barriers to rehab in surgical onc patient

Journal of Surgical Oncology 2007;95:427–435

Barriers to Pain Management in the Rehabilitationof the Surgical Oncology Patient

JULIE SILVER, MD1,2,3* AND R. SAMUEL MAYER, MD

4,5

1Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts2Spaulding Rehabilitation Hospital, New Hampshire, Massachusetts

3Massachusetts General and Brigham and Women’s Hospitals, Boston, Massachusetts4Department of PM&R, Johns Hopkins University School of Medicine, Baltimore, Maryland

5Inpatient Rehabilitation, Johns Hopkins Hospital, Baltimore, Maryland

Virtually every surgical oncology patient faces pain, and it can become a major barrierto rehabilitation and quality of life. Pain must be assessed as to its severity, etiology(somatic, visceral, or neuropathic), causation (directly from malignancy or fromtreatment side effects), and its impact on daily function. Treatments can includephysical modalities, exercise, opioids, adjuvant medications, and interventionaltechniques. Barriers to treatment may include side effects, finances, and attitudes.New technologies in medication delivery systems, intrathecal pumps, injections,and surgery have greatly strengthened the armamentarium available to manage pain.J. Surg. Oncol. 2007;95:427–435. � 2007 Wiley-Liss, Inc.

KEY WORDS: cancer pain; surgical oncology; rehabilitation; opioid

INTRODUCTION

Pain is almost a universal experience in the surgicalcancer patient. However, post-operative pain specificallydue to surgical interventions is but one type of pain thatpatients may experience. The various aspects of pain thatinclude whether it is neuropathic, somatic, or visceral;whether it is malignant or non-malignant; whether it isacute or chronic; and whether it is mild, moderate, orsevere, can all impact pain relief and function in thesurgical oncology patient.

Though pain has always been a priority in the care ofpatients undergoing surgical procedures, recently, it hasbecome of paramount importance. In fact, treating pain isnow considered the ‘‘fifth’’ vital sign, and when hospitalsundergo accreditation, they must show documentationthat during the admission of a patient the vital signs—temperature, pulse, respiration, and blood pressure aretaken along with a screening question on pain. Accordingto the Comprehensive Accreditation Manual for Hospi-tals: The Official Handbook, ‘‘The following statementon pain management is posted in all patient care areas(patient rooms, clinic rooms, waiting rooms, etc.). . .Allpatients have a right to pain relief [1].’’ Medicalpersonnel are now required to show that they worktogether with the patient and families to ‘‘establish a goalfor pain relief and develop and implement a plan to

achieve that goal.’’ These regulations are a very importantstep in trying to make pain relief a priority for everypatient who enters the hospital.

Physicians must overcome a number of barriers tomanage cancer pain, including treatment side effects,financial limitations, and negative attitudes. However,there exists a growing armamentarium of therapiesavailable to cancer patients to better control pain andimprove quality of life.

PREVALENCE OF PAIN IN CANCER SURVIVORS

One can assume that the prevalence of immediatepost-operative pain among surgical cancer patients isextremely high. In a random sample of 250 adults who

Julie Silver is an Assistant Professor in Harvard Medical School, AttendingPhysician in Spaulding Rehabilitation Hospital, and an Associate inPhysiatry in Massachusetts General and Brigham and Women’s Hospitals,Boston, Massachusetts; R. Samuel Mayer is a Clinical Associate in JohnsHopkins University School of Medicine and a Medical Director in InpatientRehabilitation, Johns Hopkins Hospital.

*Correspondence to: Julie Silver, MD, 570 Worcester Road, Boston, MA.Fax: 508-872-1205. E-mail: [email protected]

Received 8 January 2007; Accepted 9 January 2007

DOI 10.1002/jso.20780

Published online 21 March 2007 in Wiley InterScience(www.interscience.wiley.com).

� 2007 Wiley-Liss, Inc.

had undergone various surgical procedures (not specifi-cally cancer patients), a follow-up telephone surveyrevealed that approximately 80% experienced acute painafter surgery and of these, 86% had moderate, severe, orextreme pain with more patients experiencing pain afterdischarge than before discharge. The authors concluded,‘‘Despite an increased focus on pain managementprograms and the development of new standards for painmanagement, many patients continue to experienceintense pain after surgery’’ [2]. Clearly the managementof pain in surgical oncology patients both perioperativelyand during their post-operative rehabilitation needs muchmore attention from clinicians.Although pain is a significant problem in cancer

patients, its prevalence varies considerably. Approximatelyone-third of patients report pain during active therapy andin those with advanced disease, this number is approxi-mately double at two-thirds [3–10]. Moreover, the under-treatment of cancer pain has been well documented.According to the standards set by the World HealthOrganization (WHO), as many as 40% of ambulatorycancer survivors receive inadequate analgesia [11,12].Pain after surgery can be due to a variety of factors

including the type of procedure (e.g., lumpectomy versusmastectomy in breast cancer), follow-up cancer treatment(e.g., chemotherapy and radiation treatment can delaywound healing), and post-operative scarring, fibrosis, andloss of range of motion of soft tissues (e.g., frozenshoulder after mastectomy). Since pain is directly relatedto the type of surgery and the post-operative complica-tions, it is imperative to carefully consider the surgicaloptions in the context of both saving or extending apatient’s life and the quality of life post-operatively. Forexample, in a study done by van Wilgen and colleagues, atotal of 137 patients with neck dissections were followedpost-operatively up to at least 1 year, in order to identifyshoulder complaints. Shoulder complaints were mostcommon in those who had undergone postero-lateral neckdissection (66.7%) and least common in those who hadundergone supraomohyoid neck dissection (20%) [13].

