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Research
Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer Amanda Landers,1 Wendy Muircroft,2 Helen Brown1
1
Hospice Palliative Care Service, Nurse Maude Association, Christchurch, New Zealand 2 Department of Palliative Care, Queen Elizabeth Hospital, Adelaide, South Australia, Australia Correspondence to Dr Amanda Landers, Hospice Palliative Care Service, Nurse Maude Association, P O Box 36-126, Christchurch 8146, New Zealand; Amanda.Landers@nursemaude. org.nz Received 22 April 2014 Revised 23 June 2014 Accepted 13 August 2014
To cite: Landers A, Muircroft W, Brown H. BMJ Supportive & Palliative Care Published Online First: [ please include Day Month Year] doi:10.1136/bmjspcare-2014000694
ABSTRACT Purpose The diagnosis of metastatic pancreatic cancer (PC) carries a poor prognosis. PC is associated with weight loss and malabsorption in high rates secondary to pancreatic exocrine insufficiency. UK and USA guidelines exist recommending the empiric use of pancreatic enzyme replacement therapy (PERT) for quality of life in these patients. The aim of this study is to review the use of PERT in patients with metastatic PC referred to a specialist palliative care service. Methods Retrospective observational study of patients referred to the service between January 2010 and July 2012 with a diagnosis of PC. Information about PERT use, tumour site and frequency of symptoms was collected. Results 129 patients were referred, with a higher number in the eighth decade. Only 21% of this study group were prescribed PERT. Over 70% of patients had symptoms that could be attributable to malabsorption, mainly abdominal pain. Other symptoms such as bloating, wind and steatorrhoea were also common. Conclusions Guidelines recommending empiric treatment of PERT in patients with metastatic PC are not currently being utilised.
INTRODUCTION Pancreatic cancer (PC) is the fifth most common cause of death from malignancy in the Western world.1 When the diagnosis of PC is performed, it carries a poor prognosis from the outset as the 5-year survival rate is only 5%.2 3 Around 15% of patients will be eligible for curative surgery, therefore 80–90% of patients who are diagnosed with PC will have palliative treatment options alone at presentation.4 5 There is a high incidence of metastatic disease at the time of diagnosis,3 6 and
the estimated median survival is just 92 days for this group of patients.7 Referral to specialist palliative care services such as Nurse Maude Hospice in Christchurch, New Zealand, is therefore very appropriate. Pathophysiology of pancreatic exocrine insufficiency
The pancreas has endocrine and exocrine synthetic functions. It can maintain normal exocrine enzyme secretion until 5–10% of function is left, after which patients may become symptomatic.8 Weight loss in PC is associated with malabsorption arising from exocrine dysfunction. The causal relationship was first elucidated in a seminal study at the Mayo clinic in 1983.9 In this small, prospective study using breath testing as an indicator of malabsorption, weight loss and symptoms of malabsorption improved with pancreatin treatment in patients with moderate-to-severe dysfunction. There are multiple mechanisms for pancreatic exocrine insufficiency (PEI) in PC and these include tumour obstruction of the head of the pancreas, destruction of exocrine synthetic tissue of the pancreas by tumour invasion and postsurgical loss of pancreatic tissue.10–12 Ihse13 used the Lundh test in 25 patients with PC and showed 80–90% had exocrine insufficiency. Significance of malabsorption in PC
Patients who are diagnosed with PC commonly report symptoms such as jaundice, pain, nausea, bloating, flatus, vomiting, weight loss and steatorrhoea. Thirty per cent of patients with PC are malnourished at presentation and almost all are
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
1
Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research affected at their time of death.14 However, Davidson found that those given intensive nutritional input achieved weight stabilisation, survived longer and had better global Quality of Life scores.15 Malnutrition is associated with high morbidity and mortality due to the risk of related complications and cardiovascular events.8 16 Nutritional assessment is vital in those with a diagnosis of PC but not yet part of routine care. An Australian study17 utilised qualitative methods to explore the supportive care needs of patients with PC and their families. The most striking outcome related directly to the gut symptoms of malabsorption and the impact this had on every aspect of their lives. Participants particularly mentioned the lack of knowledge of health professionals and access to dietitian review. Pancreatic enzyme replacement therapy
