Showing papers on "Pancreatitis published in 2020"

ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

Abstract: Prophylaxis 1 ESGE recommends routine rectal administration of 100 mg of diclofenac or indomethacin immediately before endoscopic retrograde cholangiopancreatography (ERCP) in all patients without contraindications to nonsteroidal anti-inflammatory drug administration. Strong recommendation, moderate quality evidence. 2 ESGE recommends prophylactic pancreatic stenting in selected patients at high risk for post-ERCP pancreatitis (inadvertent guidewire insertion/opacification of the pancreatic duct, double-guidewire cannulation). Strong recommendation, moderate quality evidence. 3 ESGE suggests against routine endoscopic biliary sphincterotomy before the insertion of a single plastic stent or an uncovered/partially covered self-expandable metal stent for relief of biliary obstruction. Weak recommendation, moderate quality evidence. 4 ESGE recommends against the routine use of antibiotic prophylaxis before ERCP. Strong recommendation, moderate quality evidence. 5 ESGE suggests antibiotic prophylaxis before ERCP in the case of anticipated incomplete biliary drainage, for severely immunocompromised patients, and when performing cholangioscopy. Weak recommendation, moderate quality evidence. 6 ESGE suggests tests of coagulation are not routinely required prior to ERCP for patients who are not on anticoagulants and not jaundiced. Weak recommendation, low quality evidence. Treatment 7 ESGE suggests against salvage pancreatic stenting in patients with post-ERCP pancreatitis. Weak recommendation, low quality evidence. 8 ESGE suggests temporary placement of a biliary fully covered self-expandable metal stent for post-sphincterotomy bleeding refractory to standard hemostatic modalities. Weak recommendation, low quality evidence. 9 ESGE suggests to evaluate patients with post-ERCP cholangitis by abdominal ultrasonography or computed tomography (CT) scan and, in the absence of improvement with conservative therapy, to consider repeat ERCP. A bile sample should be collected for microbiological examination during repeat ERCP. Weak recommendation, low quality evidence.

Microbiota in pancreatic health and disease: the next frontier in microbiome research

Abstract: Diseases intrinsic to the pancreas such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus impart substantial health and financial burdens on society but identification of novel mechanisms contributing to these pathologies are slow to emerge. A novel area of research suggests that pancreatic-specific disorders might be modulated by the gut microbiota, either through a local (direct pancreatic influence) or in a remote (nonpancreatic) fashion. In this Perspectives, we examine literature implicating microorganisms in diseases of the pancreas, specifically pancreatitis, type 1 diabetes mellitus and pancreatic ductal adenocarcinoma. We also discuss evidence of an inherent pancreatic microbiota and the influence of the intestinal microbiota as it relates to disease association and development. In doing so, we address pitfalls in the current literature and areas of investigation that are needed to advance a developing field of research that has clinical potential to reduce the societal burden of pancreatic diseases.

Effect of Early Surgery vs Endoscopy-First Approach on Pain in Patients With Chronic Pancreatitis: The ESCAPE Randomized Clinical Trial

