Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

PubMed Central

Noel, Pawan; Patel, Krutika; Durgampudi, Chandra; Trivedi, Ram N; de Oliveira, Cristiane; Crowell, Michael D; Pannala, Rahul; Lee, Kenneth; Brand, Randall; Chennat, Jennifer; Slivka, Adam; Papachristou, Georgios I; Khalid, Asif; Whitcomb, David C; DeLany, James P; Cline, Rachel A; Acharya, Chathur; Jaligama, Deepthi; Murad, Faris M; Yadav, Dhiraj; Navina, Sarah; Singh, Vijay P

2016-01-01

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP. PMID:25500204

Pancreatic Necrosis and Gas in the Retroperitoneum: Treatment with Antibiotics Alone.

PubMed

Rasslan, Roberto; da Costa Ferreira Novo, Fernando; Rocha, Marcelo Cristiano; Bitran, Alberto; de Souza Rocha, Manoel; de Oliveira Bernini, Celso; Rasslan, Samir; Utiyama, Edivaldo Massazo

2017-02-01

To present our experience in the management of patients with infected pancreatic necrosis without drainage. The records of patients with pancreatic necrosis admitted to our facility from 2011 to 2015 were retrospectively reviewed. We identified 61 patients with pancreatic necrosis. Six patients with pancreatic necrosis and gas in the retroperitoneum were treated exclusively with clinical support without any type of drainage. Only 2 patients had an APACHE II score >8. The first computed tomography scan revealed the presence of gas in 5 patients. The Balthazar computed tomography severity index score was >9 in 5 of the 6 patients. All patients were treated with antibiotics for at least 3 weeks. Blood cultures were positive in only 2 patients. Parenteral nutrition was not used in these patients. The length of hospital stay exceeded three weeks for 5 patients; 3 patients had to be readmitted. A cholecystectomy was performed after necrosis was completely resolved; pancreatitis recurred in 2 patients before the operation. No patients died. In selected patients, infected pancreatic necrosis (gas in the retroperitoneum) can be treated without percutaneous drainage or any additional surgical intervention. Intervention procedures should be performed for patients who exhibit clinical and laboratory deterioration.

Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

PubMed

Pearson, E G; Snyder, S P

2000-07-15

To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

Genetic inhibition of protein kinase Cε attenuates necrosis in experimental pancreatitis

PubMed Central

Liu, Yannan; Tan, Tanya; Jia, Wenzhuo; Lugea, Aurelia; Mareninova, Olga; Waldron, Richard T.; Pandol, Stephen J.

2014-01-01

Understanding the regulation of death pathways, necrosis and apoptosis, in pancreatitis is important for developing therapies directed to the molecular pathogenesis of the disease. Protein kinase Cε (PKCε) has been previously shown to regulate inflammatory responses and zymogen activation in pancreatitis. Furthermore, we demonstrated that ethanol specifically activated PKCε in pancreatic acinar cells and that PKCε mediated the sensitizing effects of ethanol on inflammatory response in pancreatitis. Here we investigated the role of PKCε in the regulation of death pathways in pancreatitis. We found that genetic deletion of PKCε resulted in decreased necrosis and severity in the in vivo cerulein-induced pancreatitis and that inhibition of PKCε protected the acinar cells from CCK-8 hyperstimulation-induced necrosis and ATP reduction. These findings were associated with upregulation of mitochondrial Bak and Bcl-2/Bcl-xL, proapoptotic and prosurvival members in the Bcl-2 family, respectively, as well as increased mitochondrial cytochrome c release, caspase activation, and apoptosis in pancreatitis in PKCε knockout mice. We further confirmed that cerulein pancreatitis induced a dramatic mitochondrial translocation of PKCε, suggesting that PKCε regulated necrosis in pancreatitis via mechanisms involving mitochondria. Finally, we showed that PKCε deletion downregulated inhibitors of apoptosis proteins, c-IAP2, survivin, and c-FLIPs while promoting cleavage/inactivation of receptor-interacting protein kinase (RIP). Taken together, our findings provide evidence that PKCε activation during pancreatitis promotes necrosis through mechanisms involving mitochondrial proapoptotic and prosurvival Bcl-2 family proteins and upregulation of nonmitochondrial pathways that inhibit caspase activation and RIP cleavage/inactivation. Thus PKCε is a potential target for prevention and/or treatment of acute pancreatitis. PMID:25035113

Long-term results and quality of life of patients undergoing sequential surgical treatment for severe acute pancreatitis complicated by infected pancreatic necrosis.

PubMed

Cinquepalmi, Lorenza; Boni, Luigi; Dionigi, Gianlorenzo; Rovera, Francesca; Diurni, Mario; Benevento, Angelo; Dionigi, Renzo

2006-01-01

Infected pancreatic necrosis (IPN) is one of the most severe complications of acute pancreatitis (AP). Sequential surgical debridement represents one of the most effective treatments in terms of morbidity and mortality. The aim of this paper is to describe the quality of life and long-term results (e.g., nutritional, muscular, and pancreatic function) of patients treated by sequential necrosectomy at the Department of Surgery of the University of Insubria (Varese, Italy). Data were collected on patients undergoing sequential surgical debridement as treatment for IPN. The severity of AP was evaluated using the Ranson criteria, the Acute Physiology and Chronic Health Evaluation (APACHE II) Score, and the Sepsis Score, as well as the extent of necrosis. The surgical approach was through a midline or subcostal laparotomy, followed by exploration of the peritoneal cavity, wide debridement, and peritoneal lavage. The abdomen was either left open or closed partially with a surgical zipper, with multiple re-laparotomies scheduled until debridement of necrotic tissue was complete. The long-term evaluation focused on late morbidity, performance status, and abdominal wall function. In the majority of patients (68%), mixed flora were isolated. Pseudomonas aeruginosa was the microorganism identified most commonly (59%), often associated with Candida albicans or C. glabrata. The mean total hospital stay was 71+/-38 days (range 13-146 days), of which 24+/-19 days (range 0-66 days) were in the intensive care unit. Eight patients died, the deaths being caused by multiple organ dysfunction syndrome in seven patients and hemorrhage from the splenic artery in one. Normal exocrine and endocrine pancreatic function was observed in 28 patients (88%). At discharge, four patients had steatorrhea, which was temporary. Eight patients (23%) developed pancreatic pseudocysts, and in six, cystogastostomy was performed. Most patients (29/32, 91%) developed a post-operative hernia, but only five

Role of bedside pancreatic scores and C-reactive protein in predicting pancreatic fluid collections and necrosis.

PubMed

Vinish, Doraiswami Babu; Abishek, Vishnu; Sujatha, K; Arulprakash, S; Solomon, Rajkumar; Ganesh, P

2017-01-01

Acute pancreatitis is a disease with variable outcome; the course of the disease can be modified by early aggressive management in patients with severe pancreatitis. Easily calculable pancreatic scores and investigations can help to triage these patients. We aimed to determine the role of bedside index for severity in acute pancreatitis (BISAP), harmless acute pancreatitis score (HAPS), and systemic inflammatory response syndrome (SIRS) scores on day of admission and C-reactive protein (CRP) at 48 h for predicting the presence of pancreatic fluid collection (PFC) and necrosis on CT scans done at 72 h. Of a total of 114 consecutively seen patients of pancreatitis, 64 with acute pancreatitis were enrolled in the study. All individuals had the pancreatitis predicting scores calculated at the time of admission, CRP at 48 h, and contrast-enhanced computed tomography (CECT) abdomen at 72 h from admission. The study population of 64 (55 male) had a mean (+SD) age of 37.7 ± 13 years. Alcohol was the most common (68.8%) etiology in these patients. Based on CECT, patients were divided into 2 groups; group 1 with 41 patients who had mild pancreatitis and group 2 with 23 patients who had pancreatic fluid collection with or without necrosis (PFCN). PFCN were seen in 19 (29.7%) of patients with 2 or more SIRS criteria, 17 (26.6%) of patients with BISAP score ≥3, and 16 patients (25.0%) with HAPS >0 respectively. All three scores were able to predict PFCN significantly. CRP >150 mg/L was noted in 23 patients and was able to predict the presence of fluid collections (p=0.0002) and pancreatic necrosis (p = 0.0004) on CT. BISAP, HAPS, and SIRS scores and CRP of 150 mg/L all correlated significantly with the occurrence of fluid collections and pancreatic necrosis on CT at 72 h. None of the scores was superior to the other in this respect.

Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice.

PubMed

Sendler, Matthias; Dummer, Annegret; Weiss, Frank U; Krüger, Burkhard; Wartmann, Thomas; Scharffetter-Kochanek, Karin; van Rooijen, Nico; Malla, Sudarshan Ravi; Aghdassi, Ali; Halangk, Walter; Lerch, Markus M; Mayerle, Julia

2013-03-01

Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings

Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

PubMed

Tu, Jianfeng; Zhang, Jingzhu; Ke, Lu; Yang, Yue; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

2017-10-27

Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/gpancreatic insufficiency with FE-1<100μg/g. The morbidity of DM and IGT in patients with pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X 2  = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosis<30% (P = 0.012, OR = 0.061) were the protective factors of endocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic

Rare Esophageal Migration of AXIOS Stent Used for Walled-off Pancreatic Necrosis Drainage

PubMed Central

Renno, Anas; Hammad, Tariq; Nawras, Ali

2017-01-01

The AXIOS stent (Boston Scientific, Marlborough, MA) is a novel lumen-apposing self-expandable metallic stent designed for enteric drainage of nonadherent lumens. Efficacy and safety of using the AXIOS stent for pancreatic fluid drainage have been consistently shown in several studies. Although it is less common with this novel stent, stent migration still may happen. We present a case of AXIOS stent migration into the esophagus. PMID:28584846

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed

Durur-Subasi, Irmak; Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-05-01

To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant-benign differentiation of necrotic breast lesions. Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T 1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field.

Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

PubMed Central

Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

2017-01-01

Objective: To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant–benign differentiation of necrotic breast lesions. Methods: Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. Results: A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. Conclusion: The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field. PMID

Outcome of Acute Pancreatic and Peripancreatic Collections Occurring in Patients With Acute Pancreatitis.

PubMed

Manrai, Manish; Kochhar, Rakesh; Gupta, Vikas; Yadav, Thakur Deen; Dhaka, Narendra; Kalra, Naveen; Sinha, Saroj K; Khandelwal, Niranjan

2018-02-01

To study the outcome of acute collections occurring in patients with acute pancreatitis BACKGROUND:: There are limited data on natural history of acute collections arising after acute pancreatitis (AP). Consecutive patients of AP admitted between July 2011 and December 2012 were evaluated by imaging for development of acute collections as defined by revised Atlanta classification. Imaging was repeated at 1 and 3 months. Spontaneous resolution, evolution, and need for intervention were assessed. Of the 189 patients, 151 patients (79.9%) had acute collections with severe disease and delayed hospitalization being predictors of acute collections. Thirty-six patients had acute interstitial edematous pancreatitis, 8 of whom developed acute peripancreatic fluid collections, of which 1 evolved into pseudocyst. Among the 153 patients with acute necrotizing pancreatitis, 143 (93.4%) developed acute necrotic collection (ANC). Twenty-three of 143 ANC patients died, 21 had resolved collections, whereas 84 developed walled-off necrosis (WON), with necrosis >30% (P = 0.010) and Computed Tomographic Severity Index score ≥7 (P = 0.048) predicting development of WON. Of the 84 patients with WON, 8 expired, 53 patients required an intervention, and 23 were managed conservatively. Independent predictors of any intervention among all patients were Computed Tomographic Severity Index score ≥7 (P < 0.001) and interval between onset of pain to hospitalization >7 days (P = 0.04). Patients with severe AP and delayed hospitalization more often develop acute collections. Pancreatic pseudocysts are a rarity in acute interstitial pancreatitis. A majority of patients with necrotising pancreatitis will develop ANC, more than half of whom will develop WON. Delay in hospitalization and higher baseline necrosis score predict need for intervention.

Endosonography guided management of pancreatic fluid collections

PubMed Central

Vilmann, Andreas S; Menachery, John; Tang, Shou-Jiang; Srinivasan, Indu; Vilmann, Peter

2015-01-01

The revised Atlanta classification of acute pancreatitis was adopted by international consensus, and is based on actual local and systemic determinants of disease severity. The local determinant is pancreatic necrosis (sterile or infected), and the systemic determinant is organ failure. Local complications of pancreatitis can include acute peri-pancreatic fluid collection, acute necrotic collection, pseudocyst formation, and walled-off necrosis. Interventional endoscopic ultrasound (EUS) has been increasing utilized in managing these local complications. After performing a PubMed search, the authors manually applied pre-defined inclusion criteria or a filter to identify publications relevant to EUS and pancreatic collections (PFCs). The authors then reviewed the utility, efficacy, and risks associated with using therapeutic EUS and involved EUS devices in treating PFCs. Due to the development and regulatory approval of improved and novel endoscopic devices specifically designed for transmural drainage of fluid and necrotic debris (access and patency devices), the authors predict continuing evolution in the management of PFCs. We believe that EUS will become an indispensable part of procedures used to diagnose PFCs and perform image-guided interventions. After draining a PFC, the amount of tissue necrosis is the most important predictor of a successful outcome. Hence, it seems logical to classify these collections based on their percentage of necrotic component or debris present when viewed by imaging methods or EUS. Finally, the authors propose an algorithm for managing fluid collections based on their size, location, associated symptoms, internal echogenic patterns, and content. PMID:26557008

A new geographic and host record for infectious pancreatic necrosis

USGS Publications Warehouse

Parisot, T.J.; Yasutake, W.T.; Bressler, V.

1963-01-01

The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.

Endoscopic Management of Peri-Pancreatic Fluid Collections.

PubMed

Yip, Hon Chi; Teoh, Anthony Yuen Bun

2017-09-15

In the past decade, there has been a progressive paradigm shift in the management of peri-pancreatic fluid collections after acute pancreatitis. Refinements in the definitions of fluid collections from the updated Atlanta classification have enabled better communication amongst physicians in an effort to formulate optimal treatments. Endoscopic ultrasound (EUS)-guided drainage of pancreatic pseudocysts has emerged as the procedure of choice over surgical cystogastrostomy. The approach provides similar success rates with low complications and better quality of life compared with surgery. However, an endoscopic "step up" approach in the management of pancreatic walled-off necrosis has also been advocated. Both endoscopic and percutaneous drainage routes may be used depending on the anatomical location of the collections. New-generation large diameter EUS-specific stent systems have also recently been described. The device allows precise and effective drainage of the collections and permits endoscopic necrosectomy through the stents.

Infectious pancreatic necrosis: its detection and identification

USGS Publications Warehouse

Wolf, K.

1965-01-01

Ultimate control of infectious pancreatic necrosis (IPN) in hatcheries depends largely upon learning where the virus occurs. To detect the presence of virus either susceptible fish or susceptible fish cell cultures may be used as test systems. In modern virology, it is generally agreed that cell cultures are more convenient, are usually a much more sensitive test system, and allow more rapid determinations.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

PubMed

Kupčinskas, Juozas; Gedgaudas, Rolandas; Hartman, Hannes; Sippola, Tomi; Lindström, Outi; Johnson, Colin D; Regnér, Sara

2018-07-01

The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

A comparison of outcomes between a lumen-apposing metal stent with electrocautery-enhanced delivery system and a bi-flanged metal stent for drainage of walled-off pancreatic necrosis.

PubMed

Bekkali, Noor L H; Nayar, Manu K; Leeds, John S; Charnley, Richard M; Huggett, Matthew T; Oppong, Kofi W

2017-12-01

 Bi-flanged metal stents (BFMS) have shown promise in the drainage of walled-off pancreatic necrosis (WON), but their placement requires multiple steps and the use of other devices. More recently, a novel device consisting of a combined lumen-apposing metal stent (LAMS) and electrocautery-enhanced delivery system has been introduced. The aim of this study was to compare the placement and outcomes of the two devices.  This was a retrospective review of consecutive patients undergoing endoscopic ultrasound-guided placement of BFMS or LAMS for drainage of symptomatic WON. Data from procedures between October 2012 and December 2016 were taken from a prospectively maintained database. We compared technical and clinical success, procedure time, costs, and composite end point of significant events (adverse events, stent migration, additional percutaneous drainage) between BFMS and LAMS.  72 consecutive patients underwent placement of BFMS (40 patients, 44 stents) or LAMS (32 patients, 33 stents). Technical success was 91 % for BFMS and 97 % for LAMS. Clinical success was 65 % vs. 78 %, respectively. Median in-room procedure time was significantly shorter in the LAMS group (45 minutes [range 30 - 80]) than in the BFMS group (62.5 minutes [range 35 - 135]; P  < 0.001) and fewer direct endoscopic necrosectomies (DEN) were performed (median 1 [0 - 2.0] vs. 2 [0 - 3.7], respectively; P  = 0.005). If only inpatients were considered (35 BFMS and 19 LAMS), there was no significant difference in DEN 2 (range 0 - 11) and 2 (range 0 - 8), respectively. The composite end point of 32 % vs. 24 % was not significantly different. Median procedural costs for all patients with successful stent placement for WON treatment was €4427 (range 1630 - 12 926) for BFMS vs. €3500 (range 2509 - 13 393) for LAMS ( P  = 0.10).  LAMS was superior to BFMS in terms of procedure time, with comparable adverse events, success, and

Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis.

PubMed

Ridwan, B U; Koning, C J M; Besselink, M G H; Timmerman, H M; Brouwer, E C; Verhoef, J; Gooszen, H G; Akkermans, L M A

2008-01-01

Although probiotic prophylaxis has been suggested to prevent small bowel bacterial overgrowth, bacterial translocation and infection of pancreatic necrosis in severe acute pancreatitis, limited data are available on their antimicrobial activity. Using the well-diffusion method, we studied the antimicrobial properties of a multispecies probiotic product (Ecologic 641) against a collection of pathogens cultured from infected pancreatic necrosis. All individual probiotic strains included in the multispecies preparation were able to inhibit the growth of the pathogens to some extent. However, the combination of the individual strains (i.e. the multispecies preparation) was able to inhibit all pathogenic isolates. Probiotic-free supernatants adjusted to pH 7 were not able to inhibit pathogen growth. Ecologic 641 is capable of inhibiting growth of a wide variety of pathogens isolated from infected pancreatic necrosis. The antimicrobial properties are to a large extent explained by the production of organic acids. Ecologic 641 is currently being used in a Dutch nationwide double-blind, placebo-controlled, randomized multicentre trial in patients with predicted severe acute pancreatitis.

Phytoceuticals in Acute Pancreatitis: Targeting the Balance between Apoptosis and Necrosis

PubMed Central

Gaman, Laura; Robu, Georgiana Catalina; Radoi, Mugurel Petrinel; Stroica, Laura; Badea, Mihaela

2018-01-01

Despite recent advances in understanding the complex pathogenesis of pancreatitis, the management of the disease remains suboptimal. The use of phytoceuticals (plant-derived pleiotropic multitarget molecules) represents a new research trend in pancreatology. The purpose of this review is to discuss the phytoceuticals with pancreatoprotective potential in acute pancreatitis and whose efficacy is based, at least in part, on their capacity to modulate the acinar cell death. The phytochemicals selected, belonging to such diverse classes as polyphenols, flavonoids, lignans, anthraquinones, sesquiterpene lactones, nitriles, and alkaloids, target the balance between apoptosis and necrosis. Activation of apoptosis via various mechanisms (e.g., inhibition of X-linked inhibitor of apoptosis proteins by embelin, upregulation of FasL gene expression by resveratrol) and/or inhibition of necrosis seem to represent the essential key for decreasing the severity of the disease. Apart from targeting the apoptosis/necrosis balance, the phytochemicals displayed other specific protective activities: inhibition of inflammasome (e.g., rutin), suppression of neutrophil infiltration (e.g., ligustrazine, resveratrol), and antioxidant activity. Even though many of the selected phytoceuticals represent a promising therapeutic alternative, there is a shortage of human evidence, and further studies are required to provide solid basis to justify their use in the treatment of pancreatitis. PMID:29686719

[Dekasan application in treatment of infected pancreatic necrosis and its complications].

PubMed

Nichitaĭlo, M E

2010-03-01

The experience of the use of domestic antiseptic dekasan for topical use in patients over the infected pancreatic necrosis and its complications. There was significant improvement in the results of patients treatment.

Fully covered self-expanding metal stents versus lumen-apposing fully covered self-expanding metal stent versus plastic stents for endoscopic drainage of pancreatic walled-off necrosis: clinical outcomes and success.

PubMed

Siddiqui, Ali A; Kowalski, Thomas E; Loren, David E; Khalid, Ammara; Soomro, Ayesha; Mazhar, Syed M; Isby, Laura; Kahaleh, Michel; Karia, Kunal; Yoo, Joseph; Ofosu, Andrew; Ng, Beverly; Sharaiha, Reem Z

2017-04-01

Endoscopic transmural drainage/debridement of pancreatic walled-off necrosis (WON) has been performed using double-pigtail plastic (DP), fully covered self-expanding metal stents (FCSEMSs), or the novel lumen-apposing fully covered self-expanding metal stent (LAMS). Our aim was to perform a retrospective cohort study to compare the clinical outcomes and adverse events of EUS-guided drainage/debridement of WON with DP stents, FCSEMSs, and LAMSs. Consecutive patients in 2 centers with WON managed by EUS-guided debridement were divided into 3 groups: (1) those who underwent debridement using DP stents, (2) debridement using FCSEMSs, (3) debridement using LAMSs. Technical success (ability to access and drain a WON by placement of transmural stents), early adverse events, number of procedures performed per patient to achieve WON resolution, and long-term success (complete resolution of the WON without need for further reintervention at 6 months after treatment) were evaluated. From 2010 to 2015, 313 patients (23.3% female; mean age, 53 years) underwent WON debridement, including 106 who were drained using DP stents, 121 using FCSEMSs, and 86 using LAMSs. The 3 groups were matched for age, cause of the pancreatitis, WON size, and location. The cause of the patients' pancreatitis was gallstones (40.6%), alcohol (30.7%), idiopathic (13.1%), and other causes (15.6%). The mean cyst size was 102 mm (range, 20-510 mm). The mean number of endoscopy sessions was 2.5 (range, 1-13). The technical success rate of stent placement was 99%. Early adverse events were noted in 27 of 313 (8.6%) patients (perforation in 6, bleeding in 8, suprainfection in 9, other in 7). Successful endoscopic therapy was noted in 277 of 313 (89.6%) patients. When comparing the 3 groups, there was no difference in the technical success (P = .37). Early adverse events were significantly lower in the FCSEMS group compared with the DP and LAMS groups (1.6%, 7.5%, and 9.3%; P < .01). At 6-month follow

[Protocol for the treatment of severe acute pancreatitis with necrosis].

PubMed

Barreda, Luis; Targarona, Javier; Rodriguez, César

2005-01-01

The Severe Acute Pancreatic Unit of Edgardo Rebagliati Martins National Hospital was officially created in the year 2000. Up to date, we have cared for more than 195 patients with Pancreatic Necrosis. All of them have been treated under a management protocol presented by us. This has helped us to standardize treatment and also to compare results with work groups around the world. This Protocol comes from our own experience and that of our colleagues abroad with a wide knowledge in this kind of pathology abroad, with whom we maintain close ties.

The Association of Viral Hepatitis and Acute Pancreatitis

PubMed Central

Geokas, Michael C.; Olsen, Harvey; Swanson, Virginia; Rinderknecht, Heinrich

1972-01-01

The histological features of 24 pancreases obtained from patients who died of causes other than hepatitis, pancreatitis or pancreatic tumors, included a variable degree of autolysis, rare foci of inflammatory reaction but no hemorrhagic fat necrosis or destruction of elastic tissue in vessel walls (elastolysis). Assays of elastase in extracts of these pancreases showed no free enzyme, but varying amounts of proelastase. A review of autopsy findings in 33 patients with fatal liver necrosis attributed to halothane anesthesia, demonstrated changes of acute pancreatitis only in two. On the other hand, a review of 16 cases of fulminant viral hepatitis revealed changes characteristic of acute pancreatitis in seven – interstitial edema, hemorrhagic fat necrosis, inflammatory reaction and frequently elastolysis in vessel walls. Determination of elastase in extracts of one pancreas showed the bulk of the enzyme in free form. Furthermore, assays of urinary amylase in 44 patients with viral hepatitis showed increased levels of this enzyme (2583 ± 398 mean value ± standard error, Somogyi units per 100 ml in 13, or 29.5 percent). The evidence suggests that acute pancreatitis may at times complicate viral hepatitis. Although direct proof of viral pancreatic involvement is not feasible at present, a rational hypothesis is advanced which underlines similar mechanisms of tissue involvement in both liver and pancreas that may be brought about by the hepatitis viruses. PMID:5070694

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium-driven bile uptake.

PubMed

Ferdek, Pawel E; Jakubowska, Monika A; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

2016-11-01

Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca 2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca 2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells. Ca 2+ signals and necrosis are strongly dependent on extracellular Ca 2+ as well as Na + ; and Na + -dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells. Bile acid-mediated pancreatic damage can be further escalated by bradykinin-induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca 2+ signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca 2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3-sulfate (TLC-S), known to induce Ca 2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca 2+ signals on extracellular Na + and the presence of sodium-taurocholate cotransporting polypeptide (NTCP) indicate a Na + -dependent bile acid

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

PubMed Central

Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

2016-01-01

Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na

The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis.

PubMed

Baxter, K A; Pucher, P H; Berry, D P; Elberm, H; Abu-Hilal, M; Marangoni, G; Hamady, Zzr

2018-03-01

Introduction Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease. Methods A retrospective analysis was carried out of 324 patients admitted as an emergency with a diagnosis of AP to two UK hospitals. Patients were divided into two groups: those already taking NSAIDs for other co-morbidities and those not taking NSAIDs. Variables compared included: admission to a high dependency or intensive care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum inflammatory markers; modified early warning scores on days 1, 3 and 5; length of stay; and mortality. Results Patients not taking NSAIDs were more likely to have a C-reactive protein level of ≥150mg/l (p=0.007). Patients in the NSAID group experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst formation (p=0.010). Other variables showed no difference between the two groups, specifically length of stay and mortality. Conclusions Routine NSAID use may exert a protective effect on the development of AP, its severity, and complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis should be further evaluated.

Purtscher's retinopathy and renal cortical necrosis: two rare vaso-occlusive complications in a patient with acute pancreatitis: a case report.

PubMed

Haque, Wasim Md Mohosin Ul; Ananna, Mehruba Alam; Haque, Hasna Fahmima; Rahim, Muhammad Abdur; Samad, Tabassum; Iqbal, Sarwar

2016-11-15

Purtscher's retinopathy and renal cortical necrosis are two rare vaso-occlusive complications of acute pancreatitis. Purtscher's retinopathy causes sudden impairment of vision, which was first reported in a patient with head trauma. Subsequently, it was also reported as a complication of acute pancreatitis and few other clinical conditions. Acute pancreatitis also rarely causes renal cortical necrosis leading to acute kidney injury. However, the simultaneous presence of both complications is rarely reported. A 20-year-old Bengali man presented to our hospital with a history of acute upper abdominal pain, vomiting, anuria, and disorientation. He was ultimately found to have bilateral complete blindness due to Purtscher's retinopathy and acute kidney injury due to renal cortical necrosis, as sequelae of acute pancreatitis. He became dialysis-dependent, his vision did not recover, and he died 16 months after diagnosis. This case highlights Purtscher's retinopathy and renal cortical necrosis might be considered as a recognized pair complication of acute pancreatitis.

Inguinoscrotal region as an unusual site of extra-pancreatic collections in infected pancreatic necrosis.

PubMed

Kalia, Saurabh; Gupta, Rahul; Shenvi, Sunil D; Kumar, Hemanth; Gupta, Rajesh; Kang, Mandeep; Rana, Surinder Singh; Bhasin, Deepak Kumar; Singh, Rajinder

2016-08-01

Severe acute pancreatitis often leads to pancreatic and peripancreatic collections but, rarely, it can lead to collections at sites remote from the pancreas. Three male patients presented with abdominal pain and inguinoscrotal swelling. They were initially misdiagnosed with obstructed inguinal hernia, epididymo-orchitis and hydrocele, respectively. Later, their diagnosis of acute pancreatitis was revealed on laparotomy in one patient and on computed tomography (CT) in the remaining two patients. All these cases had extensive peripancreatic necrosis and paracolic collections tracking along the psoas muscle, downwards towards the pelvis. These collections were initially managed by percutaneous drainage and saline irrigation as a part of the 'step-up' approach. Two of these patients required open necrosectomy, while all required incision and drainage of inguinoscrotal collections. All the patients were discharged in satisfactory condition. Inguinoscrotal swelling is unusual as a first presentation of acute pancreatitis. A high index of suspicion, with careful study of patient's history and examination along with CT, may provide an accurate diagnosis. Local drainage may be required to control sepsis and also provide an egress route for intra-abdominal collections. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Reduced lymphocyte count as an early marker for predicting infected pancreatic necrosis.

PubMed

Shen, Xiao; Sun, Jing; Ke, Lu; Zou, Lei; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Ning; Li, Jieshou

2015-10-26

Early occurrence of immunosuppression is a risk factor for infected pancreatic necrosis (IPN) in the patients with acute pancreatitis (AP). However, current measures for the immune systems are too cumbersome and not widely available. Significantly decreased lymphocyte count has been shown in patients with severe but not mild type of AP. Whereas, the correlation between the absolute lymphocyte count and IPN is still unknown. We conduct this study to reveal the exact relationship between early lymphocyte count and the development of IPN in the population of AP patients. One hundred and fifty-three patients with acute pancreatitis admitted to Jinling Hospital during the period of January 2012 to July 2014 were included in this retrospective study. The absolute lymphocyte count and other relevant parameters were measured on admission. The diagnosis of IPN was based on the definition of the revised Atlanta classification. Patients were divided into two groups according to the presence of IPN. Thirty patients developed infected necrotizing pancreatitis during the disease course. The absolute lymphocyte count in patients with IPN was significantly lower on admission (0.62 × 10(9)/L, interquartile range [IQR]: 0.46-0.87 × 10(9)/L vs. 0.91 × 10(9)/L, IQR: 0.72-1.27 × 10(9)/L, p < 0.001) and throughout the whole clinical course than those without IPN. Logistic regression indicated that reduced lymphocyte count was an independent risk factor for IPN. The optimal cut-offs from ROC curve was 0.66 × 10(9)/L giving sensitivity of 83.7 % and specificity of 66.7 %. Reduced lymphocyte count within 48 h of AP onset is significantly and independently associated with the development of IPN.

Surgical management of pancreatic necrosis: A practice management guideline from the Eastern Association for the Surgery of Trauma.

PubMed

Mowery, Nathan T; Bruns, Brandon R; MacNew, Heather G; Agarwal, Suresh; Enniss, Toby M; Khan, Mansoor; Guo, Weidun Alan; Cannon, Jeremy W; Lissauer, Matthew E; Duane, Therese M; Hildreth, Amy N; Pappas, Peter A; Gries, Lynn M; Kaiser, Meghann; Robinson, Bryce R H

2017-08-01

Pancreatic or peripancreatic tissue necrosis confers substantial morbidity and mortality. New modalities have created a wide variation in approaches and timing of interventions for necrotizing pancreatitis. As acute care surgery evolves, its practitioners are increasingly being called upon to manage these complex patients. A systematic review of the MEDLINE database using PubMed was performed. English language articles regarding pancreatic necrosis from 1980 to 2014 were included. Letters to the editor, case reports, book chapters, and review articles were excluded. Topics of investigation included operative timing, the use of adjuvant therapy and the type of operative repair. Grading of Recommendations, Assessment, Development and Evaluations methodology was applied to question development, outcome prioritization, evidence quality assessments, and recommendation creation. Eighty-eight studies were included and underwent full review. Increasing the time to surgical intervention had an improved outcome in each of the periods evaluated (72 hours, 12-14 days, 30 days) with a significant improvement in outcomes if surgery was delayed 30 days. The use of percutaneous and endoscopic procedures was shown to postpone surgery and potentially be definitive. The use of minimally invasive surgery for debridement and drainage has been shown to be safe and associated with reduced morbidity and mortality. Acute Care Surgeons are uniquely trained to care for those with pancreatic necrosis due their training in critical care and complex surgery with ongoing shock. In adult patients with pancreatic necrosis, we recommend that pancreatic necrosectomy be delayed until at least day 12. During the first 30 days of symptoms with infected necrotic collections, we conditionally recommend surgical debridement only if the patients fail to improve after radiologic or endoscopic drainage. Finally, even with documented infected necrosis, we recommend that patients undergo a step-up approach to

Infeasibility of endoscopic transmural drainage due to pancreatic pseudocyst wall calcifications - case report.

PubMed

Krajewski, Andrzej; Lech, Gustaw; Makiewicz, Marcin; Kluciński, Andrzej; Wojtasik, Monika; Kozieł, Sławomir; Słodkowski, Maciej

2017-02-28

Postinflammatory pancreatic pseudocysts are one of the most common complications of acute pancreatitis. In most cases, pseudocysts self-absorb in the course of treatment of pancreatitis. In some patients, pancreatic pseudocysts are symptomatic and cause pain, problems with gastrointestinal transit, and other complications. In such cases, drainage or resection should be performed. Among the invasive methods, mini invasive procedures like endoscopic transmural drainage through the wall of the stomach or duodenum play an important role. For endoscopic transmural drainage, it is necessary that the cyst wall adheres to the stomach or duodenum, making a visible impression. We present a very rare case of infeasibility of endoscopic drainage of a postinflammatory pancreatic pseudocyst, impressing the stomach, due to cyst wall calcifications. A 55-year-old man after acute pancreatitis presented with a 1-year history of epigastric pain and was admitted due to a postinflammatory pseudocyst in the body and tail of pancreas. On admission, blood tests, including CA 19-9 and CEA, were normal. An ultrasound examination revealed a 100-mm pseudocyst in the tail of pancreas, which was confirmed on CT and EUS. Acoustic shadowing caused by cyst wall calcifications made the cyst unavailable to ultrasound assessment and percutaneous drainage. Gastroscopy revealed an impression on the stomach wall from the outside. The patient was scheduled for endoscopic transmural drainage. After insufflation of the stomach, a large mass protruding from the wall was observed. The stomach mucosa was punctured with a cystotome needle knife, and the pancreatic cyst wall was reached. Due to cyst wall calcifications, endoscopic drainage of the cyst was unfeasible. Profuse submucosal bleeding at the puncture site was stopped by placing clips. The patient was scheduled for open surgery, and distal pancreatectomy with splenectomy was performed. The histopathological examination confirmed the initial diagnosis

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome: MRI features of intraosseous fat necrosis involving the feet and knees.

PubMed

Kang, Dong Joo; Lee, Sun Joo; Choo, Hye Jung; Her, Minyoung; Yoon, Hye Kyoung

2017-02-01

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is extremely rare and presents as a triad of the three diseases. The patient usually presents with mild or absent abdominal symptoms. Here, we report on a case of a 66-year-old male who presented with pain and swelling in both legs and mild abdominal pain. He was diagnosed with acute pancreatitis by pancreatic enzyme analysis and abdominal computed tomography (CT) and with skin lesions of panniculitis through a biopsy. Magnetic resonance imaging (MRI) revealed multifocal intraosseous fat necrosis and arthritis involving both the feet and the knees. Therefore, we report a case of PPP syndrome with intraosseous fat necrosis involving both the feet and the knees.

Advances in the endoscopic management of pancreatic collections.

PubMed

Ruiz-Clavijo, David; de la Higuera, Belen González; Vila, Juan J

2015-04-16

Treatment of pancreatic collections has experienced great progress in recent years with the emergence of alternative minimally invasive techniques comparing to the classic surgical treatment. Such techniques have been shown to improve outcomes of morbidity vs surgical treatment. The recent emergence of endoscopic drainage is noteworthy. The advent of endoscopic ultrasonography has been crucial for treatment of these specific lesions. They can be characterized, their relationships with neighboring structures can be evaluated and the drainage guided by this technique has been clearly improved compared with the conventional endoscopic drainage. Computed tomography is the technique of choice to characterize the recently published new classification of pancreatic collections. For this reason, the radiologist's role establishing and classifying in a rigorously manner the collections according to the new nomenclature is essential to making therapeutic decisions. Ideal scenario for comprehensive treatment of these collections would be those centers with endoscopic ultrasound and interventional radiology expertise together with hepatobiliopancreatic surgery. This review describes the different types of pancreatic collections: acute peripancreatic fluid collection, pancreatic pseudocysts, acute necrotic collection and walled-off necrosis; the indications and the contraindications for endoscopic drainage, the drainage technique and their outcomes. The integrated management of pancreatic collections according to their type and evolution time is discussed.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PubMed

Karaman, Adem; Durur-Subasi, Irmak; Alper, Fatih; Durur-Karakaya, Afak; Subasi, Mahmut; Akgun, Metin

2017-10-01

To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006. © 2017 International Society for Magnetic Resonance in Medicine.

Management of patients after recovering from acute severe biliary pancreatitis.

PubMed

Dedemadi, Georgia; Nikolopoulos, Manolis; Kalaitzopoulos, Ioannis; Sgourakis, George

2016-09-14

Cholelithiasis is the most common cause of acute pancreatitis, accounting 35%-60% of cases. Around 15%-20% of patients suffer a severe attack with high morbidity and mortality rates. As far as treatment is concerned, the optimum method of late management of patients with severe acute biliary pancreatitis is still contentious and the main question is over the correct timing of every intervention. Patients after recovering from an acute episode of severe biliary pancreatitis can be offered alternative options in their management, including cholecystectomy, endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, or no definitive treatment. Delaying cholecystectomy until after resolution of the inflammatory process, usually not earlier than 6 wk after onset of acute pancreatitis, seems to be a safe policy. ERCP and sphincterotomy on index admission prevent recurrent episodes of pancreatitis until cholecystectomy is performed, but if used for definitive treatment, they can be a valuable tool for patients unfit for surgery. Some patients who survive severe biliary pancreatitis may develop pseudocysts or walled-off necrosis. Management of pseudocysts with minimally invasive techniques, if not therapeutic, can be used as a bridge to definitive operative treatment, which includes delayed cholecystectomy and concurrent pseudocyst drainage in some patients. A management algorithm has been developed for patients surviving severe biliary pancreatitis according to the currently published data in the literature.

Lumen apposing metal stents for pancreatic fluid collections: Recognition and management of complications.

PubMed

DeSimone, Michael L; Asombang, Akwi W; Berzin, Tyler M

2017-09-16

For patients recovering from acute pancreatitis, the development of a pancreatic fluid collection (PFC) predicts a more complex course of recovery, and introduces difficult management decisions with regard to when, whether, and how the collection should be drained. Most PFCs resolve spontaneously and drainage is indicated only in pseudocysts and walled-off pancreatic necrosis when the collections are causing symptoms and/or local complications such as biliary obstruction. Historical approaches to PFC drainage have included surgical (open or laparoscopic cystgastrostomy or pancreatic debridement), and the placement of percutaneous drains. Endoscopic drainage techniques have emerged in the last several years as the preferred approach for most patients, when local expertise is available. Lumen-apposing metal stents (LAMS) have recently been developed as a tool to facilitate potentially safer and easier endoscopic drainage of pancreatic fluid collections, and less commonly, for other indications, such as gallbladder drainage. Physicians considering LAMS placement must be aware of the complications most commonly associated with LAMS including bleeding, migration, buried stent, stent occlusion, and perforation. Because of the patient complexity associated with severe pancreatitis, management of pancreatic fluid collections can be a complex and multidisciplinary endeavor. Successful and safe use of LAMS for patients with pancreatic fluid collections requires that the endoscopist have a full understanding of the potential complications of LAMS techniques, including how to recognize and manage expected complications.

Recombinant scFv antibodies against infectious pancreatic necrosis virus isolated by flow cytometry.

PubMed

Xu, Li-Ming; Zhao, Jing-Zhuang; Liu, Miao; Cao, Yong-Sheng; Yin, Jia-Sheng; Liu, Hong-Bai; Lu, Tongyan

2016-11-01

Infectious pancreatic necrosis is a significant disease of farmed salmonids in China. In this study, a single chain variable fragment (scFv) antibody library derived from rainbow trout (Oncorhynchus mykiss) and viral protein VP2 of a Chinese infectious pancreatic necrosis virus (IPNV) isolate ChRtm213 were co-expressed by a bacterial display technology. The library was subjected to three rounds of screening by flow cytometry (FCM) to select IPNV specific antibodies. Six antibody clones with different mean fluorescence intensities (MFI) were obtained by picking colonies at random. The antibody clones were expressed and purified. The purified IPNV-specific scFv antibodies were used successfully in Western blotting, enzyme linked immunosorbent assay (ELISA) and an immunofluorescence antibody test (IFAT). This method provides a high throughput means to screen an antibody library by flow cytometry, and isolate a panel of antibody that can be used as potential reagents for the detection and study of IPNV that are prevalent in China. Copyright © 2016 Elsevier B.V. All rights reserved.

Peripancreatic collections in acute pancreatitis: Correlation between computerized tomography and operative findings

PubMed Central

Vege, Santhi Swaroop; Fletcher, Joel G; Talukdar, Rupjyoti; Sarr, Michael G

2010-01-01

AIM: To evaluate the ability of contrast-enhanced computerized tomography (CECT) to characterize the nature of peripancreatic collections. METHODS: Twenty five patients with peripancreatic collections on CECT and who underwent operative intervention for severe acute pancreatitis were retrospectively studied. The collections were classified into (1) necrosis without frank pus; (2) necrosis with pus; and (3) fluid without necrosis. A blinded radiologist assessed the preoperative CTs of each patient for necrosis and peripancreatic fluid collections. Peripancreatic collections were described in terms of volume, location, number, heterogeneity, fluid attenuation, wall perceptibility, wall enhancement, presence of extraluminal gas, and vascular compromise. RESULTS: Fifty-four collections were identified at operation, of which 45 (83%) were identified on CECT. Of these, 25/26 (96%) had necrosis without pus, 16/19 (84%) had necrosis with pus, and 4/9 (44%) had fluid without necrosis. Among the study characteristics, fluid heterogeneity was seen in a greater proportion of collections in the group with necrosis and pus, compared to the other two groups (94% vs 48% and 25%, P = 0.002 and 0.003, respectively). Among the wall characteristics, irregularity was seen in a greater proportion of collections in the groups with necrosis with and without pus, when compared to the group with fluid without necrosis (88% and 71% vs 25%, P = 0.06 and P < 0.01, respectively). The combination of heterogeneity and presence of extraluminal gas had a specificity and positive likelihood ratio of 92% and 5.9, respectively, in detecting pus. CONCLUSION: Most of the peripancreatic collections seen on CECT in patients with severe acute pancreatitis who require operative intervention contain necrotic tissue. CECT has a somewhat limited role in differentiating the different types of collections. PMID:20818812

Management of pancreatic fluid collections: A comprehensive review of the literature

PubMed Central

Tyberg, Amy; Karia, Kunal; Gabr, Moamen; Desai, Amit; Doshi, Rushabh; Gaidhane, Monica; Sharaiha, Reem Z; Kahaleh, Michel

2016-01-01

Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis. It is important to classify PFCs to guide management. The revised Atlanta criteria classifies PFCs as acute or chronic, with chronic fluid collections subdivided into pseudocysts and walled-off pancreatic necrosis (WOPN). Establishing adequate nutritional support is an essential step in the management of PFCs. Early attempts at oral feeding can be trialed in patients with mild pancreatitis. Enteral feeding should be implemented in patients with moderate to severe pancreatitis. Jejunal feeding remains the preferred route of enteral nutrition. Symptomatic PFCs require drainage; options include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, and an associated reduction in health care costs, minimally invasive endoscopic drainage has become the preferable approach. An endoscopic ultrasonography-guided approach using a seldinger technique is the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WOPN. Direct endoscopic necrosectomy is often required in WOPN. Lumen apposing metal stents that allow for direct endoscopic necrosectomy and debridement through the stent lumen are preferred in these patients. Endoscopic retrograde cholangio pancreatography with pancreatic duct (PD) exploration should be performed concurrent to PFC drainage. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Any pancreatic ductal disruption should be bridged with endoscopic stenting. PMID:26900288

Long-term results after endoscopic drainage and necrosectomy of symptomatic pancreatic fluid collections.

