Validation of an omega-3 substrate challenge absorption test as an indicator of global fat lipolysis.

INTRODUCTION: The coefficient of fat absorption (CFA) quantifies fat that remains in stool after digestion and is not a direct measure of lipolysis. CFA has been used to assess treatment of pancreatic insufficiency but does not correlate with pancreatic enzyme replacement therapy dose. We explored use of an omega-3 substrate absorption challenge test as a sensitive test of lipolysis and absorption. METHODS: We studied a novel microbially-derived lipase (SNSP003) employing an established surgical model commonly used to study the uptake of macronutrients, the exocrine pancreatic insufficient pig. Pigs were fed a high-fat diet and given a standardized omega-3 substrate challenge to test the effect of lipolysis on its absorption. Blood was drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following the substrate challenge and was analyzed for omega-3 and total fat levels (c14:c24). SNSP003 was also compard to porcine pancrelipase. RESULTS: The absorption of omega-3 fats was significantly increased following administration of 40, 80 and 120 mg SNSP003 lipase by 51% (p = 0.02), 89%, (p = 0.001) and 64% (p = 0.01), respectively, compared to that observed when no lipase was administered to the pigs, with Tmax at 4 hours. The two highest SNSP003 doses were compared to porcine pancrelipase and no significant differences were observed. Both doses increased plasma total fatty acids (141% for the 80 mg dose (p = 0.001) and 133% for the 120 mg dose (p = 0.006), compared to no lipase) and no significant differences were observed between the SNSP003 lipase doses and porcine pancrelipase. CONCLUSION: The omega-3 substrate absorption challenge test differentiates among different doses of a novel microbially-derived lipase and correlates with global fat lipolysis and absorption in exocrine pancreatic insufficient pigs. No significant differences were observed between the two highest novel lipase doses and porcine pancrelipase. Studies in humans should be designed to support the evidence presented here that suggests the omega-3 substrate absorption challenge test has advantages over the coefficient of fat absorption test to study lipase activity.

In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model.

The dissolution characteristics of five capsules (Next Generation Enteric [NGE], Vcaps® Enteric [VCE], VCE DUOCAP® [VCE/VCE] system, Hard Gelatin Capsule [HGC] as negative control, and Creon® 10,000 U as market reference) were evaluated using an in vitro simulation of the stomach and upper intestinal tract with an acidic duodenal incubation (pH 4.5 for the first 10 min, pH 6 for the remaining 17 min) to simulate exocrine pancreatic insufficiency. Caffeine was a marker of capsule dissolution, and tributyrin to butyrate conversion measured pancrelipase activity. All capsules were filled with pancrelipase; the NGE, VCE, VCE/VCE, and HGC capsules also contained 50 mg caffeine. Caffeine was released first from the HGC capsule, followed by the VCE, NGE, and VCE/VCE capsules. Pancrelipase activity followed this trend and demonstrated a similar activity level over time for the NGE, VCE/VCE, and Creon® capsules. The HGC formulation confirmed gastric degradation of unprotected pancrelipase. NGE capsules provided similar protection to the simple fill formulation as observed for the complex formulation of the Creon® capsule in a setting with increased pepsin activity and may hasten the time needed to go from formula development to first-in-human studies for pH sensitive drugs or those requiring small intestine targeting.

Impact of Pancreatic Enzymes on Enteral Fat and Nitrogen Absorption in Short Bowel Syndrome.

