Experimental study on operative methods of pancreaticojejunostomy with reference to anastomotic patency and postoperative pancreatic exocrine function

AIM:To assess the patency of pancreaticoenterostomy and pancreatic exocrine function after three surgical methods. METHODS: A pig model of pancreatic ductal dilation was made by ligating the main pancreatic duct. After 4 wk ligation, a total of 36 piglets were divided randomly into four groups. The piglets in the control group underwent laparotomy only; the others were treated by three anastomoses: (1) end-to-end pancreaticojejunostomy invagination (EEPJ); (2) end-to-side duct-to- mucosa sutured anastomosis (ESPJ); or (3) binding pancreaticojejunostomy (BPJ). Anastomotic patency was assessed after 8 wk by body weight gain, intrapancreatic ductal pressure, pancreatic exocrine function secretin test, pancreatography, and macroscopic and histologic features of the anastomotic site. RESULTS: The EEPJ group had significantly slower weight gain than the ESPJ and BPJ groups on postoperative weeks 6 and 8 (P < 0.05). The animals in both the ESPJ and BPJ groups had a similar body weight gain.Intrapancreatic ductal pressure was similar in ESPJ and BPJ. However, pressure in EEPJ was significantly higher than that in ESPJ and BPJ (P < 0.05). All three functional parameters, the secretory volume, the flow rate of pancreatic juice, and bicarbonate concentration, were significantly higher in ESPJ and BPJ as compared to EEPJ (P < 0.05). However, the three parameters were similar in ESPJ and BPJ. Pancreatography performed after EEPJ revealed dilation and meandering of the main pancreatic duct, and the anastomotic site exhibited a variable degree of occlusion, and even blockage. Pancreatography of ESPJ and BPJ, however, showed normal ductal patency. Histopathology showed that the intestinal mucosa had fused with that of the pancreatic duct, with a gradual and continuous change from one to the other. For EEPJ, the portion of the pancreatic stump protruding into the jejunal lumen was largely replaced by cicatricial fibrous tissue. CONCLUSION: A mucosa-to-mucosa pancreatico- jejunostomy is the best choice for anastomotic patency when compared with EEPJ. BPJ can effectively maintain anastomotic patency and preserve pancreatic exocrine function as well as ESPJ.

Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).

Considerations on pancreatic exocrine function after pancreaticoduodenectomy

The pancreaticoduodenectomy(PD) procedure may lead to pancreatic exocrine and endocrine insufficiency.There are several types of reconstruction for this kind of operation.Pancreaticogastrostomy(PG) was introduced to reduce the rate of postoperative pancreatic fistula.Although some randomized control trials have shown no differences regarding pancreatic leakage between PG and pancreaticojejunostomy(PJ),recently some reports reveal benefits from the PG over the PJ.Some surgeons concern about the performing of the PG and inactivation of pancreatic enzymes being in contact with the gastric juice,and the detrimental results over the exocrine pancreatic function.The pancreatic exocrine function can be measured with direct and indirect tests.Direct tests have the highest sensitivity and specificity for detection of exocrine insufficiency but require tube placement.Among the tubeless indirect tests,the van de Kamer stool fat analysis remains the standard to diagnose fat malabsorption.The patient compliance and time consuming makes it not so suitable for its clinical use.Fecal immunoreactive elastase test is employed for screening of exocrine insufficiency,is not cumbersome,and has been used to study pancreatic function after resection.We analyze the FE1 levels in our patients after the PD with two types of reconstruction,PG and PJ,and we discuss some considerations about the pancreaticointestinal drainage method after pancreaticoduodenectomy.

