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      Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer

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          Abstract

          Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.

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          Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors

          Prashanth Rawla, Tagore Sunkara, Vinaya Gaduputi (2019)
          Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. However, its toll is higher in more developed countries. Reasons for vast differences in mortality rates of pancreatic cancer are not completely clear yet, but it may be due to lack of appropriate diagnosis, treatment and cataloging of cancer cases. Because patients seldom exhibit symptoms until an advanced stage of the disease, pancreatic cancer remains one of the most lethal malignant neoplasms that caused 432,242 new deaths in 2018 (GLOBOCAN 2018 estimates). Globally, 458,918 new cases of pancreatic cancer have been reported in 2018, and 355,317 new cases are estimated to occur until 2040. Despite advancements in the detection and management of pancreatic cancer, the 5-year survival rate still stands at 9% only. To date, the causes of pancreatic carcinoma are still insufficiently known, although certain risk factors have been identified, such as tobacco smoking, diabetes mellitus, obesity, dietary factors, alcohol abuse, age, ethnicity, family history and genetic factors, Helicobacter pylori infection, non-O blood group and chronic pancreatitis. In general population, screening of large groups is not considered useful to detect the disease at its early stage, although newer techniques and the screening of tightly targeted groups (especially of those with family history), are being evaluated. Primary prevention is considered of utmost importance. Up-to-date statistics on pancreatic cancer occurrence and outcome along with a better understanding of the etiology and identifying the causative risk factors are essential for the primary prevention of this disease.
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            Cachexia worsens prognosis in patients with resectable pancreatic cancer.

            Markus W. Büchler, Jeannine Bachmann, Helmut Friess … (2008)
            Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries with a poor prognosis (5-year survival rates, 25% in patients after tumor resection with adjuvant treatment; overall, the 5-year survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10-30, 2005). Many patients develop a cachectic status during the progression of the disease, and this syndrome accounts for up to 80% of deaths in patients with advanced pancreatic cancer. Remarkably, there are only a few data available on the impact of cachexia in patients with pancreatic cancer scheduled for tumor resection. Therefore, in this study, 227 consecutive patients with ductal adenocarcinoma of the pancreas were documented over an 18-month period regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival in a prospectively designed database and followed up. In 40.5% of the patients, cachexia was already present at the time of operation. The cachectic patients did present in a worse nutritional status, represented by lower protein, albumins, and hemoglobin levels. Despite no significant differences in tumor size, lymph node status, and CA19-9 levels, the resection rate in patients with cachexia was reduced (77.8% vs. 48.9%) due to a higher rate of metastatic disease in patients with cachexia. The morbidity and in-hospital mortality revealed no significant difference. However, patients with and without cachexia lost weight after operation, and the weight gain started not until 6 months after operation. The survival in patients with cachexia was significantly reduced in patients undergoing tumor resection as well as in palliative treated patients. Cachexia has a significant impact on survival and performance status in palliative patients as well as in patients operated for pancreatic cancer. But tumor-related cachexia is not necessarily dependent on tumor size or load and that metastatic dedifferentiation of the tumor might be a critical step in the development of tumor-associated cachexia.
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              Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test.

              A Möllgaard, C Löser, U Fölsch (1996)
              Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency. To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard'. Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin. Fifty healthy volunteers were studied as normal controls. Morphological examinations were carried out to definitely confirm or exclude chronic pancreatitis. With a cut off of 200 micrograms elastase 1/g stool the sensitivity was 63% for mild, 100% for moderate, 100% for severe, and 93% for all patients with exocrine pancreatic insufficiency, and specificity was 93%. Values for chymotrypsin were 64% (sensitivity) and 89% (specificity). Significant (p < 0.001) correlations were found for faecal and duodenal elastase with duodenal lipase, amylase, trypsin, volume, and bicarbonate output. Individual day to day variations of faecal elastase 1 concentrations were very low (mean CV = 15%) and sample storage at room temperature is possible for at least one week. Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 22 January 2020
                Publication date Collection: February 2020
                Volume: 12
                Issue: 2
                Electronic Location Identifier: 275
                Affiliations
                [1 ]Gastroenterology Unit, San Carlo Hospital, Via P. Petrone, 85100 Potenza, Italy
                [2 ]Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy; R.Caccialanza@ 123456smatteo.pv.it
                [3 ]Clinical Research, Pancreato-Biliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy; capurso.gabriele@ 123456hsr.it
                [4 ]Medical Oncology Unit, National Cancer Institute “Giovanni Paolo II”, Viale O. Flacco 65, 70124 Bari, Italy; dr.oronzo.brunetti1983@ 123456gmail.com
                [5 ]Residency Program in Medical Oncology, University of Verona, Via S. Francesco 22, 37129 Verona, Italy; michele.milella@ 123456univr.it
                [6 ]AOUI Verona, Sede Policlinico Universitario G.B. Rossi Borgo Roma, P.le L.A. Scuro 10, 37134 Verona, Italy
                [7 ]Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy; falconi.massimo@ 123456hsr.it
                Author notes
                [* ]Correspondence: raffaele.pezzilli@ 123456gmail.com ; Tel.: +39-347-780-8983
                Author information
                https://orcid.org/0000-0001-9827-7451
                https://orcid.org/0000-0002-9379-3569
                https://orcid.org/0000-0002-0019-8753
                https://orcid.org/0000-0002-7014-6828
                https://orcid.org/0000-0002-3826-5237
                https://orcid.org/0000-0001-9654-7243
                Article
                Publisher ID: cancers-12-00275
                DOI: 10.3390/cancers12020275
                PMC ID: 7073203
                PubMed ID: 31979186
                SO-VID: 924b593c-126c-41f8-873b-162e393ec8a5
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 16 December 2019
                Date accepted : 20 January 2020
                Categories
                Subject: Review

                Keywords: pancreatic enzyme replacement therapy,pancreatic exocrine insufficiency,pancreatic cancer,chemotherapy,pancreatic resection,nutritional support
                Data availability:
                Keywords: pancreatic enzyme replacement therapy, pancreatic exocrine insufficiency, pancreatic cancer, chemotherapy, pancreatic resection, nutritional support

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