PubMed

Seewald, Stefan; Ang, Tiing Leong; Richter, Hugo; Teng, Karl Yu Kim; Zhong, Yan; Groth, Stefan; Omar, Salem; Soehendra, Nib

2012-01-01

To determine the immediate and long-term results of endoscopic drainage and necrosectomy for symptomatic pancreatic fluid collections. The data of 80 patients with symptomatic pancreatic fluid collections (mean diameter: 11.7 cm, range 3-20; pseudocysts: 24/80, abscess: 20/80, infected walled-off necrosis: 36/80) referred for endoscopic management from October 1997 to March 2008 were analyzed retrospectively. Endoscopic drainage techniques included endoscopic ultrasound (EUS)-guided aspiration (2/80), EUS-guided transenteric drainage (70/80) and non-EUS-guided drainage across a spontaneous transenteric fistula (8/80). Endoscopic necrosectomy was carried out in 49/80 (abscesses: 14/20; infected necrosis: 35/36). Procedural complications were bleeding (12/80), perforation (7/80), portal air embolism (1/80) and Ogilvie Syndrome (1/80). Initial technical success was achieved in 78/80 (97.5%) and clinical resolution of the collections was achieved endoscopically in 67/80 (83.8%), with surgery required in 13/80 (perforation: four; endoscopically inaccessible areas: two; inadequate drainage: seven). Within 6 months five patients required surgery due to recurrent fluid collections; over a mean follow up of 31 months, surgery was required in four more patients due to recurrent collections as a consequence of underlying pancreatic duct abnormalities that could not be treated endoscopically. The long-term success of endoscopic treatment was 58/80 (72.5%). Endoscopic drainage of symptomatic pancreatic fluid collections is safe and effective, with excellent immediate and long-term results. Endoscopic necrosectomy has a risk of serious complications. The underlying pancreatic duct abnormalities must be addressed to prevent recurrence of fluid collections. © 2011 The Authors. Digestive Endoscopy © 2011 Japan Gastroenterological Endoscopy Society.

Biliary versus alcohol-related infected pancreatic necrosis: similarities and differences in the follow-up.

PubMed

Reszetow, Jacek; Hać, Stanisław; Dobrowolski, Sebastian; Stefaniak, Tomasz; Wajda, Zdzisław; Gruca, Zbigniew; Sledziński, Zbigniew; Studniarek, Michał

2007-10-01

Infected pancreatic necrosis (IPN) is a serious complication of acute pancreatitis. Data concerning survivors' quality of life and pancreatic functions are scarce. Follow-up of the patients with alcohol and biliary etiology of IPN treated with open necrosectomy was performed. Twenty-eight survivors after operative treatment (Bradley procedure) of IPN were followed up 24 to 96 months after discharge from the hospital (10 biliary and 18 alcohol patients). Their exocrine and endocrine pancreatic functions and quality of life (Functional Assessment of Chronic Illness Therapy scale) were evaluated. Pancreatic tissue remaining after necrosectomy was visualized by use of contrast-enhanced computed tomography (CT). In 44.4% of alcohol-induced IPN patients, the presence of the whole pancreas was shown on the follow-up CT, contrary to the biliary group, where the partial lack of the pancreas was observed in all cases. Pancreatic tissue calcifications were present on CT in 8 patients of alcohol-induced acute pancreatitis group only. Median stool elastase 1 concentrations were 318.1 U/mL in the biliary group and 238.3 U/mL in the alcohol-induced group (not significant). The Functional Assessment of Chronic Illness Therapy scale showed significantly higher social/family and emotional well-being in patients with biliary acute necrotizing pancreatitis. Patients after alcohol-induced IPN had lower quality of life compared with biliary etiology. Biliary and alcohol-induced IPN patients after surgical treatment have nonsignificant differences of endocrine and exocrine pancreatic functions.

Pancreatic fluid collections: What is the ideal imaging technique?

PubMed

Dhaka, Narendra; Samanta, Jayanta; Kochhar, Suman; Kalra, Navin; Appasani, Sreekanth; Manrai, Manish; Kochhar, Rakesh

2015-12-28

Pancreatic fluid collections (PFCs) are seen in up to 50% of cases of acute pancreatitis. The Revised Atlanta classification categorized these collections on the basis of duration of disease and contents, whether liquid alone or a mixture of fluid and necrotic debris. Management of these different types of collections differs because of the variable quantity of debris; while patients with pseudocysts can be drained by straight-forward stent placement, walled-off necrosis requires multi-disciplinary approach. Differentiating these collections on the basis of clinical severity alone is not reliable, so imaging is primarily performed. Contrast-enhanced computed tomography is the commonly used modality for the diagnosis and assessment of proportion of solid contents in PFCs; however with certain limitations such as use of iodinated contrast material especially in renal failure patients and radiation exposure. Magnetic resonance imaging (MRI) performs better than computed tomography (CT) in characterization of pancreatic/peripancreatic fluid collections especially for quantification of solid debris and fat necrosis (seen as fat density globules), and is an alternative in those situations where CT is contraindicated. Also magnetic resonance cholangiopancreatography is highly sensitive for detecting pancreatic duct disruption and choledocholithiasis. Endoscopic ultrasound is an evolving technique with higher reproducibility for fluid-to-debris component estimation with the added advantage of being a single stage procedure for both diagnosis (solid debris delineation) and management (drainage of collection) in the same sitting. Recently role of diffusion weighted MRI and positron emission tomography/CT with (18)F-FDG labeled autologous leukocytes is also emerging for detection of infection noninvasively. Comparative studies between these imaging modalities are still limited. However we look forward to a time when this gap in literature will be fulfilled.

Cystic dystrophy of the duodenal wall is not always associated with chronic pancreatitis

PubMed Central

Pezzilli, Raffaele; Santini, Donatella; Calculli, Lucia; Casadei, Riccardo; Morselli-Labate, Antonio Maria; Imbrogno, Andrea; Fabbri, Dario; Taffurelli, Giovanni; Ricci, Claudio; Corinaldesi, Roberto

2011-01-01

Cystic dystrophy of the duodenal wall is a rare form of the disease which was described in 1970 by French authors who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of the duodenum and the head of the pancreas. German authors have defined this area as a “groove”. We report our recent experience on cystic dystrophy of the paraduodenal space and systematically review the data in the literature regarding the alterations of this space. A MEDLINE search of papers published between 1966 and 2010 was carried out and 59 papers were considered for the present study; there were 19 cohort studies and 40 case reports. The majority of patients having groove pancreatitis were middle aged. Mean age was significantly higher in patients having groove carcinoma. The diagnosis of cystic dystrophy of the duodenal wall can now be assessed by multidetector computer tomography, magnetic resonance imaging and endoscopic ultrasonography. These latter two techniques may also add more information on the involvement of the remaining pancreatic gland not involved by the duodenal malformation and they may help in differentiating “groove pancreatitis” from “groove adenocarcinoma”. In conclusion, chronic pancreatitis involving the entire pancreatic gland was present in half of the patients with cystic dystrophy of the duodenal wall and, in the majority of them, the pancreatitis had calcifications. PMID:22110260

Gastrointestinal Fistulas in Acute Pancreatitis With Infected Pancreatic or Peripancreatic Necrosis

PubMed Central

Jiang, Wei; Tong, Zhihui; Yang, Dongliang; Ke, Lu; Shen, Xiao; Zhou, Jing; Li, Gang; Li, Weiqin; Li, Jieshou

2016-01-01

Abstract Gastrointestinal (GI) fistula is a well-recognized complication of acute pancreatitis (AP). However, it has been reported in limited literature. This study aimed to evaluate the incidence and outcome of GI fistulas in AP patients complicated with infected pancreatic or peripancreatic necrosis (IPN). Between 2010 and 2013 AP patients with IPN who diagnosed with GI fistula in our center were analyzed in this retrospective study. And we also conducted a comparison between patients with and without GI fistula regarding the baseline characteristics and outcomes. Over 4 years, a total of 928 AP patients were admitted into our center, of whom 119 patients with IPN were diagnosed with GI fistula and they developed 160 GI fistulas in total. Colonic fistula found in 72 patients was the most common form of GI fistula followed with duodenal fistula. All duodenal fistulas were managed by nonsurgical management. Ileostomy or colostomy was performed for 44 (61.1%) of 72 colonic fistulas. Twenty-one (29.2%) colonic fistulas were successfully treated by percutaneous drainage or continuous negative pressure irrigation. Mortality of patients with GI fistula did not differ significantly from those without GI fistula (28.6% vs 21.9%, P = 0.22). However, a significantly higher mortality (34.7%) was observed in those with colonic fistula. GI fistula is a common finding in patients of AP with IPN. Most of these fistulas can be successfully managed with different procedures depending on their sites of origin. Colonic fistula is related with higher mortality than those without GI fistula. PMID:27057908

[Identifying the severe acute pancreatitis].

PubMed

Acevedo Tizón, Anais; Targarona Modena, Javier; Málaga Rodríguez, Germán; Barreda Cevasco, Luis

2011-01-01

To compare patients with acute necrotizing pancreatitis without any additional complications during their hospital stay (Group A) versus patients with Acute Necrotizing Pancreatitis with additional complications during their hospital stay (Group B). Data obtained from a pre-existing base from hospitalized patients with diagnosis of acute necrotizing pancreatitis in the specialized unit of "Unidad de Pancreatitis Aguda Grave del Hospital Nacional Edgardo Rebagliati Martins" between 2000 and 2010. Data included patients with diagnosis of acute necrotizing pancreatitis, of ages 18 and over. Data from 215 patients with acute necrotizing pancreatitis was included. Patients from Group A represented 32% (68) and from Group B 68% (147). Group A had a average of 39 hospitalized days and Group B had an average of 56 days (p=0.01). From Group A 22% had more than 50% of necrosis while 43% of Group B had this extension of necrosis (p <0.05, OR 3.4, IC (1.12-10)). Of the 14 deaths of the population, all part of Group B, 12 of them had more than 50% of necrosis. Not every patient classified as severe acute pancreatitis, based on the presence of necrosis, behave likewise. It is an extended necrosis, described as more than 50% of pancreatic necrosis, and not the presence itself which will determine additional complications during the course of disease and a greater mortality.

Endoscopic Ultrasound-Guided Management of Pancreatic Fluid Collections: Update and Review of the Literature

PubMed Central

Alali, Ali; Mosko, Jeffrey; May, Gary; Teshima, Christopher

2017-01-01

Severe acute pancreatitis is often complicated by the development of pancreatic fluid collections (PFCs), which may be associated with significant morbidity and mortality. It is crucial to accurately classify these collections as a pseudocyst or walled-off necrosis (WON) given significant differences in outcomes and management. Interventions for PFCs have increasingly shifted to less invasive strategies, with endoscopic ultrasound (EUS)-guided methods being shown to be safer and equally effective as more invasive surgical techniques. In recent years, many new developments have improved the safety and efficacy of EUS-guided interventions, such as the introduction of lumen-apposing metal stents (LAMS), direct endoscopic necrosectomy (DEN) and multiple other adjunctive techniques. Despite these developments, treatment of PFCs, and infected WON in particular, continues to be associated with significant morbidity and mortality. In this article, we discuss the EUS-guided management of PFCs while reviewing the latest developments and controversies in the field. We end by summarizing our own approach to managing PFCs. PMID:28391671

Transmural endoscopic necrosectomy of infected pancreatic necroses and drainage of infected pseudocysts: a tailored approach.

PubMed

Rische, Susanne; Riecken, Bettina; Degenkolb, Johannes; Kayser, Thomas; Caca, Karel

2013-02-01

Transmural endoscopic drainage and necrosectomy have become favored treatment modes for infected pancreatic pseudocysts and necroses. In this analysis, we summarize the outcome of 40 patients with complicated course of acute pancreatitis after endoscopic treatment. From January 2006 through May 2011, 40 patients of our department with complicated pancreatitis were included in this retrospective analysis. All patients underwent endosonographic transgastric puncture followed by wire-guided insertion of one or more double pigtail stents. Patients with extensive necroses were treated repeatedly with transgastric necrosectomy. Treatment success was determined by clinical, laboratory, and radiological parameters. Nine patients had interstitial pancreatitis (IP) with pancreatic pseudocysts. Thirty-one patients had necrotizing pancreatitis (NP) with acute pancreatic necroses (n = 4) or walled-off pancreatic necrosis (n = 27). All patients with IP and nine patients with NP had pseudocysts without solid material and underwent transgastric drainage only. In this group major complications occurred in 11.1% and no mortality was observed. Twenty-two NP patients were treated with additional repeated necrosectomy. In patients with localized peripancreatic necroses (n = 10) no need of surgery or mortality was observed, major complications occurred in 10%. In patients with extensive necroses reaching the lower abdomen (n = 12), three needed subsequent surgery and three died. Transgastric endoscopy is an effective minimally invasive procedure even in patients with advanced pancreatic necroses. Complication rate is low particularly in patients with sole pseudocysts or localized necroses. The extent of the fluid collections and necroses is a new predictive parameter for the outcome of the patients.

Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

PubMed Central

Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

2011-01-01

Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

Effects of Erdosteine on Experimental Acute Pancreatitis Model.

PubMed

Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

2017-10-01

To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

Evaluation of the short- and long-term effectiveness and safety of fully covered self-expandable metal stents for drainage of pancreatic fluid collections: results of a Spanish nationwide registry.

PubMed

Vazquez-Sequeiros, Enrique; Baron, Todd H; Pérez-Miranda, Manuel; Sánchez-Yagüe, Andres; Gornals, Joan; Gonzalez-Huix, Ferran; de la Serna, Carlos; Gonzalez Martin, Juan Angel; Gimeno-Garcia, Antonio Z; Marra-Lopez, Carlos; Castellot, Ana; Alberca, Fernando; Fernandez-Urien, Ignacio; Aparicio, Jose Ramon; Legaz, Maria Luisa; Sendino, Oriol; Loras, Carmen; Subtil, Jose Carlos; Nerin, Juan; Perez-Carreras, Mercedes; Diaz-Tasende, Jose; Perez, Gustavo; Repiso, Alejandro; Vilella, Angels; Dolz, Carlos; Alvarez, Alberto; Rodriguez, Santiago; Esteban, Jose Miguel; Juzgado, Diego; Albillos, Agustin

2016-09-01

Initial reports suggest that fully covered self-expandable metal stents (FCSEMSs) may be better suited for drainage of dense pancreatic fluid collections (PFCs), such as walled-off pancreatic necrosis. The primary aim was to analyze the effectiveness and safety of FCSEMSs for drainage of different types of PFCs in a large cohort. The secondary aim was to investigate which type of FCSEMS is superior. This was a retrospective, noncomparative review of a nationwide database involving all hospitals in Spain performing EUS-guided PFC drainage. From April 2008 to August 2013, all patients undergoing PFC drainage with an FCSEMS were included in a database. The main outcome measurements were technical success, short-term (2 weeks) and long-term (6 months) effectiveness, adverse events, and need for surgery. The study included 211 patients (pseudocyst/walled-off pancreatic necrosis, 53%/47%). The FCSEMSs used were straight biliary (66%) or lumen-apposing (34%). Technical success was achieved in 97% of patients (95% confidence interval [CI], 93%-99%). Short-term- and long-term clinical success was obtained in 94% (95% CI, 89%-97%) and 85% (95% CI, 79%-89%) of patients, respectively. Adverse events occurred in 21% of patients (95% CI, 16%-27%): infection (11%), bleeding (7%), and stent migration and/or perforation (3%). By multivariate analysis, patient age (>58 years) and previous failed drainage were the most important factors associated with negative outcome. An FCSEMS is effective and safe for PFC drainage. Older patients with a history of unsuccessful drainage are more likely to fail EUS-guided drainage. The type of FCSEMS does not seem to influence patient outcome. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2015-09-01

The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Osteomyelitis: A rare complication of pancreatitis and PPP-syndrome.

PubMed

Langenhan, Ronny; Reimers, Niklas; Probst, Axel

2016-03-01

Pancreatic diseases can be accompanied by periarthritis with bone necrosis and panniculitis (PPP-syndrome). It is postulated that this is caused by systemic activity of pancreatic enzymes leading to microcirculatory disturbances and fat necrosis. The morbidity and mortality of the PPP-syndrome is high. Successful treatment of pancreatitis can lead to resolution of accompanying panniculitis and periarthritis without adverse sequelae, but weeks or months after pancreatitis, asymptomatic necrosis of the bone may become symptomatic by fracturing spontaneously. In this report, we also describe osteomyelitis as a severe septic complication of bone necrosis caused by pancreatitis, in one case as acute tissue necrosis and in another case months after pancreatitis spread haematogenously. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis.

PubMed

Mangiante, G; Colucci, G; Canepari, P; Bassi, C; Nicoli, N; Casaril, A; Marinello, P; Signoretto, C; Bengmark, S

2001-01-01

Infection is the commonest cause of death in acute pancreatitis. Early reduction of commensal flora (particularly Lactobacillus species) and, at the same time, overgrowth of Enterobacteriaceae, especially Escherichia coli, have recently been described during acute pancreatitis. Lactobacillus plantarum has been shown to be effective in reducing the egress of endotoxin and microbial translocation in several experimental models such as chemically induced hepatitis and ulcerative colitis. The aim of the study was to determine whether L. plantarum 299v (Lp 299v) is capable of effectively reducing microbial translocation in experimental pancreatitis. Acute pancreatitis was induced by isolation and ligation of the biliopancreatic duct in Lewis rats weighing 250-350 g. The animals were divided into 3 groups: group A, sham operation; group B, induction of pancreatitis and no further treatment, and group C, induction of pancreatitis + daily administration by gavage of a 5-ml/day suspension of Lp 299v at 0.5-1.0 x 10(9) bacteria/ml for 8 days, 4 days before and 4 days after induction of pancreatitis. All animals were sacrificed after 96 h. Histological studies and microbiological analyses were performed. At sacrifice, 40/55 animals showed signs of severe pancreatitis. Since acute pancreatitis was the specific disease investigated, only these animals were subjected to further study. In group B, we found pathogenic micro-organisms in the mesenteric lymph nodes in 14/20 animals and in the pancreatic tissue in 10/20. The bacterial flora consisted predominantly of E. coli, Enterococcus faecalis, Pseudomonas and Proteus species. In contrast, when the animals were kept under an 'umbrella' of Lp 299v, growth of E. faecalis or E. coli were detected only in 4/20 mesenteric lymph node cultures and in 3/20 pancreatic tissue cultures. Lp 299v is effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative

Endothelial markers are associated with pancreatic necrosis and overall prognosis in acute pancreatitis: A preliminary cohort study.

PubMed

Chen, Yizhe; Ke, Lu; Meng, Lei; Yang, Qi; Tong, Zhihui; Pan, Yiyuan; Li, Weiqin; Li, Jieshou

Endothelial injury is believed to play an important role in the evolution of pancreatic microcirculatory dysfunction and pancreatic necrosis (PN) in patients with acute pancreatitis (AP). The aim of this study was to investigate the role of three endothelial markers (von Willebrand factor, vWF; E-selectin; endothelial protein C receptor, EPCR) in the early phase of AP, especially the relationship between endothelial markers and PN. From March 2015 to March 2016, 57 AP patients admitted within 72 h of symptom onset in our hospital were included for this study. Blood samples were taken on admission and the clinical characteristics and outcomes of these patients were recorded. The levels of vWF, E-selectin and EPCR were measured using ELISA for analysis and compared with other severity markers of AP. All the three markers were significantly different in healthy control, mild, moderate and severe AP patients. Moreover, the endothelial markers, especially vWF, also showed significant difference in patients with different extent of PN, as well as those with or without MODS. Additionally, the levels of endothelial markers correlated well with other commonly used markers of AP severity. Elevated endothelium-related mediators (vWF, E-selectin and EPCR) appear to participate in the development of PN and may be a potential indicator of overall prognosis. Our results may help clinicians better understand the pathophysiological process of the development of PN. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Patients With Sentinel Acute Pancreatitis of Alcoholic Etiology are at Risk for Organ Failure and Pancreatic Necrosis: A Dual-Center Experience

PubMed Central

Easler, Jeffrey J.; de-Madaria, Enrique; Nawaz, Haq; Moya-Hoyo, Neftalí; Koutroumpakis, Efstratios; Rey-Riveiro, Mónica; Singh, Vijay P.; Acevedo-Piedra, Nelly G.; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.

2016-01-01

Objectives Assess the relationship between alcoholic etiology, tobacco use and severe acute pancreatitis (SAP). Methods Smoking and alcohol exposure were recorded upon admission in a cohort of acute pancreatitis patients within the United States (U.S.). Patients with first, “sentinel” attack of acute pancreatitis (AP) were identified for analysis. Associations between alcohol, smoking and SAP were validated in an independent cohort of patients from Spain. Results U.S. cohort (n=222): Thirty-five% developed organ failure (OF), 35% Pancreatic Necrosis (PNec), and 7% died. OF (54% vs. 33%, p=0.03), PNec (62% vs. 31%, p=0.006), intensive care (ICU) admission (58% vs. 36%, p=0.03) and length of stay (LOS) (20 vs. 8 days, p= 0.007) were greater in alcoholic when compared to other etiologies. Spanish cohort (n=366): Similar differences in outcomes were also found with between alcoholic and non-alcoholic etiologies: OF (24% vs. 8%, p=0.001), PNec (38% vs. 14%, p<0.001), ICU admission (20% vs. 3%, p<0.001), and LOS (17 vs. 11 days, p=0.04). Multivariable analysis confirmed alcoholic etiology to be independently associated with OF and PNec in both cohorts. Conclusions Alcoholic etiology is independently associated with OF and PNec in patients with sentinel AP and is important when evaluating risk for severe disease in AP. PMID:27101573

[Retrograde pancreatic duct imaging and surgical tactics in hemorrhagic necrotizing pancreatitis. Preliminary report].

PubMed

Gebhardt, C; Gall, F P; Lux, G; Riemann, J; Link, W

1983-12-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past months. The results in, to date, ten patients revealed four different morphological findings of importance for the surgical tactic: 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. - 2. Contrast medium leaks via a ductal fistula: left resection including the removal of the fistulous area must be done. - 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. - 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesion resulting in drainage of the necrotic cavity into the bowel permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. - The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERP.

Virus-Specific RNA Synthesis in Cells Infected by Infectious Pancreatic Necrosis Virus

PubMed Central

Somogyi, Paul; Dobos, Peter

1980-01-01

Pulse-labeling experiments with [3H]uridine revealed that the rate of infections pancreatic necrosis virus-specific RNA synthesis was maximal at 8 to 10 h after infection and was completely diminished by 12 to 14 h. Three forms of RNA intermediates were detected: (i) a putative transcription intermediate (TRI) which comigrated in acrylamide gels with virion double-stranded RNA (dsRNA) after RNase treatment; (ii) a 24S genome length mRNA which could be resolved into two bands by polyacrylamide gel electrophoresis; and (iii) a 14S dsRNA component indistinguishable from virion RNA by gradient centrifugation and gel electrophoresis. The TRI (i) was LiCl precipitable; (ii) sedimented slightly faster and broader (14 to 16S) than the 14S virion dsRNA; (iii) had a lower electrophoretic mobility in acrylamide gels than dsRNA, barely entering acrylamide gels as a heterogenous component; (iv) yielded genome-sized pieces of dsRNA after RNase digestion; and (v) was the most abundant RNA form early in the infectious cycle. The 24S single-stranded RNA was thought to be the viral mRNA since it: (i) became labeled during short pulses; (ii) was found in the polysomal fraction of infected cells; and (iii) hybridized to denatured viral RNA, forming two segments of RNase-resistant RNA that comigrated with virion dsRNA in gels. The 24S mRNA component was formed before the synthesis of dsRNA, and radioactivity could be chased from 24S single-stranded RNA to dsRNA, indicating that 24S RNA may serve as template for the synthesis of complementary strands to form dsRNA. Similar to reovirus, infectious pancreatic necrosis viral 24S mRNA contained no polyadenylic acid tracts. Images PMID:16789184

Chaiqinchengqi decoction regulates necrosis-apoptosis via regulating the release of mitochondrial cytochrome c and caspase-3 in rats with acute necrotizing pancreatitis.

PubMed

Lin, Ziqi; Guo, Jia; Xue, Ping; Huang, Lei; Deng, Lihui; Yang, Xiaonan; Xia, Qing

2014-04-01

To explore the effect and the mechanism of Chaiqinchengqi decoction (CQCQD) on the apoptosis-necrosis switch of pancreatic acinar cells in acute necrotizing pancreatitis (ANP) in rats. Sixty Sprague-Dawley rats were randomized into the control group, the ANP group and the CQCQD group. The acute pancreatitis (AP) model was induced by intraperitoneal injections of 4 g/kg 8% L-Arginine (PH 7.0) twice with a 1 h interval. Rats in the CQCQD group were intragastrically administered CQCQD (20 mL/kg every 2 h, 3 times, then 20 mL/kg every 6 h, 3 times). Rats were killed at the 6 and 24 h after the induction of AP. The pancreatic tissues were collected for pathology and to isolate pancreatic acinar cells and mitochondria. CQCQD significantly ameliorated the severity of ANP by reducing the pancreatic histopathology score, indicated by lactate dehydrogenase levels at the 6 and 24 h. The CQCQD group promoted the apoptosis of pancreatic acinar cells by raising the apoptosis index compared with the ANP group and the control group. Mitochondrial cytochrome c at the 6 and 24 h in the ANP group were lower than that in the control group or the CQCQD group (0.67 +/- 0.13 vs 1.54 +/- 0.03 vs 0.81 +/- 0.09; 0.71 +/- 0.08 vs 1.55 +/- 0.09 vs 0.89 +/- 0.16, P < 0.01). The cytochrome c levels in the cytoplasm at the 6 and 2 h in the CQCQD group were higher than in the control group (1.36 +/- 0.15 vs 0.67 +/- 0.04, 1.46 +/- 0.08 vs 0.59 +/- 0.09, P < 0.01), or the ANP group (0.96 +/- 0.13, P > 0.05; 0.97 +/- 0.09, P < 0.05). CQCQD increased caspase-3 activity over the ANP group at the 6 h. CQCQD can induce apoptosis and relieve the necrosis of pancreatic acinar cells via promoting the release of mitochondrial cytochrome c and increasing pancreatic caspase-3 activity in ANP rats.

Recombinant infectious hematopoietic necrosis virus expressing infectious pancreatic necrosis virus VP2 protein induces immunity against both pathogens.

PubMed

Guo, Mengting; Shi, Wen; Wang, Yanxue; Wang, Yuting; Chen, Yaping; Li, Dechuan; Ren, Xuanyu; Hua, Xiaojing; Tang, Lijie; Li, Yijing; Liu, Min

2018-04-21

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are typical pathogens of rainbow trout. Their co-infection is also common, which causes great economic loss in juvenile salmon species. Although vaccines against IHNV and IPNV have been commercialized in many countries, the prevalence of IHNV and IPNV is still widespread in modern aquaculture. In the present study, two IHNV recombinant viruses displaying IPNV VP2 protein (rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE) were generated using the RNA polymerase Ⅱ system to explore the immunogenicity of IHNV and IPNV. The recombinant IHNV viruses were stable, which was confirmed by sequencing, indirect immunofluorescence assay, western blotting, transmission electron microscopy and viral growth curve assay. IHNV and IPNV challenge showed that the recombinant viruses had high protection rates against IHNV and IPNV with approximately 65% relative percent survival rates. Rainbow trout (mean weight 20 g) vaccinated with these two recombinant viruses showed a high level of antibodies against IHNV and IPNV infection. Taken together, our findings demonstrate that rIHNV-IPNV VP2 and rIHNV-IPNV VP2COE might be promising vaccine candidates against IHNV and IPNV. Copyright © 2018. Published by Elsevier Ltd.

Endoscopic pancreatic necrosectomy.

PubMed

Fogel, Evan L

2011-07-01

Traditionally, patients with symptomatic sterile pancreatic necrosis or infected necrosis have been managed by open surgical debridement and removal of necrotic tissue. Within the last decade, however, reports of endoscopic pancreatic necrosectomy, an alternative minimally invasive approach, have demonstrated high success rates and low mortality rates. This report describes the indications, technique, and study outcome data of the procedure. While our experience with this technique has recently increased, better selection criteria are needed to identify patients who are most suitable for endoscopic therapy.

Endoscopic ultrasound-guided placement of plastic vs. biflanged metal stents for therapy of walled-off necrosis: a retrospective single-center series.

PubMed

Mukai, Shuntaro; Itoi, Takao; Baron, Todd H; Sofuni, Atsushi; Itokawa, Fumihide; Kurihara, Toshio; Tsuchiya, Takayoshi; Ishii, Kentaro; Tsuji, Shujiro; Ikeuchi, Nobuhito; Tanaka, Reina; Umeda, Junko; Tonozuka, Ryosuke; Honjo, Mitsuyoshi; Gotoda, Takuji; Moriyasu, Fuminori; Yasuda, Ichiro

2015-01-01

Recently, a novel fully covered and biflanged metal stent (BFMS)dedicated to the drainage of walled-off necrosis(WON) was developed. The aim of this study was to retrospectively evaluate the safety, efficacy, and cost performance of drainage of WON using the novel BFMS compared with a traditional plastic stent. A total of 70 patients with symptomatic WON were treated under endoscopic ultrasound (EUS) guidance. Initial drainage was conducted using the single gateway technique with placement of one or more plastic stents or a single BFMS.If drainage was unsuccessful,direct endoscopic necrosectomy (DEN)was performed. There were no statistically significant differences in rates of technical success, clinical success,and adverse events between plastics stents and BFMS, despite the size of WON in the BFMS group being significantly larger than that in the plastic stent group (105.6 vs. 77.1 mm; P=0.003).The mean procedure times for the first EUS-guided drainage and for re-intervention were significantly shorter in the BFMS group than in the plastic stent group (28.8±7.1 vs. 42.6±14.2, respectively,for drainage, P<0.001; and 34.9±8.5 vs.41.8±7.6, respectively, for re-intervention, P<0.001). There was no statistically significant difference in the total cost between plastic stent and BFMS use in the treatment of WON ($5352vs. $6274; P=0.25). Plastic stents and BFMS were safe and effective for the treatment of WON. In particular,BFMS placement appeared to be preferable for initial EUS-guided drainage and additional reintervention(e.g. DEN) as it reduced the procedure time. Prospective randomized controlled trials are warranted.

Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. Roles in cell injury processes of pancreatitis.

PubMed

Gukovskaya, Anna S; Gukovsky, Ilya; Jung, Yoon; Mouria, Michelle; Pandol, Stephen J

2002-06-21

Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of which remain unknown. Many characteristics of pancreatitis can be studied in vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We show here that CCK stimulates apoptosis and death signaling pathways in rat pancreatic acinar cells, including caspase activation, cytochrome c release, and mitochondrial depolarization. The mitochondrial dysfunction is mediated by upstream caspases (possibly caspase-8) and, in turn, leads to activation of caspase-3. CCK causes mitochondrial alterations through both permeability transition pore-dependent (cytochrome c release) and permeability transition pore-independent (mitochondrial depolarization) mechanisms. Caspase activation and mitochondrial alterations also occur in untreated pancreatic acinar cells; however, the underlying mechanisms are different. In particular, caspases protect untreated acinar cells from mitochondrial damage. We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells. The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis. Protection against necrosis and trypsin activation by caspases can explain why the severity of pancreatitis in experimental models correlates inversely with the extent of apoptosis.

Acute Pancreatitis: Etiology, Pathology, Diagnosis, and Treatment.

PubMed

Majidi, Shirin; Golembioski, Adam; Wilson, Stephen L; Thompson, Errington C

2017-11-01

Acute pancreatitis is a fascinating disease. In the United States, the two most common etiologies of acute pancreatitis are gallstones and excessive alcohol consumption. The diagnosis of acute pancreatitis is made with a combination of history, physical examination, computed tomography scan, and laboratory evaluation. Differentiating patients who will have a benign course of their pancreatitis from patients who will have severe pancreatitis is challenging to the clinician. C-reactive protein, pro-calcitonin, and the Bedside Index for Severity of Acute Pancreatitis appeared to be the best tools for the early and accurate diagnosis of severe pancreatitis. Early laparoscopic cholecystectomy is indicated for patients with mild gallstone pancreatitis. For patients who are going to have a prolonged hospitalization, enteral nutrition is preferred. Total parenteral nutrition should be reserved for patients who cannot tolerate enteral nutrition. Prophylactic antibiotics are not indicated for patients with pancreatic necrosis. Surgical intervention for infected pancreatic necrosis should be delayed as long as possible to improve patient outcomes.

Oxidative stress alters mitochondrial bioenergetics and modifies pancreatic cell death independently of cyclophilin D, resulting in an apoptosis-to-necrosis shift

PubMed Central

Armstrong, Jane A.; Cash, Nicole J.; Ouyang, Yulin; Morton, Jack C.; Chvanov, Michael; Latawiec, Diane; Awais, Muhammad; Tepikin, Alexei V.; Sutton, Robert; Criddle, David N.

2018-01-01

Mitochondrial dysfunction lies at the core of acute pancreatitis (AP). Diverse AP stimuli induce Ca2+-dependent formation of the mitochondrial permeability transition pore (MPTP), a solute channel modulated by cyclophilin D (CypD), the formation of which causes ATP depletion and necrosis. Oxidative stress reportedly triggers MPTP formation and is elevated in clinical AP, but how reactive oxygen species influence cell death is unclear. Here, we assessed potential MPTP involvement in oxidant-induced effects on pancreatic acinar cell bioenergetics and fate. H2O2 application promoted acinar cell apoptosis at low concentrations (1–10 μm), whereas higher levels (0.5–1 mm) elicited rapid necrosis. H2O2 also decreased the mitochondrial NADH/FAD+ redox ratio and ΔΨm in a concentration-dependent manner (10 μm to 1 mm H2O2), with maximal effects at 500 μm H2O2. H2O2 decreased the basal O2 consumption rate of acinar cells, with no alteration of ATP turnover at <50 μm H2O2. However, higher H2O2 levels (≥50 μm) diminished spare respiratory capacity and ATP turnover, and bioenergetic collapse, ATP depletion, and cell death ensued. Menadione exerted detrimental bioenergetic effects similar to those of H2O2, which were inhibited by the antioxidant N-acetylcysteine. Oxidant-induced bioenergetic changes, loss of ΔΨm, and cell death were not ameliorated by genetic deletion of CypD or by its acute inhibition with cyclosporine A. These results indicate that oxidative stress alters mitochondrial bioenergetics and modifies pancreatic acinar cell death. A shift from apoptosis to necrosis appears to be associated with decreased mitochondrial spare respiratory capacity and ATP production, effects that are independent of CypD-sensitive MPTP formation. PMID:29626097

The clinical value of adipokines in predicting the severity and outcome of acute pancreatitis.

PubMed

Karpavicius, Andrius; Dambrauskas, Zilvinas; Gradauskas, Audrius; Samuilis, Arturas; Zviniene, Kristina; Kupcinskas, Juozas; Brimas, Gintautas; Meckovski, Artur; Sileikis, Audrius; Strupas, Kestutis

2016-08-22

Recent data shows that patients with severe acute pancreatic might benefit from early intensive therapy, enteral nutrition and timely transfer to specialized centers. The early prophylactic use of antibiotics in AP remains controversial. The role and need for new markers in stratification of acute pancreatitis is also uncertain. This study aims to evaluate the prognostic usefulness of adipokines in prediction of the severity and outcome of acute pancreatitis (AP). Prospective study was conducted in four clinical centers. The diagnosis and severity assessment of AP was established according to the revised 2012 Atlanta classification. Adipokines, IL-6 and CRP levels were measured at admission and on 3rd day of hospital stay and compared with the control group. The predictive accuracy of each marker was measured by area under the receiver operating curve. Forty healthy controls and 102 patients were enrolled in to the study. Twenty seven (26.5 %) patients had mild, 55 (53.9 %) - moderate and 20 (19.6 %) - severe AP. Only resistin (cut-off value 13.7 ng/ml) and IL-6 (cut-off value 473.4 pg/ml) were reliable early markers of SAP. IL-6 with cut-off value of 157.0 pg/ml was a predictor of necrosis. The peripancreatic necrosis volume of 112.5 ml was a marker of SAP and 433.0 ml cut-off value could be used to predict the need of interventions. The prognostic value of adipokines in AP is limited. Only admission resistin levels could serve as an early predictor for SAP. The Lithuanian Regional Ethics Committee approved the study protocol (permission No. L-12-02/1/2/3/4) and all the patients and the control group provided written informed consent.

Outbreak of infectious pancreatic necrosis virus (IPNV) in farmed rainbow trout in China.

PubMed

Zhu, Ling; Wang, Xingli; Wang, Kaiyu; Yang, Qian; He, Jie; Qin, Zhenyang; Geng, Yi; Ouyang, Ping; Huang, Xiaoli

2017-06-01

Infectious pancreatic necrosis virus (IPNV) is a member of the Aquabirnavirus genus, which caused mass mortality (nearly 100%) in farmed rainbow trout (Oncorhynchus mykiss) in aquaculture farms in 2016, China. Major clinical signs included decreased appetite, mucous-like stools, and darkened pigmentation. Pathological changes in moribund fish were observed, such as marked vacuolar degeneration of the pancreatic cells with pyknotic nucleus and decreased zymogen granules, severe hemorrhage in the liver, and tumidness of respiratory epithelium in gills. In addition, the tissue fluid of diseased fish could produce a cytopathic effect (CPE) in RTG-2 cells. The presence of specific 206bp fragments by the reverse transcription-polymerase chain reaction (RT-PCR) using tissue homogenate of diseased fish and supernatant of infected cells revealed that IPNV could be confirmed. The pathogenicity test of cell culture supernatant detected cumulative mortality of 80%, and the clinical symptoms observed in the moribund and dead fish were similar to the naturally infected fish. Furthermore, the sequence analysis of VP2 gene showed that the isolated virus strain belonged to genogroup 1, and 97% homology with the Mexican IPNV isolate was found. To our knowledge, this is the first report on IPNV natural infection in the southwest of China. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

PubMed Central

Demirag, Alp; Pastor, Catherine M; Morel, Philippe; Jean-Christophe, Copin; Sielenkämper, Andreas W; Güvener, Nilgun; Mai, Gang; Berney, Thierry; Frossard, Jean-Louis; Bühler, Leo H

2006-01-01

AIM: To investigate the effect of epidural anaesthesia (EA) on pancreatic microcirculation during acute pancreatitis (AP). METHODS: AP was induced by injection of sodium taurocholate into the pancreatic duct of Sprague-Dawley rats. To realize EA, a catheter was introduced into the epidural space between T7 and T9 and bupivacaine was injected. Microcirculatory flow was measured by laser Doppler flowmetry. Arterial blood gas analyses were performed. At the end of the experiment (≤ 5 h), pancreas was removed for histology. The animals were divided into three groups: Group 1 (n = 9), AP without EA; Group 2 (n = 4), EA without AP; and Group 3 (n = 6), AP treated by EA. RESULTS: In Group 1, pancreatic microcirculatory flow prior to AP was 141 ± 39 perfusion units (PU). After AP, microcirculatory flow obviously decreased to 9 ± 6 PU (P < 0.05). Metabolic acidosis developed with base excess (BE) of - 14 ± 3 mmol/L. Histology revealed extensive edema and tissue necrosis. In Group 2, EA did not significantly modify microcirculatory flow. BE remained unchanged and histological analysis showed normal pancreatic tissue. In Group 3, AP initially caused a significant decrease in microcirculatory flow from 155 ± 25 to 11 ± 7 PU (P < 0.05). After initiation of EA, microcirculatory flow obviously increased again to 81 ± 31 PU (P < 0.05). BE was -6 ± 4 mmol/L, which was significantly different compared to Group 1 (P < 0.05). Furthermore, histology revealed less extensive edema and necrosis in pancreatic tissue in Group 3 than that in Group 1. CONCLUSION: AP caused dramatic microcirculatory changes within the pancreas, with development of metabolic acidosis and tissue necrosis. EA allowed partial restoration of microcirculatory flow and prevented development of tissue necrosis and systemic complications. Therefore, EA should be considered as therapeutic option to prevent evolution from edematous to necrotic AP. PMID

Mortality indicators and risk factors for intra-abdominal hypertension in severe acute pancreatitis.

PubMed

Zhao, J G; Liao, Q; Zhao, Y P; Hu, Y

2014-01-01

This study assessed the risk factors associated with mortality and the development of intra-abdominal hypertension (IAH) in patients with severe acute pancreatitis (SAP). To identify significant risk factors, we assessed the following variables in 102 patients with SAP: age, gender, etiology, serum amylase level, white blood cell (WBC) count, serum calcium level, Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, computed tomography severity index (CTSI) score, pancreatic necrosis, surgical interventions, and multiple organ dysfunction syndrome (MODS). Statistically significant differences were identified using the Student t test and the χ (2) test. Independent risk factors for survival were analyzed by Cox proportional hazards regression. The following variables were significantly related to both mortality and IAH: WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, pancreatic necrosis >50%, and MODS. However, it was found that surgical intervention had no significant association with mortality. MODS and pancreatic necrosis >50% were found to be independent risk factors for survival in patients with SAP. Mortality and IAH from SAP were significantly related to WBC count, serum calcium level, serum amylase level, APACHE-II score, CTSI score, pancreatic necrosis, and MODS. However, Surgical intervention did not result in higher mortality. Moreover, MODS and pancreatic necrosis >50% predicted a worse prognosis in SAP patients.

Complete genomic sequence of an infectious pancreatic necrosis virus isolated from rainbow trout (Oncorhynchus mykiss) in China.

PubMed

Ji, Feng; Zhao, Jing-Zhuang; Liu, Miao; Lu, Tong-Yan; Liu, Hong-Bai; Yin, Jiasheng; Xu, Li-Ming

2017-04-01

Infectious pancreatic necrosis (IPN) is a significant disease of farmed salmonids resulting in direct economic losses due to high mortality in China. However, no gene sequence of any Chinese infectious pancreatic necrosis virus (IPNV) isolates was available. In the study, moribund rainbow trout fry samples were collected during an outbreak of IPN in Yunnan province of southwest China in 2013. An IPNV was isolated and tentatively named ChRtm213. We determined the full genome sequence of the IPNV ChRtm213 and compared it with previously identified IPNV sequences worldwide. The sequences of different structural and non-structural protein genes were compared to those of other aquatic birnaviruses sequenced to date. The results indicated that the complete genome sequence of ChRtm213 strain contains a segment A (3099 nucleotides) coding a polyprotein VP2-VP4-VP3, and a segment B (2789 nucleotides) coding a RNA-dependent RNA polymerase VP1. The phylogenetic analyses showed that ChRtm213 strain fell within genogroup 1, serotype A9 (Jasper), having similarities of 96.3% (segment A) and 97.3% (segment B) with the IPNV strain AM98 from Japan. The results suggest that the Chinese IPNV isolate has relative closer relationship with Japanese IPNV strains. The sequence of ChRtm213 was the first gene sequence of IPNV isolates in China. This study provided a robust reference for diagnosis and/or control of IPNV prevalent in China.

Molecular characterization of the VP1 gene of a Mexican isolate of infectious pancreatic necrosis virus.

PubMed

Barrera-Mejía, Magda; Simón-Martínez, José; Ulloa-Arvizu, Raúl; Salgado-Miranda, Celene; Soriano-Vargas, Edgardo

2010-07-01

The presence of infectious pancreatic necrosis virus (IPNV) in salmonids predominantly produces a high mortality rate in first-feeding fry. Genomic analysis of the vp2 gene sequence is most commonly used to determine the genetic diversity of IPNV isolates. Recently, information obtained from the vp1 gene allowed for efficient analysis of the genetic diversity of IPNV. In this study, the vp1 gene from a Mexican IPNV isolate was characterized and compared with IPNV isolates from Europe, North America, and Asia. The results indicate that the Mexican isolate is most closely related genetically to the 2310 strain from Spain.

Endoscopic "step-up approach" using a dedicated biflanged metal stent reduces the need for direct necrosectomy in walled-off necrosis (with videos).