Yield of testing for micronutrient deficiencies associated with pancreatic exocrine insufficiency in a clinical setting: An observational study

BACKGROUND Pancreatic exocrine insufficiency(PEI)can be difficult to diagnose and causes maldigestion symptoms and malabsorption.There has been a number of studies that have identified PEI associated micronutrient deficiencies(PEI-MD),however there is variation in both the frequency and type of PEI-MD reported,with the majority of studies including patients with PEI due to chronic pancreatitis(CP)or CP without PEI.There is a paucity of information regarding the prevalence of PEIMD in patients with PEI without CP and the yield of testing for PEI-MD in a clinical setting in patients with suspected benign pancreatic diseases.AIM To prospectively assess the yield and type of PEI–MD in patients with and without PEI secondary to benign pancreatic disease.METHODS Patients investigated for maldigestion symptoms with Faecal Elastase-1(FEL-1)and suspected or proven benign pancreatic disease were prospectively identified.At the time of FEL-1 testing,serum samples were taken for micronutrients identified by previous studies as PEI-MD:prealbumin,retinol binding protein,copper,zinc,selenium,magnesium and later in the study lipid adjusted vitamin E.FEL-1 was recorded,with a result<200μg/g considered diagnostic of PEI.Patients underwent computed tomography(CT)imaging when there was a clinical suspicion of CP,a new diagnosis of PEI recurrent,pancreatic type pain(epigastric abdominal pain radiating to back with or without previous acute pancreatitis attacks)or weight loss.RESULTS After exclusions,112 patients were recruited that underwent testing for FEL-1 and PEI-MD.PEI was identified in 41/112(36.6%)patients and a pancreatic CT was performed in 82 patients.Overall a PEI-MD was identified in 21/112(18.8%)patients.The yield of PEI-MD was 17/41(41.5%)if PEI was present which was significantly higher than those without 4/71(5.6%)(P=0.0001).The yield of PEI–MD was significantly higher when PEI and CP were seen together 13/22(59.1%)compared to CP without PEI and PEI without CP(P<0.03).Individual micronutrient assessment showed a more frequent occurrence of prealbumin 8/41(19.5%),selenium 6/41(14.6%)and magnesium 5/41(12.2%)deficiency when PEI was present(<0.02).The accuracy of using the significant micronutrients identified in our cohort as a predictor of PEI showed a positive predictive value of 80%-85.7%[95%confidence interval(CI):38%-100%]and a low sensitivity of 9.8%-19.5%[95%CI:3.3%-34.9%].CONCLUSION Testing for PEI-MD in patients with suspected pancreatic disease has a high yield,specifically when PEI and CP are found together.PEI-MD testing should include selenium,magnesium and prealbumin.

Associations with pancreatic exocrine insufficiency:An United Kingdom single-centre study

BACKGROUND Pancreatic exocrine insufficiency(PEI)is said to be associated with numerous conditions both within and outside the gastrointestinal(GI)system.The majority of research has been concerned with conditions that reduce the volume of functioning pancreatic tissue or prevent adequate drainage to the small bowel,such as chronic pancreatitis,cystic fibrosis,pancreatic cancer and pancreatic resection.However,the evidence base supporting an association with extrapancreatic conditions,such as coeliac disease,diabetes mellitus and congestive cardiac failure,is heterogeneous.AIM To strengthen the evidence base by studying all previously reported associations with PEI in a large cohort of outpatients.METHODS A single-centre retrospective study was performed.General gastroenterology outpatients tested for PEI with faecal elastase-1(FE1)were identified and information retrieved from the electronic patient record.PEI was defined as FE1<200μg/g.Patients already taking pancreatic enzyme replacement therapy were excluded.Multiple imputation was used to handle missing data.Univariable logistic regression was used to study which presenting symptoms predicted PEI.Multivariable logistic regression was used to explore the relationship between all previously reported associations and PEI.RESULTS Of 1027 patients were included.182 patients(17.7%)were diagnosed with PEI.Steatorrhoea[odds ratios(OR):2.51,95%confidence intervals(CI):1.58-3.98]and weight loss(OR:1.49,95%CI:1.08-2.06)were the only presenting symptoms that predicted PEI.Chronic pancreatitis(OR:7.98,95%CI:3.95-16.15),pancreatic cancer(OR:6.58,95%CI:1.67-25.98),upper GI surgery(OR:2.62,95%CI:1.32-5.19),type 2 diabetes(OR:1.84,95%CI:1.18-2.87),proton pump inhibitor therapy(OR:1.87,95%CI:1.25-2.80)and Asian ethnicity(OR:2.11,95%CI:1.30-3.42)were significantly associated with PEI in the multivariable analysis.None of the other historically reported associations with PEI were significant after adjustment for the other variables included in our multivariable analysis.CONCLUSION PEI is common in patients with chronic pancreatitis,pancreatic cancer,upper GI surgery and type 2 diabetes.Proton pump inhibitor therapy may also be associated with PEI or a false positive FE1.