OBJECTIVES: Patients with short bowel syndrome (SBS) can have a high morbidity rate. To minimize morbidity, enteral autonomy is the primary goal in clinical management of patients with SBS. This is often difficult to achieve because of significant malabsorption. To date, there are limited therapies that improve absorption in patients with SBS. The impact of pancreatic enzyme replacement treatment on enteral absorption has not been studied in this population and was the primary aim of this study. SUBJECTS/METHODS: This was an interventional study in 11 subjects (6 pediatric subjects ages 4.0-17.9 years, 5 adult subjects 18-75 years) that compared enteral absorption in each subject before and after pancreatic enzyme medication (Creon). Coefficient of fat absorption (CFA) and coefficient of nitrogen absorption (CNA) were used as markers of enteral absorption of fat and protein, respectively. RESULTS: There was no statistically significant mean change in CFA and CNA before and after pancreatic enzyme medication therapy. Six subjects demonstrated an increase in CFA and 8 subjects demonstrated an increase in CNA after the use of pancreatic enzyme medication therapy. CONCLUSIONS: There was no statistically significant improvement in enteral fat and protein absorption in the cohort as a whole, though several subjects demonstrated an improvement. These results suggest that some patients with SBS may benefit from treatment with pancreatic enzymes. Further studies are needed to better evaluate the effect of pancreatic enzyme therapy on enteral absorption in subjects with SBS and to characterize factors that may predict a positive response.

A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States.

OBJECTIVES: This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D). METHODS: Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline. RESULTS: A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959). CONCLUSIONS: Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.

Difference in Performance of EPI Pigs Fed Either Lipase-Predigested or Creon®-Supplemented Semielemental Diet.

Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H-healthy pigs receiving PAF; P-EPI pigs receiving PAF+PERT; and L-EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H (p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs (p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs' growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.

Effect of Pancrelipase Therapy on Exocrine Pancreatic Insufficiency Symptoms and Coefficient of Fat Absorption Associated With Chronic Pancreatitis.

OBJECTIVE: The aim of this study was to evaluate whether improvement in coefficient of fat absorption (CFA) with pancreatic enzyme replacement therapy correlates with clinical symptoms in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency. METHODS: Data were pooled from 2 randomized double-blind trials of the effects of 1 week of pancrelipase (n = 59) versus placebo (n = 57) on CFA and stool frequency, stool consistency, abdominal pain, and flatulence; 1 trial included a 51-week open-label pancrelipase treatment period (n = 34). RESULTS: Compared with placebo, significantly more patients receiving pancrelipase reported decreased stool frequency at week 1 (72% vs 38%; P < 0.001). Although 30% of patients receiving pancrelipase and 20% receiving placebo reported improved stool consistency, changes in stool consistency, abdominal pain, and flatulence were not different between groups. Mean CFA absolute change from baseline was significantly greater with pancrelipase versus placebo (24.7% vs 6.4%; P < 0.001). Improvements in stool consistency and frequency correlated with CFA improvement. Symptom improvements persisted or further improved through 52 weeks of treatment. CONCLUSIONS: Pancrelipase significantly improved exocrine pancreatic insufficiency maldigestive symptoms. Improvements in objective stool symptoms with pancreatic enzyme replacement therapy correlated with CFA improvement at 1 week.

The lived experience of adults with cystic fibrosis: what they would tell their younger selves about the gut.

BACKGROUND: Little is known about adults' experience of living with cystic fibrosis (CF) specifically in relation to the gut. However, their unique perspectives may be meaningful to children with CF and inform the understanding and practice of dietitians. The present study aimed to explore adults' lived experience of the CF gut and how they learnt to manage the gut as they were growing up. METHODS: Semi-structured interviews were conducted with adult inpatients (n = 10). Interviews were audio-recorded, transcribed verbatim and accounts analysed using interpretative phenomenological analysis. RESULTS: Three super-ordinate themes were identified: taking Creon, the learning process and this much I (now) know. Participants accounts of how CF affects the gut predominantly focused on taking Creon (pancreatin, Mylan). Various strategies were employed for coping with peer responses to taking Creon at school. Several participants reached adulthood before they understood and/or accepted that taking Creon consistently needed to be normal for them. Knowledge and understanding developed over time, with 'CF experience' and was shaped by family, CF care teams and other children with CF. All had unmet information needs when growing up. Having key explanations earlier, to make connections between eating, taking Creon, gaining weight and growth, did or would have helped most participants. Participants urged children to be assertive, ask questions and not only be involved in managing their diet and gut, but also begin to take control of this aspect of their CF. CONCLUSIONS: Supporting development of knowledge, skills and confidence to manage diet and the gut needs to be integral to care throughout childhood.

