Download document 7872400

Annals of Oncology 10 Suppl. 4: S265-S268, 1999.
© 1999 Kluwer Academic Publishers. Printed in the Netherlands.
Review
Pain management of pancreatic cancer
Ake Andren-Sandberg, Asgaut Viste, Arild Horn, Dag Hoem & Hjortur Gislason
Department of Surgery, Haukeland University Hospital, Bergen, Norway
Summary
Introduction
The majority of patients with exocrine pancreatic cancer
have pain as an initial symptom and most will suffer
significant pain at some stage before they succumb to the
disease [1]. For some patients the pain is so severe that all
waking hours are devoted to its control and the quality of life
is very poor due to the pain. While the disease is rarely
cured, the patients can, at best, be rendered symptom free.
The management of symptoms should, therefore, be of
prime concern in most individuals with pancreatic cancer.
Initially, the cornerstone of pain management is a stepwise
escalation of analgesics, but it is also wise to provide
patients with full information on their condition and its
treatment in order that they themselves may be involved in
the management process. Resectional surgery in those with
severe pain due to cancer seems to be the most logical
treatment and should be considered the first option as it
today can be performed with low morbidity and a mortality
rate of almost zero [2]. However, the indications for
palliative resections as opposed to palliative bypass are still
Key words: analgesics, pain management, quality of life,
splanchnicectomy
not clear. As only about 15 percent of the patients in
unselected series in our part of the world can be resected [3,
4], and as most of the resected patients suffer a recurrence of
their disease [5], palliative care must be given a high
priority.
Although pain is the most feared part of the terminal life of
many patients with cancer, the intensity and the quality of
the pain is often scantly described. In reviews [6,7] pain was
said to be a presenting symptom in 70-90 % of the patients
with pancreatic cancer, and in one series 83 % of 303
consecutive patients presenting with pancreatic or
periampullary cancer had pain at the time of the diagnosis
[8]. However, the characteristics of the pain were not given
[6-8] even though it was stated that the incidence of pain
was not related to the site of the primary lesion, but to the
stage of the disease [8].
Prospective studies
Studies on the natural course of pancreatic cancer and the
Downloaded from http://annonc.oxfordjournals.org/ by guest on September 9, 2014
Quality of life is receiving increasing attention as a criterion for the
assessment of treatment, not least for surgery, in pancreatic cancer.
In exocrine pancreatic cancer there are three main symptoms that
must be dealt with: pain, loss of weight and jaundice. All of them
seriously impair quality of life, but most often pain is the most
feared by the patients. Despite this, the intensity and the quality of
the pain is all too often only scantly described.
In 85 consecutive patients with newly diagnosed pancreatic cancer
we have prospectively registered the quality and quantity of their
pain and correlated it to tumor and patient characteristics. It was
found that about one fourth of the patients were totally pain free
and half of all suffered a pain decribed by two or less on a Visual
Analogue Scale. Only one in ten had severe pain. Although more
and more patients were treated with morphine, it was still about one
third of all patients that had no or only little pain in the last part of
their life. Pain had a strong correlation to survival. This may be due
to secondary effects like depressing the mood of the patient and
reducing the food intake, but is probably more often a reflection of
that generalized cancer induces more pain.
Analgesic drugs are the cornerstone of the pharmacologic
management of pain due to pancreatic cancer. A significant part of
the patients do well with only paracetamol and nonsteroidal
antiinflammatory agents. Combining these agents with narcotic
analgesics can enhance pain control while lessening the dose of
narcotics. A wide range of narcotics are available as well as
different modes for delivery: regular pills, slow release forms,
injections, subcutaneous injections, epidurals etc. Each patient's
pain management should be individualized, based on the intensity
of pain, the type of pain and the side effects. It is essential not only
to describe the medication, but also to follow-up the development
of the pain and the patient's total experience of the situation.
As an alternative to narcotics, plexus celiac blocks have been used
with somewhat different result; in the hands of the experts the
percutaneous approach is usually sufficient, but in the hands of
other also poor results are reported. During the last years
thoracoscopic splanchnicectomy has been tried as a complement
giving long-standing pain relief with little or no side effects in the
majority of patients. With this approach the sympathic fibers lead
by the symphathetic chain and further by the nervus splanchnicus
major, minor and minoris are divided. The denervation is easily
done and can be performed bilaterly in one seance. This method
will probably be used more often as the technique is now well
described.
