Curr Probl Cancer 37 (2013) 266272

Contents lists available at ScienceDirect

Curr Probl Cancer

journal homepage: www.elsevier.com/locate/cpcancer

Pain management and palliative care in

pancreatic cancer
Michael A. Erdek, MD, Lauren M. King, ANP-BC, ACHPN,
Susannah G. Ellsworth, MD

Pain medicine
Pharmacologic
Successful treatment of pain associated with pancreatic cancer begins with obtaining a
comprehensive pain-directed history and physical examination. Pain intensity is typically graded
on an 11-point scale ranging from 0-10, with 0 equaling no pain and 10 equaling the worst pain
imaginable. When assessed verbally by patient report, this is properly referred to as a numerical
rating scale. When assessed with a 10-cm card with no gradations where the patient points to
the level of his or her pain, this is referred to as a visual analog scale. Additional important
information to be garnered by the practitioner includes pain location, duration, temporal nature
(constant vs intermittent), exacerbating and alleviating factors, pain medication consumption,
and adverse effects related to pain medication.
Opioids are considered to be the rst-line medical therapy for visceral cancer pain, including
pain from cancer of the pancreas.1 Treatment is typically started with short-acting opioids such
as oxycodone or morphine, taken on an as-needed basis by patients with pain that is largely
intermittent and episodic. Once a patient's pain becomes continuous or when pain interferes
with the ability to sleep, institution of a long-acting, sustained-release opioid is appropriate.
Special consideration may be given to the use of methadone, the N-methyl-d-aspartate
antagonist properties of which may provide specic value in patients whose pain has a
neuropathic component. However, the long and unpredictable half-life of this agent and its
multiple drug-drug interactions necessitate particular expertise with regard to its dosing and
administration.2
Opioids are a double-edge sword in that their substantial pain-relieving properties must be
employed, balancing their considerable potential for signicant side effects. Common doselimiting side effects of opioids include sedation and cognitive impairment, pruritus, nausea,
constipation, and respiratory depression. The prescription of a stool softener concomitant with
these medications is of great importance.
Although opioids are the primary pharmacologic means of pain control, there may be a role
for certain adjuvant medications. Nonsteroidal anti-inammatory drugs are benecial in
0147-0272/$ - see front matter & 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.currproblcancer.2013.10.003

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

267

providing an opioid-sparing effect. The additional use of antineuropathic pain agents such as
membrane stabilizers or neurotransmitter reuptake inhibition agents may be of value in patients
with nerve involvement of the tumor and resultant neuropathic pain.

Interventional
For patients whose pain is refractory to opioids or who develop dose-limiting side effects
from opioids, a block of the celiac plexus with local anesthetic is often employed. Celiac plexus
neurolysis (CPN), a nerve destructive procedure, may follow, depending on the result of the local
anesthetic block. Neurolysis typically lasts for several months and is carried out with an agent
such as alcohol or phenol. This procedure targets the sympathetic ganglion that subserves the
upper gastrointestinal tract, including the pancreas, based on the rationale that the visceral
afferent bers travel with the sympathetic efferent nerve bers. The celiac ganglion is made up
of the greater, lesser, and least sympathetic nerves that traverse the diaphragmatic crura to
ultimately coalesce at the level of the celiac trunk.3 The diagnostic block is typically carried out
with bupivacaine or a combination of lidocaine and bupivacaine. If neurolysis is elected, alcohol
in a concentration of 50%-100% or phenol usually in a concentration of 10% is employed.4
Multiple studies have demonstrated the success of this procedure for pancreatic cancer pain.
Particularly evident has been the benet in both pain intensity and quality of life (QOL) for
patients who underwent the procedure.5 Additionally, predictors of successful outcome from
CPN have been assessed. Patients receiving lower doses of systemic opioids at the time of the
procedure, as well as those undergoing the procedure in the absence of sedation, have been
found to be more likely to achieve positive outcomes.6
Patients who undergo CPN and ultimately have recurrence of their pain may undergo a
repeat procedure. Success rate tends to be lower in such instances, and mean duration of pain
relief has been shown to be less than half of that of an initial CPN, usually in the face of disease
progression as established on radiographic imaging.7
Side effects and complications have been described in CPN. While orthostatic hypotension
due to vasodilation and diarrhea due to unopposed parasympathetic tone are seen with
sympathectomy, side effects such as alcohol intoxication, seizure, pneumothorax, incontinence,
nerve damage, and even paralysis have also been described.8 It is strongly recommended that an
experienced pain practitioner is consulted in the undertaking of this procedure.
Patients affected with who are not aided by standard pharmacologic or block therapy may be
considered candidates for intrathecal drug delivery.9 A temporary, percutaneous catheter is
often placed to assess response and help ascertain appropriate dosing of opioids and potential
agents such as local anesthetics, alpha-blockers, and calcium channel blockers. If successful, the
patient is ultimately surgically treated with an implantable pump and catheter system,
delivering analgesic agents directly into the central nervous system and bypassing systemic
administration and its inherent limitations of effect and toxicity.

