD, Kunyk D, Lappi VG, Sonnenberg B, Hagtvedt R et al (2017) Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: An overview of Cochrane Reviews. Vol. Cochrane Database of Systematic Reviews. 2017

  3. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH et al (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. ;14(2)

  4. Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M et al (2014) The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: The neuromodulation appropriateness consensus committee. Vol. 17, Neuromodulation

  5. Magee DJ, Schutzer-Weissmann J, Pereira EAC, Brown MRD (2021) Neuromodulation techniques for cancer pain management. Vol. 15, Current Opinion in Supportive and Palliative Care

  6. Perruchoud C, Dupoiron D, Papi B, Calabrese A, Brogan SE (2022) Management of Cancer-Related Pain With Intrathecal Drug Delivery: A Systematic Review and Meta-Analysis of Clinical Studies. Neuromodulation

  7. Lima MC, Fregni F (2008) Motor cortex stimulation for chronic pain: Systematic review and meta-analysis of the literature. Neurology [Internet]. ;70(24):2329–37. Available from: https://www.neurology.org/lookup/doi/https://doi.org/10.1212/01.wnl.0000314649.38527.93

  8. Honey CR, Yeomans W, Isaacs A, Honey CM (2014) The dying art of percutaneous cordotomy in Canada. J Palliat Med. ;17(5)

  9. Ivanishvili Z, Pujara S, Honey CM, Chang S, Honey CR (2016) Stereotactic mesencephalotomy for palliative care pain control: a case report, literature review and plea to rediscover this operation. Br J Neurosurg. ;30(4)

  10. Rzaev J, Moisak G, Kulikova E, Denisova N, Mikhail A, Amelina E et al (2017) Differential approach to surgical management of facial pain. Stereotactic and functional neurosurgery Conference: 17th quadrennial meeting of the world society for stereotactic and functional neurosurgery Germany. ;95

  11. Faillot M, Stammler JL, Lévêque M (2016) Histoire de la chirurgie dans la prise en charge des douleurs cancéreuses. Vol. 17, Douleurs

  12. Levin AB, Ramirez LF, Katz J (1983) The use of stereotaxic chemical hypophysectomy in the treatment of thalamic pain syndrome. 59, J Neurosurg

  13. Riechert T (1959) Die stereotaktischen Hirnoperationen. Deutsche Medizinische Wochenschrift. ;84(37)

  14. Tindall GT, Ambrose SS, Christy JH (1975) Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland. JMEDASSGEORGIA. ;64(3)

  15. Katz J, Levin AB (1977) Treatment of Diffuse Metastatic Cancer Pain by Instillation of Alcohol into the Sella Turcica. Anesthesiology [Internet]. ;46(2):115–20. Available from: https://pubs.asahq.org/anesthesiology/article/46/2/115/22918/Treatment-of-Diffuse-Metastatic-Cancer-Pain-by

  16. Wells G, Shea B, O’Connell D, Peterson J, Ottawa, ON: Ottawa Hospital Research Institute (2000). The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses

  17. Kwon K, Nam T, Im Y, Lee J (2004) Pituitary irradiation by Gamma Knife in Intractable Cancer Pain. J Korean Neurosurg Soc 36(4):286–290

    Google Scholar 

  18. Hayashi M, Taira T, Chernov M, Izawa M, Liscak R, Yu CP et al (2003) Role of Pituitary Radiosurgery for the Management of Intractable Pain and Potential Future Applications. In: Stereotactic and Functional Neurosurgery. p. 75–83

  19. Zervas NT (1969) Stereotaxic Radiofrequency surgery of the normal and the abnormal pituitary gland. N Engl J Med. ;280(8)

  20. Backlund EO, Rähn T, Sarby B, de Schryver A, Wennerstrand J (1972) Closed Stereotaxic Hypophysectomy by Means of 60 Co Gamma Radiation. Acta Radiol Ther Phys Biol [Internet]. ;11(6):545–55. Available from: http://www.tandfonline.com/doi/full/10.3109/02841867209129800

  21. Takeda F, Uki J, Fuse Y, Kitani Y, Fujita T (1986) The pituitary as a target of antalgic treatment of chronic cancer pain: A possible mechanism of pain relief through pituitary neuroadenolysis. Neurol Res [Internet]. ;8(4):194–200. Available from: http://www.tandfonline.com/doi/full/https://doi.org/10.1080/01616412.1986.11739754