Case report of oxalate nephropathy in a patient with pancreatic metastases from renal carcinoma.

BACKGROUND: Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment. CASE PRESENTATION: We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases. CONCLUSIONS: This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.

Pancreatic Function in Chronic Pancreatitis: A Cohort Study Comparing 3 Methods of Detecting Fat Malabsorption and the Impact of Short-term Pancreatic Enzyme Replacement Therapy.

OBJECTIVES: Reliable pancreatic function tests in patients with chronic pancreatitis (CP) are needed. This cohort study identified malabsorption in people with CP compared with healthy people and then investigated short-term pancreatic enzyme replacement therapy (PERT) and fat malabsorption, nutritional status, and quality of life (QOL). METHODS: Subjects with CP were evaluated before and after PERT and compared with the healthy cohort using coefficient of fat absorption (CFA), stool bomb calorimetry, and the malabsorption blood test (MBT). Anthropometrics, micronutrients, and QOL data were collected. Group means at baseline and after PERT were analyzed. RESULTS: The 24 subjects with CP had greater stool energy loss (5668 cal/g [standard deviation {SD}, 753] vs 5152 cal/g [SD, 418], P < 0.01), reduced triglyceride absorption (MBT, 8.3 mg·h/dL [SD, 4.3] vs 17.7 mg·h/dL [SD, 10.3], P < 0.001), lower fat intake, and poorer QOL. Differences in CFA were not significant (90.9% [SD, 12.8] vs 95.4% [SD, 9.3]). After PERT, triglyceride absorption (Δ = 1.7 [SD, 3], P < 0.05) and QOL increased. CONCLUSIONS: The MBT detected changes in triglyceride absorption in the absence of CFA changes. The MBT may be helpful in guiding PERT initiation in patients with CP before significant morbidity.

Frequency of Appropriate Use of Pancreatic Enzyme Replacement Therapy and Symptomatic Response in Pancreatic Cancer Patients.

OBJECTIVES: Pancreatic cancer (PC) and its treatments can result in pancreatic exocrine insufficiency that requires pancreatic enzyme replacement therapy (PERT). Appropriate PERT usage is during meals and snacks. The aim was to determine the frequency of appropriate use of PERT and its impact on symptom alleviation in PC through a patient-reported outcomes online platform. METHODS: Users in the Pancreatic Cancer Action Network's Patient Registry were prompted to answer a standalone questionnaire about their experience with PERT. RESULTS: Two hundred sixty-two users completed the PERT questionnaire (January 2016-January 2018). Patients who reported taking PERT with meals had higher alleviation of symptoms compared with those taking PERT prior to or after meals. Specifically, "feeling of indigestion," "light-colored or orange stools," and "visible food particles in stool" were significantly decreased. Patients taking PERT with meals reported weight gain and less weight loss. CONCLUSIONS: Of the 89% of PC patients prescribed PERT, 65% were prescribed PERT appropriately with all meals and snacks. Overall compliance with PERT administration guidelines was low (50% [105/208]). Improvement in symptoms significantly correlated with appropriate use of PERT. Increase in PC patient and provider education about appropriate PERT usage and administration is warranted.

Camostat Mesilate, Pancrelipase, and Rabeprazole Combination Therapy Improves Epigastric Pain in Early Chronic Pancreatitis and Functional Dyspepsia with Pancreatic Enzyme Abnormalities.

