Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan.

BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.

Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVE: Previous studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. METHODS: One hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. RESULTS: Fifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. CONCLUSIONS: SM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

Patient-reported use of pancreatic enzyme replacement treatment (PERT) in pancreatic cancer in New Zealand and Australia: a cross-sectional survey study.

PURPOSE: This study investigated pancreatic enzyme replacement therapy (PERT) use in people diagnosed with pancreatic cancer in New Zealand (NZ) and Australia (AU). METHODS: A cross-sectional survey study was conducted using a mixed-media campaign to recruit people with pancreatic cancer and collect information about current PERT use. The questionnaire gathered data on participant demographics, awareness of PERT, prescribing practices and efficacy of enzyme replacement. RESULTS: Over 300 people with pancreatic cancer were recruited, 135 from New Zealand and 199 from Australia. Every region, state and territory was represented except for the West Coast (NZ) and the Northern Territory (AU), the lowest populated areas in both countries. In New Zealand, 60% of participants had heard about PERT, compared to 69.3% in Australia. Dosing regimens were inconsistent in both countries, with 18% and 27% of participants being prescribed PERT considered best practice in New Zealand and Australia, respectively. Before PERT commencement, 70% of participants experienced symptoms of malabsorption, with all symptoms improving after therapy was established. The majority of participants were compliant with their medication. CONCLUSION: PERT use in pancreatic cancer in New Zealand and Australia was highly variable and not compliant with international guidelines in which PERT is recommended as standard therapy. Enzyme replacement is effective for improving the symptoms of malabsorption in patients with pancreatic cancer. Clinician education may be needed to help improve the use of PERT in people with pancreatic cancer.

Pancreatic exocrine insufficiency is a risk factor for kidney stones in patients with chronic pancreatitis.

INTRODUCTION: Most patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP. PATIENTS AND METHODS: We performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003-2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis. RESULTS: Some 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4-6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51-72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65-14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04-1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01-20.3, p = 0.049). CONCLUSION: PEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.

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.

DIgestive COmplications in DIabetes - the DICODI population study.

BACKGROUND: Diabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms. METHODS: An internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time. RESULTS: From focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers. CONCLUSION: The web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.

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.

Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?

BACKGROUND: Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the 'Fast Recovery' programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated. RESULTS: The N = 44 patients treated after the introduction of the 'Fast Recovery' programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m. CONCLUSIONS: The multimodal 'Fast Recovery' programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.

Pancreatic exocrine insufficiency following pancreatoduodenectomy: A prospective bi-center study.

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication following pancreatoduodenectomy (PD) leading to malnutrition. The course of PEI and related symptoms and vitamin deficiencies is unknown. This study aimed to assess the (long-term) incidence of PEI and vitamin deficiencies after PD. METHODS: A bi-centre prospective observational cohort study was performed, including patients who underwent PD for mainly pancreatic and periampullary (pre)malignancies (2014-2018). Two cohorts were formed to evaluate short and long-term results. Patients were followed for 18 months and clinical symptoms were evaluated by questionnaire. PEI was based on faecal elastase-1 (FE-1) levels and/or clinical symptoms. RESULTS: In total, 95 patients were included. After three months, all but three patients had developed PEI and 27/29 (93%) patients of whom stool samples were available showed abnormal FE-1 levels, which did not improve during follow-up. After six months, all patients had developed PEI. During follow-up, symptoms resolved in 35%-70% of patients. Vitamin D and K deficiencies were observed in 48%-79% of patients, depending on the moment of follow-up; 0%-50% of the patients with deficiencies received vitamin supplementation. DISCUSSION: This prospective study found a high incidence of PEI after PD with persisting symptoms in one-to two thirds of all patients. Limited attention was paid to vitamin deficiencies. Improved screening and treatment strategies for PEI and vitamins need to be designed.

High prevalence of gastrointestinal symptoms in patients with primary Sjögren's syndrome cannot be attributed to pancreatic exocrine insufficiency.

INTRODUCTION: Pancreatic exocrine insufficiency (PEI) results in maldigestion of fat, leading to steatorrhea, malabsorption and weight loss. Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease with unknown etiology. The exocrine pancreas and the salivary glands are functionally and histologically comparable, and pancreatic dysfunction in SS has been hypothesized. METHODS: Patients were recruited from the Department for Rheumatology at the Karolinska University Hospital in Stockholm, Sweden, between June and December 2019. PEI was assessed by fecal elastase-1 (FE-1) and 13C-mixed triglyceride breath test (13C-MTG-BT). The presence and severity of gastrointestinal symptoms were assessed by a well-established and validated survey based on a seven-point Likert scale. RESULTS: Fifty-seven patients with primary SS were included in the study, comprising 92% females with a median age of 63 years. In total, 87% of SS patients were tested for FE-1 and all had normal results. All patients who underwent a 13C-MTG-BT had a normal cumulative 13C-exhalation. Compared to the control group, significantly more patients suffered from gastrointestinal (GI) symptoms (p < .01). The same number of patients noted moderate to severe loose bowel movements or constipation (38%). Eleven GI symptom parameters were compared to controls and the highest odd ratios were noted for the following moderate to severe symptoms: bloating, feeling of incompletely emptied bowel after defecation and abdominal pain relieved by bowel action. CONCLUSION: In our study, most SS patients suffered from irritable bowel syndrome (IBS)-like GI symptoms that could not be attributed to PEI.

