Pancreatic exocrine insufficiency after non-pancreatic upper gastrointestinal surgery: meta-analysis.

BACKGROUND: Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection. METHODS: A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy. RESULTS: Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed. CONCLUSION: PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy.

Pancreatic exocrine insufficiency occurs when enzymes from the pancreas are unable to help digest food. Pancreatic exocrine insufficiency is known to cause disruptive symptoms after gastrointestinal surgery. Although such symptoms are well known after pancreatic surgery, after other gastrointestinal operations, including bariatric metabolic surgery and oesophagogastric cancer resection, pancreatic exocrine insufficiency is often overlooked as a cause of both symptoms and poor nutrition. This study looked at, and combined, all the current evidence on the rate of pancreatic exocrine insufficiency after these operations, the way it is diagnosed, and how it is treated. Pancreatic exocrine insufficiency may be more common than previously thought after bariatric metabolic surgery or oesophagogastric surgery, and clinicians working with these patients should have a low threshold for starting treatment.

Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy.

AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD. METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the 13C Mixed triglyceride breath test (13CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus. RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the 13CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI. DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe.

Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis.

BACKGROUND/OBJECTIVES: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP. METHODS: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric. RESULTS: 274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation. CONCLUSION: We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.

Symptoms, burden, and unmet needs of patients living with exocrine pancreatic insufficiency: a narrative review of the patient experience.

Exocrine pancreatic insufficiency (EPI) stems from a deficiency of functional pancreatic enzymes with consequent maldigestion and malnutrition. EPI shares clinical symptoms and manifestations with other disorders and is a considerable burden to individuals affected. In this narrative review, we analyzed the literature to identify relevant publications on living with EPI with the scope of individuating evidence gaps, including those related to symptoms, health-related quality of life (HRQoL), emotional functioning, disease burden, presence of comorbidities, and the use of pancreatic enzyme replacement therapy (PERT). Abdominal pain emerged as one of the most prominent symptoms. HRQoL was affected in EPI, but no articles examined emotional functioning. Comorbidities reported involved other pancreatic disorders, diabetes, gastrointestinal disorders, sarcopenia and osteopenia, cardiovascular disorders, bacterial overgrowth, and nutritional deficiencies. PERT was found to be effective in improving EPI symptoms and was well tolerated by most individuals. Our review revealed a dearth of literature evidence on patients' experience with EPI, such as emotional functioning and disease burden. We also revealed that studies on long-term effects of PERT are missing, as are studies that would help advance the understanding of the disease and its progression, risk/mitigating factors, and comorbidities. Future studies should address these identified gaps.

A standardised nutritional drink as a test meal for the 13 C mixed triglyceride breath test for pancreatic exocrine insufficiency: A randomised, two-arm crossover comparative study.

BACKGROUND: The 13 C mixed triglyceride breath test (13 C MTGT) is a diagnostic test for pancreatic exocrine insufficiency (PEI). It is poorly standardised with much heterogeneity of the test meal, the commonest being toast and butter. A standardised oral nutritional supplement that could be easily transported, stored and made up would be valuable for making this test accessible outside of specialist centres. METHODS: A prospective, randomised, two-arm crossover study of different test meals was carried out in 14 healthy controls. The 13 C MTGT was performed in identical conditions on two separate days. Two test meals were given in random order, either standard (toast and butter) or novel (oral nutritional supplement), with 250 mg of 13 C-labelled mixed triglyceride incorporated. Breath samples were taken postprandially to calculate cumulative percentage dose recovery (cPDR) of 13 C at 6 h. RESULTS: All 14 participants completed both arms of the study with no protocol deviations. The mean cPDR was 39.39% (standard deviation [SD] 5.19) for the standard test meal and 39.93% (SD 5.20) for the novel test meal. A one-way repeated measures analysis of variance (ANOVA) found no significant difference in cPDR between the two meals, F(1, 13) = 0.18, p = 0.68 (minimum detectable difference of 0.81 at 80% power). CONCLUSION: This study demonstrates that a standardised oral nutritional supplement can be used without compromising 13 C recovery. Using this test meal provides a standardised dietary stimulus to the pancreas, avoiding possible variation in quantity of dietary components with other test meals. Further, the ease of use of this method would help establish the 13 C MTGT test more widely.

