Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study.

INTRODUCTION: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Clinical evaluation and treatment of chronic bowel symptoms following cancer in the colon and pelvic organs.

Background: Chronic gastrointestinal symptoms are common among patients surviving surgery and/or radio-/chemotherapy for cancer in the pelvic organs. However, little is known about the pathophysiology behind symptoms or the effect of treatment. The aim of the present study was to present the results of clinical evaluation and treatment of patients with chronic bowel symptoms after treatment for cancer in the colon or pelvic organs. Material and methods: All patients referred to our department of gastroenterology between May 2016 and June 2018 with chronic bowel symptoms after treatment for cancer in the colon or pelvic organs were prospectively evaluated. Results: In total, 60 patients had been referred. The patients were treated for cancer in the right colon (n = 31), sigmoid colon (n = 1), rectum (n = 14), anal canal (n = 4), cervix uteri (n = 5), corpus uteri (n = 2), ovary (n = 2), and prostate (n = 1). The median time from cancer treatment to referral was 5.5 (range 1-36) years. Symptoms mainly included frequent bowel movements (65%), loose stools (87%), urgency for defecation (57%), and fecal incontinence (50%). A specific cause of bowel dysfunction was found in 48 (80%) of the patients and 21 (35%) had more than one cause of bowel symptoms. Bile acid malabsorption was present in 35 patients and small intestinal bacterial overgrowth was detected in 32. Treatment included bile acid sequestrants (n = 36), antibiotics (n = 33), loperamide (n = 21), and dietary intervention (n = 20). Major improvement in bowel symptoms was reported by 23 (38%) patients, while another 27 (45%) reported some improvement. Conclusion: Most patients with chronic bowel symptoms following cancer in the colon or pelvic organs will benefit from expert clinical evaluation and targeted treatment.

Quantifying bile acid malabsorption helps predict response and tailor sequestrant therapy.

Although recognised as a cause of chronic diarrhoea for over forty years, diagnostic tests and treatments for bile acid malabsorption (BAM) remain controversial. Recent National Institute for Health and Care Excellence (NICE) guidelines highlighted the lack of evidence in the field, and called for further research. This retrospective study explores the BAM subtype and severity, the use and response to bile acid sequestrants (BAS) and the prevalence of abnormal colonic histology. 264 selenium-75-labelled homocholic acid conjugated taurine (SeHCAT)-tested patient records were reviewed and the severity and subtype of BAM, presence of colonic histopathology and response to BAS were recorded. 53% of patients tested had BAM, with type-2 BAM in 45% of patients with presumed irritable bowel syndrome. Colonic histological abnormalities were similar overall between patients with (29%) or without (23%) BAM (p = 0.46) and between BAM subtypes, with no significant presence of inflammatory changes. 63% of patients with BAM had a successful BAS response which showed a trend to decreased response with reduced severity. Colestyramine was unsuccessful in 44% (38/87) and 45% of these (17/38) were related to medication intolerance, despite a positive SeHCAT. 47% (7/15) of colestyramine failures had a successful colesevelam response. No patient reported colesevelam intolerance. Quantifying severity of BAM appears to be useful in predicting BAS response. Colesevelam was better tolerated than colestyramine and showed some efficacy in colestyramine failures. Colestyramine failure should not be used to exclude BAM. Colonic histology is of no relevance.

Outcomes from treating bile acid malabsorption using a multidisciplinary approach.

