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Innovations in Pancreatic Enzyme Replacement Therapy for Enterally Fed Patients With Pancreatic Cancer

Year: 2025
Type: article
Study design: Case Report
Abstract: Patients with pancreatic cancer (PC) often develop exocrine pancreatic insufficiency (EPI), requiring the use of pancreatic enzyme replacement therapy (PERT). They may also require enteral nutrition (EN) to improve nutritional status and treatment tolerance. However, EN can present challenges with enzyme administration since PERT was designed to be taken with oral intake as opposed to tube feeding formula. A single-use immobilized lipase cartridge (ILC) was developed to address this unmet clinical need. Cartridges connect in-line with existing feeding sets and hydrolyze fats in enteral formula prior to ingestion. The lipase cartridge has been shown to improve gastrointestinal (GI) symptoms and anthropometric measures in patients with cystic fibrosis. However, description of cartridge use in patients with PC has been limited. This clinical observation describes the nutritional management of two patients with PC that utilized the lipase cartridge with supplemental enteral nutrition. After initiation of the cartridge, weight gain and GI symptoms improved in patients that were previously unable to be managed with oral pancreatic enzyme replacement therapy alone. Exocrine Pancreatic Insufficiency EPI is a common, under-recognized, and poorly understood clinical condition in patients with PC that occurs when exocrine pancreatic secretion cannot maintain normal food digestion. Only 10%–20% of patients with pancreatic cancer qualify for surgical intervention and EPI may present in the pre- or post-surgical period (Belyaev et al., 2013). Patients with unresectable PC represent a larger portion of this patient population and are estimated to develop EPI in 66%–92% of these cases (Singh et al., 2017). Patients with PC develop EPI for a variety of reasons, including loss of functional pancreatic tissue due to surgery, tumor damage to the pancreatic tissue, blockage of the pancreatic duct, or post-surgical asynchrony (Dominguez-Muñoz, 2018; Matsumoto & Traverso, 2006; Tran et al., 2008). This results in GI symptoms such as gas, bloating, abdominal pain, difficulty maintaining or gaining weight, and changes in stool consistency, causing poor nutritional status and reduced quality of life (Dominguez-Muñoz, 2018). Nurses play an important role in supporting these complex patients that may be seen in a variety of settings including gastroenterology, oncology (medical, surgical and radiation offices), home health, and the hospital setting. Treatment for EPI includes PERT and a normal, unrestricted healthy diet (Domínguez-Muñoz, 2009). Often, patients with PC may be prescribed pancreatic enzymes if they show signs and symptoms of EPI; as a result, they may not undergo diagnostic testing. Several studies show PERT increases survival in PC (Partelli et al., 2012; Roberts et al., 2019; Trestini et al., 2021). Quality of life improvements are also noted with PERT treatment (Barkin et al., 2019; Landers et al., 2019). This is because treatment improves fat and protein digestion, relieves maldigestion-related symptoms, and normalizes nutrition (Domínguez-Muñoz, 2009; de la Iglesia-garcía et al., 2017). Dosing of pancreatic enzymes is key to managing the EPI that results from PC or the surgical interventions that may be required for treatment. Patients are often underdosed or do not receive therapy, resulting in further deterioration in nutritional status (Barkin et al., 2019; Roberts et al., 2019). Only 5.5% of patients with PC were prescribed an adequate dose in a study estimating the frequency of appropriate PERT use in a U.S. insured population (Forsmark et al., 2020). A New Zealand retrospective observational study showed that only 21% of the study group were prescribed PERT (Landers et al., 2016). Due to the mortality and disease burden associated with PC, PERT may be overlooked when providing patients with cancer treatments such as surgery or other systemic treatments. In addition, some non-GI specialists may be less aware of the impact of EPI in these patients (Forsmark et al., 2020). Due to metabolic impairments and malabsorption, patients with PC have a high risk of malnutrition (Gilliland et al., 2017). Between 50% and 90% of patients with PC suffer from weight loss and malnutrition, which leads to decreased progression-free survival, chemotherapy response, quality of life, and performance status (Voss & Williams, 2021). Although strong evidence for the treatment benefit of PERT in patients with PC exists, long-term randomized placebo-control trials and data on the type and timing of nutritional support, such as EN, in PC are limited. PERT is needed when delivering EN to patients with pancreatic insufficiency; however, oral PERT medications are designed for use with oral intake at meals and not with tube feeding. Data on the efficacy of PERT use with EN is also lacking. The microspheres in PERT are not meant to be chewed or crushed, but they are still used and administered in feeding tubes and this often leads to clogging (Nguyen, 2017). Many patients will