Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis: A Decision Tree Approach.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers. MATERIALS AND METHODS: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 µg/g. The outcomes were then confirmed in a validation cohort of 26 patients. RESULTS: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort. CONCLUSIONS: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI.

Are we missing pancreatic exocrine insufficiency in 'at-risk' groups? Prospective assessment of the current practice and yield of faecal elastase testing in patients with diabetes mellitus, HIV and/or high alcohol intake.

There is cumulative evidence that pancreatic exocrine insufficiency (PEI) is under-recognised and can occur in patients with 'at-risk' conditions. Thus, we aimed to assess the current practice and yield of requesting faecal elastase (FEL-1), an indicator of PEI, in patients with 'at-risk' conditions. We prospectively recruited patients attending secondary care clinics with diabetes mellitus (DM), people living with HIV (PLHIV) and inpatients admitted to hospital with high alcohol intake (HAI). All patients underwent testing with FEL-1. Those patients with PEI (FEL-1 <200 µg/g) were contacted and offered a follow-up review in gastroenterology clinic. In total, 188 patients were recruited (HAI, n=78; DM, n=64; and PLHIV, n=46). Previous FEL-1 testing had not been performed in any of the patients. The return rate of samples was 67.9% for patients with HAI, 76.6% for those with DM and 56.5% for those with PLHIV. The presence of PEI was shown in 20.4% of patients with DM, 15.4% of patients with PLHIV and 22.6% in those with HAI. Diarrhoea and bloating were the most reported symptoms in followed-up patients with low FEL-1 (31.8% and 22.7% of patients, respectively). Follow-up computed tomography (CT) scans in those patients with PEI identified chronic pancreatitis changes in 13.6% and pancreatic atrophy in 31.8% of patients. These results suggest that there is a lack of testing for PEI in 'at-risk' groups. Our findings also suggest that using FEL-1 to test for PEI in patients with DM, PLHIV and HAI has a significant impact, although further studies are required to validate these findings.

Assessment of Exocrine Pancreatic Function Following Bariatric/Metabolic Surgery: a Prospective Cohort Study.

BACKGROUND: Exocrine pancreatic insufficiency (EPI) can be seen after bariatric/metabolic surgery. Fecal elastase level is a simple test in diagnosing and grading EPI. Quality of life changes in patients with bariatric/metabolic surgery related to gastrointestinal complaints is debated. AIM: This study aimed to investigate rates and grades of EPI via fecal elastase levels and association between EPI and quality of life in bariatric surgery patients. METHODS: A prospective study was performed for patients with bariatric/metabolic surgery at their second-year follow-up. Fecal elastase levels were used to diagnose and grade EPI as severe or moderate. Patient's gastrointestinal quality of life index (GIQLI) was calculated. Patients were grouped as sleeve gastrectomy (SG), one-anastomosis gastric bypass (OAGB), single-anastomosis sleeve ileal bypass (SASI), and transit bipartition (TB). Rates of severe or moderate EPI were primary outcome. Secondary outcome was an association between fecal elastase and GIQLI. RESULTS: There were 17, 29, 21, and 15 patients in OAGB, SG, TB, and SASI groups. There was no significant difference between groups in GIQLI scores and fecal elastase levels (p = 0.152 and p = 0.361). Rates of patients with moderate EPI in the groups OAGB, SG, TB, and SASI were 23.5%, 17.2%, 14.3%, and 20.0%. GIQLI scores were not significantly correlated with age, postoperative morphometric data, and fecal elastase values (p > 0.05). CONCLUSION: Rates of patients with moderate EPI ranged from 14.3 to 23.5% at second-year follow-up. There was no patient with severe EPI. GIQLI scores were not significantly correlated with fecal elastase levels and different types of bariatric/metabolic surgery.

Pancreatic Enzyme Replacement Therapy in Patients with Non-pancreatic Digestive Conditions: A Nationwide Claims Analysis.

