Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Digestive System Diseases

Rare Diseases

Diabetes Mellitus

Recurrence

Pancreatic Neoplasms

Pancreatitis

Pancreatitis, Chronic

Pancreatic Diseases

Gastrointestinal Diseases

Chronic Disease

Disease Attributes

Pancreatic Cancer

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

At least 2 episodes of acute pancreatitis with complete resolution of pain and a \>1 month pain-free interval between episodes.

Children with at least:

1) One irreversible structural change\* in the pancreas with or without abdominal pain +/- exocrine pancreatic insufficiency +/- diabetes.

\*irreversible structural changes:

* Ductal calculi, dilated side branches, parenchymal calcifications found in any imaging (abdominal ultrasound (abd US), magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), computerized tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), endoscopic US (EUS).
* Ductal obstruction or stricture/dilatation/irregularities that are persistent (for \>2 months) on any imaging.
* Parenchymal atrophy, irregular contour, accentuated lobular architecture, cavities alone are not diagnostic findings for CP.
* Surgical or pancreatic biopsy specimen demonstrating histopathologic features compatible with CP (acinar atrophy, fibrosis, protein plugs, infiltration with lymphocytes, plasma cells, macrophages).

Six ml of blood will be collected from patients in an EDTA tube. 2 ml saliva samples in Oragene DNA collection kits

Blood sample

Questionnaires will be completed at the baseline and annual follow-up visits to collect data that will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Patient questionnaires

2 ml saliva samples in Oragene DNA collection kits collected if no blood sample being collected.

Saliva sample

Urine sample

Ying Yuan, Ph.D

The investigators will enroll a total of 628 patients under 18 years of age with ARP or CP. Included in the total are the 357patients in the INSPPIRE 1 database who are planned to be reenrolled under this protocol over the next 4 years. Patient questionnaires and physician surveys will be applied at the time of enrollment and annually thereafter as long as possible. At the first study visit after turning 18 years of age, the patient will sign the informed consent to continue in the study. Specifically, the investigators will define the demographics of the pediatric ARP and CP cohort, describe risk factors, presence of family history of acute and chronic pancreatitis, diabetes and pancreatic cancer and assess disease burden and sequelae.

Disease Burden Pain. The pattern of the pain (constant versus episodic), its frequency, duration, visits to the emergency room or hospitalizations for pain, impact of pain on quality of life will be recorded in questionnaires. The intensity of the pain will be measured at enrollment, during an attack and annually using FACES Pain Scale-Revised, a self-report questionnaire validated for children \>4 y/o. The names, dosing and frequency of medications taken for pain will also be queried.

Health-Related Quality of Life (HRQOL). An age-specific instrument validated for United States children will be used to measure HRQOL at enrollment and annually thereafter. Parents of children 5-18 years old will complete Child Health Questionnaire Parent Form 50 questions (CHQ PF-50). Children \>10 years old will answer Child Health Questionnaire Child Form 87 questions (CHQ-87). Adults \>18 years old will not complete a health-related questionnaire. These questionnaires capture physical functioning, social, emotional, physical and behavioral limitations, bodily pain, general behavior, mental health, self-esteem, general health perceptions, change in health and parental emotional impact.

Depression and anxiety. Depression and anxiety are strong predictors of chronic pain and pain-related disability in children, but it is not known whether this applies to children with ARP or CP. The investigators will assess for depression and anxiety in the INSPPIRE cohort at the time of enrollment and annually thereafter. The investigators will utilize the Child Behavioral Checklist (CBCL), one of the most widely-used standardized measures in child psychology for evaluating maladaptive behavioral and emotional problems in preschool subjects aged 1½ to 5 years and in school-age subjects between the ages of 6 and 18. For preschool-age children, the CBCL/1½-5 (completed by parents or surrogates) will be used. For school-age children 6-18 y/o, the investigators will utilize CBCL/6-18 y/o (completed by parents or surrogates). Children who are 11-18 y/o will answer a self-report questionnaire (Youth-Self Report Form or YSR/11-18). CBCL assesses internalizing (i.e., anxious, depressive, and over controlled) and externalizing (i.e., aggressive, hyperactive, noncompliant, and undercontrolled) behaviors. Adults \>18 years old will not complete a behavioral checklist.

Patients/parents will spend approximately 2 hours answering questionnaires; their time will be compensated at $50 per visit. Patients will be enrolled during clinic visit as outpatient or as an inpatient. Alternatively, questionnaires can be applied over the phone or completed at home and returned via mail if the patient is unable to travel. Self-addressed stamped envelopes will be given to the patient/parent as needed for returning the questionnaires.