take PERT orally with EN; however, this requires frequent dosing for tube feeds delivered continuously over several hours or overnight. Additionally, asynchrony between the delivery of enzymes and enteral formula exists when PERT is taken orally, yet formula is infused into the small bowel. Thus, PERT use with EN is impractical, time-consuming, and a burden to caregivers (Freedman et al., 2017a; Nguyen, 2017; Nicolo et al., 2013). The ability of a nurse to be able to recognize the need, implications, and benefits for a novel device such as the one described in these case studies can further improve the nutrition and quality of life in a population at high nutritional risk and mortality. Immobilized Lipase Cartridge The immobilized lipase cartridge used in these two PC case studies is a novel single-use device that connects in-line with the enteral feeding set (Figure 1). The cartridge contains small white beads covalently bound to lipase, the enzyme that hydrolyzes, or breaks down, fats (Figure 2). As enteral formula flows across the beads, fat in the formula is broken down into more easily absorbed free fatty acids and monoglycerides (RELiZORB Instructions For Use, 2023). A single ILC can be used to hydrolyze fat in up to 500 mL of tube feeding formula, or two cartridges can be connected in tandem to break down the fat in up to 1000 mL of formula (Figure 3). The cartridge has been shown to improve many GI symptoms associated with fat malabsorption in patients with EPI as a result of cystic fibrosis. In addition, the cartridge increases fatty acid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in plasma and red blood cell membranes, which is a surrogate marker for overall fat absorption (Freedman et al., 2017a; Stevens et al., 2018). However, description of ILC use in patients with PC on EN is limited. The purpose of this clinical observation is to demonstrate the use of the ILC in two patients with recurrent PC who require EN for supplemental nutrition due to failure to thrive, weight loss, and malnutrition.FIGURE 1.: The immobilized lipase cartridge is a single-use device that connects in-line with the patient’s feeding set and enteral tube. Used with permission from Alcresta Therapeutics, Inc. All rights reserved.FIGURE 2.: An immobilized lipase cartridge (ILC) contains lipase enzyme bound to small white beads which are held in place by two filters. The inlet and outlet connect directly to tube feeding sets and enteral feeding tubes. Used with permission from Alcresta Therapeutics, Inc. All rights reserved.FIGURE 3.: A single immobilized lipase cartridge is used with each 500 mL of enteral formula, or two cartridges may be connected in tandem to use with up to 1000 mL of formula. Used with permission from Alcresta Therapeutics, Inc. All rights reserved. Nurses in various fields can benefit from knowing about the use and functionality of the ILC. Nurses play a key role in screening for malnutrition, recognizing symptoms of malabsorption, and coordinating care for complex patients. The use of this cartridge is not limited to PCs but can be used with any patient with fat malabsorption on enteral feeding. Being able to identify the possible need and able to correctly understand the mechanics of this device when educating and caring for a patient can help support the complex management of patients with EPI who rely on tube feeding as a primary source of nutrition. There are many nuances to learn with this device such as enteral volume limitations, enteral formula compatibility, and the existence of a tube feeding pump in the patient’s plan of care which impacts insurance coverage. Case Study 1 Patient 1 is a 70-year-old male with a history of PC and pancreaticoduodenectomy (Whipple procedure) performed in 2016. The patient was referred to a dietitian for evaluation of EPI and nutrition management recommendations in September 2019. Anthropometric data included a height of 167.6 cm (66 inches), body weight of 72.3 kg (159 pounds), and BMI of 25.7 kg/m2 (Figure 4). The patient reported a recent 5–7 kg weight loss and classic signs and symptoms of EPI, so PERT was initiated at 48,000 lipase units taken with each of the frequent small meals he consumed. Several months later, he was found to have recurrent PC and was started on FOLFIRINOX chemotherapy. In January 2020, his weight had declined to 61.2 kg (135 pounds) so PERT dosage was increased to 72,000 lipase units per meal and 36,000 lipase units with snacks. The patient was trialed on multiple brands and strengths of PERT when weight and symptoms did not improve.FIGURE 4.: Case Study 1 weight timeline. In April 2020, the patient developed failure to thrive; his weight was down to 54.5 kg (120 pounds) and BMI was 19.4 kg/m2. He had complaints of gas, bloating, and diarrhea, leading to poor oral intake. A jejunostomy tube (J-tube) was placed and he was started on a standard 1.0 kcal/mL EN formula with PERT taken by mouth. One month after EN was initiated, the patient continued to complain of gas, distention, loose stools, and further weight loss resulting in a weight of 54.1 kg (119 pounds). He was trialed on a 1.0 kcal/mL plant-based formula but continued to experience GI symptoms and weight loss. In