IDENTIFYING SOURCES OF PAIN INCANCER PATIENTS

In the immediate post-operative period, pain is oftenprimarily due to the procedure itself. However, in thegeneral cancer population, pain is usually due to one ofthree factors: (1) tumor invasion into pain-sensitivestructures, (2) pain due to treatment, including surgicalinterventions, (3) pain that is unrelated to cancer or itstreatment. Identifying the type of pain may help inassessing its underlying cause and then directingappropriate treatment. Common types of pain includethe following [14].

Somatic Pain

This is often described as a dull, sharp, aching, orthrobbing pain. Since this type of pain is often a result ofbone metastasis, it follows that it is usually constant andwell localized. This is typically seen in surgeriesinvolving muscle and bone.

Visceral Pain

This type of pain is dull, aching, or a pressuresensation. Since it is often caused by the abnormalstretching or distention of the smooth muscle wall of theviscera or ischemia or irritation of the visceral muscles ormucosa, it is characterized (and differs from somaticpain) by its intermittent ‘‘colicky’’ nature. Abdominalsurgery commonly causes visceral pain.

Neuropathic Pain

The presentation of this type of pain is considerablydifferent from the others described in that it is a burning,shooting, electrical, or lancinating type of pain that issometimes associated with paresthesias and numbness.Neuropathic pain is a result of injury to nerve structures.Etiologies include direct tumor invasion into peripheralnerves or plexusesl toxicity to peripheral nerves fromchemotherapeutic agents, and surgical procedures, whichcause injury to nerve, especially when large debulking oftumors is required.

IMPACT OF PAIN ON QUALITY OF LIFE

The impact of pain on quality of life can be quiteprofound. The concept of quality of life, somewhatcontroversial and not easily defined, is measured inresearch studies in a variety of ways (listed in Table I).The WHO definition of health is that it is a state ofcomplete physical, mental and social well-being and notmerely the absence of disease or infirmity. This definitionconsiders, though doesn’t specifically state, that qualityof life is an important aspect of health. Pain, regardless ofits origin, not only impacts the physical functioning of apatient (e.g., someone with severe low back pain may notbe able to sit at her desk and work in her usual manner),

Journal of Surgical Oncology DOI 10.1002/jso

TABLE I. Measures of Quality of Life 67–76

Functional Assessment of Cancer Treatment (FACT)

Cancer Rehabilitation Evaluation System (CARES)

Visual Analog Scale Global Quality of Life (VASQOL)

Sickness Impact Profile (SIP)

Nottingham Health Profile (NHR)

Medical Outcomes Study Short Form 36 (SF-36)

European Organization for Research and Treatment of Cancer

(EORTC) modular questionnaire

Rotterdam Symptom Checklist (RSCL)

428 Silver and Mayer

but also many other aspects of daily life includingattending to family, social and work obligations. Table IIlists some of the important ways in which pain caninterfere with quality of life.

Pain is a physical symptom with many psychologicalramifications, particularly in cancer survivors. Forexample, in a study by Tishelman and colleagues [15]assessing symptoms in 400 patients who were newlydiagnosed with inoperable lung carcinoma, the research-ers found that breathing, pain, and fatigue wereassociated with the most distress. They concluded,‘‘Breathing and pain appeared to function as iconsrepresenting threats associated with lung carcinoma,with distress described as related to the past and thepresent and to expectations for the future.’’ In anotherstudy by Rustoen and colleagues [16] in which theyexamined to what extent demographic and disease-specific variables affected pain in cancer patients, theyfound that of the 1,435 patients who complete ques-tionnaires, 60% reported some pain. Significant predic-tors of pain included the type of cancer, presence ofmetastases, and time until death. Interestingly sex, age,level of education, and co-habitation were not related topain, but employment status was.

Another important pain issue is that in cancer it is oftenfound as part of a ‘‘symptom cluster.’’ For example,fatigue, pain and depression are frequently simulta-neously present and each contributes to the severity of theother two symptoms. In the case of a patient with pain aspart of a cluster of other symptoms, this cluster cansignificantly negatively impact quality of life and it isimportant to address not only the pain, but the othersymptoms as well.

PAIN RELIEF AS A DETERMINANT OFFUNCTION AND IMPROVED QUALITY OF LIFE

The research in this area is quite deficient and it isdifficult to draw generalized conclusions. Seemingly,improving pain in cancer patients would lead to betterfunction and improved quality of life, though there is adistinct lack of literature to demonstrate this. For

example, in one study Talbot and colleagues [17]evaluated surgery substantially improved functional andquality of life outcomes in 67 patients with nonspinalbone metastases. Their conclusions were, ‘‘There were noimprovements in the Short Form-36 mental andphysical summary scales of the patients. The number ofpatients using pain medication did not decrease. Patientshad functional improvement after surgical treatmentof bone metastases, even patients with a limited lifeexpectancy.’’ This study was complicated by a highrate of attrition due to death and loss to follow-up. Theauthors of this study also noted, ‘‘. . .improvements inpain control and function occurred as early as 6 weekspostoperatively. . .Our findings support the rule of a6-week life expectancy to consider surgery’’ [17].

In another study of 216 Chinese cancer patients withmetastatic disease, the findings were that increasingseverity of pain was associated with poorer functioningand that patients with well-controlled (mild) pain didnot differ significantly from that of patients withoutpain [18]. Meurser and colleagues [19] surveyed theprevalence, etiology, and severity of pain in 593cancer patients. These authors concluded that the ‘‘highprevalence and severity of many symptoms in faradvanced cancer can be reduced, if pain treatment iscombined with systematic symptom control.’’ Systemicsymptoms included nausea, constipation, mood changes,fatigue, anorexia, and a host of others.