Disease Sequelae

The presence of exocrine pancreatic insufficiency and glucose intolerance/diabetes will be monitored at the time of enrollment and annually thereafter. Monitoring will include specifically:

1. Exocrine pancreatic insufficiency: defined as the presence of abnormal fecal elastase (\< 100 ug/ g stool on 2 separate samples ≥ 1 month apart) or abnormal serum trypsin or serum trypsinogen.
2. Diabetes or prediabetes: Monitoring for diabetes in our cohort will include once yearly assessments with fasting glucose (diabetes range if ≥ 126 mg/dL), HbA1c (abnormal if \>6; diabetic if \>6.5%) and oral glucose tolerance test (OGTT). For OGTT, 1.75 grams/kg of standard glucose beverage (glucola, maximum 75 grams) will be consumed within 10 minutes at time 0. Glucose will be drawn prior to the beverage and at time 120 minutes. From this test, glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose \<100 mg/dL, 2 hour \<140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose \>126 mg/dL or 2 hour glucose \>200 mg/dL).
3. Nutritional status including micronutrient deficiency: To determine the nutritional sequelae of ARP or CP in children, the investigators will assess for malnutrition/obesity (weight, height, BMI, z scores; body fat mass and lean mass as measured by DXA scan), fat soluble vitamin deficiencies (serum vitamin levels for A, D, and E and bone density (DXA scan) in children with ARP or CP at the time of enrollment and annually thereafter.

The investigators will identify subjects within our cohort that presented with acute recurrent pancreatitis episodes, normal exocrine and endocrine pancreas function and normal pancreas imaging without any signs of chronicity (ARP cohort). The investigators will identify the development of CP on an annual basis as long as possible, as well as development of sequelae and disease burden as listed above.

Prospective Registry

The investigators will develop a database of children with ARP and CP. This will provide a cohort of well-phenotyped subjects for future studies targeting pathogenesis and novel therapies. The investigators will establish a process by which investigators outside of the consortium may have access to the data and biospecimens.

At enrollment, via the informed consent, subjects will choose whether or not to allow use of their biological samples for this study, future research, genetic analysis, genetic analysis for future research, and any type of future research. They will also choose whether or not we may keep their name and personal information in a registry to allow us to contact them for other future research.

BIOSPECIMEN COLLECTION

Sample collection for deoxyribonucleic acid (DNA): The subject will be able to give either blood or saliva. Six ml of blood will be collected from subjects in an ethylenediaminetetraacetic acid tube or 2 ml saliva samples in Oragene DNA collection kits then labeled with the barcoded specimen labels provided by the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) Coordinating Center. The specimen labels provided by CPDPC include a specimen identification (ID) number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the patient information in the CPDPC's secure IIMS Specimen Manager system. After the specimen ID number is linked to the subject in the CPDPC system the samples will be submitted to the central repository for the study via overnight courier. The central repository for DNA will be at the University of Iowa. The central repository at Iowa will not have access to the link that connects to the patient's personal identifiers in the Integrated Information Management System (IIMS). The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The central repository will process the specimens into aliquots for the extraction of genomic DNA following the CPDPC specimen processing described in the appendices. The aliquots will be labeled with CPDPC supplied labels and stored in a freezer at -80 degree Centigrade. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at National Institute of Diabetes and Digestive and Kidney Diseases.

Urine collection for bio-markers: To be completed only at sites identified by the lead site to collect urine samples. Not all sites will be collecting urine. See Appendix 14.27 for collection and processing instructions. The subject will be instructed to collect a minimum of 50 mL clean-catch urine sample. A dipstick urine analysis will be performed immediately after urine collection. Urine samples will then be kept on wet ice or refrigerated until processed. Samples will be processed within 4 hours of collection. Samples will be labeled with the barcoded specimen labels provided by the CPDPC Coordinating Center. The specimen labels provided by CPDPC include a specimen ID number and barcode. Subject identifiers (for example names or initials) are not included on the labels. Before shipping the specimens to the central repository the specimen ID number from the label will be connected to the subject information in the CPDPC's secure IIMS Specimen Manager system. After processing, samples will be frozen at -80ºC. The urine processing log sheet will be completed. Samples will be stored and batch shipped to the Central repository at University of Iowa annually. The central repository will log receipt of the specimens into the CPDPC IIMs Specimen Manager system using the specimen ID from the labeled vials. The central repository at University of Iowa will not have access to the link that connects the subject's personal identifiers in the IIMS system. The central repository will log receipt of the specimens into the CPDPC IIMS Specimen Manager system using the specimen ID from the labeled vials. The CPDPC aliquots labels contain barcodes and specimen ID numbers that do not link the aliquots to each other. The only link to the subject information resides in the secured database at the CPDPC coordinating and data management center. The central repository laboratory staff and the study researchers do not have access to this link. At the end of the study the specimens stored in the central repository at Iowa will be transferred to a central repository at NIDDK.