June 2020, his EN formula was changed to a 1.5 kcal/mL peptide-based formula and ILC was initiated. A weight increase of 3.2 kg (7 pounds) was noted within the next 11 days. In June 2020, he was receiving 1900 mL, or 8 cartons, of formula at a rate of 100 mL/hr for 19 hours per day. The patient requested 24-hour feeds to help speed weight gain, so he was placed on nocturnal EN with ILC and took 48,000 lipase units of PERT orally every 2–3 hours with EN during waking hours. Though GI symptoms were improved once ILC was initiated, the patient continued to struggle with some persistent GI side effects related to multi-modality chemotherapy treatments. However, his weight continued to increase to 61.5 kg (135 pounds), a 7.3 kg (16 pound) weight gain in 5 weeks. In July 2020, the patient continued on 1650–1900 mL of formula via J-tube daily. Over the next couple of months, his weight fluctuated from 57 to 60 kg. By December 2020, the patient’s weight and BMI were up to 65.9 kg (145 lbs) and 23.4 kg/m2, respectively, so he began to reduce his daily EN volume and transitioned to nocturnal EN only. By January 2021, the patient continued to use ILC with nightly feedings of 1200 mL of 1.5 kcal/mL peptide-based formula and took PERT with oral meals and snacks during the day. Despite being on chemotherapy, his weight continued to improve and was stabilized between 66 and 68 kgs (145–150 pounds). Case Study 2 Patient 2 is a 73-year-old male who was diagnosed with PC in 2018 and underwent surgery (distal pancreatectomy and celiac axis resection), chemotherapy (gemcitabine + abraxane), and radiation. Initial anthropometric data in March 2018 included a height of 178 cm (70 inches), weight of 96.4 kg (212 pounds), and BMI of 30.4 kg/m2 (Figure 5). By the end of November 2019, the patient’s weight had decreased 34% to 63.6 kg (140 lbs), with a BMI of 20.1 kg/m2. In 2019, chemotherapy was stopped due to a severe reaction. In March 2020, the patient was found to have disease recurrence. In July 2020, the patient had a weight of 45.9 kg (101 lbs) and BMI of 14.5 kg/m2, representing a 52% weight loss over the course of 2 years. A gastrojejunostomy (G-J) tube was placed due to continued weight loss and EN was initiated with a standard fiber-free 1.2 kcal/mL formula with intact protein. He received 5 cartons, approximately 1200 mL, of formula via G-J tube at 80 mL/hr for 15 hours per day and oral PERT.FIGURE 5.: Case Study 2 weight timeline. In August 2020, the patient had multiple hospital admissions for weakness, fever, sepsis, urinary tract infection, and pneumonia. Nutrition-focused physical exams revealed moderate-to-severe muscle wasting in the temporal region. In October 2020, the patient was admitted with a small bowel obstruction due to stricture at the junction of his duodenum and jejunum. Another nutrition-focused physical exam was performed and revealed subcutaneous fat loss in his orbital and cheek region and severe muscle wasting in the temporal region, suggesting worsening malnutrition. His weight decreased further to 45.4 kg (99.8) lbs with a BMI of 14.3 kg/m2. He was placed on total parenteral nutrition (TPN) and transferred to the hospital where he received initial cancer treatment. After discharge, the patient was referred to an outpatient oncology dietitian. At the initial visit in mid-October 2020, the patient had successfully weaned from TPN and was infusing 6 cartons or 1400 mL of standard fiber-free 1.2 kcal/mL formula per day at 120 mL/hour via G-J tube. He was taking 12,000 lipase units of PERT with each meal and was dosing PERT intermittently with EN. At the initial evaluation, he was reporting 3–4 episodes of diarrhea per day, so he his EN formula was changed to a peptide-based 1.5 kcal/mL formula. Oral PERT dose was increased to 80,000 lipase units per meal and the patient was instructed to take PERT intermittently with EN. At a visit in late October 2020, the patient continued to report 3–4 episodes of diarrhea despite higher PERT dose and use of peptide-based formula. Due to continued GI symptoms, ILC was initiated with EN. The patient reported immediate improvements in diarrhea. By the end of November 2020, the patient’s weight was up to 56.4 kg (124 lbs) and he was tolerating EN well at 120 mL/hour with use of the ILC. This patient’s nutritional goal was to increase his weight to 59.1 kg (130 lbs), which would allow him to have his G-J tube removed. By January 2021, this weight was achieved and feeding tube was removed. He experienced no further hospitalizations after initiating ILC with EN. Discussion Patients with cancer have a high prevalence of cancer-related malnutrition, which contributes to negative consequences and poor outcomes. More than 70% of patients with PC and upper GI cancers suffer from malnutrition (Silva et al., 2015). A lower BMI causes a longer post-operative hospital stay and affects survival (Hendifar et al., 2016). Additionally, cachexia is a widely described process in patients with PC, which is characterized by muscle wasting and poor nutritional status. Patients with this syndrome have poor outcomes in PC and no therapies have established efficacy (Hendifar et al., 2014; Hendifar et al., 2016). Despite high nutritional