In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.
Humans ; Nivolumab/adverse effects* ; Immune Checkpoint Inhibitors/adverse effects* ; Antineoplastic Agents, Immunological/adverse effects* ; Pancreatitis/drug therapy* ; Stomach Neoplasms

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.
Aged ; Humans ; Male ; Abdominal Pain/drug therapy* ; Acute Disease ; Bilirubin ; Duodenal Ulcer/etiology* ; Immunoglobulin G ; Immunoglobulin G4-Related Disease/diagnosis* ; Pancreatitis/drug therapy* ; Positron Emission Tomography Computed Tomography ; Prednisone/therapeutic use* ; Pruritus/drug therapy*

The network pharmacology was used to investigate the material basis and molecular mechanism of Dachengqi Decoction(DCQD) in the treatment of acute pancreatitis(AP). Potential targets of components from DCQD and relevant pathogenic genes of AP were identified through database retrieval. Then, crucial targets were verified with relevant active chemical components via molecular docking. DAVID database was used to explore the functions and pathways involved in the treatment of AP. A total of 108 components were correlated with 28 targets. Molecular docking showed a strong binding ability of key targets and their corresponding compounds. DAVID enrichment analysis showed 438 biological process, 31 molecular functions, 17 cellular components and 96 KEGG pathways. DCQD may achieve its pharmacological effects through anti-inflammatory and anti-oxidative effects, negative regulation of apoptosis and regulation of pancreatic secretion, involving multiple signals, such as IL-17, TNF and NF-κB signaling pathway. In this study, it is the first time to use the method of network pharmacology to reveal the molecular mechanism of DCQD in the treatment of AP by multiple components and multi-signaling pathways, which provides a basis for further biological experiments of AP.
Acute Disease ; Animals ; Molecular Docking Simulation ; Pancreatitis/drug therapy* ; Plant Extracts/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

A 44-year-old woman was transferred to the ICU of the First Affiliated Hospital of Jinan University for 2 days of persistent epigastric pain and 7 hours of unconsciousness. Her admission diagnosis was severe acute necrotizing pancreatitis (hypertriglyceridemia type) with multiple organ dysfunctions. The results of CT revealed a small area of necrotizing pancreatitis, which was not consistent with the severe clinical manifestations. Considering lack of hair and history of postpartum hemorrhage, hormone examination was carried out. According to the results of the examination, she was further diagnosed as Sheehan's syndrome and pituitary crisis. After hormone replacement therapy, her condition improved rapidly.
Acute Disease ; Adult ; Female ; Hormone Replacement Therapy/methods* ; Humans ; Hypopituitarism/drug therapy* ; Pancreatitis, Acute Necrotizing/diagnostic imaging* ; Tomography, X-Ray Computed/methods*

Acute pancreatitis(AP)is an inflammatory condition of the pancreas following the activationt of pancreatic enzymes induced by a variety of factors,with or without other organ dysfunction.The production and release of inflammatory factors is generally considered as a key link during pathogenesis.Non-steroidal anti-inflammatory drugs(NSAIDs)are the most commonly applied agents for inflammatory diseases.Many studies have proved that indomethacin can reduce the risk of pancreatitis after endoscopic retrograde cholangiopancreatography;however,few high-quality evidences have demonstrated the roles of NSAIDs in treating,rather than preventing AP.Most animal experiments have shown that NSAIDs can protect organs,although the currently available findings remained inconsistent.Randomized controlled trials with large sample sizes are warranted to elucidate the roles of NSAIDs in treating AP.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Indomethacin ; therapeutic use ; Pancreatitis ; drug therapy

We report a case of a 13-year-old girl who presented with a 2-month history of intermittent abdominal pain. Laboratory examination showed hepatitis and pancreatitis. Because of persistent vomiting, computed tomography (CT) was performed, which revealed a circumferential soft tissue density in the duodenal wall, causing partial obstruction. Supportive therapy failed. Repeat CT showed no significant change from the initial study. The patient underwent upper endoscopy, which revealed a mass in the second portion of the duodenum, which occluded most parts of the lumen. The histopathological finding was consistent with an anaplastic large cell lymphoma, a rare form of small bowel neoplasm. After the third course of chemotherapy, complete resolution of the mass was noted, and her symptoms were relieved.
Abdominal Pain ; Adolescent ; Drug Therapy ; Duodenum ; Endoscopy ; Female ; Hematoma ; Hepatitis ; Humans ; Lymphoma, Large-Cell, Anaplastic ; Pancreatitis ; Vomiting

