Bilateral Open Thoracic Cordotomy for Refractory Cancer Pain: A Neglected Technique?

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1 924 Journal of Pain and Symptom Management Vol. 39 No. 5 May 2010 Palliative Care Rounds Bilateral Open Thoracic Cordotomy for Refractory Cancer Pain: A Neglected Technique? Nicola Atkin, MBBS, MA, MRCP, Kate A. Jackson, MBBS, DTM&H, FRCA, FAChPM (RACP), FFPMANZCA, and R. Andrew Danks, MBBS, MD, FRACS Supportive and Palliative Care Unit (K.A.J.) and Neurosurgery Unit (R.A.D.), Monash Medical Centre (Southern Health), and Monash University (K.A.J., R.A.D.), Clayton, Victoria; and Palliative Care Department (N.A.), The Royal Melbourne Hospital, Melbourne, Victoria, Australia Abstract At least 10% of patients with cancer have pain that is refractory to systemic analgesics. For most of these patients, interventional techniques may be of benefit but are often not considered or are difficult to access. Of these techniques, spinal analgesia is most commonly used in Australia and the United Kingdom, and neurosurgical procedures, such as open cordotomy with sectioning of the spinothalamic tract, are rarely used. We describe a case illustrating the successful use of bilateral open thoracic cordotomy in a patient with refractory mixed nociceptive and neuropathic pain secondary to a lumbosacral tumor. We discuss the various interventional options and review the recent literature regarding the use of both percutaneous and open cordotomy for cancer pain. J Pain Symptom Manage 2010;39:924e929. Ó 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Refractory cancer pain, open cordotomy, bilateral cordotomy, spinothalamic tractotomy Introduction It is estimated that use of the World Health Organization (WHO) analgesic ladder can provide adequate pain relief for up to 90% of adults with cancer. 1e3 However, there remains a small minority for whom this approach is ineffective because of incomplete response or adverse effects limiting dose escalation of systemic analgesics. Up to 90% of this minority Address correspondence to: Kate A. Jackson, MBBS, Supportive and Palliative Care Unit, Southern Health, Monash Medical Center, 246 Clayton Road, Clayton, Victoria 3168, Australia. pallcare@ southernhealth.org.au Accepted for publication: September 28, Ó 2010 U.S. Cancer Pain Relief Committee Published by Elsevier Inc. All rights reserved. group may benefit from interventional pain management techniques, 3 of which spinal analgesia continues to be the most commonly used technique. However, for some patients, this may not be feasible or may be ineffective, and more definitive, often neurodestructive, procedures are required. Neurosurgical approaches, such as cordotomy, can dramatically improve pain control for carefully selected patients. However, in many countries, open, and to a lesser extent, percutaneous cervical cordotomies have been displaced over the past 15e20 years by improved systemic analgesics and the accessibility of long-term spinal infusions, including in the domiciliary setting. Recent data are available for large case series of percutaneous cervical cordotomies, but recent /$esee front matter doi: /j.jpainsymman

2 Vol. 39 No. 5 May 2010 Cordotomy: A Neglected Technique? 925 published data on open cordotomy are very limited. This case report illustrates the successful use of bilateral open cordotomy in a patient with severe refractory pain secondary to a lumbosacral tumor. Case Report A 24-year-old man was referred to an inpatient palliative care unit with a large, ulcerated, recurrent malignant peripheral nerve sheath tumor overlying the lumbar and sacral vertebrae. His history dated back to 1999, when he underwent partial excision of a lumbosacral plexiform neurofibroma, leaving a 5 cm residual mass. By 2006, the tumor had increased on magnetic resonance imaging (MRI) scans to cm, with paraspinal muscle and bony infiltration. Two further surgical excisions plus radiotherapy (54 Gy) and chemotherapy (doxorubicin then dacarbazine) were ineffective, and he developed pulmonary metastases and further encroachment into the sacral canal with nerve root compression. At this point, the multidisciplinary consensus was that the tumor was beyond surgical, radiotherapy, or chemotherapy salvage. By this time, he had developed a cauda equina syndrome, with loss of bladder and bowel control, saddle anesthesia, left leg weakness, and reduced left lower leg sensation. He suffered from constant severe pain arising from the sacrum and hips and radiating down both legs. The pain proved to be refractory to further radiotherapy and multiple high-dose analgesics (as listed below). He was, therefore, transferred from an oncology center to an inpatient palliative care unit for consideration of a painrelieving interventional technique. On admission, he was grossly cushingoid and had a 15 cm diameter fungating ulcerated tumor overlying the sacral and lower lumbar vertebrae. His medications included a continuous subcutaneous infusion of ketamine 500 mg, midazolam 30 mg, and hydromorphone 100 mg over 24 