BACKGROUND AND AIMS: Pancreatic enzyme replacement therapy (PERT) is most commonly used to treat exocrine insufficiency related to pancreatic diseases, but can be used for non-pancreatic digestive conditions (NPDC). We aimed to determine the prevalence of PERT use and describe prescription patterns in individuals with NPDC. METHODS: A nationally representative claims database of 48.6 million enrollees was used to identify individuals who received PERT prescription(s) in the absence of any pancreas-related diagnosis. Data on demographics, enrolment, comorbidities, exocrine function testing, treatment and potential indications for PERT were retrieved, and compared with individuals who received PERT for primary diagnosis of chronic pancreatitis (CP). RESULTS: A total of 29,234 individuals (64.1% female, mean age 52.4 ± 16.5 years) received PERT for NPDC. The overall estimated US population prevalence rate for PERT use for NDPC was 60.2/100,000 persons. Rates increased significantly with age and were higher in women in all age groups except 1-20 years old. When compared with CP, individuals with NPDC receiving PERT were more likely to be older (52.4 vs. 50.1 years), female (64.1% vs. 51.0%), have lower prevalence of alcoholism (3.6% vs. 25.0%), tobacco abuse (8.4% vs. 30.1%), and received PERT for shorter mean duration (5.3 vs. 8.2 months) (all p < 0.001). Median dose of PERT in individuals with NPDC was 2880 lipase units/day. CONCLUSIONS: Although proportionally low, a sizable population receives PERT for NPDC. PERT for NPDC is usually prescribed at a low dose and for shorter duration, suggesting it is used mostly as a trial for or until resolution of symptoms.

[Assessment of exo- and endocrine function of pancreas following distal pancreatectomy].

AIM: The assessment of pancreatic resection volume influence on exo- and endocrine pancreatic functions. MATERIALS AND METHODS: The resected pancreatic volume influence was assessed in 47 patients: 31 (66%) patients after resections of pancreatic body and tail, and 16 (34%) patients after distal resections. The exocrine pancreatic function was assessed by pancreatic fecal elastase 1 as well as endocrine pancreatic function was assessed by C-peptide level measurement. Computed tomography with intravenous contrast enhancement and postprocessing was used for pre- and postoperative pancreatic volume assessment. All tests were performed before and 1, 3, and 6 months after surgery. RESULTS: Type of surgery had no influence on C-peptide and pancreatic fecal elastase 1 levels (p>0.05). Exo- and endocrine pancreatic functions markers tended to decrease in 1st month after surgery with consequent functions restoration towards 6 months after surgery. There were 15 (35.7%) patients from 42 patients with normal exocrine pancreatic function with a fecal elastase 1 level decrease to 114.7±61.8 µg/g; exocrine insuficiency remained only in 2 (4.8%) patients after 6 months after surgery. C-peptide concentration decrease before surgery to less than 1.1 ng/ml was noticed only in 8 (17%) patients. C-peptide concentration decreased in 30 (63.8%) patients in 1st month after surgery, but after 6 months after surgery, C-peptide level decrease was only in 7 (14.9%) patients. CONCLUSION: The exo- and endocrine function of the pancreas is restored in more than 80% of patients after DR. Probably it could be associated with the activation of the pancreatic compensatory abilities.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Incidence, Diagnosis and Management of Malabsorption Following Oesophagectomy: a Systematic Review.

BACKGROUND: Survival following oesophagectomy for cancer is improving, resulting in increased focus on quality of life and survivorship. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM). The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. METHODS: A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until December 2021. RESULTS: Of 464 identified studies, eight studies (n = 7 non-randomised longitudinal studies) were included where patients were identified with malnutrition following oesophagectomy. Studies included a combined sample of 328 (range 7-63) patients. Malabsorption syndromes including EPI, SIBO and BAM occurred in 15.9-100%, 37.8-100% and 3.33-100% over 21 days-60 months, 1-24 months and 1-24 months respectively. There was no consensus definition for EPI, SIBO or BAM, and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin or colesevelam showed improvement in symptoms and weight in all studies, where investigated. CONCLUSIONS: Malabsorption syndromes following oesophagectomy are under-recognised, and thus under-reported. The resultant gastrointestinal symptoms may have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies; however, greater understanding of these conditions, their diagnosis and management is required to further understand which patients will benefit from treatment.

