Cystic Fibrosis Treatment Options Discrepancy Globally

Cystic fibrosis, or rather known as CF, is a common monogenic disease caused by genetic mutation on CFTR on chromosome 7. Progressive obstructive pulmonary disease, sinusitis, exocrine pancreatic insufficiency leading to malabsorption and malnutrition, liver and pancreatic dysfunction, and male infertility are all characteristics of the disease. Persistent pulmonary infections are caused by a lack of CFTR or its decreased function, leading to bronchiectasis and progressive lung destruction. Despite the fact that CF patients' lives are shortening, early diagnosis has helped improve patients' life span to a median age of around 50 years, including newborn screening, mild form identification, and a proactive therapy approach. Pancreatic enzyme replacement, respiratory physiotherapy, mucolytics, and strong antibiotic therapy are among treatments for CF. For the majority of people with severe symptoms, a lung or liver transplant is necessary. The CFTR protein is affected by a large number of mutations, each of which have diverse effects. Despite advances in our understanding of CFTR function and contemporary therapy, most of our knowledge of cystic fibrosis remains unclear. With the recent addition of mutation-specific treatments, future advances in health and quality of life for people with CF are likely to improve. The focus of research is on novel medications that restore CFTR function, some of which are now accessible and have a positive therapeutic impact, while others are showing promising preliminary results.

LAPAROSCOPIC SANTULLI INTESTINAL ANASTOMOSIS IN AN INFANT WITH CYSTIC FIBROSIS

The aim of the study was to evaluate the technical feasibility of performing a Santulli-type side-toend inter-intestinal anastomosis in infants with cystic fibrosis (CF) using laparoscopy. A clinical case of a 3-month-old child with CF who was operated on in the neonatal period for meconium ileus is presented. The baby's gestational age was 32 weeks. The primary operation consisted of the formation of a terminal enterostomy. In the postoperative period, a malabsorption syndrome was noted, accompanied by a lack of growth. As a temporary measure to restore nutritional status, a Santulli-style side-to-end laparoscopic intestinal anastomosis was performed. The observed child was found to have the F508del mutation in both alleles of the CFTR gene. The patient's weight at the time of the Santulli anastomosis construction was 2900 g, the age – 3 months. During the operation, there were no difficulties associated with the mobilization of the separated segments of the ileum. The duration of the surgical intervention was 70 min. Enteral nutrition was started on the 3rd day after the operation. The recovery period for intestinal transit through the rectum was 15 days. The postoperative period was uneventful. The duration of hospitalization was 18 days. No electrolyte imbalance or excessive fluid loss or underweight associated with enterostomy was observed. Over the next 6 months, the normalization of age-related weight and height parameters was achieved, after which the continuity of the digestive tract was restored by closing the terminal enterostomy. Currently, the patient has minimal respiratory symptoms and is receiving adequate CF therapy with pancreatic enzyme replacement therapy included with each meal. The initial experience of performing laparoscopic Santulli inter-intestinal anastomosis in an infant with CF presented in the study showed the possibility and reproducibility of this technique, expanding the boundaries of laparoscopy in pediatric practice. The decision to close the enterostomy in these patients should be deferred until a full diet is introduced and should be made in conjunction with a pediatrician specializing in the treatment of CF.

Causes of Exocrine Pancreatic Insufficiency Other Than Chronic Pancreatitis

Exocrine pancreatic insufficiency (EPI), an important cause of maldigestion and malnutrition, results from primary pancreatic disease or is secondary to impaired exocrine pancreatic function. Although chronic pancreatitis is the most common cause of EPI, several additional causes exist. These include pancreatic tumors, pancreatic resection procedures, and cystic fibrosis. Other diseases and conditions, such as diabetes mellitus, celiac disease, inflammatory bowel disease, and advanced patient age, have also been shown to be associated with EPI, but the exact etiology of EPI has not been clearly elucidated in these cases. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Pancreatic enzyme replacement therapy (PERT) is indicated for the conditions described above presenting with clinically clear steatorrhea, weight loss, or symptoms related to maldigestion and malabsorption. This review summarizes the current literature concerning those etiologies of EPI less common than chronic pancreatitis, the pathophysiology of the mechanisms of EPI associated with each diagnosis, and treatment recommendations.

Russian marketing analysis of biologically active additives with pancreatic enzyme

The Russian market of biologically active additives, which include pancreatine and pancreatic enzymes — amylase, protease, lipase, has been analyzed. It was established that the study group is represented by a wide range (approximately 150 names), which is represented mainly by foreign manufacturers (approximately 80%). The monotonous tendency to increase sales by volume in all regions of the Russian Federation over the past 5 years has been analyzed. It should be noted that, today consumer preferences biologically active additives of domestic production despite the significant share of imported dietary supplements in the supply structure. High demand is primarily due to the accessibility and increased trust and loyalty of modern consumers to national producers of biologically active additives .