BACKGROUND/AIMS: The aims of the study are to clarify the pathophysiological differences among early chronic pancreatitis (ECP), functional dyspepsia with pancreatic (FD-P) enzyme abnormalities and FD patients and to determine whether camostat mesilate, pancrelipase, and rabeprazole triple therapy improve FD symptoms in the ECP patients and FD-P patients in cross-over way. METHODS: We enrolled 84 consecutive patients presenting with typical symptoms of FD patients (n = 42), ECP patients (n = 15), and FD-P patients (n = 27). Gastric emptying was assessed by the 13C-acetate breath test. ECP was diagnosed based on the criteria recommended by the Japan Pancreatic Association. RESULTS: The proportions of female in ECP patients and FD-P were significantly higher compared to that in FD patients. The early phase of gastric emptying in ECP and FD-P patients was significantly disturbed compared to that in FD patients. The primary outcome of this study is that 4 weeks of camostat mesilate, pancrelipase, and rabeprazole triple therapy significantly ameliorated epigastric pain in ECP patients compared to acotiamide and rabeprazole combination therapy. CONCLUSION: Although there were no significant differences in pathophysiology between ECP patients and FD-P patients, triple therapy can significantly ameliorate epigastric pain in ECP patients. Further studies will be needed to clarify why triple therapy can improve epigastric pain in ECP patients.

Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and malnutrition are prevalent among patients with pancreatic adenocarcinoma. Pancreatic enzyme replacement therapy (PERT) can correct PEI but its use among patients with pancreatic cancer is unclear as are effects upon survival. This population-based study sought to address these issues METHODS: Subjects with pancreatic adenocarcinoma were identified from the UK Clinical Practice Research Datalink (CPRD). Propensity score matching generated matched pairs of subjects who did and did not receive PERT. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables RESULTS: PERT use among the whole cohort (987/4554) was 21.7%. Some 1614 subjects generated 807 matched pairs. This resulted in a total, censored follow-up period of 1643 years. There were 1403 deaths in total, representing unadjusted mortality rates of 748 and 994 deaths per 1000 person-years for PERT-treated cases and their matched non-PERT-treated controls, respectively. With reference to the observed survival in pancreatic adenocarcinoma patients, adjusted median survival time was 262% greater in PERT-treated cases (survival time ratio (STR) = 2.62, 95% CI 2.27-3.02) when compared with matched, non-PERT-treated controls. Survival remained significantly greater among subjects receiving PERT regardless of the studied subgroup with respect to use of surgery or chemotherapy CONCLUSIONS: This population based study observes that the majority of patients with pancreatic adenocarcinoma do not receive PERT. PERT is associated with increased survival among patients with pancreatic adenocarcinoma suggesting a lack of clinical awareness and potential benefit of addressing malnutrition among these patients.

Pancreatic Enzyme Supplementation in Patients with Atopic Dermatitis and Food Allergies: An Open-Label Pilot Study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects both patients and their families. Current therapies often alleviate symptoms but do not prevent or eradicate the disease. OBJECTIVES: Our objective was to determine whether pancreatic enzyme supplementation is an effective and safe treatment in refractory pediatric AD associated with food allergies. METHODS: We conducted an open-label pilot study using a case-control design. Patients with severe AD and known food allergies refractory to conventional therapies and exclusion diets were recruited and treated for 6 weeks with oral supplementation of pancreatic enzymes. The primary endpoint was the severity of AD, using the Scoring Atopic Dermatitis (SCORAD) index. Secondary measures included markers of intestinal permeability (urinary sucrose and lactulose/mannitol excretion). RESULTS: A total of 11 patients met all eligibility criteria and completed the trial. Significant improvement in AD was observed after 6 weeks of pancreatic enzyme supplementation (SCORAD index 52.3 ± 5.5 vs. 34.6 ± 7.6; p = 0.0008). Beneficial effect was observed in 9 of 11 patients, without adverse events. Fractional urinary sucrose excretion improved to a level comparable to that of age-matched controls (p < 0.05). However, urinary lactulose:mannitol ratios remained abnormally high compared with those of controls (p = 0.01). CONCLUSIONS: Pancreatic enzyme supplementation was associated with improved AD and gastroduodenal permeability. Additional randomized placebo-controlled studies are required before this treatment can be recommended in this clinical setting.

Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency.

BACKGROUND: Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be advantageous. HYPOTHESIS/OBJECTIVES: Enteric coated enzyme supplements are superior to uncoated supplements in dogs with clinical EPI. ANIMALS: Eleven dogs with naturally occurring EPI that were apparently free from other diseases. METHODS: Randomized, blinded, controlled cross-over clinical trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a commercially available uncoated product in dogs with clinical EPI. Search of serum canine serum trypsin-like immunoreactivity concentration ≤ 2.5 µg/L in the Gastrointestinal Laboratory database was used to identify dogs with EPI. RESULTS: There was no difference -4.46% (95% CI: -7.97%--0.96%; P = .15) in the % acid hydrolysis fecal fat (primary outcome) between the enteric coated formulation (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the study. Other variables did not differ between treatments. CONCLUSIONS AND CLINICAL IMPORTANCE: This study, which had low statistical power, did not detect a difference between formulations.

A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer.

OBJECTIVE: Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients. METHODS: Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival. RESULTS: A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070). CONCLUSIONS: In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis.

BACKGROUND: Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer. METHODS: A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan-Meier and Cox regression; groups were compared using the log-rank test. RESULTS: Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28-100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19-9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0-211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4-114.6 days) (HR 2.117, 95% CI 1.493-3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55-4.11; P < 0.001). CONCLUSIONS: In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

Use of an In-line Digestive Cartridge With Enteral Nutrition Improves the Weight Trajectory of 2 Children With Cystic Fibrosis Complicated by Another Medical Diagnosis.

This clinical observation describes the enteral nutrition (EN) management of 2 toddlers at high nutrition risk due to cystic fibrosis (CF), exocrine pancreatic insufficiency, and comorbid medical conditions. The first case report describes a boy with severe malabsorption after intestinal resection. The second case report reviews a boy with CF and neuroblastoma. When pancreatic enzyme replacement therapy with EN was not effective or appropriate, use of an in-line digestive cartridge was initiated. While using the digestive cartridge, both children showed improvements in their anthropometric measures. This observation reviews the nutrition management throughout their clinical course and describes the use of a digestive cartridge with EN.

¿Es una alternativa terapéutica la pancrelipasa (Zenpep®) para pacientes con fibrosis quística? / Is pancrelipase (Zenpep®) a therapeutic alternative for patients with cystic fibrosis?