  22. Levin AB, Ramirez LF, Katz J (1983) The use of stereotaxic chemical hypophysectomy in the treatment of thalamic pain syndrome. J Neurosurg [Internet]. ;59(6):1002–6. Available from: https://thejns.org/view/journals/j-neurosurg/59/6/article-p1002.xml

  23. Tindall GT, Payne NS, Nixon DW (1979) Transsphenoidal hypophysectomy for disseminated carcinoma of the prostate gland. J Neurosurg [Internet]. ;50(3):275–82. Available from: https://thejns.org/view/journals/j-neurosurg/50/3/article-p275.xml

  24. Tindall GT, Nixon DW, Christy JH, Neill JD (1977) Pain relief in metastatic cancer other than breast and prostate gland following transsphenoidal hypophysectomy. J Neurosurg [Internet]. ;47(5):659–62. Available from: https://thejns.org/view/journals/j-neurosurg/47/5/article-p659.xml

  25. SCHWARZ M, TINDALL GT (1981) NIXON DW. Transsphenoidal Hypophysectomy in Disseminated Breast Cancer. South Med J [Internet]. ;74(3):315–7. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00007611-198103000-00016

  26. Silverberg GD, Britt RH (1979) Transsphenoidal Hypophysectomy in the treatment of metastatic breast and prostate carcinoma. West J Med 130(2):191

    PubMed  PubMed Central  CAS  Google Scholar 

  27. Chernov MF, Hayashi M (2021) Pituitary Radiosurgery for Management of Intractable Pain: Tokyo women’s Medical University Experience and Literature Review. In: Acta Neurochirurgica, Supplementum

    Google Scholar 

  28. May J, Hospital NH, Liščák R (2022) Effectiveness of Leksell gamma knife hypophysectomy on cancer-related intractable pain-a single-center experience. https://doi.org/10.21203/rs.3.rs-1626044/v1

  29. COBB NL, SCOVILLE WB. Hypophysectomy for palliation of breast cancer with especial reference to surgical technique. Calif Med [Internet] (1959) ;90(4):261–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13638835

  30. Smith JA, Middleton RG, Eyre HJ, Roberts TS (1984) Transphenoidal hypophysectomy in the management of carcinoma of the prostate. Cancer [Internet]. ;53(11):2385–7. Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1002/1097-0142(19840601)53:11<2385::AID-CNCR2820531102>3.0.CO;2-M

  31. Yanagida H, Corssen G, Trouwborst A, Erdmann W (1984) Relief of cancer pain in man: alcohol-induced neuroadenolysis vs. electrical stimulation of the pituitary gland. Pain [Internet]. ;19(2):133–41. Available from: http://journals.lww.com/00006396-198406000-00003

  32. RAWLINSON LLOYDJW WAL, EVANS PJD, SELECTIVE HYPOPHYSECTOMY FOR METASTATIC, PAIN (1981) : A review of ethyl alcohol ablation of the anterior pituitary in a Regional Pain Relief Unit. Br J Anaesth [Internet]. ;53(11):1129–33. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0007091217428728

  33. Corssen G, Clifford Holcomb M, Moustapha I, Langford K, Vitek JJ, Ceballos R et al (1977) Alcohol-Induced Adenolysis of the Pituitary Gland: a New Approach to Control of Intractable Cancer Pain. Anesth Analg 56(3):414–421

    Article  PubMed  CAS  Google Scholar 

  34. Lipton S, Miles J, Williams N, Bark-Jones N (1978) Pituitary injection of alcohol for widespread cancer pain. Pain. ;5(1)

  35. Deshpande N, Moricca G, Saullo F, Martino L, Di, Kwa G (1981) SOME ASPECTS OF PITUITARY FUNCTION AFTER NEUROADENOLYSIS IN PATIENTS WITH METASTATIC CANCER. Vol. 67, Tumori

  36. Waldman SD, Feldstein GS, Allen ML (1987) Neuroadenolysis of the pituitary:Description of a modified technique. J Pain Symptom Manage [Internet]. ;2(1):45–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0885392487800453

