The effect of CFTR modulators on a cystic fibrosis patient presenting with recurrent pancreatitis in the absence of respiratory symptoms: a case report.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder of the epithelial CFTR apical chloride channel resulting in multi-organ manifestations, including pancreatic exocrine secretion. In the pancreas, CFTR abnormality results in abnormally viscous secretions that obstruct proximal ducts leading to fibrotic injury and ultimately pancreatic insufficiency in 85% of the CF population. CFTR modulators, including the potentiator ivacaftor, augment channel gating to restore 30-50% of CFTR-mediated anion transport. While CFTR modulation has been shown to alkalinize the pH of the alimentary tract and potentially augment pancreatic enzyme activity, the effect of ivacaftor on recurrent pancreatitis is emerging. Here we describe a case of a patient with CF (R117H/7 T/F508del) who presented with recurrent pancreatitis who was effectively treated with ivacaftor in the absence of respiratory symptoms. CASE PRESENTATION: A 24-year-old white male with past medical history of recurrent acute pancreatitis presented for evaluation following a referral from an outside hospital. The patient reported a lifetime of gastrointestinal symptoms requiring over 20 hospitalizations for pancreatitis in the last 10 years. Prior U/S and CT imaging for pancreatitis ruled out gallstones or anatomical etiologies. Family history included a brother with CF carrier status who suffered from recurrent acute pancreatitis. Sweat chloride testing was suggestive of CFTR dysfunction (57 mmol/L). Genetic testing demonstrated disease causing CFTR mutations: R1117H/7 T/F508del. Patient was prescribed pancrelipase, however, he reported worsened gas and diarrhea symptoms. Pancrelipase was discontinued and the patient was prescribed ivacaftor 150 mg BID. After 6 weeks of ivacaftor treatment, patient reported improved gastrointestinal symptoms. For an additional 19 months, patient reported no episodes of pancreatitis until he discontinued ivacaftor. Over the next 3 weeks, patient experienced progressive nausea and sharp epigastric pain and laboratory studies confirmed pancreatitis. Patient was subsequently lost to follow up. CONCLUSIONS: These findings support a possible relationship between the use of CFTR modulators, such as ivacaftor, in the management of recurrent pancreatitis in the setting of patients with cystic fibrosis and a CFTR mutation with residual CFTR activity or otherwise known to be responsive in vitro. Ivacaftor may be useful for recurrent pancreatitis, even in the absence of respiratory morbidity.

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.

Supplementation of pancreatic digestive enzymes alters the composition of intestinal microbiota in mice.

Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.

Pancrelipase-Induced Hypersensitivity Reaction: Case Report and Review of Literature.

INTRODUCTION: Drug-induced exanthems are commonly associated with NSAIDs, antibiotics, and anti-epileptics. Pancrelipase is frequently used for conditions resulting in pancreatic exocrine insufficiency. Published case reports of pancrelipase hypersensitivity focus on the respiratory manifestations. CASE REPORT: Here we report a case of skin hypersensitivity resulting from pancrelipase use. To further assess this association, we used a Naranjo nomogram, which determines the likelihood that an adverse drug reaction is the result of the drug itself. Our patient had a score of seven, suggesting our patient had a probably adverse drug reaction. DISCUSSION: As pancrelipase is a commonly prescribed drug, clinicians should be aware of the potential hypersensitivity skin reactions associated with pancrelipase.

Impact of Preoperative Osteosarcopenia and Postoperative Administration of Pancrelipase on the Prognosis of Borderline Resectable and Unresectable Locally Advanced Pancreatic Cancer.

BACKGROUND: This study aimed to identify postoperative recurrence and prognostic factors, including osteosarcopenia for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer and to examine the impact of postoperative pancreatic enzyme replacement therapy (PERT). METHODS: We retrospectively examined 32 resected patients with BR and UR-LA pancreatic cancer. We investigated independent factors in the disease-free survival and overall survival. The relation of osteosarcopenia with the clinicopathological factors was investigated. Additionally, the association of the administration of a standard dose of pancrelipase, the amount of lipase required for patients with pancreatic exocrine insufficiency, for ≥6 months postoperatively with improvement of sarcopenia, osteopenia, and osteosarcopenia and completion rate of adjuvant chemotherapy was investigated. RESULTS: Multivariate analyses identified osteosarcopenia (P = 0.049) and lymph node metastasis (P = 0.01) as independent recurrence predictors, and osteosarcopenia (P = 0.002), maximum tumor diameter ≥40 mm (P = 0.006), and no adjuvant therapy (P = 0.01) as independent prognostic predictors. In the osteosarcopenia group, serum CA19-9 levels were higher (P = 0.03). The administration of a standard dose of pancrelipase for ≥6 months postoperatively was none in the osteosarcopenia group (0% vs 42.9%, P = 0.01), while significantly improved postoperative sarcopenia (33% vs 0%, P = 0.004), increased number of cycles of adjuvant chemotherapy (n = 6 vs n = 3, P = 0.03), and the completion rate of adjuvant chemotherapy in excluding cases interrupted because of recurrence (86% vs 25%, P = 0.007). CONCLUSIONS: Osteosarcopenia was an independent recurrent and prognostic factor in patients after pancreatectomy for locally advanced pancreatic cancer. Appropriate postoperative PERT may contribute to a better prognosis by improving sarcopenia and increasing the completion rate of adjuvant chemotherapy.