266
effect of different treatment modalities have most often
focused on survival. Lately, there has been more interest in
the quality of life of these patients [10, 11], but the
discussion has been hampered by the multidimensionality of
quality of life as well as a lack of knowledge of the
importance of different components of sensitive and
functional aspects of day-to-day living. Patients adjust their
expectations of the quality of life according to their
perception of their health and function. However, for
patients with cancer-related pain, controlling pain is the most
critical factor which will improve their life [12]. Therefore
it is important to gather as much information as possible on
the epidemiology, the pathophysiology and the effects of
different options of management of pain.
There are several ways to describe pain in cancer patients.
The best documented is the Visual Analogue Scale, VAS,
which has been shown to be a highly valid and reliable tool
for measuring pain intensity [13, 14], also specifically in
pancreatic cancer patients [15].
Pain per se has a strong correlation with survival in days.
Lillemoe et al [22] performed a prospective, randomized
study of the use of chemical splanchnicectomy in patients
with nonresectable pancreatic cancer. Although their study
confirmed the benefit in treating established pain and in
preventing the development of future back pain, they also
found a longer survival in the well treated patients. The same
was found in the Lund-Bergen study [24]. This may be
explained by a direct correlation between pain and tumor
biology, but more probable the effect is at least partly
indirect. Pain may influence survival by producing a
depressed mood and reducing food intake, and the secondary
effects of analgesic drugs have an influence of on
mobilization, socialization, life expectations, etc.
We have earlier advocated a more standardized reporting of
patients with pancreatic cancer [25]. A plea for uniform
reporting of patient outcome in the treatment of pain in
patients with pancreatic disease was recently made and
proposed: (1) the patient's description of the pain should be
given with a VAS, (2) the use of narcotics should be
quantified, i.e. none, minimal (1-3 times per month),
moderate (daily or weekly), or major (stronger than
moderate), and (3) the quality of life should be assessed
using tools that focus both on the patient's perception of
his/her health status and on the nonmedical aspects of his/her
life [26]. There are also other ways to describe the quality of
life in these patients [27,28], e.g. with EORTC QLQ, which,
however, focus less on pain and more on a global
assessment of the situation for the patient.
Procedures directed against nerves
Pain relief in patients with pancreatic cancer can also be
provided by means of procedures directed against the
afferent nerves that carry the painful stimuli from the
diseased pancreas to the brain. The sympathetic innervation
of the pancreas, including the nerves mediating pain, leaves
from cells in tractus intermediolateralis in the spinal cord
from Th 5 to Th 11. The sympathetic fibres are led to the
sympathetic chain and further by the nervus splanchnicus
major (from Th 5 to Th 10) and one or more nervi
splanchnici minor (from Th 9 to Th 11) to synapses in
prevertebral abdominal plexa, at first hand the coeliac
ganglion. The postganglionic fibres pass along the arteries
of the liver and spleen and the superior mesenteric artery
into pancreatic tissue. Some sympathetic axons run directly
to the pancreas without intraabdominal synapses, mainly
from the lower portion of the sympathetic chain (which
partly may explain the limitation of pain control after
surgical celiacectomy). From a theoretical point of view the
pain can be inhibited by cutting the nerve fibres anywhere
along these paths. The procedure most often tried is
chemical blockage of the coelicaus ganglion, and a newer
alternative is thoracoscopic splanchnicectomy.
The coeliacus block can be done during laparotomy (not
taken into account here) or percutaneously, usually from the
Downloaded from http://annonc.oxfordjournals.org/ by guest on September 9, 2014
The clinical appearance of the pain pattern in pancreatic
cancer is infrequently discussed, and attempts to tailor the
treatment systematically to the symptoms and signs are
almost totally lacking. The management of pain must be
based on knowledge of not only the available treatment
possibilities, but also of the natural history of the disease. In
Lund, Sweden, and Bergen, Norway, a group of patients
were prospectively followed to describe the quality, quantity
and development of their pain and to investigate whether the
pain at the time of diagnosis could give information on the
prognosis. It was then found that pain at the time of
diagnosis was not so frequent and severe as is usually stated
[8, 16-20], but in accordance with the results of a recent
prospective american study [21]. They demonstrated that 40
percent of the patients with pancreatic cancer reported no
pain at the time of refferal, and another 30 percent had only
minimal complaints of pain. Similarly, prospectivel data
collected from the Johns Hopkins Hospital demonstrated that
only 20 percent of patients reported clinically relevant pain,
as assessed by a visual analogue scale [22]. Moreover, after
a 10 week follow-up of the Scandinavian patients about one
third of the patients were still completely pain free. This
underlines the fact that each patient must be treated in his or
her own way and it is important not to give analgesics
routinely just because of the diagnosis.