Abstract: Importance: For patients with painful chronic pancreatitis, surgical treatment is postponed until medical and endoscopic treatment have failed. Observational studies have suggested that earlier surgery could mitigate disease progression, providing better pain control and preserving pancreatic function. Objective: To determine whether early surgery is more effective than the endoscopy-first approach in terms of clinical outcomes. Design, Setting, and Participants: The ESCAPE trial was an unblinded, multicenter, randomized clinical superiority trial involving 30 Dutch hospitals participating in the Dutch Pancreatitis Study Group. From April 2011 until September 2016, a total of 88 patients with chronic pancreatitis, a dilated main pancreatic duct, and who only recently started using prescribed opioids for severe pain (strong opioids for ≤2 months or weak opioids for ≤6 months) were included. The 18-month follow-up period ended in March 2018. Interventions: There were 44 patients randomized to the early surgery group who underwent pancreatic drainage surgery within 6 weeks after randomization and 44 patients randomized to the endoscopy-first approach group who underwent medical treatment, endoscopy including lithotripsy if needed, and surgery if needed. Main Outcomes and Measures: The primary outcome was pain, measured on the Izbicki pain score and integrated over 18 months (range, 0-100 [increasing score indicates more pain severity]). Secondary outcomes were pain relief at the end of follow-up; number of interventions, complications, hospital admissions; pancreatic function; quality of life (measured on the 36-Item Short Form Health Survey [SF-36]); and mortality. Results: Among 88 patients who were randomized (mean age, 52 years; 21 (24%) women), 85 (97%) completed the trial. During 18 months of follow-up, patients in the early surgery group had a lower Izbicki pain score than patients in the group randomized to receive the endoscopy-first approach group (37 vs 49; between-group difference, -12 points [95% CI, -22 to -2]; P =.02). Complete or partial pain relief at end of follow-up was achieved in 23 of 40 patients (58%) in the early surgery vs 16 of 41 (39%)in the endoscopy-first approach group (P =.10). The total number of interventions was lower in the early surgery group (median, 1 vs 3; P <.001). Treatment complications (27% vs 25%), mortality (0% vs 0%), hospital admissions, pancreatic function, and quality of life were not significantly different between early surgery and the endoscopy-first approach. Conclusions and Relevance: Among patients with chronic pancreatitis, early surgery compared with an endoscopy-first approach resulted in lower pain scores when integrated over 18 months. However, further research is needed to assess persistence of differences over time and to replicate the study findings. Trial Registration: ISRCTN Identifier: ISRCTN45877994.

TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation

Abstract: Elevated pressure in the pancreatic gland is the central cause of pancreatitis following abdominal trauma, surgery, endoscopic retrograde cholangiopancreatography, and gallstones. In the pancreas, excessive intracellular calcium causes mitochondrial dysfunction, premature zymogen activation, and necrosis, ultimately leading to pancreatitis. Although stimulation of the mechanically activated, calcium-permeable ion channel Piezo1 in the pancreatic acinar cell is the initial step in pressure-induced pancreatitis, activation of Piezo1 produces only transient elevation in intracellular calcium that is insufficient to cause pancreatitis. Therefore, how pressure produces a prolonged calcium elevation necessary to induce pancreatitis is unknown. We demonstrate that Piezo1 activation in pancreatic acinar cells caused a prolonged elevation in intracellular calcium levels, mitochondrial depolarization, intracellular trypsin activation, and cell death. Notably, these effects were dependent on the degree and duration of force applied to the cell. Low or transient force was insufficient to activate these pathological changes, whereas higher and prolonged application of force triggered sustained elevation in intracellular calcium, leading to enzyme activation and cell death. All of these pathological events were rescued in acinar cells treated with a Piezo1 antagonist and in acinar cells from mice with genetic deletion of Piezo1. We discovered that Piezo1 stimulation triggered transient receptor potential vanilloid subfamily 4 (TRPV4) channel opening, which was responsible for the sustained elevation in intracellular calcium that caused intracellular organelle dysfunction. Moreover, TRPV4 gene-KO mice were protected from Piezo1 agonist- and pressure-induced pancreatitis. These studies unveil a calcium signaling pathway in which a Piezo1-induced TRPV4 channel opening causes pancreatitis.

Gastrointestinal Complications in Critically Ill Patients With and Without COVID-19

Abstract: Coronavirus disease 2019 (COVID-19) appears to have significant extrapulmonary complications affecting multiple organ systems.1-3 Critically ill patients with COVID-19 often develop gastrointestinal complications during their hospital stay, including bowel ischemia, transaminitis, gastrointestinal bleeding, pancreatitis, Ogilvie syndrome, and severe ileus.3 Whether the high incidence of gastrointestinal complications is a manifestation of critical illness in general or is specific to COVID-19 remains unclear. We compared the incidence of gastrointestinal complications of critically ill patients with COVID-19–induced acute respiratory distress syndrome (ARDS) vs comparably ill patients with non–COVID-19 ARDS using propensity score analysis.