PubMed

Lakhtakia, Sundeep; Basha, Jahangeer; Talukdar, Rupjyoti; Gupta, Rajesh; Nabi, Zaheer; Ramchandani, Mohan; Kumar, B V N; Pal, Partha; Kalpala, Rakesh; Reddy, P Manohar; Pradeep, R; Singh, Jagadish R; Rao, G V; Reddy, D Nageshwar

2017-06-01

EUS-guided drainage using plastic stents may be inadequate for treatment of walled-off necrosis (WON). Recent studies report variable outcomes even when using covered metal stents. The aim of this study was to evaluate the efficacy of a dedicated covered biflanged metal stent (BFMS) when adopting an endoscopic "step-up approach" for drainage of symptomatic WON. We retrospectively evaluated consecutive patients with symptomatic WON who underwent EUS-guided drainage using BFMSs over a 3-year period. Reassessment was done between 48 and 72 hours for resolution. Endoscopic reinterventions were tailored in nonresponders in a stepwise manner. Step 1 encompassed declogging the blocked lumen of the BFMS. In step 2, a nasocystic tube was placed via BFMSs with intermittent irrigation. Step 3 involved direct endoscopic necrosectomy (DEN). BFMSs were removed between 4 and 8 weeks of follow-up. The main outcome measures were technical success, clinical success, adverse events, and need for DEN. Two hundred five WON patients underwent EUS-guided drainage using BFMSs. Technical success was achieved in 203 patients (99%). Periprocedure adverse events occurred in 8 patients (bleeding in 6, perforation in 2). Clinical success with BFMSs alone was seen in 153 patients (74.6%). Reintervention adopting the step-up approach was required in 49 patients (23.9%). Incremental success was achieved in 10 patients with step 1, 16 patients with step 2, and 19 patients with step 3. Overall clinical success was achieved in 198 patients (96.5%), with DEN required in 9.2%. Four patients failed treatment and required surgery (2) or percutaneous drainage (2). The endoscopic step-up approach using BFMSs was safe, effective, and yielded successful outcomes in most patients, reducing the need for DEN. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

PubMed Central

Navina, Sarah; Acharya, Chathur; DeLany, James P.; Orlichenko, Lidiya S.; Baty, Catherine J.; Shiva, Sruti S.; Durgampudi, Chandra; Karlsson, Jenny M.; Lee, Kenneth; Bae, Kyongtae T.; Furlan, Alessandro; Behari, Jaideep; Liu, Shiguang; McHale, Teresa; Nichols, Larry; Papachristou, Georgios Ioannis; Yadav, Dhiraj; Singh, Vijay P.

2012-01-01

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID:22049070

PKD signaling and pancreatitis

PubMed Central

Yuan, Jingzhen; Pandol, Stephen J.

2016-01-01

Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

Natural resolution or intervention for fluid collections in acute severe pancreatitis.

PubMed

Sarathi Patra, P; Das, K; Bhattacharyya, A; Ray, S; Hembram, J; Sanyal, S; Dhali, G K

2014-12-01

Revisions in terminology of fluid collections in acute pancreatitis have necessitated reanalysis of their evolution and outcome. The course of fluid collections in patients with acute pancreatitis was evaluated prospectively. Consecutive adults with acute pancreatitis, who had contrast-enhanced CT (CECT) within 5-7 days of symptom onset, were enrolled in a prospective cohort study in a tertiary-care centre. Patients were treated according to standard guidelines. Follow-up transabdominal ultrasonography was done at 4-week intervals for at least 6 months. CECT was repeated at 6-10 weeks, or at any time if there were new or persistent symptoms. Asymptomatic collections were followed until spontaneous resolution. Risk factors for pancreatic pseudocysts or walled-off necrosis (WON) were assessed in multivariable analyses. Of 122 patients with acute pancreatitis, 109 were analysed. Some 91 patients (83·5 per cent) had fluid collections at baseline. Eleven of 29 with interstitial oedematous pancreatitis had acute peripancreatic fluid collections, none of which evolved into pseudocysts. All 80 patients with acute necrotizing pancreatitis had at least one acute necrotizing collection (ANC); of these, five patients died (2 after drainage), three underwent successful drainage within 5 weeks, and collections resolved spontaneously in 33 and evolved into WON in 39. By 6 months' follow-up, WON had required drainage in eight patients, resolved spontaneously in 23 and was persistent but asymptomatic in seven. Factors associated with increased risk of WON were blood urea nitrogen 20 mg/dl or more (odds ratio (OR) 10·96, 95 per cent c.i. 2·57 to 46·73; P = 0·001) and baseline ANC diameter greater than 6 cm (OR 14·57, 1·60 to 132·35; P = 0·017). Baseline ANC diameter over 6 cm was the only independent predictor of either the need for drainage or persistence of such collections beyond 6 months (hazard ratio 6·61, 1·77 to 24·59; P = 0·005

Histopathological changes in the pancreas of cattle with abdominal fat necrosis

PubMed Central

TANI, Chikako; PRATAKPIRIYA, Watanyoo; TANI, Mineto; YAMAUCHI, Takenori; HIRAI, Takuya; YAMAGUCHI, Ryoji; ANO, Hitoshi; KATAMOTO, Hiromu

2016-01-01

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process. PMID:27795463

Histopathological changes in the pancreas of cattle with abdominal fat necrosis.

PubMed

Tani, Chikako; Pratakpiriya, Watanyoo; Tani, Mineto; Yamauchi, Takenori; Hirai, Takuya; Yamaguchi, Ryoji; Ano, Hitoshi; Katamoto, Hiromu

2017-01-20

The association between pancreatic disorder and abdominal fat necrosis in cattle remains unclear. The pancreases of 29 slaughtered cattle with or without fat necrosis were collected to investigate pathological changes. Japanese Black (JB) cattle were classified into the FN group (with abdominal fat necrosis; n=9) and N group (without fat necrosis; n=5). The pancreases were also collected from 15 Holstein Friesian (HF) cows. All JB cattle showed high body condition scores. Regarding the pathological findings, fatty pancreas which involves adipocyte infiltration into the pancreas and fat necrosis (saponification) were observed in 25 and 27 cases, respectively. Immunohistochemical staining with anti-Iba-1 antibody showed large numbers of macrophages surrounding the saponified fat in the pancreas. CD3-positive T cells were significantly more common in the pancreas of both the FN and N groups compared with the HF group (P<0.05). Furthermore, fibrosis in the pancreas exhibited a correlative tendency with the formation of necrotic fat mass in the peritoneal cavity (P<0.1). These results indicate that obesity leads to increased severity of pancreatic disorder, including fatty pancreas and pancreatitis. The pathological lesions in the pancreas may play a key role in abdominal fat necrosis through the inflammatory process.

Inhibitory effect of aromatic geranyl derivatives isolated from Heliotropium filifolium on infectious pancreatic necrosis virus replication.

PubMed

Modak, Brenda; Sandino, Ana María; Arata, Loredana; Cárdenas-Jirón, Gloria; Torres, René

2010-02-24

Infectious pancreatic necrosis is a disease caused by a birnavirus affecting several wild and commercial aquatic organisms. This infectious disease results in significant losses in the farming industry and therefore effective therapeutic agents are needed to control outbreaks caused by this pathogen. Our goal was to evaluate in vitro antiviral effect of a group of natural compounds (geranyl aromatic derivatives) isolated from the resinous exudate of the plant Heliotropium filifolium (Heliotropiaceae), semi-synthetics compounds obtained from them, and the resinous exudate, on CHSE-214 cell line infected with infectious pancreatic necrosis virus (IPNV) using a virus plaque inhibition assay at various concentrations. The compound ester filifolinyl senecionate was the best antiviral with EC(50) 160 microg/mL and a cytotoxic concentration required to reduce cell viability by 50% up to 400 microg/mL. In order to obtain information about the mechanism of the antiviral action, was evaluated the influence of ester filifolinyl senecionate on the viral RNA synthesis. This compound produced inhibition of the synthesis of viral genomic RNA, suggesting that the ester could be interacting with the viral RNA during the viral cycle. Additionally, a preliminary study of the interaction between ester and a sample of single-stranded RNA was studied at the level of theory Restricted Hartree Fock PM3 method. The results showed that the ester formed hydrogen bonds mainly with nitrogenous bases but not with ribose and phosphate. These results allow propose that the ester filifolinyl senecionate is a good candidate for used as antiviral therapy for IPN virus in salmon fry. Copyright 2009 Elsevier B.V. All rights reserved.

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus).

PubMed

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-05-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors.

Endoscopic treatment of large pancreatic fluid collections (PFC) using self-expanding metallic stents (SEMS) - a two-center experience.

PubMed

Chaves, Dalton Marques; Mönkemüller, Klaus; Carneiro, Fred; Medrado, Bruno; Dos Santos, Marcos; Wodak, Stephanie; Reimão, Sílvia; Sakai, Paulo; de Moura, Eduardo

2014-12-01

Background/study aim: During the last several years, endoscopic ultrasound (EUS)-guided pancreatic fluid collections' (PFC) drainage has evolved into the preferred drainage technique. Recently, self-expanding metallic stents (SEMS) have been used as an alternative to double pigtail stents, with the advantage of providing a larger diameter fistula, thereby decreasing the risk of early obstruction and also allowing for direct endoscopic exploration of the cavity. The aim of this study was to evaluate the technical and clinical success, safety, and outcome of patients undergoing EUS-guided drainage of complex PFC using SEMS. The study was conducted at two tertiary hospitals from January 2010 to January 2013. All patients with PFC referred for endoscopic drainage were enrolled in a prospective database. The inclusion criteria were: (1) patients with pseudocysts or walled-off necrosis based on the revised Atlanta classification; (2) symptomatic patients with thick PFC; (3) PFC that persisted more than 6 weeks; and (4) large PFC diameter (≥ 9 cm). The exclusion criteria consisted of coagulation disorders, PFC bleeding or infection, and failure-to-inform written consent. A total of 16 patients (9 females, 7 males; mean age 52.6, range 20 - 82) underwent EUS drainage with SEMS. There were 14 cases of pseudocysts and 2 cases of walled-off necrosis. The etiologies of the PFC were mainly gallstones (8 of 16 patients, 50 %) and alcohol (5 of 16 patients, 31 %). Technical success was achieved in 100 % of the cases. All patients had a complete resolution of the PFC. Transmural EUS-guided drainage of complex PFC using SEMS is feasible, appears safe, and is efficacious. However, the exchange of the UC (uncovered)-SEMS for plastic stents is mandatory within 1 week. Future prospective studies, preferably multicenter studies, comparing SEMS versus traditional plastic stents for the drainage of PFC are warranted.

Isolation of infectious pancreatic necrosis virus (serotype Ab) from diverse species of estuarine fish

NASA Astrophysics Data System (ADS)

McAllister, P. E.; Newman, M. W.; Sauber, J. H.; Owens, W. J.

1984-03-01

Two significant fish kills occurred in the Pamlico River estuary (North Carolina, USA), one in December 1981 and January 1982, and the other in June 1982. The first involved only the southern flounder (Paralichthys lethostigma). Histopathologic examination of morbid and moribund flounder revealed extensive sloughing and necrosis of the mucosa of the pyloric caeca and intestine, and inflammation of the submucosa of the pyloric caeca. Brain and internal organ homogenates from morbid and moribund flounder were assayed on CHSE-214 cells, and a virus was isolated. Virus titers ranged from≤8.4 · 102 to 6.3 · 107 TCID50 per gram of tissue. Cross-plaque neutralization assays indicated that the southern flounder virus was infectious pancreatic necrosis virus serotype Ab. Immersion challenge showed the isolate is only slightly virulent for fry of brook trout (Salvelinus fontinalis). The second fish kill involved the southern flounder and six other species: hogchoker (Trinectes maculatus), Atlantic silverside (Menidia menidia), spot (Leiostomus xanthurus), Atlantic croaker (Micropogon undulatus), silver perch (Bairdiella chrysura), and striped mullet (Mugil cephalus). Virus was isolated from southern founder, hogchoker, Atlantic silverside, and spot. Neutralization assays indicated that the four isolates were nearly identical; however, the diversity of species affected suggests that the virus might not have been the specific cause of mortality.

[PREVENTION AND CORRECTION OF PULMONARY COMPLICATIONS FOR SEVERE ACUTE PANCREATITIS].

PubMed

Fedorkiv, M B

2015-06-01

Increased of proinflammatory cytokines levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) on severe acute pancreatitis causes vasodilatation, increased permeability of the wall, accumulation of fluid in lung tissue and pleural sinuses. Transudate from acute parapancreatyc clusters of hot liquid and abdomen falls into the chest cavity through microscopic defects in the diaphragm due to the formation of pathological pleural-peritoneal connections or the relevant pressure gradient between the abdominal and pleural cavities. Remediation and removal of acute parapancreatyc clusters combined with the use of a multicomponent drug infusion therapy Cytoflavin provide a reduction in the frequency of pulmonary complications of acute pancreatitis from 48.3 to 31.0%. Use of the drug Cytoflavin reduces the severity of endogenous intoxication and mortality from acute lung injury from 12.9 to 6.1%.

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.

PubMed

Ammann, R W; Heitz, P U; Klöppel, G

1996-07-01

The pathogenesis of alcoholic chronic pancreatitis and its relationship to alcoholic acute pancreatitis are debated. According to our recent clinical long-term study, alcoholic chronic pancreatitis seems to evolve from severe acute pancreatits. The aim of this study was to correlate clinical findings to the pancreatic histopathology at early and advanced stages of the disease. Morphological changes (pseudocysts, autodigestive necrosis, calcification, and perilobular and intralobular fibrosis) were recorded in 37 surgical and 46 postmortem pancreas specimens of 73 patients from our long-term series, who progressed from clinically acute to chronic pancreatitis (mean follow-up, 12 years). Pancreatic function was monitored at yearly intervals. Surgical interventions were performed at a mean of 4.1 years from onset. Histologically, focal necrosis (49%) and mild perilobular fibrosis (54%) predominated, Pseudocysts (n = 41, mostly postnecrotic) occurred in 88% within 6 years from onset. Autopsy specimens were obtained at a mean of 12 years. These pancreata often showed severe perilobular and intralobular fibrosis (85%) and calcifications (74%), but rarely necrosis (4%). Fibrosis correlated with progressive pancreatic dysfunction (P < 0.001), particularly in the 10 patients with two histological assessments (mean interval between biopsy and autopsy, 8 years). The data support an evolution from severe alcoholic acute pancreatitis to chronic pancreatitis.

Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma.

PubMed

Zhao, Xianda; Fan, Wei; Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

2016-12-06

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma.

The effect of activated protein C on experimental acute necrotizing pancreatitis

PubMed Central

Yamenel, Levent; Mas, Mehmet Refik; Comert, Bilgin; Isik, Ahmet Turan; Aydin, Sezai; Mas, Nuket; Deveci, Salih; Ozyurt, Mustafa; Tasci, Ilker; Unal, Tahir

2005-01-01

Introduction Acute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis. Materials and method Forty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured. Results Acute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis

Fatal hemorrhagic-necrotizing pancreatitis associated with pancreatic and hepatic lipidosis in an obese Asian palm civet (Paradoxurus hermaphroditus)

PubMed Central

Laura, Bongiovanni; Nicola, Di Girolamo; Alessandro, Montani; Leonardo, Della Salda; Paolo, Selleri

2014-01-01

Asian palm civets (Paradoxurus hermaphroditus), or toddy cats, belong to the family Viverridae. Little is known about the pathology of these animals and few articles have been published, mainly concerning their important role as wild reservoir hosts for severe infectious diseases of domestic animals and human beings. A 4-year-old, female Asian palm civet was found dead by the owner. At necropsy, large amount of adipose tissue was found in the subcutis and in the peritoneal cavity. Most of the pancreas appeared red, translucent. Hepatomegaly, discoloration of the liver were evident, with multifocal areas of degeneration, characterized by white nodular lesions. Histologically, the pancreas showed severe interstitial and perilobular necrosis and extensive haemorrhages, with separation of the interstitium, mild reactive inflammation at the periphery of the pancreatic lobules. Liver showed multifocal foci of vacuolar degeneration, lipidic accumulation, sometimes associated to hepatocyte necrosis. A diagnosis of acute severe hemorrhagic-necrotizing pancreatitis (or acute pancreatic necrosis) associated with pancreatic and hepatic lipidosis was made. To the best of our knowledge, this represents the first case report of acute lethal pancreatitis in an Asian palm civet. Although the exact cause of the disease remains undetermined, a hypothesis of the cause and pathogenesis is discussed, pointing out dietary indiscretion and consequent overweight as possible important risk factors. PMID:25183148

IMMUNOMODULATION AND TREATMENT OF ACUTE DESTRUCTIVE PANCREATITIS IN A MULTIDISCIPLINARY SURGICAL HOSPITAL.

PubMed

Vinokurov, M M; Saveliev, V V; Gogolev, N M; Yalynskya, T V

2015-01-01

This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital No2-Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications--sterile pancreatic necrosis phase--from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality--from 17.6% to 7.2% lethality in patients with non-operated group--from 15.6% to 2.2% lethality in the group of patients operated--18.4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%.

Asparaginase-associated pancreatitis in children.

PubMed

Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

2012-10-01

l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis. © 2012 Blackwell Publishing Ltd.

Acute pancreatitis.

PubMed

Talukdar, Rupjyoti; Vege, Santhi S

2015-09-01

To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

Study of RNA-A Initiation Translation of The Infectious Pancreatic Necrosis Virus.

PubMed

Rivas-Aravena, Andrea; Muñoz, Patricio; Jorquera, Patricia; Diaz, Alvaro; Reinoso, Claudia; González-Catrilelbún, Sebastián; Sandino, Ana María

2017-08-15

The infectious pancreatic necrosis virus (IPNV) is a salmonid pathogen that causes significant economic losses to the aquaculture industry. IPNV is a non-enveloped virus containing two uncapped and non-polyadenylated double strand RNA genomic segments, RNA-A and RNA-B. The viral protein Vpg is covalently attached to the 5' end of both segments. There is little knowledge about its viral cycle, particularly about the translation of the RNAs. Through experiments using mono and bicistronic reporters, in this work we show that the 120-nucleotide-long 5'-UTR of RNA-A contains an internal ribosome entry site (IRES) that functions efficiently both in vitro and in salmon cells. IRES activity is strongly dependent on temperature. Also, the IRES structure is confined to the 5'UTR and is not affected by the viral coding sequence. This is the first report of IRES activity in a fish virus and can give us tools to generate antivirals to attack the virus without affecting fish directly. Copyright © 2017. Published by Elsevier B.V.

Inhibiting tumor necrosis factor-alpha diminishes desmoplasia and inflammation to overcome chemoresistance in pancreatic ductal adenocarcinoma

PubMed Central

Xu, Zhigao; Chen, Honglei; He, Yuyu; Yang, Gui; Yang, Gang; Hu, Hanning; Tang, Shihui; Wang, Ping; Zhang, Zheng; Xu, Peipei; Yu, Mingxia

2016-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancer death reasons. Anti-tumor necrosis factor-alpha (TNF-α) antibodies have shown promising effects in PDAC pre-clinical models. However, the prognostic values of TNF-α, underlying mechanisms by which anti-TNF-α treatments inhibit PDAC, and potential synergistic effects of anti-TNF-α treatments with chemotherapy are still unclear. Results and Methods To identify the targeting values of TNF-α in PDAC, we measured TNF-α expression in different stages of PDAC initiation and evaluated its prognostic significance in a pancreatic cancer cohort. We found that TNF-α expression elevated in PDAC initiation process, and high expression of TNF-α was an independent prognostic marker of poor survival. We further evaluated anti-tumor effects of anti-TNF-α treatments in PDAC. Anti-TNF-α treatments resulted in decreased cell viability in both PDAC tumor cells and pancreatic satellite cells in similar dose in vitro. In vivo, anti-TNF-α treatments showed effects in reducing desmoplasia and the tumor promoting inflammatory microenvironment in PDAC. Combination of anti-TNF-α treatments with chemotherapy partly overcame chemoresistance of PDAC tumor cells and prolonged the survival of PDAC mouse model. Conclusions In conclusion, our findings indicated that TNF-α in PDAC can be a prognostic and therapeutic target. Inhibition of TNF-α synergized with chemotherapy in PDAC resulted in better pre-clinical responses via killing tumor cells as well as diminishing desmoplasia and inflammation in PDAC tumor stroma. PMID:27835602

Laparoscopic necrosectomy in acute necrotizing pancreatitis: Our experience

PubMed Central

Mathew, Mittu John; Parmar, Amit Kumar; Sahu, Diwakar; Reddy, Prasanna Kumar

2014-01-01

CONTEXT: Pancreatic necrosis is a local complication of acute pancreatitis. The development of secondary infection in pancreatic necrosis is associated with increased mortality. Pancreatic necrosectomy is the mainstay of invasive management. AIMS: Surgical approach has significantly changed in the last several years with the advent of enhanced imaging techniques and minimally invasive surgery. However, there have been only a few case series related to laparoscopic approach, reported in literature to date. Herein, we present our experience with laparoscopic management of pancreatic necrosis in 28 patients. MATERIALS AND METHODS: A retrospective study of 28 cases [20 men, 8 women] was carried out in our institution. The medical record of these patients including history, clinical examination, investigations, and operative notes were reviewed. The mean age was 47.8 years [range, 23-70 years]. Twenty-one patients were managed by transgastrocolic, four patients by transgastric, two patients by intra-cavitary, and one patient by transmesocolic approach. RESULTS: The mean operating time was 100.8 min [range, 60-120 min]. The duration of hospital stay after the procedure was 10-18 days. Two cases were converted to open (7.1%) because of extensive dense adhesions. Pancreatic fistula was the most common complication (n = 8; 28.6%) followed by recollection (n = 3; 10.7%) and wound infection (n = 3; 10.7%). One patient [3.6%] died in postoperative period. CONCLUSIONS: Laparoscopic pancreatic necrosectomy is a promising and safe approach with all the benefits of minimally invasive surgery and is found to have reduced incidence of major complications and mortality. PMID:25013328

Thermal inactivation of infectious pancreatic necrosis virus in a peptone-salt medium mimicking the water-soluble phase of hydrolyzed fish by-products.

PubMed

Nygaard, Halvor; Modahl, Ingebjørg; Myrmel, Mette

2012-04-01

Infectious pancreatic necrosis virus (IPNV) (serotype Sp) was exposed to temperatures between 60 and 90°C in a medium mimicking the water-soluble phase of hydrolyzed fish by-products. D values ranged from 290 to 0.5 min, and the z value was approximately 9.8°C. Addition of formic acid to create a pH 4 medium did not enhance heat inactivation. Predicted inactivation effects at different temperature-time combinations are provided.

Necrotizing pancreatitis: new definitions and a new era in surgical management.

PubMed

Rosenberg, Andrew; Steensma, Elizabeth A; Napolitano, Lena M

2015-02-01

Necrotizing pancreatitis is a challenging condition that requires surgical treatment commonly and is associated with substantial morbidity and mortality. Over the past decade, new definitions have been developed for standardization of severity of acute and necrotizing pancreatitis, and new management techniques have emerged based on prospective, randomized clinical trials. Review of English-language literature. A new international classification of acute pancreatitis has been developed by PANCREA (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace the Atlanta Classification. It is based on the actual local (whether pancreatic necrosis is present or not, whether it is sterile or infected) and systemic determinants (whether organ failure is present or not, whether it is transient or persistent) of severity. Early management requires goal-directed fluid resuscitation (with avoidance of over-resuscitation and abdominal compartment syndrome), assessment of severity of pancreatitis, diagnostic computed tomography (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic antibiotics are required for treatment of documented infected pancreatic necrosis. The initial treatment of infected pancreatic necrosis is percutaneous catheter or endoscopic (transgastric/transduodenal) drainage with a second drain placement as required. Lack of clinical improvement after these initial procedures warrants consideration of minimally invasive techniques for pancreatic necrosectomy including video-assisted retroperitoneal debridement (VARD), minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial morbidity, but to date no randomized trial has documented superiority of either

P-HPB-21: Isolated pancreatic tuberculosis mimicking inoperable pancreatic cancer

PubMed Central

Sahu, Manoj Kumar; Singh, Ayashkanta; Behera, Debasmita; Behera, Manas; Narayan, Jimmy

2017-01-01

Background: Pancreatic tuberculosis is an uncommon disease, presenting as hypoechoic mass on imaging mimicking malignancy. Consequently, it represents a diagnostic challenge necessitating a tissue diagnosis. Case Report: A 75-year-old female presented with progressive jaundice and weight loss; imaging with computed tomography (CT) showed a large (5.8 cm × 4.6 cm) pancreatic head mass with encasement of portal and superior mesenteric veins, peripancreatic nodes, atrophic pancreatic parenchyma, and dilated main pancreatic duct. Cancer antigen 19-9 was moderately elevated. With a diagnosis of inoperable pancreatic malignancy, she was planned for tissue diagnosis and palliative chemotherapy. Endoscopic ultrasonography (EUS) showed a heterogeneous mass with vascular invasion as in the CT. Fine needle aspiration (FNA) and biliary decompression with a plastic stent performed in the same sitting. Cytology demonstrated granuloma with caseous necrosis and presence of acid-fast bacilli. Antituberculosis treatment was started, and repeat CT after 6 months showed resolution of the mass. Discussion and Conclusion: A diagnosis of isolated pancreatic tuberculosis is rare and is difficult by clinical presentation alone; in India, it should be considered as a differential diagnosis of a pancreatic tumor. Benign lesions can also present with vascular invasions mimicking inoperable malignancy. EUS FNA is a very useful tool in accurate diagnosis of pancreatic head mass avoiding unnecessary surgeries.

Resolving external pancreatic fistulas in patients with disconnected pancreatic duct syndrome: using rendezvous techniques to avoid surgery (with video).

PubMed

Irani, Shayan; Gluck, Michael; Ross, Andrew; Gan, S Ian; Crane, Robert; Brandabur, John J; Hauptmann, Ellen; Fotoohi, Mehran; Kozarek, Richard A

2012-09-01

An external pancreatic fistula (EPF) generally results from an iatrogenic manipulation of a pancreatic fluid collection (PFC), such as walled-off pancreatic necrosis (WOPN). Severe necrotizing pancreatitis can lead to complete duct disruption, causing disconnected pancreatic duct syndrome (DPDS) with viable upstream pancreas draining out of a low-pressure fistula created surgically or by a percutaneous catheter. The EPF can persist for months to years, and distal pancreatectomy, often the only permanent solution, carries a high morbidity and defined mortality. To describe 3 endoscopic and percutaneous rendezvous techniques to completely resolve EPFs in the setting of DPDS. A retrospective review of a prospective database of 15 patients who underwent rendezvous internalization of EPFs. Tertiary-care pancreatic referral center. Fifteen patients between October 2002 and October 2011 with EPFs in the setting of DPDS and resolved WOPN. Three rendezvous techniques that combined endoscopic and percutaneous procedures to internalize EPFs by transgastric, transduodenal, or transpapillary methods. EPF resolution and morbidity. Fifteen patients (12 men) with a median age of 51 years (range 24-65 years) with EPFs and DPDS (cutoff/blowout of pancreatic duct, with inability to demonstrate upstream body/tail of pancreas on pancreatogram) resulting from severe necrotizing pancreatitis underwent 1 of 3 rendezvous procedures to eliminate the EPFs. All patients were either poor surgical candidates or refused surgery. At the time of the rendezvous procedure, WOPN had fully resolved, DPDS was confirmed on pancreatography, and the EPF had persisted for a median of 5 months (range 1-48 months), producing a median output of 200 mL/day (range 50-700 mL/day). The rendezvous technique in 10 patients used the existing percutaneous drainage fistula to puncture into the stomach/duodenum to deliver wires that were captured endoscopically. The transenteric fistula was dilated and two

Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome caused by post-pancreatitis pseudocyst with mesenteric fistula. Diagnosis and successful surgical treatment. Case report and review of literature.

PubMed

Dieker, Wulf; Derer, Johannes; Henzler, Thomas; Schneider, Alexander; Rückert, Felix; Wilhelm, Torsten J; Krüger, Bernd

2017-01-01

Pancreatitis, panniculitis and polyarthritis syndrome is a very rare extra-pancreatic complication of pancreatic diseases. While in most cases this syndrome is caused by acute or chronic pancreatitis, we report a case of a 62-year-old man presenting with extensive intraosseous fat necrosis, polyarthritis and panniculitis caused by a post-pancreatitis pseudocyst with a fistula to the superior mesenteric vein and extremely high blood levels of lipase. This became symptomatic 2.5 years after an episode of acute pancreatitis and as in most cases abdominal symptoms were absent. Treatment by surgical resection of the pancreatic head with the pseudocyst and mesenteric fistula led to complete remission of all symptoms. A review of the literature revealed that all publications are limited to case reports. Most authors hypothesize that an unspecific damage can cause a secretion of pancreatic enzymes to the bloodstream leading to a systemic lipolysis and fat tissue necrosis, especially of subcutaneous tissue, bone marrow, inducing panniculitis, polyarthritis and osteonecrosis. Even if caused by an acute pancreatitis abdominal symptoms are often mild or absent in most cases leading to misdiagnosis and poor prognosis. While symptomatic treatment with NSAR and cortisone showed poor to moderate response, causal treatment can be successful depending on the underlying pancreatic disease. Copyright © 2017. Published by Elsevier Ltd.

Endoscopic management of pancreatic fluid collections-revisited

PubMed Central

Nabi, Zaheer; Basha, Jahangeer; Reddy, D Nageshwar

2017-01-01

The development of pancreatic fluid collections (PFC) is one of the most common complications of acute severe pancreatitis. Most of the acute pancreatic fluid collections resolve and do not require endoscopic drainage. However, a substantial proportion of acute necrotic collections get walled off and may require drainage. Endoscopic drainage of PFC is now the preferred mode of drainage due to reduced morbidity and mortality as compared to surgical or percutaneous drainage. With the introduction of new metal stents, the efficiency of endoscopic drainage has improved and the task of direct endoscopic necrosectomy has become easier. The requirement of re-intervention is less with new metal stents as compared to plastic stents. However, endoscopic drainage is not free of adverse events. Severe complications including bleeding, perforation, sepsis and embolism have been described with endoscopic approach to PFC. Therefore, the endoscopic management of PFC is a multidisciplinary affair and involves interventional radiologists as well as GI surgeons to deal with unplanned adverse events and failures. In this review we discuss the recent advances and controversies in the endoscopic management of PFC. PMID:28487603

Necrosis of the tail of pancreas following proximal splenic artery embolization

PubMed Central

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-01-01

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. PMID:27177891

High incidence of coagualopathy in phase II studies of recombinant tumor necrosis factor in advanced pancreatic and gastric cancers.

PubMed

Muggia, F M; Brown, T D; Goodman, P J; Macdonald, J S; Hersh, E M; Fleming, T R; Leichman, L

1992-06-01

This multi-center trial was carried out to assess the therapeutic potential of recombinant tumor necrosis factor (rTNF) as the first form of systemic therapy for advanced carcinomas of gastric and pancreatic origin. To be eligible patients were required to have no overt sign of coagulopathy and hepatic function studies with enzymes less than two times beyond the normal range. Twenty nine patients with gastric cancer and 26 with pancreatic cancer were entered from various institutions in the Southwest Oncology Group with 27 and 22, respectively, meeting eligibility criteria. Drug treatment consisted of rTNF (Genentech) given at a dose of 150 micrograms intravenously for five consecutive days every 3 weeks; 50% dose reduction was made for acute intolerance such as hypotension or severe fever and chills. Although eight patients with gastric cancer and five patients with pancreatic cancer received four or more courses of treatment, no objective antitumor responses were recorded. As in other trials common toxicities of rTNF included nausea and vomiting, chills and fever, hypotension, headache, myalgias, fatigue and malaise. However, in this trial, other toxicities became prominent: four episodes of symptomatic disseminated intravascular clotting occurred among patients with pancreatic cancer. Eleven with this disease and five with gastric cancer manifested laboratory findings of abnormal amounts of fibrin split products, and/or hypofibrinogenemia, and/or thrombocytopenia after treatment began. Other laboratory abnormalities that were commonly encountered included hyperglycemia, hypertriglyceridemia, anemia, neutropenia and an elevation in liver enzymes. We conclude that rTNF does not demonstrate antitumor efficacy against adenocarcinomas of the stomach and the pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

PubMed

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the

Novel findings in the management of acute pancreatitis.

PubMed

Bolado, Federico; de-Madaria, Enrique

2016-09-01

Acute pancreatitis (AP) is a potentially serious disease whose incidence is on the increase. Pancreas divisum does not meet the required criteria to be considered an aetiological factor. Sphincter of Oddi dysfunction may be another cause of idiopathic AP. Less invasive methods cannot replace Sphincter of Oddi manometry in diagnosis. Almost half of patients with systemic inflammatory response syndrome develop organ failure, but the mechanisms involved are not completely understood. Obesity is a risk factor for severity in AP; the cause could be the presence of free unsaturated fatty acids, which have pro-inflammatory activity. Prognosis is better in patients with isolated extra-pancreatic necrosis than in those with parenchymal necrosis or with both. The mortality rate among those with infected pancreatic necrosis is 15-20%. The "moderately severe" group is widely heterogeneous and this category may require redefinition. Laparoscopic treatment of pseudocysts is an alternative to endoscopic drainage and could be the first-line option in patients requiring cholecystectomy. The use of lumen-apposing metal stents to treat pancreatic necrosis is cost-effective. Quality of life in some patients following an attack of AP is significantly impaired even at 1 year. Aggressive fluid therapy is not superior to standard fluid therapy in preventing post-ERCP AP. The role of statins in AP prevention is still unclear. Aggressive fluid resuscitation and the use of lactated Ringer solution seem to be beneficial in the treatment of AP. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Efficacy of certain disinfectants against infectious pancreatic necrosis virus

USGS Publications Warehouse

Elliott, Diane G.; Amend, Donald F.

1978-01-01

The virucidal properties of iodophor, chlorine (sodium hypochlorite), formalin, thimerosal (organic mercurial compound), malachite green, and acriflavine were tested on infectious pancreatic necrosis virus (IPNV). Iodine and chlorine showed good activity, but efficacy depended on the concentration of virus, the presence of organic matter (calf serum), and water pH. Water hardness (0-300 mg 1−1 as CaCO3) did not affect virucidal activity. In a 5 min exposure, 4 mg 1−1available iodine inactivated 103.9 TCID50 m1−1 IPNV but 16 mg 1−1 iodine were needed for inactivation of 106.3TCID50m1−1. The addition of 0-5% calf serum significantly reduced the iodine concentration and the virucidal activity. In comparison, 4 mg 1−1 chlorine were needed to inactivate 1046 TCID50 m1−1 IPNV in 5 min. However, the addition of 0-07 % serum greatly reduced the chlorine concentration and extended the virucidal contact time to 30 min or more. IPNV at 106.3 TCID60 m1−1 was not inactivated by exposures for 60 min to 0-2% formalin, 10 min to 0-2% thimerosal, 60 min to 5 mg 1−1 malachite green, or 20 min to 500 mg 1−1 acriflavine. However, acriflavine at 0-5 mg 1−1 in cell culture media prevented the development of cytopathology caused by IPNV and may be useful in the treatment of the disease.

Necrotizing pancreatitis: challenges and solutions.

PubMed

Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

2016-01-01

Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications.

UNDERSTANDING THE INTERNATIONAL CONSENSUS FOR ACUTE PANCREATITIS: CLASSIFICATION OF ATLANTA 2012

PubMed Central

de SOUZA, Gleim Dias; SOUZA, Luciana Rodrigues Queiroz; CUENCA, Ronaldo Máfia; JERÔNIMO, Bárbara Stephane de Medeiros; de SOUZA, Guilherme Medeiros; VILELA, Vinícius Martins

2016-01-01

ABSTRACT Introduction: Contrast computed tomography and magnetic resonance imaging are widely used due to its image quality and ability to study pancreatic and peripancreatic morphology. The understanding of the various subtypes of the disease and identification of possible complications requires a familiarity with the terminology, which allows effective communication between the different members of the multidisciplinary team. Aim: Demonstrate the terminology and parameters to identify the different classifications and findings of the disease based on the international consensus for acute pancreatitis ( Atlanta Classification 2012). Methods: Search and analysis of articles in the "CAPES Portal de Periódicos with headings "acute pancreatitis" and "Atlanta Review". Results: Were selected 23 articles containing radiological descriptions, management or statistical data related to pathology. Additional statistical data were obtained from Datasus and Population Census 2010. The radiological diagnostic criterion adopted was the Radiology American College system. The "acute pancreatitis - 2012 Rating: Review Atlanta classification and definitions for international consensus" tries to eliminate inconsistency and divergence from the determination of uniformity to the radiological findings, especially the terminology related to fluid collections. More broadly as "pancreatic abscess" and "phlegmon" went into disuse and the evolution of the collection of patient fluids can be described as "acute peripancreatic collections", "acute necrotic collections", "pseudocyst" and "necrosis pancreatic walled or isolated". Conclusion: Computed tomography and magnetic resonance represent the best techniques with sequential images available for diagnosis. Standardization of the terminology is critical and should improve the management of patients with multiple professionals care, risk stratification and adequate treatment. PMID:27759788

Acute and chronic pancreatitis: surgical management.

PubMed

Dzakovic, Alexander; Superina, Riccardo

2012-08-01

Pancreatitis is becoming increasingly prevalent in children, posing new challenges to pediatric health care providers. Although some general adult treatment paradigms are applicable in the pediatric population, diagnostic workup and surgical management of acute and chronic pancreatitis have to be tailored to anatomic and pathophysiological entities peculiar to children. Nonbiliary causes of acute pancreatitis in children are generally managed nonoperatively with hydration, close biochemical and clinical observation, and early initiation of enteral feeds. Surgical intervention including cholecystectomy or endoscopic retrograde cholangiopancreatography is often required in acute biliary pancreatitis, whereas infected pancreatic necrosis remains a rare absolute indication for pancreatic debridement and drainage via open, laparoscopic, or interventional radiologic procedure. Chronic pancreatitis is characterized by painful irreversible changes of the parenchyma and ducts, which may result in or be caused by inadequate ductal drainage. A variety of surgical procedures providing drainage, denervation, resection, or a combination thereof are well established to relieve pain and preserve pancreatic function. Copyright © 2012. Published by Elsevier Inc.

A low-cost through-the-wall FMCW radar for stand-off operation and activity detection

NASA Astrophysics Data System (ADS)

Chetty, Kevin; Chen, Qingchao; Ritchie, Matthew; Woodbridge, Karl

2017-05-01

In this paper we present a new through-wall (TW) FMCW radar system. The architecture of the radar enables both high sensitivity and range resolutions of <1.5 m. Moreover, the radar employs moving target indication (MTI) signal processing to remove the problematic primary wall reflection, allowing higher signal-to- noise and signal-to-interference ratios, which can be traded-off for increased operational stand-off. The TW radar operates at 5.8 GHz with a 200 MHz bandwidth. Its dual-frequency design minimises interference from signal leakage, and permits a baseband output after deramping which is digitized using an inexpensive 24-bit off-the-shelf sound card. The system is therefore an order of magnitude lower in cost than competitor ultrawideband (UWB) TW systems. The high sensitivity afforded by this wide dynamic range has allowed us to develop a wall removal technique whereby high-order digital filters provide a flexible means of MTI filtering based on the phases of the returned echoes. Experimental data demonstrates through-wall detection of individuals and groups of people in various scenarios. Target positions were located to within +/-1.25 m in range, allowing us distinguish between two closely separated targets. Furthermore, at 8.5 m standoff, our wall removal technique can recover target responses that would have otherwise been masked by the primary wall reflection, thus increasing the stand-off capability of the radar. Using phase processing, our experimental data also reveals a clear difference in the micro-Doppler signatures across various types of everyday actions

Factors and outcomes associated with pancreatic duct disruption in patients with acute necrotizing pancreatitis.

PubMed

Jang, Ji Woong; Kim, Myung-Hwan; Oh, Dongwook; Cho, Dong Hui; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung Koo; Moon, Sung-Hoon

Acute necrotizing pancreatitis (ANP) can affect main pancreatic duct (MPD) as well as parenchyma. However, the incidence and outcomes of MPD disruption has not been well studied in the setting of ANP. This retrospective study investigated 84 of 465 patients with ANP who underwent magnetic resonance cholangiopancreatography and/or endoscopic retrograde cholangiopancreatography. The MPD disruption group was subclassified into complete and partial disruption. MPD disruption was documented in 38% (32/84) of the ANP patients. Extensive necrosis, enlarging/refractory pancreatic fluid collections (PFCs), persistence of amylase-rich output from percutaneous drainage, and amylase-rich ascites/pleural effusion were more frequently associated with MPD disruption. Hospital stay was prolonged (mean 55 vs. 29 days) and recurrence of PFCs (41% vs. 14%) was more frequent in the MPD disruption group, although mortality did not differ between ANP patients with and without MPD disruption. Subgroup analysis between complete disruption (n = 14) and partial disruption (n = 18) revealed a more frequent association of extensive necrosis and full-thickness glandular necrosis with complete disruption. The success rate of endoscopic transpapillary pancreatic stenting across the stricture site was lower in complete disruption (20% vs. 92%). Patients with complete MPD disruption also showed a high rate of PFC recurrence (71% vs. 17%) and required surgery more often (43% vs. 6%). MPD disruption is not uncommon in patients with ANP with clinical suspicion on ductal disruption. Associated MPD disruption may influence morbidity, but not mortality of patients with ANP. Complete MPD disruption is often treated by surgery, whereas partial MPD disruption can be managed successfully with endoscopic transpapillary stenting and/or transmural drainage. Further prospective studies are needed to study these items. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Severe acute pancreatitis and pregnancy.

PubMed

Robertson, K W; Stewart, I S; Imrie, C W

2006-01-01

For most patients with pregnancy-associated pancreatitis there is little maternal survival threat and only occasionally are there foetal deaths. We describe 4 young women with pregnancy-associated severe acute pancreatitis who each had gallstones. Their ages were 17, 18, 20 and 24 years. Each was a tertiary referral to our unit in Glasgow and each pursued a life-threatening course with hospital stays ranging from 37 to 90 days. One patient required pancreatic necrosectomy for infected necrosis, another had percutaneous management of a pancreatic abscess and 2 had cystogastrostomy as treatment for pancreatic pseudocyst. All underwent early endoscopic sphincterotomy and later cholecystectomy. It is important to be aware that pregnancy-associated acute pancreatitis may be severe, posing a survival threat even in the youngest patients. Gallstones, as we reported almost 20 years ago, are the most common aetiological factor in such patients. Copyright (c) 2006 S. Karger AG, Basel and IAP.

Power break off in a bulb turbine: wall pressure sensor investigation

NASA Astrophysics Data System (ADS)

Duquesne, P.; Maciel, Y.; Aeschlimann, V.; Ciocan, G. D.; Deschênes, C.

2014-03-01

A measurement campaign using unsteady wall pressure sensors on a bulb turbine draft tube was performed over the power and efficiency break off range of a N11 curve. This study is part of the BulbT project, undertaken by the Consortium on hydraulic machines and the LAMH (Hydraulic Machine Laboratory of Laval University). The chosen operating points include the best efficiency point for a high runner blade angle and a high N11. Three other points, with the same N11, have been selected in the break off zone of the efficiency curve. Flow conditions have been set using the guide vanes while the runner blade angle remained constant. The pressure sensors were developed from small piezoresistive chips with high frequency response. The calibration gave an instrumental error lower than 0.3% of the measurement range. The unsteady wall pressure was measured simultaneously at 13 locations inside the first part of the draft tube, which is conical, and at 16 locations in the circular to rectangular transition part just downstream. It was also measured at 11 locations along a streamwise line path at the bottom left part of the draft tube, where flow separation occurs, covering the whole streamwise extent of the draft tube. For seven radial-azimuthal planes, four sensors were distributed azimuthally. As confirmed by tuft visualizations, the break off phenomenon is correlated to the presence of flow separation inside the diffuser at the wall. The break off is linked to the appearance of a large recirculation in the draft tube. The efficiency drop increases with the size of the separated region. Analysis of the draft tube pressure coefficients confirms that the break off is related to diffuser losses. The streamwise evolution of the mean pressure coefficient is analyzed for the different operating conditions. An azimuthal dissymmetry of the mean pressure produced by the separation is detected. The pressure signals have been analyzed and used to track the separation zone depending on

Redox signaling in acute pancreatitis

PubMed Central

Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

2015-01-01

Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

Necrosis of the tail of pancreas following proximal splenic artery embolization.

PubMed

Talving, Peep; Rauk, Mariliis; Vipp, Liisa; Isand, Karl-Gunnar; Šamarin, Aleksandr; Põder, Kalle; Rätsep, Indrek; Saar, Sten

2016-05-13

The current case report presents a rare complication of a significant pancreatic tail necrosis following proximal splenic artery embolization in a 32-year-old male patient involved in a motorcycle accident. Proximal angiographic embolization of the splenic injury after trauma is a widely accepted method with excellent success rate; however, possible complications may occur and has been described in the literature. Nevertheless, only a few case reports pertinent to clinically significant pancreatic tail necrosis after the SAE has been reported. Thus, we add a case report to the scarce literature pertinent to this detrimental and rare complication. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

The impact of an underground cut-off wall on nutrient dynamics in groundwater in the lower Wang River watershed, China.

PubMed

Kang, Pingping; Xu, Shiguo

2017-03-01

Underground cut-off walls in coastal regions are mainly used to prevent saltwater intrusion, but their impact on nutrient dynamics in groundwater is not clear. In this study, a combined analysis of multiple isotopes ([Formula: see text]) and nitrogen and phosphorus concentrations is used in order to assess the impact of the underground cut-off walls on the nutrient dynamics in groundwater in the lower Wang River watershed, China. Compared with the nitrogen and phosphorus concentrations in groundwater downstream of the underground cut-off walls, high [Formula: see text] and total dissolved nitrogen concentrations and similar concentration levels of [Formula: see text] and total dissolved phosphorus are found in groundwater upstream of the underground cut-off walls. The isotopic data indicated the probable occurrence of denitrification and nitrification processes in groundwater upstream, whereas the fingerprint of these processes was not shown in groundwater downstream. The management of fertilizer application is critical to control nitrogen concentrations in groundwater restricted by the underground cut-off walls.

Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters

USGS Publications Warehouse

Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.

1978-01-01

Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity

PubMed Central

Liu, Yong; Chen, Xiao-Dong; Yu, Jiang; Chi, Jun-Lin; Long, Fei-Wu; Yang, Hong-Wei; Chen, Ke-Ling; Lv, Zhao-Ying; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

2017-01-01

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that

Pathogenic mechanisms of pancreatitis

PubMed Central

Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

2017-01-01

Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

[Prevention and treatment of post-traumatic pancreatic necrosis in patients with blunt abdominal trauma].

PubMed

Cherdantsev, D V; Pervova, O V; Vinnik, Iu S; Kurbanov, D Sh

2016-01-01

High incidence of necrotic and suppurative complications is feature of acute post-traumatic pancreatitis. Severe trauma of the pancreas and post-traumatic pancreatitis lead to depressurization of ductal system that requires adequate drainage of damaged area and retroperitoneal fat. 95 patients in group 1 received standardized treatment. The victims of the 2nd group (44 patients) were treated using immunoreactive therapy (roncoleukin) and octreotide (the dose depended on the severity of pancreatitis) at early stages. The efficacy of treatment was assessed based on clinical, laboratory and instrumental parameters. Regardless severity of pancreatic injury overall mortality in groups 1 and 2 was 41% and 20.5% respectively. The main causes of adverse outcomes are severe destructive pancreatitis, postnecrotic suppurative complications. Adequacy rather radicalism of surgery should be preferred for blunt pancreatic trauma management. Minimally invasive surgical techniques and new methods of biological hemostasis may be applied. Timely use of anti-enzymatic and immunoactive therapy reduces the risk of severe post-traumatic pancreatitis, suppurative complications and improves outcomes in patients with blunt pancreatic trauma.

Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

PubMed

Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

2016-05-01

episode of acute pancreatitis leads to recurrent pancreatitis in 17% of patients, and almost 8% of patients progress to CP within 5 years. Progression was associated independently with alcoholic etiology, smoking, and a history of pancreatic necrosis. Smoking is the predominant risk factor for recurrent disease, whereas the combination of alcohol abuse and smoking produces the highest cumulative risk for chronic pancreatitis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

The importance of ERCP for the surgical tactic in haemorrhagic necrotizing pancreatitis (preliminary report).

PubMed

Gebhardt, C; Riemann, J F; Lux, G

1983-03-01

In patients with haemorrhagic necrotizing pancreatitis who are scheduled for surgery, we have been carrying out a preoperative retrograde investigation of the pancreatic duct system for the past 3 months. The results in, to date, ten patients, all of whom survived their severe illness, revealed four different morphological findings of importance for the surgical tactic. 1. A normal pancreatic duct system with no signs of fistulae: only peripancreatic necrosectomy is required. 2. Contrast medium leaks via a ductal fistula: left resection, including the removal of the fistulous area, must be done. 3. Normal duct system with complete segmental parenchymal staining, representing total necrosis in this region: left resection of the pancreas. 4. Duodenoscopically demonstrable perforation into the duodenum of a necrotic cavity in the head of the pancreas: conservative management only, no surgery, since this lesions, resulting in drainage of the necrotic cavity into the bowel, permits self-healing, while the site of the perforation within the necrotic wall cannot be dealt with by surgery. The experience gained so far indicates that the surgical tactic can be determined with greater selectivity by the use of ERCP.

Drug induced acute pancreatitis: incidence and severity.

PubMed Central

Lankisch, P G; Dröge, M; Gottesleben, F

1995-01-01

To determine the incidence and severity of drug induced acute pancreatitis, data from 45 German centres of gastroenterology were evaluated. Among 1613 patients treated for acute pancreatitis in 1993, drug induced acute pancreatitis was diagnosed in 22 patients (incidence 1.4%). Drugs held responsible were azathioprine, mesalazine/sulfasalazine, 2',3'-dideoxyinosine (ddI), oestrogens, frusemide, hydrochlorothiazide, and rifampicin. Pancreatic necrosis not exceeding 33% of the organ was found on ultrasonography or computed tomography, or both, in three patients (14%). Pancreatic pseudocysts did not occur. A decrease of arterial PO2 reflecting respiratory insufficiency, and an increase of serum creatinine, reflecting renal insufficiency as complications of acute pancreatitis were seen in two (9%) and four (18%) patients, respectively. Artificial ventilation was not needed, and dialysis was necessary in only one (5%) case. Two patients (9%) died of AIDS and tuberculosis, respectively; pancreatitis did not seem to have contributed materially to their death. In conclusion, drugs rarely cause acute pancreatitis, and drug induced acute pancreatitis usually runs a benign course. PMID:7489946

Optimum wall impedance for spinning modes: A correlation with mode cut-off ratio

NASA Technical Reports Server (NTRS)

Rice, E. J.

1978-01-01

A correlating equation relating the optimum acoustic impedance for the wall lining of a circular duct to the acoustic mode cut-off ratio, is presented. The optimum impedance was correlated with cut-off ratio because the cut-off ratio appears to be the fundamental parameter governing the propagation of sound in the duct. Modes with similar cut-off ratios respond in a similar way to the acoustic liner. The correlation is a semi-empirical expression developed from an empirical modification of an equation originally derived from sound propagation theory in a thin boundary layer. This correlating equation represents a part of a simplified liner design method, based upon modal cut-off ratio, for multimodal noise propagation.

Mitochondrial function and malfunction in the pathophysiology of pancreatitis.

PubMed

Gerasimenko, Oleg V; Gerasimenko, Julia V

2012-07-01

As a primary energy producer, mitochondria play a fundamental role in pancreatic exocrine physiology and pathology. The most frequent aetiology of acute pancreatitis is either gallstones or heavy alcohol consumption. Repeated episodes of acute pancreatitis can result in the development of chronic pancreatitis and increase the lifetime risk of pancreatic cancer 100-fold. Pancreatic cancer is one of the most common causes of cancer mortality with only about 3-4 % of patients surviving beyond 5 years. It has been shown that acute pancreatitis involves Ca²⁺ overload and overproduction of reactive oxygen species in pancreatic acinar cells. Both factors significantly affect mitochondria and lead to cell death. The pathogenesis of inflammation in acute and chronic pancreatitis is tightly linked to the induction of necrosis and apoptosis. There is currently no specific therapy for pancreatitis, but recent findings of an endogenous protective mechanism against Ca²⁺ overload--and particularly the potential to boost this protection--bring hope of new therapeutic approaches.

Animal models for investigating chronic pancreatitis

PubMed Central

2011-01-01

Chronic pancreatitis is defined as a continuous or recurrent inflammatory disease of the pancreas characterized by progressive and irreversible morphological changes. It typically causes pain and permanent impairment of pancreatic function. In chronic pancreatitis areas of focal necrosis are followed by perilobular and intralobular fibrosis of the parenchyma, by stone formation in the pancreatic duct, calcifications in the parenchyma as well as the formation of pseudocysts. Late in the course of the disease a progressive loss of endocrine and exocrine function occurs. Despite advances in understanding the pathogenesis no causal treatment for chronic pancreatitis is presently available. Thus, there is a need for well characterized animal models for further investigations that allow translation to the human situation. This review summarizes existing experimental models and distinguishes them according to the type of pathological stimulus used for induction of pancreatitis. There is a special focus on pancreatic duct ligation, repetitive overstimulation with caerulein and chronic alcohol feeding. Secondly, attention is drawn to genetic models that have recently been generated and which mimic features of chronic pancreatitis in man. Each technique will be supplemented with data on the pathophysiological background of the model and their limitations will be discussed. PMID:22133269

[Acute pancreatitis associated with hypercalcaemia].

PubMed

Tun-Abraham, Mauro Enrique; Obregón-Guerrero, Gabriela; Romero-Espinoza, Larry; Valencia-Jiménez, Javier

2015-01-01

Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5 to 8%. There is no clear pathophysiological basis, but elevated parathyroid hormone and high serum calcium levels could be responsible for calcium deposit in the pancreatic ducts and activation of pancreatic enzymes, which may be the main risk factor for developing acute pancreatitis. The aim of this report is to describe four cases. Four cases are reported of severe pancreatitis associated with hypercalcaemia secondary to primary hyperparathyroidism; three of them with complications (two pseudocysts and one pancreatic necrosis). Cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, studies showed the parathyroid adenoma. Surgical resection was the definitive treatment in all four cases. None of the patients had recurrent acute pancreatitis events during follow-up. Acute pancreatitis secondary to hypercalcaemia of primary hyperparathyroidism is rare; however, when it occurs it is associated with severe pancreatitis. It is suspected in patients with elevated serum calcium and high parathyroid hormone levels. Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, should be performed, to confirm clinical suspicion. Surgical resection is the definitive treatment with excellent results. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Necroptosis: a potential, promising target and switch in acute pancreatitis.

PubMed

Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

2016-02-01

Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets.

[Percutaneous ultrasound-guided drainage in the surgical treatment of acute severe pancreatitis].

PubMed

Delattre, J-F; Levy Chazal, N; Lubrano, D; Flament, J-B

2004-11-01

To report results of percutaneous ultrasound-guided drainage, performed by a surgeon, in the treatment of complications of acute pancreatitis (AP), and to determine the role of this technique in the therapeutic armamentarium of severe AP. From 1986 to 2001, 59 patients were included in this retrospective study. All patients initially had severe necrotizing AP (mean Ranson score = 4.1 ; range : 2-7). Anatomical lesions included pancreatic abscess in 6 patients and necrosis in 53 (17 stage D and 36 stage E according to Balthazar's classification). Necrosis was infected in 42 and sterile in 11 respectively. Drainage was performed under ultrasound guidance and local anaesthesia using small-diameter drains (7-14 French). Drainage was performed on average 23 days after onset of AP. Infection was proven by fine-needle aspiration in 47 (80 %) patients (41 infected necrosis and 6 localized abscess). In one patient, culture of aspirated fluid was negative but necrosis was infected (one false negative). Culture of aspirated fluid was negative and necrosis was sterile in 11 patients. Nineteen (32%) patients healed without subsequent surgery: 7 (16%) in the infected necrosis group, 6(55%) in the sterile necrosis group, and 6 (100%) in the abscess group. Forty (68%) patients had subsequent necrosectomy including 8 (14%) who died. Twenty (34 %) digestive fistulas healed spontaneously, except one treated by diversion stomia. Of the 16 (27 %) pancreatic fistulas, 6 needed subsequent interventional treatment. In selected patients, percutaneous drainage can represent an alternative to surgery with a 14% mortality rate. The high rate of subsequent necrosectomy suggests that drains with larger diameter, possibly associated with continuous irrigation, should be used.

Legumain is activated in macrophages during pancreatitis

PubMed Central

Wartmann, Thomas; Fleming, Alicia K.; Gocheva, Vasilena; van der Linden, Wouter A.; Withana, Nimali P.; Verdoes, Martijn; Aurelio, Luigi; Edgington-Mitchell, Daniel; Lieu, TinaMarie; Parker, Belinda S.; Graham, Bim; Reinheckel, Thomas; Furness, John B.; Joyce, Johanna A.; Storz, Peter; Halangk, Walter; Bogyo, Matthew; Bunnett, Nigel W.

2016-01-01

Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer. PMID:27514475

Sequence analysis of infectious pancreatic necrosis virus isolated from Iranian reared rainbow trout (Oncorhynchus mykiss) in 2012.

PubMed

Dadar, Maryam; Peyghan, Rahim; Memari, Hamid Rajabi; Shapouri, Masod Reza Seifi Abad; Hasanzadeh, Reza; Goudarzi, Laleh Moazzami; Vakharia, Vikram N

2013-12-01

Infectious pancreatic necrosis virus (IPNV) is the causal agent of a highly contagious disease that affects many species of fish and shellfish. This virus causes economically significant diseases of farmed rainbow trout, Oncorhynchus mykiss (Walbaum), in Iran, which is often associated with the transmission of pathogens from European resources. In this study, moribund rainbow trout fry samples were collected during an outbreak of IPNV in three different fish farms in north and west provinces of Iran in 2012; and we investigated the full genome sequence of Iranian IPNV and compared it with previously identified IPNV sequences. The sequences of different structural and nonstructural-protein genes were compared to those of other aquatic birnaviruses sequenced to date. Our results show that the Iranian isolate falls within genogroup 5, serotype A2 strain SP, having 99% identity with the strain 1146 from Spain. These results suggest that the Iranian isolate may have originated from Europe.

Infectious pancreatic necrosis virus in Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland: virus identification, histopathology, immunohistochemistry and genetic comparison with Scottish mainland isolates.

PubMed

Smail, D A; Bain, N; Bruno, D W; King, J A; Thompson, F; Pendrey, D J; Morrice, S; Cunningham, C O

2006-01-01

During mid-June 1999 peak mortalities of 11% of the total stock per week were seen at a sea cage site of Atlantic salmon, Salmo salar L., post-smolts in the Shetland Isles, Scotland. Virus was isolated on chinook salmon embryo (CHSE) cells in a standard diagnostic test and infectious pancreatic necrosis virus (IPNV) identified by enzyme-linked immunosorbent assay. IPNV was confirmed as serogroup A by a cell immunofluorescent antibody test using the cross-reactive monoclonal antibody AS-1. Four weeks after the main outbreak, virus titres in surviving moribund fish were assayed at >10(10) TCID50 g(-1) kidney. Histopathology of moribund fish was characterized by pancreatic acinar cell necrosis and a marked catarrhal enteritis of the intestinal mucosa. In the liver, necrosis, leucocytic infiltration and a generalized cell vacuolation were noted. IPNV-specific immunostaining was demonstrated in pancreas, liver, heart, gill and kidney tissue. The nucleotide sequence of the coding region of segment A was determined from the Shetland isolate. A 1180 bp fragment of the VP2 gene of this isolate was compared with a 1979 reference isolate from mainland Scottish Atlantic salmon, La/79 and another more recent mainland isolate, 432/00. Both A2 isolates were derived from carrier fish without signs of IPN and serotyped by a plaque neutralization test. The Shetland isolate shows a different nucleotide and amino acid sequence compared with the two isolates from carrier fish. These latter isolates showed identical amino acid sequences in the fragment examined, despite the 21 years separating the isolations. Sequence comparisons with other A2 (Sp) isolates on the database confirm all three Scottish isolates are A2 (Sp).

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer

PubMed Central

Martínez-Bosch, Neus; Guerrero, Pedro Enrique; Moreno, Mireia; José, Anabel; Iglesias, Mar; Munné-Collado, Jessica; Anta, Héctor; Gibert, Joan; Orozco, Carlos Alberto; Vinaixa, Judith; Fillat, Cristina; Viñals, Francesc; Navarro, Pilar

2016-01-01

Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc– derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment. PMID:27374084

Effect of the disease severity on the risk of developing new-onset diabetes after acute pancreatitis.

PubMed

Tu, Jianfeng; Yang, Yue; Zhang, Jingzhu; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Ke, Lu; Li, Weiqin; Li, Jieshou

2018-06-01

Endocrine pancreatic insufficiency secondary to acute pancreatitis (AP) drew increasing attention in the recent years. The aim of the present study was to assess the impact of pancreatic necrosis and organ failure on the risk of developing new-onset diabetes after AP.The follow-up study was conducted for patients recovered from AP in the treatment center of Jinling Hospital. Endocrine function was evaluated by simplified oral glucose tolerance test (OGTT). Pancreatic necrosis was examined by abdominal contrast-enhanced CT (CECT) scan during hospitalization. The data including APACHE II score, Balthazar's score, organ failure (AKI and ARDS) was also collected from the medical record database. All patients were divided into group diabetes mellitus (DM) and group non-DM according to the endocrine function and group pancreatic necrosis (PN) and persistent organ failure (OF), group PN and non-OF, group non-PN and OF, and group non-PN and non-OF according to the occurrence of pancreatic necrosis and persistent organ failure.Around 256 patients were included for the final analysis. 154 patients (60.2%) were diagnosed with DM (include impaired glucose tolerance, IGT), while 102 patients (39.8%) were deemed as normal endocrine function. APACHE II score and Balthazar score of the patients in the group DM were significant higher than those in the non-DM group (F = 6.09, P = .01; F = 10.74, P = .001). The incidence of pancreatic necrosis in group DM and group non-DM was, respectively, 64.7% and 53.0% (χ = 3.506, P = .06). The patients underwent necrosis debridement by percutaneous catheter drainage (PCD) and/or the operative necrosectomy (ON) were more likely to developed new onset DM than the patients without PCD or ON (χ = 2.385, P = .02). The morbidity of new-onset DM after AP gradually increased from group non-PN and non-OF, group non-PN and OF, group PN and non-OF to group PN and OF in order (χ = 4.587, P = .03). The value of

[Necrotic acute pancreatitis in the intensive care unit: a comparison between conservative and surgical medical treatment].

PubMed

Milian J, William; Portugal S, José; Laynez Ch, Richard; Rodríguez A, Cesar; Targarona, Javier; Barreda C, Luis

2010-01-01

To determine the prognosis of patients with necrotic acute pancreatitis receiving medical and surgical treatments. The severe acute pancreatitis treatment is multidisciplinary and requires a daily evaluation of the patient that will allow to observe changes and apply therapy in due time. The treatment includes: Admission in the ICU, fluids, nutrition and antibiotics, as well as other life supports for high-risk patients. Thus, patients undergo conservative treatment or, if it is necessary, surgery. A retrospective study of patients with necrotic acute pancreatitis admitted to the ICU between January 2004 and August 2006. The patients with necrotic acute pancreatitis without signs of sepsis underwent a conservative medical treatment, while fine needle punction-aspiration was performed in all patients who were suffering from necrotic acute pancreatitis and persistent sepsis four weeks after their admission and after discarding and eradicating every non-pancreatic focus of infection. All Gram stain or culture positive patients underwent surgery immediately. Seventy patients with necrotic acute pancreatitis were included in the study. Thirty-six patients (51%) suffered acute pancreatitis with sterile necrosis and underwent a conservative treatment, while 34 patients (49%) developed acute pancreatic with infected necrosis and underwent surgery. The average age was 55.19 vs. 57.65 (p=0.57). The average amylase was 1421.74 vs. 1402.45. (p=0.96). The tomography severity index was 8.47 vs. 8.79 (p=0.36). The Apache II was 8.22 vs. 9 (p=0.46). The average number of failed organs was 0.39 vs. 0.68. (p=0.19). The ICU stay was 10.75 vs. 26.5 days (p<0.05) while the total hospital stay was 46.47 vs. 57.26 days (p<0.05). The mortality rate was (3/36) 8.3% vs. (9/34) 26.5% (p<0.05) for conservative medical treatment vs. surgical treatment, respectively. Between the first and the twelfth month the evaluated patients who attended consultation, after discharge, showed: pancreatic

Effect of inhibition of prostaglandin E2 production on pancreatic infection in experimental acute pancreatitis

PubMed Central

Coelho, Ana Maria M.; Sampietre, Sandra; Patzina, Rosely; Jukemura, Jose; Cunha, Jose Eduardo M.; Machado, Marcel C.C.

2007-01-01

Objective. Acute pancreatitis is one the important causes of systemic inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction that allows bacterial translocation and pancreatic infection to occur. Indomethacin has been used to reduce inflammatory process and bacterial translocation in experimental models. The purpose of this study was to determine the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic infection. Materials and methods. An experimental model of severe acute pancreatitis (AP) was utilized. The animals were divided into three groups: sham (surgical procedure without AP induction); pancreatitis (AP induction); and indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)-α were measured 2 h after the induction of AP. We analyzed the occurrence of pancreatic infection with bacterial cultures performed 24 h after the induction of AP. The occurrence of pancreatic infection (considered positive when the CFU/g was >105), pancreatic histologic analysis, and mortality rate were studied. Results. In spite of the reduction of IL-6, IL-10, and PGE2 levels in the indomethacin group, TNF-α level, bacterial translocation, and pancreatic infection were not influenced by administration of indomethacin. The inhibition of PGE2 production did not reduce pancreatic infection, histologic score, or mortality rate. Conclusion. The inhibition of PGE2 production was not able to reduce the occurrence of pancreatic infection and does not have any beneficial effect in this experimental model. Further investigations will be necessary to discover a specific inhibitor that would make it possible to develop an anti-inflammatory therapy. PMID:18345325

Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.

PubMed

Malsy, Manuela; Graf, Bernhard; Bundscherer, Anika

2017-12-06

Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro. Cell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay. Metamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation. The oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts.

PubMed

Yamaguchi, Rin; Okabe, Yoshinobu; Jimi, Atsuo; Shiota, Koji; Kodama, Takahito; Naito, Yoshiki; Yasunaga, Masafumi; Kinoshita, Hisafumi; Kojiro, Masamichi

2006-10-01

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.

Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

PubMed Central

Binker, Marcelo G; Binker-Cosen, Andres A; Richards, Daniel; Gaisano, Herbert Y; de Cosen, Rodica H; Cosen-Binker, Laura I

2010-01-01

AIM: To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. METHODS: Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. RESULTS: In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases’ activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases’activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues’ ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. CONCLUSION: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. PMID:21105189

Chronic stress sensitizes rats to pancreatitis induced by cerulein: role of TNF-α.

PubMed

Binker, Marcelo-G; Binker-Cosen, Andres-A; Richards, Daniel; Gaisano, Herbert-Y; de Cosen, Rodica-H; Cosen-Binker, Laura-I

2010-11-28

To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases'activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues' ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.

Pleiotrophin promotes perineural invasion in pancreatic cancer.

PubMed

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-10-21

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer.

Pleiotrophin promotes perineural invasion in pancreatic cancer

PubMed Central

Yao, Jun; Hu, Xiu-Feng; Feng, Xiao-Shan; Gao, She-Gan

2013-01-01

Perineural invasion (PNI) in pancreatic cancer is an important cause of local recurrence, but little is known about its mechanism. Pleiotrophin (PTN) is an important neurotrophic factor. It is of interest that our recent experimental data showed its involvement in PNI of pancreatic cancer. PTN strongly presents in the cytoplasm of pancreatic cancer cells, and high expression of PTN and its receptor may contribute to the high PNI of pancreatic cancer. Correspondingly, PNI is prone to happen in PTN-positive tumors. We thus hypothesize that, as a neurite growth-promoting factor, PTN may promote PNI in pancreatic cancer. PTN is released at the time of tumor cell necrosis, and binds with its high-affinity receptor, N-syndecan on pancreatic nerves, to promote neural growth in pancreatic cancer. Furthermore, neural destruction leads to a distorted neural homeostasis. Neurons and Schwann cells produce more N-syndecan in an effort to repair the pancreatic nerves. However, the abundance of N-syndecan attracts further PTN-positive cancer cells to the site of injury, creating a vicious cycle. Ultimately, increased PTN and N-syndecan levels, due to the continuous nerve injury, may promote cancer invasion and propagation along the neural structures. Therefore, it is meaningful to discuss the relationship between PTN/N-syndecan signaling and PNI in pancreatic cancer, which may lead to a better understanding of the mechanism of PNI in pancreatic cancer. PMID:24151381

Significant inter-observer variation in the diagnosis of extrapancreatic necrosis and type of pancreatic collections in acute pancreatitis - An international multicenter evaluation of the revised Atlanta classification.

PubMed

Sternby, Hanna; Verdonk, Robert C; Aguilar, Guadalupe; Dimova, Alexandra; Ignatavicius, Povilas; Ilzarbe, Lucas; Koiva, Peeter; Lantto, Eila; Loigom, Tonis; Penttilä, Anne; Regnér, Sara; Rosendahl, Jonas; Strahinova, Vanya; Zackrisson, Sophia; Zviniene, Kristina; Bollen, Thomas L

2016-01-01

For consistent reporting and better comparison of data in research the revised Atlanta classification (RAC) proposes new computed tomography (CT) criteria to describe the morphology of acute pancreatitis (AP). The aim of this study was to analyse the interobserver agreement among radiologists in evaluating CT morphology by using the new RAC criteria in patients with AP. Patients with a first episode of AP who obtained a CT were identified and consecutively enrolled at six European centres backwards from January 2013 to January 2012. A local radiologist at each center and a central expert radiologist scored the CTs separately using the RAC criteria. Center dependent and independent interobserver agreement was determined using Kappa statistics. In total, 285 patients with 388 CTs were included. For most CT criteria, interobserver agreement was moderate to substantial. In four categories, the center independent kappa values were fair: extrapancreatic necrosis (EXPN) (0.326), type of pancreatitis (0.370), characteristics of collections (0.408), and appropriate term of collections (0.356). The fair kappa values relate to discrepancies in the identification of extrapancreatic necrotic material. The local radiologists diagnosed EXPN (33% versus 59%, P < 0.0001) and non-homogeneous collections (35% versus 66%, P < 0.0001) significantly less frequent than the central expert. Cases read by the central expert showed superior correlation with clinical outcome. Diagnosis of EXPN and recognition of non-homogeneous collections show only fair agreement potentially resulting in inconsistent reporting of morphologic findings. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

N-acetylcysteine amid reduces pancreatic damage in a rat model of acute necrotizing pancreatitis.

PubMed

Turkyilmaz, Serdar; Usta, Arif; Cekic, Arif Burak; Alhan, Etem; Kural, Birgül Vanizor; Ercin, Cengiz

2016-06-15

Inflammatory explosion and oxidative stress are important mechanisms of injury in acute necrotizing pancreatitis (ANP). This study investigated the effects of N-acetylcysteine amid (NACA), a novel cell-permeant antioxidant with anti-inflammatory activity, on experimental ANP in rats. Fifty-two adult male Sprague-Dawley rats were used, and ANP was induced by cerulein. The animals were divided into four groups which were sham + saline, sham + NACA, ANP + saline, and ANP + NACA. NACA (2.2 mg/kg, i.p) was administered for 6 h, after the induction of ANP. The extent of acinar cell injury, mortality, systemic cardiorespiratory variables, functional capillary density, renal/hepatic functions, and changes in some enzyme markers for pancreas and lung tissues were investigated. Induction of ANP increased mortality from 0% in the sham group to 43.75% in the ANP + saline group (P < 0.05), and administration of NACA significantly reduced mortality to 12.5% (P < 0.05). Induction of ANP also caused increases in pancreatic necrosis, serum amylase, alanine aminotransferase (ALT), interleukin-6, LDH in bronchoalveolar lavage fluid, serum urea, tissue myeloperoxidase in pancreas and lung tissues and malondialdehyde. There was less pronounced increase in these parameters in NACA treated group. Compared with ANP group, ANP + NACA group had lower levels of pancreatic necrosis (0.5 ± 0.2 versus 1.45 ± 0.2, P < 0.05) and inflammation (0.6 ± 0.2 versus 1.29 ± 00.3, P < 0.05) scores. Administration of NACA significantly decreased the ANP-induced mortality and also provided significant improvements in hemodynamic changes. The obtained positive effects of NACA on the course of pancreatitis indicates its potential usefulness in the management of ANP. Copyright © 2016 Elsevier Inc. All rights reserved.

EVALUATION OF CONTRAST-ENHANCED ULTRASONOGRAPHY AS A METHOD FOR DETECTING GALLBLADDER NECROSIS OR RUPTURE IN DOGS.

PubMed

Bargellini, Paolo; Orlandi, Riccardo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Peterson, Mark E; Rishniw, Mark; Boiti, Cristiano

2016-11-01

Gall bladder necrosis and rupture are life-threatening conditions in dogs requiring surgical intervention and early diagnosis is essential. Human patients with suspected gall bladder necrosis/rupture are commonly evaluated with contrast-enhanced ultrasonography (CEUS), however this procedure has not been described in dogs with suspected gall bladder necrosis/rupture. In a prospective diagnostic cohort study, CEUS (using SonoVue contrast medium) was performed in 93 dogs with gallbladder lesions identified by abdominal conventional ultrasonography. Necrosis/rupture was identified by CEUS as a focal lack of enhancement of the gallbladder wall. Dogs with positive CEUS finding for necrosis/rupture (complete lack of regional wall enhancement) underwent immediate surgery as did dogs with other biliary disorders requiring surgery. Dogs with negative CEUS findings or those not requiring surgery were managed medically. In cases undergoing surgery, necrosis/rupture was confirmed intraoperatively (and via histopathology). Absence of necrosis/rupture was confirmed either intraoperatively (via histopathology) or was assumed to be absent by complete recovery with medical management. Forty-nine dogs underwent surgery and cholecystectomy: 24 had necrosis/rupture. CEUS was more accurate (100% sensitive and specific) in diagnosing gallbladder wall necrosis/rupture than conventional ultrasonography (75% sensitive and 81% specific) (P < 0.03). In conclusion, CEUS provides accurate characterization of gallbladder wall integrity that can impact decisions regarding clinical management, either surgical or medical. © 2016 American College of Veterinary Radiology.

[Pancreatic functional status after wedge resection of the duodenal wall and para-pancreatic micro-irrigation].

PubMed

Voskanian, S E; Naĭdenov, E V

2011-01-01

To study influence parapancreatic microirrigation on morphological and functional condition of a pancreas and transformations of enzymatic activity of blood serum and enzymatic activity of lymph of a chest lymphatic channel after an operative trauma of a duodenum. Research is executed on 140 not purebred dogs which have been divided into six groups and united in two series. In the first series (30 dogs) were studied changes pancreatic exosecretion in the postoperative period of resection of duodenum (group 1.1), in the postoperative period of resection of duodenum with preliminary infiltration of a parapancreatic tissue of 0.5% by a solution of Novocain (group 1.2) and after resection of duodenum with application parapancreatic microirrigation (group 1.3). In the second series (110 dogs) were studied frequency of development of acute pancreatitis, enzymatic activity of blood serum and enzymatic activity of lymph of thoracal lymphatic duct after resection of duodenum (group 2.1) and in the postoperative period of resection of duodenum with preliminary infiltration of a parapancreatic tissue of 0.5% by a solution of Novocain (group 2.2) and after resection of duodenum with application parapancreatic microirrigation (group 2.3). Application parapancreatic microirrigation does not lead to oppression pancreatic exosecretion at the first o'clock after duodenotomy, and substantially reduces the pancreatic hypersecretion observed in the postoperative period of resection of a duodenum. In addition, application parapancreatic microirrigation reduces frequency of development of acute pancreatitis and promotes less expressed increase enzymatic activity of blood serum and enzymatic activity of lymph thoracal lymphatic duct at development of the given complication after operational trauma of duodenum in comparison with resection of duodenum and after a resection of a duodenum executed against infiltration of a parapancreatic tissue of 0.5% by a solution of Novocain.

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition].

PubMed

Layer, P; Dellinger, E P; Forsmark, C E; Lévy, P; Maraví-Poma, E; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2013-06-01

The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America

High fat diet and GLP-1 drugs induce pancreatic injury in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron

Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) weremore » administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.« less

The role of melatonin in pancreatic protection: could melatonin be used in the treatment of acute pancreatitis?

PubMed

Jaworek, Jolanta; Leja-Szpak, Anna; Kot, Michalina; Jaworek, Andrzej; Nawrot-Porbka, Katarzyna; Bonior, Joanna; Szklarczyk, Joanna

2014-01-01

Acute pancreatitis is a disease, which could be manifested as either a mild edematous form or a more severe necrotizing pancreatitis which has a poor prognosis. The etiology and pathogenesis of this ailment is not completely clear. Melatonin is an indoleamine which is produced from L-tryptophan in the pineal gland and in the other tissue including gastrointestinal tract. Both melatonin and its precursor have been demonstrated to protect the pancreas against acute pancreatitis and to attenuate pancreatic tissue damage. In the pancreas melatonin and L-tryptophan activate complex mechanisms which involve direct scavenging of the radical oxygen and nitrogen species, activation of antioxidant enzymes (catalase, superoxide dysmutase, glutation peroxidase), reduction of pro-inflammatory cytokines and prostaglandins, activation of heat shock protein, and a decrease of necrosis and increase of regeneration in the pancreas. There are several arguments for the idea that endogenous melatonin produced in the pineal gland and in the gastrointestinal system could be the part of a native mechanisms for protecting the pancreas against acute damage: 1/ the melatonin precursor L-tryptophan exerts similar protective effect as melatonin, 2/ application of the melatonin receptor antagonist, luzindole aggravates acute pancreatitis, 3/ pinealectomy results in the exacerbation of acute pancreatitis, 4/ low melatonin plasma levels are associated with an increased risk of severe acute pancreatitis. These observations leads to the idea that perhaps melatonin could be used in clinical trials as supportive therapy in acute pancreatitis.

Prophylactic antibiotics in acute pancreatitis: endless debate.

PubMed

Mourad, M M; Evans, Rpt; Kalidindi, V; Navaratnam, R; Dvorkin, L; Bramhall, S R

2017-02-01

INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Ge; Wan, Rong; Hu, Yanling

2014-01-31

Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration ofmore » sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.« less

Specific prognostic factors for secondary pancreatic infection in severe acute pancreatitis.

PubMed

Armengol-Carrasco, M; Oller, B; Escudero, L E; Roca, J; Gener, J; Rodríguez, N; del Moral, P; Moreno, P

1999-01-01

The aim of the present study was to investigate whether there are specific prognostic factors to predict the development of secondary pancreatic infection (SPI) in severe acute pancreatitis in order to perform a computed tomography-fine needle aspiration with bacteriological sampling at the right moment and confirm the diagnosis. Twenty-five clinical and laboratory parameters were determined sequentially in 150 patients with severe acute pancreatitis (SAP) and univariate, and multivariate regression analyses were done looking for correlation with the development of SPI. Only APACHE II score and C-reactive protein levels were related to the development of SPI in the multivariate analysis. A regression equation was designed using these two parameters, and empiric cut-off points defined the subgroup of patients at high risk of developing secondary pancreatic infection. The results showed that it is possible to predict SPI during SAP allowing bacteriological confirmation and early treatment of this severe condition.

[Gas gangrene of the abdominal wall due to underlying GI pathology: seven cases].

PubMed

Monneuse, O; Gruner, L; Barth, X; Malick, P; Timsit, M; Gignoux, B; Tissot, E

2007-01-01

Gas gangrene of the abdominal wall is a rare clinical occurrence with high rates of morbidity and mortality. The primary source of the infection is often unknown. To analyze the primary underlying intestinal etiologies and diagnostic approaches of gas gangrene of the abdominal wall, and to highlight specific treatment problems, particularly that of constructing a colostomy exteriorized through a massively infected abdominal wall. Seven cases of abdominal wall gas gangrene due to a gastrointestinal etiology were identified. (Cases arising from proctologic sources or related to recent abdominal surgery were excluded.) During the same period, 39 other patients presenting with abdominal wall gangrene from non-intestinal sources were treated. The etiologies were: perforated sigmoid diverticulitis (n=2), perforated appendicitis (n=1), acute pancreatitis with associated cecal perforation (n=1), and perforated colorectal cancer (n=3). Four of the seven patients died despite treatment (mortality of 57%). The clinical presentations of these seven cases demonstrate that a GI source must be suspected whenever a patient presents with abdominal wall gas gangrene, even when there are no specific GI symptoms. Imaging, particularly with CT scan, is essential both to visualize the extent of tissue necrosis and to reveal underlying primary GI pathology. This optimizes the surgical approach both by allowing for complete debridement and drainage of infected tissue, and by focussing the intervention on correction of the underlying primary GI source of infection.

Evaluation of the BISAP scoring system in prognostication of acute pancreatitis - A prospective observational study.

PubMed

Hagjer, Sumitra; Kumar, Nitesh

2018-04-21

Severe acute pancreatitis has a high mortality and its early identification is important for management and risk stratification. The bedside index for severity in acute pancreatitis (BISAP) is a simple scoring system done at admission which predicts the severity of pancreatitis. Procalcitonin is an inflammatory marker which is raised very early and helps in early prediction of the severity of disease. This study aims to evaluate the BISAP score and Procalcitonin in prognostication of acute pancreatitis. A prospective observational study of 60 patients presenting with acute pancreatitis was done at XXX Medical College and Hospital from July 2015 to June 2016. BISAP, APACHE-II, Ranson criteria, and CT severity index (CTSI) of all patients were calculated. Procalcitonin card test was done for all patients. The patients were stratified according by BISAP score and procalcitonin positivity into categories of severe pancreatitis, organ failure and pancreatic necrosis, as well as the number of deaths. The comparison of BISAP with other scoring systems, Procalcitonin (PCT), C-reactive protein (CRP), hematocrit, and body mass index (BMI) was done by the area under the receiver-operating curve (AUC) to prediction of severe acute pancreatitis, organ failure, necrosis, and death. Of the 60 patients, 14 (23.3%) developed severe acute pancreatitis, 11 (18.3%) Organ failure, 21 (35%) pancreatic necrosis and 7 (11.6%) died. A BISAP score of ≥3 was a statistically significant cutoff value. AUCs for predicting severe pancreatitis and death of BISAP were 0.875 and 0.740respectively, similar to those for Ranson criteria (0.802, 0.763) and APACHE-II (0.891, 0.769) and greater than AUCs for CTSI (0.641, 0.554). The AUC for prediction of organ failure were 0.906, 0.833, 0.874 and 0.623 for BISAP, Ranson criteria, APACHE-II, and CTSI respectively. AUCs for PCT predicting severity, organ failure, and death were 0.940, 0.923 and 0.769 respectively were similar to BISAP but greater than

Anti-inflammatory effect of α,β-amyrin, a triterpene from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice.

PubMed

Melo, Caroline M; Morais, Talita C; Tomé, Adriana R; Brito, Gerly Anne C; Chaves, Mariana H; Rao, Vietla S; Santos, Flávia A

2011-07-01

To evaluate the anti-inflammatory effect of α,β-amyrin, a pentacyclic triterpenoid from Protium heptaphyllum, on cerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced in Swiss mice by five intraperitoneal injections of cerulein (50 μg/kg), at 1 h intervals. Mice received α,β-amyrin (10, 30 and 100 mg/kg), thalidomide (200 mg/kg), or vehicle (3% Tween 80) orally 1 h before and 12 h after the cerulein challenge. The severity of pancreatitis was evaluated 24 h after cerulein by assessing serum pro-inflammatory cytokines and amylase activity, pancreatic myeloperoxidase (MPO), and thiobarbituric acid-reactive substances (TBARS), as well as by histology. α,β-Amyrin and thalidomide significantly attenuated the cerulein-induced increase in tumor necrosis factor (TNF)-α, interleukin-6, lipase, amylase, MPO, and TBARS. Moreover, α,β-amyrin greatly suppressed the pancreatic edema, inflammatory cell infiltration, acinar cell necrosis, and expressions of TNFα and inducible nitric oxide synthase. α,β-Amyrin ameliorates cerulein-induced acute pancreatitis by acting as an anti-inflammatory and antioxidant agent.

[Pathophysiology of hormonal, immune, metabolic changes in acute and chronic pancreatitis. Experimental and clinical studies].

PubMed

Trubitsyna, I E; Chikunova, B Z; Tkachenko, E V; Tsaregorodtseva, T M; Vinokurova, L V; Varvanina, G G

2008-01-01

There is literature review of the acute and chronic pancreatitis experimental models. Patogenetic necrosis mechanisms with fibrosis progress in pancreas were revealed. The stimulation of the proteolytic enzymes synthesis and secretion, that was examined in experiments were compared with clinical examinations. The patients with chronic pancreatitis were investigated in the Central Research Institute of Gastroenterology.

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013].

PubMed

Uomo, G; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Maravì-Poma, E; Shimosegawa, T; Siriwardena, A K; Whitcomb, D C; Windsor, J A; Petrov, M S

2013-12-01

The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. This classification provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research.

A Retroperitoneal Neuroendocrine Tumor in Ectopic Pancreatic Tissue

PubMed Central

Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

2013-01-01

Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor. PMID:24949389

Amylase in drain fluid for the diagnosis of pancreatic leak in post-pancreatic resection.

PubMed

Davidson, Tsetsegdemberel Bat-Ulzii; Yaghoobi, Mohammad; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-07

The treatment of people with clinically significant postoperative pancreatic leaks is different from those without clinically significant pancreatic leaks. It is important to know the diagnostic accuracy of drain fluid amylase as a triage test for the detection of clinically significant pancreatic leaks, so that an informed decision can be made as to whether the patient with a suspected pancreatic leak needs further investigations and treatment. There is currently no systematic review of the diagnostic test accuracy of drain fluid amylase for the diagnosis of clinically relevant pancreatic leak. To determine the diagnostic accuracy of amylase in drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection. We searched MEDLINE, Embase, the Science Citation Index Expanded, and the National Institute for Health Research Health Technology Assessment (NIHR HTA) websites up to 20 February 2017. We searched the references of the included studies to identify additional studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We also performed a 'related search' and 'citing reference' search in MEDLINE and Embase. We included all studies that evaluated the diagnostic test accuracy of amylase in the drain fluid at 48 hours or more for the diagnosis of pancreatic leak in people who had undergone pancreatic resection excluding total pancreatectomy. We planned to exclude case-control studies because these studies are prone to bias, but did not find any. At least two authors independently searched and screened the references produced by the search to identify relevant studies. Two review authors independently extracted data from the included studies. The included studies reported drain fluid amylase on different postoperative days and measured at different cut-off levels, so it was not possible to perform a meta-analysis using the

Bladder necrosis: 'A man without a bladder'.

PubMed

Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

2018-02-17

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Biliary Stenosis and Gastric Outlet Obstruction: Late Complications After Acute Pancreatitis With Pancreatic Duct Disruption.

PubMed

Sugimoto, Motokazu; Sonntag, David P; Flint, Greggory S; Boyce, Cody J; Kirkham, John C; Harris, Tyler J; Carr, Sean M; Nelson, Brent D; Bell, Don A; Barton, Joshua G; Traverso, L William

2018-07-01

Pancreatic duct disruption (PDD) after acute pancreatitis can cause pancreatic collections in the early phase and biliary stenosis (BS) or gastric outlet obstruction (GOO) in the late phase. We aimed to document those late complications after moderate or severe acute pancreatitis. Between September 2010 and August 2014, 141 patients showed pancreatic collections on computed tomography. Percutaneous drainage was primarily performed for patients with signs or symptoms of uncontrolled pancreatic juice leakage. Pancreatic duct disruption was defined as persistent amylase-rich drain fluid or a pancreatic duct cut-off on imaging. Clinical course of the patients who developed BS or GOO was investigated. Among the 141 patients with collections, 33 patients showed PDD in the pancreatic head/neck area. Among them, 9 patients (27%) developed BS 65 days after onset and required stenting for 150 days, and 5 patients (15%) developed GOO 92 days after onset and required gastric decompression and jejunal tube feeding for 147 days (days shown in median). All 33 patients recovered successfully without requiring surgical intervention. Anatomic proximity of the bile duct or duodenum to the site of PDD and severe inflammation seemed to contribute to the late onset of BS or GOO. Conservative management successfully reversed these complications.

Dendritic cell-based vaccines for pancreatic cancer and melanoma.

PubMed

Mulé, James J

2009-09-01

Based on leads from our recent animal studies, we are embarking on a series of new clinical trials to evaluate potential improvements in dendritic cell (DC)-based vaccines for melanoma and pancreatic cancer. The first new strategy involves the use of a powerful chemokine (denoted secondary lymphoid tissue chemokine; SLC/CCL-21), which can both create functioning lymph node-like structures at sites of vaccination with tumor-loaded DCs and dramatically enhance vaccine efficacy in animal tumor models. Using this strategy, we are embarking on a clinical trial in melanoma patients with the intent to create functioning, ectopic, lymph node-like structures to enhance host antitumor immunity. The second strategy, in the setting of pancreatic cancer, involves a gene therapy and immunotherapy combination of a locally administered tumor necrosis factor-alpha gene vector followed by radiation (to induce tumor apoptosis/necrosis) and intratumorally administered monocyte-derived DCs (to uptake and present antigens from dying tumor cells to elicit potent, systemic, antitumor immunity).

Acute pancreatitis at the beginning of the 21st century: The state of the art

PubMed Central

Tonsi, Alfredo F; Bacchion, Matilde; Crippa, Stefano; Malleo, Giuseppe; Bassi, Claudio

2009-01-01

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century. PMID:19554647

Polyarthritis and bone lesions complicating traumatic pancreatitis in two children.

PubMed Central

Goluboff, N.; Cram, R.; Ramgotra, B.; Singh, A.; Wilkinson, G. W.