On the same time it is important to state that some patients
were inadequately treated with regard to pain. If patients are
judged to have pain of a type and intensity that needs
morphine, it is illogical to undertreat them so that they still
suffer significant pain. If morphine is given it should instead
always be given in sufficient doses.
In the literature it is stated that patients with cancer in the
head of the pancreas have less pain compared to those with
cancer of the body or tail [23], or the opposite [6]. The
results of the prospective study favor the view that patients
with cancer of the head of the pancreas have less pain than
those of the body and tail, but also we are of the opinion that
the differences documented are not of major clinical
importance.
Pain and survival
267
a change of mood and even personality. A major concept in
prescription is therefore to divide the analgesic treatement
into three stages, the principle in each stage being
paracetamol, dextropropoxiphene and morphine, and never
to proceed to the next step without minute consideration of
the short and long-term effects of the escalation.
Overall, standard theraphy with at most oral opiates and
adjuvant drugs can be successful in up to 90 percent of
patients with pancreatic cancer pain [35]. Most opiates are
now available as rectal suppositorier with an efficacy about
equal that of oral administration, which is of importance near
the terminal state when the patients have difficulties with
peroral medication. Also the potent, lipid-soluble opiate
fentanyl can then be used transdermally. Recently, patientcontrolled analgesic techniques have been offered to
ambulatory patients with cancer. Subcutaneous continous
infusions of opioates with patient-directed boluses, as
needed, can be valuable in minimizing the fluctuations in
blood levels, toxicity and anagesia seen with intermittentdosing schedules [35].
For the present, the best long-term results of treatment of
the pain of in pancreatic cancer are likely to come from a
careful appraisal of the patient's situation and a treatment
that is tailored to the individual as well as to his or her
disease. Prognosis also related to the attitude and
expectations of the patient and the relatives and it may
depend as much on awareness of the situation and
confidence in the treatment as on technical aspects of
medical and surgical management. We experience that if the
patient has confidence in the doctor's management over all
he or she will be able to cope with the pain in a better way.
Therefore, we think that the continuity in the patient-doctor
relationship is of the utmost importance in these patients.
References
1.
2.
3.
4.
5.
6.
7.
Conservative treatment
Analgesic drugs are still the most commonly adopted
method for pain relief, such as paracetamol,
dextropropoxiphene, prednisolon, non-steroidal antiinflammatory drugs, tricyclic antidepressants or narcotic
analgesic drugs given orally or rectally, opioids also
subcutaneously or intrathecally. A problem is that due to the
chronic nature of the pain many patients subsequently have
8.
9.
10.
11.
Grahm AL, Andrdn-Sandberg A. Prospective evaluation of pain in exocrine
pancreatic cancer. Digestion 1997; 58: 542-9.
Eckhauser FE, Knol JA, Mulholland MW et al. Pancreatic surgery. Curr Opin
Gastroenterol 1996; 12:448-56.
Ihse I, Andersson H, Andrdn-Sandberg A. Total pancreatectomy for cancer of
the pancreas: is it appropriate? World J Surg 1996; 20: 288-94.
Andrfn-Sandberg A, Ahren B, Tranberg KG et al. Surgical treatment of
pancreatic cancer. The Swedish experience. Int J Pancreatol 1991; 9: 145-52.
Andrjn-Sandberg
A, Inse I. Pattern
of recurrence after
pancreaticoduodenectomy for exocrine pancreatic cancer correlation with
survival. In: Hanyu F, Takasaki K (eds). Pancreatoduodenectomy. Tokyo:
Springer, 1997:417-23.