Teste de elastase pancreática fecal para pacientes com dúvida diagnóstica de insuficiência pancreática exócrina em pacientes com Fibrose Cística / Fecal pancreatic elastase test for patients with diagnostic doubt of pancreatic insufficiency exocrine in patients with Cystic Fibrosis

INTRODUÇÃO: A FC é uma doença genética, com incidência nacional de aproximadamente 1:7.576 nascidos vivos. A FC é uma doença complexa e multissistêmica, de característica progressiva e potencialmente letal, que afeta o epitélio do sistema respiratório, gastrintestinal, hepático e genitourinário e que ocorre mais frequentemente em populações descendentes de caucasianos. Estima-se que ao final do primeiro ano de vida, cerca de 85% dos pacientes tenham Insuficiência Pancreática Exócrina (IPE). De 10 a 15% dos pacientes, os quais possuem suficiência pancreática, podem desenvolver insuficiência em qualquer fase da vida. Atualmente, os testes fornecidos pelo Sistema Único de Saúde (SUS) são dois, o qualitativo (Sudam III) e o quantitativo de gordura nas fezes. O método quantitativo (método de Van de Kamer) é considerado o padrão-ouro na detecção da esteatorreia. Entretanto, este método exige dieta com ingestão controlada de gordura e coleta de fezes por três dias consecutivos, além de não diferenciar a razão da esteatorreia. Nos pacientes com FC, a esteatorreia é majoritariamente causada pela IPE, embora pacientes com IPE com quadros mais leves nem sempre apresentem esteatorreia. Neste contexto, o teste de elastase pancreática fecal (EL-1) apresenta-se como uma alternativa ao diagnóstico com o método quantitativo de Van de Kamer, principalmente pelo fato das alteraç

Risk factors and assessment considerations for essential fatty acid deficiency in nonparenterally fed patients using a case example.

Essential fatty acid deficiency (EFAD) has most commonly been reported in parenterally fed individuals but may also present in patients receiving fat-restricted diets and in patients with fat-malabsorption disorders. This article reviews the physical and biochemical assessment for EFAD in clinical practice and disorders of fat malabsorption as potential risk factors for EFAD. A case report is included to describe the fatty acid profile of a patient with exocrine pancreatic insufficiency receiving low-dose pancreatic enzyme replacement therapy after a self-imposed fat-restricted diet. The current challenges with laboratory interpretation of essential fatty acid status are also discussed.

Identification of "Digital Sarcopenia" Can Aid the Detection of Pancreatic Exocrine Insufficiency and Malnutrition Assessment in Patients with Suspected Pancreatic Pathology.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and subsequent malnutrition can be difficult to diagnose but lead to sarcopenia and increased mortality and morbidity even in benign disease. Digital skeletal muscle analysis has been increasingly recognised as a tool to diagnose sarcopenia. OBJECTIVE: The aim of the study was to assess the prevalence of sarcopenia in patients with PEI secondary to benign disease using novel skeletal muscle recognition software. METHODS: Prospective recruitment of patients referred for endoscopic ultrasound (EUS) with suspected pancreatic pathology. Patients with suspected pancreatic cancer on initial computed tomography (CT) were excluded. The diagnosis of chronic pancreatitis (CP) was based on CT and EUS findings. PEI was assessed with faecal elastase-1. Digital measurement of skeletal muscle mass identified sarcopenia, with demographic and comorbidity data also collected. RESULTS: PEI was identified in 45.1% (46/102) of patients recruited, and 29.4% (30/102) had changes of CP. Sarcopenia was significantly more prevalent in PEI 67.4% (31/46) than no-PEI 37.5% (21/56) (37.5%), regardless of CP changes (p < 0.003). The prevalence of sarcopenia (67% vs. 35%; p = 0.02) and sarcopenic obesity (68.4% vs. 25%; p = 0.003) was significantly higher when PEI was present without a radiological diagnosis of CP. Multivariate analysis identified sarcopenia and diabetes to be independently associated with PEI (odds ratio 4.8 and 13.8, respectively, p < 0.05). CONCLUSION: Sarcopenia was strongly associated with PEI in patients undergoing assessment for suspected benign pancreatic pathology. Digital skeletal muscle assessment can be used as a tool to aid identification of sarcopenia in patients undergoing CT scan for pancreatic symptoms.

Comparação de custos da terapia de reposição enzimática empírica com terapia guiada por diagnóstico laboratorial da insuficiência pancreática / Costs comparison of empirical enzymatic replacement therapy with laboratory diagnosis guided therapy of pancreatic insufficiency