1978-01-01

The association of bone lesions, polyarthritis and cutaneous nodules with pancreatic disease is being recognized and reported more frequently. In adults all forms of pancreatitis and carcinoma of the pancreas have been involved, but in the few children described these complications have been associated with acute traumatic pancreatitis. This paper describes two cases of acute traumatic pancreatitis in which polyarthritis and limb pains were noted after 2 to 3 weeks. In one child osteolytic lesions and periostitis were seen on roentgenograms 7 weeks after the onset of pancreatitis. In the other child minor roentgenographic changes were not seen until 5 months after the onset; however, bone scans showed clear-cut abnormalities after 1 month. Almost complete resolution could be expected within a year. Serum lipase and amylase concentrations remained elevated during the acute illness. Disseminated fat necrosis is apparently related to the excess amounts of circulating lipase. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:647564

Surgical resection after TNFerade therapy for locally advanced pancreatic cancer.

PubMed

Chadha, Manpreet K; Litwin, Alan; Levea, Charles; Iyer, Renuka; Yang, Gary; Javle, Milind; Gibbs, John F

2009-09-04

Treatment of pancreatic cancer remains a major oncological challenge and survival is dismal. Most patients, present with advanced disease at diagnosis and are not candidates for curative resection. Preoperative chemoradiation may downstage and improve survival in locally advanced pancreatic cancer. This has prompted investigators to look for novel neoadjuvant therapies. Gene therapy for pancreatic cancer is a novel investigational approach that may have promise. TNFerade is a replication deficient adenovirus vector carrying the human tumor necrosis factor (TNF)-alpha gene regulated under control of a radiation-inducible gene promoter. Transfection of tumor cells with TNFerade maximizes the antitumor effect of TNF-alpha under influence of radiation leading to synergistic effects in preclinical studies. We describe a case of locally advanced unresectable pancreatic cancer treated with a novel multimodal approach utilizing gene therapy with TNFerade and concurrent chemoradiation that was followed by successful surgical resection. Neoadjuvant TNFerade based chemoradiation therapy may be a useful adjunct to treatment of locally advanced pancreatic cancer.

Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis

PubMed Central

Meher, Susanta; Mishra, Tushar Subhadarshan; Sasmal, Prakash Kumar; Rath, Satyajit; Sharma, Rakesh; Rout, Bikram; Sahu, Manoj Kumar

2015-01-01

Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis. PMID:26345247

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

Utility of serum IgG, IgG4 and carbonic anhydrase II antibodies in distinguishing autoimmune pancreatitis from pancreatic cancer and chronic pancreatitis.

PubMed

Talar-Wojnarowska, Renata; Gąsiorowska, Anita; Olakowski, Marek; Dranka-Bojarowska, Daria; Lampe, Paweł; Śmigielski, Jacek; Kujawiak, Magdalena; Grzegorczyk, Janina; Małecka-Panas, Ewa

2014-09-01

Autoimmune pancreatitis (AIP) can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. The aim of our study was to compare IgG, IgG4 and anti-CAIIAb serum levels in patients with AIP, pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) and to assess their clinical significance and utility in differential diagnosis of pancreatic diseases. The study included 124 patients: 45 with PA, 24 with AIP and 55 with CP. Peripheral venous blood samples were obtained from all analyzed patients at the time of hospital admission and total IgG, IgG4 and anti-CAIIAB serum levels were measured using ELISA tests. Serum levels of IgG, IgG4 and anti-CAIIAb were significantly higher in patients with AIP compared to PA and CP patients (p<0.001). In AIP patients the median IgG levels were 19.7 g/l, IgG4 levels - 301.9 mg/dl and anti-CAIIAb - 81.82 ng/ml, compared to 10.61 g/l, 123.2mg/dl and 28.6 ng/ml, respectively, in PA patients. IgG4 for the cut-off 210 mg/dl showed the best sensitivity and specificity (83.8% and 89.5%) in AIP diagnosis compared to IgG (69.3% and 87.3%, respectively) and anti-CAIIAb (45.3% and 74.3%). However, 16 (35.5%) patients with PA and 14 (25.4%) patients with CP had IgG4 levels greater than 140 mg/dl. Moreover, in 3 (6.67%) patients with pancreatic cancer those values were greater than 280 mg/dl. No patients with CP had IgG4 more than 280 mg/dl. IgG4 at cut-off 210 mg/dl showed the best sensitivity and specificity in AIP diagnosis compared to IgG and anti-CAIIAb, however elevations of serum IgG4 may be seen in subjects without AIP, including pancreatic cancer. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Oxalate nephropathy associated with chronic pancreatitis.

PubMed

Cartery, Claire; Faguer, Stanislas; Karras, Alexandre; Cointault, Olivier; Buscail, Louis; Modesto, Anne; Ribes, David; Rostaing, Lionel; Chauveau, Dominique; Giraud, Patrick

2011-08-01

Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.

Pancreatic head cryosurgery: safety and efficiency in vivo--a pilot study.

PubMed

Li, Jialiang; Zhou, Liang; Chen, Jibing; Wu, Binghui; Zeng, Jianying; Fang, Gang; Deng, Chunjuan; Huang, Shengquan; Yao, Fei; Chen, Zhixian; Leng, Yin; Deng, Min; Deng, Chunmei; Zhang, Bo; Zhou, Gang; He, Lihua; Liao, Maoxin; Chiu, David; Niu, Lizhi; Zuo, Jiansheng; Xu, Kecheng

2012-11-01

Pancreatic cancer is the fourth leading cause of cancer-related death. Cryosurgery has emerged as a promising new technique for treatment. Although 80% of pancreatic cancers are located in the pancreatic head, no research has been conducted on the safety and efficacy of cryosurgery for these tumors. Two groups of Tibetan miniature pigs (n = 4 per group) underwent cryosurgery to the pancreatic head with either the deep freezing protocol (100% argon output) or shallow freezing protocol (10% argon output), and compared to sham-operated pigs. Serum inflammatory factors and amylase increased during the 5 days after cryoablation in both groups but acute pancreatitis did not occur. Adhesions were observed between the pancreatic head and adjacent organs, and only minor trauma was caused to the stomach, duodenum, small intestine, and liver. Ice balls with a radius of 0.5 cm beyond the tumor edge were sufficient to cause complete necrosis of the pancreatic tissue, and decreased the degree of cold injury to surrounding tissues. Shallow freezing protocol seemed to be safer than, and just as effective as, the deep freezing protocol. This preliminary study suggests that cryosurgery could potentially be an effective treatment of cancer of the pancreatic head.

Infectious pancreatic necrosis virus triggers antiviral immune response in rainbow trout red blood cells, despite not being infective

PubMed Central

Nombela, Ivan; Carrion, Aurora; Puente-Marin, Sara; Chico, Verónica; Mercado, Luis; Perez, Luis; Coll, Julio; Ortega-Villaizan, Maria del Mar

2017-01-01

Background: Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet. Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques. Results: IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genes ifn-1, pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line. Conclusions: Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs. PMID:29333244

Infectious pancreatic necrosis virus triggers antiviral immune response in rainbow trout red blood cells, despite not being infective.

PubMed

Nombela, Ivan; Carrion, Aurora; Puente-Marin, Sara; Chico, Verónica; Mercado, Luis; Perez, Luis; Coll, Julio; Ortega-Villaizan, Maria Del Mar

2017-01-01

Background : Some fish viruses, such as piscine orthoreovirus and infectious salmon anemia virus, target red blood cells (RBCs), replicate inside them and induce an immune response. However, the roles of RBCs in the context of infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet. Methods : Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll purified and exposed to IPNV in order to analyze infectivity and immune response using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting techniques. Results : IPNV could not infect RBCs; however, IPNV increased the expression of the INF1-related genes ifn-1 , pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred protection against IPNV infection in CHSE-214 fish cell line. Conclusions : Despite not being infected, rainbow trout RBCs could respond to IPNV with increased expression of antiviral genes. Fish RBCs could be considered as mediators of the antiviral response and therefore targets of new strategies against fish viral infections. Further research is ongoing to completely understand the molecular mechanism that triggers this antiviral response in rainbow trout RBCs.

Utility of CT classifications to predict unfavorable outcomes in children with acute pancreatitis.

PubMed

Izquierdo, Yojhan E; Fonseca, Eileen V; Moreno, Luz-Ángela; Montoya, Rubén D; Guerrero Lozano, Rafael

2018-02-21

Computed tomography (CT) is useful for the diagnosis of local complications in children with acute pancreatitis but its role as a prognostic tool remains controversial. To establish the correlation between the CT Severity Index and the Revised Atlanta Classification regarding unfavorable outcomes such as severe acute pancreatitis and need for Pediatric Special Care Unit attention in children with acute pancreatitis. We conducted a retrospective and concordance cohort study in which we obtained abdominal CT scans from 30 patients ages 0 to 18 years with acute pancreatitis. Two pediatric radiologists interpreted the results using the CT Severity Index and the Revised Atlanta Classification. The kappa coefficient was determined for each scale. The association among severe acute pancreatitis, need for admission to the Pediatric Special Care Unit and CT systems were established using chi-square or Mann-Whitney U tests. The best CT Severity Index value to predict the need for admission to the Pediatric Special Care Unit was estimated through a receiver operating characteristic (ROC) curve. Mean CT Severity Index was 5.1±2.8 (mean ± standard deviation on a scale of 0 to 10) for the severe acute pancreatitis group vs. 3.8±2.7 for the mild acute pancreatitis group (P=0.230). The CT Severity Index for the children who were not hospitalized at the Pediatric Special Care Unit was 2.2±2.2 vs. 5.6±2.4 for the group hospitalized at the Pediatric Special Care Unit (P=0.001). Only parenchymal necrosis >30% was associated with severe acute pancreatitis (P=0.021). A CT Severity Index ≥3 has a sensitivity of 89% and specificity of 72% to predict need for admission to the Pediatric Special Care Unit. None of the Revised Atlanta Classification categories was associated with severe acute pancreatitis or admission to the Pediatric Special Care Unit. A CT Severity Index ≥3 in children with acute pancreatitis who require CT assessment based on clinical criteria is associated with

[Pancreatic mucinous cystadenoma doubly complicated by acute pancreatitis and retroperitoneal rupture].

PubMed

Maghrebi, Houcine; Makni, Amine

2017-01-01

Mucinous cystadenomas are benign tumors with malignant potential. They are often revealed by non-specific abdominal pain, jaundice or an episode of acute pancreatitis. We here report an exceptional case of mucinous cystadenoma doubly complicated by acute pancreatitis and retroperitoneal rupture. The study involved a 30-year old non-weighted female patient, presenting with epigastric pain associated with left hypochondrium evolving over the last three months and which had intensified without fever or jaundice in the last 3 days. Clinical examination showed impingement on palpation of the epigastrium and of the left hypochondrium. There was no palpable mass. Laboratory tests were without abnormalities, except for lipasemia that was 8-times the upper normal. Abdominal CT scan showed bi-loculated cystic mass in the pancreas tail, measuring 111 mm * 73 mm, with a thin wall and a fluid content, associated with an infiltration of the left perirenal fascia. MRI (Panel A) showed mucinous cystadenoma with retroperitoneal rupture. The caudal portion of the main pancreatic duct was slightly dilated and communicated with the pancreatic cyst. The patient underwent surgery via bi-sub-costal approach. A cystic mass in the pancreas tail with retroperitoneal rupture associated with acute pancreatitis (outflow of necrotic content from left anterior prerenal space) was found. Caudal splenopancreatectomy was performed (Panel B). The postoperative course was uneventful. The anatomo-pathological examination of the surgical specimen showed pancreatic mucinous cystadenoma with low-grade dysplasia.

Disease progression of acute pancreatitis in pediatric patients.

PubMed

Hao, Fabao; Guo, Hongjie; Luo, Qianfu; Guo, Chunbao

2016-05-15

Approximately 10% of patients with acute pancreatitis (AP) progress to chronic pancreatitis. Little is known about the factors that affect recurrence of pancreatitis after an initial episode. We retrospectively investigated patients with AP, focusing on their outcomes and the predictors for disease progression. Between July 2003 and June 2015, we retrospectively enrolled first-time AP patients with medical records on disease etiology, severity (according to the Atlanta classifications), and recurrence of AP. Independent predictors of recurrent AP (RAP) and chronic pancreatitis were identified using the logistic regression model. Of the total 159 patients, 45 (28.3%) developed RAP, including two episodes of RAP in 19 patients, and 9 (5.7%) developed chronic pancreatitis. The median duration from the time of AP to the onset of RAP was 5.6 ± 2.3 months. RAP patients were identified as more common among patients with idiopathic first-time AP. The presence of severe ascites, pancreatic necrosis, and systemic complications was independent predictors of RAP in pediatric patients. Experiencing over two RAP episodes was the predictor for developing chronic pancreatitis. No influence of age or number of AP episodes was found on the occurrence of abdominal pain, pain severity, and the prevalence of any pain. Severity of first-time AP and idiopathic first-time AP are related to RAP. Recurrence increases risk for progression to chronic pancreatitis. The risk of recurrence increased with increasing numbers of AP episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition].

PubMed

Maraví-Poma, E; Patchen Dellinger, E; Forsmark, C E; Layer, P; Lévy, P; Shimosegawa, T; Siriwardena, A K; Uomo, G; Whitcomb, D C; Windsor, J A; Petrov, M S

2014-05-01

To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and

Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.

PubMed

Xiong, Guang-Su; Wu, Shu-Ming; Wang, Zhen-Hua; Mo, Jian-Zhong; Xiao, Shu-Dong

2007-03-01

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model. A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated. Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue. Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.

Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation.

PubMed

Dellinger, E Patchen; Forsmark, Christopher E; Layer, Peter; Lévy, Philippe; Maraví-Poma, Enrique; Petrov, Maxim S; Shimosegawa, Tooru; Siriwardena, Ajith K; Uomo, Generoso; Whitcomb, David C; Windsor, John A

2012-12-01

To develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides

Diagnostic ultrasonography in cattle with abdominal fat necrosis.

PubMed

Tharwat, Mohamed; Buczinski, Sébastien

2012-01-01

This study describes the ultrasonographic findings in 14 cows with abdominal fat necrosis. Ultrasonography of the abdomen revealed the presence of heterogeneous hyperechoic masses and hyperechoic omentum with localized masses floating in a hypoechoic peritoneal fluid. A hyperechogenic rim was imaged around both kidneys. The intestines were coated with hyperechoic capsules and the intestinal lumens were constricted. Ultrasonographic examination of the pancreatic parenchyma showed an overall increased echogenicity which was homogenously distributed in 3 cases. A diagnosis of abdominal fat necrosis was made with ultrasound-guided biopsy of the echogenic masses, and thereafter at postmortem examination. Results from this study demonstrate the efficacy of ultrasonography as an imaging modality for antemortem diagnosis of abdominal lipomatosis in cattle. To the authors' knowledge, this study is the first that illustrates ultrasonographic findings in cattle affected with abdominal lipomatosis.

Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

PubMed

Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

2018-01-22

Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Antibiotic prophylaxia in patients with severe acute pancreatitis.

PubMed

Zhou, Yan-Ming; Xue, Zuo-Liang; Li, Yu-Min; Zhu, You-Quan; Cao, Nong

2005-02-01

The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients

Computed Tomography Evaluation of Esophagogastric Necrosis After Caustic Ingestion.

PubMed

Chirica, Mircea; Resche-Rigon, Matthieu; Zagdanski, Anne Marie; Bruzzi, Matthieu; Bouda, Damien; Roland, Eric; Sabatier, François; Bouhidel, Fatiha; Bonnet, Francine; Munoz-Bongrand, Nicolas; Marc Gornet, Jean; Sarfati, Emile; Cattan, Pierre

2016-07-01

Endoscopy is the standard of care for emergency patient evaluation after caustic ingestion. However, the inaccuracy of endoscopy in determining the depth of intramural necrosis may lead to inappropriate decision-making with devastating consequences. Our aim was to evaluate the use of computed tomography (CT) for the emergency diagnostic workup of patients with caustic injuries. In a prospective study, we used a combined endoscopy-CT decision-making algorithm. The primary outcome was pathology-confirmed digestive necrosis. The respective utility of CT and endoscopy in the decision-making process were compared. Transmural endoscopic necrosis was defined as grade 3b injuries; signs of transmural CT necrosis included absence of postcontrast gastric/ esophageal-wall enhancement, esophageal-wall blurring, and periesophageal-fat blurring. We included 120 patients (59 men, median age 44 years). Emergency surgery was performed in 24 patients (20%) and digestive resection was completed in 16. Three patients (3%) died and 28 patients (23%) experienced complications. Pathology revealed transmural necrosis in 9/11 esophagectomy and 16/16 gastrectomy specimens. Severe oropharyngeal injuries (P = 0.015), increased levels of blood lactate (P = 0.007), alanine aminotransferase (P = 0.027), bilirubin (P = 0.005), and low platelet counts (P > 0.0001) were predictive of digestive necrosis. Decision-making relying on CT alone or on a combined CT-endoscopy algorithm was similar and would have spared 19 unnecessary esophagectomies and 16 explorative laparotomies compared with an endoscopy-alone algorithm. Endoscopy did never rectify a wrong CT decision. Emergency decision-making after caustic injuries can rely on CT alone.

Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death

PubMed Central

Athwal, T; Huang, W; Mukherjee, R; Latawiec, D; Chvanov, M; Clarke, R; Smith, K; Campbell, F; Merriman, C; Criddle, D; Sutton, R; Neoptolemos, J; Vlatković, N

2014-01-01

Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore

Clinical Study on Acute Pancreatitis in Pregnancy in 26 Cases

PubMed Central

Qihui, Cheng; Xiping, Zhang; Xianfeng, Ding

2012-01-01

Aim. This paper investigated the pathogenesis and treatment strategies of acute pancreatitis (AP) in pregnancy. Methods. We analyzed retrospectively the characteristics, auxiliary diagnosis, treatment strategies, and clinical outcomes of 26 cases of patients with AP in pregnancy. Results. All patients were cured finally. (1) Nine cases of 22 mild acute pancreatitis (MAP) patients selected automatic termination of pregnancy because of the unsatisfied therapeutic efficacy or those patients' requirements. (2) Four cases of all patients were complicated with severe acute pancreatitis (SAP); 2 cases underwent uterine incision delivery while one of them also received cholecystectomy, debridement and drainage of pancreatic necrosis, and percutaneous jejunostomy. One case had a fetal death when complicated with SAP; she had to receive extraction of bile duct stones and drainage of abdominal cavity after induced abortion. The other one case with hyperlipidemic pancreatitis was given induced abortion and hemofiltration. Conclusions. The first choice of MAP in pregnancy is the conventional therapy. Apart from the conventional therapy, we need to terminate pregnancy as early as possible for patients with SAP. Removing biliary calculi and drainage is supposed to be considered for acute biliary pancreatitis. Lowering blood lipids treatment should be applied to hyperlipidemic pancreatitis or given to hemofiltration when necessary. PMID:23213326

Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

PubMed Central

Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

2016-01-01

Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

PubMed

Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

2016-08-05

Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. © 2016 The Authors.

[Retrieval of a migrated plastic stent in a 51-year-old man].

PubMed

Poszler, A; Klare, P; Weber, A; Abdelhafez, M; Holzapfel, K; Schmid, R M; von Delius, S

2018-04-16

Endosonographically guided transgastric drainage is the first-line interventional therapy of walled-off necrosis and symptomatic pancreatic pseudocysts in necrotizing pancreatitis. Plastic stents or lumen apposing metal stents are commonly used. A possible complication of endoscopic therapy is stent migration. We report upon a 51-year-old man who presented with acute necrotizing pancreatitis. Transgastric necrosectomy was performed and 5 transmural double-pigtail stents (DPS) were left in situ to drain the residual retroperitoneal cavity. The patient recovered and 4 stents were endoscopically removed 5 weeks later on an outpatient basis, whereas the fifth stent was suspected to have passed spontaneously via the natural route. The asymptomatic patient presented 3 months later for follow-up computed tomography. The necrosis had healed but one DPS was seen beyond the gastric wall near the kidney. Transmural access to the stent could be achieved by an endosonographically guided puncture toward the proximal portion of the stent followed by placement of a hydrophilic guidewire alongside the stent. A new gastrostomy was created by using a 6F cystotome followed by wire-guided dilation with a 12 mm balloon. The stent could then be grasped with transmurally inserted rat-tooth forceps and repositioned across the gastrostomy site. The patient was given prophylactic antibiotics. After removal of the stent, the patient could be discharged. Herein, we present the successful endosonographically guided transmural removal of a retroperitoneally migrated plastic stent. Of note, in our patient we had to rely completely on endosonography and radiography for localization and targeting of the stent, since the former necrotic cavity had meanwhile completely healed.

Gastroduodenal artery aneurysm - A rare complication of traumatic pancreatic injury.

PubMed

Babu, Annu; Rattan, Amulya; Singhal, Maneesh; Gupta, Amit; Kumar, Subodh

2016-12-01

Aneurysm of gastroduodenal artery (GDA) is rare. Most reported cases are due to pancreatitis and atherosclerosis; however, those following pancreatic trauma have not been reported. We encoun- tered GDA aneurysm in a patient of blunt abdominal trauma, who had pancreatic contusion and retroduodenal air on contrast enhanced computed tomography of abdomen. Emergency laparotomy for suspected duodenal injury revealed duodenal wall and pancreatic head contusion, mild hemo- peritoneum and no evidence of duodenal perforation. In the postoperative period, the patient developed upper gastrointestinal hemorrhage on day 5. Repeat imaging revealed GDA aneurysm, which was managed successfully by angioembolization. This case highlights, one, delayed presen- tation of GDA aneurysm after blunt pancreatic trauma and two, its successful management using endovascular technique.

Pancreaticoportal Fistula and Disseminated Fat Necrosis After Revision of a Transjugular Intrahepatic Portosystemic Shunt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Seth J., E-mail: kleins@mir.wustl.edu; Saad, Nael; Korenblat, Kevin

A 59-year old man with alcohol related cirrhosis and portal hypertension was referred for transjugular intrahepatic portosystemic shunt (TIPS) to treat his refractory ascites. Ten years later, two sequential TIPS revisions were performed for shunt stenosis and recurrent ascites. After these revisions, he returned with increased serum pancreatic enzyme levels and disseminated superficial fat necrosis; an iatrogenic pancreaticoportal vein fistula caused by disruption of the pancreatic duct was suspected. The bare area of the TIPS was subsequently lined with a covered stent-graft, and serum enzyme levels returned to baseline. In the interval follow-up period, the patient has clinically improved.

Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

PubMed Central

del Hierro, Piedad Magdalena

2011-01-01

Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

Effects of urtica dioica extract on experimental acute pancreatitis model in rats.

PubMed

Yilmaz, Baris; Basar, Omer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Oztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

2014-01-01

Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study.

Effects of urtica dioica extract on experimental acute pancreatitis model in rats

PubMed Central

Yilmaz, Baris; Basar, Ömer; Aktas, Bora; Altinbas, Akif; Ekiz, Fuat; Büyükcam, Fatih; Albayrak, Aynur; Ginis, Zeynep; Öztürk, Gülfer; Coban, Sahin; Ucar, Engin; Kaya, Oskay; Yüksel, Osman; Caner, Sedat; Delibasi, Tuncay

2014-01-01

Acute pancreatitis is the acute inflammation of pancreas and peripancreatic tissues, and distant organs are also affected. The aim of this study was to investigate the effect of Urtica dioica extract (UDE) treatment on cerulein induced acute pancreatitis in rats. Twenty-one Wistar Albino rats were divided into three groups: Control, Pancreatitis, and UDE treatment group. In the control group no procedures were performed. In the pancreatitis and treatment groups, pancreatitis was induced with intraperitoneal injection of cerulein, followed by intraperitoneal injection of 1 ml saline (pancreatitis group) and 1 ml 5.2% UDE (treatment group). Pancreatic tissues were examined histopathologically. Pro-inflammatory cytokines (tumor necrosis factor-α), amylase and markers of apoptosis (M30, M65) were also measured in blood samples. Immunohistochemical staining was performed with Caspase-3 antibody. Histopathological findings in the UDE treatment group were less severe than in the pancreatitis group (5.7 vs 11.7, p = 0.010). TNF-α levels were not statistically different between treated and control groups (63.3 vs. 57.2, p = 0.141). UDE treatment was associated with less apoptosis [determined by M30, caspase-3 index (%)], (1.769 vs. 0.288, p = 0.056; 3% vs. 2.2%, p = 0.224; respectively). UDE treatment of pancreatitis merits further study. PMID:24995088

Effect of aging and diffuse chronic pancreatitis on pancreas elasticity evaluated using semiquantitative EUS elastography.

PubMed

Janssen, J; Papavassiliou, I

2014-06-01

Endosonographic elastography has been introduced as a method of estimating the stiffness of pancreatic tumors. This prospective single-center study was conducted to evaluate changes in the stiffness of the pancreas related to age and diffuse chronic pancreatitis. 46 individuals each up to age 60 (group 1) and over age 60 (group 2) with healthy pancreata and 26 patients with diffuse chronic pancreatitis (group 3) were included. Three elastograms were obtained in each case by endosonography in a defined section through the pancreatic body. Elastograms were further evaluated by histogram analysis. Mean strain values, based on a range from 0 (hardest) to 255 (softest), and their standard deviation were calculated from the histogram. The three groups were compared statistically with regard to pancreatic stiffness. A cut-off level for the diagnosis of chronic pancreatitis was defined by testing receiver operating characteristics curves. The strain values (mean, SD) measured in the pancreatic body in groups 1 - 3 were 110.2 (23.9), 80.0 (16.4), and 32.4 (11.9), respectively. Pairwise comparison of the groups revealed highly significant differences (p < 0.001). At a cut-off value of 50, the area under the curve was 0.993 for distinguishing between chronic pancreatitis and healthy pancreata in people aged over 60. Semiquantitative elastography shows that pancreata become significantly harder during aging, but remain softer than in chronic pancreatitis. A cut-off value of 50 is suggested as a possible diagnostic criterion for diffuse chronic pancreatitis. © Georg Thieme Verlag KG Stuttgart · New York.

Percutaneous transgastric irrigation drainage in combination with endoscopic necrosectomy in necrotizing pancreatitis (with videos).

PubMed

Raczynski, Susanne; Teich, Niels; Borte, Gudrun; Wittenburg, Henning; Mössner, Joachim; Caca, Karel

2006-09-01

Endoscopic drainage of pancreatic acute and chronic pseudocysts and pancreatic necrosectomy have been shown to be beneficial for critically ill patients, with complete endoscopic resolution rates of around 80%. Our purpose was to describe an improved endoscopic technique used to treat pancreatic necrosis. Case report. University hospital. Two patients with large retroperitoneal necroses were treated with percutaneous transgastric retroperitoneal flushing tubes and a percutaneous transgastric jejunal feeding tube by standard percutaneous endoscopic gastrostomy access in addition to endoscopic necrosectomy. Intensive percutaneous transgastric flushing in combination with percutaneous normocaloric enteral nutrition and repeated endoscopic necrosectomy led to excellent outcomes in both patients. Small number of patients. The "double percutaneous endoscopic gastrostomy" approach for simultaneous transgastric drainage and normocaloric enteral nutrition in severe cases of pancreatic necroses is safe and effective. It could be a promising improvement to endoscopic transgastric treatment options in necrotizing pancreatitis.

Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L-arginine-induced acute pancreatitis rat model.

PubMed

Wang, Yunlong; Guo, Weiting; Li, Yuan; Pan, Xinting; Lv, Wenshan; Cui, Lingling; Li, Changgui; Wang, Yangang; Yan, Shengli; Zhang, Jidong; Liu, Bin

2014-04-01

This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1β (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Arginase-II Promotes Tumor Necrosis Factor-α Release From Pancreatic Acinar Cells Causing β-Cell Apoptosis in Aging.

PubMed

Xiong, Yuyan; Yepuri, Gautham; Necetin, Sevil; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

2017-06-01

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice. © 2017 by the American Diabetes Association.

Infectious pancreatic necrosis virus isolated from farmed rainbow trout and tilapia in Kenya is identical to European isolates.

PubMed

Mulei, I R; Nyaga, P N; Mbuthia, P G; Waruiru, R M; Njagi, L W; Mwihia, E W; Gamil, A A A; Evensen, Ø; Mutoloki, S

2018-05-28

Infectious pancreatic necrosis virus (IPNV) is an aquabirnavirus that causes serious diseases in a variety of fish species worldwide. It has been isolated from a large number of healthy fresh and marine water fish. Prior to this study, there was no record of the presence of IPNV infection in Kenya. Here, the presence of IPNV in farmed rainbow trout and tilapia was examined in Nyeri County of central Kenya. Head kidney samples taken from five rainbow trout and three tilapia farms and stored in RNALater ® were processed by PCR followed by sequencing of a segment A fragment covering nucleotide positions 2,120-2,343 bp. IPNV was detected in all the farms sampled with infection ratios ranging from 0.3 to 0.78 although the infections were not associated with any specific clinical signs of disease. These findings were supported by immunohistochemistry staining of the virus in the kidney and exocrine pancreas of rainbow trout. Sequence alignment and phylogenetic analysis revealed that the Kenyan isolates were identical to European isolates, suggesting a common origin. These findings highlight the need for better biosecurity procedures with more stringent surveillance programmes and control for fish diseases, especially focusing on imported breeding materials to Kenya. © 2018 John Wiley & Sons Ltd.

Managing Incidental Pancreatic Cysts.

PubMed

Phan, Jennifer; Raman Muthusamy, V

2018-06-09

The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging. Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.

The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lou, Hai-zhou; Weng, Xiao-chuan; Pan, Hong-ming

Highlights: • INK-128 inhibits the survival and growth of human pancreatic cancer cells. • INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. • INK-128 blocks mTORC1/2 activation simultaneously in pancreatic cancer cells. • INK-128 down-regulates cyclin D1 and causes pancreatic cancer cell cycle arrest. • INK-128 significantly increases sensitivity of pancreatic cancer cells to gemcitabine. - Abstract: Pancreatic cancer has one of worst prognosis among all human malignancies around the world, the development of novel and more efficient anti-cancer agents against this disease is urgent. In the current study, we tested the potential effect of INK-128, a novel mammalianmore » target of rapamycin (mTOR) complex 1 and 2 (mTORC1/2) dual inhibitor, against pancreatic cancer cells in vitro. Our results demonstrated that INK-128 concentration- and time-dependently inhibited the survival and growth of pancreatic cancer cells (both primary cells and transformed cells). INK-128 induced pancreatic cancer cell apoptosis and necrosis simultaneously. Further, INK-128 dramatically inhibited phosphorylation of 4E-binding protein 1 (4E-BP1), ribosomal S6 kinase 1 (S6K1) and Akt at Ser 473 in pancreatic cancer cells. Meanwhile, it downregulated cyclin D1 expression and caused cell cycle arrest. Finally, we found that a low concentration of INK-128 significantly increased the sensitivity of pancreatic cancer cells to gemcitabine. Together, our in vitro results suggest that INK-128 might be further investigated as a novel anti-cancer agent or chemo-adjuvant for pancreatic cancer treatment.« less

Outcome of video-assisted translumbar retroperitoneal necrosectomy and closed lavage for severe necrotizing pancreatitis.

PubMed

Ulagendra Perumal, Srinivasan; Pillai, Sastha Ahanatha; Perumal, Senthilkumar; Sathyanesan, Jeswanth; Palaniappan, Ravichandran

2014-04-01

Surgery for necrotizing pancreatitis is associated with a high rate of morbidity and mortality. We present a series of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and analyse their outcomes. Records of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and closed drainage for infected pancreatitic necrosis between January 2008 and March 2012 were reviewed, retrospectively. Twenty-three out of 26 patients were males, with a mean age of 38.6 (±9.9) years. Alcohol was the aetiology in 18 patients, gall stones in 7, and in 1 it was idiopathic. The mean duration of symptoms before patients were taken up for surgery was 47.2 (±34.8) days. The mean computed tomography severity index was 7.7 (±1.2). All patients had undergone video-assisted retroperitoneal necrosectomy through a limited left lumbar incision. Post-operative lavage was given through drains placed in the retroperitoneum. Three patients required re-exploration. Eleven patients developed complications and there were two mortalities. The median intensive care unit (ICU) stay was 4 days (range 2-14 days). The mean post-operative hospital stay was 22.5 (±6.6) days. Video-assisted translumbar retroperitoneal necrosectomy followed by closed lavage of infected pancreatic necrosis in select cases of infected pancreatic necrosis was associated with a low rate of ICU stay, hospital stay and need for re-entry. © 2013 The Authors. ANZ Journal of Surgery © 2013 Royal Australasian College of Surgeons.

Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models

PubMed Central

Wen, Li; Voronina, Svetlana; Javed, Muhammad A.; Awais, Muhammad; Szatmary, Peter; Latawiec, Diane; Chvanov, Michael; Collier, David; Huang, Wei; Barrett, John; Begg, Malcolm; Stauderman, Ken; Roos, Jack; Grigoryev, Sergey; Ramos, Stephanie; Rogers, Evan; Whitten, Jeff; Velicelebi, Gonul; Dunn, Michael; Tepikin, Alexei V.; Criddle, David N.; Sutton, Robert

2015-01-01

Background & Aims Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release–activated calcium modulator ORAI1 is the most abundant Ca2+ entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice. Methods Mouse and human acinar cells, as well as HEK 293 cells transfected to express human ORAI1 with human stromal interaction molecule 1, were hyperstimulated or incubated with human bile acid, thapsigargin, or cyclopiazonic acid to induce calcium entry. GSK-7975A or CM_128 were added to some cells, which were analyzed by confocal and video microscopy and patch clamp recordings. Acute pancreatitis was induced in C57BL/6J mice by ductal injection of taurolithocholic acid 3-sulfate or intravenous' administration of cerulein or ethanol and palmitoleic acid. Some mice then were given GSK-7975A or CM_128, which inhibit ORAI1, at different time points to assess local and systemic effects. Results GSK-7975A and CM_128 each separately inhibited toxin-induced activation of ORAI1 and/or activation of Ca2+ currents after Ca2+ release, in a concentration-dependent manner, in mouse and human pancreatic acinar cells (inhibition >90% of the levels observed in control cells). The ORAI1 inhibitors also prevented activation of the necrotic cell death pathway in mouse and human pancreatic acinar cells. GSK-7975A and CM_128 each inhibited all local and systemic features of acute pancreatitis in all 3 models, in dose- and time-dependent manners. The agents were significantly more effective, in a range of parameters, when given at 1 vs 6 hours after induction of pancreatitis. Conclusions Cytosolic calcium overload, mediated via ORAI1, contributes to the pathogenesis of acute pancreatitis. ORAI1 inhibitors might be developed

[Latest advances in acute pancreatitis].

PubMed

de-Madaria, Enrique

2013-10-01

The present article analyzes the main presentations on acute pancreatitis (AP) in Digestive Disease Week 2013. Perfusion computed tomography allows early diagnosis of pancreatic necrosis. Neutrophil gelatinase-associated lipocalin predicts the development of acute renal failure, severe AP and death. Factors associated with greater fluid sequestration in AP are alcoholic etiology, an elevated hematocrit, and the presence of criteria of systemic inflammatory response syndrome; fluid sequestration is associated with a worse outcome. True pseudocysts (fluid collections without necrosis for more than 4 weeks) are a highly infrequent complication in AP. Patients with necrotic collections have a poor prognosis, especially if associated with infection. A meta-analysis on fluid therapy suggests that early aggressive fluid administration is associated with higher mortality and more frequent respiratory complications. According to a meta-analysis, enteral nutrition initiated within 24 hours of admission improves the outcome of AP compared with later initiation of enteral nutrition. Pentoxifylline could be a promising alternative in AP; a double-blind randomized study showed that this drug reduced the length of hospital and intensive care unit stay, as well as the need for intensive care unit admission. The association of octreotide and celecoxib seems to reduce the frequency of organ damage compared with octreotide alone. Mild AP can be managed in the ambulatory setting through hospital-at-home units after a short, 24-hour admission. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Src kinases play a novel dual role in acute pancreatitis affecting severity but no role in stimulated enzyme secretion.

PubMed

Nuche-Berenguer, Bernardo; Ramos-Álvarez, Irene; Jensen, R T

2016-06-01

In pancreatic acinar cells, the Src family of kinases (SFK) is involved in the activation of several signaling cascades that are implicated in mediating cellular processes (growth, cytoskeletal changes, apoptosis). However, the role of SFKs in various physiological responses such as enzyme secretion or in pathophysiological processes such as acute pancreatitis is either controversial, unknown, or incompletely understood. To address this, in this study, we investigated the role/mechanisms of SFKs in acute pancreatitis and enzyme release. Enzyme secretion was studied in rat dispersed pancreatic acini, in vitro acute-pancreatitis-like changes induced by supramaximal COOH-terminal octapeptide of cholecystokinin (CCK). SFK involvement assessed using the chemical SFK inhibitor (PP2) with its inactive control, 4-amino-7-phenylpyrazol[3,4-d]pyrimidine (PP3), under experimental conditions, markedly inhibiting SFK activation. In CCK-stimulated pancreatic acinar cells, activation occurred of trypsinogen, various MAP kinases (p42/44, JNK), transcription factors (signal transducer and activator of transcription-3, nuclear factor-κB, activator protein-1), caspases (3, 8, and 9) inducing apoptosis, LDH release reflective of necrosis, and various chemokines secreted (monocyte chemotactic protein-1, macrophage inflammatory protein-1α, regulated on activation, normal T cell expressed and secreted). All were inhibited by PP2, not by PP3, except caspase activation leading to apoptosis, which was increased, and trypsin activation, which was unaffected, as was CCK-induced amylase release. These results demonstrate SFK activation is playing a dual role in acute pancreatitis, inhibiting apoptosis and promoting necrosis as well as chemokine/cytokine release inducing inflammation, leading to more severe disease, as well as not affecting secretion. Thus, our studies indicate that SFK is a key mediator of inflammation and pancreatic acinar cell death in acute pancreatitis, suggesting it

Acoustic radiation force impulse shear wave elastography (ARFI) of acute and chronic pancreatitis and pancreatic tumor.

PubMed

Goertz, Ruediger S; Schuderer, Johanna; Strobel, Deike; Pfeifer, Lukas; Neurath, Markus F; Wildner, Dane

2016-12-01

Acoustic Radiation Force Impulse (ARFI) elastography evaluates tissue stiffness non-invasively and has rarely been applied to pancreas examinations so far. In a prospective and retrospective analysis, ARFI shear wave velocities of healthy parenchyma, pancreatic lipomatosis, acute and chronic pancreatitis, adenocarcinoma and neuroendocrine tumor (NET) of the pancreas were evaluated and compared. In 95 patients ARFI elastography of the pancreatic head, and also of the tail for a specific group, was analysed retrospectively. Additionally, prospectively in 100 patients ARFI was performed in the head and tail of the pancreas. A total of 195 patients were included in the study. Healthy parenchyma (n=21) and lipomatosis (n=30) showed similar shear wave velocities of about 1.3m/s. Acute pancreatitis (n=35), chronic pancreatitis (n=53) and adenocarcinoma (n=52) showed consecutively increasing ARFI values, respectively. NET (n=4) revealed the highest shear wave velocities amounting to 3.62m/s. ARFI elastography showed relevant differences between acute pancreatitis and chronic pancreatitis or adenocarcinoma. With a cut-off value of 1.74m/s for the diagnosis of a malignant disease the sensitivity was 91.1% whereas the specificity amounted to 60.4%. ARFI shear wave velocities present differences in various pathologies of the pancreas. Acute and chronic pancreatitis as well as neoplastic lesions show high ARFI values. Very high elasticity values may indicate malignant disease of the pancreas. However, there is a considerable overlap between the entities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Wall characterization for through-the-wall radar applications

NASA Astrophysics Data System (ADS)

Greneker, Gene; Rausch, E. O.

2008-04-01

There has been continuing interest in the penetration of multilayer building materials, such as wood walls with air gaps and concrete hollow core block, using through-the-wall (TTW) radar systems. TTW operational techniques and signal propagation paths vary depending on how the TTW system is intended to be operated. For example, the operator of a TTW radar may be required to place the radar against the intervening wall of interest while collecting data. Other operational doctrines allow the radar to be operated in a stand-off mode from the wall. The stand-off distances can vary from feet to hundreds of feet, depending on the type of radar being used. When a signal is propagated through a multilayer wall with air gaps between the material and the wall construction uses materials of radically different dielectric constants, attenuation may not be the only effect that the probing signal experiences passing through the wall. This paper presents measurements of a hollow core concrete block wall and the measurement of a standard wall constructed of siding and wallboard. Both types of walls are typically found in most U.S. homes. These limited measurements demonstrate that the type of wall being penetrated by a wideband signal can modify the probing signal.

[Glutamate dehydrogenase activity in the pancreatic tissue in acute experimental pancreatitis and under the action of sodium thiosulphate].

PubMed

Simavorian, P S; Saakian, I L; Gevorkian, D A

1991-04-01

It has been established that the development of acute pancreatitis is accompanied by the reduced activity of glutamate dehydrogenase in the mitochondrial fraction of pancreas, pronounced in the focus of tissue necrosis and less expressed in the reactive inflammation focus. Besides this in the pancreas redistribution of enzyme, activity in the subcellular organelles takes place and enzyme activity emerges in the cytosol and further--in the blood and peritoneum liquid. Sodium thiosulfate has a marked correlation effect.

External pancreatic fistula as a sequel to management of acute severe necrotizing pancreatitis.

PubMed

Sikora, Sadiq S; Khare, Ritu; Srikanth, Gadiyaram; Kumar, Ashok; Saxena, Rajan; Kapoor, Vinay K

2005-01-01

External pancreatic fistula (EPF) is a common sequel to surgical or percutaneous intervention for infective complications of acute severe pancreatitis. The present study was aimed at studying the clinical profile, course and outcome of patients with EPF following surgical or percutaneous management of these infective complications. A retrospective analysis of clinical data of patients with EPF following intervention (surgical or percutaneous) for acute severe pancreatitis managed between January 1989 and April 2002 recorded on a prospective database was done. Univariate analysis of various factors (etiology, imaging findings prior to intervention, fistula characteristics and management) that could predict early closure of fistula was performed. Of 210 patients with acute severe pancreatitis, 43 (20%) patients developed EPF (mean age 38 (range 16-78) years, M:F ratio 5:1) following intervention for infected pancreatic necrosis (n=23) and pancreatic abscess (n=20) and constituted the study group. The fistula output was categorized as low (<200 ml), moderate (200-500 ml) and high (>500 ml) in 29 (67%), 11 (26%) and 3 (7%) patients, respectively. Fifteen patients (35%) had morbidity in the form of abscess (n=5), bleeding (n=1), pseudoaneurysm (n=2) and fever with no other focus of infection (n=7). Spontaneous closure of the fistula occurred in 38 (88%) patients. The average time to closure of fistula was 109+/- 26 (median 70) days. Fistula closed after intervention in 5 patients (2 after endoscopic papillotomy, 1 after fistulojejunostomy and 2 after downsizing the drains). Of the 38 patients with spontaneous closure, 9 (24%) patients developed a pseudocyst after a mean interval of 123 days of which 7 underwent surgical drainage of the cyst. Univariate analysis of various factors (etiology, imaging findings prior to intervention, fistula characteristics and management) failed to identify any factors that could predict early closure of fistula. EPF is a common sequel

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

PubMed

Maa, J; Grady, E F; Yoshimi, S K; Drasin, T E; Kim, E H; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-08-01

The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Off-wall boundary conditions for turbulent flows obtained from buffer-layer minimal flow units

NASA Astrophysics Data System (ADS)

Garcia-Mayoral, Ricardo; Pierce, Brian; Wallace, James

2012-11-01

There is strong evidence that the transport processes in the buffer region of wall-bounded turbulence are common across various flow configurations, even in the embryonic turbulence in transition (Park et al., Phys. Fl. 24). We use this premise to develop off-wall boundary conditions for turbulent simulations. Boundary conditions are constructed from DNS databases using periodic minimal flow units and reduced order modeling. The DNS data was taken from a channel at Reτ = 400 and a zero-pressure gradient transitional boundary layer (Sayadi et al., submitted to J . FluidMech .) . Both types of boundary conditions were first tested on a DNS of the core of the channel flow with the aim of extending their application to LES and to spatially evolving flows. 2012 CTR Summer Program.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1.

PubMed

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-03-14

To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.

Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1

PubMed Central

Jo, Il-Joo; Bae, Gi-Sang; Park, Kyoung-Chel; Choi, Sun Bok; Jung, Won-Seok; Jung, Su-Young; Cho, Jung-Hee; Choi, Mee-Ok; Song, Ho-Joon; Park, Sung-Joo

2013-01-01

AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model. METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated. RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB. CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB. PMID:23539679

Ex vivo human bile duct radiofrequency ablation with a bipolar catheter.