Perioperative management of pancreatic exocrine insufficiency-evidence-based proposal for a paradigm shift in pancreatic surgery.

BACKGROUND: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT). METHODS: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured. RESULTS: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT. CONCLUSION: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.

Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing.

Pediatric patients with exocrine pancreatic insufficiency (EPI) have symptoms that include abdominal pain, weight loss or poor weight gain, malnutrition, and steatorrhea. This condition can be present at birth or develop during childhood for certain genetic disorders. Cystic fibrosis (CF) is the most prevalent disorder in which patients are screened for EPI; other disorders also are associated with pancreatic dysfunction, such as hereditary pancreatitis, Pearson syndrome, and Shwachman-Diamond syndrome. Understanding the clinical presentation and proposed pathophysiology of the pancreatic dysfunction of these disorders aids in diagnosis and treatment. Testing pancreatic function is challenging. Directly testing aspirates produced from the pancreas after stimulation is considered the gold standard, but the procedures are not standardized or widely available. Instead, indirect tests are often used in diagnosis and monitoring. Although indirect tests are more widely available and easier to perform, they have inherent limitations due to a lack of sensitivity and/or specificity for EPI.

Evaluation and management of exocrine pancreatic insufficiency: pearls and pitfalls.

PURPOSE OF REVIEW: The diagnosis and management of exocrine pancreatic dysfunction (EPD) can be challenging. EPD classically results from conditions that cause loss of pancreatic acinar cell function and decreased digestive enzyme production. However, several conditions may contribute to signs or symptoms of EPD with otherwise normal pancreatic exocrine function. A thoughtful approach to considering these conditions, along with their specific therapies, can guide a tailored management approach. RECENT FINDINGS: An EPD severity classification schema has been proposed, which emphasizes a shift towards a more restrictive prescription of pancreas enzyme replacement therapy (PERT) for patients with milder EPD. In contrast, PERT use has been associated with a measurable survival benefit among individuals with EPD and pancreatic cancer, so the prescription of PERT may be more liberal in this population. Recent publications in the cystic fibrosis population offer pearls guiding the titration and optimization of PERT. SUMMARY: Among individuals with severe EPD, PERT is an effective therapy. Among individuals with milder EPD, although PERT is effective, there may be opportunities to provide additional and potentially more effective therapies.

Utility of Fecal Elastase-1 to diagnose severe exocrine insufficiency in chronic pancreatitis: Real world experience.

INTRODUCTION: Quantitative fecal fat estimation is the gold standard test to diagnose steatorrhea (fecal fat >7 g/day) in chronic pancreatitis (CP), but cumbersome and inconvenient. So, fecal elastase-1 (FE) is proposed as a good alternative but the data on the diagnostic utility of FE to diagnose steatorrhea is variable. METHODS: This retrospective study included adult CP patients evaluated with both 24-h fecal-fat and FE tests within a 3-month period. The objective was to evaluate the diagnostic performance of FE to diagnose steatorrhea and to evaluate the FE progression over 9-month period. RESULTS: Among the 147 included patients, the frequency of steatorrhea (fecal fat >7 g/day) was 34%. The sensitivity, specificity, and negative likelihood ratio (LR) of FE was 90%, 28.9% and 0.35 at cut-off of <100 µg/g stool to diagnose steatorrhea; and 96%, 11.3% and 0.35 at cut-off of <200 µg/g stool, respectively. The optimal cut-off of FE was <20 on receiver operating characteristic curve (sensitivity 66%; specificity 69%; positive LR 2.14). There was no statistically significant variation in FE levels over 9 months interval among a hundred patients. CONCLUSION: Compared to FE ≥ 200 µg/g stool, FE ≥ 100 can used to exclude steatorrhea (better specificity and negative LR). FE < 20 alone cannot replace fecal fat estimation to confirm steatorrhea but to be interpreted with clinical features. Repeat FE testing for exocrine insufficiency progression can be done at least a year later.