Introdução: a fibrose cística, também conhecida como mucoviscidose, é uma doença genética cujas manifestações resultam da disfunção do gene cystic fibrosis transmembrane conductorance regulator. Cerca de 85% dos indivíduos com essa doença desenvolvem insuficiência pancreática exógena. Objetivo: comparar os custos da terapia de reposição enzimática empírica com a terapia de reposição enzimática empírica guiada pelo teste da elastase fecal, em indivíduos com fibrose cística, acompanhados em um centro de referência para assistência à doença. Metodologia: realizou-se um estudo descritivo e comparativo, que incluiu indivíduos de 0 a 21 anos, com fibrose cística. Coletaram-se dados referentes ao período de janeiro de 2016 a fevereiro de 2020, com registros clínicos, demográficos e laboratoriais. Inicialmente, com base em critérios clínicos, os participantes foram classificados como suficientes pancreáticos ou insuficientes pancreáticos. Após o resultado da dosagem da elastase fecal, o diagnóstico do status pancreático foi reavaliado. Realizouse a estimativa dos custos do teste da elas tase fecal por participante e da terapia por reposição enzimática empírica da insuficiência pancreática em indivíduos que, posteriormente, foram diagnostica dos como suficientes pancreáticos. Resultados: incluíram-se 50 participantes, com média de idade de 9,4 anos, sendo 52% do sexo masculino. Após o resultado da dosagem da elastase fecal, 7 participantes considerados insuficientes pancreáticos e foram reclassificados como suficientes pancreáticos. No período estudado, a economia média estimada, por participante suficiente pancreático, com a suspensão das enzimas, após resultado da elastase fecal, foi de R$ 6.770,13. Conclusão: a terapia de reposição enzimática empírica no tratamento da insuficiência pancreática pode levar a custos desnecessários. A medida de dosagem da elastase fecal contribui para decisão mais objetiva da avaliação da função pancreática.

Introduction: Cystic fibrosis, also known as mucoviscidosis, is a genetic disorder whose manifestations result from dysfunction of the cystic fibrosis transmembrane conductance regulator gene. About 85% of individuals with this disease develop exogenous pancreatic insufficiency. Objetivo: to compare the costs of empirical enzyme replacement therapy with fecal elastase test-guided empirical enzyme replacement therapy in individuals with cystic fibrosis followed up at a referral center for disease care. Methodology: a descriptive and comparative study was carried out, which included individuals aged 0 to 21 years, with cystic fibrosis. Data for the period from January 2016 to February 2020 were collected, with clinical, demographic and laboratory records. Initially, based on clinical criteria, participants were classified as pancreatic sufficient or pancreatic insufficient. After the result of the fecal elastase measurement, the diagnosis of pancreatic status was reassessed. Estimates were made of the costs of the fecal elastase test per participant and of the empiric enzyme replacement therapy for pancreatic insufficiency in individuals who were later diagnosed as pancreatic sufficient. Results: fifty participants were included, with a mean age of 9.4 years, 52% male. After the result of the fecal elastase measurement, 7 participants considered as pancreatic insufficient were reclassified as pancreatic sufficient. In the period studied, the estimated mean savings, per sufficient pancreatic participant, with the suspension of enzymes, after the result of fecal elastase, was R$ 6,770.13. Conclusion: empirical enzyme replacement therapy in the treatment of pancreatic insufficiency can lead to unnecessary costs. The measurement of fecal elastase dosage contributes to a more objective decision on the assessment of pancreatic function.

Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol.

INTRODUCTION: Pancreatic exocrine insufficiency (PEI) in patients with pancreatic malignancy is well documented in the literature and is known to negatively impact on overall survival and quality of life. A lack of consensus opinion remains on the optimal diagnostic test that can be adapted for use in a clinical setting for this cohort of patients. This study aims to better understand the prevalence of PEI and the most suitable diagnostic techniques in patients with advanced pancreatic malignancy. METHODS AND ANALYSIS: This prospective observational study will be carried out in patients with pancreatic malignancy (including adenocarcinoma and neuroendocrine neoplasms). Consecutive patients with inoperable pancreatic malignancy referred for consideration of first-line chemotherapy will be considered for eligibility. The study comprises three cohorts: demographic cohort (primary objective to prospectively investigate the prevalence of PEI in patients with inoperable pancreatic malignancy); sample size 50, diagnostic cohort (primary objective to design and evaluate an optimal diagnostic panel to detect PEI in patients with inoperable pancreatic malignancy); sample size 25 and follow-up cohort (primary objective to prospectively evaluate the proposed PEI diagnostic panel in a cohort of patients with inoperable pancreatic malignancy); sample size 50. The following is a summary of the protocol and methodology. ETHICS AND DISSEMINATION: Full ethical approval has been granted by the North West Greater Manchester East Research and Ethics Committee, reference: 17/NW/0597. This manuscript reflects the latest protocol V.8 approved 21 April 2020. Findings will be disseminated by presentation at national/international conferences, publication in peer-review journals and distribution via patient advocate groups. TRIAL REGISTRATION NUMBER: 194255, NCT0361643.