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.

Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice.

BACKGROUND: RCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status. OBJECTIVE: In this study we evaluated factors responsible for persistence of malnutrition after PERT. METHODS: In this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT. RESULTS: 377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition. CONCLUSION: Even though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.

Risk factors for development of endocrine insufficiency in chronic pancreatitis.

Endocrine insufficiency is a common and frequent complication of chronic pancreatitis. Identifying the role of pancreatic damage in the development of diabetes is important for early identification and appropriate management. METHODS: All consecutive CP patients between January 2019 and May 2020 were retrospectively studied. Relevant statistical tests were performed. A two sided p value < 0.05 was considered statistically significant. RESULTS: Total 587 chronic pancreatitis patients were included of which 118 (20.1%) patients developed diabetes with duration of 12 (IQR 4-48) months. Older age (OR 1.079; 95% CI 1.045-1.113; p < 0.001), presence of pancreatic parenchymal (OR 2.284; 95% CI 1.036-5.038; p = 0.041) and ductal (OR 2.351; 95% CI 1.062-5.207; p = 0.035) calcifications, exocrine insufficiency (OR 6.287; 95% CI 2.258-17.504; p < 0.001), and pancreatic duct stricture (OR 3.358; 95% CI 1.138-9.912; p = 0.028) were independently associated with development of diabetes mellitus in chronic pancreatitis patients. On cox-regression analysis, smoking (HR 2.370; 95% CI 1.290-4.354; p = 0.005) and pancreatic ductal calcification (HR 2.033; 95% CI 1.286-3.212; p = 0.002) were independently associated with earlier onset of diabetes mellitus in patients with chronic pancreatitis. CONCLUSION: Pancreatic calcification, pancreatic duct stricture and pancreatic exocrine insufficiency are associated with development of diabetes mellitus in chronic pancreatitis indicating disease progression. Smoking is the modifiable risk factors associated with early onset of diabetes mellitus in CP patients.

Pancreatic exocrine insufficiency in diabetes is associated with autonomic dysfunction.

OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is prevalent in diabetes. Pathophysiological theories imply autoimmune destruction, lack of trophic effects of insulin or impaired neuronal stimulation, but the relationship between PEI and autonomic dysfunction is largely unknown. In a pilot study, we aimed to investigate if patients with diabetes and PEI had impaired autonomic function. METHODS: We measured faecal elastase in 59 patients with type 1 or 2 diabetes, using a cut-off-value <200 µg/g to define PEI. Based on faecal elastase results, patients were stratified into matched case (n = 8) and control groups (n = 13). We used heart rate variability, baroreflex sensitivity and orthostatic hypotension tests to assess autonomic dysfunction. RESULTS: All baroreflex sensitivity parameters were reduced in cases with PEI compared with controls (all p < .05). The heart rate variability parameters root mean square of successive RR interval differences (p = .05) and high frequency (p = .04) were also reduced. We found no difference in orthostatic hypotension between the groups. CONCLUSIONS: In this first-of-its-kind study, we found that diabetes patients with PEI had reduced autonomic function compared with matched controls. Although numbers are small, results support the hypothesis that autonomic dysfunction could be a contributor to PEI in diabetes.

Assessment of small intestinal bacterial overgrowth in chronic pancreatitis patients using jejunal aspirate culture and glucose hydrogen breath test.

BACKGROUND: A subset of chronic pancreatitis patients respond poorly to pancreatic enzyme replacement therapy. Small intestinal bacterial overgrowth (SIBO) is considered to be one of the major reasons for this poor response. Previous studies have reported a wide range of prevalence of SIBO in patients with chronic pancreatitis. We aimed to assess the prevalence of SIBO in chronic pancreatitis using quantitative jejunal aspirate culture and glucose hydrogen breath test (GHBT). The sensitivity and specificity of GHBT for the diagnosis of SIBO in chronic pancreatitis were also estimated. METHODS: Newly diagnosed chronic pancreatitis patients were recruited into the study. A detailed history and relevant laboratory tests were done. All patients underwent an endoscopy and jejunal fluid aspiration for bacterial cultures and GHBT to detect SIBO. The results of GHBT were compared with jejunal fluid aspirate culture. RESULTS: The jejunal aspirate culture was positive in 18/48 (37.5%) patients while the GHBT showed that 14/48 (29%) patients had SIBO. The sensitivity, specificity, positive and negative predictive value of GHBT in our study was 44.4, 80, 57.14 and 70.59%, respectively. CONCLUSIONS: SIBO is not uncommon in chronic pancreatitis patients. One-third of our study population had SIBO. GHBT has low sensitivity but had high specificity in the diagnosis of SIBO in chronic pancreatitis.