risk, patients with PC may not be referred to a dietitian nor receive an adequate dose of PERT. A 2014 study showed that only 33% of post-surgical patients are seen by a dietitian (Sikkens et al., 2014). Patients with PC are at a higher risk of malnutrition due to multiple factors, which include EPI. As a result, they may require EN. Patients receiving EN may suffer from malabsorption. Semi-elemental or elemental enteral formulas are designed to address malabsorption since they are predigested, contain a greater percentage of fat as medium-chain triglycerides, and are lower in total fat. However, some of these formulas still contain 30–50 g of long-chain triglycerides, which are not hydrolyzed. These fats cannot be pre-hydrolyzed due to poor shelf life and stability and are provided at a higher amount than some patients with severe EPI can absorb, contributing to malabsorption (Berry, 2014). PERT has limited effectiveness with continuous feeds, which leads to inadequate absorption. Patients can have asynchrony of pancreatic stimulation and secretion in response to the J-tube terminating in the small bowel, while enzymes are taken by mouth. This results in the patient developing gastroparesis, worsening this issue. The intestinal pH in patients with EPI is often acidic because of a low pancreatic bicarbonate secretion and this is not ideal for PERT to be optimized or enteric coating removal (Dominguez-Muñoz, 2018). In contrast, the digestive cartridge is effective at the pH of the enteral formula. Furthermore, PERT is only active for 45–60 minutes and requires frequent dosing with continuous feeds. The digestive cartridge continuously hydrolyzes fat in formula prior to infusion into the gastrointestinal (GI) tract. Enzymes found in the digestive system include lipase, amylase, and protease. Lipase hydrolyzes fats, amylase hydrolyzes starches, and protease acts on proteins. Pancreatic lipase accounts for up to 90% of fat digestion and fats remain mostly unchanged until they reach the small intestine. Starch and protein digestion, however, are not dependent upon enzymes released by the pancreas. Therefore, lipase-containing cartridges aid in fat absorption, which is beneficial since fat is the most poorly absorbed macronutrient. Patients with PC suffer from the consequences of EPI along with the negative effects that PC treatments have on the GI system. Long-term survivors of PC have often undergone surgery to remove all or part of the pancreas. Patients with operable PC often undergo either a pancreaticoduodenectomy (Whipple procedure) or distal pancreatectomy. During a Whipple procedure, the head of the pancreas, gallbladder, duodenum, and part of the stomach are removed (Figure 6). In a distal pancreatectomy, the tail of the pancreas is removed (Figure patients are at a high risk of nutrition including EPI, and & 2017). of patients with operable develop EPI prior to surgery and develop EPI after surgery et al., et al., et al., 2014). This at a higher risk for malnutrition & of the head of the pancreas, duodenum, gallbladder, distal and part of the in a classic pancreaticoduodenectomy or Whipple after surgery, Whipple Used with permission of for and all rights reserved.FIGURE of the tail of the pancreas or the tail and a portion of the body of the pancreas in a distal pancreatectomy. pancreatectomy after Used with permission of for and all rights reserved. and radiation can to GI symptoms that with by EPI, the of GI symptoms are related to side effects or EPI. This can present challenges when the of PERT or ILC Patients and may struggle to an initial benefit of PERT or ILC if treatment side effects at the As seen with Patient several GI symptoms were improved while on but some due to side effects from chemotherapy. However, with continued ILC he was able to increase his weight and his EN The survival rate for all cancers that were diagnosed during was but this is only for PC et al., 2020). and GI symptoms into a poor quality of life and survival Quality of life and survival are improved with weight in patients with unresectable GI symptoms can be an of poor quality of life in long-term survivors after a Whipple et al., 2018). Thus, quality of life patients for pancreatic insufficiency and GI symptoms be beneficial for survival in patients with for Patients with PC surgery often develop EPI and require EN to maintain Patients are at increased risk of malnutrition, which can impact survival and quality of Despite increased nutrition risk, patients may not on a if at However, have with which an ideal of the to patients for malnutrition and signs and symptoms of malabsorption. Nurses play a role in complex disease management of with exocrine pancreatic Patients with feeding tubes are to be to Nurses in various settings with these patients including in home health, gastroenterology, oncology and hospital The case studies in this report demonstrate that an immobilized lipase cartridge use results in improvements in GI symptoms, nutritional and weight in patients with recurrent
DOI: 10.1097/sga.0000000000000900
Language: English
Field: Nursing
Open Access status: hybrid
OpenAlex ID: W4410906969
FWCI:
Cites: 29
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