Estimation of exocrine pancreatic insufficiency in children with acute pancreatitis using the 13C mixed triglyceride breath test.

BACKGROUND: /Objective: The extent of exocrine pancreatic insufficiency (EPI) in the paediatric population with acute pancreatitis (AP) is unknown. The primary objective was to use a 6 h stable-isotope breath test to determine the prevalence of EPI in children with AP. The secondary objective was to determine the diagnostic ability of a 4 h abbreviated breath test in the detection of EPI. METHODS: 13C-mixed triglyceride (MTG) breath test was used to measure fat digestibility in 12 children with AP and 12 normal children. EPI was diagnosed based on a cumulative dose percentage recovery (cPDR) cut-off value < 26.8% present in literature. To reduce the test burden, the diagnostic accuracy of an abbreviated 4 h test was evaluated, using a cPDR cut-off that was the 2.5th percentile of its distribution in control children. RESULTS: The cPDR of cases was significantly lower than that of controls (27.71 ± 7.88% vs 36.37 ± 4.70%, p = 0.005). The cPDR during acute illness was not significantly different to that at 1 month follow up (24.69 ± 6.83% vs 26.98 ± 11.10%, p = 0.52). The 4 h and 6 h breath test results correlated strongly (r = 0.93, p < 0.001) with each other. The new 4 h test had 87.5% sensitivity and 93.8% specificity for detecting EPI. CONCLUSION: Two-thirds (66.7%) of this sample of children with AP had EPI during admission, which persisted at 1 month follow up. The 4 h abbreviated 13C-MTG breath test has good diagnostic ability to detect EPI in children and may improve its clinical utility in this age group.

Prevalence of pancreatic exocrine insufficiency after pancreatic surgery measured by 13C mixed triglyceride breath test: A prospective cohort study.

BACKGROUND: Patients undergoing pancreatic surgery are at risk of pancreatic exocrine insufficiency (PEI) and needing pancreatic enzyme replacement therapy (PERT). METHODS: This study included 254 patients undergoing pancreatic surgery for oncologic indications. A13C mixed triglyceride breath test was performed immediately preoperative and postoperative. This test analyzes the pancreatic remnant lipase activity measuring 13CO2 in breath samples after a test meal with 1.3-distearyl-(13C-Carboxyl)octanol-glycerol. Cumulative percent dose recovery after 6 h of less than 23% confirms PEI. In addition, PEI was compared between pathology subgroups. RESULTS: In 197 patients undergoing pancreaticoduodenectomy, cPDR-6h decreased significantly from a median of 32.84% before to 15.80% after surgery (p < 0.0001). This decrease in exocrine function was significant in all pathology subgroups except in pancreatic neuroendocrine tumors. Exocrine function decreased most in pancreatic ductal adenocarcinoma (PDAC). In addition, the percentage of patients needing PERT because of PEI increased from 25.9% to 68.0% postoperative (p < 0.001). Overall, patients with an MPD diameter of more than 3 mm had a higher risk of developing postoperative PEI: 62.7% compared to 37.3% (p = 0.009), OR = 3.11. In contrast, the majority of the 57 patients undergoing a distal pancreatectomy did not experience any significant change in exocrine function. CONCLUSIONS: The vast majority of patients undergoing pancreaticoduodenectomy for oncologic indications experience a significant drop in exocrine function, are at high risk of developing pancreatic exocrine insufficiency and consequently need to be treated with pancreatic enzyme replacement therapy. Therefore, systematic screening for pancreatic exocrine insufficiency is needed after pancreaticoduodenectomy.

Differential Diagnosis of Chronic Diarrhea: An Algorithm to Distinguish Irritable Bowel Syndrome With Diarrhea From Other Organic Gastrointestinal Diseases, With Special Focus on Exocrine Pancreatic Insufficiency.