6 ml blood sample or 2 ml saliva sample collected 1 time. Urine 50 ml collected one time

Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) CPDPC16-03 Pediatric Longitudinal Cohort Study of Chronic Pancreatitis

Date of diagnosis of first acute pancreatitis to date of diagnosis of chronic pancreatitis presented as minimum, maximum, median number of days and no progression to chronic pancreatitis.

Presence of abdominal pain in the past year presented as number with "Yes", "No", "I don't know" and missing responses.

Presence of constant abdominal pain described as number of subjects with "Yes", "No", "I don't know" and missing responses.

Number of subjects who are usually pain free with episodes of abdominal pain described as number with "Yes", "No", "I don't know" and missing responses..

Number of emergency room visits subjects experienced in the past 12 months presented as minimum, maximum, and median number of emergency room visits and number of missing responses.

Number of emergency room visits the subject experienced in their whole life presented as minimum, maximum, and median number of visits and number of missing responses..

Number of hospitalizations subject experienced in the past 12 months presented as minimum, maximum, and median number and number of missing responses..

Number of hospitalizations subject had in their whole life presented as minimum, maximum, and median number and number of missing responses..

Number of school days subject missed in the last month presented as minimum, maximum, and median number and number of missing responses..

Number of subjects with abnormal fecal elastase (\< 100 micrograms/ gram of stool on 2 separate samples ≥ 1 month apart) presented as number of subjects with abnormal and normal lab values and number of subjects who did not have test done.

Number of subjects with fasting glucose ≥126 milligrams per deciliter presented as number of subjects with abnormal and normal lab value and number of subjects who did not have test done.

Number of subjects with HbA1c (abnormal if \>6; diabetic if \>6.5%) results that were normal, abnormal, and diabetic and number who did not have test done.

Number of subjects with abnormal OGTT test results. OGTT performed with 1.75 grams/kilogram of standard glucose beverage (glucola, maximum 75 grams) consumed within 10 minutes at time 0. Glucose drawn prior to the beverage and at time 120 minutes. Glycemic status will be defined as: (1) normal glucose tolerance (NGT, fasting glucose \<100 mg/dL, 2 hour \<140 mg/dL); (2) pre-diabetic based on impaired fasting glucose (IFG, fasting glucose 100-125 mg/dL) and/or impaired glucose tolerance (IGT, 2 hour glucose 140-199 mg/dL); or (3) diabetic (DM, fasting glucose \>126 mg/dL or 2 hour glucose \>200 mg/dL). Findings presented as number of subjects with normal, pre-diabetic, impaired, and diabetic results and number that did not have test done.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

National Cancer Institute (NCI)

Aliye Uc

Professor

Immune System Diseases

Substance Related Disorders

Carcinoma

Inflammation

Carcinoma, Pancreatic Ductal

Pancreatitis, Acute Necrotizing

Autoimmune Pancreatitis

Pancreatic Intraductal Neoplasms

Pancreatitis, Alcoholic

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Autoimmune Diseases

Hematinics

Anti-Infective Agents

Central Nervous System Depressants

Liver Extracts

Ethanol

Patients with high suspicion of solid pancreas neoplasia: carcinoma, intrapapillary mucinous neoplasia (IPMN), neuroendocrine tumor, lymphoma, or intrapancreatic metastasis; based on CT/MR.

Patients with high suspicion of solid inflammatory lesions: acute, chronic, or autoimmune pancreatitis; based on CT/MR.

Patients without a history of any type of solid or hematologic malignancy, hepato-pancreato-biliary disease (including fatty liver and pancreas disease), tobacco/alcohol habits, or morbid obesity with bariatric surgery criteria; who require EUS evaluation (e.g., suspicious of a subepithelial lesion in the context of chronic dyspepsia).

EUS Shear wave elastography (SWE) is a form of ultrasound elastography used in transabdominal ultrasonography. It measures tissue elasticity by generating shear waves inside the organ using the acoustic radiation force impulse (ARFI). The ultrasound machine monitors shear wave propagation and measures the velocity. The shear wave velocity, displayed in kilopascals \[kPa\] or meters per second. Also, the dispersion slope or ultrasound shear wave dispersion (SWD) will be recorded. It is the measure of viscosity \[(m/sec)/kHz\] using SWE.

A first endoscopist will perform EUS over pancreas tissue. Without any elastography assessment (strain ratio/histogram) , the endoscopist will take ten shear wave measurements of pancreas tissue elasticity by generating shear waves inside the pancreas using the ARFI.

Pancreas EUS shear wave

Pancreas EUS-elastography measures the pancreatic tissue stiffness through strain ratio (SR) and strain histogram (SH).