Owing to the high incidence of PEI in patients with PC, there is a growing body of expert opinion that empiric treatment with pancreatic enzyme replacement therapy (PERT) without evaluation of faecal fat or breath-testing should be started.10 18–20 The only published randomised, controlled trial comparing the use of PERT with inactive placebo in patients with irresectable cancer of the head of the pancreas showed favourable results.21 The group using PERT had an average weight gain of 1.2%, whereas those without enzyme replacement lost 3.7% of their body weight. The National Comprehensive Cancer Network (NCCN USA) recommends PERT for patients with PC who have symptoms of exocrine dysfunction and for postoperative patients as the incidence is so high.22 It is also thought that PERT may be indicated in mild PEI.23 The Pancreatic Section of the British Society of Gastroenterology recommends the use of PERT to maintain weight and increase quality of life.24 The introduction of a proton pump inhibitor (PPI) is recommended if PERT is not effective in spite of patient compliance with the enzymes.25 Despite these recommendations it is unknown how often PERT is being routinely prescribed in those with metastatic PC who are referred to Nurse Maude Hospice. Palliative care services for patients with PC
Palliative care is an approach taken with those diagnosed with life-limiting illness focused on the whole person.26 The Nurse Maude Hospice Palliative Care service provides specialist support for patients at home, working closely with general practitioners and district nurses. The team has a wide range of skills including a dietician who is trained in the evaluation and management of patients who would benefit from PERT. The aim of this study was to review those referred to the service with metastatic PC and frequency of PERT use. 2
METHODS Study design and sample
A retrospective patient case note review was undertaken for all patients referred to the Nurse Maude Hospice Palliative care service between January 2010 and July 2012 with metastatic PC. This included mostly community-based patients. Patient management systems were utilised to generate a list of patients coded with a diagnosis of PC from the original referrals. Those with a diagnosis of cholangiocarcinoma or ampullary cancer were not included. The notes were comprehensively reviewed by three of the authors and some missing data were found using a shared information system with the local tertiary hospital. The following data were collected: A. Age, gender B. Tumour site according to imaging and referral documentation C. Length of survival after referral to the service D. Number of patients prescribed PERT before admission E. Number of patients prescribed a PPI before admission F. Recorded frequency and nature of PEI symptoms on initial assessment to the palliative care service ▸ abdominal pain ▸ wind ▸ bloating ▸ diarrhoea ▸ weight loss ▸ steatorrhoea
This low risk research protocol did not require approval by the regional Health and Disability Ethics Committee but the Nurse Maude Hospice Palliative Care Ethics Committee reviewed and approved the study.
RESULTS Demographics
Over the 30 months, 129 patients were identified as having a PC. Seventy-one patients (55%) were male and 58 (45%) were female. The graph below (figure 1) illustrates the age distribution of the patients, with more in the 80–89 age group. This is consistent with the demographics of the ageing population in Christchurch. Of those referred to the palliative care service, 126 (96.9%) patients had died in the study period. Approximately 25% had died by day 25 and 50% by day 58, in keeping with the median survival of this group. The audit did not capture the referral source; however, regardless of the source, the results indicate that few patients were receiving PERT. Fifty-six patients (43%) of the study group had received surgical or gastroenterology intervention, the majority in the form of a biliary stent. The other 57% of the patients had supportive care alone.
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research
Figure 3 Percentage of patients with pancreatic cancer prescribed pancreatic enzyme replacement therapy (PERT). Figure 1
Age distribution of study patients in years.
Tumour site
Tumour site was grouped into head of pancreas, body, tail, other and unknown (figure 2). Head of pancreas tumours were the most common. The ‘unknown’ group either had no biopsy or the results were unavailable. The one patient labelled as ‘other’ was diagnosed with an extrapancreatic mass after a pancreatectomy.
surrounding structures but this was not clarified in the patient record. Steatorrhoea was documented in only three of the patients. It is likely that steatorrhoea, a hallmark symptom of malabsorption which is associated with diarrhoea, was responsible for much of the weight loss.