Impacts of pancreatic exocrine insufficiency on gut microbiota

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal p H as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

Pancreatic exocrine insufficiency guidelines:more questions than answers!

Pancreatic exocrine insufficiency(PEI)has classically been described as a maldigestive disorder resulting from decreased secretion or altered function of pancreatic digestive enzymes(1).As a result of this maldigestion and ensuing malabsorption,patients can experience symptoms such as steatorrhea and weight loss as well as complications related to the loss of fat-soluble vitamins and micronutrients.PEI has been most extensively studied in cystic fibrosis,but other causes include acute and chronic pancreatitis(CP),pancreatic adenocarcinoma(PDAC),and rarely,congenital syndromes such as Shwachman-Diamond and Johnson-Blizzard(2).

A Chinese consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatic surgery(2018)

A consensus statement on the diagnosis and treatment of pancreatic exocrine insufficiency(PEI)after pancreatic surgery was developed based on the latest references,combined with China’s actual situation.More than 20 Chinese excellent experts participated in this work and contributed many thorough discussions.This consensus discusses the definition,epidemiology,diagnosis,treatment,and follow-up of PEI after pancreatic surgery.The authors hope this consensus will promote the standard procedure of diagnosis and treatment of PEI in China.

Less common etiologies of exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency(EPI), an important cause of maldigestion and malabsorption, results from primary pancreatic diseases or secondarily impaired exocrine pancreatic function. Besides cystic fibrosis and chronic pancreatitis, the most common etiologies of EPI, other causes of EPI include unresectable pancreatic cancer, metabolic diseases(diabetes); impaired hormonal stimulation of exocrine pancreatic secretion by cholecystokinin(CCK); celiac or inflammatory bowel disease(IBD) due to loss of intestinal brush border proteins; and gastrointestinal surgery(asynchrony between motor and secretory functions, impaired enteropancreatic feedback, and inadequate mixing of pancreatic secretions with food). This paper reviews such conditions that have less straightforward associations with EPI and examines the role of pancreatic enzyme replacement therapy(PERT). Relevant literature was identified by database searches. Most patients with inoperable pancreatic cancer develop EPI(66%-92%). EPI occurs in patients with type 1(26%-57%) or type 2 diabetes(20%-36%) and is typically mild to moderate; by definition, all patients with type 3 c(pancreatogenic) diabetes have EPI. EPI occurs in untreated celiac disease(4%-80%), but typically resolves on a gluten-free diet. EPI manifests in patients with IBD(14%-74%) and up to 100% of gastrointestinal surgery patients(47%-100%; dependent on surgical site). With the paucity of published studies on PERT use for these conditions, recommendations for or against PERT use remain ambiguous. The authors conclude that there is an urgent need to conduct robust clinical studies to understand the validity and nature of associations between EPI and medical conditions beyond those with proven mechanisms, and examine the potential role for PERT.