Pancreatitis, Pancreatic Cancer, and Their Metabolic Sequelae: Projected Burden to 2050.

INTRODUCTION: Future burden has been modeled from population-based data for several common gastrointestinal diseases. However, as we enter the third decade in the 21st century, there are no such data on diseases of the pancreas holistically. The study aimed to estimate future incidence of pancreatitis, pancreatic cancer, diabetes of the exocrine pancreas (DEP), and exocrine pancreatic dysfunction (EPD) as well as years of life lost (YLL) due to premature death in individuals with those diseases up to 2050. METHODS: Historical New Zealand nationwide data on hospital discharge, pharmaceutical dispensing, cancer, and mortality were obtained. Annual incidence of each disease and annual YLLs due to premature death in individuals with each disease were calculated. A time series analysis using the stepwise autoregressive method was conducted. RESULTS: Pancreatitis yielded the highest projected incidence (123.7 per 100,000; 95% confidence interval, 116.7-130.7) and YLL (14,709 years; 13,642-15,777) in 2050. The projected incidence and YLL of pancreatic cancer were 18.6 per 100,000 (95% confidence interval, 13.1-24.1) and 14,247 years (11,349-17,144) in 2050, respectively. Compared with pancreatitis and pancreatic cancer, DEP and EPD yielded lower but more steeply increasing projected incidence rates and YLLs. DISCUSSION: The findings suggest that the burden of pancreatitis, pancreatic cancer, DEP, and EPD will rise in the next 3 decades unless healthcare systems introduce effective prevention or early treatment strategies for diseases of the pancreas and their sequelae.

A new ultrasound score for the assessment and follow-up of chronic pancreatitis: The 'Gemelli USCP score'.

BACKGROUND: Ultrasound (US) is frequently the first line imaging technique used in patients with abdominal pain and clinical suspicion of chronic pancreatitis (CP), but its role in the diagnosis and follow-up of CP is still controversial. AIMS: We aimed to develop a dedicated score for the US staging of CP and to evaluate the agreement of this score with standard imaging techniques. METHODS: Ninety consecutive patients with a diagnosis of CP referred to the pancreatic outpatient clinic of A. Gemelli Hospital between June and September 2018 were recruited in the study. Patients underwent pancreatic US to evaluate different morphological parameters to develop an US based score system, called the Gemelli UltraSound Chronic Pancreatitis (USCP) score. RESULTS: The Gemelli USCP score significantly increased according to the Cambridge score for both mean value (p<0.0001) and each parameter evaluated (p<0.0001). Moreover, we found a significant correlation between the score and laboratory parameters related to pancreatic exocrine insufficiency such as vitamin D, B9, and B12 deficiency and fecal elastase values (p<0.0001). CONCLUSIONS: The development of a dedicated US score could be useful in the follow up of patients with CP as alternative non-invasive technique to standard radiological imaging.

The assessment of pancreatic exocrine function in patients with inoperable pancreatic cancer: In need of a new gold-standard.

BACKGROUND: Pancreatic exocrine insufficiency is commonplace in patients with pancreatic cancer, adversely impacting on quality of life and survival. Whilst the management of exocrine insufficiency is well established, diagnosis remains challenging in clinical practice. A plethora of diagnostic tests exist. Nevertheless, a lack of consensus remains about the optimal diagnostic method, specifically in patients with pancreatic cancer. Research, to date, has primarily been undertaken in patients with chronic pancreatitis and cystic fibrosis. This manuscript will review the current literature and will examine the evidence around the diagnostic tests available for pancreatic exocrine insufficiency and whether any exists specifically for pancreatic cancer cohorts. FINDINGS: Evidence to recommend an individual test for the diagnosis of pancreatic exocrine insufficiency in clinical practice is lacking. Direct testing (by direct sampling of pancreatic secretions) has the highest specificity and sensitivity but is no longer routinely deployed or feasible in practice. Indirect testing, such as faecal elastase, is less accurate with high false-positive rates, but is routinely available in clinical practice. The 13C-mixed triglyceride breath test and the gold-standard 72-h faecal fat test have high specificity for indirect tests, but are not routinely available and cumbersome to undertake. A combination approach including nutritional markers and faecal elastase has more recently been proposed. CONCLUSION: Further research is required to identify the most optimal and accurate diagnostic tool to diagnose pancreatic exocrine insufficiency in patients with pancreatic cancer in clinical practice.