It was found that incomplete documentation was a feature of this retrospective study. It appears health professionals did not specifically ask about malabsorption symptoms. However, in total 95 (72%) patients reported symptoms that were documented. Abdominal pain was the most common symptom, followed by diarrhoea (figure 4). Abdominal pain may be attributable to direct invasion by PC into the
DISCUSSION The Nurse Maude Hospice Palliative Care service has approximately 50 patients with metastatic PC referred annually. The majority of them are in their eighth decade, older than previously reported in the literature. This would fit with demographic changes occurring in developed countries where overall survival of the general population is extended.3 The site of tumour location within the pancreas has a significant effect on overall survival. The vast majority of the study subjects had tumours in the head of the pancreas as has been previously reported.3 Nearly all of these patients are likely to have a blocked pancreatic duct and require PERT to help maintain weight and quality of life.24 Patients were referred to the Nurse Maude Hospice Palliative Care service soon after diagnosis, allowing time for optimisation of symptom control and nutritional review. However, only a fifth had been started on PERT prior to the referral to the specialist palliative service. The literature reports approximately 80– 90% of patients with metastatic PC are malabsorbing at diagnosis.14 There are also guidelines which exist
Figure 2
Figure 4 Patients with symptoms of possible malabsorption and those with no documentation.
Medication
PERT was prescribed in 21% of patients with metastatic PC (figure 3). Almost 10% of patients did not have their medication documented on their referral to palliative care services. The frequency of PPI prescription was also documented. PPIs were prescribed in 49.2% of the total group of patients, not prescribed in 42% and not documented in 8%. Frequency of symptoms
Tumour site of pancreatic cancer in study patients.
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
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Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research throughout the world, recommending PERT in this setting.22 24 20 In this retrospective study, the main limitation to interpretation is that data collection on the frequency of prescriptions of PERT, PPIs and symptoms was incomplete. Incomplete documentation is a weakness of retrospective research. The referral source was also not collected. The nature of the study means that clinicians responsible for patient care may not be aware of the significance of observations made at a later date. There are several factors that may be contributory to this: ▸ Lack of awareness of the significance of PEI and weight loss amongst staff members in this group. Hence not all the patients were screened for symptoms of malabsorption. ▸ Most clinical staff may not be aware of the benefits of PERT and PPI on symptom control for this group of patients. ▸ Staff may have relied on patient reporting of symptoms instead of screening all patients which is unreliable.
Over 80% of patients reported abdominal pain as a symptom. Classically, PC causes pain in the epigastrium radiating to the back. This is often due to infiltration of the coeliac plexus. However, pain after meals suggests malabsorption and the review did not distinguish between these two entities. This is another limitation of the study. The main strength of this study is that it demonstrates low rates of PERT prescribing in a group of patients likely to have high rates of malabsorption. There are clear guidelines from the US and UK to support the use of enzyme replacement for maintenance of weight and quality of life. However, only one randomised-controlled trial exists.21 Little research has been performed on the quality of life with patients on PERT and its role in symptom control.
CONCLUSION There is scope for improvement in the frequency of PERT prescription in PC. Since the effective use of PERT is hypothesised to improve patient quality of life and symptoms caused by PEI, the next step for research is to evaluate these parameters in a prospective study. This is currently being undertaken at the Nurse Maude Hospice Palliative Care service with empiric PERT treatment of patients diagnosed with PC and using validated QOL tools such as the EORTC QLQ-C30 and PAN-26. It will also include a performance status measure to stratify patients with PC and highlight those which may benefit the most. The future plan is to write an algorithm for patients referred with PC, including appropriate assessment and PERT for these patients. Acknowledgements The study was supported by the New Zealand Institute of Community Health Care and in particular Helen Gibson and Gill Coe.
