Vol. 39 No. 4 April 2010 Journal of Pain and Symptom Management e1

Letters

Management of Treatment-RelatedIntermittent Partial Small BowelObstruction: The Use of Octreotide

To the Editor:We submit to you the following case and

brief discussion intended to outline a possiblerole for the independent use of octreotide inthe setting of cancer treatment-related inter-mittent bowel obstruction. In addition, andof great significance in the setting of cancersurvivorship, we identify an innovative aspectto the symbiotic partnership between the fieldsof palliative care and oncology.

Case

At the age of 40 years, after having lived withsevere endometriosis for many years, the patientunderwent a total abdominal hysterectomy-bilateral salpingo-oophorectomy. During rou-tine follow-up 14 years after the surgery, a largepelvic mass was discovered and subsequently de-termined to be a Grade 2 endometrioid adeno-carcinoma of the vagina. It was hypothesizedthat the mass originated from an endometrioidnodule in the vagina, and a low anterior surgicalresection was felt to be the most appropriate in-tervention. Postoperatively, the patient received45 Gy in 25 fractions of radiation to the pelvisand 550 cGy in two fractions of high-dose-ratebrachytherapy to the vaginal vault. Two yearspost-treatment, follow-up imaging studies re-ported no evidence of residual, recurrent, oractive disease.

Two-and-a-half years after the end of her can-cer treatment, the patient began to experiencea cyclical pattern of abdominal symptoms, con-sisting of pain, distension, nausea, vomiting,and obstipation. On multiple occasions,

� 2010 U.S. Cancer Pain Relief CommitteePublished by Elsevier Inc. All rights reserved.

symptom severity led to an emergency depart-ment visit, and on two occasions, within a six-month period, she required hospitalization.Imaging obtained during each admission con-firmed a moderate-grade small bowel obstruc-tion but no associated mass. This led to theopinion that postsurgical and/or postradiationadhesions were likely to be the underlying cause.During both admissions, the patient’s symptomsresolved with conservative management alone,consisting of nasogastric (NG) tube place-ment/suction and intravenous hydration. Ofnote, her hospital stays were five days and twoweeks in length. Follow-up colonoscopy was un-remarkable; specifically, no sign of anastomoticstricture was found.

The cycle of symptoms the patient was experi-encing progressively increased in both severityand frequency over the subsequent ninemonths. Under the guidance of a clinical nutri-tion specialist, major dietary changes proved tobe of no benefit, and on a daily basis, she wasable to take in only small amounts of a nutri-tional supplement. The patient had not eatensolid food for a year and had not been able toreturn to work. Nearly four years post-cancertreatment, magnetic resonance imaging of theabdomen and pelvis confirmed ‘‘subtle thicken-ing of rectal wall likely from chronic changes ofprior radiation treatment’’ and ‘‘neither evi-dence of obstruction nor of recurrent disease.’’As a result, surgical intervention was consideredthe only possible long-term management strat-egy for her intermittent obstructive symptoms.As a final effort to explore medical manage-ment of her symptoms, and despite havingcured disease, the patient’s radiation oncologistreferred her to palliative care for an assessment.

The patient was first seen by a palliative carespecialist 11 months after her initial admissionfor bowel obstruction. The pattern of hersymptoms was as follows: Day 1, severe

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e2 Vol. 39 No. 4 April 2010Letters

diarrhea; Day 2, abdominal pain and disten-sion with no passage of stool; Day 3, progres-sive increase in pain and distension; and Day4, severe vomiting, which persisted for one totwo days. The patient would remain symptomfree for at most two days before the cyclebegan again.

Despite a lack of evidence for the efficacy ofoctreotide in the setting of nonmalignantbowel obstruction (NMBO), it was felt thatthe clear evidence for its efficacy in the malig-nant bowel obstruction (MBO) populationwarranted a trial for this profoundly symptom-atic patient. She was instructed and taught tosubcutaneously administer 300 mg of octreo-tide three times daily at the first sign of symp-tom onset. Given the pattern of her symptoms,it was agreed that she would continue theinjections for a five-day course.