Eficacia y seguridad de pancreatina en pacientes con insuficiencia pancreática exocrina moderada-severa de diversa etiología / Efficacy and safety of pancreatin in patients with moderate-severe exocrine pancreatic insufficiency of diverse etiology

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de pancreatina comparada con la mejor terapia de soporte (placebo) en pacientes con insuficiencia pancreática exocrina moderada-severa de diversa etiología. Esta evaluación se realiza en respuesta a una solicitud de modificación en el Petitorio Farmacológico de EsSalud de la indicación para el producto farmacéutico pancreatina. La insuficiencia pancreática exocrina (IPE) se define como una disminución en la secreción de enzimas pancreáticas que provoca una malabsorción de los nutrientes provenientes de la comida. Poco se conoce sobre la prevalencia de IPE en población general, sin embargo, se sabe que la IPE suele estar asociada a enfermedades pancreáticas como fibrosis quística, pancreatitis crónica, entre otras. El manejo efectivo de la IPE es necesario para prevenir la malnutrición y sus efectos a largo plazo en la salud y calidad de vida del paciente (Gubergrits et al. 2011a). El tratamiento recomendado para pacientes con IPE es la terapia de reemplazo con enzimas pancreáticas (TREP) acompañada de una dieta alta en grasas. El objetivo de esta terapia es restituir la absorción normal de las grasas. La TREP consiste en la ingesta de suplementos enzimáticos, que contienen una combinación de enzimas digestivas de origen porcino (amilasa, lipasa y proteasa). Hoy en día, existe una gran variedad de suplementos de enzimas pancreáticas en polvo o en cápsula y con diferentes preparaciones enzimáticas, como por ejemplo pancreatina Creon® 25,000 en cápsula que contiene lipasa 25,000 UI, amilasa ≥ 18,000 UI, proteasa ≥ 1000 UI. En el contexto de EsSalud, en el Petitorio Farmacológico Institucional, se cuenta con pancreatina (Creon® 25,000) ≥ 300 mg con actividad lipasa 25,000 UI, amilasa ≥ 18,000 UI, proteasa ≥ 1000 UI para el tratamiento de pacientes con malabsorción con fibrosis quística e insuficiencia pancreática, para ser utilizada por las unidades de gastroenterología y gastroenterología pediátrica. No obstante, los especialistas de la unidad de cirugía pancreática del Hospital Nacional Edgardo Rebagliati Martins, envían una solicitud para que se amplíe el uso pancreatina a las unidades de cirugía de páncreas. De acuerdo con la Directiva N° 001-IETSI-ESSALUD-2015, "Normativa de uso del Petitorio Farmacológico de EsSalud", el Hospital Nacional Edgardo Rebagliati Martins solicitó a IETSI la ampliación del uso de pancreatina para la unidad de cirugía de páncreas. Sin embargo, debido a que la pancreatina no forma parte del Petitorio Nacional Único de Medicamentos Esenciales (PNUME), al cual se rige EsSalud, ni en sus listas complementarias, no es posible realizar modificaciones en el Petitorio de EsSalud. En ese sentido, se procede a realizar la evaluación del producto farmacéutico pancreatina, a través de la Directiva N° 003-IETSI-ESSALUD-2016 "Normativa para la Autorización y Uso de Productos Farmacéuticos No incluidos en el Petitorio Farmacológico de EsSalud. METODOLOGÍA: La búsqueda de la literatura se realizó con el objetivo de identificar evidencia sobre la eficacia y seguridad de pancreatina comparada con la mejor terapia de soporte (placebo) en pacientes con insuficiencia pancreática exocrina moderada-severa de diversa etiología. La búsqueda de la evidencia se realizó en las bases de datos bibliográficas: PubMed, Scopus (Acceso a través de CONCYTEC) y The Cochrane Library. Adicionalmente, se revisó la evidencia generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como The National Institute for Health and Care Excellence (NICE), The Guidelines International Network (G-I-N), el portal de la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), The Canadian Agency for Drugs