4
Funding This study was funded by the Canterbury Medical Research Foundation. Competing interests None. Ethics approval Nurse Maude Hospice Palliative Care Ethics Committee. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1 Cancer Research UK [Internet]. Twenty most common causes of cancer death. 2011. http://www.cancerresearchuk.org/ cancer-info/cancerstats/mortality/cancerdeaths/#Twenty (accessed Oct 2013). 2 National Cancer Institute [Internet]. Bethesda; SEER Cancer Statistics Review, 1975–2006; 2009 [cited 24 May 2013]. http://srab.cancer.gov/joinpoint 3 Speer AG, Thursfield VJ, Torn-Broers Y, et al. Pancreatic cancer: surgical management and outcomes after 6 years of follow-up. Med J Aust 2012;196:511–15. 4 Brennan MF, Moccia RD, Klimstra D. Management of adenocarcinoma of the body and tail of the pancreas. Ann Surg 1996;223:506–11. 5 Ghaneh P, Costello E, Neoptolemos JP. Recent advances in clinical practice—biology and management of pancreatic cancer. Gut 2007;56:1134–52. 6 Gupta D, Rodheighier M, Grutsch JF, et al. Predicting survival in advanced pancreatic cancer: the role of symptom clusters. 2010 ASCO Gastrointestinal Cancers Symposium. Abstract No 265. 7 Phillips AJR, Lawes CM, Cooper GJ, et al. Ethnic disparity of pancreatic cancer in New Zealand. Int J Gastrointest Cancer 2002;31:137–45. 8 Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005;54(Suppl VI):vi1–28. 9 Perez MM, Newcomer AD, Moertel CG, et al. Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer. Cancer 1983;52:346–52. 10 Halloran CM, Cox TF, Chauhan S, et al. Partial pancreatic resection for pancreatic malignancy is associated with sustained pancreatic exocrine failure and reduced quality of life: a prospective study. Pancreatology 2011;11:535–45. 11 Kato H, Nakao A, Kishimoto W, et al. 13C-labeled trioctanoin breath test for exocrine pancreatic function test in patients after pancreatoduodenectomy. Am J Gastroenterol 1993;88:64–9. 12 DiMagno EP, Malagelado JR, Go VL. The relationships between pancreatic ductal obstruction and pancreatic secretion in man. Mayo Clin Proc 1979;54:157–62. 13 Ihse I, Arnesjö B, Kugelberg C, et al. Intestinal activities of trypsin, lipase, and phospholipase after a test meal: an evaluation of 474 examinations. Scand J Gastroenterol 1977;12:663–8. 14 Wigmore SJ, Plester CE, Richardson RA, et al. Changes in nutritional status associated with unresectable pancreatic cancer. Br J Cancer 1997;75:106–9. 15 Davidson W, Ash S, Capra S, et al. Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr 2004;23:239–47. 16 Ockenga J. Importance of nutritional management in diseases with exocrine pancreatic insufficiency. HPB 2009;11(Suppl 3): s11–15.
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
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Research 17 Gooden HM, White KJ. Pancreatic cancer and supportive care—pancreatic exocrine insufficiency negatively impacts on quality of life. Support Care Cancer 2013;21:1835–41. 18 Damerla V, Gotlieb V, Larson H, et al. Pancreatic enzyme supplementation in pancreatic cancer. J Support Oncol 2008;6:393–6. 19 Dominguez-Munoz JE. Pancreatic exocrine insufficiency: diagnosis and treatment. J Gastroenterol Hepatol 2011;26(Suppl 2):12–16. 20 Toouli J, Biankin AV, Oliver MR, et al. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. MJA 2010;193:461–7. 21 Bruno MJ, Haverkort EB, Tijssen GP, et al. Placebo controlled trial of enteric coated pancreatic microsphere treatment in patients with unresectable cancer of the pancreatic head region. Gut 1998;42:92–6. 22 NCCN Guidelines Verson 2.2012 Pancreatic Adenocarcinoma [Internet]. NCCN. 2012 [cited Jan 2013]. 23 Sikkens ECM, Djuna LC, van Eijck C, et al. The daily practice of pancreatic enzyme replacement therapy after pancreatic
surgery: a Northern European Survey. J Gastrointest Surg 2012;16:1487–92. 24 Pancreatic Section of the British Society of Gastroenterology; Pancreatic Society of Great Britain and Ireland; Royal College of Pathologists; Special Interest Group for Gastro-Intestinal Radiology. Guidelines for the management of patients with pancreatic cancer periampullary and ampullary carcinomas. Gut 2005;54(Suppl V):v1–16. 25 Domínguez-Muñoz JE, Iglesias-Garcia J, Iglesias-Rey M, et al. Optimising the therapy of exocrine pancreatic insufficiency by the association of a proton pump inhibitor to enteric coated pancreatic extracts. Gut 2006;55:1056–7. 26 World Health Organisation. Definition of Palliative Care. 1998. http://www.who.int/cancer/palliative/definition (accessed Oct 2013). United Nations Department of Economics and Social Affairs, Population Division. World Population Ageing: 1950–2050. 2002. http://www.un.org/esa/ population/publications/worldageing19502050/ (accessed 30 Oct 2013).