Within four weeks, the patient had improveddramatically, having experienced an onset ofonly two symptom cycles, each significantly lesssevere than previous. Four months after the in-troduction of octreotide and with minor doseadjustments, she established the routine ofa five-day course of octreotide 200 mg twice daily,initiated at symptom onset. This is required ap-proximately once per month, and the patientremains symptom free in the interim threeweeks. While taking the octreotide, no sideeffects are experienced, and with this interven-tion, she is now able to eat a full diet, has gained8 pounds, and has returned to work.

Comment

Regardless of the underlying etiology, an ob-struction of the bowel results in accumulationof ingested fluids, digestive secretions, and intes-tinal gas. In response to the subsequent luminaldistension, the secretion of several gastrointesti-nal hormones mediates a further increase inthe accumulation of water and electrolytes.1

Ongoing peristaltic activity leads to a cycle ofdistension-secretion-motor activity and a self-perpetuating worsening of the clinical condition.

In 1992, case reports addressing medicalmanagement of MBO first suggested a possiblerole for octreotide.2 Clear evidence of the use ofthis medication now exists in the MBO setting,as it is has been found to improve both survivaland symptom management of patients with

advanced cancer.3,4 Administration of octreo-tide, a synthetic analog of somatostatin, resultsin a reduction of gastric and intestinal secre-tions, a slowing of intestinal motility, and areduction of splanchnic blood flow.5 At theintracellular level, octreotide acts at theinterstitial epithelium to decrease secretion ofwater, sodium, and chloride, and improve bothion and water absorption.6 These effects may beattributed to the inhibition of vasoactive intesti-nal peptide, a gastrointestinal hormone knownto have increased levels in patients with anyform of bowel obstruction.7 Peak plasma con-centration of octreotide occurs 30 minutes afteradministration, and its duration of action canbe up to 12 hours. The medication is particu-larly well tolerated and causes rare side effects,such as diarrhea, nausea, and biliary sludge.8

Long-acting formulations are now availableand administered as monthly intramuscularinjections.9

In contrast to MBO, a few reports haveaddressed the efficacy of medical interventionsin the management of NMBO. As outlined ina recently published set of management guide-lines, only water-soluble contrast has been foundto have Level 2 evidence for its role in improvingthe bowel function of NMBO patients.10 Noother medical therapy is addressed in the report.Only one randomized controlled trial has exam-ined octreotide and its use in the setting ofNMBO management. Comparing a controlgroup of patients receiving conservative therapyalone (NG suction and fluid replacement) witha treatment group receiving a combination ofboth water-soluble contrast and octreotide,Zhang et al. reported the time to resolution ofobstructive symptoms to be significantly less inthe treatment group.11 Given its mechanism ofaction, the authors propose octreotide as beingresponsible for the rapid effect.

To our knowledge, this is the first case reportsuggesting a possible independent role for oc-treotide in the prophylaxis and/or managementof post-cancer treatment/adhesion-related in-termittent partial bowel obstruction. Given thepatient population, most of the studies examin-ing the medical and symptom management ofMBO patients are found in the palliative careliterature. As targeted cancer therapies improve,complex clinical syndromes related to survivor-ship are becoming increasingly common. Inaddition to identifying a possible independent

Vol. 39 No. 4 April 2010 e3Letters

role for octreotide in the management ofNMBO, this case also highlights the unique rolepalliative care expertise may play in supportingthe management of complex clinical conditionsassociated with cancer survivorship.

Jeff Myers, MD, CCFP, MSEdAnoo Tamber, MD, CCFPMacey Farhadian, RNOdette Cancer CentreSunnybrook Health Sciences CentreToronto, Ontario, Canada

doi:10.1016/j.jpainsymman.2009.11.309

References1. Mercadante S. Assessment and management of

mechanical bowel obstruction. In: Portenoy RK,Bruera E, eds, Topics in palliative care, vol. 1. NewYork, NY: Oxford University Press, 1997. p. 13e16.