P-P10 The survival benefit of pancreatic enzyme replacement therapy in adult patients undergoing treatment of pancreatic neuroendocrine tumours

Background Patients with pancreatic neuroendocrine tumours (pNETs), treated with somatostatin analogues (SSAs) or pancreaticoduodenectomy, are at risk of exocrine pancreatic insufficiency. This is frequently undiagnosed but can be treated with pancreatic enzyme replacement therapy (PERT). PERT improves survival and nutritional status in other exocrine pancreatic insufficiency-associated conditions such as pancreatic adenocarcinoma. This single-centre retrospective cohort study aimed to establish whether PERT increases survival or weight maintenance in SSA or pancreaticoduodenectomy-treated patients with pNETs. Methods Departmental databases identified patients (n = 82) diagnosed with pNETs between 2009 and 2019 and managed with SSAs and/or pancreaticoduodenectomy. Their baseline characteristics, treatments and outcomes were established from clinical records. Cases (n = 47) received PERT 3 months after either pancreaticoduodenectomy or commencement of SSAs, controls (n = 35) did not. Overall survival was analysed using the Kaplan-Meier method, the log-rank test and multivariable Cox regression. Percentage monthly weight changes were compared using the Mann-Witney U test. The cohort was investigated as a whole and stratified by intervention (pancreaticoduodenectomy or SSAs) as more cases having undergone pancreaticoduodenectomy was a potential confounder. Results Median survival was not reached in either group. Cases experienced significantly greater 5-year overall survival (81% vs 53%, p = 0.010), however, PERT was not independently associated with survival (Hazard ratio 0.47, 95% CI 0.17-1.30, p = 0.143). Cases showed superior median weight maintenance (+0.04% vs -0.10% per month, p = 0.013), but had lower mean baseline weights (70.0kg vs 81.9kg, p = 0.003). Considering SSA-treated patients (n = 55) only, cases (n = 27) showed greater median weight maintenance (+0.04% vs -0.21% per month, p = 0.025) and a trend towards improved median overall survival (55.5, 95% CI 10.3-100.7 vs 47.7, 95% CI 19.1-76.4 months, p = 0.054). Conclusions PERT may improve the maintenance of weight and therefore nutrition in patients with pNETs, treated with SSAs or pancreaticoduodenectomy. PERT may also convey a survival benefit in this same population, however, due to the numerous factors which affect survival, this study appears underpowered to reliably explore this outcome. Further studies are required to accurately define the use and benefits of PERT in this population.

Indocyanine green fluorescence to ensure perfusion in middle segment-preserving pancreatectomy: a case report

Background Middle segment-preserving pancreatectomy (MSPP) is an alternative to total pancreatectomy that allows for the preservation of the endocrine and exocrine functions of the pancreas. However, maintaining perfusion to the pancreatic remnant is of critical importance. We describe the first case to our knowledge in which indocyanine green (ICG) fluorescence was used to confirm perfusion to the pancreatic remnant during MSPP. Case presentation A 79-year-old man with diabetes mellitus was referred to our hospital for treatment of a pancreatic tumor. Computed tomography revealed a hypovascular mass in the uncus of the pancreas and dilatation of the main pancreatic duct, measuring 13 mm in the tail of the pancreas. He was diagnosed with cancer of the pancreatic uncus via endoscopic ultrasound and fine-needle aspiration revealed a mixed-type intraductal papillary mucinous neoplasm (IPMN), along with high-risk stigmata in the tail of the pancreas. We performed MSPP and the length of the pancreatic remnant was 4.6 cm. The dorsal pancreatic artery was preserved and perfusion to the pancreatic remnant was confirmed by ICG fluorescence. Histopathological examination showed a pancreatic ductal adenocarcinoma in the uncus (pT1cN1M0, pStage 2B) and IPMN in the tail of the pancreas. The postoperative course was complicated by a grade B pancreatic fistula, but this was successfully treated with conservative management. The patient was transferred to a hospital 33 days after surgery. Insulin administration was necessary, but C-peptide was detectable and blood glucose was relatively well-controlled. He did not exhibit any exocrine dysfunction when pancreatic enzyme supplementation was administered. Conclusion ICG fluorescence can be used to evaluate perfusion to the pancreatic remnant during MSPP.