Radiation therapy
Treatment paradigms for patients with locally advanced pancreatic cancer (LAPC) are
changing rapidly as options for systemic treatment increase both in number and in efcacy.10,11
Early cooperative group studies suggested that concurrent chemoradiation is likely more
effective than radiation alone in patients with LAPC.12 However, subsequent randomized trials of
chemoradiation vs chemotherapy alone in this population have generated mixed results, even
when intensied chemoradiation regimens are used.13-15 This may be because of high rates of
occult metastatic disease at the time of diagnosis in patients with LAPC. Although most patients
with pancreatic cancer die of metastatic disease, local failure is still fairly common, even in
patients who have undergone surgical resection in addition to adjuvant therapy.16-18

268

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

Chemoradiation
Current standards therefore recommend that patients begin treatment with chemotherapy
alone and receive radiation therapy only if there is no evidence of distant progression after a few
months of chemotherapy and restaging. This approach theoretically selects out patients with
treatment-refractory metastatic disease who are least likely to benet from aggressive attempts
at local control of the tumor. In the largest single-institution study to date investigating the use
of induction chemotherapy to select patients without distant metastatic disease, who
presumably would be most likely to benet from chemoradiation therapy, Krishnan et al.19
demonstrated better overall and progression-free survival in patients who received induction
chemotherapy followed by chemoradiation as compared with those who received up-front
chemoradiation. At a dose of 30 Gy in 10 fractions, local control was achieved in 53% of patients
in the up-front chemoradiation group and in 59% of patients in the induction chemotherapy
group. However, no data on control of pain or other symptoms were provided, and it is by no
means clear that radiographic disease control is correlated with symptom control.

Symptom control
Few studies provide direct guidance regarding the optimal management of patients with
severe symptoms related to an uncontrolled primary tumor (regardless of whether or not
metastatic disease is present). In these cases, local treatments like radiation may be able to
control troublesome symptoms such as pain, biliary obstruction, or gastric outlet or duodenal
obstruction. To date, only 1 clinical trial in LAPC has specied pain control as a study end point.
This was a small randomized study from Taiwan; it demonstrated higher rates of pain control
(39% vs 6%) in patients who received gemcitabine-RT (50.4-61.2 Gy) compared with 5-FU-RT.20
The results of this study are somewhat difcult to interpret given the small sample size of 34
patients and the fact that outcomes in the 5-FU group were signicantly worse than would be
expected based on historical data. Another study conducted by the Eastern Cooperative
Oncology Group compared gemcitabine alone to gemcitabine plus radiation therapy (1 cycle of
gemcitabine followed by combination gemcitabine-RT to a total dose of 50.4 Gy) and attempted
to evaluate QOL outcomes.14 The overall survival was 11.1 months in the chemoradiation arm
and 9.2 months in the gemcitabine-alone arm, a difference that was statistically signicant. Pain
control was not a study end point. Health-related QOL declined similarly in both groups during
treatment. The results of this study must be interpreted with caution as it was closed early
because of slow accrual and QOL data may have been biased by patient attrition.
Chemoradiation has also been compared with best supportive care (with no antineoplastic
therapy) in a small randomized trial conducted in Japan.21 The study enrolled 31 patients, 16 of
whom were randomized to 5-FU-based chemoradiation and 15 of whom received supportive
care. Ten patients had pain before starting treatment, 8 of whom had improvement in pain after
treatment. The median duration of pain control was 5.2 months. Although this study is unlikely
to be replicated in the current era, it does support the use of radiation to control pain caused by
pancreatic cancer in patients with locally advanced disease.
In selected patients, salvage reirradiation with hypofractionated stereotactic body radiation
therapy may be an option, as suggested by a recent retrospective series.22 Median radiation dose
was 25 Gy (given in 5 fractions) prescribed to gross tumor alone (plus a small margin). Although
the number of patients treated was fairly small at 18, the rate of pain control among patients
with pain at baseline was 57%. Therapy was well tolerated with no acute grade 3 toxicity and a
single episode of late grade 3 late toxicity (small bowel obstruction).
In summary, the (albeit limited) available evidence suggests that radiation is a potentially
effective option for symptom palliation in patients with pancreatic cancer. The expected
response rate is probably between 40% and 80%. As rates of acute treatment-related toxicity are
fairly low with the use of modern radiation techniques including intensity-modulated radiation
therapy and stereotactic body radiation therapy,23,24 radiation therapy should be considered as a

