Abstract
Medically refractory pain in those with advanced cancer significantly reduces one’s quality of life. Therefore, palliative interventions to mitigate cancer pain and reduce opioid requirements are necessary to reduce patient suffering and opioid-induced side effects. Hypophysectomy, a largely forgotten pain procedure with several technical variations, has been repeatedly studied in small series with encouraging results, though historically has been fraught with complications. As a result, the minimally invasive and more tolerable stereotactic radiosurgery (SRS) hypophysectomy has resurfaced as a possible treatment for cancer-related pain. While the mechanism of pain relief is not entirely understood, the hypothalamohypophyseal axis appears to play an essential role in pain perception and transmission and involves C fiber signal processing and downstream modulation of the brainstem and spinal cord via the hypothalamus. This review highlights the role of hypophysectomy in alleviating advanced cancer pain, both in hormonal and nonhormonal malignancy and the current mechanistic understanding of pain relief for the three primary hypophysectomy modalities used historically: surgical and chemical adenolysis, as well as the more recent, SRS hypophysectomy. Given the lack of high-quality evidence for stereotactic radiosurgery hypophysectomy, there is a need for further rigorous and prospective clinical studies despite its ideal and noninvasive approach.
Highlights
A significant subset of patients with advanced cancer suffer from refractory pain
While no difference in pain threshold was detected between patient groups using radiant heat dolorimetry, patients with complete cancer pain relief following NALP had significantly increased resistance to ischemic pain measured with tourniquet time, suggesting NALP may be more effective at relieving pain transmitted via C-fibers but not Ad-fibers [29, 63]
Stereotactic hypophysectomy has a long history for the palliation of refractory cancer pain
Summary
A significant subset of patients with advanced cancer suffer from refractory pain. As supported by World Health Organization guidelines, aggressive opioid management has been shown to control pain in 70% of cancer patients, with 30% of patients continuing to have refractory pain [1]. Hypophysectomy is a largely forgotten palliative pain procedure in the modern era It was used for the palliative treatment of refractory pain in patients with hormone-sensitive cancer, with particular efficacy for diffuse bony metastatic pain. While further clinical trials are needed, radiosurgery hypophysectomy may be a promising approach for palliative pain relief in patients who are refractory to other treatments. Other terminal thalamic endpoints for the paleospinothalamic tract fibers became radiosurgery targets for non-malignant refractory pain. These included the mediodorsal, centromedian, intralaminar, and parafascicular nuclei [31,32,33,34,35,36]. For refractory malignant pain, stereotactic radiosurgical ablation of the pituitary is superior to thalamic ablation [37]
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