Two Cases of Rapidly Progressive Fatty Liver Disease due to Pancreatic Exocrine Insufficiency without a History of Surgery.

We herein report two cases of rapidly progressive fatty liver (FL) disease due to pancreatic exocrine insufficiency (PEI) without a surgical history. Two women, 59 and 72 years old, with no history of abdominal surgery presented to our hospital with severe anorexia and nausea persisting for one week. Examinations revealed progressive, marked FL disease with hepatomegaly and PEI, for which pancreatic enzyme replacement therapy was effective. Commonly known causes of PEI include chronic pancreatitis, abdominal surgery (e.g. pancreaticoduodenectomy), pancreatic cancer, and obstruction of the pancreatic duct, none of which were present in either of these two cases.

Therapeutic interventions alter ecological interactions among cystic fibrosis airway microbiota.

The airways of people with cystic fibrosis (CF) often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the CF airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK CF Registry. This longitudinal dataset (covering the period 2008-2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their CF genotype. Specifically, we wanted to identify trends in ecological relationships between the CF microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the "gut-lung axis" or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications.

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.

Pancreatic Exocrine Insufficiency in Intraductal Papillary Mucinous Carcinoma Presenting with Leg Edema Treated with Pancreatic Exocrine Replacement Therapy.

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.

Effect of pancrelipase in preventing pancreatic dysfunction after pancreaticoduodenectomy.

OBJECTIVES: Patients who have undergone pancreaticoduodenectomy (PD) may experience a long-term decrease in quality of life because of postoperative pancreatic dysfunction (such as digestive and absorption disorders) and fatty liver as a result of combined resection of the duodenum, gallbladder, and bile duct. The present study investigated the usefulness of pancrelipase for the prevention of pancreatic dysfunction after PD. METHODS: The data from 73 patients who underwent PD in a single institution were analyzed. Patients who underwent PD during 2007-2011 were administered the low-titer pancreatic enzyme preparations berizym® and pancreatin® (first period group), while patients who underwent PD during 2012-2017 were administered the high-titer pancreatic enzyme preparation pancrelipase (second period group). The following measures of the nutrition status were examined before and after PD: serum albumin concentration, total lymphocyte count, serum total cholesterol concentration, body mass index, controlling nutrition status (CONUT) index, Onodera's prognostic nutrition index (PNI), and liver computed tomography values. RESULTS: The second period group had significantly higher serum albumin concentrations at 3 and 6 months postoperatively, serum total cholesterol concentrations at 1 month postoperatively, and Onodera's PNI values at 3 and 6 months postoperatively than the first period group. The CONUT index values at 6 months after PD were significantly lower in the second period group than in the first period group. CONCLUSIONS: Pancrelipase is useful in improving the nutrition status and preventing fatty liver after PD.

Anasarca, steatorrhea, and hypoalbuminemia 18 years after total gastrectomy: a case report.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is known to occur after total gastrectomy. We experienced a case of PEI occurring 18 years after surgery, leading to a potentially fatal condition of capillary leak syndrome (CLS). CASE PRESENTATION: The case is a 58-year-old man on a healthy diet who underwent total gastrectomy 18 years before. He was admitted for a 3-month history of anasarca, steatorrhea, and hypoalbuminemia. An episode of fever occurred during workup, followed by pulmonary edema and shock. The patient was transferred to the intensive care unit and was started on fluid management with albumin infusion. A multidisciplinary team meeting was held, and a clinical diagnosis of PEI resulted in CLS was made and we started administration of oral pancrelipase to show clinical improvement. The patient was discharged, and he remained asymptomatic for 13 months. CONCLUSION: In a post-gastrectomy patient with malnutrition, PEI should be suspected regardless of the period since surgery. When recognized, immediate replenishment of albumin and pancreatic enzymes should be initiated to prevent clinical deterioration.