and Technologies in Health (CADTH), Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), Scottish Intercollegiate Guidelines Network (SIGN), Institute for Quality and Efficiency in Health Care (IQWiG), European Medicines Agency (EMA), y Scottish Medicines Consortium (SMC). Finalmente, se realizó una búsqueda manual en el portal ClinicalTrials.gov del National Institutes of Health (NIH) para identificar ensayos clínicos en desarrollo o que no hayan sido publicados aún. RESULTADOS: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de pancreatina en pacientes con IPE moderada-severa de diversa etiología. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: En el presente documento, se evaluó la mejor evidencia científica disponible hasta enero del 2020 en relación con la eficacia y seguridad de pancreatina comparada con la mejor terapia de soporte (placebo) en pacientes con insuficiencia pancreática exocrina moderada-severa de diversa etiología. En la búsqueda sistemática de la evidencia se identificaron seis GPC y un ECA elaborado por Seiler et al., 2013, que responden a la pregunta PICO planteada en el presente dictamen. Las seis GPC recomiendan el uso de las terapias de reemplazo de enzimas pancreáticas (TREP) en pacientes con IPE, con fibrosis quística e IPE, con pancreatitis crónica e IPE y para pacientes con cirugías pancreáticas. Sin embargo, ninguna brinda información específica sobre la composición de las cápsulas empleadas en la TREP. El ensayo clínico realizado por Seiler et al., 2013 es el único ECA que responde a la pregunta PICO de interés. El estudio se realizó en cuatro etapas: fase de tamizaje (visita 1); fase de run-in (dos semanas); fase doble ciego, aleatorizada, placebo controlada y grupo paralelo (una semana) y, una extensión de etiqueta abierta (OLE por sus siglas en inglés; duración 51 semanas). Con el objetivo de demostrar la eficacia de pancreatina de 25,000 minimicrosferas (Creon 25,000 MMS) en comparación con placebo para el tratamiento de IPE en pacientes que han tenido una resección pancreática. En total participaron 58 pacientes con IPE severa debido a una resección total o parcial del páncreas, 32 en el grupo de pancreatina y 26 en el grupo placebo. La duración promedio del tratamiento fue de 6.6 días en el grupo de pancreatina y 6.7 días en el grupo placebo. Los cambios en el coeficiente de absorción de grasas (CFA) basal comparado con la medición al final de la fase doble ciego entre los grupos de pancreatina y placebo fueron significativamente diferentes, a favor del uso de pancreatina (diferencia 25.6 IC95 %: 13.9 - 37.3; p<0.001), al comparar la medición basal con la medición final de la fase OLE (donde todos recibieron pancreatina), se mantuvo la diferencia significativa (53.6 ± 20.6 vs 78.4 ± 20.7; p<0.001). No se reportaron diferencias estadísticamente significativas en el desenlace de calidad de vida, durante la fase de doble ciego. No se reportaron eventos adversos serios debido al tratamiento durante el estudio. En la evaluación de la tecnología de interés del presente dictamen, se tomaron en cuenta, 1) los resultados del estudio de Seiler et al., 2013, 2) el vacío terapéutico, 3) la experiencia de uso en EsSalud, 4) el no reporte de sospechas de reacciones adversas de pancreatina por el Centro de Referencia de Farmacovigilancia y Tecnovigilancia de EsSalud (CRI-EsSalud), 5) las recomendaciones de las GPC internacionales, 6) la plausibilidad biológica del mecanismo de acción de la pancreatina, y, 7) la opinión del especialista. Por lo expuesto, el Instituto de Evaluaciones de Tecnologías en Salud e Investigación ­ IETSI aprueba el uso de pancreatina en pacientes con insuficiencia pancreática exocrina moderada-severa de diversa etiología. La vigencia del presente dictamen es de dos años, según lo establecido en el Anexo N°1. Así, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de nueva evidencia que pueda surgir en el tiempo.