hours; gabapentin 900 mg three times daily; clonidine 150 mcg three times daily; dexamethasone 8 mg daily; methadone 20 mg daily; and paracetamol (acetaminophen) 1 g daily. He had severe pain despite multiple subcutaneous doses of morphine at 150 mg/dose. The decision was made to insert an intrathecal catheter (ITC), which because of the ulcerated infected tumor overlying the lumbar vertebrae, was tunneled down to T12 from a T7 minilaminectomy. The proximal end of the catheter was then tunneled to the lateral chest wall and connected to a subcutaneous port-a-cath device. An infusion of morphine, midazolam, and bupivacaine was commenced and titrated over 24 hours to 15 mg morphine, 30 mg midazolam, and 45 mg bupivacaine, with some success (verbal rating score of 4 out of 10 at best). However, within a week, pain had escalated again, the port-a-cath was found to be leaking cerebrospinal fluid (CSF), and a CT myelogram demonstrated displacement of the catheter out of the spine with a large paraspinous CSF leak. It was thought that the catheter displacement was secondary to a raised CSF pressure. At this point, he was experiencing constant pain, with a verbal rating scale score of 10 out of 10 and made comments, such as the pain is killing me, and I want to die. Although extremely drowsy, he was unable to lie on his back or sleep because of pain. (Fortuitously, in retrospect, he had very little memory of this period.) The intrathecal infusion was discontinued, and he was converted back to his admission medications and had medications for breakthrough pain totaling 1,260 mg subcutaneous morphine and 120 mg subcutaneous ketamine over 24 hours, with little effect. The neurosurgical and palliative care teams discussed management options with the patient and his family. The options of continuing the current medication with increased sedation or attempted repositioning of the ITC after one week of CSF drainage were both rejected. The possibility of a bilateral high thoracic cordotomy was raised, and after weighing the risks and benefits, this was accepted. He underwent a T2/T3 laminectomy and microsurgical bilateral anterolateral cordotomy under general anesthetic without any serious complications. Postoperatively, he was completely free of back or leg pain. Breakthrough analgesia requirements dropped dramatically, with only 140 mg of breakthrough subcutaneous morphine required in the 24 hours postsurgery. He remained free of his preoperative pain but temporarily experienced the anticipated

3 926 Atkin et al. Vol. 39 No. 5 May 2010 wound pain and also pleuritic chest pain associated with a postoperative chest infection. Perhaps surprisingly, there was no CSF leak from the cordotomy wound, which had healed well at the end of two weeks. As a consequence of his cauda equina syndrome, the patient had already lost bowel and bladder function preoperatively, as well as power and sensation in the left lower leg, with a milder deficit on the right leg. This remained unchanged postoperatively, with no evidence of additional neurological impairment resulting from the surgical procedure. By three weeks postsurgery, he was pain free, alert, and interactive, able to lie on his back, participate in upper body muscle strengthening exercises, sit in a reclining chair, and use his computer to communicate with his friends. His medication at this stage had been weaned down to methadone 30 mg twice daily, dexamethasone 2 mg daily, and paracetamol (acetaminophen) 1 g daily; he required no breakthrough analgesia. Unfortunately, after five weeks of good pain control, he became septic, failed to respond to antibiotics, and died comfortably. His family and many friends had all very much appreciated the month of good quality interactive time he had had subsequent to the bilateral cordotomy. Discussion This article details an unusual patient with severe refractory cancer pain managed by bilateral open cordotomy. It also illustrates the value of multidisciplinary input, including a neurosurgical opinion, in the management of refractory cancer pain. This multidisciplinary stance was facilitated by our level 3 inpatient hospice unit being onsite within a tertiary referral hospital. The WHO ladder approach to cancer pain results in reasonable pain control in 80%e90% of patients. The better understanding of the importance of pain mechanisms, 4 the wider use of adjuvants, such as burst ketamine, 5 dexamethasone, antineuropathic pain agents, 6 and the practice of opioid switching for adverse effects or inefficacy 7,8 have all further improved pain control, although there is as yet no high level evidence to support these interventions. The common approach to otherwise refractory cancer pain below the head and neck and upper limbs is a spinal (epidural or currently more commonly intrathecal) infusion of an opioid supplemented frequently by lowdose bupivacaine and/or midazolam or clonidine. 