Chronic diarrhea, defined as diarrhea persisting for more than 4 weeks, affects up to 5% of the population regardless of patient age, sex, race, or socioeconomic status. The impact on patient health and quality of life is substantial, and diagnosis and management of these patients have significant economic consequences for health care services. The differential diagnosis of chronic diarrhea is broad, with etiologies including infections, endocrinopathies, maldigestive/malabsorptive conditions, and disorders of gut-brain interaction. The considerable overlap of symptoms across this spectrum makes accurate diagnosis problematic and may lead to delays in diagnosis or misdiagnosis. In this narrative review, we consider the differential diagnosis of chronic diarrhea, focusing on irritable bowel syndrome with diarrhea and exocrine pancreatic insufficiency, two conditions that may present similarly but have very different underlying causes and require significantly different management strategies. We outline a 4-step diagnostic strategy and propose a straightforward algorithm to assist in efficiently differentiating irritable bowel syndrome from exocrine pancreatic insufficiency and other causes of chronic diarrhea. We anticipate that these aids will improve diagnostic accuracy, which ultimately should lead to improvements in patients' health-related quality of life and reduce the societal burden on health care services.

Non-alcoholic fatty pancreas disease and pancreatic exocrine insufficiency: pilot study and systematic review.

INTRODUCTION: The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is estimated as 2-46% among patients without known pancreatic diseases. An association between NAFPD and non-alcoholic fatty liver disease (NAFLD) has been proposed, as well as an association between NAFPD and pancreatic exocrine insufficiency (PEI). PATIENTS AND METHODS: Patients with histologically confirmed NAFLD were included in the study. The control group consisted of individuals included in a surveillance screening program. Magnetic resonance imaging (MRI) of the pancreas was performed in all patients and fat measurement was made using 2-point Dixon imaging. Fecal elastase-1 (FE-1) was performed to evaluate pancreatic exocrine function. Additionally, a 13C-mixed triglyceride breath test (13 C-MTG-BT) was performed in patients with FE-1 < 200 µg/g. RESULTS: Imaging signs of NAFPD were present in 17 (71%) patients; 11 (85%) from the NAFLD group and 6 (55%) from the control group. FE-1 < 200 µg/g was found in six (25%) patients (four in the NAFLD group and two in the control group); however, none of them had clinical symptoms of PEI. Therefore, in five out of six patients with low FE-1, a 13C-MTG-BT was performed, showing normal results (>20.9%) in all tested patients. Furthermore, the serum nutritional panel was normal in all patients with low FE-1. A systematic review identified five studies relevant to the topic. CONCLUSION: NAFPD was found in 85% of patients with NAFLD and in 55% of control patients. We did not diagnose PEI in either group. A literature review showed PEI in 9-56% of patients with NAFPD.

Prevalence of Exocrine Pancreatic Dysfunction Based on Direct Function Testing in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) frequently have extraintestinal manifestations. The goal of this pilot study was to assess exocrine pancreatic function in cases with suspicion for or an established diagnosis of IBD. METHODS: Direct stimulated endoscopic pancreatic function test (ePFT) was performed in 74 children with IBD, in both newly diagnosed and established cases. Demographic, clinical, and laboratory parameters were entered into a database and analyzed. RESULTS: Among the 74 children, 49 were newly diagnosed and 25 had an established diagnosis of IBD. A majority had the diagnosis of Crohn disease (CD) (n = 48; 32 new and 16 established cases) with male predominance (64.6%). Altogether, 42 (56.7%) children had either generalized or partial exocrine pancreatic insufficiency (EPI). Twenty-four of the 48 CD children (50%) had abnormal ePFT. In those with ulcerative colitis (UC), 18 of the 26 (62.9%) had abnormal ePFT. The highest abnormality rate was in lipase enzyme activity. Weight z scores were significantly lower in those with abnormal ePFT (Crohn cases: P = 0.008; UC cases: P = 0.046). Peak protein concentration in collected pancreatic fluid was significantly lower in children with CD who had abnormal ePFT ( P = 0.013). CONCLUSIONS: This pilot study revealed a relatively high prevalence of EPI in children with IBD through use of ePFT. EPI can result in maldigestion, with decreased capacity to digest fat. Further prospective studies are needed to assess need and efficacy of pancreatic enzyme replacement therapy in children with IBD and abnormal ePFT.