Assessment of Weight Loss and Gastrointestinal Symptoms Suggestive of Exocrine Pancreatic Dysfunction After Acute Pancreatitis.

INTRODUCTION: Studies evaluating the natural history of exocrine pancreatic dysfunction (EPD) after acute pancreatitis (AP) are sparse. This study aims to assess incidence and predictors of weight loss and gastrointestinal (GI) symptoms suggestive of EPD 12 months after an AP episode. METHODS: Patients enrolled in the Pancreatitis-associated Risk of Organ Failure Study at the time of an AP episode were included. Weight and GI symptom data were prospectively collected by self-report at enrollment and at 3- and 12-month (windows 2-7 and 8-20) telephone follow-ups. Multivariable logistic regression was used to assess factors associated with ≥10% total body weight loss (EPD surrogate) at 12 months. A generalized estimating equation was used to measure each factor's population effect (in pounds) over 12 months after AP. RESULTS: Follow-up at 12 months in 186 patients (median age = 54 years, 46% men, 45% biliary, 65% first AP attack) revealed weight loss ≥10% from baseline, occurring in 44 patients (24%). Risk of weight loss increased with higher baseline body mass index, previous diagnosis of diabetes mellitus, and worsening AP severity (all P < 0.010). GI symptoms were reported in 13/31 (42%) patients at 12 months. AP severity was independently associated with ≥10% weight loss at 12 months. Over 12 months, men lost more weight than women (average 9.5 lbs); patients with severe AP lost, on average, 14 lbs. DISCUSSION: Weight loss after AP occurs in one-quarter of patients and is associated with AP severity. EPD incidence after AP is likely underappreciated. Further work is needed to assess EPD and potential for pancreatic enzyme supplementation.

Pancreas-specific plasma amylase for assessment and diagnosis of chronic pancreatitis: New insights on an old topic.

Background: Pancreatic function testing and imaging are used to inform the diagnosis of chronic pancreatitis, but most of these methods are time- and cost-consuming or lack diagnostic accuracy. Objective: We investigated the utility of pancreas-specific plasma amylase for assessment and diagnosis of chronic pancreatitis. Design: This was a prospective study of 121 consecutive patients with chronic pancreatitis and a reference population of 94 healthy controls. Pancreas-specific plasma amylase level was determined and analysed for its association with exocrine pancreatic insufficiency, diabetes and other clinical variables. Receiver operating characteristic curve analyses were performed to determine the diagnostic utility of plasma amylase for diagnosing chronic pancreatitis and to study associations with disease severity. The findings were validated in a further cohort of 57 patients with chronic pancreatitis. Results: Significant and independent associations between plasma amylase level and duration of chronic pancreatitis as well as the presence of exocrine pancreatic insufficiency and diabetes were observed (all p < 0.001). An amylase level below 17.3 U/l had a high specificity (94%) and moderate sensitivity (59%) for the diagnosis of chronic pancreatitis. Diagnostic performance was influenced by disease stage with the best performance observed for advanced disease. The findings were replicated in the validation cohort. Conclusion: Pancreas-specific plasma amylase may provide a clinically useful mean for assessment and diagnosis of chronic pancreatitis.

Symptoms that are associated with decreased pancreatic enzyme flow: MRCP assessment.

BACKGROUND: Pancreatic exocrine insufficiency is one of the causes of malabsorption syndrome. In many cases of malabsorption syndrome, pancreatic exocrine insufficiency can be treated with pancreatic enzyme replacement therapy. Therefore, it is important to detect pancreatic endocrine insufficiency as early and accurately as possible. Recent studies have shown that cine-dynamic MR cholangiopancreatography (MRCP) may be useful to evaluate pancreatic exocrine function PURPOSE: To identify abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion for which cine-dynamic MRCP should be performed to diagnose pancreatic exocrine insufficiency. STUDY TYPE: Prospective. POPULATION: In all, 111 patients with various types of abdominal symptoms. FIELD STRENGTH/SEQUENCE: 5 T or 3 T, MRCP with spatially selective inversion recovery pulse (cine-dynamic MRCP). ASSESSMENT: Cine-dynamic MRCP was performed and an 18-question clinical questionnaire on abdominal symptoms was administered. The secretion grade derived from cine-dynamic MRCP was compared between those answering "yes" and "no" for all 18 items STATISTICAL TESTS: Univariate analysis and further analyzed using multiple regression analysis. The associations between the secretion grade and the items in the clinical questionnaire were analyzed by univariate analysis and further analyzed using multiple regression analysis. RESULTS: The following three items showed significantly negative correlations with secretion grade: Q9, Does your rectal gas smell foul? (ß = -0.44, P = 0.001); Q13, Is stool quantity large? (ß = -0.41, P = 0.001); and Q18, Are your stools soft? (ß = -0.53, P < 0.001). No significant correlations with exocrine pancreatic function measured by cine-dynamic MRCP were seen for the remaining 15 abdominal symptom items. DATA CONCLUSION: Abdominal symptoms that suggest decreased flow of pancreatic enzyme secretion were foul rectal gas, large stool, and soft stool. Pancreatic exocrine insufficiency due to decreased pancreatic enzyme flow may be suspected in patients with these abdominal symptoms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:417-423.