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

269

palliative option in patients whose pain is not adequately controlled by optimal medical
management or interventional procedures such as celiac block or both. Further studies are
needed to better quantify the expected clinical benet of radiation therapy in this setting,
particularly in terms of pain control, which should be considered for use as a secondary end
point in clinical trials of radiation therapy among patients with pancreatic cancer.

Palliative care
Pancreatic cancer disease and treatment can cause many physical and emotional challenges.
Palliative medicine's goal is to relieve suffering and to improve QOL by addressing each patient's
specic needs. Control of pain and non-pain symptoms, clear and effective communication, and
addressing psychosocial needs are pillars of palliative care. These services can be provided
concurrently with regular oncologic care to aid both patients and providers in choosing
therapies consistent with patients' health care goals and to address any physical-psychosocialspiritual needs. Palliative care should be offered upon diagnosis, given the poor relative survival
rate and the symptom prole associated with pancreatic malignancies.
Some burdensome physical symptoms of pancreatic cancer include pain, depression, anxiety,
weight loss, malabsorption, nausea, vomiting, pruritus, and jaundice. Psychosocial consequences
of a cancer diagnosis can enhance physical symptoms and negatively affect QOL. Conversely,
controlling physical symptoms can allow for a person to concentrate on dening their social and
cultural identity in the context of serious illness, working through unresolved issues, nishing
legacy work, and addressing their spiritual needs. Owing to a shortage of palliative care
specialists within many communities, it is essential that all oncologists acquire primary
palliative care skills: basic communication techniques and management of common symptoms.
Communication
Cancer generates a greater sense of dread than other life-threatening illnesses with similar
prognoses.25 Being aware of and recognizing psychosocial burdens may allow for emotional
growth and ease distress. Open, honest communication during the entire course of a disease
trajectory is paramount (Table). In a study conducted in Canada, 90% of family members reported
that it was very important to complete critical and desired tasks, resolve conicts, and say their
goodbyes toward the end of the patient's life.26 Having open discussions about prognosis,
advance care planning, and preference of treatments allow patients and families to complete
these critical tasks before the end of life. These conversations often cannot be fully addressed in
a single clinic visit and needs to be an on-going discussion. Giving people time to process the
information, as well as encouraging them to record questions for future visits, can allow for
adequate family planning and identication of psychosocial needs.
According to patients, family members, and health care providers, goals for communication
at the end of life include talking in an honest and straightforward way, being willing to talk
Table
Seven steps allow successful communication, a key concept to ensure emotional
growth and the ease of distress throughout palliative care in patients with cancer.28
7-Step approach to communication
1.
2.
3.
4.
5.
6.
7.

Prepare for the discussion

Establish what the patient (and) family knows
Determine how information is to be handled
Deliver the information
Respond to emotions
Establish goals for care and treatment priorities
Establish plan