The prevalence and impact of low faecal elastase-1 in community-based patients with type 2 diabetes.

AIMS: To determine the prevalence of low faecal elastase-1 (FE-1) (≤200 µg/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement therapy (PERT) would reduce postprandial glycaemia after a high-fat, high-carbohydrate meal in T2DM subjects with low FE-1. METHODS: Of 109 community-based patients who submitted stool samples, 10 had low FE-1 and 8 were recruited (6 male, 2 female, 67.8 ±â€¯3.0 years). Participants were given a high-fat, high-carbohydrate meal (718 kcal) with either pancrelipase (50,000 units) or placebo in a randomised, double-blind, crossover fashion. The primary outcome was the difference in postprandial glycaemia following PERT vs placebo, as evaluated by the incremental area under the postprandial plasma glucose curve (iAUC). Secondary outcomes included differences in gastric half-emptying time (T50) measured using scintigraphy, and C-peptide iAUC. RESULTS: The prevalence of low FE-1 in T2DM was 9.2% (95% CI 3.8-14.6%). There was no difference in postprandial glycaemia iAUC (P = 0.38), gastric emptying T50 (P = 0.69) or C-peptide iAUC (P = 0.25) after PERT compared to placebo. CONCLUSIONS: Decreased FE-1 has a relatively low prevalence in community-based patients with T2DM, and PERT does not reduce postprandial glycaemia in these patients. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617000349347.

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.

Drug-induced dyspnea versus cystic fibrosis exacerbation: a diagnostic dilemma.

Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.

Do pancrelipase delayed-release capsules have a protective role against nonalcoholic fatty liver disease after pancreatoduodenectomy in patients with pancreatic cancer? A randomized controlled trial.

BACKGROUND: The aim of this randomized controlled trial (RCT) was to investigate whether pancrelipase protects against nonalcoholic fatty liver disease (NAFLD) development after pancreatoduodenectomy in patients with pancreatic cancer better than conventional pancreatic enzyme supplementation. METHODS: A total of 57 patients were randomly assigned to the study group (n = 29; pancrelipase replacement therapy) or the control group (n = 28; conventional pancreatic enzyme supplementation). NAFLD was defined as a liver-to-spleen attenuation ratio less than 0.9 on CT. Clinical and laboratory findings were also assessed. RESULTS: NAFLD was observed in 6/29 patients (21%) in the study group, and 11/28 patients (39%) in the control group, but this was not a statistically significant difference. In the control group, crossover to pancrelipase replacement therapy upon NAFLD diagnosis produced improvement in five out of 10 patients. Multivariate analysis showed that advanced age and extended resection were independent risk factors for NAFLD development. CONCLUSION: This RCT did not show a significant protective effect of pancrelipase replacement therapy over conventional pancreatic enzyme supplementation on NAFLD development after pancreatoduodenectomy for pancreatic cancer. Further studies are clearly required to investigate the etiology of and new therapeutic strategies for treatment-resistant NAFLD (UMIN 000019817).

Pretreatment of gastric outlet obstruction with pancrelipase: Report of a case.

INTRODUCTION: Gastric outlet obstruction is characterized by the retention of gastric contents. Removal of gastric contents is an important part of the treatment strategy. The use of a nasogastric tube alone can result in inadequate removal of gastric contents. We treated a patient with advanced gastric cancer and gastric outlet obstruction with pancrelipase to aid in the removal of gastric contents. PRESENTATION OF CASE: The patient is an 81-year-old man with a Type 3 gastric cancer nearly circumferentially involving the antrum, resulting in gastric outlet obstruction. A nasogastric tube was placed for four days, but drainage of gastric contents was inadequate. Pancrelipase was then given orally for four days, and gastric contents were evacuated. The patient underwent distal gastrectomy with Roux-en-Y reconstruction and was discharged from the hospital on postoperative day 14. DISCUSSION: This report suggests that pancrelipase may be beneficial in the treatment of patients with gastric outlet obstruction. CONCLUSION: Pancrelipase allowed gastric contents to be evacuated in a short period of time in a patient with gastric outlet obstruction.

Nutrition and pancreatic enzyme intake in patients with cystic fibrosis with distal intestinal obstruction syndrome.