Watanapa P, Williamsson RCN. Surgical palliation of pancreatic cancer. In
Johnson CD, Imrie CW (eds) Pancreatic diseases, progress and prospects.
London: Springer-Verlag, 1991: 71-87.
Schaimerich J. Diagnosis of pancreatic cancer. In: Beger HG, BUchler M,
Malfertheiner P, (eds). Standards in pancreatic surgery. Berlin: Springer-Verlag;
1993. p. 578-90.
Trede M, Carter DC. Clinical evaluation and preoperative assessment In Trede
M, Carter DC (eds) Surgery of the pancreas. Edinburgh: Churchill Livingstone,
1993:423-31.
KlBppel G, Solcia E, Longnecker DS et al. Histological typing of tumors of the
exocrine pancreas. World Health Organization. International histological
classification of tumours, ed 2. Berlin: Springer-Verlag; 1996.
Gill TM, Feinstein AR. A critical appraisal of the quality of quality-of-life
measurement. JAMA 1994; 272: 619-26.
McLeod RS, Taylor BR, O'Connor BI et al. Quality of life, nutritional status,
and gastrointestinal hormone profile following the Whipple procedure. Am J
Surg 1995; 169: 179-85.
Downloaded from http://annonc.oxfordjournals.org/ by guest on September 9, 2014
back. The placement of the injection can be done simply by
using anatomical landmarks or by checking the position by
fluoroscopy, scout X-ray films, ultrasonography, CT, or at
angiography. A nerve block with 25 ml of 50 percent alcohol
on each side should be preceded by a positive diagnostic
block with long-acting local anaesthesia, carried out at least
one day earlier. The method aims at blockage of the
splanchnic nerves before they reach the coeliac plexus rather
than blockage of more than part of the coeliac plexus itself.
There are several different ways to acertain that the needle
tips and the fluid injected, respectively, are in the right place.
The site of the needle can be documented with scout films
[29]. Theoretically more appealing, is to guide the injections
of local anaesthetics (and later neurolytica) with fluoroscopy
and contrast media in the injected fluid [30, 31].
In a critical review Sharfman and Walsh in 1990 [32]
analysed data from 15 series published 1964-1983, including
480 patients, on coeliac plexus blocking in pancreatic
patients. At least a satisfactory response to the procedure
was reported in 87 percent of the patients. The authors
claimed, however, that there were major deficiencies in the
reporting of the results. In our practice the results of coeliac
block has been rather unpredictable, and as the pain tended
to recur in about three months time [33] we think that the
indication for this procedure is at present limited to those
who are well experienced with it.
As the pain fibres run in the sympathetic chain, pain stimli
can be overcome from within the thoracic cavity where the
chain lies immediately subpleural in a wave-like disposition
over the ribs in the posterior mediastinum. These nerves are
identified easily at thoracoscopy. Thoracoscopic splachnicectomy may be performed bilaterally under general
anaesthesia using double-lumen endothraceal intubation.
Usually two ports are used on each side: one optical cannula
(10.0 mm) and another 5.5 mm operating cannula. A small
hole in the pleura on each side of a splanchnic nerve, 10 mm
from the sympathetic chain, is burnt with the hook and the
nerves are then cut off completely so that the ends are seen
to be well retracted from each other. In uncomplicated cases
the patient can be discharged from the hospital the day after
the operation. In a series of 30 patients treated at the
Department of Surgery in Lund, satisfactory stable pain
relief was obtained from the first week after surgery [34].
All patients reported clearly reduced pain, but only about 20
per cent of individuals reported immediate complete pain
relief. One may concluded that thoracoscopic
splanchnicectomy is a good alternative, as a safe and
relatively simple treatment for severe pancreatic cancer pain.
268
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
Correspondence to:
Ake Andren-Sandberg
Department of Surgery
Haukeland University Hospital
Bergen, Norway
Downloaded from http://annonc.oxfordjournals.org/ by guest on September 9, 2014
23.
Padilla GV, Ferrell BR, Grant MM et al. Defining the content domain of quality
of life for cancer patients with pain. Cancer Nurs 1990; 13:108-15.
Carlsson AM. Assessment of chronic pain. Aspects of the reliability and validity
of the visual analogue scale. Pain 1983; 16: 87-101.