Exocrine pancreatic insufficiency after bariatric surgery: a bariatric surgery center of excellence experience.

INTRODUCTION: Gastrointestinal symptoms such as diarrhea, bloating, abdominal pain, and nausea are common after bariatric surgery (BS) and can lead to significant morbidity. While many diagnoses can explain these symptoms, post-bariatric exocrine pancreatic insufficiency (EPI) is becoming increasingly recognized as contributor to gastrointestinal symptoms. The frequency and outcomes of EPI after BS are not well understood. We investigated the prevalence and outcomes of EPI over 18 years at a tertiary bariatric referral center. METHODS: A retrospective review of patients who underwent primary or revisional BS from 2002 to 2020 was performed. Patients were included if they were suspected of having EPI or underwent fecal elastase testing (FE-1). EPI diagnosis was defined as positive FE-1 testing or improvement with empiric pancreatic enzyme replacement therapy (PERT). RESULTS: EPI was suspected in 261 patients, and 190 were tested via FE-1 (89.5%) or empirically treated (10.5%). EPI was diagnosed in 79 (41.6%) patients and was associated with older age and lower BMI. Therapeutic PERT was given to 65 patients diagnosed with EPI, and 56 (86.2%) patients reported improved symptoms. Patients who underwent RYGB and BPD-DS were more likely to have EPI than those after SG (47.9% and 70.0% vs 17.4%, p < 0.01). EPI diagnosis was associated with a history chronic pancreatitis. While diarrhea and abdominal pain were the most common symptoms prompting FE-1 testing, no symptoms were significantly associated with EPI. EPI was also associated with abnormal fecal fat results and treatment with bile acid sequestrants, but not small intestinal bacterial overgrowth. CONCLUSION: This study highlights that exocrine pancreatic insufficiency can account to for previously unexplained GI complaints after bariatric surgery. Therefore, bariatric surgery programs should consider this diagnosis in symptomatic patients, especially following RYGB and BPD-DS. Further work to define patient factors that should prompt evaluation, optimal treatment, and prevention is necessary.

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.

Pancreatic Dysfunction and Reduction in Quality of Life Is Common After Pancreaticoduodenectomy.

BACKGROUND: Improvements in survival after pancreaticoduodenectomy has increased the number of patients potentially at risk of pancreatic insufficiency. AIMS: We studied long-term (> 1 year) pancreatic functions (endocrine and exocrine) after pancreaticoduodenectomy and aimed to recognize the impact of various clinicopathological factors and postoperative complications on pancreatic functions. METHODS: All patients who underwent pancreaticoduodenectomy at least 1 year prior were recruited from July 2020 to December 2021. Endocrine function was assessed using HbA1c, fasting blood sugar and postprandial blood sugar levels. Pancreatic exocrine function was assessed clinically with history of steatorrhea and objectively with quantitative estimation of fecal elastase-1 levels in stool samples. Volume of remnant pancreas, parenchymal thickness and duct diameter were assessed by computed tomography. Quality of life assessment was done using SF-36 questionnaire. RESULTS: Of the 106 patients assessed, 64 patients met the inclusion criteria. Endocrine insufficiency was noted in 51.6%, and 34.3% had new onset diabetes mellitus. The incidence of pancreatic exocrine insufficiency was 87.5% and severe insufficiency was found in 62.5% of patients. Twenty-nine (45.3%) patients had both exocrine and endocrine insufficiency. Patients with CRPOPF had higher risk of severe exocrine insufficiency (5 vs. 2, OR 1.57(0.28-8.81) p = 0.6). The SF-36 scores were lower than general population especially in role limitation due to physical health, role limitation due to emotional problems, energy/fatigue, general health perception and health change domains. CONCLUSION: Post-pancreaticoduodenectomy patients have a high frequency of pancreatic insufficiency and should be screened for same. The post-operative pancreatic fistula increases the risk of pancreatic exocrine insufficiency.