PubMed

Atar, Mustafa; Kadayifci, Abdurrahman; Daglilar, Ebubekir; Hagen, Catherine; Fernandez-Del Castillo, Carlos; Brugge, William R

2018-06-01

Management of the primary and secondary tumors of the bile ducts still remains as a major clinical challenge. Radiofrequency (RF) ablation (RFA) of these tumors is feasible but the effect of RF energy on the human common bile duct (CBD) and surrounding tissues has not been investigated. This pilot study aimed to determine the relationship between RF energy and the depth of ablation in the normal human CBD. The study was performed on fresh ex vivo human biliary-pancreatic tissue which had been resected for a pancreatic cyst or mass. The study was conducted within 15 min after resection. A bipolar Habib RFA catheter was placed into the middle of the intact CBD, and three different (5, 7, 10 W) power settings were applied over a 90-s period by an RF generator. Gross and histological examinations were performed. The depth of coagulation necrosis in CBD and the effect of RFA on CBD wall and surrounding pancreas tissue were determined by microscopic examination. The study included eight tissue samples. 5 W power was applied to three sites and RFA caused only focal epithelial necrosis limited to the CBD mucosa. 7 and 10 W were applied to five sites and coagulation necrosis occurred in all cases. Microscopically, necrosis was transmural, involved accessory bile duct glands, and extended to the surrounding pancreatic tissue in four of these cases. Macroscopically, RFA resulted in circumferential white-yellowish color change extending approximately 2 cm of the CBD. Bipolar RF energy application with 5 W resulted in limited ablation on CBD wall. However, 7 and 10 W generated tissue necrosis which extended through the CBD wall and into surrounding pancreas tissue. Endoscopic biliary RFA is an effective technique for local biliary tissue ablation but the use of high energy may injure surrounding tissue.

Reduction of Decoy Receptor 3 Enhances TRAIL-Mediated Apoptosis in Pancreatic Cancer

PubMed Central

Wang, Wei; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy. PMID:24204567

Reduction of decoy receptor 3 enhances TRAIL-mediated apoptosis in pancreatic cancer.

PubMed

Wang, Wei; Zhang, Mei; Sun, Weimin; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy.

CLINICAL AND THERAPEUTIC CORRELATIONS IN PATIENTS WITH SLIGHT ACUTE PANCREATITIS

PubMed Central

MUNHOZ-FILHO, Clewis Henri; BATIGÁLIA, Fernando; FUNES, Hamilton Luiz Xavier

2015-01-01

Background Acute pancreatitis is an inflammatory disease of the pancreas due to enzymatic autodigestion which can cause necrosis or multiple organ failure; its pathophysiology is not fully known yet. Aim To evaluate the correlation between clinical and therapeutic data in patients with mild acute pancreatitis. Methods A retrospective study in 55 medical records of patients admitted with acute mild pancreatitis was realized to analyze the association between age, leukocytosis, serum glutamic-oxaloacetic transaminase and lactate dehydrogenase, glucose, antibiotics, time admission and Ranson´s scores. Results There was a positive association between less intensive care (strict hydration, analgesia and monitoring of vital signs), early antibiotic therapy (monotherapy), early return to diet after 48 hours and laboratory control of the serum amylase and lipase (high in the first week and decreasing after 10 days, without any prognostic value). Conclusions Changes in the management of patients with mild acute pancreatitis, such as enteral nutrition, rational use of lower spectrum antibiotics and intensive care, have contributed significantly to the reduction of hospitalization time and mortality. PMID:25861064

Ablation of Phosphoinositide 3-Kinase-γ Reduces the Severity of Acute Pancreatitis

PubMed Central

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P.; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-01-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-γ (PI3Kγ) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3Kγ, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3Kγ significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3Kγ-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3Kγ, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3Kγ. Our results thus suggest that inhibition of PI3Kγ may be of therapeutic value in acute pancreatitis. PMID:15579443

Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system

USGS Publications Warehouse

Shivappa, R.B.; McAllister, P.E.; Edwards, G.H.; Santi, N.; Evensen, O.; Vakharia, V.N.; ,

2005-01-01

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also co-expressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56 %) than in the control fish (77 %), showing a dose-response pattern.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment of severe acute pancreatitis and its complications

PubMed Central

Zerem, Enver

2014-01-01

Severe acute pancreatitis (SAP), which is the most serious type of this disorder, is associated with high morbidity and mortality. SAP runs a biphasic course. During the first 1-2 wk, a pro-inflammatory response results in systemic inflammatory response syndrome (SIRS). If the SIRS is severe, it can lead to early multisystem organ failure (MOF). After the first 1-2 wk, a transition from a pro-inflammatory response to an anti-inflammatory response occurs; during this transition, the patient is at risk for intestinal flora translocation and the development of secondary infection of the necrotic tissue, which can result in sepsis and late MOF. Many recommendations have been made regarding SAP management and its complications. However, despite the reduction in overall mortality in the last decade, SAP is still associated with high mortality. In the majority of cases, sterile necrosis should be managed conservatively, whereas in infected necrotizing pancreatitis, the infected non-vital solid tissue should be removed to control the sepsis. Intervention should be delayed for as long as possible to allow better demarcation and liquefaction of the necrosis. Currently, the step-up approach (delay, drain, and debride) may be considered as the reference standard intervention for this disorder. PMID:25320523

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

PubMed

Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

2017-08-01

Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

PubMed Central

Pendharkar, Sayali A.; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S.

2017-01-01

Background Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Methods Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. Results A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. Conclusion GRP is significantly increased in patients with AGM after pancreatitis and is

Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis*

PubMed Central

Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F. Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M.

2016-01-01

Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. PMID:27226576

Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

PubMed

Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M

2016-07-08

Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Lap-Protector and Circular Stapler Are Useful in Cystogastrostomy for Large Pancreatic Pseudocyst with Severe Infection

PubMed Central

Kadowaki, Yoshihiko; Kurokawa, Takefumi; Tamura, Ryuji; Okamoto, Takahiro; Ishido, Nobuhiro; Mori, Takashi

2010-01-01

Lap-Protector, which is an abdominal wall sealing device, is usually used for wound protection from implantation of malignant cells or pyogenic fluid. A circular stapler is a common easy-to-use device for anastomosis of the digestive tract. We report the case of an infected pancreatic pseudocyst which was treated by surgical procedure using these useful devices. A 69-year-old man was followed up in our hospital after severe acute pancreatitis. He had undergone drainage surgeries twice for intractable pancreatic abscess followed by severe acute pancreatitis. He was admitted to our hospital complaining of loss of appetite, hiccups, and high fever. Computed tomography of the abdomen revealed an infected pancreatic pseudocyst which compressed the gastric wall. Internal drainage into the stomach was performed using Lap-Protector and circular stapler. The patient recovered uneventfully. Recently many endoscopic or laparoscopic procedures in cystogastrostomy are reported; however, a conventional open surgical approach is also important. This easy method may be useful for operative cystogastrostomy. PMID:20805947

A prospective study of the Bedside Index for Severity in Acute Pancreatitis (BISAP) score in acute pancreatitis: an Indian perspective.

PubMed

Senapati, Debadutta; Debata, Prasanna Kumar; Jenasamant, Saumya Sekhar; Nayak, Anil Kumar; Gowda S, Manoj; Swain, Narendra Nath

2014-01-01

A simple and easily applicable system for stratifying patients with acute pancreatitis is lacking. The aim of our study was to evaluate the ability of BISAP score to predict mortality in acute pancreatitis patients from our institution and to predict which patients are at risk for development of organ failure, persistent organ failure and pancreatic necrosis. All patients with acute pancreatitis were included in the study. BISAP score was calculated within 24 h of admission. A Contrast CT was used to differentiate interstitial from necrotizing pancreatitis within seven days of hospitalization whereas Marshall Scoring System was used to characterize organ failure. Among 246 patients M:F = 153:93, most common aetiology among men was alcoholism and among women was gallstone disease. 207 patients had no organ failure and remaining 39 developed organ failure. 17 patients had persistent organ failure, 16 of those with BISAP score ≥3. 13 patients in our study died, out of which 12 patients had BISAP score ≥3. We also found that a BISAP score of ≥3 had a sensitivity of 92%, specificity of 76%, a positive predictive value of 17%, and a negative predictive value of 99% for mortality. The BISAP score is a simple and accurate method for the early identification of patients at increased risk for in hospital mortality and morbidity. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

PubMed Central

Durgampudi, Chandra; Noel, Pawan; Patel, Krutika; Cline, Rachel; Trivedi, Ram N.; DeLany, James P.; Yadav, Dhiraj; Papachristou, Georgios I.; Lee, Kenneth; Acharya, Chathur; Jaligama, Deepthi; Navina, Sarah; Murad, Faris; Singh, Vijay P.

2015-01-01

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O–positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate–induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction. PMID:24854864

[Inflammatory pancreatic disease due to enzyme autodigestion: an exceptional model of glandular crinophagy].

PubMed

Sánchez-Fayos Calabuig, P; Martín Relloso, M Jesús; González Guirado, Agustina; Porres Cubero, Juan Carlos

2007-01-01

The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases a <necrosis-fibrosis> sequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of an pancreatic disease due to enzyme autodigestion>.

Early Assessment of Pancreatic Infections and Overall Prognosis in Severe Acute Pancreatitis by Procalcitonin (PCT)

PubMed Central

Rau, Bettina M.; Kemppainen, Esko A.; Gumbs, Andrew A.; Büchler, Markus W.; Wegscheider, Karl; Bassi, Claudio; Puolakkainen, Pauli A.; Beger, Hans G.

2007-01-01

Background: Pancreatic infections and sepsis are major complications in severe acute pancreatitis (AP) with significant impact on management and outcome. We investigated the value of Procalcitonin (PCT) for identifying patients at risk to develop pancreatic infections in severe AP. Methods: A total of 104 patients with predicted severe AP were enrolled in five European academic surgical centers within 96 hours of symptom onset. PCT was measured prospectively by a semi-automated immunoassay in each center, C-reactive protein (CRP) was routinely assessed. Both parameters were monitored over a maximum of 21 consecutive days and in weekly intervals thereafter. Results: In contrast to CRP, PCT concentrations were significantly elevated in patients with pancreatic infections and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels revealed only a moderate increase in patients with pancreatic infections in the absence of MODS (n = 7), all of whom were managed nonoperatively without mortality. A PCT value of ≥3.5 ng/mL on 2 consecutive days was superior to CRP ≥430 mg/L for the assessment of infected necrosis with MODS or nonsurvival as determined by ROC analysis with a sensitivity and specificity of 93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single or combined prediction of the two major complications was already possible on the third and fourth day after onset of symptoms with a sensitivity and specificity of 79% and 93% for PCT ≥3.8 ng/mL compared with 36% and 97% for CRP ≥430 mg/L, respectively (P = 0.002). Conclusion: Monitoring of PCT allows early and reliable assessment of clinically relevant pancreatic infections and overall prognosis in AP. This single test parameter significantly contributes to an improved stratification of patients at risk to develop major complications. PMID:17457167

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis

PubMed Central

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-01-01

BACKGROUND AND PURPOSE Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. EXPERIMENTAL APPROACH Rats were given CER (80 µg·kg−1 for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg−1 i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B4 and prostaglandin (PG)E2; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. KEY RESULTS Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B4 and prostaglandin E2 levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. CONCLUSIONS AND IMPLICATIONS Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. PMID:20977452

Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis.

PubMed

Polito, F; Bitto, A; Irrera, N; Squadrito, F; Fazzari, C; Minutoli, L; Altavilla, D

2010-11-01

Acute pancreatitis is an autodigestive process resulting in acute inflammation of the pancreas. Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. Rats were given CER (80 µg·kg⁻¹ for each of four injections at hourly intervals) or vehicle (Sham-CER). Animals were then randomized to receive flavocoxid (20 mg·kg⁻¹ i.p.) or vehicle, 30 min after the first CER injection. Two hours after the last CER injection, we evaluated damage to the pancreas by histological methods; serum levels of amylase, lipase, leukotriene (LT)B₄ and prostaglandin (PG)E₂ ; pancreatic expression of COX-2 and 5-LOX and tumour necrosis factor-α (TNF-α) gene expression by real-time polymerase chain reaction. Caerulein induced inflammatory changes in the pancreas and raised values of the other variables measured. In CER-treated animals, but not in those given saline, flavocoxid inhibited COX-2 and 5-LOX expression, reduced serum levels of lipase and amylase and the degree of pancreatic oedema. Treatment with flavocoxid blunted the increased pancreatic TNF-α mRNA expression, serum leukotriene B₄ and prostaglandin E₂ levels, and protected against histological damage in terms of vacuolization and leukocyte infiltration. Our results confirm the key role of both COX-2 and 5-LOX in the inflammatory response to acute pancreatitis. Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Pancreatitis associated with the helminth Serpinema microcephalus (Nematoda: Camallanidae) in exotic red-eared slider turtles (Trachemys scripta elegans).

PubMed

Hidalgo-Vila, Judit; Martínez-Silvestre, Albert; Ribas, Alexis; Casanova, Joan Carles; Pérez-Santigosa, Natividad; Díaz-Paniagua, Carmen

2011-01-01

Pancreatitis associated with the helminth Serpinema microcephalus was found in three of 19 free-ranging red-eared slider turtles (Trachemys scripta elegans) captured between March 2003 and September 2004 in southern Spain. Microscopic changes were associated with parasite migrations and were characterized by central areas of necrosis surrounded by leukocytes and resulted in destruction of exocrine tissue. The blood profile of one of the three female turtles revealed eosinophilia and hyperglycemia, common in helminth infections and pancreatic disorders respectively. These are the first reported cases of pancreatitis caused by the nematode S. microcephalus in the exotic and newly colonized host T. s. elegans.

Infectious pancreatic necrosis virus in fish by-products is inactivated with inorganic acid (pH 1) and base (pH 12).

PubMed

Myrmel, M; Modahl, I; Nygaard, H; Lie, K M

2014-04-01

The aquaculture industry needs a simple, inexpensive and safe method for the treatment of fish waste without heat. Microbial inactivation by inorganic acid (HCl) or base (KOH) was determined using infectious pancreatic necrosis virus (IPNV) as a model organism for fish pathogens. Salmonella and spores of Clostridium perfringens were general hygiene indicators in supplementary examinations. IPNV, which is considered to be among the most chemical- and heat-resistant fish pathogens, was reduced by more than 3 log in 4 h at pH 1.0 and pH 12.0. Salmonella was rapidly inactivated by the same treatment, whereas spores of C. perfringens were hardly affected. The results indicate that low and high pH treatment could be particularly suitable for fish waste destined for biogas production. pH treatment at aquaculture production sites could reduce the spread of fish pathogens during storage and transportation without disturbing the anaerobic digestion process. The treatment could also be an alternative to the current energy-intensive steam pressure sterilization of fish waste to be used by the bioenergy, fertilizer and soil improver industries. © 2013 John Wiley & Sons Ltd.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

PubMed

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-04-21

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

PubMed Central

Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

2017-01-01

Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats. PMID:28430136

Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis.

PubMed

Lupia, Enrico; Goffi, Alberto; De Giuli, Paolo; Azzolino, Ornella; Bosco, Ornella; Patrucco, Enrico; Vivaldo, Maria Cristina; Ricca, Marco; Wymann, Matthias P; Hirsch, Emilio; Montrucchio, Giuseppe; Emanuelli, Giorgio

2004-12-01

In pancreatic acini, the G-protein-activated phosphoinositide 3-kinase-gamma (PI3K gamma) regulates several key pathological responses to cholecystokinin hyperstimulation in vitro. Thus, using mice lacking PI3K gamma, we studied the function of this enzyme in vivo in two different models of acute pancreatitis. The disease was induced by supramaximal concentrations of cerulein and by feeding mice a choline-deficient/ethionine-supplemented diet. Although the secretive function of isolated pancreatic acini was identical in mutant and control samples, in both models, genetic ablation of PI3K gamma significantly reduced the extent of acinar cell injury/necrosis. In agreement with a protective role of apoptosis in pancreatitis, PI3K gamma-deficient pancreata showed an increased number of apoptotic acinar cells, as determined by terminal dUTP nick-end labeling and caspase-3 activity. In addition, neutrophil infiltration within the pancreatic tissue was also reduced, suggesting a dual action of PI3K gamma, both in the triggering events within acinar cells and in the subsequent neutrophil recruitment and activation. Finally, the lethality of the choline-deficient/ethionine-supplemented diet-induced pancreatitis was significantly reduced in mice lacking PI3K gamma. Our results thus suggest that inhibition of PI3K gamma may be of therapeutic value in acute pancreatitis.

Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-long Pancreatic Organogenesis

PubMed Central

Wang, Yunfang; Lanzoni, Giacomo; Carpino, Guido; Cui, Cai-Bin; Dominguez-Bendala, Juan; Wauthier, Eliane; Cardinale, Vincenzo; Oikawa, Tsunekazu; Pileggi, Antonello; Gerber, David; Furth, Mark E.; Alvaro, Domenico; Gaudio, Eugenio; Inverardi, Luca; Reid, Lola M.

2013-01-01

Peribiliary glands (PBGs) in bile duct walls, and pancreatic duct glands (PDGs) associated with pancreatic ducts, in humans of all ages, contain a continuous, ramifying network of cells in overlapping maturational lineages. We show that proximal (PBGs)-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency (NANOG,OCT4,SOX2), proliferation (Ki67), self-replication (SALL4), and early hepato-pancreatic commitment (SOX9,SOX17,PDX1,LGR5), transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes (PDX1), and expression of markers of pancreatic endocrine maturation (NGN3,MUC6,insulin). Radial-axis lineages start in PBGs near the ducts’ fibromuscular layers with stem cells and end at the ducts’ lumens with cells devoid of stem cell traits and positive for pancreatic endocrine genes. Biliary tree-derived cells behaved as stem cells in culture under expansion conditions, culture plastic and serum-free Kubota’s Medium, proliferating for months as undifferentiated cells, whereas pancreas-derived cells underwent only ∼8-10 divisions, then partially differentiated towards an islet fate. Biliary tree-derived cells proved precursors of pancreas’ committed progenitors. Both could be driven by 3-dimensional conditions, islet-derived matrix components and a serum-free, hormonally defined medium for an islet fate (HDM-P), to form spheroids with ultrastructural, electrophysiological and functional characteristics of neoislets, including glucose regulatability. Implantation of these neoislets into epididymal fat pads of immuno-compromised mice, chemically rendered diabetic, resulted in secretion of human C-peptide, regulatable by glucose, and able to alleviate hyperglycemia in hosts. The biliary tree-derived stem cells and their connections to pancreatic committed progenitors constitute a biological framework for life-long pancreatic organogenesis. PMID

Pancreatic thickness as a predictive factor for postoperative pancreatic fistula after distal pancreatectomy using an endopath stapler.

PubMed

Okano, Keiichi; Oshima, Minoru; Kakinoki, Keitaro; Yamamoto, Naoki; Akamoto, Shintaro; Yachida, Shinichi; Hagiike, Masanobu; Kamada, Hideki; Masaki, Tsutomu; Suzuki, Yasuyuki

2013-02-01

No consistent risk factor has yet been established for the development of pancreatic fistula (PF) after distal pancreatectomy (DP) with a stapler. A total of 31 consecutive patients underwent DP with an endopath stapler between June 2006 and December 2010 using a slow parenchymal flattening technique. The risk factors for PF after DP with an endopath stapler were identified based on univariate and multivariate analyses. Clinical PF developed in 7 of 31 (22 %) patients who underwent DP with a stapler. The pancreata were significantly thicker at the transection line in patients with PF (19.4 ± 1.47 mm) in comparison to patients without PF (12.6 ± 0.79 mm; p = 0.0003). A 16-mm cut-off for pancreatic thickness was established based on the receiver operating characteristic (ROC) curve; the area under the ROC curve was 0.875 (p = 0.0215). Pancreatic thickness (p = 0.0006) and blood transfusion (p = 0.028) were associated with postoperative PF in a univariate analysis. Pancreatic thickness was the only significant independent factor (odds ratio 9.99; p = 0.036) according to a multivariate analysis with a specificity of 72 %, and a sensitivity of 85 %. Pancreatic thickness is a significant independent risk factor for PF development after DP with an endopath stapler. The stapler technique is thus considered to be an appropriate modality in patients with a pancreatic thicknesses of <16 mm.

A post-labeling strategy based on dye-induced peeling of the aptamer off single-walled carbon nanotubes for electrochemical aptasensing.

PubMed

Fu, Yingchun; Wang, Ting; Bu, Lijuan; Xie, Qingji; Li, Penghao; Chen, Jinhua; Yao, Shouzhuo

2011-03-07

A simple and efficient post-labeling strategy based on dye-induced peeling of the aptamer molecules off single-walled carbon nanotubes was developed for electrochemical aptasensing of thrombin with a detection limit down to 3 pM.

Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells.

PubMed

Masamune, Atsushi; Yoshida, Naoki; Hamada, Shin; Takikawa, Tetsuya; Nabeshima, Tatsuhide; Shimosegawa, Tooru

2018-01-01

Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment. Copyright © 2017 Elsevier Inc. All rights reserved.

The preclinical evaluation of TIC10/ONC201 as an anti-pancreatic cancer agent.

PubMed

Zhang, Qiangbo; Wang, Hong; Ran, Lin; Zhang, Zongli; Jiang, Runde

2016-08-05

Here we evaluated the potential anti-pancreatic cancer activity by TIC10/ONC201, a first-in-class small-molecule inducer of tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL). The in vitro results showed that TIC10 induced potent cytotoxic and cytostatic activities in several human pancreatic cancer cell lines (Panc-1, Mia-PaCa2, AsPC-1 or L3.6). TIC10 activated both extrinsic (TRAIL-caspase-8-dependent) and endogenous/mitochondrial (caspase-9-dependent) apoptosis pathways in the pancreatic cancer cells. Molecularly, we showed that TIC10 inhibited Akt-Erk activation, yet induced TRAIL expression in pancreatic cancer cells. Significantly, TIC10, at a relatively low concentration, sensitized gemcitabine-induced growth inhibition and apoptosis against pancreatic cancer cells. Further, TIC10 and gemcitabine synergistically inhibited Panc-1 xenograft growth in SCID mice. The combination treatment also significantly improved mice survival. In addition, Akt-Erk in-activation and TRAIL/cleaved-caspase-8 induction were observed in TIC10-treated Panc-1 xenografts. Together, the preclinical results of the study demonstrate the potent anti-pancreatic cancer activity by TIC10, or with gemcitabine. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of biophysical tumor response to PDT in pancreatic cancer using localized reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Isabelle, Martin; Klubben, William; He, Ting; Laughney, Ashley M.; Glaser, Adam; Krishnaswamy, Venkataramanan; Hoopes, P. Jack; Hasan, Tayyaba; Pogue, Brian W.

2011-02-01

Biophysical changes such as inflammation and necrosis occur immediately following PDT and may be used to assess the treatment response to PDT treatment in-vivo. This study uses localized reflectance measurements to quantify the scatter changes in tumor tissue occurring in response to verteporfin-based PDT treatment in xenograft pancreas tumors. Nude mice were implanted with subcutaneous AsPC-1 pancreatic tumors cells in matrigel, and allowed to establish solid tumors near 100mm3 volume. The mice were sensitized with 1mg/kg of the active component of verteporfin (benzoporphryin derivative, BPD), one hour before light delivery. The optical irradiation was performed using a 1 cm cylindrical interstitial diffusing tip fiber with 20J of red light (690nm). Tumor tissue was excised progressively and imaged, from 1 day to 4 weeks, after PDT treatment. The tissue sections were stained and analyzed by an expert veterinary pathologist, who provided information on tissue regions of interest. This information was correlated with variations in scattering and absorption parameters elucidated from the spectral images and the degree of necrosis and inflammation involvement was identified. Areas of necrosis and dead cells exhibited the lowest average scatter irradiance signature (3.78 and 4.07 respectively) compared to areas of viable pancreatic tumor cells and areas of inflammation (5.81 and 7.19 respectively). Bilirubin absorbance parameters also showed a lower absorbance value in necrotic tissue and areas of dead cells (0.05 and 0.1 respectively) compared to tissue areas for viable pancreatic tumor cells and areas of inflammation (0.28 and 0.35). These results demonstrate that localized reflectance spectroscopy is an imaging modality that can be used to identify tissue features associated with PDT treatment (e.g. necrosis and inflammation) that can be correlated with histopathologically-reviewed H&E stained slides. Further study of this technique may provide means for automated

Current immunotherapeutic strategies in pancreatic cancer.

PubMed

Plate, Janet M D

2007-10-01

The immune systems of patients with newly diagnosed pancreatic cancers are functional, with T-cell responses capable of responding to tumor antigen presentation. Pancreatic tumors have been demonstrated to express tumor antigens as mutated, altered, underglycosylated and/or inappropriately overexpressed proteins. Considering these two facts, it should be possible for patients' bodies to recognize their tumors as foreign and to reject them. A number of clinical trials have been initiated to exploit this immune activation to eradicate or stabilize tumor growth. Immunotherapeutic trials include the specific testing of a variety of tumor vaccines, of cytokines as adjuvants or directed cytotoxicity, and of monoclonal antibodies to target specific molecules. This article reviews evidence for immune-cell activation and function in patients with pancreatic cancer, and evidence that pancreatic tumor cells express tumor antigens, or mutated (or altered) proteins. Nevertheless, tumors survive immune attacks by producing products that help them to circumvent effector T cells. The article thus examines complications of immune evasion by cancer cells, as well as the challenges of trying to exploit the immune system in solid tumors where tumor cell products can turn off invading immune T cells set to kill them. Finally, the article discusses the choices of a variety of clinical trials using immune modulation for patients with pancreatic cancer.

Fluoroscopy-assisted vs fluoroless endoscopic ultrasound-guided transmural drainage of pancreatic fluid collections: A comparative study.

PubMed

Consiglieri, Claudia F; Gornals, Joan B; Busquets, Juli; Peláez, Nuria; Secanella, Lluis; De-La-Hera, Meritxell; Sanzol, Resurrección; Fabregat, Joan; Castellote, José

2018-01-01

The need for fluoroscopy guidance in patients undergoing endoscopic ultrasound-guided transmural drainage (EUS-TMD) of peripancreatic fluid collections (PFCs) remains unclear. The aim of this study was to compare general outcomes of EUS-TMD of PFCs under fluoroscopy (F) vs fluoroless (FL). This is a comparative study with a retrospective analysis of a prospective and consecutive inclusion database at a tertiary centre, from 2009 to 2015. All patients were symptomatic pseudocyst (PSC) and walled-off pancreatic necrosis (WON). Two groups were assigned depending on availability of fluoroscopy. The groups were heterogeneous in terms of their demographic characteristics, PFCs and procedure. The main outcome measures included technical and clinical success, incidences, adverse events (AEs), and follow-up. Fifty EUS-TMD of PFCs from 86 EUS-guided drainages were included during the study period. Group F included 26 procedures, PSC 69.2%, WON 30.8%, metal stents 61.5% (46.1% lumen-apposing stent) and plastic stents 38.5%. Group FL included 24 procedures, PSC 37.5%, WON 62.5%, and metal stents 95.8% (lumen-apposing stents). Technical success was 100% in both groups, and clinical success was similar (F 88.5%, FL 87.5%). Technical incidences and intra-procedure AEs were only described in group F (7.6% and 11.5%, respectively) and none in group FL. Procedure time was less in group FL (8min, p=0.0341). Fluoroless in the EUS-TMD of PFCs does not involve more technical incidences or intra-procedure AEs. Technical and clinical success was similar in the two groups. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Predictors of severity in childhood pancreatitis: correlation with nutritional status and racial demographics.

PubMed

Vasilescu, Alexandra; Cuffari, Carmen; Santo Domingo, Lisa; Scheimann, Ann O

2015-04-01

Acute pancreatitis is one of the leading causes of rising pediatric hospitalizations in North America. The aim of this study was to assess the role of nutritional status and racial influences on the severity of acute pancreatitis in children. The institutional review board approved this retrospective chart review of children with the diagnosis of acute pancreatitis between the ages of 0 and 18 years hospitalized at the Johns Hopkins Hospital between 1998 and 2008. Parameters studied included biochemical markers associated with pancreatitis, review of severity of illness reflected through the length of stay, and pediatric intensive care unit admission. The length of in-patient hospitalization was longer for children with imaging findings of pseudocyst or pancreatic necrosis (23.1 ± 26.4 days vs 4.4 ± 10.6 days; P = 0.0074) and malnourished children versus normal weight and obese children (16.5 days for malnourished vs 10.6 days for normal weight vs 10.7 days for obese; P = 0.04). There was also a significant difference in the need for pediatric intensive care unit admission across ethnic groups (18% African American vs 7% white) (P = 0.04). Ethnicity and nutritional status may influence the severity and duration of hospitalization among children with pancreatitis.

Pathogenesis of chronic pancreatitis: an evidence-based review of past theories and recent developments.

PubMed

Stevens, Tyler; Conwell, Darwin L; Zuccaro, Gregory

2004-11-01

In the past several decades, four prominent theories of chronic pancreatitis pathogenesis have emerged: the toxic-metabolic theory, the oxidative stress hypothesis, the stone and duct obstruction theory, and the necrosis-fibrosis hypothesis. Although these traditional theories are formulated based on compelling scientific observations, substantial contradictory data also exist for each. Furthermore, the basic premises of some of these theories are directly contradictory. Because of the recent scientific progress in the underlying genetic, cellular, and molecular pathophysiology, there have been substantial advances in the understanding of chronic pancreatitis pathogenesis. This paper will provide an evidence-based review and critique of the traditional pathogenic theories, followed by a discussion of the new advances in pancreatic fibrogenesis. Moreover, we will discuss plausible pathogenic sequences applied to each of the known etiologies.

Metabolic epidermal necrosis in two dogs with different underlying diseases.

PubMed

Bond, R; McNeil, P E; Evans, H; Srebernik, N

1995-05-06

Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis. Results of a controlled clinical trial of selective decontamination.

PubMed

Luiten, E J; Hop, W C; Endtz, H P; Bruining, H A

1998-05-01

To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. Surgical intensive care units of 16 hospitals. A total of 2,159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patients) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73%) these infections occurred within 1 week following

First evidence of infectious hematopoietic necrosis virus (IHNV) in the Netherlands.

PubMed

Haenen, O L M; Schuetze, H; Cieslak, M; Oldenburg, S; Spierenburg, M A H; Roozenburg-Hengst, I; Voorbergen-Laarman, M; Engelsma, M Y; Olesen, N J

2016-08-01

In spring 2008, infectious hematopoietic necrosis virus (IHNV) was detected for the first time in the Netherlands. The virus was isolated from rainbow trout, Oncorhynchus mykiss (Walbaum), from a put-and-take fishery with angling ponds. IHNV is the causative agent of a serious fish disease, infectious hematopoietic necrosis (IHN). From 2008 to 2011, we diagnosed eight IHNV infections in rainbow trout originating from six put-and-take fisheries (symptomatic and asymptomatic fish), and four IHNV infections from three rainbow trout farms (of which two were co-infected by infectious pancreatic necrosis virus, IPNV), at water temperatures between 5 and 15 °C. At least one farm delivered trout to four of these eight IHNV-positive farms. Mortalities related to IHNV were mostly <40%, but increased to nearly 100% in case of IHNV and IPNV co-infection. Subsequent phylogenetic analysis revealed that these 12 isolates clustered into two different monophyletic groups within the European IHNV genogroup E. One of these two groups indicates a virus-introduction event by a German trout import, whereas the second group indicates that IHNV was already (several years) in the Netherlands before its discovery in 2008. © 2016 John Wiley & Sons Ltd.

Efficacy of conservative treatment, without necrosectomy, for infected pancreatic necrosis: a systematic review and meta-analysis.

PubMed

Mouli, Venigalla Pratap; Sreenivas, Vishnubhatla; Garg, Pramod Kumar

2013-02-01

Conservative treatment (intensive care, a combination of antimicrobial agents, and nutritional support, with or without drainage of the infected fluid) has recently been shown to be effective for patients with infected pancreatic necrosis (IPN), but the data from individual studies are not robust enough to recommend it as the standard of care. We performed a systematic review and meta-analysis of studies related to primary conservative management for IPN. We performed a literature search of MEDLINE/PubMed from January 1990 to March 2012 for studies of a priori protocols for primary conservative treatment, without necrosectomy, for consecutive patients with IPN. We analyzed data from 8 studies, comprising 324 patients with IPN who received primary conservative management. We then analyzed an additional 4 studies (comprising 157 patients) that reported the efficacy of percutaneous drainage in nonconsecutive patients with IPN. Outcome measures were the success of conservative management strategy, need for necrosectomy, and mortality. There was significant heterogeneity in results among the studies. Based on a random effects model, conservative management was successful for 64% of patients (95% confidence interval [CI], 51%-78%); mortality was 12% (95% CI, 6%-18%), and 26% of patients required necrosectomy or additional surgery for complications (95% CI, 15%-37%). A separate analysis of 4 studies that reported outcomes of nonconsecutive patients with IPN following percutaneous drainage had comparable results; 50% had successful outcomes (95% CI, 43%-58%), mortality was 18% (95% CI, 6%-30%), and 38% of patients required surgery (95% CI, 20%-56%). Conservative management without necrosectomy is a successful approach for 64% of patients with IPN. This approach has low mortality and prevents surgical necrosectomy. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

[253 patients with acute pancreatitis treated at the surgical clinic in Zagreb].

PubMed

Bakran, I

1977-01-01

253 patients with acute pancreatitis were treated in clinic for surgery in Zagreb through last 23 years. The most frequent cause of pancreatitis were diseases of biliary tract, obesity, vascular deseases, alcoholism etc. In the symtomatology, the pain was present in all patients and majority of them had abdominal symptoms as well. Most of the patients came to the treatment within the firsts 24 to 48 hours. Besides Trasylol various conservative therapy was applied and some patients were operated either on billiary ducts or on pancreas. 85 patients had to be operated again on billiary tract afterwards. From 253 patients treated 24 died (9,48%) because of the necrosis of pancreas and alterations on various other organs.

A possible case of saw palmetto-induced pancreatitis.

PubMed

Wargo, Kurt A; Allman, Elena; Ibrahim, Farrah

2010-07-01

A 65-year-old male with a history of diabetes, hypertension, hyperlipidemia, gout, Barrett esophagitis, and chronic gastritis developed acute pancreatitis after taking one week of the herbal medicine, saw palmetto, for symptoms related to benign prostatic hyperplasia (BPH). Ultrasound and computed tomography ruled out cholelithiasis and obstruction, triglycerides were normal, and he had no recent infection or trauma. He had a history of occasional alcohol consumption, though there was no recent increased intake. The most likely cause of pancreatitis in this case was saw palmetto. Saw palmetto (Serenoa repens) is an herbal medication used primarily in the treatment of symptoms related to BPH. It has a high content of fatty acids and phytosterols which are thought to exert their effects by inhibiting the enzyme 5-alpha-reductase, thereby preventing the conversion of testosterone into dihydrotestosterone (DHT). It has been postulated that saw palmetto directly stimulates estrogenic receptors and inhibits progesterone receptors in the prostate tissue. A previous report implicated the estrogen/antiandrogen properties of saw palmetto as inducing hepatotoxicity in a patient. Additionally, it has also been postulated that stimulation of the estrogenic receptors may lead to increased triglyceride levels or induction of a hypercoagulable state that leads to pancreatic necrosis. Finally, inhibition of cyclooxygenase, a property of saw palmetto, may be linked to acute pancreatitis. Acute pancreatitis, a serious and sometimes fatal disorder may occur secondary to medications. Although the mechanism is not fully known, this is the second case of acute pancreatitis that has been documented secondary to the herbal medication saw palmetto. It is important for clinicians to obtain detailed medication histories, including over-the-counter and herbal medications, in order to prevent further complications from occurring.

FH535, a β-catenin pathway inhibitor, represses pancreatic cancer xenograft growth and angiogenesis

PubMed Central

Gong, Fei-Ran; Zhou, Binhua P.; Lian, Lian; Shen, Bairong; Chen, Kai; Duan, Weiming; Wu, Meng-Yao; Tao, Min; Li, Wei

2016-01-01

The WNT/β-catenin pathway plays an important role in pancreatic cancer carcinogenesis. We evaluated the correlation between aberrant β-catenin pathway activation and the prognosis pancreatic cancer, and the potential of applying the β-catenin pathway inhibitor FH535 to pancreatic cancer treatment. Meta-analysis and immunohistochemistry showed that abnormal β-catenin pathway activation was associated with unfavorable outcome. FH535 repressed pancreatic cancer xenograft growth in vivo. Gene Ontology (GO) analysis of microarray data indicated that target genes responding to FH535 participated in stemness maintenance. Real-time PCR and flow cytometry confirmed that FH535 downregulated CD24 and CD44, pancreatic cancer stem cell (CSC) markers, suggesting FH535 impairs pancreatic CSC stemness. GO analysis of β-catenin chromatin immunoprecipitation sequencing data identified angiogenesis-related gene regulation. Immunohistochemistry showed that higher microvessel density correlated with elevated nuclear β-catenin expression and unfavorable outcome. FH535 repressed the secretion of the proangiogenic cytokines vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and tumor necrosis factor-α, and also inhibited angiogenesis in vitro and in vivo. Protein and mRNA microarrays revealed that FH535 downregulated the proangiogenic genes ANGPT2, VEGFR3, IFN-γ, PLAUR, THPO, TIMP1, and VEGF. FH535 not only represses pancreatic CSC stemness in vitro, but also remodels the tumor microenvironment by repressing angiogenesis, warranting further clinical investigation. PMID:27323403

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

PubMed

Toyonaga, Takuya; Hirata, Kenji; Yamaguchi, Shigeru; Hatanaka, Kanako C; Yuzawa, Sayaka; Manabe, Osamu; Kobayashi, Kentaro; Watanabe, Shiro; Shiga, Tohru; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Kuge, Yuji; Tamaki, Nagara

2016-07-01

Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for

Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL6 mice.

PubMed

Zhang, Jun; Rouse, Rodney L

2014-09-01

Three classical rodent models of acute pancreatitis were created in an effort to identify potential pre-clinical models of drug-induced pancreatitis (DIP) and candidate non-invasive biomarkers for improved detection of DIP. Study objectives included designing a lexicon to minimize bias by capturing normal variation and spontaneous and injury-induced changes while maintaining the ability to statistically differentiate degrees of change, defining morphologic anchors for novel pancreatic injury biomarkers, and improved understanding of mechanisms responsible for pancreatitis. Models were created in male Sprague-Dawley rats and C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein; 2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine morphologically detectable processes were used in the lexicon; acinar cell hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis; vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis; ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each lexicon component. Consistent with previous studies, histopathology scores were significant greater in rats compared to mice at baseline and after treatment. The histopathology scores in caerulein and ligation-treated rats and mice were significantly greater than those of arginine-treated rats and mice. The present study supports a multifaceted pathogenesis for acute pancreatitis in which intra-acinar trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as well as activation/degranulation of mast cells and activated macrophages all contribute to the initiation and/or progression of acute inflammation of the exocrine pancreas.

[Skin necrosis during long-term fluindione treatment revealing protein C deficiency].

PubMed

Merklen-Djafri, C; Mazurier, I; Samama, M-M; Alhenc-Gelas, M; Tortel, M-C; Cribier, B; Roth, B; Batard, M-L

2012-03-01

Cutaneous necrosis is a rare complication of vitamin K antagonist therapy. It presents as cutaneous hemorrhagic necrosis and usually occurs at the start of treatment. We describe an atypical case of recurrent skin necrosis after two years of treatment with fluindione. A 70-year old woman with a history of venous thromboembolism and obesity presented with a large haemorrhagic necrosis of the abdominal wall. She had been treated with fluindione for two years. Genetic protein C deficiency was discovered. Resumption of vitamin K antagonist therapy was followed by recurrence of skin necrosis despite concomitant administration of heparin. Treatment with vitamin K antagonists could not be continued. This observation is unusual due to the late onset of skin necrosis. The condition usually begins shortly after initiation of vitamin K antagonist therapy, generally between the third and the sixth day of treatment. It is due to a transient hypercoagulable state in patients with protein C deficiency or, in rare cases, protein S deficiency. This late-onset skin necrosis, occurring many years after initiation of anticoagulant therapy, may be explained by a sudden worsening of pre-existing protein C deficiency due to infectious and iatrogenic factors. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Metastatic pancreatic cancer presenting as linitis plastica of the stomach.

PubMed

Garg, Shivani; Mulki, Ramzi; Sher, Daniel

2016-03-08

Metastatic disease from pancreatic carcinoma involving the stomach is an unusual event, and the pattern of spread in the form of linitis plastica, to our knowledge, has not been reported previously. Local recurrence after curative resection for pancreatic cancer is the most common pattern of disease. We report a case of metastatic pancreatic adenocarcinoma presenting as linitis plastica of the stomach 4 years after curative resection. A 52-year-old man presented with epigastric pain and melaena 4 years after undergoing a Whipple's procedure for a poorly-differentiated pancreatic adenocarcinoma, stage IB; T2N0M0. CT imaging of the abdomen revealed thickening of the gastric wall, and subsequent oesophagogastroduodenoscopy (OGD) revealed diffuse friable erythaematous tissue. The biopsy specimen obtained during the OGD revealed a poorly differentiated adenocarcinoma, with similar appearance to the prior specimen obtained from the pancreas. 2016 BMJ Publishing Group Ltd.

Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: a key role for protein phosphatases.

PubMed

Escobar, Javier; Pereda, Javier; Arduini, Alessandro; Sandoval, Juan; Sabater, Luis; Aparisi, Luis; López-Rodas, Gerardo; Sastre, Juan

2009-01-01

Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreatitis and reactive oxygen species are also associated with the inflammatory process. Changes in thiol homestasis and redox signaling decisively contribute to amplification of the inflammatory cascade through mitogen activated protein kinase (MAP kinase) pathways. This review focuses on the relationship between oxidative stress, pro-inflammatory cytokines and MAP kinase/protein phosphatase pathways as major modulators of the inflammatory response in acute pancreatitis. Redox sensitive signal transduction mediated by inactivation of protein phosphatases, particularly protein tyrosin phosphatases, is highlighted.

The Epidemiology of Pancreatitis and Pancreatic Cancer

PubMed Central

Yadav, Dhiraj; Lowenfels, Albert B.

2013-01-01

Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

PubMed

Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

2017-01-01

The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

Pathophysiology of chronic pancreatitis.

PubMed

Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

2013-11-14

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful.

The epidemiology of pancreatitis and pancreatic cancer.

PubMed

Yadav, Dhiraj; Lowenfels, Albert B

2013-06-01

Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice.

PubMed

Criscimanna, Angela; Coudriet, Gina M; Gittes, George K; Piganelli, Jon D; Esni, Farzad

2014-11-01

Although the cells that contribute to pancreatic regeneration have been widely studied, little is known about the mediators of this process. During tissue regeneration, infiltrating macrophages debride the site of injury and coordinate the repair response. We investigated the role of macrophages in pancreatic regeneration in mice. We used a saporin-conjugated antibody against CD11b to reduce the number of macrophages in mice following diphtheria toxin receptor-mediated cell ablation of pancreatic cells, and evaluated the effects on pancreatic regeneration. We analyzed expression patterns of infiltrating macrophages after cell-specific injury or from the pancreas of nonobese diabetic mice. We developed an in vitro culture system to study the ability of macrophages to induce cell-specific regeneration. Depletion of macrophages impaired pancreatic regeneration. Macrophage polarization, as assessed by expression of tumor necrosis factor-α, interleukin 6, interleukin 10, and CD206, depended on the type of injury. The signals provided by polarized macrophages promoted lineage-specific generation of acinar or endocrine cells. Macrophage from nonobese diabetic mice failed to provide signals necessary for β-cell generation. Macrophages produce cell type-specific signals required for pancreatic regeneration in mice. Additional study of these processes and signals might lead to new approaches for treating type 1 diabetes or pancreatitis. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Treatment outcome of selective digestive decontamination and enteral nutrition in patients with severe acute pancreatitis.

PubMed

Sawa, Hidehiro; Ueda, Takashi; Takeyama, Yoshifumi; Yasuda, Takeo; Shinzeki, Makoto; Matsumura, Naoki; Nakajima, Takahiro; Matsumoto, Ippei; Fujita, Tsunenori; Ajiki, Tetsuo; Fujino, Yasuhiro; Kuroda, Yoshikazu

2007-01-01

Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP. We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C. The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN. SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.

Autoimmune pancreatitis can develop into chronic pancreatitis

PubMed Central

2014-01-01

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

Autoimmune pancreatitis can develop into chronic pancreatitis.

PubMed

Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Kawa, Shigeyuki

2014-05-21

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

Chronic pancreatitis

MedlinePlus

Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

Chronic pancreatitis.