BACKGROUND & AIM: Despite bile acid malabsorption affecting >1 % of the population, the outcomes of treatment are largely unreported. This study evaluated the effectiveness of a structured intervention for this condition. METHOD: This was a retrospective evaluation of prospectively recorded patient reported outcome measures in a consecutive cohort of patients diagnosed with bile acid malabsorption seen in a cancer centre gastroenterology clinic. Every patient completed a 7-day food diary, a gastrointestinal symptom rating scale questionnaire and Bristol stool chart before the first clinic appointment and the symptom questionnaire and Bristol stool chart before all subsequent appointments. Patients who reported any episodes of type 6 or 7 stool were referred for a (75)Selenium (Se) homocholic acid taurine scan. Abnormal gastrointestinal symptoms were investigated and treated systematically using a peer reviewed management algorithm. RESULTS: Between 2011 and 2013, 136 men, 146 women, median age 66 years (range 19-89) underwent a scan. 143 (51 %) had 7-day isotope retention of ≤20 %. 105 (73 %) had previously undergone pelvic radiotherapy and 67 (47 %) GI surgery. 123 (86 %) were treated with low-fat diets, 79 (55 %) with a bile acid sequestrant, 73 (51 %) both. On discharge, 100 (70 %) patients reported an overall symptom improvement (mean -4.2 points, p < 0.0001). In patients who had only bile acid malabsorption and no other gastrointestinal diagnoses, 77 % (41/53) reported a mean improvement of -5.4 points (p < 0.0005). Patients reported a clinically significant improvement in urgency, faecal incontinence, wind, nocturnal defaecation, tiredness, abdominal pain, bloating, and steatorrhoea, (p = <0.0005). Stool frequency was reduced and stool consistency was improved. CONCLUSION: In this large cohort of complex patients, bile acid malabsorption is common and a multidisciplinary approach to managing gastrointestinal symptoms is effective.

Pancreatitis crónica: nuevas terapias / Chronic pancreatitis: new therapies

Chronic pancreatitis occurs by the prolonged inflammation of pancreatic tissue that induces the irreversible destruction of the organ, leading to a global pancreatic insufficiency. The most common manifestations are abdominal pain, diarrhea, malabsorption, and possibly diabetes mellitus. Chronic pancreatitis treatment includes dietary restrictions, enzymatic supplementation, vitamins, and endoscopic or surgical methods depending on the degree of ductal involvement. In addition to the known therapies, new therapies are under development and research.

La pancreatitis crónica se desarrolla por la inflamación prolongada del tejido pancreático que induce la destrucción irreversible del órgano, llevando a una insuficiencia pancreática global. Las manifestaciones más frecuentes son dolor abdominal, diarrea, malabsorción y eventualmente diabetes mellitus. El tratamiento en pancreatitis crónica incluye restricciones dietarias, suplementación enzimática, vitamínica, y métodos endoscópicos o quirúrgicos, dependiendo del grado de compromiso ductal. Además de lo descrito, están en desarrollo y experimentación nuevas terapias.

Chronic pancreatitis.

Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-duct form. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals) and genetic factors (eg, mutation in a trypsin-controlling gene or the cystic fibrosis transmembrane conductance regulator); a few patients have hereditary or autoimmune disease. Pain in the form of recurrent attacks of pancreatitis (representing paralysis of apical exocytosis in acinar cells) or constant and disabling pain is usually the main symptom. Management of the pain is mainly empirical, involving potent analgesics, duct drainage by endoscopic or surgical means, and partial or total pancreatectomy. However, steroids rapidly reduce symptoms in patients with autoimmune pancreatitis, and micronutrient therapy to correct electrophilic stress is emerging as a promising treatment in the other patients. Steatorrhoea, diabetes, local complications, and psychosocial issues associated with the disease are additional therapeutic challenges.

Development of an indirect method for measuring porcine pancreatic lipase in human duodenal fluid.

Patients with exocrine pancreatic insufficiency are usually treated with porcine pancreatic enzymes but the bioavailability of these enzymes in the gut remains a matter of discussion. In order to determine the duodenal availability of porcine pancreatic lipase (PPL) present in pancreatic extracts (PE) taken orally, we developed a method for quantifying PPL in samples containing both PPL and human pancreatic lipase (HPL). Total pancreatic lipase activity measurements using the pH-stat technique and tributyrin as substrate were combined with an HPL-specific ELISA. Based on the known specific activity of the purified HPL, its activity was deduced from the ELISA measurements, and the PPL activity was obtained by subtracting the HPL activity from the total pancreatic lipase activity. This assay was established and validated using various samples containing pure PPL and recombinant HPL or PE, mixed or not with human duodenal juice. Samples collected in vivo from patients treated with PE were also tested. It was found that PPL did not affect the HPL ELISA, and the indirect PPL assay gave a measurement accuracy of 6.6% with the samples containing pure PPL and 10% with those containing PE. This assay was also used successfully to discriminate between PPL and the endogenous HPL present in the duodenal contents of patients with severe pancreatic insufficiency treated with PE. This method might provide a useful means of assessing the availability of PEs at their site of action, in the absence of a PPL-specific ELISA.