MEDICATIONS

Physicians should tailor pain medications to individualpatient’s needs. Certain drug classes can help moreeffectively treat specific pain generators—visceral versusmusculoskeletal versus neuropathic origins [20] (NCCNcategory 1). Table III delineates these medications. Onemust, of course, also take into account side effects andcontraindications. Furthermore, an accurate history of thepatient’s previous pain medication use with the responseand dosing can tremendously aid the physician inadjusting or modifying pain regimens.

Opioids

Opioids act on several receptor sites in the brain andspinal cord (delta, kappa, mu, and others) by complexmechanisms, which are active areas of research inneuron-psycho-pharmacology [21]. While it is a grossover simplification for this brief overview, delta receptorsprimarily affect nocioception, kappa affect mood anddependence and mu affect gastrointestinal motility.Pharmacologists are working to design new drugs, whichpreferentially bind to the intended receptor, but currentopioids on the market are fairly indiscriminant in theirbindings. This accounts for their side effects. The


TABLE II. Pain Interfering With Quality of Life

Interference with appetite, sleep, and other physical functions

Reduced memory and concentration

Decreased ability to work

Loss of interest or other barriers to physical intimacy

Difficulty participating in home activities (e.g., household chores,

caring for children, etc.)

Limited social activity and engagements

Decline in financial resources

Change in spiritual connections (e.g., fear of dying, etc.)

Loss of autonomy and marginalized at home, work, and in social

contexts

Pain Management in the Surgical Oncology Patient 429

differences in efficacy and tolerability among oraloxycodone, hydromorphone, and morphine are insigni-ficant [22] (NCCN category 1); hence prescription for anindividual patient may take trial and error. Geneticdifferences among individuals probably play a large rolein the variable responsiveness seen.Despite their side effects, opioids are highly effective

in treating cancer pain, and generally well tolerated. In awell-designed RCT, early use of ‘‘strong’’ opioids inadvanced cancer patients with mild to moderate painshowed better pain control, fewer changes in therapy andgreater satisfaction than those treated with non-opioid or‘‘weak’’ opioid analgesics [23] (NCCN category 1). Thisargues against the use of the 1986 World HealthOrganization’s guidelines for treatment of cancer pain,which had advocated a step-wise approach from‘‘milder’’ medications to ‘‘strong’’ opioids [24].Perhaps the most exciting advance in opioid medica-

tions in the last decade is the development of novel drugdelivery systems. This allows medications to be deliveredby numerous routes—oral, intravenous, intramuscular,sublingual, suppository, transdermal, epidural, andintrathecal. This not only allows flexibility in adminis-tration when one route of delivery is unavailable (e.g., thepatient is NPO), but also flexibility in the onset andduration of the medication dose [25] (NCCN category 1).Long-acting opioids include extended release forms oforal morphine, oxycodone, and tramadol (an opioidreceptor agonist), as well as transdermal fentanyl. Theyvary in duration from 8 to 72 hr. This allows the patient amore even basal pain relief—‘‘getting ahead of thepain’’—and may reduce the total dose of medication andhence the side effects, while providing more effectiverelief. Short acting opioids are useful for breakthroughpain, especially during painful events such as woundcare dressing changes, physical therapy, or diagnosticprocedures. They have onset in 15 to 30 min, and duration

of 1–4 hr, allowing quick ‘‘on–off’’ pain relief [26](NCCN category 1). Intrathecal programmable pumpsallow the ultimate in dosing flexibility with the capabilityof complex basal dosing or periodic boluses. Further-more, since medication is delivered directly into thecerebral spinal fluid, there tends to be fewer systemic sideeffects. In one study of patients with intractable cancerpain, intrathecal pumps not only provided significantlybetter pain relief and less toxicity, but overall 6 monthsurvival increased to 53.9% versus 37.2% in the controlgroup [27] (NCCN category 1).

ADJUVANT MEDICATIONS

Non-malignant pain, whether it is due to post-operativehealing or other issues, can be treated with a variety ofnon-opioids including non-steroidal anti-inflammatories(NSAIDS), antidepressants (e.g., tricyclics and selectiveserotonin reuptake inhibitors), anticonvulsants, musclerelaxants and antispasmodics (refer to Table IV). Theefficacy of a particular medication or class of medicationsmay depend on the etiology and character of the pain.Oral pain medications may be used in combination with


TABLE III. Classes of Pain Medications and Their Uses

Class Uses Examples

Opioids Visceral, soft tissue, bone, neuropathic Fentanyl, hydromorphone, methadone,

morphine, oxycodone

NSAIDS* Soft tissue, bone Celecoxib (COX-2), ibuprofen,

nabumetone, naproxen

TCAs** Neuropathic, myofascial Amitriptyline, desipramine,

nortriptyline, cyclobenzaprine

SSRIs*** Neuropathic, depressive component Duloxetine, tramadol****

Anticonvulsants Neuropathic Carbamazapine, clonazepam,

gabepentin, pregabelin

Antispasmodics Spasticity Baclofen, dantrolene, tizanidine

Benzodiazepines Muscle spasm, anxious component Alprazolam, diazepam, lorazepam

*Non-steroidal anti-inflammatory medications.**Tricylclic anti-depressant.***Selective serotonin reuptake inhibitor; ****has properties of SSRI and opioid receptor agonist.

TABLE IV. Chemotherapy Agents That Can Cause PeripheralNeuropathy

Acetyl-L-carnitine

Altretamine

Amifostine

Cytarabine

Docetaxel

Ifosfamide

Methotrexate

Methylene blue

Mitotane

Oxaliplatin

Paclitaxel

Thalidomide

Vincristine


each other or with other treatment such as physicalmodalities or injections.