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Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer Amanda Landers, Wendy Muircroft and Helen Brown BMJ Support Palliat Care published online August 27, 2014
doi: 10.1136/bmjspcare-2014-000694
Updated information and services can be found at: http://spcare.bmj.com/content/early/2014/08/27/bmjspcare-2014-000694.full.html
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References
This article cites 21 articles, 4 of which can be accessed free at: http://spcare.bmj.com/content/early/2014/08/27/bmjspcare-2014-000694.full.html#ref-list-1
P
Research
Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer Amanda Landers,1 Wendy Muircroft,2 Helen Brown1
1
Hospice Palliative Care Service, Nurse Maude Association, Christchurch, New Zealand 2 Department of Palliative Care, Queen Elizabeth Hospital, Adelaide, South Australia, Australia Correspondence to Dr Amanda Landers, Hospice Palliative Care Service, Nurse Maude Association, P O Box 36-126, Christchurch 8146, New Zealand; Amanda.Landers@nursemaude. org.nz Received 22 April 2014 Revised 23 June 2014 Accepted 13 August 2014
To cite: Landers A, Muircroft W, Brown H. BMJ Supportive & Palliative Care Published Online First: [ please include Day Month Year] doi:10.1136/bmjspcare-2014000694
ABSTRACT Purpose The diagnosis of metastatic pancreatic cancer (PC) carries a poor prognosis. PC is associated with weight loss and malabsorption in high rates secondary to pancreatic exocrine insufficiency. UK and USA guidelines exist recommending the empiric use of pancreatic enzyme replacement therapy (PERT) for quality of life in these patients. The aim of this study is to review the use of PERT in patients with metastatic PC referred to a specialist palliative care service. Methods Retrospective observational study of patients referred to the service between January 2010 and July 2012 with a diagnosis of PC. Information about PERT use, tumour site and frequency of symptoms was collected. Results 129 patients were referred, with a higher number in the eighth decade. Only 21% of this study group were prescribed PERT. Over 70% of patients had symptoms that could be attributable to malabsorption, mainly abdominal pain. Other symptoms such as bloating, wind and steatorrhoea were also common. Conclusions Guidelines recommending empiric treatment of PERT in patients with metastatic PC are not currently being utilised.
INTRODUCTION Pancreatic cancer (PC) is the fifth most common cause of death from malignancy in the Western world.1 When the diagnosis of PC is performed, it carries a poor prognosis from the outset as the 5-year survival rate is only 5%.2 3 Around 15% of patients will be eligible for curative surgery, therefore 80–90% of patients who are diagnosed with PC will have palliative treatment options alone at presentation.4 5 There is a high incidence of metastatic disease at the time of diagnosis,3 6 and
the estimated median survival is just 92 days for this group of patients.7 Referral to specialist palliative care services such as Nurse Maude Hospice in Christchurch, New Zealand, is therefore very appropriate. Pathophysiology of pancreatic exocrine insufficiency
The pancreas has endocrine and exocrine synthetic functions. It can maintain normal exocrine enzyme secretion until 5–10% of function is left, after which patients may become symptomatic.8 Weight loss in PC is associated with malabsorption arising from exocrine dysfunction. The causal relationship was first elucidated in a seminal study at the Mayo clinic in 1983.9 In this small, prospective study using breath testing as an indicator of malabsorption, weight loss and symptoms of malabsorption improved with pancreatin treatment in patients with moderate-to-severe dysfunction. There are multiple mechanisms for pancreatic exocrine insufficiency (PEI) in PC and these include tumour obstruction of the head of the pancreas, destruction of exocrine synthetic tissue of the pancreas by tumour invasion and postsurgical loss of pancreatic tissue.10–12 Ihse13 used the Lundh test in 25 patients with PC and showed 80–90% had exocrine insufficiency. Significance of malabsorption in PC
Patients who are diagnosed with PC commonly report symptoms such as jaundice, pain, nausea, bloating, flatus, vomiting, weight loss and steatorrhoea. Thirty per cent of patients with PC are malnourished at presentation and almost all are
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
1
Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research affected at their time of death.14 However, Davidson found that those given intensive nutritional input achieved weight stabilisation, survived longer and had better global Quality of Life scores.15 Malnutrition is associated with high morbidity and mortality due to the risk of related complications and cardiovascular events.8 16 Nutritional assessment is vital in those with a diagnosis of PC but not yet part of routine care. An Australian study17 utilised qualitative methods to explore the supportive care needs of patients with PC and their families. The most striking outcome related directly to the gut symptoms of malabsorption and the impact this had on every aspect of their lives. Participants particularly mentioned the lack of knowledge of health professionals and access to dietitian review. Pancreatic enzyme replacement therapy