A second endoscopist blind to pancreas tissue shear wave findings will perform EUS-elastography with corresponding SR and SH measurements. The SR/SH will be measured and documented. Finally, a pancreas tissue biopsy will be performed. The impossibility of biopsy is an exclusion criterion (except in control patients). Due to ethical purposes, a biopsy will not be performed on patients from the control group.

Pancreas EUS-elastography and EUS-guided biopsy

Carlos Robles-Medranda, MD FASGE

The diagnosis of pancreas diseases is based on a combination of clinical signs, symptoms, and laboratory tests, but mainly on imaging techniques such as computed tomography (CT) and magnetic resonance (MR). However, CT/MR have variable sensitivity and specificity, with certain disadvantages. Endoscopic ultrasound with elastography is an important resource with higher diagnostic accuracy in assessing solid pancreas lesions. Shear wave velocities of healthy parenchyma, acute, chronic and autoimmune pancreatitis, neoplastic lesions of the pancreas must be evaluated and compared.

The pancreas is a retroperitoneal organ that can cause inflammatory and neoplastic diseases, significantly impacting the quality of life to survival. Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in industrialized countries. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreas cancer is one of the neoplastic diseases with high mortality worldwide. Those diseases have been associated with significant morbidity, mortality, and hospitalization costs

The diagnosis of pancreas diseases is based on a combination of clinical signs, symptoms, and laboratory tests, but mainly on imaging techniques such as computed tomography (CT) and magnetic resonance (MR). Imaging provides a significant contribution to the diagnosis of pancreatic diseases and severity estimation or staging for inflammatory and neoplastic lesions, respectively. However, CT/MR have variable sensitivity and specificity, with certain disadvantages.

Endoscopic ultrasound with elastography is an important resource with higher diagnostic accuracy in assessing solid pancreas lesions. Shear wave elastography is a novel technique that can measure tissue elasticity by generating shear waves inside the organ using the acoustic radiation force impulse.

EUS Shear wave velocities of healthy parenchyma and solid pancreas lesions as acute, chronic, autoimmune pancreatitis and neoplasia are under described and must be evaluated and contrasted. Therefore, the present study pursues to estimate the diagnostic accuracy of EUS Shear wave for neoplasia assessment among solid pancreas lesions.

EUS Shear Wave for Solid Pancreatic Lesions.

Endoscopic Ultrasound Shear Wave for Neoplasia and Inflammation Assessment Among Solid Pancreas Lesions: a Case-control Observational Trial.

The median of ten SWE/SWD measures will be calculated to represent the final pancreas tissue shear wave measure per case. The higher the median, the more suspicious for neoplasia.

The SR/SH measures will be recorded per case. A SR\>15 kPa and a SH≤45 will be considered as highly suspicious for neoplasia.

The pathologist will have access to all the clinical data of each patient, including EUS-elastography findings, except shear wave measurements, to determine if the assessed pancreas lesion was neoplasia or inflammatory. In addition, a preliminary diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of pancreas EUS shear wave measurements and pancreas EUS-elastography will be calculated using histopathology results as gold standard.

A gastroenterologist will follow patients for one year after the procedure. During this follow-up, there will record cases who undergo exploratory or onco-specific surgery (histopathology) and the number of patients who undergo onco-specific treatment (radiotherapy, radiosurgery, chemotherapy, and biological therapy) or clinical management/surveillance. Survival and cause of death will also be recorded when corresponding. This follow-up purposes of determining definitively if the assessed pancreas lesion was neoplasia or inflammatory. A definitive diagnostic accuracy (sensitivity, specificity, positive and negative predictive value) of pancreas EUS shear wave measurements and pancreas EUS-elastography will be calculated using a one-year follow-up as the gold standard.

Instituto Ecuatoriano de Enfermedades Digestivas

Necrosis

Pancreatic Pseudocyst

Cysts

Pancreatic Cyst

The group of participants with post-inflammatory pancreatic and peripancreatic fluid collections with double pigtail plastic stents introduced through the LAMS during endoscopic transmural drainage.

The group of participants with post-inflammatory pancreatic and peripancreatic fluid collections without double pigtail plastic stents introduced through the LAMS during endoscopic transmural drainage.

During endoscopic procedure of endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections the operator introduces double pigtail plastic stents through the LAMS.

Introduction of double pigtail plastic stents through the LAMS during endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections

During endoscopic procedure of transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections the operator introduces transmurally the LAMS only, without the double pigtail plastic stents.

Endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections with use of LAMS only

Mateusz Jagielski, Prof.

The goal of this clinical trial is to learn about clinical usefulness of double pigtail plastic stents during endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections with use of lumen-apposing metal stents (LAMS).

The main question it aims to answer is:

Does introduction of double pigtail plastic stents through the LAMS increases efficacy and safety of endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections?