PHYSICAL MODALITIES

Most physical modalities have not been well studied incancer patients due to the concern of exacerbating anunderlying malignancy. Those which are generallybelieved to be safe include cryotherapy, biofeedback,iontophoresis (transdermal delivery of medication byelectrical current), transcutaneous electrical nerve stimu-lation (TENS), and massage [28]. (NCCN category 2A)Electrical stimulation, regardless of how it is delivered, isgenerally not done directly over a tumor site. The same istrue for massage therapy and superficial heat. Deep heat(e.g., ultrasound and phonophoresis) is usually contra-indicated in cancer patients. Spinal traction is contra-indicated in those patients with spinal metastases or withsignificant osteoporosis.

EXERCISE

Exercise is certainly helpful in post-operative recoveryand can assist with pain reduction if prescribed appro-priately. In patients with head and neck cancers or breastcancer, gentle range of motion exercises can help patientsresume their ability to function without developingexcessive contractures and painful joint motion limita-tions. Exercise may help immune system functioning andpost-operative healing [34] (NCCN category 2B). Cancerpatients often become more sedentary during treatmentand need encouragement and guidance when it comes toexercise. Exercise has also been shown to help preventprimary cancers from developing and more recently someevidence suggests that it may be helpful in preventingcancer recurrence [29–32]. (NCCN category 2A) Theeffects of obesity on survival have been well studied inbreast cancer patients in more than three-dozen cohortstudies [33]. Contraindications to exercise include severecardiopulmonary limitations or blood dyscrasias.

Complementary and Alternative Medicine (CAM)

This is a huge field of medicine that covers a widevariety of treatments, somewhich have been studied quiteextensively and found to be useful (e.g., meditation,acupuncture, and massage) and many others, which havenot been well studied, and may in fact be harmful. In1993, David Eisenberg and colleagues [35] published areport in the New England Journal of Medicinetitled ‘‘Unconventional Medicine in the United States:Prevalence, Costs, and Patterns of Use.’’ They reportedthat approximately one out of three Americans wereusing CAM therapies and that approximately two out ofthree people were not sharing this information with their

primary health provider. Since cancer patients often useCAM therapies without confiding in their doctors orseeking medical advice, it is important for practitioners totake the initiative and inquire as to what treatmentspatients are already utilizing. This includes dietaryregimens, supplements, mind-body therapies, etc. In anexcellent review article titled ‘‘Advising Patients WhoSeek Complementary and alternative Medical Therapiesfor Cancer,’’ acupuncture and massage therapy wereacceptable CAM pain treatments that may be recom-mended based on the level of scientific evidence [36](NCCN category 2A). The National ComprehensiveCancer Network guidelines recommend considerationof the following CAM therapies if pain scores remain 4 orabove on a visual analog scale up to 10 points: massage,acupuncture, imager/hypnosis, and relaxation [37]. Ofnote is that they also recommend reevaulation ofpharmacologic management simultaneously.

Interventional Techniques and Surgery

Pain control may warrant a more aggressive approachin some cases. Naturally, risks and benefits must becarefully weighed, particularly in terminally ill patients.Nevertheless, interventional techniques are sometimesthe only way to improve quality of life for these patients.Implantable intrathecal pumps are discussed above as adelivery system for opioids. Percutaneous vertebroplastymay help some patients with pathologic compressionfractures from spinal metastases [38] (NCCN category2A). In some patients with radicular symptoms orcomplex regional pain syndromes, spinal cord stimula-tion may offer pain reduction and a decreased reliance onmedications. Cordotomy, myelotomy, and dorsal rootentry zone surgeries on the spinal cord are irreversibleand reserved for the most desperate of situations [39](NCCN category 2A).

BARRIERS TO PAIN MANAGEMENT IN THESURGICAL ONCOLOGY PATIENT

Pain itself is, of course, one of the major impedimentsin the rehabilitation of surgical oncology patients (NCCNcategory 1) [40]. Multiple barriers limit optimal painmanagement in surgical oncology patients. Factors,which make pain management so difficult include paucityof literature, side effects from cancer treatments and painmedications, depression, fatigue, and special precautionsfor cancer patients [41]. Sadly, attitudinal barriers amongmany health care providers and payers still exist. Well-intentioned governmental regulations to battle the war ondrug abuse often catch cancer patients in the crossfire.Financial barriers created by the dysfunctional Americanhealth care system exist both in the private and publicsectors.



Evidenced-Based Practice Barriers

One important barrier to understanding the results ofpain treatment in cancer patients is that there is a lack ofliterature in this area and the studies that have been donehave frequently focused on palliative measures for thosewith metastatic cancer. There is a great deal of researchthat needs to be done on pain control and quality of life insurgical patients who do not have metastases. Moreover,the research to date has focused primarily on pain reliefwith opioids, while rehabilitative measures have not beenwell studied.

Cancer Treatment Side Effects

Because cancer is usually life-threatening, physiciansoften prescribe aggressive treatments with many sideeffects, including pain. Surgery is almost by definitionpainful, despite the many advances in peri-operativeanesthesia and post-operative pain management [42].Newer minimally invasive techniques, for example,laparoscopic gastrectomy, certainly help minimize pain[43]. However, as many as one in four surgical oncologypatients may suffer painful nerve damage from surgery,usually at the microscopic level [44]. Radiation therapyalso can produce painful side effects including mucositis,headaches, avascular necrosis of the bone, and skin burns.Chemotherapy can lead to painful peripheral neuropathy[45]. Table IV lists chemotherapy agents most oftenassociated with peripheral neuropathy.