Scott J, Huskisson EC. Graphic representation of pain. Pain 1976; 2. 175-84.
Bloechle C, Izbicki JR. Knoefel WTet al. Quality of life in chronic pancreatitis
- results after duodenum-preserving resection of the head of the pancreas.
Pancreas 1995; 11:77-85.
Coutsoftides T, Macdonald J, Shibata HR. Carcinoma of the pancreas and
periampullary region: a 41 year experience. Ann Surg 1977; 186: 730-3.
Kairaluoma MI, Stahlberg M, Kiviniemi H et al. Results of
pancreaticoduodenectomy for carcinoma of the head of the pancreas.
Hepatogastroenterology 1989; 36:412-8.
Lee YT, Williams M. Clinical and laboratory findings of carcinoma of the
pancreas and periampullary structures. J Surg Oncol 1984; 25: 1-7.
Thomas FJ, Krall J, Hendrickson F et al. Evaluation of neutron irradiation of
pancreatic cancer results of a randomized radiation therapy oncology group
clinical trial. Am J Clin Oncol 1989; 12: 283-9.
Ventafridda GV, Caraceni AT, Sbanotto AM et al. Pain treatment in cancer of
the pancreas. Eur J Surg Oncol 1990; 16:1-6.
Hudis C, Kelsen D, Niedzwiecki D et al. Pain is not a prominent symptom in
most patients with early pancreatic cancer. Proc Am Soc Clin Oncol 1991; 10:
326.
Lillemoe KD, Cameron JL, Kaufman HS et al. Chemical splanchnicectomy in
patients with unresectable pancreatic cancer: a prospective randomized trial.
Ann Surg 1993; 217: 447-57.
Raijman I, Levin B. Exocrine tumours of the pancreas. In Go VLW, DiMagno
E, Gardner JD et al (eds) The pancreas, biology, pathobiology, and diseases, ed
2. New York: Raven Press.1993: 899-912.
Grahm AL, Anditn-Sandberg A. Pain at the time of diagnosis as a prognostic
sign for survival in palliatively treated patients with exocrine pancreatic cancer.
Int J Pancreatol 1998; 23: 223.
Andr£n-Sandberg A, Cedercrantz C. Review of standards for reporting results
of treatment of exocrine pancreatic cancer. Int J Pancreatol 1993; 14:213-7.
Frey CF, Pitt HA, Yeo CJ et al. A plea for uniformreportingof patient outcome
in chronic pancreatitis. Am J Surg 1996; 131: 233-4.
Eypasch E, Troidl H, Wood-Dauphinee S et al. Quality of life and
gastrointestinal surgery - a clinimetric approach to developing an instrument for
its measurement Theor Surg 1990; 5: 3-10.
Grahm AL, Fitzsimmons D, George S et al. Quality of life assessment in
patients with exocrine pancreatic cancer using the EORTC QLQ-30 and QLQPAN26. A pilot study. Digestion 1998; 59: 214.
Bengtsson M, USfstrdm JB. Nerve block in pancreatic pain. Acta Chir Scand
1990; 156: 285-91.
HegedUs V. Relief of pancreatic pain by radiography-guided block. AIR
1979;133: 1101-3.
Ischia S, Ischia A, Polati E et al. Three posterior percutaneous celiac plexus
block techniques. A prospective, randomised study in 61 patients with
pancreatic cancer pain. Anaesthesiology 1992; 76: 534-40.
Sharfman WH, Walsh TD. Has the analgesic efficacy of neurolytic celiac plexus
block been demonstrated in pancreatic cancer pain? Pain 1990; 41: 267-71.
Dise I, Borch K, Larsson I. Chronic pancreatitis: Results of operations for relief
of pain. World J Surg 1990; 14: 53-8.
Andren-Sandberg A, Zoucas E, Lillo-Gil R et al. Thoracoscopic
splanchnicectomy for chronic, severe pancreatic pain. Sem Laparscopic Surg
1996; 3: 29-33.
Lillemoe KD. Treatment of pancreatic cancer pain. In: Howard J, Idezuki Y,
Dise I, Prinz R. ed. Surgical diseases of the pancreas. Third edition. Baltimore:
Williams and Wilkins 1998:627-32.