Acute pancreatitis (AP) of moderate-to-severe clinical course is associated with a high risk of local complications and organ failure leading to increased mortality. Pancreatic and peripancreatic fluid collections (PPFCs) that can appear in the late phase of pancreatitis can take the form of pancreatic pseudocysts and walled-off pancreatic necrosis (WOPN). These types of PPFCs are the most common local complications of acute and chronic pancreatitis. For many years, the traditional treatment of post-inflammatory PPFCs in the late phase of pancreatitis relied on surgical methods. However, there has been a recent dynamic development of minimally invasive techniques, including endoscopic transluminal methods. While endoscopic treatment is an established method of managing these complications, some aspects of endotherapy are still a source of much controversy. One of the most debated issues in interventional endoscopy of local complications in pancreatitis is the use of transmural self-expanding metallic stents (SEMSs).

Endoscopic transmural drainage consists of creating a fistula between the lumen of the PPFC and gastrointestinal tract to allow for a free outflow of fluid out of the PPFC and into the gastrointestinal tract. During an endoscopic ultrasound (EUS)-guided procedure of endoscopic transmural drainage of post-inflammatory PPFCs, this can be visualized in the endosonographic image through the wall of the upper gastrointestinal tract. Afterwards, a transmural puncture of the PPFC is performed under EUS guidance and widened with a cystotome to a diameter of 10 Fr using coagulation. This forms a transmural cystostomy, which joins the gastrointestinal tract and the lumen of the PPFC. The next step of the endoscopic procedure is mechanical (with a dilator) or pneumatic (with a high-pressure balloon) dilation of the pancreaticocystogastrostomy or pancreaticocystoduodenostomy. Once dilated, a transmural SEMS or plastic stent(s) is introduced through the cystostomy to facilitate free passive transmural drainage of the collection contents into the gastrointestinal tract. Passive transmural drainage is an effective method of endoscopic treatment of pancreatic pseudocysts, whose contents are entirely liquid. In the case of necrotic PPFCs that contain both liquefied necrotic material and tissue fragments, it is necessary to use active transmural drainage, which consists of inserting an additional nasal drain through the transmural cystostomy to enable flushing of the collection cavity in the postoperative period.

The development of advanced endoscopic techniques has led to rapid advancements in biomedical materials, including polymers for manufacturing endoscopic devices. Currently, there is a wide variety of transmural endoprostheses of different sizes, shapes, and designs for endoscopic treatment of post-inflammatory PPFCs. These endoprostheses were divided into two groups. The first group includes plastic stents, usually made of Teflon or polyethylene. The second group is SEMSs, often referred to as "lumen-apposing metal stents" (LAMSs), that are used in the treatment of post-inflammatory pancreatic local complications. For many years, the only type of endoprosthesis available for use in transmural drainage was plastic double-pigtail stents. However, LAMSs have been attracting increasing interest as a relatively new option in endoscopy. LAMSs are a special type of SEMS used in a variety of gastrointestinal endoscopic procedures. They are made of nitinol wire and are fully covered with a silicone membrane.

However, the role of LAMSs in transmural drainage remains unclear. Many authors believe that use of LAMS during endoscopic transmural drainage increases risk of complications in form of bleeding. Despite the development of advanced endoscopic techniques and devices, the high rates of bleeding into the PPFC lumen remain a major challenge in transmural drainage treatment. This type of complication is often caused by blood vessels adjacent to the fluid collection being damaged by the distal flange of the LAMS. It seems that inserting a plastic double-pigtail stent through the LAMS limits the risk of this kind of complication by moving the back wall of the PPFC away from the distal flange, PPFC cavity bleeding during transmural drainage is still a major complication associated with a high risk of fatal outcomes.

In this trial the participants with post-inflammatory PPFCs will be divided into two arms.

The first arm will consist of participants who underwent traditional transmural drainage procedure with use of LAMS only.

The second arm will consist of participants with PPFCs who underwent endoscopic transmural drainage with use of LAMS and during the procedure double pigtail plastic stents will be introduced through the LAMS in order to prevent bleeding.

Each arm will consist of at least 50 participants with post-inflammatory PPFCs.

The Role of Double Pigtail Plastic Stents During Endoscopic Transmural Drainage of Pancreatic Fluid Collections.

The Assessment of Effectiveness and Safety of Double Pigtail Plastic Stents During Endoscopic Transmural Drainage of Post-inflammatory Pancreatic and Peripancreatic Fluid Collections With Use of Lumen-apposing Metal Stents (LAMS).

Evaluation of efficacy based on clinical picture and results of imaging examinations.

Evaluation of safety based on clinical picture and results of imaging examinations.

Evaluation of early complications within thirty days from onset of endoscopic drainage.

Evaluation of late complications of endoscopic drainage.

Assessment of clinical results of endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections with use of double pigtail plastic stents introduced through the LAMS.