Exocrine pancreatic function during the early recovery phase of acute pancreatitis

BACKGROUND:Exocrine pancreatic dysfunction has been reported in humans in the convalescent period after acute pancreatitis,but the data are scarce and conflicting.This study aimed to prospectively assess the exocrine pancreatic function in patients with acute pancreatitis at the time of their refeeding. METHODS:Fecal elastase-1 was determined on the day of refeeding in all consecutive acute pancreatitis patients with their first episode of the disease.They were 75 patients including 60(80.0%)patients with mild acute pancreatitis and 15(20.0%)patients with severe acute pancreatitis. Etiologically 61 patients(81.3%)had biliary disease,1(1.3%) had alcoholic disease and 3(4.0%)had hypertriglyceridemia. No causes of acute pancreatitis were found in the remaining 10 patients(13.3%).The mean(±SD)refeeding time after the attack of acute panereatitis was 11.2±10.2 days. RESULTS:Pathological values of FE-1 were found in 9 of the 75 patients(12.0%):7(9.3%)patients with mild pancreatitis and 2(2.7%)patients with severe pancreatitis(P=1.000). The frequency of the pathological values of fecal elastase-1 was significantly different from that of various etiologies of the disease(P=0.030).It was significantly lower in patients with biliary pancreatitis(9.8%;P=0.035)than in one patient with alcoholic pancreatitis(P=0.126),one patient with hypertriglyceridemia-induced pancreatitis(33.3%; P=0.708),and one patient with idiopathic pancreatitis (10.0%;P=0.227).Pathological fecal elastase-1 was not significantly related to sex,age or day of refeeding.CONCLUSION:Exocrine pancreatic function should be routinely assessed in patients with acute pancreatitis at the time of refeeding in order to supplement their diet with pancreatic extracts.

Relationship between the exocrine and endocrine pancreas after acute pancreatitis

AIM: To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.

Update on endoscopic pancreatic function testing

Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis.This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditional fluid analysis.

The in vitro digestion fates of diacylglycerol under different intestinal conditions:a potential lipid source for lipid indigestion patients

The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diacylglycerols(DAGs)are potential good lipid sources for these patients.Linseed oil-based DAG(LD)and linseed oil(LT)were selected.LD-based emulsion((83.74±1.23)%)had higher lipolysis degree than LT-based emulsion((74.47±1.16)%)when monitoring the GI tract of normal population as previously reported.Indigestion conditions seriously decreased the digestive degree of LT-based emulsion((40.23±2.48)%-(66.50±3.70)%)while showed less influence on LD-based emulsion((64.18±2.41)%-(81.85±3.45)%).As opposed to LT-based emulsion,LD-based emulsion exhibited preference for releasing unsaturated fatty acids(especially oleic acid andα-linolenic acid)due to their different glycerolipid compositions.LD-based emulsion showed potential for providing lipids and nutrients(including essential fatty acids)for lipid indigestion patients.

Multiple roles for cholinergic signaling in pancreatic diseases

Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities,including sensory,motor,and visceral activities,through cholinergic signaling.Cholinergic signaling plays an important role in pancreatic exocrine secretion.A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors,participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis,and can also inhibit the progression of pancreatic cancer.However,cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors,but enhances the proliferation and invasion of pancreatic tumor cells.This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.

Pancreatitis and pancreatic cancer:A case of the chicken or the egg

Acute pancreatitis(AP),chronic pancreatitis(CP)and pancreatic cancer are three distinct pancreatic diseases with different prognoses and treatment options.However,it may be difficult to differentiate between benign and malignant disease.AP may be a first symptom of pancreatic cancer,particularly in patients between the ages of 56 and 75 with presumed idiopathic AP who had a concomitant diagnosis of new-onset diabetes mellitus or patients who present with CP at diagnosis of AP.In these patients,additional imaging is warranted,preferably by endoscopic ultrasonography.CP may lead to pancreatic cancer through oncogenic mutations,mostly in patients with hereditary CP,and in patients in whom risk factors for pancreatic cancer(e.g.,nicotine and alcohol abuse)are also present.Patients with PRSS1-mediated CP and patients with a history of autosomal dominant hereditary CP without known genetic mutations may be considered for surveillance for pancreatic cancer.Pancreatic inflammation may mimic pancreatic cancer by appearing as a focal mass-forming lesion on imaging.Differentiation between the above mentioned benign and malignant disease may be facilitated by specific features like the duct-penetrating sign and the duct-to-parenchyma ratio.Research efforts are aimed towards developing a superior discriminant between pancreatitis and pancreatic cancer in the form of imaging modalities or biomarkers.This may aid clinicians in timely diagnosing pancreatic cancer in a potentially curable stage.