270

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

about dying, giving bad news in a sensitive way, listening to patients, encouraging questions,
and being responsive to patients' readiness to talk about death.27 Von Guten et al.28 describe a
7-step approach for physicians for structuring communication regarding care at the end of life.
Physicians should (1) prepare for discussions by conrming medical facts and establishing an
appropriate environment, (2) establish what the patient (and family) knows by using openended questions, (3) determine how information is to be handled, (4) deliver the information in
a sensitive but straightforward manner, (5) respond to emotions of the patients and families,
(6) establish goals for care and treatment priorities, and (7) establish an overall plan. These
7 steps can be used when delivering difcult news, discussing advance care planning, managing
conict, eliciting preferences in care, and discussing death.
Clayton et al.29 reported that controlling physical symptoms, providing emotional support,
preserving dignity, exploring realistic goals, and discussing day-to-day living are important to
maintain hope in terminally ill patients with cancer and their families. Asking what one hopes
for and developing a plan to hope for the best but plan for the worst can help patients think
about a limited future and may allow them to focus on what is personally most important to
them. It is not the job of the provider to correct a person's hope for a miracle, instead allow
them an empathetic ear and avoid false reassurances. Perpetuating false hope may prevent the
patient and family from nding meaning and value in the time remaining to them.30 Hoping for
unrealistic goals may prevent reconciliation, nancial planning, emotional growth, resolution,
and closure. A patient may say, I am hoping that my pancreatic cancer will be cured by this
second chemotherapy, and a response could be, I am also hopeful for this, and I am also
interested in other goals that you want to focus on. Acknowledging a patient's hope and
allowing him or her to discuss uncompleted goals or tasks can help the patient identify the need
for future planning. Letting the patient know that one would be there for them throughout this
illness is also paramount as feelings of abandonment near the end of life and transition to
hospice care can exist.
Introducing hospice to a patient or family member can be challenging to a provider.30,31 A
recommendation is to standardize the hospice introduction process to include all patients with
prognosis of 6 months or less rather than waiting until all therapies are exhausted. Normalizing
this informational visit and applying it to a standard of care in practice can help familiarize
patients with hospice services and clarify any misconceptions. Introducing hospice to patients
and family early while relatively healthy can also facilitate transition to hospice in the future as
patients and families already have a basic understanding of its services.

Symptom management
In addition to exercising therapeutic communication, identifying and adequately managing
symptoms common to pancreatic cancer can improve a person's QOL. Two symptoms that are
common in pancreatic cancer are nausea and depression. Furthermore, approximately 40% of
patients with pancreatic cancer have depressive symptoms.32 According to Massie,33 the
prevalence of depression in people with pancreatic cancer ranges from 33%-50%. Symptoms of
clinical depression may include anorexia and weight loss (also common symptoms of cancer),
negative thoughts and behavior, sleep disturbances, anhedonia, fatigue, and feelings of
hopelessness. Depression can be related to psychosocial factors (nancial concerns or emotional
support), medical factors (prognosis or metabolic derangements), and psychological factors
(coping ability or perceptions of illness).34 Treatment of depression requires looking into these
3 factors and identifying any underlying issues. Although no controlled clinical trials evaluate
the efcacy of combined interventions in the pancreatic cancer population, most experts
recommend an approach that combines supportive psychotherapy, patient and family
education, and stimulants or antidepressants or both.35 Chaplains, social workers, and mental
health counselors can help patients work through psychosocial and spiritual challenges. In
choosing an antidepressant, one should target individual symptoms and limit unwanted side
effects. Persons with limited life expectancy can have a trial of methylphenidate starting at