Measurement of fasting breath hydrogen concentration as a simple diagnostic method for pancreatic exocrine insufficiency.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is associated with the outcome of pancreatic disease. However, there is no method for assessing PEI that can be used noninvasively and easily for outpatient. It has been reported that changes in intestinal bacteria caused by PEI may increase breath hydrogen concentration (BHC) levels during glucose or lactose loading. We have evaluated the usefulness of fasting breath hydrogen concentration (FBHC) measurement without glucose loading for the evaluation of PEI. METHODS: Sixty patients underwent FBHC measurement, BT-PABA testing, and microbiome analysis. They were classified into PEI group (PABA excretion rate < 73.4%, n = 30) and non-PEI group (n = 30). The FBHC of the two groups were compared, and the diagnostic ability of PEI by them was evaluated. The 16 s rRNA (V3-V4) from fecal samples was analyzed by MiSeq. RESULTS: FBHC levels was higher in the PEI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P < 0.0001). FBHC was negatively correlated with PABA excretion rate (r = - 0.523, P < 0.001). The cutoff value of FBHC of 10.7 ppm (95% CI: 0.678-0.913, P < 0.001) showed a sensitivity of 73.3% and specificity of 83.3% for PEI diagnosis. In the PEI group, there was a significant increase of relative abundance of phylum Firmicutes (P < 0.05) and the genus Clostridium (P < 0.05). CONCLUSION: FBHC shows good potential as a simple and repeatable test for the diagnosis of PEI. The elevated FBHC levels may be caused by hydrogen-producing bacteria such as Clostridium.

Acute recurrent and chronic pancreatitis in children.

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.

Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Gut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis. METHODS: The fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity. RESULTS: Patients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05). CONCLUSIONS: The current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.

Three-dimensional remnant pancreatic volume ratio indicates postoperative pancreatic exocrine insufficiency in pancreatic cancer patients after distal pancreatectomy.

BACKGROUND: Pancreatectomy may cause serious pancreatic exocrine insufficiency (PEI), which can lead to some nutritional problems, including new-onset diabetes mellitus (DM) or non-alcoholic fatty liver disease (NAFLD). Recent studies have reported that remnant pancreatic volume (RPV) significantly influences postoperative PEI. However, the specific correlation between RPV and postoperative PEI remains unclear. Here, we compare various pre-, peri-, and postoperative risk factors in a retrospective cohort to address whether preoperatively measured RPV is a predictor of postoperative PEI in pancreatic cancer patients after distal pancreatectomy (DP). METHODS: Sixty-one pancreatic cancer patients who underwent DP were retrospectively enrolled. Pancreatic volume was measured using preoperative 3D images, which simulated the actual intraoperative pancreatic parenchymal volume. We obtained the 3D-measured RPV and resected pancreatic volume. We calculated the ratio of the RPV to the total pancreatic volume and then divided the cohort into high- and low-RPV ratio groups based on a cut-off value (>0.35, n = 37 and ≤ 0.35, n = 24). Using multivariate analysis, the RPV ratio as well as pre-, peri- and postoperative PEI risk factors were independently assessed. RESULTS: The multivariate analysis revealed that a low RPV ratio (odds ratio [OR], 5.911; p = 0.001), a hard pancreatic texture (OR, 3.313; p = 0.023) and TNM stage III/IV (OR, 3.515; p = 0.031) were strong predictors of the incidence of PEI. CONCLUSIONS: The present study indicates that the RPV ratio is an additional useful predictor of postoperative nutrition status in pancreatic cancer patients.

Clinical importance of main pancreatic duct variants and possible correlation with pancreatic diseases.

Background: Except for pancreas divisum (PD), the prevalence of anatomic variants of the main pancreatic duct (MPD) seems to be insufficiently investigated. To date, their role in the occurrence of pancreatic exocrine insufficiency (PEI) and morphological changes suggestive of chronic pancreatitis (CP) has remained unclear.Methods: A systematic review was performed, searching MEDLINE and Web of Science, limited to articles published between 1960 and 1 June 2019.Results: Our review included a total number of 3234 subjects. The most common variant of MPD was type 3, followed by type 1, indicating MPD drainage pattern into major papilla (MP) as the most frequent. A sub-variant of type 3, known as 'reverse pancreas divisum' had a prevalence of 2.2%. Type 4 variant- PD, was found in 6.4% of all cases. The most common sub-variant of PD was complete PD, followed by incomplete PD and variant with MPD as only pancreatic duct. Type 5 variant (including ansa pancreatica) was present in 2.9% of subjects. Apart from one study with a significantly higher frequency of morphological changes suggestive of CP in patients with ansa pancreatica, the studies stated no significant association between pancreatic disease and MPD variants. Furthermore, only one study examined the influence of MPD variants on exocrine pancreatic function. Although equivocal, this association is most likely found to be insignificant.Conclusion: To elucidate linkage between MPD variants and the occurrence of chronic pancreatitis and impairment of pancreatic exocrine function, further clinical investigations are warranted.