9 A Cochrane review in of 59 uncontrolled studies involving about 2,000 patients suggested that spinal infusions should result in excellent analgesia in more than 70% of patients. This is supported by Smith et al. s 11 randomized controlled trial of 202 patients comparing intrathecal drug delivery systems (IDDS) and comprehensive medical management (CMM). At four weeks, 60% of the IDDS patients had pain scores less than 4 compared with 42% of the CMM group. Median oral morphine dose equivalents, which were initially approximately 250 mg per day in both groups, fell to 50 mg in the IDDS group and increased to 290 mg per day in the CMM group. Along with these changes, fatigue and depressed level of consciousness were significantly less (P < 0.05) in the IDDS group. The ability to access a long-term intrathecal infusion is frequently suboptimal in Australia and apparently also in the United Kingdom. In the United Kingdom, national guidelines exist, whereby cancer networks should have a named lead pain specialist, and the multidisciplinary palliative care team should have access to a named anesthetist with expertise in invasive pain-relieving techniques. However, Kay et al. s survey of the provision of advanced pain management techniques to palliative care units (essentially nerve blocks and intrathecal or epidural infusions) showed that these are still underused, with only approximately 10% of patients likely to benefit being referred. But, even with the addition of spinal infusions, there remains a small percentage of patients who fail to achieve fair to good pain control. It is this group, as illustrated by our patient, that needs to be considered for neurodestructive techniques, such as cordotomy. Spinal cordotomy or spinothalamic tractotomy results in selective loss of pain and temperature perception on the contralateral side, up to several segments (which in time can drop to six segments) below the level of the sectioning. The area sectioned is shown in Fig. 1. As can be seen from Fig. 1, the lateral spinothalamic tract (STT) has a somatotropic distribution

4 Vol. 39 No. 5 May 2010 Cordotomy: A Neglected Technique? 927 Fig. 1. Diagram of a representational cross-section of the high cervical cord. (Reprinted with permission from Cousins M. Neural blockade. In: Clinical anesthesia & management of pain, 1st ed., Figure 29.1, p. 683.) with fibers from higher levels (e.g., the arm and chest) located anteromedially, whereas those from lower levels (e.g., the leg and sacrum) lie posterolaterally. Fig. 1 also illustrates that the normal site of the corticospinal (pyramidal) tract is posterior to the dentate ligament, a landmark readily identifiable both at open and percutaneous cordotomy. Open cordotomy was first described in It is performed under general anesthesia via a minilaminectomy technique at the high thoracic level. The technique of percutaneous cordotomy first described in 1965, 14 and subsequently refined by CT or MRI guidance to visualize the spinal cord has largely replaced open cordotomy. 15,16 Percutaneous cordotomy is performed under local anesthesia and minimal sedation; the patient is able to cooperate to refine localizing the position of the probe before the application of the radiofrequency cutting current. This localization, combined with the known somatotropic representation within the STT, enables relatively selective cordotomy. This reduces the risk of inadvertent damage to anatomically adjacent or aberrant tracts, thus minimizing the incidence of incontinence and significant motor weakness in the good, that is, ipsilateral arm or leg. Bilateral cervical cordotomy carries the risk of Ondine s Curse (sleep-associated apnea) because of the potential for damage to the anteromedially-placed reticulospinal fibers present in the upper cervical cord that are responsible for spontaneous respiration. Bilateral cordotomy, as in our patient, is usually considered for midline and bilateral lumbar or sacral pain. With the availability of CT or MRI guidance, relatively selective percutaneous sectioning of the posterolateral STT may be possible, that is, relatively removed from the anteromedial reticulospinal respiration fibers. Despite this, if required, bilateral cervical cordotomy is usually still performed as a two-stage procedure, with one to two weeks between the two procedures. Open rather than percutaneous cordotomy was considered to be the optimal technique for our patient because of his difficulty tolerating the prone position, the need for bilateral cordotomy, the desire to avoid a two-stage procedure in the context of his poor prognosis and uncontrolled symptoms, and the greater