Assessment of long-term results of endoscopic transmural drainage of post-inflammatory pancreatic and peripancreatic fluid collections with use of double pigtail plastic stents introduced through the LAMS.

Nicolaus Copernicus University

Pathological Conditions, Anatomical

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Reproductive Control Agents

Indomethacin

Patients assigned to the Indomethacin group will receive100 mg of indomethacin administered per rectal route (two tablets of 50 mg indomethacin suppositories)

Patients assigned to the Placebo group will receive two glycerin suppositories.

Patients with pancreatic cysts requiring fine needle aspiration will be enrolled in this randomized trial

EUS-guided fine needle aspiration of pancreatic cysts

Barbara J Broome

Ji Young Bang, MD, MPH

Ji Young Bang, MD MPH

The aim of this randomized trial is to compare the rate of post-procedure pancreatitis in patients undergoing EUS-FNA of pancreatic cysts; patients will receive either a single dose of indomethacin or placebo administered rectally, during EUS-FNA.

Pancreatic cysts are pre-malignant lesions and are being increasingly diagnosed on cross-sectional imaging. Endoscopic ultrasound (EUS) is performed to further evaluate pancreatic cysts, and fine needle aspiration (FNA) is conducted to obtain a sample of the cystic fluid for analysis and examination for malignant cells. Acute pancreatitis is a complication of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic cysts, which can lead to significant morbidity and substantial health care costs. The aim of this randomized trial is to compare the rate of post-procedure pancreatitis in patients undergoing EUS-FNA of pancreatic cysts; patients will receive either a single dose of indomethacin or placebo administered rectally, during EUS-FNA.

Rectal Indomethacin to Prevent Acute Pancreatitis in EUS-FNA of Pancreatic Cysts

Randomized Trial of Rectal Indomethacin to Prevent Acute Pancreatitis in Patients Undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration of Pancreatic Cysts

Post-procedure pancreatitis is defined as the development of new or increased abdominal pain consistent with acute pancreatitis, and elevated amylase or lipase at least three times the upper limit of normal .

Rate of adverse events resulting from EUS-FNA

Any adverse event occurring as a result of underlying pancreatic cyst

Rate of mild, moderate and severe pancreatitis post-FNA

Length of hospitalization in any patient hospitalized with any adverse event

Length of hospitalization in any patient hospitalized with acute pancreatitis

Orlando Health, Inc.

Ulcer

Stomach Neoplasms

Malnutrition

Crohn Disease

Inflammatory Bowel Diseases

Intestinal Diseases

Colitis

Colitis, Ulcerative

Esophageal Neoplasms

Gastroenteritis

Nutrition Disorders

Head and Neck Neoplasms

Esophageal Diseases

Stomach Cancer

Esophageal Cancer

The "Intervention arm" includes an intervention in the groups of patients who, after screening, are identified as having disease-related malnutrition (DRM) or at risk of DRM, and a follow-up of the rest of the patients

The "By demand arm" will include patients in whom the nutritional intervention, if given, is performed by demand by the medical staff responsible for each patient.

In the "Usual care arm" usual hospital practice is followed without any explicit nutritional intervention

The intervention will be carried out by the Endocrinology and Nutrition Service of hospital 1, where the type of therapeutic action to be developed will be established (Dietary advice, Oral Nutritional Supplementation (SNO), Enteral Feeding or Parenteral Nutrition). The Total Calorie Balance, calories from feeding or with Oral Nutritional Supplementation (ONS), enteral, parenteral, and protein intake will be recorded. The steps to be taken are the following: A.-In patients with preserved oral intake capacity apply the most appropriate dietary measures in each case. B.-If the oral route is contraindicated, it will be assessed if it is possible to use the gastrointestinal tract and enteral nutrition will begin until the patient recovers the oral intake capacity. C.-If the use of the gastrointestinal tract is not indicated, parenteral nutrition will be assessed until digestive function is restored.

Nutritional dietary intervention

In the "By demand" arm, it is by clinical judgement of the doctor responsible of each patient that can be demanded a nutritional intervention to the nutrition unit of the center's endocrinology service that will judge the type of intervention. This is their usual care right now

By demand

In th "Usual care" arm, there is no explicit nutritional intervention performed at this time for those patients and, therefore, their usual regular nutritional care will be provide