Exocrine Pancreatic Insufficiency Is Common in Celiac Disease: A Systematic Review and Meta-Analysis.

The prevalence of celiac disease (CD) is approximately 1% in the US. Studies have shown possible association between exocrine pancreatic insufficiency (EPI) and CD, with numerous hypothesized biological mechanisms including small bowel mucosal damage causing disruption of enteric-mediated hormonal secretion such as cholecystokinin and loss of enterokinase. The overall prevalence of EPI in CD remains unknown. We performed systematic review and metanalysis and examined the prevalence of EPI in patients who were first diagnosed with CD versus those who had been on treatment with gluten-free diet (GFD). Results  Six studies were included in the analysis totaling 446 CD patients (Avg age 44.1 years; 34% Males). One hundred and forty-four patients had newly diagnosed CD, and 302 patients had known CD with at least 9 months treatment with GFD. Four studies examined newly diagnosed CD patients. The individual rates of EPI in new CD patients ranged from 10.5 to 46.5%. The pooled prevalence of EPI in newly diagnosed CD patients was 26.2% (95% CI 8.43-43.92%, Q = 2.24, I2 = 0%). Five studies examined CD patients on GFD. The rate of EPI ranged from 1.9% to 18.2%. The prevalence of EPI in patients treated with GFD is 8% (95% CI 1.52-14.8%, Q = 4.42, I2 = 9.59%). Patients with newly diagnosed CD are significantly more likely to have EPI compared to those patients treated with GFD (p = 0.031). CD patients on GFD with persistent symptoms have a significantly higher rate of EPI (28.4%) compared to CD patients on GFD who are asymptomatic (3%) (p < 0.001).

Clinical features, epidemiology, and treatment of Shwachman-Diamond syndrome: a systematic review.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS. METHODS: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included. RESULTS: The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years. CONCLUSIONS: Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

Association of pancreatic fat on imaging with pediatric metabolic co-morbidities.

BACKGROUND: The relationship between pancreatic fat on imaging and metabolic co-morbidities has not been established in pediatrics. We sought to investigate the relationship between pancreatic fat measured by MRI and endocrine/exocrine dysfunctions along with the metabolic co-morbidities in a cohort of children. OBJECTIVE: To investigate relationships between pancreatic fat quantified by MRI and endocrine and exocrine conditions and metabolic co-morbidities in a cohort of children. MATERIALS AND METHODS: This was a retrospective review of pediatric patients (n = 187) who had a clinically indicated MRI examination between May 2018 and February 2020. After 51 patients without useable imaging data were excluded, the remaining 136 subjects comprised the study sample. Laboratory studies were assessed if collected within 6 months of MRI and patient charts were reviewed for demographic and clinical information. MRI proton density fat fraction (PDFF) sequence had been acquired according to manufacturer's specified parameters at a slice thickness of 3 mm. Two blinded radiologists independently collected PDFF data. RESULTS: The median age at MRI was 12.1 (IQR: 9.0-14.8) years and the majority of patients were Caucasian (79%), followed by African American and Hispanic at 12% and 11% respectively. There was a higher median pancreas fat fraction in patients with exocrine conditions (chronic pancreatitis or exocrine insufficiency) compared to those without (3.5% vs 2.2%, p = 0.03). There was also a higher median fat fraction in the head of pancreas in patients with endocrine insufficient conditions (insulin resistance, pre-diabetes, type 1 and type 2 diabetes) compared to those without endocrine insufficiency when excluding patients with active acute pancreatitis (3.5% vs 2.0%, p = 0.04). Patients with BMI > 85% had higher mean fat fraction compared to patients with BMI ≤ 85% (head: 3.8 vs 2.4%, p = 0.01; body: 3.8 vs 2.5%, p = 0.005; tail: 3.7 vs 2.7%, p = 0.049; overall pancreas fat fraction: 3.8 vs 2.6%, p = 0.002). CONCLUSION: Pancreas fat is elevated in patients with BMI > 85% and in those with exocrine and endocrine insufficiencies.