Pain Medication Side Effects

Management of cancer pain most often involvesmedications. Side effects of many of these medicationsoften present barriers to treatment, and must be balancedwith treatment efficacy. This is true of all classes of painmedications; thus prescriptions should be tailored toindividual patient situations. Table V lists common sideeffects of various classes of drugs used for cancer pain.Opioids are a mainstay of pain management in cancer

patients, but often result in delirium, gastrointestinaldistress, urinary retention, and, in rare cases, respiratorydepression and death. Issues of tolerance, withdrawal,abuse, and divergence are important considerations as

well when prescribing these medications. All of theseside effects can be managed to some degree byexperienced clinicians. Only rarely should that lead to apatient unable to tolerate enough medication to managepain [46] (NCCN category 2A).Delirium and somnolence frequently occur with

opioids, particularly at higher doses and in elderly ordebilitated patients. Delirium occurs in 26–44% ofhospitalized cancer patients. It is important to excludeother causes of delirium such as dehydration or CNSmetastasis. The cause is usually multi-factorial, butopioids are a factor in over 60% of delirious cancerpatients [47]. Cognitive dysfunction often can be avoidedwith careful dose titration. When it does occur, doses canbe reduced or the medication can be withdrawn astolerated [48]. In these situations, the prescriber must setgoals with the patient and family in terms of pain reliefversus cognitive dysfunction. Some patients prefer painrelief at virtually any cost; others are willing to toleratemoderate pain in order to maintain their ‘‘faculties.’’Alternative medications can sometimes be substituted.Tramadol is a weak opioid analog that may produce lessdelirium than traditional opiates [49] (NCCN category2B). Switching from sustained released morphine totransdermal fentanyl significantly reduced cognitivedysfunction among delirious patients in one open labeltrial [50] (NCCN category 2B). Opiate-induced somno-lence has been counter-acted with methylphenidate in asmall Phase 2 trial in breast cancer patients [51] (NCCNcategory 2B). Donepazil has also been used in a smalltrial of 40 patients [52] (NCCN category 2B). Neurolep-tics such as haloperidol have been used in delusionalpatients [53] (NCCN category 2B).Opioids can cause gastrointestinal dysmotility, fre-

quently leading to nausea, emesis, and constipation. Thisis mediated by the Mu receptors in the gut [54]. Nauseaand vomiting occur frequently with opioid use, usually innew use among opioid naive users or with rapid increasein dosage. In most cases, this can be controlled by moregradual dose increases. Anti-emetics are often useful, andare available in oral, parenteral, or suppository formula-tions. Emesis also can occur when the patient becomesconstipated. Treating the constipation frequently relievesthe upper gastrointestinal tract symptoms. It is importantto prevent constipation among opioid users, and most ofthese patients should be on prophylactic stool softeners.When constipation does result, a number of medicationoptions are available. Senna in one RCT had similarefficacy to lactulose for opioid-induced constipationamong cancer patients, but the cost was significantlylower [55] (NCCN category 1). Adding poletheyleneglycol (MiralaxTM) in a step-wise approach to standardmanagement was found to be effective in 78.4% ofpatients [56] (NCCN category 2B). A promising new


TABLE V. Side Effects by Pain Medication Drug Classification

Opioids Delirium, somnolence, nausea, constipation,

urine retention, respiratory depression

NSAIDs, COX 2 Peptic ulcers, hypertension, renal insufficiency,

cardiovascular events

Anticonvulsants Delirium, somnolence, hepatic impairment,

Stevens-Johnson, aplastic anemia, hyponatremia

Antidepressants Orthostasis, drowsiness, dry mouth, urine retention,

cardiac arrhythmias


experimental treatment is the use of Mu receptorantagonists (alvimopan and methylnatrexone), whichare not readily absorbed in the gut [57] (NCCN category3). There is some evidence that switching from oralopioids to transdermal fentanyl may reduce GI sideeffects [58] (NCCN category 2B).

Opioids not only impair GI motility, but also bladderdetrussor contraction. Patients should be monitored forsymptoms of urinary retention. Those patients at high riskof detrussor dysfunction (due to spinal cord or lumbo-sacral plexus compression from metastasis) or outletobstruction (e.g., prostate or vulvar cancers) should bewatched particularly closely. In these patients, considera-tion should be given to bladder scan post-void residuals,where available. Urinary retention can be managed byfrequent toileting, preferably in the upright position on acommode, as gravity can aid in emptying. Pharmacother-apy may include sphincter relaxants (i.e., alpha receptorblockers such as tamusolin) or cholinergic agonists toincrease detrussor contractility (e.g., bethanechol). Inter-mittent or Foley catherization may be needed in somecircumstances.

Respiratory depression is perhaps the most feared ofopioid side effects. Fortunately, it rarely occurs amongchronic opioid users who have developed tolerance. It canoccur in opioid naı̈ve patients. Two situations are ofparticular concern, and have led to deaths among patientsusing long-acting opioid formulations. Patients whochew, either inadvertently or intentionally, sustainedrelease capsules may receive the full 12 or 24-hr doseof medication immediately, leading to overdose. Trans-dermal patches have led to overdoses in patients withhigh fevers, and increased skin temperature hastensabsorption [59].

Pain management experts have long advocated for theuse of adjuvant medications along with opioids, sincebefore the original WHO step-ladder. These medicationsmay treat specific pain generators (e.g., bone or nerve)and enhance efficacy. In combinations with opioids,lower doses of each medication may reduce side effects.However, it must be remembered that these medications,too, have serious side effects. Non-steroidal anti-inflammatory medications and COX-2 inhibitors not onlycan cause peptic ulcer disease, but also may increasecardiovascular events. Anti-epileptics may cause asmuch, if not more, somnolence than opioids [60] (NCCNcategory 2B). Tricyclic anti-depressants can causeurinary retention and orthostatic hypotension.