Usual current care

Natalia Covadonga Iglesias, MD

Alfredo Yoldi, MD

Objectives: To evaluate the effectiveness, and cost-effectiveness, of three hospitalized patient care strategies in relation to disease-related malnutrition (DRM) hospital admissions based on results such as length of stay of the index admission, and from admission until one year after admission, mortality rate, appearance of complications, changes in weight and nutritional state, changes in their health related quality of life and functional status, readmissions, use of health services resources (primary care, hospital and emergency consultations) and costs. Methodology: Intervention study involving three hospitals with three branches in which, after nutritional screening in all centers, the first branch / hospital includes a intervention strategy for nutritional improvement in patients who after screening are identified as having DRE or at risk of DRE, and follow-up of other patients; a second cohort / hospital will include similar patients in which if there is any nutritional intervention it will be carried out by demand of the medical staff in charge of the patient; and a third branch /hospital in which the usual practice of the center will be followed without any explicit intervention. Subjects of the study: At least 300 patients in each center admitted to the digestive services, due to digestive pathologies, and surgery services due to tumor and digestive system pathologies. In all patients, sociodemographic and clinical data will be collected and of the outcomes described above during admission and until the year of follow-up. Statistical analysis: through appropriate multiple regression models for each outcome variable and with adjustments through propensity scores to compare the three centers based on each outcome parameter. A cost-effectiveness analysis will be carried out through of the incremental cost for each year of quality-adjusted life (QALY) .

Objectives

1. -After a nutritional screening of all patients, evaluate the effectiveness of an intervention in patients admitted to a hospital in relationship to disease-related malnutrition (DRM) by comparing 3 cohorts: cohort-1: organized intervention to patients with DRM or at risk; group 2: intervention on demand by health personnel; Group 3: usual care without any explicit intervention. Effectiveness will be evaluated in relation to multiple outcomes such as: length of hospital stay of the index admission; and the following parameters during admission and until one year after admission, mortality, occurrence of complications (mainly infectious, or surgical in surgical patients), readmissions, use of health resources after discharge (primary care consultations, hospital and emergency consultations), changes in weight during admission and up to one year, changes in their health related quality of life (SF-36 and/or EQ-5d) and fragility (Barthel I.) from admission to one year after admission.
2. -Evaluate the cost and cost-effectiveness of those strategies.
3. - Evaluate in the three groups the evolution of patients in relation to the previous parameters of results according to their classification after screening at the time of admission to DRM, risk of DRM or no problem of DRM detected.

   Secondary Objectives
4. - Evaluate the three groups of patients classified according to their level of DRM according to their level of fragility and in relation to their evolution during admission and up to one year (based on all the outcome parameters indicated above)
5. - Identify risk factors of worse evolution during hospital admission and up to one year of follow up based on the previously described outcome parameters and study the role that the DRM level plays as predictor of evolution.

DESIGN: Prospective cohorts with three branches. SCOPE: Three public hospitals. The first center, where the study intervention will be carried out (branch 1), is the Galdakao - Usánsolo University Hospital that serves a population of about 300,000 urban inhabitants and semi-urban The second center, the University Hospital of Basurto (HUB), where the intervention will be carried out by demand (branch 2), serves the population of Bilbao, some 350,000 urban inhabitants. The third center, Donostia University Hospital (HUD) where there will be no specific organized intervention (branch 3), attends the population of San Sebastián-Donostia and surrounding areas covering a population of about 400,000 inhabitants of urban and semi-urban characteristics. All of them have similar human and technological resources being the population that attend similar on sociodemographic and clinical characteristics.

SUBJECTS OF THE STUDY. See detailed information in other sections. SAMPLE SIZE. It is estimated at least 10-15% of DRM and up to 30-35% of patients at risk of DRM (with a global of almost 40-50%) in the selected pathologies of patients.

Sample size calculation. We have made the estimates for an alpha error of 0.05 and a power of 80%. We have chosen the following outcome parameter in which we expect relevant differences between branches: we estimate that the average length of stay will decrease from an average of 12 days (DS: 5) in the DRM group or at risk without any explicit intervention (HUD) to an average of 10 days (DS: 5) in the DRM group or at risk where the intervention will be performed (HGU) for which we will need 100 patients by each comparisons group but we will try to recruit at least 100 patients from the previous three nutritional groups per center. We estimate a percentage of losses in the follow-up of 10-15% so, overall, 350 patients per center will be sufficient to meet the objectives and respond to the hypotheses of the study. Data from 2017 for each hospital and established patients selection criteria indicate that we should have more than those patients admitted by hospital in 12 months.

DESCRIPTION OF THE SCREENING: all admitted patients of the three centers that meet the selection criteria will be evaluated in the first 72 hours after admission and again upon discharge (if a patient remained admitted more than one week, this assessment will be repeated weekly). The nutritional risk assessment will be done by applying the Malnutrition Universal Screening Tool (MUST) and the Global Leadership Initiative on Malnutrition (GLIM) questionnaires.