2. Mercadante S, Maddaloni S. Octreotide in themanagement of inoperable gastrointestinal obstruc-tion in terminal cancer patients. J Pain SymptomManage 1992;7:496e498.

3. Cascinu S, Del Ferro E, Catalano G. A rando-mised trial of octreotide vs best supportive care onlyin advanced gastrointestinal cancer patients refrac-tory to chemotherapy. Br J Cancer 1995;71:97e101.

4. Ripamonti CI, Easson AM, Gerdes H. Manage-ment of malignant bowel obstruction. Eur J Cancer2008;44:1105e1115.

5. Neville R, Fielding P, Cambria RP, Modin I. Vas-cular responsiveness in obstructed gut. Dis ColonRectum 1991;34:229e235.

6. Nellgard P, Bojo L, Cassuto J. Importance of va-soactive intestinal peptide and somatostatin forfluid losses in small-bowel obstruction. Scand J Gas-troenterol 1995;30:464e469.

7. Basson MD, Fielding LP, Bilchik AJ, et al. Doesvasoactive intestinal polypeptide mediate the patho-physiology of bowel obstruction? Am J Surg 1989;157:109e115.

8. Reichlin S. Somatostatin. N Engl J Med 1983;309:1495e1501.

9. Matulonis UA, Seiden MV, Roche M, et al.Long-acting octreotide for the treatment and symp-tomatic relief of bowel obstruction in advancedovarian cancer. J Pain Symptom Manage 2005;30:563e569.

10. Diaz JJ Jr, Bokhari F, Mowery NT, Acosta JA,Block EF. Guidelines for management of smallbowel obstruction. J Trauma 2008;64:1651e1664.

11. Zhang Y, Gao Y, Ma Q, et al. Randomised clini-cal trial investigating the effects of combined ad-ministration of octreotide and methylglucaminediatrizoate in the older persons with adhesive smallbowel obstruction. Dig Liver Dis 2006;38:188e194.

Effectiveness of Mirtazapinein the Treatment of PostherpeticNeuralgia

To the Editor:Mirtazapine is described as a noradrenergic

and specific serotonergic antidepressant, indi-cated for the treatment of all types of depressiveillnesses. It is a potent serotonin2 (5-HT2), sero-tonin3 (5-HT3), and central a2-adrenergicreceptor antagonist.1,2 Some studies havereported the efficacy of mirtazapine in patientswith chronic or recurrent pain symptoms, suchas chronic tension-type headache, migraineheadache, and cluster headaches.3e5 Further-more, an open-label pilot study suggested thatmirtazapine (15e30 mg/day) may be effectivefor reducing pain and other unpleasant symp-toms in cancer patients.6 A case series in whichmirtazapine (15e30 mg/day) was used in 29 pa-tients suffering from fibromyalgia syndromehad promising results.7 A recent study suggestedthat repeated administration of mirtazapine(20e30 mg/kg) can improve the mechanicaland thermal hyperalgesia/allodynia producedby nerve transection in a rat model of neuro-pathic pain.8 Together, these data suggest thatmirtazapine has analgesic effects and may alsohave a potential beneficial effect in the treat-ment of patients with chronic pain and concom-itant depression.9 The most common sideeffects of mirtazapine are drowsiness, sedation,increased appetite, and weight gain.10 In theproduct monograph, edema and peripheraledema are reported to occur in 1%e2% ofpatients receiving mirtazapine.11

The role of antidepressant medication inthe treatment of neuropathic pain, includingpostherpetic neuralgia (PHN) and diabeticneuropathy, is established.12 There have beenno reports of benefit from mirtazapine inPHN. We present the case of a woman receiv-ing mirtazapine, who, on initiation of treat-ment, had a total remission of PHN. Lateron, she developed bilateral ankle edema, andthe drug was stopped. After mirtazapine cessa-tion, the neuralgia returned.

Case

A 54-year-old woman, married, with twochildren, presented to the outpatient clinic