Barriers to Physical Modalities and Exercise

Physical modalities and exercise certainly have fewerand less serious side effects than medications for painmanagement. However, other barriers may limit their use

as well. Most physical modalities cannot be used overopen wounds (diathermy and infrared light are excep-tions). Deep heating modalities should not be used nearprimary tumors or metastatic lesions as they may increasecirculation to the area and increase the risk of tumorgrowth. Transcutaneous electrical nerve stimulation(TENS) should not be used in patients with pacemakersor implanted pumps. Manipulation and deep tissuemassage must be used with extreme caution in patientswith bony metastases as pathologic fractures may result.Similarly weight-bearing precautions in patients withbone metastasis may limit exercise regimes (Category2A). A bigger barrier to exercise is fatigue, oftenprominent among cancer symptoms. Furthermore,depression may limit motivation to exercise.

Financial and Attitudinal Barriers

In the American health care system, financial barriersto medications, therapies, and physician visits abound.Nearly 46 million Americans are uninsured, and must payout of pocket for all medical care. Even among those withprivate insurance or government coverage, large gapsexist with high deductibles and co-pays. Restrictivepharmaceutical formularies often limit access to painmedications, particularly newer drugs and formulationroutes. Many insurers, including Medicare, have capson coverage for physical therapy. Managed care plansoften limit access to specialists. This behavior on thepart of payers is regrettable, since guideline-basedpain management in cancer patients only modestlyincreases costs (approximately $265) [61]. Furthermore,in minority neighborhoods, pharmacies are far lessinclined to stock opioid medications, indeed 52 timesless likely in one study of Michigan pharmacies by zipcode [62].

The transition from hospital to rehabilitation center,nursing facility, and/or home can also be a barrier to painmanagement. Only recently have clinicians begun torecognize the importance of medication reconciliationwhen patients are transferred among levels of care, andcareless errors can lead to unnecessary pain andsuffering. Furthermore, some treatments may be unavail-able in outside facilities or at home due to formularyrestrictions, or intensity of nursing care required (e.g.,patient controlled anesthesia pumps).

In pain management, perhaps the highest barriers of allto overcome are the attitudinal barriers [63]. Physicians,nurses and pharmacists are poorly trained in painmanagement [64]. This leads to unwarranted fears ofside effects, and confusion about the meaning andincidence of tolerance and addiction [65]. The problemis further exacerbated by state and federal drug enforce-ment regulations aimed at decreasing illicit street use of



prescription medications. This has generated con-siderable fear among physicians and pharmacist toprescribe and dispense opioids because of the perceivedthreat of wrongful prosecution [66].

CONCLUSION

The prevalence of pain in the surgical oncology patientis extremely high and the importance of this topic isparamount. Pain is now considered the fifth vital sign andhealthcare providers should go beyond simply document-ing its presence and intensity. The relief of pain, whetherit is complete or partial, is essential to improve qualityof life and help patients to function optimally.The rehabilitation model for treating pain is a multi-disciplinary approach that utilizes a variety of treatmentsincluding medications, physical modalities, exercise,CAM, injections, and surgical interventions.

SUMMARY POINTS

(1) Pain itself is a barrier to the rehabilitation of surgicaloncology patients (NCCN category 1).

(2) Physical modalities, exercise, complementary med-icine, medications, and surgical interventions canhelp manage pain in most patients (NCCN category2A).

(3) Barriers to pain management include contraindica-tions to certain modalities or exercises, medicationside effects, and financial limitations (NCCN cate-gory 2B).

(4) Attitudinal barriers among clinicians, governmentofficials, and even patients and their families, must beovercome (NCCN category 2B).

REFERENCES

1. Silver JK: Chronic pain and the family. Cambridge: HarvardUniversity Press; 2004; p. 10.

2. Apfelbaum JL, Chen C, Mehta SS, et al.: Postoperative painexperience: Results from a national survey suggest postoperativepain continues to be undermanaged. Anesth Analg 2003;97:534–540.

3. Cherny NI, Portenoy RK: The management of cancer pain. CACancer J Clin 2000;44:262–303.

4. Johanson GA: Symptom character and prevalence duringcancer patients’ last days of life. Am J Hosp Palliat Care 1991;8:6–8, 18.

5. Bonica JJ, Ventafridda V, Twycross RG: Cancer pain. In: BonicaJJ, editor. The Management of Pain, ed. 2. Philadelphia: Lea &Febiger; 1990; pp 400–460.

6. Coyle N, Adelhardt J, Foley KM, et al.: Character of terminalillness in the advanced cancer patient: Pain and other symptomsduring last four weeks of life. J Pain SymptomManag 1990;5:83–93.

7. Portenoy RK, Miransky J, Thaler HT, et al.: Pain in ambulatorypatients with lung or colon cancer: Prevalence, characteristics,and effect. Cancer 1992;70:1616–1624.

8. Twycross RG, Fairfield S: Pain in far-advanced cancer. Pain1982;14:303–310.

9. Brescia FJ, Adler D, Gray G, et al.: Hospitalized advanced cancerpatients: A profile. J Pain Symptom Manage 1990;5:221–227.

10. Ventafridda V, Ripamonti C, De Conno F, et al.: Symptomprevalence and control during cancer patients’ last days of life.J Palliat Care 1990;6:7–11.

11. Massie MJ, Holland JC: The cancer patient with pain: Psychiatriccomplications and their management. Med Clin North Am1987;71:243–258.

12. Cheville AL: Pain management in cancer rehabilitation. ArchPhys Med Rehabil 2001;82:S84–S87.

13. VanWilgen CP, Dijkstra PU, van der Laan BFAM, et al.: Shouldercomplaints after nerve sparing neck dissections. Int J OralMaxillofac Surg 2004;33:253–257.