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

271

2.5 mg orally and increased every few days up to a maximum dose of 30 mg. Methylphenidate
has a rapid onset of action and can improve energy, alertness, and weakness.36 When the patient
has a greater life expectancy, selective serotonin reuptake inhibitors are chosen owing to their
limited side-effect prole; however, they may take up to 4-6 weeks to become effective.
During the course of disease, 70%-80% of patients with pancreatic head tumors develop
obstructive jaundice and 10%-20% develop duodenal obstruction.37 Both can cause intractable
nausea and vomiting, which can be difcult to treat owing to the multiple underlying
mechanisms and pathophysiology. Chemotherapy, motility dysfunction, opioids, constipation,
anxiety, and cholangitis are other causes of nausea and vomiting in this population. Nausea and
vomiting cause substantial psychological distress for patients during end of life, with poorly
controlled symptoms contributing to fears of starvation and dehydration.38,39 Evaluation for
metabolic abnormalities, constipation, adverse drug effect, increased tumor burden, and
obstruction is paramount in locating the root causes for symptoms of nausea. Surgical
and endoscopic options for outlet obstructions include biliary drainage, gastrojejunostomy, and
duodenal stenting.
Nasogastric tube decompression can also aid in resolving partial bowel obstructions, with a
motility agent (metoclopramide) and an anticholinergic (glycopyrrolate) to decrease secretions
and colicky pain.40 In appropriate cases, adding dexamethasone can reduce inammation
surrounding the tumor and bowel edema. Additionally, a Japanese multicenter study showed
improved QOL scores and decreased overall symptoms of nausea in 56% of patients treated with
octreotide.41 For nonobstructive nausea and vomiting, Gupta et al.42 developed a literaturebased, single-drug, stepwise protocol to aid in the treatment of nausea and vomiting. The
authors describe excluding reversible causes of nausea, then using metoclopramide or
haloperidol as rst-line treatment, olanzapine or chlorpromazine as second-line therapy, and
ondansetron as third-line nausea therapy.
Ultimately, clinicians build strong relationships with patients with cancer and their families
in the hopes of nding a way through the symptoms and distress, to cope with the illness
experience, and to make each day as good as it can be. Working in a multidisciplinary team
including social work, nursing, and pastoral care can aid this vulnerable cancer group.43
References
1. Wolfgang CL, Herman JM, Laheru DA, et al. Recent progress in pancreatic cancer. CA Cancer J Clin 2013;63:31848.
2. Halpert D, Erdek MA. Pain management for hepatobiliary cancer. Curr Treat Options Oncol 2008;9:23441.
3. Bahn BM, Erdek MA. Celiac plexus block and neurolysis for pancreatic cancer. Curr Pain Headache Rep 2013;17:
31016.
4. Benzon H, Raja S, Fishman S. (eds.) Essentials of Pain Medicine, 3rd ed. Philadelphia: Elsevier; 2011.
5. Wong GY, Schroeder DR, Carns PE, et al. Effect of neurolytic celiac plexus block on pain relief, quality of life, and
survival in patients with unresectable pancreatic cancer. J Am Med Assoc 2004;291:10929.
6. Erdek MA, Halpert DE, Gonzalez-Fernandez M, et al. Assessment of celiac plexus block and neurolysis outcomes and
technique in the management of refractory visceral cancer pain. Pain Med 2010;11:92100.
7. McGreevy K, Hurley RW, Erdek MA, et al. The effectiveness of repeat celiac plexus neurolysis for pancreatic cancer: A
pilot study. Pain Pract 2013;13:8995.
8. Neal JM, Rathmell JP. Complications in Regional Anesthesia and Pain Medicine, 2nd ed. Philadelphia: Lippincott
Williams & Wilkins; 2013.
9. Hameed M, Hameed H, Erdek M. Pain management in pancreatic cancer. Cancers 2011;3:4360.
10. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med
2011;364:181725.
11. von Hoff D, Ervin T, Arena F, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New
Engl J Med 2013;369:1691703.
12. Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: A randomized trial of
high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads plus 5-uorouracil), and high dose
radiation plus 5-uorouracil: The Gastrointestinal Tumor Study Group. Cancer 1981;48(8):170510.
13. Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: Comparison of
combined-modality therapy (chemotherapy plus radiotherapy) to radiotherapy alone. J Natl Cancer Inst 1988;80:
7515.
14. Loehrer PJ, Feng Y, Cardenes H, et al. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with
locally advanced pancreatic cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol 2011;29:410512.
15. Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy,
infusional 5-FU, and intermittent cisplatin) followed by maintenance gemcitabine versus gemcitabine alone for

272

16.
17.
18.
19.
20.
21.

22.

23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.