DNA Content in Pancreatic ExocrinalCells after Vagotom yand Electron Microscopy in Rats

Fifty six SD rats were randomly divided into the normal control group and the operation group. The operating group was subdivided into six groups on the basis of killing time (the 12th h, the first day, 3rd day, first week, 2nd week and 4th week) after vagotomy (VG). The pancreatic tissues were taken for HE and Feulgen staining. The DNA content of pancreatic exocrine cells was determined by a domestically fabricated computer image analyzing system. In the control group, on the first day or in the first week after VG, the pancreatic samples were taken for transmission electron microscopic examination. The DNA content of pancreatic exocrinal cells was decreased from 1 to 3 days after VG. The secretion was found to be in inhibitory state and One week later, it gradually restored. The results indicated that the proliferation and the function of the SD rat's pancreatic exocrinal cells were prohibited at initial stage after VG, which might be concerned, at least in part, with dominance and nutrition of vagus.

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn&rsquo;s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD.

Staging chronic pancreatitis with exocrine function tests: Are we better?

Chronic pancreatitis(CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1(EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.

Perioperative Care of the Adult Patient with Johanson-Blizzard Syndrome

Johanson-Blizzard syndrome (JBS) is a rare genetic disorder characterized by multiple craniofacial abnormalities, intellectual disability, sensorineural hearing loss, pancreatic exocrine insufficiency, and involvement of other organ systems to varying degrees. Patients with JBS may require surgical intervention to address the underlying phenotypic abnormalities. The many craniofacial abnormalities found in patients with JBS are a concern for the anesthesiologist. We present the case of an adult patient with JBS who is undergoing implantation of a leadless pacemaker. Considering the many cardiac and craniofacial abnormalities in these patients, the anesthesiologist should order diagnostic tests such as echocardiography to assess cardiac function, as well as be prepared to perform advanced airway techniques for difficult airways. The anesthetic provider should be aware of the varied phenotypic expression of JBS and should individualize the anesthetic plan to each patient. Prior medical literature on the anesthetic management of these patients is scarce and limited to pediatric patients. This is the first case report addressing anesthetic concerns in an adult patient with JBS.

Hypothesis that alpha-amylase evokes regulatory mechanisms originating in the pancreas,gut and circulation,which govern glucose/insulin homeostasis

The anti-incretin theory involving the abolishment of diabetes type(DT)II by some of methods used in bariatric surgery,first appeared during the early years of the XXI century and considers the existence of anti-incretin substances.However,to date no exogenous or endogenous anti-incretins have been found.Our concept of the acini-islet-acinar axis assumes that insulin intra-pancreatically stimulates alpha-amylase synthesis(“halo phenomenon”)and in turn,alphaamylase reciprocally inhibits insulin production,thus making alpha-amylase a candidate for being an anti-incretin.Additionally,gut as well as plasma alphaamylase,of pancreatic and other origins,inhibits the appearance of dietary glucose in the blood,lowering the glucose peak after iv or oral glucose loading.This effect of alpha-amylase can be interpreted as an insulin down regulatory mechanism,possibly limiting the depletion of pancreatic beta cells and preventing their failure.Clinical observations agree with the above statements,where patients with high blood alpha-amylase concentrations are seldom obese and seldom develop DT2.Obese-DT2,as well as DT1 patients,usually develop exocrine pancreatic insufficiency(EPI)and vice versa.Ultimately,DT2 patients develop DT1,when the pancreatic beta cells are exhausted and insulin production ceases.Studies on biliopancreatic diversion(BPD)and on BPD with duodenal switch,a type of bariatric surgery,as well as studies on EPI pigs,allow us to observe and investigate the above-mentioned phenomena of intra-pancreatic interactions.