14. Chang HM: Cancer pain management. Med Clin North Am1999;83:711–736.

15. Tishelman C, Degner LF, Rudman A, et al.: Symptoms in patientswith lung carcinoma. Cancer 2005;104:2013–2021.

16. Rustoen T, Fossa SD, Skarstein J, et al.: The impact ofdemographic and disease-specific variables on pain in cancerpatients. J Pain Symptom Manage 2003;26:696–704.

17. Talbot M, Turcotte RE, Isler M, et al.: Function and health statusin surgically treated bone metastases. Clin Orthop Relat Res2005;438:215–220.

18. Wang XS, Cleeland CS, Mendoza TR, et al.: The effects of painseverity on health-related quality of life. Cancer 1999;86:1848–1855.

19. Meuser T, Pietruck C, Radbruch L, et al.: Symptoms duringcancer pain treatment following WHO-guidelines: A longitudinalfollow-up study of symptom prevalence, severity and etiology.Pain 2001;93:247–257.

20. Lucas LK, Lipman AG: Recent advances in pharmacotherapy forcancer pain management. Cancer Pract 2002;10:S14–S20.

21. Przewlocki R, Przewlocka B: Opioids in chronic pain. Eur JPharmacol 2001;429:79–91.

22. Reid CM, Martin RM, Sterne JA, et al.: Oxycodone for cancerrelated pain: Meta-analysis of randomized control trials. ArchIntern Med 2006;166:837–843.

23. Marinangeli F, Ciccozzi A, Leonardis M, et al.: Use of strongopioids in advanced cancer pain: A randomized trial. J PainSymptom Manage 2004;27:409–416.

24. Zech DF, Grond S, Lynch J, et al.: Validation of World HealthOrganization Guidelines for cancer pain relief: A 10-yearprospective study. Pain 1995;63:65–76.

25. Walsh D: Advances in opioid therapy and formulations. SupportCare Cancer 2005;13:138–144.

26. Hanks GW, Nugent M, Higgs CM, et al.: OTFC MulticentreStudy Group. Oral transmucosal fentanyl citrate in the manage-ment of breakthrough pain in cancer: An open, multi-centre,dose-titration and long-term use study. Palliat Med 2004;18:698–704.

27. Smith TJ, Staats PS, Deer T, et al.: Implantable DrugDelivery Systems Study Group. Randomized clinical trial of animplantable drug delivery system compared with comprehensivemedical management for refractory cancer pain: Impact on pain,drug-related toxicity, and survival. J Clin Oncol 2002;20:4040–4049.

28. Watkins T, Maxeiner A: Musculoskeletal effects of ovarian cancerand treatment: A physical therapy perspective. Rehabil Oncol2003;21:12–17.

29. McTiernan A: Physical activity after cancer: Physiologic out-comes. Cancer Invest 2004;22:68–81.

30. Lee I-M: Physical activity and cancer prevention—Data fromepidemiologic studies. Med Sci Sports Exerc 2003;35:1823–1827.

31. Courneya KS: Exercise in cancer survivors: An overview ofresearch. Med Sci Sports Exerc 2003;35:1846–1852.

32. Westerlind KC: Physical activity and cancer prevention—Mechanisms. Med Sci Sports Exerc 2003;35:1834–1840.

33. Chlebowski RT, Aiello E, McTiernan A: The potential for weightloss in breast cancer management. J Clin Oncol 2002;20:1128–1143.



34. Fairey AS, Courneya KS, Field CJ, et al.: Physical exercise andimmune system function in cancer survivors. Cancer 2002;94:539–551.

35. Eisenberg DM, Kessler RC, Foster C, et al.: Unconventionalmedicine in the United States. Prevalence, costs, and patterns ofuse. N Engl J Med 1993;328:246–252.

36. Weiger WA, Smith M, Boon H, et al.: Advising patients who seekcomplementary and alternative medical therapies for cancer. AnnIntern Med 2002;137:889–903.

37. Benedetti C, Brock C, Cleeland C, et al.: NCCN practiceguidelines for cancer pain. Oncology 2000;14:135–150.

38. Burton AW, Reddy SK, Shah HN, et al.: Percutaneousvertebroplasty—A technique to treat refractory spinal pain inthe setting of advanced metastatic cancer: A case series. J PainSymptom Manage 2005;30:87–95.

39. Meyerson BA: Neurosurgical approaches to pain treatment. ActaAnesthesiol Scand 2001;45:1108–1113.

40. Cheville AL: Pain management in cancer rehabilitation. ArchPhys Med Rehabil 2001;82:S84–S87.

41. Turk DC, Monarch ES, Williams AD: Cancer patients in pain:Considerations for assessing the whole person. Hematol OncolClin North Am 2002;16:511–525.

42. Juarez G, Cullinane CA, Borneman T, et al.: Management of painand nausea in outpatient surgery. Pain Manag Nurs 2005;6:175–181.

43. Kim MC, Kim KH, Kim HH, et al.: Comparison of laparoscopy-assisted by conventional open distal gastrectomy and extraper-igastric lymph node dissection in early gastric cancer. J SurgOncol 2005;91:90–94.

44. Marchettini P, Formaglio F, Lacerenza M: Iatrogenic painfulneuropathic complications of surgery in cancer. Acta Anaesthe-siol Scand 2001;45:1090–1094.

45. Cavaliere R, Schiff D: Neurologic toxicities of cancer therapies.Curr Neurol Neurosci Rep 2006;6:218–226.

46. Zech DF, Grond S, Lynch J, et al.: Validation of World HealthOrganization Guidelines for cancer pain relief: A 10-yearprospective study. Pain 1995;63:65–76.