Acute pancreatitis in a COVID-19 patient.

Abstract: Editor We read with interest Spinelli and Pellino’s Leading Article1, highlighting their experience of COVID-19, a global pandemic that is rapidly changing and challenging the scope of surgical practice2. Recent intercollegiate guidance has recommended a drastic change of approach in the management of surgical patients, including the suspension of all but emergency operations3. We highlight a case of acute pancreatitis in a patient with recently diagnosed COVID-19. A 59-year-old female patient, with a history of cholecystectomy and thrombophilia, initially presented to the emergency department with fever, cough, sore throat and myalgia having recently returned from a cruise in the Caribbean. Polymerase Chain Reaction confirmed COVID-19 and she was treated with simple supportive measures. She was commenced on intravenous vancomycin for a streptococcal pneumonia complicating COVID-19 infection, and discharged on day 5 with a course of doxycycline. Five days following discharge, she was readmitted with fever, abdominal pain and constipation, and treated for presumed adhesional bowel obstruction. Laboratory investigations demonstrated a white cell count of 14⋅3× 109/l, Creactive protein of 62⋅7 g/l, international normalized ratio (INR) of 5⋅2, and normal liver function. Unfortunately, no amylase was done on admission. As symptoms were not improving with conservative management, a CT was obtained on day 3. This demonstrated a previously atrophic pancreas that had increased markedly in size and had features of diffuse oedematous changes, suspicious for acute pancreatitis. The patient was managed conservatively and discharged after 7 days. The aetiology of pancreatitis in this case is idiopathic given the history of cholecystectomy, minimal alcohol use and lack of precipitating risk factors. Up to 10 per cent of acute pancreatitis is thought to have an infectious aetiology through an immune-mediated inflammatory response, most notably mumps and Coxsackie B viruses4. The recent positive COVID-19 diagnosis and reports of gastrointestinal symptoms in this disease raise the suspicion that there may be an association between this novel virus and acute pancreatitis. E. R. Anand , C. Major, O. Pickering and M. Nelson Department of General Surgery, St Mary’s Hospital, Isle of Wight NHS Trust, Newport, UK

Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection

Abstract: The ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the end of 2019 in China has triggered a global public health crisis. Previous studies have shown that SARS-CoV-2 infects cells by binding angiotensin-converting enzyme 2 (ACE2), which is the same as SARS-CoV. The expression and distribution of ACE2 in the pancreas are unknown. At the same time, the injury of pancreas after SARS-CoV-2 infection has not been concerned. Here, we collected public datasets (bulk RNA-seq and single-cell RNA-seq) to indicate the expression and the distribution of ACE2 in pancreas (in both exocrine glands and islets). And further, clinical data including mild and severe patients with COVID-19 demonstrated there existed mild pancreatitis. In the 67 severe cases, 11 patients (16.41%) showed elevated levels of both amylase and lipase, and 5 patients (7.46%) showed imaging alterations. Only one patient (1.85%) showed elevated levels of both amylase and lipase in 54 mild cases, without imaging changes. Our study revealed the phenomenon and possible cause of mild pancreatic injury in patients with COVID-19. This suggests that pancreatitis after SARS-CoV-2 infection should also be paid attention in clinical work.

Intense FAPI Uptake in Inflammation May Mask the Tumor Activity of Pancreatic Cancer in 68Ga-FAPI PET/CT.

Abstract: Contrast CT revealed diffuse enlargement of the pancreas with a suspicious lesion in the uncinate process in a 57-year-old man who presented with jaundice. F-FDG PET/CT showed increased radioactivity in the enlarged pancreas with a nodular lesion with even higher uptake in the uncinate process. To differentiate autoimmune pancreatitis and pancreatic cancer, Ga-FAPI PET/CT was performed. It revealed intense Ga-FAPI uptake in the pancreas, but the FDG-avid lesion in the uncinate process was not shown. The patient was finally diagnosed with pancreatic cancer with tumor-induced pancreatitis with endoscopic ultrasonography-guided biopsy.

Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

Abstract: Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure.

Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment.

Abstract: This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied malignant tumor. At present, we urgently need to identify high-risk patients with precancerous diseases through screening approaches, so that medical professionals and the general public may better understand prevention strategies or early detection measures. Pancreatic cancer is a highly invasive malignant tumor with a fatal risk, mainly seen in men and older adults (60-85 years old). Pancreatic cancer is now increasingly observed in young patients. Because the disease has no early symptoms and can quickly invade surrounding tissues and organs, it is one of the deadliest cancers. With a view to identify the important factors for the development of pancreatic cancer, previous studies have found that smoking, alcohol, and chronic pancreatitis are considered high-risk factors. Recent studies have shown that abnormal metabolism of human microorganisms, blood type, and glucose and lipid levels are also important factors in the development of pancreatic cancer. Identifying early diagnosis options is an important way to improve detection and survival rates of pancreatic cancer. None of the many tumor markers associated with pancreatic cancer are highly specific, which also indicates further research is required to improve the early detection rate. Future directions in terms of treatment evaluating the relationship between the microbiology-free system and immunotherapy will bring a major breakthrough and is expected to bring exciting clinical applications in improving the life-cycle of pancreatic cancer patients.

Superiority of endoscopic interventions over minimally invasive surgery for infected necrotizing pancreatitis: meta-analysis of randomized trials.

Abstract: BACKGROUND AND AIM Infected necrotizing pancreatitis is a highly morbid disease managed by minimally invasive surgical (MIS) or endoscopy-based interventions. This meta-analysis compared the clinical outcomes of patients treated using either approach. METHODS MEDLINE and EMBASE databases were searched to identify all randomized trials that compared MIS and endoscopy-based interventions for treatment of infected necrotizing pancreatitis. Main outcome measure was to compare rates of complications or death during 6-month follow-up. RESULTS Three studies involving 184 patients met inclusion criteria. While there was no significant difference in mortality (14.5% vs. 16.1%, risk ratio [RR] = 1.02, P = 0.963), new onset multiple organ failure (5.2% vs. 19.7%, RR = 0.34, P = 0.045), enterocutaneous fistula/perforation (3.6% vs. 17.9%, RR = 0.34, P = 0.034) and pancreatic fistula (4.2% vs. 38.2%, RR = 0.13, P < 0.001) were significantly lower for endoscopic interventions compared to MIS. There was no significant difference in intraabdominal bleeding, endocrine or exocrine pancreatic insufficiency between cohorts. Length of hospital stay was significantly shorter for endoscopy (standardized mean difference, -0.41, P = 0.010). CONCLUSIONS An endoscopy-based treatment approach, as compared to minimally invasive surgery, significantly reduces complications in patients with infected necrotizing pancreatitis.

Coronavirus disease-19 (COVID-19) associated with acute necrotising pancreatitis (ANP).

Abstract: Coronavirus is a severe infectious disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has led to increased mortality worldwide. Multiple reports have been published citing that gastrointestinal symptoms are common in patients with COVID-19 infection. It has also been found that the ACE2 receptor of SARS-CoV-2 is expressed more in the pancreas than the lungs. Despite this, little attention has been paid to the extent and details of pancreatic injury caused by COVID-19. Lack of awareness regarding the COVID-19 status of patients presenting with pancreatitis may expose healthcare workers to SARS-CoV-2 while performing interventions to manage complications of pancreatitis such as necrosis. We report a case of COVID-19-induced acute necrotising pancreatitis in the absence of any known risk factors.

Laser-assisted 3D bioprinting of exocrine pancreas spheroid models for cancer initiation study.