VARIABLES TO COLLECT: in summary, A.-From the clinical history: Sociodemographic data will be collected (age, gender, educational level ..) and clinical data such as: comorbidities, based on the Charlson Comorbidity Index , weight, height, health habits, usual treatments (dose, number of drugs), diagnosis of admission (Major Diagnostic Categories ICD-10), severity of pathology (TNM if pathology tumor), source of admission (emergency vs scheduled), admission service. During admission: complications, treatments, procedures and referral to special units (ICU,...). Analytical data available (biochemistry and blood cells count, including urea, creatinine, glucose, electrolytes, albumin, pre-albumin, lymphocytes, total cholesterol, triglycerides, transferrin, and liver function tests). This analytics will be obtained in the first 48 hours of admission and in surgical patients before the intervention if scheduled. They will be repeated at discharge and weekly in prolonged income.

Main results of interest: see separate section. B.-Health-related quality of life questionnaires: 1.- The patient's functional will be calculated using the Barthel index. 2. - General health and utilities: they will be measured by the EuroQol-5d questionnaire, which will mainly be used for economic analysis. 3.-SF-36.

STATISTIC ANALYSIS. A descriptive analysis of the entire sample and univariate analysis to determine potential variables related to the outcomes of interest will be performed. In the multivariable analysis, different models will be used according to the dependent/outcome variable of interest. In the case of dichotomous dependent variables (mortality, complications, readmissions ...) logistic regression models will be used. For continuous dependent variables (changes in HRQoL) generalized linear models will be used; and for dependent variables that have other distributions, such as length of stay, Poisson regression models will be used. The main comparison will be between the intervention groups (HGU) versus intervention by demand (HUB) versus control group (HUD). In all multivariables analyzes, the use of a Propensity Score (PS) as an adjustment system for the differences between the characteristics of the patients of the three centers will be considered.

Economic analysis: A cost-effectiveness analysis of the intervention corresponding to the first branch will be carried out with respect to the second and third branches. Only medical costs associated with medical assistance will be included. The measure for the cost-effectiveness analysis will be the incremental cost for each year of life adjusted by Quality Adjusted Life Year (QALY) earned. The QALY will be calculated from the EuroQol-5d-5l questionnaire scores, in the baseline moment and one year after admission, and the mortality variable up to the year.

PROBLEMS AND LIMITATIONS OF THE STUDY. 1.-As in any study prospective study, main problem is the losses in the follow up. To reduce them, patients will be fully informed and a close contact will be established during follow-up to all patients. 2.-This project is proposed as an intervention study adapted to the current circumstances of the usual clinical care practice, which should guarantee a greater feasibility of a subsequent implementation of this patient care strategy if our results show its benefits. 3.- The comparability between the different cohorts will be guaranteed in the statistical analysis by the adjustment by the propensity scores. 4.-The strategy of the study poses an ethical problem since after screening in all the centers some of the patients will be identified as with DRM or at risk and therefore this will be communicated to the physicians in charge of each patient so that they proceed in the way they create timely by writing down their attitude therapy. We will collect information about any additional nutritional strategy given to any patient.

ETHICAL AND CONFIDENTIALITY ASPECTS. The project has been evaluated and approved by the research commissions of all the participant centers and approved by the accredited Clinical Research Ethics Committee (CEIC) of the Basque Country. EU and Spanish laws on personal data protection will be followed, ensuring that patient information data obtained cannot be associated with identifiable persons. Study data base will be encrypted and protected to assure confidentiality. Only research personal will have access to it with specific passwords.

After hospital admission, a nutritional screening in all patients who fulfill the selection criteria of the selected centers will be performed. The first branch includes an intervention in the groups of patients who, after screening, are identified as having disease-related malnutrition (DRM) or at risk of DRM, and a follow-up of the rest of the patients; a second cohort / branch will include patients in whom the intervention, if given, is performed by demand by the medical staff responsible for each patient. The third branch / cohort where usual hospital practice will be provided without any explicit nutritional intervention, except the screening to be carried out in all branches

Cost Effectiveness of an Intervention in Hospitalized Patients With Disease-related Malnutrition

Evaluation of the Effectiveness and Cost Effectiveness of an Intervention in Hospitalized Patients With Disease-related Malnutrition

Data from the study will be available after main publications

Mean weight changes from admission to discharge, at hospital at the index admission, and until one year of follow up

Mean length of stay at the index admission

Mortality rate at different points in time

Clinical complications, especially infectious complications during admission (CHADx classification) or events during admission, surgical complications (Clavien- Dindo classification ), surgical procedures performed

Number of Participants with primary care consultations, hospital consultations, emergency consultations, separately.

Infections, Hyperglycemia, Digestive intolerance, Bronchoaspiration, Refeeding syndrome.

General HRQoL: It will be measured through the EuroQol-5d questionnaire. Scores from 0 to 100. Higher values indicate best health status

The patient's functional will be calculated using the Barthel index. Scores 0 to 100. Higher values indicate best functional status

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