Owing to the high incidence of PEI in patients with PC, there is a growing body of expert opinion that empiric treatment with pancreatic enzyme replacement therapy (PERT) without evaluation of faecal fat or breath-testing should be started.10 18–20 The only published randomised, controlled trial comparing the use of PERT with inactive placebo in patients with irresectable cancer of the head of the pancreas showed favourable results.21 The group using PERT had an average weight gain of 1.2%, whereas those without enzyme replacement lost 3.7% of their body weight. The National Comprehensive Cancer Network (NCCN USA) recommends PERT for patients with PC who have symptoms of exocrine dysfunction and for postoperative patients as the incidence is so high.22 It is also thought that PERT may be indicated in mild PEI.23 The Pancreatic Section of the British Society of Gastroenterology recommends the use of PERT to maintain weight and increase quality of life.24 The introduction of a proton pump inhibitor (PPI) is recommended if PERT is not effective in spite of patient compliance with the enzymes.25 Despite these recommendations it is unknown how often PERT is being routinely prescribed in those with metastatic PC who are referred to Nurse Maude Hospice. Palliative care services for patients with PC
Palliative care is an approach taken with those diagnosed with life-limiting illness focused on the whole person.26 The Nurse Maude Hospice Palliative Care service provides specialist support for patients at home, working closely with general practitioners and district nurses. The team has a wide range of skills including a dietician who is trained in the evaluation and management of patients who would benefit from PERT. The aim of this study was to review those referred to the service with metastatic PC and frequency of PERT use. 2
METHODS Study design and sample
A retrospective patient case note review was undertaken for all patients referred to the Nurse Maude Hospice Palliative care service between January 2010 and July 2012 with metastatic PC. This included mostly community-based patients. Patient management systems were utilised to generate a list of patients coded with a diagnosis of PC from the original referrals. Those with a diagnosis of cholangiocarcinoma or ampullary cancer were not included. The notes were comprehensively reviewed by three of the authors and some missing data were found using a shared information system with the local tertiary hospital. The following data were collected: A. Age, gender B. Tumour site according to imaging and referral documentation C. Length of survival after referral to the service D. Number of patients prescribed PERT before admission E. Number of patients prescribed a PPI before admission F. Recorded frequency and nature of PEI symptoms on initial assessment to the palliative care service ▸ abdominal pain ▸ wind ▸ bloating ▸ diarrhoea ▸ weight loss ▸ steatorrhoea
This low risk research protocol did not require approval by the regional Health and Disability Ethics Committee but the Nurse Maude Hospice Palliative Care Ethics Committee reviewed and approved the study.
RESULTS Demographics
Over the 30 months, 129 patients were identified as having a PC. Seventy-one patients (55%) were male and 58 (45%) were female. The graph below (figure 1) illustrates the age distribution of the patients, with more in the 80–89 age group. This is consistent with the demographics of the ageing population in Christchurch. Of those referred to the palliative care service, 126 (96.9%) patients had died in the study period. Approximately 25% had died by day 25 and 50% by day 58, in keeping with the median survival of this group. The audit did not capture the referral source; however, regardless of the source, the results indicate that few patients were receiving PERT. Fifty-six patients (43%) of the study group had received surgical or gastroenterology intervention, the majority in the form of a biliary stent. The other 57% of the patients had supportive care alone.
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research
Figure 3 Percentage of patients with pancreatic cancer prescribed pancreatic enzyme replacement therapy (PERT). Figure 1
Age distribution of study patients in years.
Tumour site
Tumour site was grouped into head of pancreas, body, tail, other and unknown (figure 2). Head of pancreas tumours were the most common. The ‘unknown’ group either had no biopsy or the results were unavailable. The one patient labelled as ‘other’ was diagnosed with an extrapancreatic mass after a pancreatectomy.
surrounding structures but this was not clarified in the patient record. Steatorrhoea was documented in only three of the patients. It is likely that steatorrhoea, a hallmark symptom of malabsorption which is associated with diarrhoea, was responsible for much of the weight loss.