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas. It has shown a poor prognosis and a rising incidence in the developed world. Other pathologies associated with this tissue include pancreatitis, a risk condition for pancreatic cancer. The onset of both pancreatitis and pancreatic cancer follows a common pattern: exocrine pancreatic acinar cells undergo a transdifferentiation to duct cells that triggers a 3D restructuration of the pancreatic tissue. However, the exact mechanism underlying this process remains partially undefined. Further understanding the cellular events leading to PDAC could open new avenues in the development of novel therapeutic approaches. Since current 2D cell culture models fail to mimic the tridimensional complexity of the pancreatic tissue, new in vitro models are urgently needed. Here, we generated 3D pancreatic cell spheroid arrays using laser-assisted bioprinting and characterized their phenotypic evolution over time through image analysis and phenotypic characterization. We show that these bioprinted spheroids, composed of both acinar and ductal cells, can replicate the initial stages of PDAC development. This bioprinted miniaturized spheroid-based array model should prove useful for the study of the internal and external factors that contribute to the formation of precursor PDAC lesions and to cancer progression, and may therefore shed light on future PDAC therapy strategies.

Drug Induced Pancreatitis: A Systematic Review of Case Reports to Determine Potential Drug Associations

Abstract: Objective A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations. Methods A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency. Results Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis. Discussion Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations. Registration CRD42017060473.

Molecular Mechanism of Pancreatic Stellate Cells Activation in Chronic Pancreatitis and Pancreatic Cancer

Abstract: Activated pancreatic stellate cells (PSCs) are the main effector cells in the process of fibrosis, a major pathological feature in pancreatic diseases that including chronic pancreatitis and pancreatic cancer. During tumorigenesis, quiescent PSCs change into an active myofibroblast-like phenotype which could create a favorable tumor microenvironment and facilitate cancer progression by increasing proliferation, invasiveness and inducing treatment resistance of pancreatic cancer cells. Many cellular signals are revealed contributing to the activation of PSCs, such as transforming growth factor-β, platelet derived growth factor, mitogen-activated protein kinase (MAPK), Smads, nuclear factor-κB (NF-κB) pathways and so on. Therefore, investigating the role of these factors and signaling pathways in PSCs activation will promote the development of PSCs-specific therapeutic strategies that may provide novel options for pancreatic cancer therapy. In this review, we systematically summarize the current knowledge about PSCs activation-associated stimulating factors and signaling pathways and hope to provide new strategies for the treatment of pancreatic diseases.

Surgical Transgastric Necrosectomy for Necrotizing Pancreatitis: A Single-stage Procedure for Walled-off Pancreatic Necrosis

Abstract: OBJECTIVE The aim of this study was to evaluate the role of surgical transgastric necrosectomy (TGN) for walled-off pancreatic necrosis (WON) in selected patients. BACKGROUND WON is a common consequence of severe pancreatitis and typically occurs 3 to 5 weeks after the onset of acute pancreatitis. When symptomatic, it can require intervention. METHODS A retrospective review of patients with WON undergoing surgical management at 3 high-volume pancreatic institutions was performed. Surgical indications, intervention timing, technical methodology, and patient outcomes were evaluated. Patients undergoing intervention <30 days were excluded. Differences across centers were evaluated using a P value of <0.05 as significant. RESULTS One hundred seventy-eight total patients were analyzed (mean WON diameter = 14 cm, 64% male, mean age = 51 years) across 3 centers. The majority required inpatient admission with a median preoperative length of hospital stay of 29 days (25% required preoperative critical care support). Most (96%) patients underwent a TGN. The median duration of time between the onset of pancreatitis symptoms and operative intervention was 60 days. Thirty-nine percent of the necrosum was infected. Postoperative morbidity and mortality were 38% and 2%, respectively. The median postoperative length of hospital length of stay was 8 days, with the majority of patients discharged home. The median length of follow-up was 21 months, with 91% of patients having complete clinical resolution of symptoms at a median of 6 weeks. Readmission to hospital and/or a repeat intervention was also not infrequent (20%). CONCLUSION Surgical TGN is an excellent 1-stage surgical option for symptomatic WON in a highly selected group of patients. Precise surgical technique and long-term outpatient follow-up are mandatory for optimal patient outcomes.

Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury.

Abstract: Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.