47. Centeno C, Sanz A, Bruera E: Delirium in advanced cancerpatients. Palliat Med 2004;18:184–194.

48. Lawlor PG: The panorama of opioid-related cognitive dysfunc-tion in patients with cancer: Pa critical literature appraisal. Cancer2002;94:1836–1853.

49. Leppert W, Luczak J: The role of tramadol in cancer paintreatment—A review. Support Care Cancer 2005;13:5–17. Epub2004 Nov 18.

50. Morita T, Takigawa C, Onishi H, et al.: Japan Pain, Rehabilitation,PalliativeMedicine, and Psycho-Oncology (PRPP) Study Group.Opioid rotation from morphine to fentanyl in delirious cancerpatients: An open-label trial. J Pain Symptom Manage 2005;30:96–103.

51. Hanna A, Sledge G, Mayer ML, et al.: A phase II study ofmethylphenidate for the treatment of fatigue. Support CareCancer 2006;14:210–215. Epub 2005.

52. Slatkin NE, Rhiner M: Treatment of opiate-related sedation:Utility of the cholinesterase inhibitors. J Support Oncol 2003;53–63.

53. Mazzocato C, Stiefel F, Buclin T, et al.: Psychopharmacology insupportive care of cancer: A review for the clinician: II.Neuroleptics. Support Care Cancer 2000; 89–97.

54. De Schepper HU, Cremonini F, Park MI, et al.: Opioids and thegut: Pharmacology and current clinical experience. Neurogas-troenterol Motil 2004;16:383–394.

55. Agra Y, Sacristan A, Gonzalez M, et al.: Efficacy of senna versuslactulose in terminal cancer patients treated with opioids. J PainSymptom Manage 1998;15:1–7.

56. Wirz S, Klaschik E: Management of constipation in palliative carepatients undergoing opioid therapy: Is polyethylene glycol anoption? Am J Hosp Palliat Care 2005;22:375–381.

57. Kurz A, Sessler DI: Opioid-induced bowel dysfunction: Patho-physiology and potential new therapies. Drugs 2003;63:649–671.

58. Van Seventer R, Smit JM, Schipper RM, et al.: Comparison ofTTS-fentanyl with sustained-release oral morphine in thetreatment of patients not using opioids for mild-to-moderatepain. Curr Med Res Opin 2003;19:457–469.

59. FDA Consum. Warning on fentanyl patch FDA Consum 2005;39:4.

60. Wiffen P, Collins S, McQuay H, et al.: Anticonvulsant drugs foracute and chronic pain. Cochrane Database Syst Rev 2005;CD001133.

61. Abernethy AP, Samsa GP, Matchar DB: A clinical decision andeconomic analysis model of cancer pain management. Am JManag Care 2003;9:651–664.

62. Green Cr,Ndao-Brumbley SK, West B, et al.: Differences inprescription opioid analgesic availability: Comparing minorityand white pharmacies across Michigan. J Pain 2005;6:689–699.

63. Peretti-Watel P, Bendiane MK, Obadia Y, et al.: The South-Eastern France Palliative Care Group. The prescription of opioidanalgesics to terminal cancer patients: Impact of physicians’general attitudes and contextual factors. Palliat Support Care2003;1:345–352.

64. Furstenberg CT, Ahles TA, Whedon MB, et al.: Knowledge andattitudes of health-care providers toward cancer pain manage-ment: A comparison of physicians, nurses, and pharmacists in thestate of New Hampshire. J Pain Symptom Manage 1998;15:335–349.

65. Von Roenn JH, Cleeland CS, Gonin R, et al.: Physician attitudesand practice in cancer pain management. A survey from theEastern Cooperative Oncology Group. Ann Intern Med 1993;119:121–126.

66. Dahl JL: How to reduce fears of legal/regulatory scrutiny inmanaging pain in cancer patients. J Support Oncol 2005;3:384–388.

67. Cella DF, Tulsky DS, Gray G, et al.: The functional assessment ofcancer therapy scale: Development and validation of the generalmeasure. J Clin Oncol 1993;11:570–579.

68. Coscarelli Schag CA, Heinrich RL: Development of a compre-hensive quality of life measurement tool: CARES. Oncology1990;4:135–138.

69. Coscarelli Schag CA, Ganz PA, Heinrich RL: Cancer rehabilita-tion evaluation system—Short form (CARES-SF). Cancer1991;68:1406–1413.

70. Spitzer WO, Dobson AJ, Hall J, et al.: Measuring the quality oflife of cancer patients: A concise QL index for use by physicians.J Chron Dis 1981;34:585–597.

71. Watt-Watson JH, Graydon JE: Sickness impact profile: A measureof dysfunction with chronic pain patients. J Pain Sympt Mgmt1989;4:152–156.

72. Bardsley MJ, Astell S, McCallum A, et al.: The performance ofthree measures of health status in an outpatient diabetespopulation. Diabet Med 1993;10:619–626.

73. Hays RD, Sherbourne CD, Mazel RM, The RAND: 36-itemhealth survey 1.0. Health Econ 1993;2:217–227.

74. Aaronson NK, Bullinger M, Ahmedzai S: A modular approach toquality of life assessment in cancer clinical trials. Recent ResultsCancer Res 1988;111:231–249.

75. Aaronson NK, Ahmedzai S, Bergman B, et al.: TheEuropean organisation for research and treatment of cancerQLQ-C30: A quality-of-life instrument for use in internationalclinical trials in oncology. J Natl Cancer Inst 1993;85:365–376.

76. Watson M, Law M, Maguire GP, et al.: Further developmentof a quality of life measure for cancer patients: TheRotterdam symptom checklist (revised). Psycho-Oncol 1992;1:35–44.



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