5 928 Atkin et al. Vol. 39 No. 5 May 2010 local experience with open as compared with percutaneous cordotomy. The literature relating to open cordotomy is limited, with most being case studies or small case series, often from the 1980s or earlier, prior to the widespread use of spinal opioids and the expanding use of percutaneous cordotomy. A recent UK paper, Is there still a role for open cordotomy in cancer pain management?, 17 describes nine patients over a 10-year period who underwent unilateral open cordotomy for pain associated with recurrent pelvic tumors (seven with rectal or gynecological malignancies, one with sarcoma of the ischium, and one with a presacral recurrence of a renal tumor). Similarly to our patient, all had had diverse high-dose opioids with one or more opioid rotations and multiple adjuvant medications, and six out of nine had had a minimal response to spinal medication. All patients achieved good pain control, with their oral morphine dose equivalents per 24 hours falling from 360 to 2600 mg (median 580) presurgery to 40e1000 mg per 24 hours (median 160) postprocedure. Open cordotomy, particularly in Australia and the United Kingdom, is now a rare procedure, and there are no recent large case series from which to obtain information on the likelihood of good pain control or the incidence of the major potential complications, such as significant motor weakness and urinary incontinence. In contrast, large case series of percutaneous cordotomies are available, predominantly from countries in which there is poor access to opioids for cancer pain and/or long-term intrathecal infusions (including management of these in the home). Kanpolat 15 reported on his and other studies totaling many thousands of patients using CTor MRI guidance and the newer electrode systems. These case series report good pain control in up to 95% of patients initially, which was maintained at six months in 75% of surviving patients. Two other recent studies support the safety and tolerability of percutaneous cordotomy. Raslan s 16 series of 51 patients reported no severe or persistent complications. Crul et al. s 18 series of 43 patients carried out using image intensifier control reported one case of partial but permanent ipsilateral weakness. All other complications were transient and had minimal impact on patients well-being. Conclusion Although open thoracic cordotomy will not commonly be required, it remains a valuable option for a small group of patients with refractory cancer pain. We suggest that only a few specialist centers perform these, so that optimal patient selection and operative and perioperative management skills can be developed. Access to these procedures should be available to pain and palliative care services, and referral should be considered in select cases of otherwise refractory cancer pain. References 1. World Health Organization. Cancer pain relief and palliative care: Report of a WHO expert committee. Geneva, Switzerland: WHO, Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization guidelines for cancer pain relief: a 10-year prospective study. Pain 1995;63:65e Schug SA, Zech D, Dorr U. Cancer pain management according to the WHO analgesic guidelines. J Pain Symptom Manage 1990;5:27e Ashby M, Jackson K. When the WHO ladder fails: approaches to refractory or unstable pain. In: Sykes N, Fallon MT, Pratt RB, eds. Clinical pain management: Cancer pain. London, UK: Edward Arnold, 2002: 143e Jackson K, Ashby M, Martin P, et al. Burst ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage 2001;23:450e Stillman M. Clinical approach to patients with neuropathic pain. Cleve Clin J Med 2006;73(8): 726e Ashby M, Martin P, Jackson K. Opioid substitution to reduce adverse effects in cancer pain management. Med J Aust 1999;170:68e de Stoutz ND, Bruera E, Suarez-Almazor M. Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 1995;10:378e Hassenbusch SJ, Cherny NI. Neurosurgical approaches in palliative medicine. In: Doyle D, Hanks G, Cherny N, Calman K, eds. Oxford textbook of palliative medicine, 3rd ed Oxford, UK: Oxford University Press, 2003:396e Ballantyne JC, Carwood CM. Comparative efficacy of epidural, subarachnoid and intracerebroventricular opioids in patients with pain due to cancer. Cochrane Database Syst Rev 2005;(2) DOI: / CD Smith T, Staats P, Deer T, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for

6 Vol. 39 No. 5 May 2010 Cordotomy: A Neglected Technique? 929 refractory cancer pain: impact on pain, drug-related toxicity and survival. J Clin Oncol 2002;20(19): 4040e Kay S, Husbands E, Antrobus JH, Munday D. Provision for advanced pain management techniques in adult palliative care: a national survey of anaesthetic pain specialists. Palliat Med 2007;21:279e Spiller WG, Martin E. The treatment of persistent pain of organic origin in the lower part of the body by division of the anterolateral column of the spinal cord. JAMA 1912;58:1489e Mullan S, Heckmatpanak J, Dobben G, Beckman F. Percutaneous intramedullary cordotomy utilizing the unipolar anodal electrolytic lesion. J Neurosurg 1965; 22:548e Kanpolat Y. The surgical treatment of chronic pain: destructive therapies of the spinal cord. Neurosurg Clin N Am 2004;3:307e Raslan AM. Percutaneous computed tomography-guided radiofrequency ablation of upper spinal cord pain pathways for cancer-related pain. Neurosurgery 2008;62:226e James B, Finlay I, Ray A, Simpson B. Is there still a role for open cordotomy in cancer pain management? J Pain Symptom Manage 2003;25: 179e Crul B, Blok L, van Egmond J, van Dongen R. The present role of percutaneous cervical cordotomy for the treatment of cancer pain. J Headache Pain 2005;6:24e29.