BACKGROUND: The etiology of distal intestinal obstruction syndrome (DIOS) remains unclear. Food intake and pancreatic enzyme replacement therapy (PERT) are often blamed for its occurrence. This study evaluates the nutrition intake and PERT of patients with cystic fibrosis (CF) at a first episode of DIOS. METHODS: All patients with CF perform annually a 3-day intake diary to evaluate their caloric, protein, fat, dietary fiber, liquid, and PERT intake. Patients diagnosed with a first episode of DIOS (n = 12) retrospectively completed an intake diary of the 3 days preceding the DIOS episode supervised by an expert dietitian. RESULTS were compared with those of 1 year before and also with 36 CF controls matched for age, sex, genotype, and disease severity. All were pancreatic insufficient. RESULTS: A first DIOS episode was diagnosed in 12 patients with CF. Only the absolute median fat intake (P = .015) and pancreatic enzyme intake (P = .035) were higher at the time of the DIOS attack in comparison to the preceding year. This could result from the difference in data collection or from the recommendations to increase fat intake and concomitant enzyme intake, since this trend was also found in the control group. The significant difference disappears when enzyme intake is expressed as units of lipase/g of fat. No other significant dietary differences were found. CONCLUSIONS: This study provides no indications for a potential role of nutrition factors or pancreatic enzymes in the first occurrence of DIOS.

Effects of pancrelipase on nonalcoholic fatty liver disease after pancreaticoduodenectomy.

BACKGROUND: Postoperative nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has recently become recognized. However, the pathoetiology of postoperative NAFLD is largely unknown. Furthermore, the optimal treatment has not been established. The aim of this prospective study was to clarify whether pancrelipase, which contains digestive pancreatic enzymes, could reverse NAFLD. METHODS: A collaborative clinical trial has been conducted (UMIN000006841). A total of 30 patients who developed NAFLD after PD were prospectively treated with pancrelipase. NAFLD was defined and evaluated by the liver-to-spleen attenuation ratio on computed tomography (CT). Clinical symptoms and laboratory findings were also assessed. RESULTS: The mean liver-to-spleen CT ratio before surgery in 30 patients was 1.233. It declined to 0.453 at diagnosis of NAFLD. It was significantly improved by the treatment and the CT ratios at 1, 3 and 6 months after treatment were 0.762, 0.958 and 0.904, respectively (vs. pretreatment, P < 0.001). The mild liver dysfunction was also improved. Total protein, albumin and total cholesterol levels were significantly improved by the treatment. Importantly, relatively severe diarrhea seen in 11 patients was also ameliorated. CONCLUSIONS: Pancrelipase has a significant beneficial impact on NAFLD after PD. Maldigestion after pancreatic surgery may be a main cause for the development of postoperative NAFLD.

Efficacy and safety of a unique enteric-coated bicarbonate-buffered pancreatic enzyme replacement therapy in children and adults with cystic fibrosis.

BACKGROUND: Pancreatic enzyme replacement therapy (PERT) is used to treat exocrine pancreatic insufficiency in cystic fibrosis. RESULTS/METHODS: Efficacy and safety of a unique enteric-coated (EC) bicarbonate-buffered PERT product (PERTZYE®/PANCRECARB®; Digestive Care, Inc., Bethlehem, PA, USA) was studied in a randomized, double-blind, placebo-controlled cross-over design. Subjects were stabilized on EC-bicarbonate-buffered PERT and a high-fat diet. During two treatment periods, subjects were randomized to EC-bicarbonate-buffered PERT or placebo, followed by a 72-h stool collection employing an ingested stool dye marker. Mean coefficient of fat absorption with EC-bicarbonate-buffered PERT was 82.5% compared with 46.3% with the placebo (absolute difference 36.2%; p < 0.001), a 78.2% improvement for active over placebo. Similar improvements in nitrogen absorption were observed. Overall stool frequency and stool weight decreased (p < 0.001). No safety concerns were identified. SUMMARY: EC-bicarbonate-buffered PERT is effective in treating cystic fibrosis-associated exocrine pancreatic insufficiency.

Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis.

Pancreatic enzyme replacement therapy (PERT) is the only treatment for malabsorption in cystic fibrosis (CF) caused by pancreatic insufficiency (PI). PI occurs in approximately 85% of patients with CF. PERT overcomes some, but not all the signs and symptoms of malabsorption. Clinical parameters such as growth, abdominal pain, diarrhea and gassiness, commonly used to adjust PERT dosing, are shown not to be good indicators of their effectiveness. The FDA does not provide oversight of preparations of pancreatic enzymes consistent with the oversight it provides for all other drugs. The FDA intends to rectify this situation. Measures of the effectiveness of PERT are limited to the coefficient of fat absorption, a difficult and unpleasant exercise for patients.