INTRODUCCIÓN: La fibrosis quística es una enfermedad multisistémica asociada a un componente genético, que se caracteriza por la presencia constante de secreciones en múltiples órganos, siendo las exacerbaciones pulmonares las que conllevan la mayor morbilidad y mortalidad Dentro de las consecuencias de esta condición de salud, la complicación gastrointestinal más frecuente es la insuficiencia pancreática, la cual es causada por una baja en la producción de enzimas. En estos casos, las terapias de reemplazo enzimático son una alternativa terapéutica utilizada, especialmente en niños y adolescentes. El Ministerio de Salud, a través del plan de Garantías Explícitas en Salud (GES), comprende dentro de su cobertura para esta condición de salud, las terapias de reemplazo enzimático para insuficiencia pancreática. Sin embargo, existe un único laboratorio que cuenta con registro sanitario en Chile (pancreatina). De esta forma, se le ha solicitado al Ministerio la inclusión de otras alternativas terapéuticas disponibles y, en particular de pancrelipasa (Zenpep®). Esta síntesis rápida de evidencia pretende aportar con la evidencia disponible que compare el uso de pancrelipasa con placebo para pacientes con fibrosis quística. METODOLOGÍA: fueron seleccionados por dos revisores independientes, discutiendo cada uno de los disensos encontrados. Se encontraron inicialmente 2 revisiones sistemáticas. Sin embargo, estos estudios comparaban principalmente distintas formas farmacéuticas o dosis de enzimas pancreáticas, por lo que se consideró que no abordaba la pregunta formulada. De esta forma, se realizó una búsqueda de estudios primarios, la cual también fue seleccionada por dos revisores independientes, con discusión de cada uno de los disensos. Finalmente, se seleccionaron 8 estudios primarios (7­14) publicados entre 2000 y 2013. Todos fueron ensayos controlados aleatorizados con crossover, con excepción de uno que fue paralelo. RESULTADOS: Los hallazgos aquí presentados son separados según la población que se está estudiando. De esta forma, el hallazgo 1 reporta la eficacia de la pancrelipasa en niños, el hallazgo 2 en adultos, y el hallazgo 3 reporta los estudios que no reportaron los resultados según grupo de edad. Cada hallazgo contiene además una tabla resumen con los resultados, mostrando la certeza en la evidencia de cada uno de los desenlaces encontrados, de acuerdo al sistema GRADE. CONSIDERACIONES: Consideraciones de Aplicabilidad: La evidencia aquí contemplada se aplica a niños y adultos con insuficiencia pancreática por fibrosis quística. Se contemplaron todo tipo de presentaciones de pancreatina, las que podrían ser distintas a la que se está solicitando comercializar en el país. Los niveles de absorción de grasa de los pacientes que no recibieron pancrelipasa fueron obtenidos de los grupos control de los estudios incluidos. Sin embargo, algunos estudios sugieren que estos niveles podrían ser aún menores, por lo que convendría evaluar el efecto reportado en los hallazgos de esta síntesis. Consideraciones Económicas: Se desconoce el costo del medicamento, ya que no se encuentra disponible en venta a nivel nacional. Consideraciones de Equidad: La indisponibilidad de una alternativa terapéutica efectiva en nuestro país, limita de forma transversal el acceso a la salud, de forma equitativa, a la población, considerando que solo tendrán acceso a este quienes puedan importarlo. La inclusión de la pancrelipasa como alternativa terapéutica en el GES mejoraría la cobertura de la terapia de reemplazo enzimático en pacientes con fibrosis quística, garantizándolo para toda la población. Consideraciones de Monitoreo y Evaluación: Es necesario asegurar, que la alternativa terapéutica sería utilizada por los profesionales prescriptores a nivel nacional, para contar con el correcto acceso de la tecnología sanitaria. El principio activo no cuenta con registro sanitario vigente en el Instituto de Salud Pública (ISPCH). No se encontró movimiento de venta o compra del medicamento en el año 2017, tanto en el mercado público nacional (mercado público), como en el mercado privado (IMSHealth), la única enzima pancreática que se encontró comercializada fue Pancreatina (Creon®). Se debe evaluar el interés de laboratorios proveedores de pancrelipasa de registrar su producto en Chile. En la guía de práctica clínica del año 2017, se especifica como manejo habitual, que todos los pacientes con Fibrosis Quística reciban enzimas pancreáticas. Se ha estudiado la eficacia de la adyuvancia de otros tratamientos a la pancrelipasa para mejorar la absorción de grasa en pacientes con fibrosis quística. De esta forma, sería importante evaluar la necesidad de incorporar fármacos como ranitidina u omeprazol en caso de que las preparaciones de enzimas pancreáticas no alcancen un nivel adecuado de absorción. Existe una revisión Cochrane que comparó distintas presentaciones de enzimas pancreáticas, concluyendo que no existiría un beneficio adicional de las preparaciones con recubrimiento entérico. Además, señala la importancia de realizar estudios aleatorizados con grupos paralelos, para contar con evidencia de mejor calidad. De esta forma, sería conveniente monitorear la publicación de nueva evidencia en este campo de acción.