M.A. Erdek et al. / Curr Probl Cancer 37 (2013) 266272

locally advanced unresectable pancreatic cancer. Denitive results of the 2000-01 FFCD/SFRO study. Ann Oncol
2012;19:15929.
Berger AC, Winter K, Hoffman JP, et al. Five year results of US intergroup/RTOG 9704 with postoperative CA19-9
o 90 U/mL and comparison to the CONKO-001 trial. Int J Radiat Oncol Biol Phys 2012;84:2917.
Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing
curative-intent resection of pancreatic cancer: A randomized controlled trial. J Am Med Assoc 2007;297:26777.
Iacobuzio-Donahue C, Fu B, Yachida S, et al. DPC4 gene status of the primary carcinoma correlates with patterns of
failure in patients with pancreatic cancer. J Clin Oncol 2009;27:180613.
Krishnan S, Rana V, Janjan NA, et al. Induction chemotherapy selects locally advanced unresectable pancreatic cancer
patients for optimal benet from consolidative chemoradiation therapy. Cancer 2007;110:4755.
Li CP, Chao Y, Chi KH, et al. Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer:
Gemcitabine versus 5-uorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys 2003;57:98104.
Shinchi H, Takao S, Noma H, et al. Length and quality of survival after external-beam radiotherapy with concurrent
continuous 5-uorouracil infusion for locally unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 2002;53:
14650.
Wild AT, Hiniker S, Chang DT, et al. Re-irradiation with stereotactic body radiation therapy as a novel treatment
option for isolated local recurrence of pancreatic cancer after multimodality therapy: Experience from two
institutions. J Gastrointest Oncol 2013 [Epub ahead of print]. doi:10.3978/j.issn.2078-6891.2013.044.
Yovino S, Poppe M, Jabbour S, et al. Intensity-modulated radiation therapy signicantly improves acute
gastrointestinal toxicity in pancreatic and ampullary cancers. Int J Radiat Oncol Biol Phys 2011;79:15862.
Schellenberg D, Kim J, Christman-Skieller C, et al. Single-fraction stereotactic radiation therapy and sequential
gemcitabine for the treatment of locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;81(1):1818.
Mishel MH. Reconceptualization of the uncertainty in illness theory. Image J Nurse Sch 1990;22:256.
Heyland DK, Dodek P, Rocker G, et al. What matters most in end-of-life care: Perceptions of seriously ill patients and
their family members. Can Med Assoc J 2006;174:62733.
Enrich W, Curtis JR, Shannon SE, et al. Communicating with dying patients within the spectrum of medical care from
terminal diagnosis to death. Arch Intern Med 2001;161(6):86874.
von Gunten CF, Ferris FD, Emanuel LL. Ensuring competency in end-of-life care: Communication and relational skills.
J Am Med Assoc 2000;284(23):30517.
Clayton JM, Butow PN, Tattersall MH, et al. Fostering coping hope and nurturing hope when discussing the future
with terminally ill cancer patients and their caregivers. Cancer 2005;103:196575.
Casarett DJ, Quill TE. I'm Not Ready for Hospice: Strategies for timely and effective hospice discussions. Ann Intern
Med 2007;146(6):4439.
Shin J, Casarett D. Facilitating hospice discussions: A six-step road map. J Support Oncol 2011;9(3):97102.
Pezzilli R, Campana D, Morselli-Labate AM, et al. Patient-reported outcomes in subjects with neuroendocrine tumors
of the pancreas. World J Gastroenterol 2009;15(40):506773.
Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr 2004;32:5771.
Makrilia N, Indeck B, Syrigos K, et al. Depression and pancreatic cancer: A poorly understood link. JOP 2009;10(1):
6976.
Block SD. Perspectives on care at the close of life. Psychological considerations, growth, and transcendence at the
end of life: The art of the possible. J Am Med Assoc 2001;285:2898905.
Ellison NM, Chevlen E, Still CD, et al. Supportive care for patients with pancreatic adenocarcinoma: Symptom control
and nutrition. Hematol Oncol Clin North Am 2002;16:10521.
Crippa S, Dominguez I, Rodriguez JR, et al. Quality of life in pancreatic cancer: Analysis by stage and treatment.
J Gastrointest Surg 2008;12(5):78393.
Portney RK, Thaler HT, Kornbilth AB, et al. Symptom prevalence, characteristics, and distress in a cancer population.
Qual Life Res 1994;3(3):1839.
McPhee S, Winker M, Rabow M, et al. Care at the close end of life, evidence and experience. Jama Archives and
Journals. United States of America: McGraw Hill; 74.
Davis MP, Furste A. Glycopyrrolate: A useful drug in the palliation of mechanical bowel obstruction. J Pain Symptom
Manage 1999;18(3):1534.
Hisanaga T, Shinjo T, MOrta T, et al. Multicenter prospective study on the efcacy and safety of octreotide for
inoperable malignant bowel obstruction. Jpn J Clin Oncol 2010;40(8):73945.
Gupta M, Davis M, LeGrand S, et al. Nausea and vomiting in advanced cancerThe Cleveland Clinic Protocol.
J Support Oncol 2013;11(1):813.
Pawlik TM, Laheru D, Hruban RH, et al. Evaluating the impact of a single-day multidisciplinary clinic on the
management of pancreatic cancer. Ann Surg Oncol 2008;15(8):20818. [Epub 2008 May 7].