Serine protease inhibitor Kazal-type 1 (SPINK1) is a gene expressed from pancreatic acinar cell which its mutation is known to be associated with chronic pancreatitis (CP) and pancreatic cancer. We report a case of a 47-years-old female with nausea and weight loss with yellow discoloration of skin. Initial imaging and endoscopic study led us to an impression of chronic pancreatitis with pancreatic cancer with common bile-duct dilation. Biopsy result was confirmed with pancreatic adenocarcinoma and additional imaging revealed lymph node and bone metastasis. Our genetic analysis revealed 194+2T>C mutation of SPINK1. Biliary obstruction was successfully decompressed by stent insertion and underwent chemotherapy and radiotherapy. Although there is accumulating evidence of association between SPINK1 mutation and CP, the relationship between SPINK1 mutation and pancreatic cancer in CP patient is an emerging concept. Genetic analysis should be considered in patients with young age especially when diagnosed with both CP and pancreatic cancer.
Acinar Cells ; Adenocarcinoma ; Biopsy ; Drug Therapy ; Female ; Genes, vif ; Humans ; Jaundice, Obstructive ; Lymph Nodes ; Nausea ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Pancreatitis, Chronic ; Radiotherapy ; Serine Proteases ; Skin ; Stents ; Weight Loss

A 54-year old man diagnosed with advanced hepatocellular carcinoma began treatment with sorafenib. After 3 weeks of treatment, he complained of abdominal pain and nausea. Abdominal sonography showed multiple hepatic lesions only. Serum amylase and lipase levels were 35 U/L and 191 U/L, respectively. The patient was diagnosed with sorafenib-induced acute pancreatitis. After 10 days of discontinuing sorafenib he still complained of nausea and loss of appetite. Esophagogastroduodenoscopy showed a large bulging lesion, which was suspected to cause extrinsic compression on the high body of the gastric anterior wall. Computed tomography scan revealed a cystic lesion, 8.3 cm in size, in the pancreatic tail, suggesting a pancreatic pseudocyst. After the withdrawal of sorafenib, systemic chemotherapy with Adriamycin and cisplatin was administered. Four months after the discontinuation of sorafenib, the size of the pancreatic pseudocyst decreased from 8.3 cm to 3 cm. The patient's symptoms were also relieved.
Abdominal Pain ; Amylases ; Appetite ; Carcinoma, Hepatocellular ; Cisplatin ; Doxorubicin ; Drug Therapy ; Endoscopy, Digestive System ; Humans ; Lipase ; Nausea ; Pancreatic Pseudocyst ; Pancreatitis ; Tail

OBJECTIVE: This study demonstrated that dexamethasone (DEX) protects the endothelial glycocalyx from damage induced by the inflammatory stimulus tumor necrosis factor-α (TNF-α) during severe acute pancreatitis (SAP), and improves the renal microcirculation. METHODS: Ninety mice were evenly divided into 3 groups (Sham, SAP, and SAP+DEX). The SAP mice model was established by ligature of pancreatic duct and intraperitoneal injection of cerulein. Renal perfusion and function, and morphological changes of the glycocalyx were evaluated by laser Doppler velocimetry, electron microscopy, and histopathology (hematoxylin and eosin (H&E) staining), respectively. Serum levels of syndecan-1 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). The protective effects of dexamethasone on the glycocalyx and renal microcirculation were evaluated. RESULTS: Significantly high levels of serum TNF-α were detected 3 h after the onset of SAP. These levels might induce degradation of the glycocalyx and kidney hypoperfusion, resulting in kidney microcirculation dysfunction. The application of dexamethasone reduced the degradation of the glycocalyx and improved perfusion of kidney. CONCLUSIONS Dexamethasone protects the endothelial glycocalyx from inflammatory degradation possibly initiated by TNF-α during SAP. This is might be a significant discovery that helps to prevent tissue edema and hypoperfusion in the future.
Acute Disease ; Animals ; Dexamethasone/pharmacology* ; Disease Models, Animal ; Edema/metabolism* ; Endothelium, Vascular/metabolism* ; Enzyme-Linked Immunosorbent Assay ; Glycocalyx/drug effects* ; Kidney/drug effects* ; Male ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Pancreatitis/drug therapy* ; Perfusion ; Protective Agents/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.
Adult ; Anti-Bacterial Agents/administration & dosage* ; Critical Illness ; Extracorporeal Membrane Oxygenation ; Female ; Hemofiltration ; Humans ; Pancreatitis/drug therapy* ; Vancomycin/administration & dosage*