P-OGC03 Pancreatic enzyme supplementation improves quality of life in patients following surgery for upper GI cancer

Background Unpleasant abdominal symptoms are common following surgery for upper gastrointestinal (UGI) cancer and may occur secondary to pancreatic exocrine insufficiency (EPI). This study investigated symptoms of EPI in patients following surgery and assessed the effect of pancreatic enzyme supplementation (PERT) on these symptoms and the effect of supplementation on quality of life. Methods Patients were assessed for symptoms of EPI using a novel questionnaire. Patients who reported two or more symptoms suggestive of EPI were prescribed PERT. Abdominal symptoms were reassessed following treatment. Quality of life (QoL) was studied using the SF-36 questionnaire before and after treatment. Faecal elastase was also measured in a patient subgroup. Results Fifty-six out of 57 patients (98%) reported at least two symptoms of EPI. Following PERT every patient reported fewer abdominal symptoms; median 5 symptoms before treatment reduced to two symptoms following treatment (p < 0.0001; Wilcoxon rank). Reduced faecal elastase concentration was associated with more frequent abdominal symptoms; median 5 symptoms versus 3 symptoms (p = 0.043; Mann Whitney U test). PERT increased quality of life scores for every patient in each of the 5 principle health domains. Conclusions Symptoms of EPI are common among patients following UGI cancer surgery. PERT reduces unpleasant abdominal symptoms and this leads to significant improvements in quality of life across global health domains. PERT should be offered to all post-operative UGI cancer patients with symptoms suggestive of EPI.

P-O18 Pancreatic Enzyme Replacement Therapy in Upper GI Surgery- A Retrospective Audit

Background Pancreatic enzyme insufficiency (PEI) appears to be under recognised and under treated in upper GI surgery due to limited clinical data regarding the prevalence of PEI after gastric surgery, therefore potentially leading to malnutrition in an already vulnerable patient group. This retrospective audit looked at a total of 197 resections in a two year time period and aimed to determine what type of upper GI surgery pancreatic enzyme replacement therapy (PERT) was used in, if use of PERT improved malabsorption symptoms and/or nutritional markers (weight and grip strength) and finally if there was a consistent PERT dosage that was prescribed with good effect. Methods Retrospective audit recorded all patients that had undergone a total gastrectomy, subtotal gastrectomy, oesophagectomy, colonic interposition, palliative bypass and GIST resections between 2018-2019 that were undertaken in a regional centre for upper GI cancer surgery. Through means of patient electronic records it was recorded which of these patients started on PERT and if there was any improvement in their symptoms. Nutritional markers were recorded at specific intervals and the final dosage of PERT used with good effect. Results 66.6% of total gastrectomies were commenced on PERT with 68.1% reporting an improvement in symptoms and 27.2% reporting some improvement. 34.7% of subtotal gastrectomies were commenced on PERT and 100% of these patients experienced symptomatic relief. 22.4% of oesophagectomies were commenced on PERT with 68% reporting an improvement in symptoms and 9% some improvement. 33% of the colonic interpositions were commenced on PERT with 100% of patients reporting an improvement with symptoms. PEI was not identified in palliative bypass or GIST surgery. No significant improvement in weight was seen 9-12 months post-operatively in patients who began Creon 0-3 months after their operation, with a p-value of 0.19. Not enough grip strength data was available to analyse. The average final PERT dosage in patients that reported some improvement to improvement in symptoms was 50,000 – 75,000 units with every meal and snack. Conclusions More prevalent usage of PERT seen in total gastrectomy resections with good effect. This finding would benefit from further higher quality research to determine the mechanism behind this to support wider PERT usage in this patient group. In view of the overall positive outcomes in regards to symptom control across gastrectomies and oesophagectomies, albeit in small numbers, it should be a considered treatment and regularly screened for. In order to get a statistically significant result in regards to weight improvement when commenced on PERT a bigger sample size would be needed

Case Report: Development of Type 1 Autoimmune Pancreatitis in an Adolescent With Ulcerative Colitis Mimicking Pancreatic Cancer

Introduction: Autoimmune pancreatitis (AIP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) which is typically responsive to corticosteroid treatment.Case Presentation: We report a case of a 17-year-old male diagnosed with ulcerative colitis who subsequently developed acute pancreatitis. Blood tests demonstrated elevated pancreatic enzyme levels of amylase (1319 U/L) and lipase (809 U/L). Abdominal computed tomography revealed peripancreatic fat stranding and the presence of a perisplenic pseudocyst. Azathioprine and mesalazine were stopped as possible causes of drug-induced pancreatitis. However, pancreatic enzymes remained elevated and corticosteroid treatment was started. Despite corticosteroid therapy, amylase and lipase levels continued to increase. Infliximab was started due to a flare in gastrointestinal symptoms of ulcerative colitis. Follow-up abdominal ultrasonography revealed a pancreatic tail mass. Tumor markers, including CA 19-9, were elevated and atypical cells were seen on histological examination of an endoscopic ultrasonography-guided fine needle aspiration biopsy. Surgical pancreaticosplenectomy was performed for suspected pancreatic neoplasm. Surprisingly, histology revealed chronic pancreatitis with storiform fibrosis and infiltration of IgG4-positive cells, compatible with AIP type 1. Thereafter, pancreatic enzymes gradually decreased to normal levels and the patient has been in remission for 9 months on infliximab monotherapy.Conclusion: Pediatric gastroenterologists should keep in mind that AIP may develop during the natural course of pediatric IBD. Moreover, the development of pancreatic fibrosis may be non-responsive to corticosteroid treatment and mimic pancreatic neoplasia.