  37. Lovo EE, Campos F, Caceros VE, Minervini M, Cruz CB, Arias JC et al (2019) Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain. Cureus [Internet]. Available from: https://www.cureus.com/articles/19054-automated-stereotactic-gamma-ray-radiosurgery-to-the-pituitary-gland-in-terminally-ill-cancer-patients-with-opioid-refractory-pain

  38. DUTHIE AM, INGHAM V, DELL AE (1983) DENNETT JE. Pituitary cryoablation. Anaesthesia [Internet]. ;38(5):448–51. Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1111/j.1365-2044.1983.tb14028.x

  39. FITZPATRICK JM, GARDINER RA, WILLIAMS JP, RIDDLE PR, O’DONOGHUE EPN (1980) Pituitary Ablation in the Relief of Pain in Advanced Prostatic Carcinoma. Br J Urol [Internet]. ;52(4):301–4. Available from: https://onlinelibrary.wiley.com/doi/https://doi.org/10.1111/j.1464-410X.1980.tb08921.x

  40. Liampas A, Velidakis N, Georgiou T, Vadalouca A, Varrassi G, Hadjigeorgiou GM et al (2020) Prevalence and Management challenges in Central Post-stroke Neuropathic Pain: a systematic review and Meta-analysis. Adv Ther. ;37(7)

  41. Klit H, Finnerup NB, Jensen TS (2009) Central post-stroke pain: clinical characteristics, pathophysiology, and management. 8, Lancet Neurol

  42. Portenoy RK, Lesage P (1999) Management of cancer pain. Vol. 353, Lancet

  43. Pituitary Ablation for Pain Relief (1981) Lancet 317(8234):1348–1349

    Article  Google Scholar 

  44. DUTHIE AM. Pituit Cryoablation Anaesth. (1983) ;38(5)

  45. Rand RW, Dashe AM, Paglia DE, Conway LW, Solomon DH (1964) Stereotactic Cryohypophysectomy. JAMA: J Am Med Association. ;189(4)

  46. Trouwborst A, Yanagida H, Erdmann W, Kok A (1984) Mechanism of neuroadenolysis of the pituitary for cancer pain control. Appl Neurophysiol. ;47(3)

  47. Gonski A, Sackelariou R (1984) Cryohypophysectomy for the relief of pain in malignant disease. Med J Aust. ;140(3)

  48. Ramirez LRF, Levin AB (1984) Pain relief after hypophysectomy. Vol. 14, Neurosurgery

  49. Lovo EE, Moreira A, Cruz C, Carvajal G, Barahona KC, Caceros V et al (2022) Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience. Cureus

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Miami, Miami, USA

    Timoteo Almeida & Ifeanyichukwu Ogobuiro

  2. Department of Neurosurgery, University of Miami, Miami, USA

    Timoteo Almeida

  3. Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Paraná, Brazil

    Timoteo Almeida, Bernardo A. Monaco, Guilherme S. Piedade, Alexis Morell, Carolina Benjamin, Jonathan R. Jagid & Joacir G. Cordeiro

  4. Department of Neurosurgery, McGovern Medical School at UT Health Houston, Houston, USA

    Fernando Vasconcelos

  5. Department of Neurosurgery, University of Sao Paulo, Sao Paulo, Brazil

    Guilherme A. Lepski & Luciano L. Furlanetti

  6. Department of Anesthesiology, University of Miami, Miami, USA

    Karina K. Cordeiro

Authors
  1. Timoteo Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernardo A. Monaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernando Vasconcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guilherme S. Piedade
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexis Morell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ifeanyichukwu Ogobuiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guilherme A. Lepski
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luciano L. Furlanetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Karina K. Cordeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carolina Benjamin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jonathan R. Jagid
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Joacir G. Cordeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TA and JC developed the concept and screened the databases. BM, FV helped with the methodology and independently assessed the risk of bias. GP, AM and IO participated in the data extraction. GL, LF, KC, CB and JJ participated in the manuscript editing and critical review. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Timoteo Almeida.

Ethics declarations

Ethical approval

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Almeida, T., Monaco, B.A., Vasconcelos, F. et al. Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review. Neurosurg Rev 47, 111 (2024). https://doi.org/10.1007/s10143-024-02347-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10143-024-02347-7

Keywords

Search

Navigation