It was found that incomplete documentation was a feature of this retrospective study. It appears health professionals did not specifically ask about malabsorption symptoms. However, in total 95 (72%) patients reported symptoms that were documented. Abdominal pain was the most common symptom, followed by diarrhoea (figure 4). Abdominal pain may be attributable to direct invasion by PC into the
DISCUSSION The Nurse Maude Hospice Palliative Care service has approximately 50 patients with metastatic PC referred annually. The majority of them are in their eighth decade, older than previously reported in the literature. This would fit with demographic changes occurring in developed countries where overall survival of the general population is extended.3 The site of tumour location within the pancreas has a significant effect on overall survival. The vast majority of the study subjects had tumours in the head of the pancreas as has been previously reported.3 Nearly all of these patients are likely to have a blocked pancreatic duct and require PERT to help maintain weight and quality of life.24 Patients were referred to the Nurse Maude Hospice Palliative Care service soon after diagnosis, allowing time for optimisation of symptom control and nutritional review. However, only a fifth had been started on PERT prior to the referral to the specialist palliative service. The literature reports approximately 80– 90% of patients with metastatic PC are malabsorbing at diagnosis.14 There are also guidelines which exist
Figure 2
Figure 4 Patients with symptoms of possible malabsorption and those with no documentation.
Medication
PERT was prescribed in 21% of patients with metastatic PC (figure 3). Almost 10% of patients did not have their medication documented on their referral to palliative care services. The frequency of PPI prescription was also documented. PPIs were prescribed in 49.2% of the total group of patients, not prescribed in 42% and not documented in 8%. Frequency of symptoms
Tumour site of pancreatic cancer in study patients.
Landers A, et al. BMJ Supportive & Palliative Care 2014;0:1–5. doi:10.1136/bmjspcare-2014-000694
3
Downloaded from spcare.bmj.com on September 9, 2014 - Published by group.bmj.com
Research throughout the world, recommending PERT in this setting.22 24 20 In this retrospective study, the main limitation to interpretation is that data collection on the frequency of prescriptions of PERT, PPIs and symptoms was incomplete. Incomplete documentation is a weakness of retrospective research. The referral source was also not collected. The nature of the study means that clinicians responsible for patient care may not be aware of the significance of observations made at a later date. There are several factors that may be contributory to this: ▸ Lack of awareness of the significance of PEI and weight loss amongst staff members in this group. Hence not all the patients were screened for symptoms of malabsorption. ▸ Most clinical staff may not be aware of the benefits of PERT and PPI on symptom control for this group of patients. ▸ Staff may have relied on patient reporting of symptoms instead of screening all patients which is unreliable.
Over 80% of patients reported abdominal pain as a symptom. Classically, PC causes pain in the epigastrium radiating to the back. This is often due to infiltration of the coeliac plexus. However, pain after meals suggests malabsorption and the review did not distinguish between these two entities. This is another limitation of the study. The main strength of this study is that it demonstrates low rates of PERT prescribing in a group of patients likely to have high rates of malabsorption. There are clear guidelines from the US and UK to support the use of enzyme replacement for maintenance of weight and quality of life. However, only one randomised-controlled trial exists.21 Little research has been performed on the quality of life with patients on PERT and its role in symptom control.
CONCLUSION There is scope for improvement in the frequency of PERT prescription in PC. Since the effective use of PERT is hypothesised to improve patient quality of life and symptoms caused by PEI, the next step for research is to evaluate these parameters in a prospective study. This is currently being undertaken at the Nurse Maude Hospice Palliative Care service with empiric PERT treatment of patients diagnosed with PC and using validated QOL tools such as the EORTC QLQ-C30 and PAN-26. It will also include a performance status measure to stratify patients with PC and highlight those which may benefit the most. The future plan is to write an algorithm for patients referred with PC, including appropriate assessment and PERT for these patients. Acknowledgements The study was supported by the New Zealand Institute of Community Health Care and in particular Helen Gibson and Gill Coe.
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Funding This study was funded by the Canterbury Medical Research Foundation. Competing interests None. Ethics approval Nurse Maude Hospice Palliative Care Ethics Committee. Provenance and peer review Not commissioned; externally peer reviewed.
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Pancreatic enzyme replacement therapy (PERT) for malabsorption in patients with metastatic pancreatic cancer Amanda Landers, Wendy Muircroft and Helen Brown BMJ Support Palliat Care published online August 27, 2014
doi: 10.1136/bmjspcare-2014-000694
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References
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