PubMed

DiMagno, Matthew J; DiMagno, Eugene P

2012-09-01

We review important new clinical observations in chronic pancreatitis reported in 2011. Smoking increases the risk of nongallstone acute pancreatitis and the progression of acute pancreatitis to chronic pancreatitis. Binge drinking during Oktoberfest did not associate with increased hospital admissions for acute pancreatitis. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in chronic pancreatitis is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90 000 United States Pharmacopeia units of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared with endoscopic treatment in patients advanced chronic pancreatitis with a dilated main duct ± pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with chronic pancreatitis but approximately 30% of patients have significant side effects. Patients with nongallstone-related acute pancreatitis or chronic pancreatitis of any cause should cease smoking. Results of this year's investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in chronic pancreatitis, and the mechanisms and treatment of neuropathic pain in chronic pancreatitis.

Serratia marcescens Necrotizing Fasciitis Presenting as Bilateral Breast Necrosis

PubMed Central

Rehman, Tayyab; Moore, Thomas A.

2012-01-01

Serratia marcescens is an extremely rare cause of necrotizing fasciitis. We report the first case of necrotizing fasciitis of the chest wall due to infection with S. marcescens that initially manifested as bilateral breast necrosis. The patient had a fulminant course leading to death within 72 h of presentation. Literature pertinent to S. marcescens-mediated necrotizing fasciitis is also reviewed. PMID:22837315

[MECHANISMS OF OSTEOPENIC SYNDROME IMPLEMENTATION IN PATIENTS WITH COMORBIDITY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND CHRONIC PANCREATITIS].

PubMed

Zhelezniakova, N

2016-10-01

Objective -to identify mechanisms of osteopenic syndrome implementation in patients with comorbid course of COPD and chronic pancreatitis (CP). 51 patients with comorbidity of CP and COPD (main group), 47 - with isolated COPD (compared group) have been examined. Assessment of excretory function of the pancreas was performed by determination of elastase-1 in the feces. Concentrations of interleukin-1β, interleukin-6 and tumor necrosis factor-α were determined by ELISA. It has been found out that patients with comorbid pathology are characterized by the significant decrease of bone mineral density than in the compared group. The progression of pancreatic dysfunction exacerbates the processes of bone resorption. It was estimated that increasing of proinflammatory cytokines concentration leads to considerable enhancement of osteopenic processes. The presence of concomitant chronic pancreatitis in patients with COPD brings in an aggravation of resorptive processes in bone tissue, the severity of which depends on the degree of excretory pancreatic insufficiency and expressivity of proinflammatory cytokine cascade.

50 CFR 16.13 - Importation of live or dead fish, mollusks, and crustaceans, or their eggs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... necrosis, and infectious pancreatic necrosis have not been detected in the fish stocks from which the... hemorrhagic septicemia, infectious hematopoietic necrosis, and infectious pancreatic necrosis have not been... necrosis, and infectious pancreatic necrosis have been killed. (d) Any fish caught in the wild in North...

50 CFR 16.13 - Importation of live or dead fish, mollusks, and crustaceans, or their eggs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... necrosis, and infectious pancreatic necrosis have not been detected in the fish stocks from which the... hemorrhagic septicemia, infectious hematopoietic necrosis, and infectious pancreatic necrosis have not been... necrosis, and infectious pancreatic necrosis have been killed. (d) Any fish caught in the wild in North...

50 CFR 16.13 - Importation of live or dead fish, mollusks, and crustaceans, or their eggs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... necrosis, and infectious pancreatic necrosis have not been detected in the fish stocks from which the... hemorrhagic septicemia, infectious hematopoietic necrosis, and infectious pancreatic necrosis have not been... necrosis, and infectious pancreatic necrosis have been killed. (d) Any fish caught in the wild in North...

50 CFR 16.13 - Importation of live or dead fish, mollusks, and crustaceans, or their eggs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... necrosis, and infectious pancreatic necrosis have not been detected in the fish stocks from which the... hemorrhagic septicemia, infectious hematopoietic necrosis, and infectious pancreatic necrosis have not been... necrosis, and infectious pancreatic necrosis have been killed. (d) Any fish caught in the wild in North...

On/off ratio enhancement in single-walled carbon nanotube field-effect transistor by controlling network density via sonication

NASA Astrophysics Data System (ADS)

Jang, Ho-Kyun; Choi, Jun Hee; Kim, Do-Hyun; Kim, Gyu Tae

2018-06-01

Single-walled carbon nanotube (SWCNT) is generally used as a networked structure in the fabrication of a field-effect transistor (FET) since it is known that one-third of SWCNT is electrically metallic and the remains are semiconducting. In this case, the presence of metallic paths by metallic SWCNT (m-SWCNT) becomes a significant technical barrier which hinders the networks from achieving a semiconducting behavior, resulting in a low on/off ratio. Here, we report on an easy method of controlling the on/off ratio of a FET where semiconducting SWCNT (s-SWCNT) and m-SWCNT constitute networks between source and drain electrodes. A FET with SWCNT networks was simply sonicated under water to control the on/off ratio and network density. As a result, the FET having an almost metallic behavior due to the metallic paths by m-SWCNT exhibited a p-type semiconducting behavior. The on/off ratio ranged from 1 to 9.0 × 104 along sonication time. In addition, theoretical calculations based on Monte-Carlo method and circuit simulation were performed to understand and explain the phenomenon of a change in the on/off ratio and network density by sonication. On the basis of experimental and theoretical results, we found that metallic paths contributed to a high off-state current which leads to a low on/off ratio and that sonication formed sparse SWCNT networks where metallic paths of m-SWCNT were removed, resulting in a high on/off ratio. This method can open a chance to save the device which has been considered as a failed one due to a metallic behavior by a high network density leading to a low on/off ratio.

Chronic Pancreatitis.

PubMed

Stram, Michelle; Liu, Shu; Singhi, Aatur D

2016-12-01

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

PubMed

Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

2008-01-01

Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

Natural History After Acute Necrotizing Pancreatitis: a Large US Tertiary Care Experience.

PubMed

Umapathy, Chandraprakash; Raina, Amit; Saligram, Shreyas; Tang, Gong; Papachristou, Georgios I; Rabinovitz, Mordechai; Chennat, Jennifer; Zeh, Herbert; Zureikat, Amer H; Hogg, Melissa E; Lee, Kenneth K; Saul, Melissa I; Whitcomb, David C; Slivka, Adam; Yadav, Dhiraj

2016-11-01

Most studies of acute necrotizing pancreatitis (ANP) focus on short-term outcomes. We evaluated long-term survival and outcomes following ANP. Patients treated for ANP at the University of Pittsburgh Medical Center from 2001 to 2008 were studied. Data on presentation and course during initial hospitalization and follow-up (median 34 months) was extracted. Mean age of patients (n = 167) was 53 ± 16 years; 70 % were male, 94 % white, 71 % transfers, 52 % biliary etiology, and 78 % had first-attack of acute pancreatitis. Majority had severe disease with high Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (median 11), length of stay (median 26 days), intensive care unit (ICU) admission (87 %), presence of systemic inflammatory response syndrome (SIRS) (90 %), persistent organ failure (60 %), and infected necrosis (50 %). Intervention was needed in 74 %. Eighteen (10.8 %) patients died during index hospitalization, 9 (5.4 %) during the first year, and 13 (7.8 %) after 1 year. Median survival was significantly shorter when compared with age- and sex-matched US general population (9.1 vs. 26.1 years, p < 0.001). Increasing age (HR 1.05), persistent organ failure (HR 4.5), and >50 % necrosis (HR 3.8) were independent predictors of death at 1 year. In eligible patients, new-onset diabetes, oral pancreatic enzyme replacement therapy, and disability were noted in 45, 25, and 53 %, respectively. ANP significantly impacts long-term survival. A high proportion of patients develop functional derangement and disability following ANP.

Avascular Necrosis

MedlinePlus

... Financial Reports Watchdog Ratings Feedback Contact Select Page Avascular Necrosis Home > Cancer Resources > Late Effects of Treatment > Avascular Necrosis Avascular necrosis (AVN) is a disorder resulting from ...

[Mediastinal Pancreatic Pseudocyst with Pancreatic Pleural Effusion].

PubMed

Sasajima, Motoko; Kawai, Hideki; Suzuki, Yohei; Saito, Yoshitaro; Eto, Takeshi

2017-06-01

A 72-year-old man with chronic alcohol related pancreatitis was admitted for dyspnea and pain at the upper body. Chest X-ray showed right massive pleural effusion. Chest and abdominal contrast enhanced thin slice computed tomography revealed the route from the pancreatic head reaching the right thoracic cavity via the esophagus hiatus and the communication between the cystic lesion and main pancreatic duct. We drained the pleural effusion that showed abnormally high amylase activity. We diagnosed his illness as mediastinal pancreatic pseudocyst with pancreatic pleural effusion. Endoscopic Nasopancreatic Drainage catheter was placed in the main pancreatic duct, and the pleural effusion disappeared.

Pathophysiology of chronic pancreatitis

PubMed Central

Brock, Christina; Nielsen, Lecia Møller; Lelic, Dina; Drewes, Asbjørn Mohr

2013-01-01

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by progressive fibrotic destruction of the pancreatic secretory parenchyma. Despite the heterogeneity in pathogenesis and involved risk factors, processes such as necrosis/apoptosis, inflammation or duct obstruction are involved. This fibrosing process ultimately leads to progressive loss of the lobular morphology and structure of the pancreas, deformation of the large ducts and severe changes in the arrangement and composition of the islets. These conditions lead to irreversible morphological and structural changes resulting in impairment of both exocrine and endocrine functions. The prevalence of the disease is largely dependent on culture and geography. The etiological risk-factors associated with CP are multiple and involve both genetic and environmental factors. Throughout this review the M-ANNHEIM classification system will be used, comprising a detailed description of risk factors such as: alcohol-consumption, nicotine-consumption, nutritional factors, hereditary factors, efferent duct factors, immunological factors and miscellaneous and rare metabolic factors. Increased knowledge of the different etiological factors may encourage the use of further advanced diagnostic tools, which potentially will help clinicians to diagnose CP at an earlier stage. However, in view of the multi factorial disease and the complex clinical picture, it is not surprising that treatment of patients with CP is challenging and often unsuccessful. PMID:24259953

A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

PubMed

Sugimoto, Motokazu; Sonntag, David P; Flint, Greggory S; Boyce, Cody J; Kirkham, John C; Harris, Tyler J; Carr, Sean M; Nelson, Brent D; Barton, Joshua G; Traverso, L William

2015-11-01

According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P < 0.001), and polymicrobial culture fluid in drains (P = 0.015). A proactive PCD protocol persistently maintaining drain patency advanced to the site of leak controlled the prolonged amylase in drainage fluid resulting in a mortality rate of zero.

Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis.

PubMed

Klar, E; Endrich, B; Messmer, K

1990-02-01

A rabbit model was designed to study the microcirculation of the pancreas with special reference to changes occurring during acute pancreatitis. Intravital microscopy was used in conjunction with video techniques allowing for continuous observation and off-line evaluation of microvessel diameters and blood cell velocities. Based on the microvessel geometry a functional microvascular unit could be defined at the level of the pancreatic lobule consisting of intralobular arteries and veins and an arcade-like preferential pathway framing the capillary network. Experimental acute pancreatitis resulted in immediate leakage of the macromolecular plasma marker (FITC-Dextran 70) from the microvasculature suggesting increased permeability. In contrast to control conditions, pancreatic capillaries were excluded from the circulation during acute pancreatitis starting 30 min after induction with only single capillaries remaining perfused after 3 hours. At the same time, there was constant blood flow through the preferential pathways representing shunt perfusion.

Diagnosis and classification of pancreatic and duodenal injuries in emergency radiology.

PubMed

Linsenmaier, Ulrich; Wirth, Stefan; Reiser, Maximilian; Körner, Markus

2008-10-01

Pancreatic and duodenal injuries after blunt abdominal trauma are rare; however, delays in diagnosis and treatment can significantly increase morbidity and mortality. Multidetector computed tomography (CT) has a major role in early diagnosis of pancreatic and duodenal injuries. Detecting the often subtle signs of injury with whole-body CT can be difficult because this technique usually does not include a dedicated protocol for scanning the pancreas. Specific injury patterns in the pancreas and duodenum often have variable expression at early posttraumatic multidetector CT: They may be hardly visible, or there may be considerable exudate, hematomas, organ ruptures, or active bleeding. An accurate multidetector CT technique allows optimized detection of subtle abnormalities. In duodenal injuries, differentiation between a contusion of the duodenal wall or mural hematoma and a duodenal perforation is vital. In pancreatic injuries, determination of involvement of the pancreatic duct is essential. The latter conditions require immediate surgical intervention. Use of organ injury scales and a surgical classification adapted for multidetector CT enables classification of organ injuries for trauma scoring, treatment planning, and outcome control. In addition, multidetector CT reliably demonstrates potential complications of duodenal and pancreatic injuries, such as posttraumatic pancreatitis, pseudocysts, fistulas, exudates, and abscesses. (c) RSNA, 2008.

Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis

PubMed Central

Jeon, Tae Joo; Park, Ji Young

2017-01-01

AIM To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. METHODS We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. RESULTS Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. CONCLUSION Elevated baseline NLR correlates with severe acute pancreatitis and organ failure. PMID:28638228

Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis.

PubMed

Jeon, Tae Joo; Park, Ji Young

2017-06-07

To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. Elevated baseline NLR correlates with severe acute pancreatitis and organ failure.

Salutary and prophylactic effect of pentadecapeptide BPC 157 on acute pancreatitis and concomitant gastroduodenal lesions in rats.

PubMed

Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Jurina, L; Konjevoda, P; Hanzevacki, M; Ljubanović, D; Separović, J; Gjurasin, M; Bratulić, M; Artuković, B; Jelovac, N; Buljat, G

1996-07-01

The superior effectiveness of a new pentadecapeptide, BPC 157, on gastrointestinal and liver lesions, in conjunction with an antiinflammatory and analgetic activity was recently noted. In the present study, BPC 157 was tested as either a protective or healing agent in bile duct ligation-induced acute pancreatitis in rats. In addition, the positive influence of BPC 157 on concomitantly developed gastric and duodenal lesions was simultaneously investigated. BPC 157 (10 microg, 10 ng/kg body wt, intraperitoneally or intragastrically) was given prophylactically 1 hr before ligation, whereas the therapy was given once daily beginning with the 24 hr following ligation (last application 24 hr before killing). The effect was investigated at daily intervals until the end of the fifth day after ligation. In the pretreatment regimen, a strong pancreas protection was obtained. When applied in the condition of already established severe acute pancreatitis, an obvious salutory effect was consistently noted. Assessing the appearance of the necrosis, edema, neutrophils, and mononuclears, consistently less necrosis, edema, and neutrophils, but more mononuclears, were found in BPC-treated rats. Likewise, in studies of the serum amylase values, relative to control data, a markedly lower rise (BPC pretreatment regimen) as well as a worsening of the already raised values (BPC therapy regimen) was noted. Along with its beneficial effect on pancreatitis, a positive influence of BPC 157 on the gastric and duodenal lesion course in bile duct-ligated rats was noted in both the pre- and posttreatment regimen. Taken together, in further studies of acute pancreatitis therapy, BPC could be an interesting and useful agent with an additional positive impact on concomitant gastroduodenal pathology.

One-step cross-genogroup multiplex RT-qPCR with an internal control system for the detection of infectious pancreatic necrosis virus (IPNV).

PubMed

Hoferer, Marc; Braun, Anne; Skrypski, Julia; Bock, Sabine; Thalheim, Sabine; Sting, Reinhard

2017-09-01

Infectious pancreatic necrosis virus (IPNV) causes great losses in fish hatcheries world-wide. The detection of IPNV can be challenging in certain circumstances, particularly due to low viral load and the genetic variability of this RNA virus. For the first time, this project created a quantitative triplex real-time reverse transcription PCR (RT-qPCR), including an endogenous control system, for specific, sensitive and rapid detection of IPNV in routine diagnostics. Multiple sequence alignment of 46 nucleotide sequences of the segment A genome obtained from the NCBI database allowed the design of two RT-qPCR systems covering the IPNV genogroup 1 and genogroups 2-5, respectively. The completed triplex RT-qPCR including a salmonid-specific endogenous control showed high specificity and an analytical sensitivity of 20-40 oligonucleotide copies. Testing of dilution series of virus-loaded cell culture suspensions proved equality of the triplex RT-qPCR with virus detection in cell culture and a higher sensitivity than conventional RT-PCR in field samples. In comparative studies of a total of 77 field samples tested, 51 showed identical positive and 19 identical negative results in cell culture and the triplex RT-qPCR. However, seven other samples yielded positive results in the triplex RT-qPCR, but negative results in cell culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Coupling of Rigor Mortis and Intestinal Necrosis during C. elegans Organismal Death.

PubMed

Galimov, Evgeniy R; Pryor, Rosina E; Poole, Sarah E; Benedetto, Alexandre; Pincus, Zachary; Gems, David

2018-03-06

Organismal death is a process of systemic collapse whose mechanisms are less well understood than those of cell death. We previously reported that death in C. elegans is accompanied by a calcium-propagated wave of intestinal necrosis, marked by a wave of blue autofluorescence (death fluorescence). Here, we describe another feature of organismal death, a wave of body wall muscle contraction, or death contraction (DC). This phenomenon is accompanied by a wave of intramuscular Ca 2+ release and, subsequently, of intestinal necrosis. Correlation of directions of the DC and intestinal necrosis waves implies coupling of these death processes. Long-lived insulin/IGF-1-signaling mutants show reduced DC and delayed intestinal necrosis, suggesting possible resistance to organismal death. DC resembles mammalian rigor mortis, a postmortem necrosis-related process in which Ca 2+ influx promotes muscle hyper-contraction. In contrast to mammals, DC is an early rather than a late event in C. elegans organismal death. VIDEO ABSTRACT. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Development of an endoluminal high-intensity ultrasound applicator for image-guided thermal therapy of pancreatic tumors

NASA Astrophysics Data System (ADS)

Adams, Matthew S.; Scott, Serena J.; Salgaonkar, Vasant A.; Jones, Peter D.; Plata-Camargo, Juan C.; Sommer, Graham; Diederich, Chris J.

2015-03-01

An ultrasound applicator for endoluminal thermal therapy of pancreatic tumors has been introduced and evaluated through acoustic/biothermal simulations and ex vivo experimental investigations. Endoluminal therapeutic ultrasound constitutes a minimally invasive conformal therapy and is compatible with ultrasound or MR-based image guidance. The applicator would be placed in the stomach or duodenal lumen, and sonication would be performed through the luminal wall into the tumor, with concurrent water cooling of the wall tissue to prevent its thermal injury. A finite-element (FEM) 3D acoustic and biothermal model was implemented for theoretical analysis of the approach. Parametric studies over transducer geometries and frequencies revealed that operating frequencies within 1-3 MHz maximize penetration depth and lesion volume while sparing damage to the luminal wall. Patient-specific FEM models of pancreatic head tumors were generated and used to assess the feasibility of performing endoluminal ultrasound thermal ablation and hyperthermia of pancreatic tumors. Results indicated over 80% of the volume of small tumors (~2 cm diameter) within 35 mm of the duodenum could be safely ablated in under 30 minutes or elevated to hyperthermic temperatures at steady-state. Approximately 60% of a large tumor (~5 cm diameter) model could be safely ablated by considering multiple positions of the applicator along the length of the duodenum to increase coverage. Prototype applicators containing two 3.2 MHz planar transducers were fabricated and evaluated in ex vivo porcine carcass heating experiments under MR temperature imaging (MRTI) guidance. The applicator was positioned in the stomach adjacent to the pancreas, and sonications were performed for 10 min at 5 W/cm2 applied intensity. MRTI indicated over 400C temperature rise in pancreatic tissue with heating penetration extending 3 cm from the luminal wall.

Comparison of complication outcomes in acute pancreatitis following ERCP and conservative management at UKM medical centre: a six years retrospective study.

PubMed

Zamri, Z; Razman, J

2012-11-01

cases (72%) the treatment was conservative. Among 28 cases that ERCP was done within 72 hours after admission, 20 cases are mild where as only 8 cases are severe. However, in conservative group about 56 cases are mild and the other 16 are severe. Among the conservative group there are 12 cases which have complications. The complications are respiratory failure, renal failure, sepsis, shock and pancreatic necrosis. There are 7 cases whose have respiratory failure alone, 1 case developed renal failure and 1 case has a shock. 1 case developed both pancreatic necrosis with sepsis. 1 case each developed respiratory failure with sepsis and respiratory failure with renal failure. However no complications were noted in early ERCP group. As a conclusion in this study we found out that early ERCP have a significant role in acute pancreatitis compare to conservative management.

[Acute pancreatitis as the presenting feature of an IgA vasculitis: An unusual presentation].

PubMed

Fertitta, L; Noel, N; Ackermann, F; Lerolle, N; Benoist, S; Rocher, L; Lambotte, O

2017-10-01

IgA vasculitis is a systemic small vessel leukocytoclastic vasculitis characterized by skin purpura, arthritis, abdominal pain and nephritis. Most of the abdominal complications are due to edema and hemorrhage in the small bowel wall, but rarely to acute secondary pancreatitis. Here, we report a 53-year-old woman who presented with acute pancreatitis and, secondarily, developed skin purpura and arthritis at the seventh day of the clinical onset. Biological tests and computed tomographic scan allowed to rule out another cause of pancreatitis and IgA vasculitis was diagnosed as its etiology. The outcome was favorable without any relapse on glucocorticoids. Despite its rarity, pancreatitis is a potential life-threatening complication of IgA vasculitis in which the role of glucocorticoids and immunosuppressive drugs remains uncertain. A prompt elimination of other usual pancreatitis etiologies is mandatory to improve the management of the patients. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

[Surgical technique for the treatment of the serious acute necrotic pancreatitis in the National Hospital Edgardo Rebagliati Martins].

PubMed

Barreda Cevasco, Luis Alberto; Targarona Modena, Javier; Rodriguez Alegría, César

2002-01-01

A surgical technique for the treatment of severe acute pancreatitis with necrosis is presented as an alternative in the surgical treatment of this pathology; 60 patients underwent a surgery by the author et al. between October 1997 and January 2002, at the National Hospital Edgardo Rebagliati Martins, Lima, Peru. The mortality rate was 25%.

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis.

PubMed

Kawakubo, Kazumichi; Ohnishi, Shunsuke; Fujita, Hirotoshi; Kuwatani, Masaki; Onishi, Reizo; Masamune, Atsushi; Takeda, Hiroshi; Sakamoto, Naoya

2016-01-01

Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine and can be isolated from fetal membranes (FMs), particularly amniotic membranes. We investigated the effect of rat FM-derived MSCs (rFM-MSCs) and human amnion-derived MSCs (hAMSCs) on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. Effect of rFM-MSCs or hAMSC-conditioned medium was investigated in vitro. Acute pancreatitis was induced by intraductal injection of 4% taurocholate, and rFM-MSCs were transplanted intravenously. Chronic pancreatitis was induced by intravenous injection of 5 mg/kg dibutyltin dichloride, and hAMSCs were transplanted intravenously. The inflammatory reaction of macrophages induced by lipopolysaccharide and trypsin was significantly suppressed by rFM-MSC coculture. Pancreatic acinar cell injury induced by cerulein was significantly ameliorated by hAMSC-conditioned medium. Pancreatic stellate cell activation induced by tumor necrosis factor-α was significantly decreased by hAMSC-conditioned medium. Transplantation of rFM-MSCs significantly reduced the histological score and infiltration of CD68-positive macrophages in the rat pancreas. The hAMSC transplantation significantly decreased the expression of MCP-1 and attenuated the downregulation of amylase expression in the pancreas. Transplantation of FM-MSCs and AMSCs suppressed the inflammatory reaction of acute and chronic pancreatitis in rats.

Avascular Necrosis

MedlinePlus

Avascular necrosis Overview Avascular necrosis is the death of bone tissue due to a lack of blood supply. Also called osteonecrosis, it can lead to ... blood flow to a section of bone. Avascular necrosis is also associated with long-term use of ...

[Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

PubMed

Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

2016-02-01

One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

Increased Risk of Acute Pancreatitis in Patients with Rheumatoid Arthritis: A Population-Based Cohort Study

PubMed Central

Chang, Chi Ching; Chiou, Chi Sheng; Lin, Hsiu Li; Wang, Li Hsuan; Chang, Yu Sheng; Lin, Hsiu-Chen

2015-01-01

The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non- RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI [confidence interval] 1.43–1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73–0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis. PMID:26262880

[Acute pancreatitis and afferent loop syndrome. Case report].

PubMed

Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

2013-01-01

The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

Theoretical design and evaluation of endoluminal ultrasound applicators for thermal therapy of pancreatic cancer under image guidance

NASA Astrophysics Data System (ADS)

Adams, Matthew; Scott, Serena; Salgaonkar, Vasant; Sommer, Graham; Diederich, Chris

2017-03-01

An image-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. By considering a directional transducer array of planar, tubular, or curvilinear transducers, this design offers the potential for fast volumetric therapy and 3D spatial control over the energy deposition profile. Treatment of pancreatic tumor tissue would be performed in a minimally invasive fashion with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal wall would be achieved with a water-cooled balloon surrounding the transducers. A theoretical evaluation of this design was performed by developing a 3D acoustic and bioheat transfer model, with temperature and thermal dose solutions obtained using a FEM solver (COMSOL Multiphysics). Parametric studies were performed on a generalized anatomical model of the pancreas, tumor, and adjacent luminal wall to determine preferred transducer configurations and frequencies for maximizing lesion volume and penetration while sparing the luminal wall. Patient-specific models of pancreatic tumors were generated from CT studies and used to assess the feasibility of performing thermal ablation or hyperthermia on small (˜2 cm diameter) pancreatic head tumors with an endoluminal applicator positioned within the duodenum. Simulation results indicate lower transducer operating frequencies (1-3 MHz) are necessary to mitigate damage to the luminal wall, and a tradeoff between penetration depth and lesion volume emerges as the degree of focusing increases. For patient-specific ablation modeling of tumors within 30 mm of the luminal wall, approximately 95% of the volume could be ablated within 15 min using a planar or lightly focused transducer configuration without duodenal damage. Over 90% of the volume could be elevated above 40°C at steady state for hyperthermia applications (e.g., radiation sensitization, drug delivery) using a tubular transducer. For

Ca(2+) signals mediated by bradykinin type 2 receptors in normal pancreatic stellate cells can be inhibited by specific Ca(2+) channel blockade.

PubMed

Gryshchenko, Oleksiy; Gerasimenko, Julia V; Gerasimenko, Oleg V; Petersen, Ole H

2016-01-15

Bradykinin may play a role in the autodigestive disease acute pancreatitis, but little is known about its pancreatic actions. In this study, we have investigated bradykinin-elicited Ca(2+) signal generation in normal mouse pancreatic lobules. We found complete separation of Ca(2+) signalling between pancreatic acinar (PACs) and stellate cells (PSCs). Pathophysiologically relevant bradykinin concentrations consistently evoked Ca(2+) signals, via B2 receptors, in PSCs but never in neighbouring PACs, whereas cholecystokinin, consistently evoking Ca(2+) signals in PACs, never elicited Ca(2+) signals in PSCs. The bradykinin-elicited Ca(2+) signals were due to initial Ca(2+) release from inositol trisphosphate-sensitive stores followed by Ca(2+) entry through Ca(2+) release-activated channels (CRACs). The Ca(2+) entry phase was effectively inhibited by a CRAC blocker. B2 receptor blockade reduced the extent of PAC necrosis evoked by pancreatitis-promoting agents and we therefore conclude that bradykinin plays a role in acute pancreatitis via specific actions on PSCs. Normal pancreatic stellate cells (PSCs) are regarded as quiescent, only to become activated in chronic pancreatitis and pancreatic cancer. However, we now report that these cells in their normal microenvironment are far from quiescent, but are capable of generating substantial Ca(2+) signals. We have compared Ca(2+) signalling in PSCs and their better studied neighbouring acinar cells (PACs) and found complete separation of Ca(2+) signalling in even closely neighbouring PACs and PSCs. Bradykinin (BK), at concentrations corresponding to the slightly elevated plasma BK levels that have been shown to occur in the auto-digestive disease acute pancreatitis in vivo, consistently elicited substantial Ca(2+) signals in PSCs, but never in neighbouring PACs, whereas the physiological PAC stimulant cholecystokinin failed to evoke Ca(2+) signals in PSCs. The BK-induced Ca(2+) signals were mediated by B2 receptors and B2

Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG12D/Pdx-1-Cre Mice

PubMed Central

LIAO, JIE; HWANG, SUNG HEE; LI, HAONAN; LIU, JUN-YAN; HAMMOCK, BRUCE D.; YANG, GUANG-YU

2016-01-01

Mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. In the process of long-standing chronic inflammation, aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we determined the effect of our newly-synthesized novel compound trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM), a dual inhibitor of sEH and RAF1 proto-oncogene serine/threonine kinase (c-RAF), on inhibiting the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) in LSL-KrasG12D/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III was significantly suppressed. Inhibition of mutant Kras-transmitted phosphorylation of mitogen-activated protein kinase’s kinase/extracellular signal-regulated kinases was demonstrated in pancreatic tissues by western blots. Quantitative real-time polymerase chain reaction analysis revealed that t-CUPM treatment significantly reduced the levels of inflammatory cytokines including tumor necrosis facor-α, monocyte chemoattractant protein-1, as well as vascular adhesion molecule-1, and the levels of Sonic hedgehog and Gli transcription factor (Hedgehog pathway). Analysis of the eicosanoid profile revealed a significant increase of the EETs/dihydroxyeicosatrienoic acids ratio, which further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-RAF by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis

Antibiotic use in acute pancreatitis: An audit of current practice in a tertiary centre.

PubMed

Baltatzis, Minas; Mason, J M; Chandrabalan, Vishnu; Stathakis, Panagiotis; McIntyre, Ben; Jegatheeswaran, Santhalingam; Jamdar, Saurabh; O'Reilly, Derek A; Siriwardena, Ajith K

Intravenous antibiotic prophylaxis is not recommended in acute pancreatitis. According to current international guidelines antibiotics together with further intervention should be considered in the setting of infected necrosis. Appropriate antibiotic therapy particularly avoiding over-prescription is important. This study examines antibiotic use in acute pancreatitis in a tertiary centre using the current IAP/APA guidelines for reference. Data were collected on a consecutive series of patients admitted with acute pancreatitis over a 12 month period. Data were dichotomized by patients admitted directly to the centre and tertiary transfers. Information was collected on clinical course with specific reference to antibiotic use, episode severity, intervention and outcome. 111 consecutive episodes of acute pancreatitis constitute the reported population. 31 (28%) were tertiary transfers. Overall 65 (58.5%) patients received antibiotics. Significantly more tertiary transfer patients received antibiotics. Mean person-days of antibiotic use was 23.9 (sd 29.7) days in the overall study group but there was significantly more use in the tertiary transfer group as compared to patients having their index admission to the centre (40.9 sd 37.1 vs 10.2 sd 8.9; P < 0.005). Thirty four (44%) of patients with clinically mild acute pancreatitis received antibiotics. There is substantial use of antibiotics in acute pancreatitis, in particular in patients with severe disease. Over-use is seen in mild acute pancreatitis. Better consideration must be given to identification of prophylaxis or therapy as indication. In relation to repeated courses of antibiotics in severe disease there must be clear indications for use. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Pancreatic trauma.

PubMed

Lahiri, R; Bhattacharya, S

2013-05-01

Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

Chronic pancreatitis.

PubMed

Yang, Dennis; Forsmark, Chris E

2017-09-01

Summarize key clinical advances in chronic pancreatitis reported in 2016. Early diagnosis of chronic pancreatitis remains elusive. Recent studies suggest that endoscopic ultrasound may be less accurate than previously thought and new MRI techniques may be helpful. Genetic predisposition may independently affect the clinical course of chronic pancreatitis and the risk for pancreatic cancer. Cigarette smoking may have a greater negative impact on chronic pancreatitis than previously thought and moderate alcohol consumption may be protective. A multidisciplinary approach is necessary for the treatment of type 3 diabetes and nutritional deficiencies in chronic pancreatitis. Although endoscopic therapy remains a reasonable first-line option in treating chronic pancreatitis and its complications, early surgical intervention may be indicated for pain in select patients. Newer endoscopic ultrasound and MRI techniques are being evaluated to help with the early diagnosis of chronic pancreatitis. Both genetic predisposition and cigarette smoking are increasingly recognized as having a major impact in the course of the disease and the risk for pancreatic cancer. Endoscopic therapy is well tolerated and effective for the treatment of chronic pancreatitis and its complications although an early surgical approach for pain may be associated with improved clinical outcomes.

Pancreatitis in Children.

PubMed

Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

2016-11-01

Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

The utility of vitamin K3 (menadione) against pancreatic cancer.

PubMed

Osada, Shinji; Tomita, Hiroyuki; Tanaka, Yoshihiro; Tokuyama, Yasuharu; Tanaka, Hidenori; Sakashita, Fumio; Takahashi, Takao

2008-01-01

To evaluate the efficacy of vitamin K3 (VK3) against pancreatic cancer, the molecular mechanism of VK3 or gemcitabine (GEM)-induced inhibition of proliferation was characterized. The cell viability was determined using the 3-[4,5-dimethylthiazol]-2,5-diphenyl tetrazolium bromide (MTT) test method. The expressions of cellular proteins were evaluated by Western blot analysis. For morphological studies of the in vivo transplanted cancer cells, the tissues were stained with hematoxylin and eosin. The IC50 of VK3 for pancreatic cancer cells was calculated for 42.1 +/- 3.5 microM. Western blot analysis showed that VK3 induced rapid phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) 30 minutes after application. ERK but not JNK phosphorylation was maintained for at least 12 hours. Activation of apoptosis by VK3, as shown by molecular weight shifts of the pro-activated 32-kDa form of caspase-3 and poly(ADP-ribose)polymerase (PARP) cleavage of the 112-kDa form, was found. Treatment with the thiol antioxidant, L-cysteine (>0.2 mM), completely abrogated the VK3-induced phosphorylation of ERK, but not the JNK, and inhibition of proliferation. A caspase-3 inhibitor antagonized caspase-3 activation, but had no inhibitory effect on the proliferative activity of VK3. GEM at concentrations >0.1 microg/ml was found to inhibit cell proliferation after 24 hours. GEM also induced phosphorylation of JNK, activation of caspase-3 and accumulation of cyclin B1. Local application of VK3 was found to induce extensive tumor tissue necrosis, but slight hematemesis without necrosis was observed 48 hours after GEM injection. In Western blot, ERK but not JNK phosphorylation, was clearly detected in response to VK3 injection into the tumor tissue. The action of VK3 may lead to a favorable outcome against pancreatic cancer, and the detection of ERK phosphorylation in the tissue is important for predicting this effect.

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

PubMed Central

LU, KAI; YANG, JIAN; LI, DE-CHUN; HE, SONG-BING; ZHU, DONG-MING; ZHANG, LI-FENG; ZHANG, XU; CHEN, XIAO-CHEN; ZHANG, BING; ZHOU, JIAN

2016-01-01

Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer. PMID:27347132

Chronic pancreatitis with multiple pseudocysts and pancreatic panniculitis: A case report.

PubMed

Gu, Yuqing; Qian, Zhuyin

2018-06-01

Pancreatic pseudocyst can present single or multiple, inside or outside the pancreas. Pancreatic panniculitis is a rare skin lesion in pancreatic disease patients. The purpose of this study is to report a case of chronic pancreatitis coexisting with multiple pseudocysts and pancreatic panniculitis. A 46-year-old man with chronic pancreatitis presented multiple small cystic lesions inside the head of the pancreas and two large cystic lesions adjacent to the tail of the pancreas. The patient also developed subcutaneous nodules involving upper and lower limbs, hands, and lower abdomen bilaterally. The patient was diagnosed with pancreatic pseudocyst and pancreatic panniculitis resulted from chronic pancreatitis. Bile duct stent and pancreatic duct stent placement was performed endoscopicly. Panniculitis faded three weeks later and the pancreatic pseudocysts disappeared six weeks later. Clinicians should be aware of the manifestation of multiple pancreatic pseudocyst and pancreatic panniculitis, and endoscopic transpapillary drainage may be a effective way in this scenario.

Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

PubMed Central

Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

2015-01-01

Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma. PMID:27785295

Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol.

PubMed

Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, Birgitte K; Prunsild, Kaie; Zeller, Bernward; Vaitkeviciene, Goda; Abrahamsson, Jonas; Heyman, Mats; Taskinen, Mervi; Harila-Saari, Arja; Kanerva, Jukka; Frandsen, Thomas L

2014-04-01

L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe. © 2014 John Wiley & Sons Ltd.

Cystic dystrophy of the gastric and duodenal wall developing in heterotopic pancreas: an unrecognised entity.

PubMed Central

Fléjou, J F; Potet, F; Molas, G; Bernades, P; Amouyal, P; Fékété, F

1993-01-01

Ten patients in whom cystic dystrophy developed in a heterotopic pancreas of the duodenal (nine patients) or gastric (one patient) wall are reported. All were young or middle aged white men, only two of whom were alcoholic. The symptoms were caused by intestinal or biliary stenosis, or both, secondary to the inflammation and fibrosis. Only endosonography provided strong evidence for the diagnosis in three patients. All patients underwent surgery: a pancreaticoduodenectomy was performed in eight patients. The surgical specimen showed cystic lesions of the gut wall, occurring in inflammatory and fibrous heterotopic pancreatic tissue. The pancreas proper was normal in all patients. It is suggested that cystic dystrophy is an uncommon and serious complication of heterotopic pancreas. Similar cases associated with chronic pancreatitis of the pancreas have been observed and it is suggested that this process could be responsible for some of the chronic pancreatitis encountered in young, non-alcoholic patients. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8097180

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice

PubMed Central

Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

2016-01-01

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. METHODS: The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 m

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

PubMed

Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

2016-03-14

To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group

Roles of the bacterial cell wall and capsule in induction of tumor necrosis factor alpha by type III group B streptococci.

PubMed Central

Vallejo, J G; Baker, C J; Edwards, M S

1996-01-01

Group B streptococci (GBS) are the major cause of sepsis and fatal shock in neonates in the United States. The precise role of tumor necrosis factor alpha (TNF-alpha) in the development of human GBS sepsis has not been defined; however, whole GBS have been shown to induce the production of this inflammatory cytokine. We sought to determine which bacterial cell wall components of GBS are responsible for triggering TNF-alpha production. Human cord blood monocytes were stimulated with encapsulated (COH1) or unencapsulated (COH1-13) whole type III GBS or with purified bacterial components, including type III capsular polysaccharide (III-PS), group B polysaccharide (GB-PS), lipoteichoic acid (LTA), or peptidoglycan (PG). Lipopolysaccharide from Escherichia coli served as a control. Supernatants were harvested at specific timed intervals, and TNF-alpha levels were measured by enzyme-linked immunosorbent assay. Monocytes exposed to COH1 and COH1-13 induced similar amounts of TNF-alpha. III-PS, GB-PS, LTA, and PG each induced TNF-alpha in a time- and concentration-dependent manner. However, TNF-alpha release was significantly greater after stimulation by the GB-PS or PG than after stimulation by III-PS or LTA (P < 0.05). Our findings indicate that GB-PS and PG are the bacterial cell wall components primarily evoking TNF-alpha release. These, alone or in concert with other factors, may be responsible for septic shock accompanying GBS sepsis. PMID:8945544

Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

PubMed

Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

2017-09-01

Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

Pancreatic trauma

PubMed Central

Bhattacharya, S

2013-01-01

Introduction Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. Methods A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: ‘pancreatic trauma’, ‘pancreatic duct injury’, ‘radiology AND pancreas injury’, ‘diagnosis of pancreatic trauma’, and ‘management AND surgery’. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Results Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. Conclusions The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important

Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

PubMed Central

Tian, Yu-Feng; He, Chih-Tsueng; Chen, Yu-Ting; Hsieh, Po-Shiuan

2013-01-01

AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (FPV), with intraportal saline plus administration of LA (FPV + LA), with lipopolysaccharide (LPS) infusion (FPLPS), and with LPS infusion plus administration of LA (FPLPS + LA). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal

VP2 (PTA motif) encoding DNA vaccine confers protection against lethal challenge with infectious pancreatic necrosis virus (IPNV) in trout.

PubMed

Ahmadivand, Sohrab; Soltani, Mehdi; Behdani, Mahdi; Evensen, Øystein; Alirahimi, Ehsan; Soltani, Elahe; Hassanzadeh, Reza; Ashrafi-Helan, Javad

2018-02-01

IPNV in Atlantic salmon is represented by various strains with different virulence and immunogenicity linked to various motifs of the VP2 capsid. IPNV variant with P 217 , T 221 , A 247 (PTA) motif is found to be avirulent in Atlantic salmon, but virulent in rainbow trout, and other salmonid species. This study describes a DNA vaccine delivered intramuscularly encoding the VP2 protein of infectious pancreatic necrosis virus (IPNV) with PTA motif that confers high protection in rainbow trout (Oncorhynchus mykiss). Intramuscular injection of 2, 5 and 10 μg of DNA (pcDNA3.1-VP2) in rainbow trout fry (4-5 g), confers relative protection of 75-83% in the different vaccine groups at 30 days post vaccination (450° days). The VP2 gene is expressed in spleen, kidney, muscle and liver at day 30 post-vaccination (RT-PCR), and IFN-1 and Mx-1 mRNA are upregulated at early time post vaccination, and so also for IgM, IgT, CD4 and CD8 in the head kidney of vaccinated fish compared to controls, 15 and 30 days post vaccination. Significant increase of serum anti-IPNV antibodies was found 30-90 days post-vaccination that was correlated with protection levels. Mortality corresponded with viral VP4 gene expression were significantly decreased in vaccinated and challenged fish. This shows for the first time that a VP2-encoding DNA vaccine delivered intramuscularly elicits a high level of protection alongside with high levels of circulating antibodies in rainbow trout and a lowered viral replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Experimental Transmission of Infectious Pancreatic Necrosis Virus from the Blue Mussel, Mytilus edulis, to Cohabitating Atlantic Salmon (Salmo salar) Smolts

PubMed Central

Pietrak, Michael R.; Bricknell, Ian

2013-01-01

Integrated multitrophic aquaculture (IMTA) reduces the environmental impacts of commercial aquaculture systems by combining the cultivation of fed species with extractive species. Shellfish play a critical role in IMTA systems by filter-feeding particulate-bound organic nutrients. As bioaccumulating organisms, shellfish may also increase disease risk on farms by serving as reservoirs for important finfish pathogens such as infectious pancreatic necrosis virus (IPNV). The ability of the blue mussel (Mytilus edulis) to bioaccumulate and transmit IPNV to naive Atlantic salmon (Salmo salar) smolts was investigated. To determine the ability of mussels to filter and accumulate viable IPNV, mussels were held in water containing log 4.6 50% tissue culture infective dose(s) (TCID50) of the West Buxton strain of IPNV ml−1. Viable IPNV was detected in the digestive glands (DGs) of IPNV-exposed mussels as early as 2 h postexposure. The viral load in mussel DG tissue significantly increased with time and reached log 5.35 ± 0.25 TCID50 g of DG tissue−1 after 120 h of exposure. IPNV titers never reached levels that were significantly greater than that in the water. Viable IPNV was detected in mussel feces out to 7 days postdepuration, and the virus persisted in DG tissues for at least 18 days of depuration. To determine whether IPNV can be transmitted from mussels to Atlantic salmon, IPNV-exposed mussels were cohabitated with naive Atlantic salmon smolts. Transmission of IPNV did occur from mussels to smolts at a low frequency. The results demonstrate that a nonenveloped virus, such as IPNV, can accumulate in mussels and be transferred to naive fish. PMID:23872575

Bacteriological profile of pancreatic juice in patients with chronic pancreatitis.

PubMed

Parida, Salil Kumar; Pottakkat, Biju; Raja, Kalayarasan; Vijayahari, Ranjit; Lakshmi, Chandrasekharan Padma

2014-09-28

Information regarding the association of bacteria in the pancreatic fluid in patients with chronic pancreatitis is limited. This study was designed to analyze the prevalence of bacteria in pancreatic juice in patients with chronic pancreatitis and the association of positive pancreatic fluid culture with pre-operative and post-operative parameters. All patients with chronic pancreatitis who underwent operation from November 2011 to October 2013 were prospectively included in the study. Intra-operatively pancreatic duct fluid was collected and sent for culture sensitivity in all patients. The bacteriology of the fluid was analyzed and was correlated with preoperative, intraoperative and postoperative parameters. A total of 26 patients were analyzed. Two patients underwent endoscopic retrograde cholangio-pancreatography (ERCP) preoperatively. Bacteria was present in pancreatic duct fluid in 11 (42%) patients. Both patients who underwent ERCP had positive cultures. Most common organism observed was Escherichia coli (6/11, 55%) followed by Klebsiella pneumonia (3/11, 27%). Five patients with positive culture developed wound infection. Bacteria isolated from the wound were similar to pancreatic fluid. Bacteria is commonly present in the pancreatic juice in patients with chronic pancreatitis and its presence may have an effect on the post-operative infections following operations. Based on the pancreatic fluid culture results appropriate antibiotic can be given to the patients who will develop septic complications following surgery. Role of bacteria in the pathogenesis of the chronic calcific pancreatitis needs to be investigated in future studies.

Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors.

PubMed

Adrian, T E; Uttenthal, L O; Williams, S J; Bloom, S R

1986-07-31

Pancreatic polypeptide is often secreted by pancreatic endocrine tumors and is considered a marker for such tumors. To investigate the diagnostic value of this marker, we studied 323 patients with proved pancreatic endocrine tumors. We found plasma concentrations of pancreatic polypeptide to be elevated (more than 300 pmol per liter) in 144 patients (diagnostic sensitivity, 45 percent). However, plasma levels of pancreatic polypeptide can also be elevated in the absence of a pancreatic tumor. To ascertain whether the administration of atropine could distinguish between normal and tumor-associated polypeptide secretion, we studied 30 patients with pancreatic tumors and high plasma levels of pancreatic polypeptide, 18 patients without tumors who had elevated levels of pancreatic polypeptide, and eight normal controls. Polypeptide levels in the 18 patients without tumors were substantially lower than in the 30 patients with tumors. Atropine (1 mg intramuscularly) did not suppress polypeptide levels in patients with tumors, but did suppress plasma levels by more than 50 percent in all subjects without tumors. Thus, although its diagnostic sensitivity is low, pancreatic polypeptide appears to be a useful adjunctive marker of many pancreatic endocrine tumors, and the atropine suppression test can be used to distinguish normal from tumor-related secretion of the polypeptide. Identification of the type of pancreatic endocrine tumor still requires measurement of the hormone that is specific for the tumor.

Pancreatic cancer

PubMed Central

Vincent, Audrey; Herman, Joseph; Schulick, Rich; Hruban, Ralph H; Goggins, Michael

2011-01-01

Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients’ management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80–85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma. PMID:21620466

Chronic pancreatitis.

PubMed

Majumder, Shounak; Chari, Suresh T

2016-05-07

Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine pancreatic function changes after acute pancreatitis.

PubMed

Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

2011-10-01

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Environmental risk factors for chronic pancreatitis and pancreatic cancer.

PubMed

Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

2011-01-01

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

Chronic pancreatitis.

PubMed

Gupte, Anand R; Forsmark, Chris E

2014-09-01

We review selected important clinical observations in chronic pancreatitis reported in 2013. Early diagnosis of chronic pancreatitis remains difficult, although newer techniques utilizing endoscopic ultrasonography-elastography and MRI hold promise. Patients with chronic pancreatitis are at risk of nutritional deficiencies. Osteoporosis, osteopenia, and bone fracture are particularly common in these patients, and require active intervention and treatment. Diabetes caused by chronic pancreatitis, type 3c diabetes, has specific characteristics and requires careful management. Antioxidants and neuromodulators may decrease pain in some patients with chronic pancreatitis. Endoscopic treatment is effective and can be utilized in patients with painful chronic pancreatitis, although randomized trials demonstrate that surgical therapy is somewhat more durable and effective. Although surgery has typically been a last resort, some advocate early surgical intervention but the optimal time remains unknown. Early diagnosis of pancreatitis may be improved by newer techniques associated with endoscopic ultrasonography imaging. Treatment of nutritional deficiencies and diabetes is an important aspect of treating chronic pancreatitis. Pain relief with adjunct means of pain modulation should be tried before starting narcotics for pain control. Endoscopic therapy is appropriate for treating chronic pancreatitis and its local complications and surgical intervention can be considered early in carefully selected individuals.

Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells.

PubMed

Xiao, Huijie; Li, Shasha; Zhang, Dapeng; Liu, Tongjun; Yu, Ming; Wang, Feng

2013-01-01

Unrestrained glycolysis characterizes energy meta-bolism in cancer cells. Thus, antiglycolytic reagents such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (3-BrPA) may be used as anticancer drugs. In the present study, we examined the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells and investigated whether these effects were regulated by hypoxia-inducible factor-1α (HIF-1α). To this end, 2-DG and 3-BrPA were administered to wild-type (wt) MiaPaCa2 and Panc-1 pancreatic cancer cells that were incubated under hypoxic (HIF-1α-positive) or normoxic (HIF-1α-negative) conditions. In addition, 2-DG and 3-BrPA were also administered to si-MiaPaCa2 and si-Panc-1 cells that lacked HIF-1α as a result of RNA interference. Following drug exposure, cell population was measured using a viability assay. Both HIF-1α-positive and HIF-1α-negative MiaPaCa2 cells were further studied for their expression of Cu/Zn-superoxide dismutase (SOD1) and poly(ADP-ribose) polymerase (PARP) and for their contents of ATP and fumarate. In the viability assay, either 2-DG or 3-BrPA decreased the tested cells. Concurrent use of 2-DG and 3-BrPA resulted in a greater decrease of cells and also facilitated ATP depletion. In addition, 3-BrPA was seen to both decrease SOD1 and increase fumarate, which suggests that the reagent impaired the mitochondria. 3-BrPA also decreased both full-length PARP and cleaved PARP, which suggests that 3-BrPA-induced decrease in cell population was a result of cell necrosis rather than apoptosis. When HIF-1α was induced in wt-MiaPaCa2 cells by hypoxia, some effects of 2-DG and 3-BrPA were attenuated. We conclude that: i) concurrent use of 2-DG and 3-BrPA has better anticancer effects in pancreatic cancer cells, ii) 3-BrPA impairs the mitochondria of pancreatic cancer cells and induces cell necrosis, and iii) HIF-1α regulates the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells.

Circumportal Pancreas-a Must Know Pancreatic Anomaly for the Pancreatic Surgeon.

PubMed

Luu, Andreas Minh; Braumann, C; Herzog, T; Janot, M; Uhl, W; Chromik, A M

2017-02-01

Circumportal pancreas is a rare congenital pancreatic anomaly with encasement of the portal vein and/or the superior mesenteric vein by pancreatic tissue. It is often overlooked on cross-sectional imaging studies and can be encountered during pancreatic surgery. Pancreatic head resection with circumportal pancreas is technically difficult and bears an increased risk of postoperative pancreatic fistula. A retrospective chart review of our data base for all patients who had undergone pancreatic head resection between 2004 and 2015 was performed. We identified six patients out of 1102 patients who had undergone pancreatic head surgery in the study period. CT-scan and MRI were never able to identify circumportal pancreas prior to surgery. The right hepatic an artery derived from the superior mesenteric artery in four cases (67%). Additional resection of the pancreatic body was always performed. Postoperative course was uneventful in all cases without occurrence of pancreatic fistula. Circumportal pancreas is a rare entity every pancreatic surgeon should be aware of. It is difficult to identify on cross-sectional imaging studies. A right hepatic artery arising from the superior mesenteric artery should raise suspicion of circumportal pancreas. Additional pancreatic tissue resection should be performed during pancreatic head resections to avoid pancreatic fistula.

Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

PubMed

Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

2017-09-01

Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

Pancreatic Cancer

PubMed Central

Maitra, Anirban; Hruban, Ralph H.

2009-01-01

The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies. PMID:18039136

A novel quantitative immunomagnetic reduction assay for Nervous necrosis virus.

PubMed

Yang, Shieh Yueh; Wu, Jen Leih; Tso, Chun Hsi; Ngou, Fang Huar; Chou, Hsin Yiu; Nan, Fan Hua; Horng, Herng Er; Lu, Ming Wei

2012-09-01

Rapid, sensitive, and automatic detection platforms are among the major approaches of controlling viral diseases in aquaculture. An efficient detection platform permits the monitoring of pathogen spread and helps to enhance the economic benefits of commercial aquaculture. Nervous necrosis virus (NNV), the cause of viral encephalopathy and retinopathy, is among the most devastating aquaculture viruses that infect marine fish species worldwide. In the present study, a highly sensitive magnetoreduction assay was developed for detecting target biomolecules with a primary focus on NNV antigens. A standard curve of the different NNV concentrations that were isolated from infected Malabar grouper (Epinephelus malabaricus) was established before experiments were conducted. The test solution was prepared by homogeneous dispersion of magnetic nanoparticles coated with rabbit anti-NNV antibody. The magnetic nanoparticles in the solution were oscillated by magnetic interaction with multiple externally applied, alternating current magnetic fields. The assay's limit of detection was approximately 2 × 10(1) TCID(50)/ml for NNV. Moreover, the immunomagnetic reduction readings for other aquatic viruses (i.e., 1 × 10(7) TCID(50)/ml for Infectious pancreatic necrosis virus and 1 × 10(6.5) TCID(50)/ml for grouper iridovirus) were below the background noise in the NNV solution, demonstrating the specificity of the new detection platform.

Pancreatic surgery.

PubMed

Donahue, Timothy R; Reber, Howard A

2013-09-01

To summarize published research on pancreatic surgery over the past year. A number of studies aiming to reduce the costs associated with pancreatic surgery were reported. Retrospective analyses confirmed previous findings that neither the routine use of pancreatic duct stents decreases the rate of fistula formation nor does placement of a drain at the time of surgery change the morbidity in patients who develop one. Minimally invasive approaches, both laparoscopic and robot-assisted, are being performed more frequently to remove pancreatic cancers. A randomized trial confirmed that reinforcement of stapled closure during distal pancreatectomy reduces the rate of fistula formation. Controversy remains over whether small pancreatic neuroendocrine tumors need to be surgically resected or can be treated nonoperatively. Patients with chronic pancreatitis should be screened thoroughly before being offered surgical treatment; two studies reported preoperative factors that can be used to identify those most likely to experience pain relief. Studies published on pancreatic surgery last year focused on a wide-range of topics. The morbidity and mortality of patients undergoing pancreatic surgery continues to improve, and we anticipate that incorporation of these new findings will lead to even better outcomes.

Pancreatic Cancer

MedlinePlus

... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

PubMed Central

Bonior, Joanna; Warzecha, Zygmunt; Ceranowicz, Piotr; Gajdosz, Ryszard; Pierzchalski, Piotr; Kot, Michalina; Leja-Szpak, Anna; Nawrot-Porąbka, Katarzyna; Link-Lenczowski, Paweł; Olszanecki, Rafał; Bartuś, Krzysztof; Trąbka, Rafał; Kuśnierz-Cabala, Beata; Dembiński, Artur; Jaworek, Jolanta

2017-01-01

Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect. PMID:28665321

Molecular characterization of infectious pancreatic necrosis virus strains isolated from the three types of salmonids farmed in Chile.

PubMed

Manríquez, René A; Vera, Tamara; Villalba, Melina V; Mancilla, Alejandra; Vakharia, Vikram N; Yañez, Alejandro J; Cárcamo, Juan G

2017-01-31

The infectious pancreatic necrosis virus (IPNV) causes significant economic losses in Chilean salmon farming. For effective sanitary management, the IPNV strains present in Chile need to be fully studied, characterized, and constantly updated at the molecular level. In this study, 36 Chilean IPNV isolates collected over 6 years (2006-2011) from Salmo salar, Oncorhynchus mykiss, and Oncorhynchus kisutch were genotypically characterized. Salmonid samples were obtained from freshwater, estuary, and seawater sources from central, southern, and the extreme-south of Chile (35° to 53°S). Sequence analysis of the VP2 gene classified 10 IPNV isolates as genogroup 1 and 26 as genogroup 5. Analyses indicated a preferential, but not obligate, relationship between genogroup 5 isolates and S. salar infection. Fifteen genogroup 5 and nine genogroup 1 isolates presented VP2 gene residues associated with high virulence (i.e. Thr, Ala, and Thr at positions 217, 221, and 247, respectively). Four genogroup 5 isolates presented an oddly long VP5 deduced amino acid sequence (29.6 kDa). Analysis of the VP2 amino acid motifs associated with clinical and subclinical infections identified the clinical fingerprint in only genogroup 5 isolates; in contrast, the genogroup 1 isolates presented sequences predominantly associated with the subclinical fingerprint. Predictive analysis of VP5 showed an absence of transmembrane domains and plasma membrane tropism signals. WebLogo analysis of the VP5 BH domains revealed high identities with the marine birnavirus Y-6 and Japanese IPNV strain E1-S. Sequence analysis for putative 25 kDa proteins, coded by the ORF between VP2 and VP4, exhibited three putative nuclear localization sequences and signals of mitochondrial tropism in two isolates. This study provides important advances in updating the characterizations of IPNV strains present in Chile. The results from this study will help in identifying epidemiological links and generating specific

[Chronic Pancreatitis and Pancreatic Cancer - Tumor Risk and Screening].

PubMed

Beyer, Georg; D'Haese, Jan G; Ormanns, Steffen; Mayerle, Julia

2018-06-01

Chronic pancreatitis is a fibroinflammatory syndrome of the exocrine pancreas, which is characterized by an increasing incidence, high morbidity and lethality. Common etiologies besides alcohol and nicotine consumption include genetic causes and risk factors. The life time risk for the development of pancreatic cancer is elevated 13- to 45-fold depending on the underlying etiology. In patients with chronic pancreatitis clinical, laboratory and imaging surveillance for early detection of complications, including pancreatic cancer, is recommended, although the available methods lack the desired sensitivity and specificity. In this article we review the epidemiology, etiologies and risk factors for chronic pancreatitis and pancreatic cancer and discuss current recommendations for screening and management of patients at risk for tumor development. © Georg Thieme Verlag KG Stuttgart · New York.

Pancreatic Cysts

MedlinePlus

... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

Laparoscopic pancreatic cystogastrostomy.

PubMed

Obermeyer, Robert J; Fisher, William E; Salameh, Jihad R; Jeyapalan, Manjula; Sweeney, John F; Brunicardi, F Charles

2003-08-01

The purpose of the review was to evaluate the feasibility and outcome of laparoscopic pancreatic cystogastrostomy for operative drainage of symptomatic pancreatic pseudocysts. A retrospective review of all patients who underwent laparoscopic pancreatic cystogastrostomy between June 1997 and July 2001 was performed. Data regarding etiology of pancreatitis, size of pseudocyst, operative time, complications, and pseudocyst recurrence were collected and reported as median values with ranges. Laparoscopic pancreatic cystogastrostomy was attempted in 6 patients. Pseudocyst etiology included gallstone pancreatitis (3), alcohol-induced pancreatitis (2), and post-ERCP pancreatitis (1). The cystogastrostomy was successfully performed laparoscopically in 5 of 6 patients. However, the procedure was converted to open after creation of the cystgastrostomy in 1 of these patients. There were no complications in the cases completed laparoscopically and no deaths in the entire group. No pseudocyst recurrences were observed with a median followup of 44 months (range 4-59 months). Laparoscopic pancreatic cystgastrostomy is a feasible surgical treatment of pancreatic pseudocysts with a resultant low pseudocyst recurrence rate, length of stay, and low morbidity and mortality.

Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial.

PubMed

Schepers, Nicolien J; Bakker, Olaf J; Besselink, Marc G H; Bollen, Thomas L; Dijkgraaf, Marcel G W; van Eijck, Casper H J; Fockens, Paul; van Geenen, Erwin J M; van Grinsven, Janneke; Hallensleben, Nora D L; Hansen, Bettina E; van Santvoort, Hjalmar C; Timmer, Robin; Anten, Marie-Paule G F; Bolwerk, Clemens J M; van Delft, Foke; van Dullemen, Hendrik M; Erkelens, G Willemien; van Hooft, Jeanin E; Laheij, Robert; van der Hulst, René W M; Jansen, Jeroen M; Kubben, Frank J G M; Kuiken, Sjoerd D; Perk, Lars E; de Ridder, Rogier J J; Rijk, Marno C M; Römkens, Tessa E H; Schoon, Erik J; Schwartz, Matthijs P; Spanier, B W Marcel; Tan, Adriaan C I T L; Thijs, Willem J; Venneman, Niels G; Vleggaar, Frank P; van de Vrie, Wim; Witteman, Ben J; Gooszen, Hein G; Bruno, Marco J

2016-01-05

Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant cholangitis, early ERC is not recommended in patients with mild biliary pancreatitis. Evidence on the role of routine early ERC with endoscopic sphincterotomy in patients without cholangitis but with biliary pancreatitis at high risk for complications is lacking. We hypothesize that early ERC with sphincterotomy improves outcome in these patients. The APEC trial is a randomized controlled, parallel group, superiority multicenter trial. Within 24 hours after presentation to the emergency department, patients with biliary pancreatitis without cholangitis and at high risk for complications, based on an Acute Physiology and Chronic Health Evaluation (APACHE-II) score of 8 or greater, Modified Glasgow score of 3 or greater, or serum C-reactive protein above 150 mg/L, will be randomized. In 27 hospitals of the Dutch Pancreatitis Study Group, 232 patients will be allocated to early ERC with sphincterotomy or to conservative treatment. The primary endpoint is a composite of major complications (that is, organ failure, pancreatic necrosis, pneumonia, bacteremia, cholangitis, pancreatic endocrine, or exocrine insufficiency) or death within 180 days after randomization. Secondary endpoints include ERC-related complications, infected necrotizing pancreatitis, length of hospital stay and an economical evaluation. The APEC trial investigates whether an early ERC with sphincterotomy reduces the composite endpoint of major complications or death compared with conservative treatment in patients with biliary pancreatitis at high risk of complications. Current Controlled Trials ISRCTN97372133 (date registration: 17-12-2012).

Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer.

PubMed

Talamini, G; Bassi, C; Falconi, M; Sartori, N; Salvia, R; Rigo, L; Castagnini, A; Di Francesco, V; Frulloni, L; Bovo, P; Vaona, B; Angelini, G; Vantini, I; Cavallini, G; Pederzoli, P

1999-07-01

The aim of this study was to compare alcohol and smoking as risk factors in the development of chronic pancreatitis and pancreatic cancer. We considered only male subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47 extrapancreatic cancers; (2) 69 patients with histologically well documented pancreatic cancer and no clinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona polling list and submitted to a complete medical check-up. Chronic pancreatitis subjects drink more than control subjects and more than subjects with pancreatic cancer without chronic pancreatitis (P<0.001). The percentage of smokers in the group with chronic pancreatitis is significantly higher than that in the control group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P<0.001] and in the group with pancreatic carcinomas but with no history of chronic pancreatitis (OR 5.3; 95% CI 3.0-9.4; P<0.001). In conclusion, our study shows that: (1) the risk of chronic pancreatitis correlates both with alcohol intake and with cigarette smoking with a trend indicating that the risk increases with increased alcohol intake and cigarette consumption; (2) alcohol and smoking are statistically independent risk factors for chronic pancreatitis; and (3) the risk of pancreatic cancer correlates positively with cigarette smoking but not with drinking.

Impaired small-bowel barrier integrity in the presence of lumenal pancreatic digestive enzymes leads to circulatory shock.

PubMed

Kistler, Erik B; Alsaigh, Tom; Chang, Marisol; Schmid-Schönbein, Geert W

2012-08-01

In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small-bowel lumen. It is unresolved, however, whether ischemically mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. To test this possibility, the small intestinal lumen of nonischemic rats was perfused for 2 h with either digestive enzymes, a mucin disruption strategy (i.e., mucolytics) designed to increase mucosal permeability, or both, and animals were observed for shock. Digestive enzymes perfused included trypsin, chymotrypsin, elastase, amylase, and lipase. Control (n = 6) and experimental animals perfused with pancreatic enzymes only (n = 6) or single enzymes (n = 3 for each of the five enzyme groups) maintained stable hemodynamics. After mucin disruption using a combination of enteral N-acetylcysteine, atropine, and increased flow rates, rats (n = 6) developed mild hypotension (P < 0.001 compared with groups perfused with pancreatic enzymes only after 90 min) and increased intestinal permeability to intralumenally perfused fluorescein isothiocyanate-dextran 20 kd (P < 0.05) compared with control and enzyme-only groups, but there were no deaths. All animals perfused with both digestive enzymes and subjected to mucin disruption (n = 6) developed hypotension and increased intestinal permeability (P < 0.001 after 90 min). Pancreatic enzymes were measured in the intestinal wall of both groups subjected to mucin disruption, but not in the enzyme-only or control groups. Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress

IMPAIRED SMALL BOWEL BARRIER INTEGRITY IN THE PRESENCE OF LUMENAL PANCREATIC DIGESTIVE ENZYMES LEADS TO CIRCULATORY SHOCK

PubMed Central

Kistler, Erik B.; Alsaigh, Tom; Chang, Marisol; Schmid-Schönbein, Geert W.

2012-01-01

In bowel ischemia, impaired mucosal integrity may allow intestinal pancreatic enzyme products to become systemic and precipitate irreversible shock and death. This can be attenuated by pancreatic enzyme inhibition in the small bowel lumen. It is unresolved, however, whether ischemically-mediated mucosal disruption is the key event allowing pancreatic enzyme products systemic access, and whether intestinal digestive enzyme activity in concert with increased mucosal permeability leads to shock in the absence of ischemia. To test this possibility, the small intestinal lumen of non-ischemic rats was perfused for two hours with either digestive enzymes, a mucin disruption strategy (i.e., mucolytics) designed to increase mucosal permeability, or both, and animals were observed for shock. Digestive enzymes perfused included trypsin, chymotrypsin, elastase, amylase and lipase. Control (n=6) and experimental animals perfused with pancreatic enzymes only (n=6) or single enzymes (n=3 for each of the five enzyme groups) maintained stable hemodynamics. After mucin disruption using a combination of enteral N-acetylcysteine, atropine, and increased flow rates, rats (n=6) developed mild hypotension (p<0.001 compared to groups perfused with pancreatic enzymes only after 90 minutes) and increased intestinal permeability to intralumenally perfused FITC-dextrans-20kD (p<0.05) compared to control and enzyme-only groups, but there were no deaths. All animals perfused with both digestive enzymes and subjected to mucin disruption (n=6) developed hypotension and increased intestinal permeability (p<0.001 after 90 minutes). Pancreatic enzymes were measured in the intestinal wall of both groups subjected to mucin disruption, but not in the enzyme-only or control groups. Depletion of plasma protease inhibitors was found only in animals perfused with pancreatic enzymes plus mucin disruption, implicating increased permeability and intralumenal pancreatic enzyme egress in this group. These

[Pancreatic anastomosis in operative treatment of chronic pancreatitis].

PubMed

Bellon, E; Izbicki, J R; Bockhorn, M

2017-01-01

Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V‑shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.

Improved function and growth of pancreatic cells in a three-dimensional bioreactor environment.

PubMed

Samuelson, Lisa; Gerber, David A

2013-01-01

Methods of three-dimensional (3D) cell culture have made significant progress in recent years due to a better understanding of cell to cell interactions and the cell's interface with their surrounding environment. We hypothesized that a microgravity 3D culture system would improve upon the growth and function of a pancreatic progenitor cell population. We developed a rotating wall vessel bioreactor and established a culture system using a pancreatic cell line. Cells in the bioreactors showed robust proliferation, enhanced transcriptional signaling, and improved translation of pancreatic genes compared with two-dimensional static culture. Cells also gained the ability to respond to glucose stimulation, which was not observed in the control cultures. These findings suggest that a 3D microgravity bioreactor environment mimics the niche of the pancreas yielding a cell source with potential for cell-based therapy in the treatment of diabetes.

Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

PubMed

Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

2011-01-01

Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

Intracellular hyperthermia mediated by nanoparticles in radiofrequency fields in the treatment of pancreatic cancer

NASA Astrophysics Data System (ADS)

Glazer, Evan Scott

Intracellular hyperthermic therapy may prove to be a unique and novel approach to the management of pancreatic cancer. Utilizing the principle of photothermal destruction, selective killing of cancer cells with minimal injury to normal tissues may be possible. This dissertation investigated the role of antibody targeted metal nanoparticles and the cytotoxic effects of nonionizing radiofrequency fields in pancreatic cancer. Cancer cell death was induced by heat release from intracellular metal nanoparticles after radiofrequency field exposure. Fluorescent and gold nanoparticles were delivered with two antibodies, cetuximab and PAM-4, to pancreatic cancer cells in vitro and mouse xenografts in vivo. Selective delivery of these nanoparticles induced cell death in vitro and decreased tumor burden in vivo after whole animal RF field exposure. This occurred through both apoptosis and necrosis. In addition, activated caspase-3 was increased after antibody treatment and RF field exposure. Furthermore, although there was non-specific uptake by the liver and spleen in vivo, there was no evidence of acute or chronic toxicity in the animals. These results are in agreement with the principle that malignant cells are more thermally sensitive than normal cells or tissues. Selective intracellular delivery of metal nanoparticles coupled with whole body RF field exposure may be a beneficial therapy against micrometastases and unresectable pancreatic cancer in the future. Further studies are planned with more specific antibodies, other nanoparticles, and other cancer targets.

Antioxidant Effect of Ukrain Versus N-Acetylcysteine Against Acute Biliary Pancreatitis in An Experimental Rat Model.

PubMed

Zeren, Sezgin; Bayhan, Zulfu; Koçak, Cengiz; Koçak, Fatma Emel; Metineren, Mehmet Huseyin; Savran, Bircan; Kocak, Havva; Algin, Mustafa Cem; Kahraman, Cuneyt; Kocak, Ahmet; Cosgun, Suleyman

2017-04-01

Purpose/Aim: Oxidative stress plays an important role in the pathogenesis of acute pancreatitis (AP). We compared the therapeutic effects of Ukrain (NSC 631570) and N-acetylcysteine (NAC) in rats with AP. Forty male Sprague Dawley rats were divided into four groups: controls; AP; AP with NAC; and AP with Ukrain. AP was induced via the ligation of the bile-pancreatic duct; drugs were administered intraperitoneally (i.p.) 30 min and 12 h after AP induction. Twenty-four hours after AP induction, animals were sacrificed and the pancreas was excised. Levels of malondialdehyde (MDA) and nitric oxide (NO), and activity levels of tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO) were measured in tissue samples. Total oxidant status (TOS), total antioxidant status (TAS), and total bilirubin, as well as activity levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase and lipase were measured in serum samples. Pancreatic tissue histopathology was also evaluated. Test drugs reduced levels of MDA, NO, TNF-α, total bilirubin, AST, ALT, TOS and MPO, amylase and lipase activities (P < 0.001), and increased TAS (P < 0.001). Rats treated with test drugs attenuated AP-induced morphologic changes and decreased pancreatic damage scores compared with the AP group (P < 0.05). Both test drugs attenuated pancreatic damage, but the therapeutic effect was more pronounced in rats that received Ukrain than in those receiving NAC. These results suggest that treatment with Ukrain or NAC can reduce pancreatic damage via anti-inflammatory and antioxidant effects.

Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikuta, Kazuhiro; Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp; Watanabe, Takashi

2010-12-17

Research highlights: {yields} Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. {yields} Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. {yields} PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. {yields} This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There ismore » accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated {beta}-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not

Unraveling Pancreatic Segmentation.

PubMed

Renard, Yohann; de Mestier, Louis; Perez, Manuela; Avisse, Claude; Lévy, Philippe; Kianmanesh, Reza

2018-04-01

Limited pancreatic resections are increasingly performed, but the rate of postoperative fistula is higher than after classical resections. Pancreatic segmentation, anatomically and radiologically identifiable, may theoretically help the surgeon removing selected anatomical portions with their own segmental pancreatic duct and thus might decrease the postoperative fistula rate. We aimed at systematically and comprehensively reviewing the previously proposed pancreatic segmentations and discuss their relevance and limitations. PubMed database was searched for articles investigating pancreatic segmentation, including human or animal anatomy, and cadaveric or surgical studies. Overall, 47/99 articles were selected and grouped into 4 main hypotheses of pancreatic segmentation methodology: anatomic, vascular, embryologic and lymphatic. The head, body and tail segments are gross description without distinct borders. The arterial territories defined vascular segments and isolate an isthmic paucivascular area. The embryological theory relied on the fusion plans of the embryological buds. The lymphatic drainage pathways defined the lymphatic segmentation. These theories had differences, but converged toward separating the head and body/tail parts, and the anterior from posterior and inferior parts of the pancreatic head. The rate of postoperative fistula was not decreased when surgical resection was performed following any of these segmentation theories; hence, none of them appeared relevant enough to guide pancreatic transections. Current pancreatic segmentation theories do not enable defining anatomical-surgical pancreatic segments. Other approaches should be explored, in particular focusing on pancreatic ducts, through pancreatic ducts reconstructions and embryologic 3D modelization.

Protective effect of asiatic acid in an experimental cerulein-induced model of acute pancreatitis in mice

PubMed Central

Xiao, Wenqin; Jiang, Weiliang; Li, Kai; Hu, Yangyang; Li, Sisi; Zhou, Li; Wan, Rong

2017-01-01

Asiatic acid (AA), a triterpenoid derived from the medicinal plant Centella asiatica, is considered to have anti-inflammatory, anti-fibrotic and anti-tumor effects, but its effects in acute pancreatitis (AP) are unknown. Our purpose of this study was to investigate the effects of AA in a mouse model of cerulein-induced pancreatitis. We evaluated AA in an experimental model of AP induced in mice by six hourly intraperitoneal injections of cerulein 50 µg/kg. Mice were pretreated with vehicle or AA 50 mg/kg 2 h before the first cerulein injection. The severity of AP was evaluated histologically and by biochemistry, myeloperoxidase activity, proinflammatory cytokine production, and nuclear factor (NF)-κB activity. Administration of AA significantly reduced the severity of AP, and was associated with reduction of serum amylase and lipase levels, decreased pancreatic histological damage, and decreased myeloperoxidase activity. The serum levels and mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and NF-κB activity were reduced. AA also significantly improved the in vitro viability of pancreatic acinar cells induced by cholecystokinin (CCK) and suppressed NF-κB activity. AA protected against experimental AP, possibly by reducing production of proinflammatory cytokines via suppression NF-κB activation. PMID:28861174

[External pancreatic fistulas management].

PubMed

Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

Mortality and morbidity in necrotizing pancreatitis managed on principles of step-up approach: 7 years experience from a single surgical unit.

PubMed

Aparna, Deshpande; Kumar, Sunil; Kamalkumar, Shukla

2017-10-27

To determine percentage of patients of necrotizing pancreatitis (NP) requiring intervention and the types of interventions performed. Outcomes of patients of step up necrosectomy to those of direct necrosectomy were compared. Operative mortality, overall mortality, morbidity and overall length of stay were determined. After institutional ethics committee clearance and waiver of consent, records of patients of pancreatitis were reviewed. After excluding patients as per criteria, epidemiologic and clinical data of patients of NP was noted. Treatment protocol was reviewed. Data of patients in whom step-up approach was used was compared to those in whom it was not used. A total of 41 interventions were required in 39% patients. About 60% interventions targeted the pancreatic necrosis while the rest were required to deal with the complications of the necrosis. Image guided percutaneous catheter drainage was done in 9 patients for infected necrosis all of whom required further necrosectomy and in 3 patients with sterile necrosis. Direct retroperitoneal or anterior necrosectomy was performed in 15 patients. The average time to first intervention was 19.6 d in the non step-up group (range 11-36) vs 18.22 d in the Step-up group (range 13-25). The average hospital stay in non step-up group was 33.3 d vs 38 d in step up group. The mortality in the step-up group was 0% (0/9) vs 13% (2/15) in the non step up group. Overall mortality was 10.3% while post-operative mortality was 8.3%. Average hospital stay was 22.25 d. Early conservative management plays an important role in management of NP. In patients who require intervention, the approach used and the timing of intervention should be based upon the clinical condition and local expertise available. Delaying intervention and use of minimal invasive means when intervention is necessary is desirable. The step-up approach should be used whenever possible. Even when the classical retroperitoneal catheter drainage is not feasible

Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

PubMed

Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

2018-06-06

Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

Targeting Trysin-Inflammation Axis for Pancreatitis Therapy in a Humanized Pancreatitis Model

DTIC Science & Technology

2017-10-01

pancreatitis especially due to alcohol and smoking goes onto chronic pancreatitis which, in turn, is a risk factor for pancreatic cancer . Because only a...proportional risk for pancreatic cancer of any known environmental risk factor. Because only a relatively small portion of patients with alcohol...progression to pancreatic cancer . Targeting the ER stress and inflammatory cascade will be beneficial for pancreatitis prevention and therapy. We expect that

Fatal acute pancreatitis associated with reactive AA amyloidosis in rheumatoid arthritis with end-stage renal disease: a report of three cases.

PubMed

Kuroda, Takeshi; Sato, Hiroe; Hasegawa, Hisashi; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

2011-01-01

We report three cases of fatal pancreatitis associated with systemic AA amyloidosis in rheumatoid arthritis (RA). All of the patients showed end-stage renal failure, and hemodialysis was introduced during the course of treatment. Autopsy was performed on two of the three patients, and this revealed amyloid deposition on the vascular walls in the pancreas. It was strongly suggested that the acute pancreatitis in all three patients was attributable to deposition of amyloid in vascular and pancreatic tissues. Acute pancreatitis is considered to be a rare complication of end-stage amyloidosis associated with RA, and is frequently fatal. It is important to treat RA patients intensively to avoid such deposition of amyloid.

[Best time to administer coagulation factor XIII( Fibrogammin P) for postoperative intractable pancreatic fistula following gastrectomy for gastric cancer].

PubMed

Shoda, Katsutoshi; Komatsu, Shuhei; Ichikawa, Daisuke; Kubota, Takeshi; Okamoto, Kazuma; Arita, Tomohiro; Konishi, Hirotaka; Murayama, Yasutoshi; Shiozaki, Atsushi; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Fujiwara, Hitoshi; Otsuji, Eigo

2013-11-01

Coagulation factor XIII( Fibrogammin P, F XIII) has been used to treat postoperative pancreatic fistulas following gastrectomy for gastric cancer in Japan. However, little is known about the best timing to start this treatment for early recovery. This study was designed to examine the appropriate time to start Fibrogammin P treatment for pancreatic fistulas, based on nutritional and inflammatory parameters. We retrospectively examined 27 consecutive patients with Grade B or C pancreatic fistulas as defined by the International Study Group of Pancreatic Fistula( ISGPF) classification who underwent gastrectomy at our institute between 1997 and 2011. We analyzed data on total protein( TP), albumin (Alb), C-reactive protein( CRP), and hemoglobin( Hb) concentrations and white blood cell( WBC) and lymphocyte counts. We used this information to determine laboratory cut-off values that indicate the most advantageous time to start the administration of Fibrogammin P in order to achieve early recovery within 2 weeks. When Fibrogammin P administration was based on more than 2 cut-off values such as Alb>2.6 g/dL and Hb>9.0 g/dL and WBC<9,000/μL (p= 0.1563), early cure of pancreatic fistulas was achieved. The use of nutritional and inflammatory parameter values to determine the best time to administer Fibrogammin P may shorten the treatment period.

Relationship between Plasma Triglyceride Level and Severity of Hypertriglyceridemic Pancreatitis.

PubMed

Wang, Sheng-Huei; Chou, Yu-Ching; Shangkuan, Wei-Chuan; Wei, Kuang-Yu; Pan, Yu-Han; Lin, Hung-Che

2016-01-01

Hypertriglyceridemia is the third most common cause of acute pancreatitis, but whether the level of triglyceride (TG) is related to severity of pancreatitis is unclear. To evaluate the effect of TG level on the severity of hypertriglyceridemic pancreatitis (HTGP). Retrospective cohort study. We reviewed the records of 144 patients with HTGP from 1999 to 2013 at Tri-Service General Hospital. Patients with possible etiology of pancreatitis, such as gallstones, those consuming alcohol or drugs, or those with infections were excluded. The classification of severity of pancreatitis was based on the revised Atlanta classification. We allocated the patients into high-TG and low-TG groups based on the optimal cut-off value (2648 mg/dL), which was derived from the receiver operating characteristic (ROC) curve between TG level and severity of HTGP. We then compared the clinical characteristics, pancreatitis severity, and mortality rates of the groups. There were 66 patients in the low-TG group and 78 patients in the high-TG group. There was no significant difference in the age, sex ratio, body mass index, and comorbidity between the 2 groups. The high-TG group had significantly higher levels of glucose (P = 0.022), total cholesterol (P = 0.002), and blood urea nitrogen (P = 0.037), and lower levels of sodium (P = 0.003) and bicarbonate (P = 0.002) than the low-TG group. The incidences of local complication (P = 0.002) and severe and moderate form of pancreatitis (P = 0.004) were significantly higher in the high-TG group than in the low-TG group. The mortality rate was higher in the high-TG group than in the low-TG group (P = 0.07). Higher TG level in patients with HTGP may be associated with adverse prognosis, but randomized and prospective studies are needed in the future verify this relationship.

Activation Of Wild-Type Hras Suppresses The Earliest Stages Of Pancreatic Cancer.

PubMed

Weyandt, Jamie

2015-08-01

The RAS family of small GTPases is comprised of HRAS, NRAS, and KRAS. KRAS is invariably oncogenically mutated in pancreatic cancers, which is known to induce this disease. Beyond oncogenic KRAS, redox-dependent reactions have been implicated in the activation of the remaining wild-type RAS proteins in pancreatic cancer cell lines. These results suggest a possible involvement of wild-type RAS proteins in pancreatic cancer. To evaluate the impact of genetically suppressing wild-type RAS expression on pancreatic cancer. Hras homozygous null mice (Hras -/- ) were crossed into a Pdx-Cre; LSL-Kras G12D/+ (KC) murine background in which oncogenic Kras is activated in the pancreas to promote preinvasive pancreatic cancer. Tumor burden was then measured at different stages of disease. HRas -/- ;KC mice exhibited more precancerous lesions in the pancreas and more off-target skin papillomas compared to their wild-type counterparts, suggesting that Hras suppresses early oncogenic Kras-driven tumorigenesis, possibly at the time of initiation. Loss of Hras also reduced the survival of mice engineered to develop aggressive pancreatic cancer by the additional disruption of one allele of the tumor suppressor p53 (Trp53 R172H/+ ). However, this survival advantage was lost when both alleles of Trp53 were mutated, suggesting that wild-type Hras inhibits tumorigenesis in a p53-dependent fashion. Loss of wild-type Hras promotes the earliest stages of pancreatic tumorigenesis, and moreover results in more rapid progression of the disease. As such, mechanisms leading to activation of wild-type Ras proteins, including but not limited to redox-dependent reactions, may influence the development of pancreatic cancer. Copyright © 2015. Published by Elsevier B.V.

Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

PubMed

Kaur, Jagdeep; Sidhu, Shabir; Chopra, Kanwaljit; Khan, M U

2016-07-01

Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-β1 (TGF-β1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-β1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

Pancreatitis-imaging approach

PubMed Central

Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C

2014-01-01

Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

PubMed

Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

2013-03-01

Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

Safety and efficacy of pancreatic sphincterotomy in chronic pancreatitis.

PubMed

Ell, C; Rabenstein, T; Schneider, H T; Ruppert, T; Nicklas, M; Bulling, D

1998-09-01

Endoscopic pancreatic sphincterotomy (EPS) is being performed with increasing frequency as a prerequisite to interventional measures in the pancreatic duct. The aim of this study was to evaluate EPS with regard to technique, success, complications, and mortality in patients with chronic pancreatitis. Between January 1989 and September 1996, the results of all consecutive EPSs in patients with chronic pancreatitis were documented in a standardized form. Patients were followed by clinical investigation and blood sample analysis at 4, 24, and 48 hours after EPS. Complications were classified according to commonly accepted criteria. EPS was performed in 118 patients with chronic pancreatitis (men 75%, women 25%, 48+/-10 years). Ninety-four patients (80%) underwent guidewire-assisted EPS, and 24 patients (20%) underwent needle-knife EPS. Seventy-seven EPS procedures (65%) were primarily successful (guidewire EPS: 60 of 94, 64%; needle-knife EPS: 17 of 24, 71%). Additional endoscopic cutting techniques (needle-knife papillotomy, biliary endoscopic sphincterotomy) were required in 41 patients (35%). In total, EPS was successful in 116 patients (98%). The complication rate was 4.2% (4 cases of moderate pancreatitis, 1 severe bleeding, no deaths). All complications were managed nonoperatively. In patients with chronic pancreatitis, EPS with a standard sphincterotome or with a needle-knife offers an effective and reliable approach to the pancreatic duct system. Additional cutting techniques may be necessary in approximately one third of cases before an EPS can be successfully performed. The complication rate of EPS in patients with chronic pancreatitis appears to be lower than the complication rate of biliary sphincterotomy for other indications.

Pancreatitis

MedlinePlus

... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes.

PubMed

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-08-06

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes

PubMed Central

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-01-01

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain. PMID:27602238

A pylorus-retaining pancreatic head-duodenectomy for cancers of the duodenal papilla and the lower bile duct.

PubMed

Iwamoto, M; Sasahara, H; Kawabata, S; Hoshiko, M; Yasumoto, K; Imamura, K; Takagi, K; Morimatsu, M; Fujii, T; Shirouzu, K

1996-01-01

With the development of diagnostic technology, the surgical methods of cancer therapy have been expanded, and operations have been performed using a procedure corresponding to the stage of cancer to improve the postoperative QOL. A 79-year-old man with cancer of the duodenal papilla and obstructive jaundice, and a 63-year-old woman with cholangiocarcinoma in the lower region complicated by cholangitis caused by Candida underwent resections of the pancreatic head and duodenum, and pancreaticogastrostomies retaining the pylorus. Satisfactory results were obtained in both cases. The merits of the procedure were that there were few complaints, sufficient food could be ingested and the QCL was maintained. The benefits of pancreaticogastrostomy are that the anastomosis procedure is simple, the gastric wall is thicker than the jejunum and blood flow is plentiful. The dorsal gastric wall is located close to the pancreatic cut-end, therefore tension is not created, and the pancreatic enzymes are not activated because the anastomosis site does not contact the intestinal fluid. These characteristics should decrease the rate of anastomosis failure which can be a fetal complication. A safer operation is desirable, particularly for elderly patients or patients who have complications.

Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

PubMed

Noronha, M; Dreiling, D A; Bordalo, O

1983-11-01

A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

Off-axis fishbone-like instability and excitation of resistive wall modes in JT-60U and DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okabayashi, M.; Solomon, W. M.; Budny, R. V.

2011-05-15

An energetic-particle (EP)-driven ''off-axis-fishbone-like mode (OFM)'' often triggers a resistive wall mode (RWM) in JT-60U and DIII-D devices, preventing long-duration high-{beta}{sub N} discharges. In these experiments, the EPs are energetic ions (70-85 keV) injected by neutral beams to produce high-pressure plasmas. EP-driven bursting events reduce the EP density and the plasma rotation simultaneously. These changes are significant in high-{beta}{sub N} low-rotation plasmas, where the RWM stability is predicted to be strongly influenced by the EP precession drift resonance and by the plasma rotation near the q=2 surface (kinetic effects). Analysis of these effects on stability with a self-consistent perturbation tomore » the mode structure using the MARS-K code showed that the impact of EP losses and rotation drop is sufficient to destabilize the RWM in low-rotation plasmas, when the plasma rotation normalized by Alfven frequency is only a few tenths of a percent near the q=2 surface. The OFM characteristics are very similar in JT-60U and DIII-D, including nonlinear mode evolution. The modes grow initially like a classical fishbone, and then the mode structure becomes strongly distorted. The dynamic response of the OFM to an applied n=1 external field indicates that the mode retains its external kink character. These comparative studies suggest that an energetic particle-driven 'off-axis-fishbone-like mode' is a new EP-driven branch of the external kink mode in wall-stabilized plasmas, analogous to the relationship of the classical fishbone branch to the internal kink mode.« less

Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

NASA Astrophysics Data System (ADS)

Hu, Wenyan; Fu, Ling

2013-05-01

Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (p<0.001, analysis of variance linear contrast; n=8 for each group). Pathological events relating to these components were observed, including presence of inflammatory cells, deposited collagen, and phenotype conversion of PSCs. We demonstrate that label-free nonlinear optical microscopy is an efficient tool for dissecting PSCs and other pancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

Negative-pressure wound therapy and early pedicle flap reconstruction of the chest wall after epirubicin extravasation.

PubMed

Papadakis, Marios; Rahmanian-Schwarz, Afshin; Bednarek, Marzena; Arafkas, Mohamed; Holschneider, Philipp; Hübner, Gunnar

2017-05-15

Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. To the best of the authors' knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.

TRAUMATIC PANCREATITIS

PubMed Central

Berne, Clarence J.; Walters, Robert L.

1953-01-01

Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation. Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained. PMID:13094537

Treatment of pancreatic insufficiency using pancreatic extract in patients with advanced pancreatic cancer: a pilot study (PICNIC).

PubMed

Zdenkowski, Nicholas; Radvan, George; Pugliese, Leanna; Charlton, Julie; Oldmeadow, Christopher; Fraser, Allison; Bonaventura, Antonino

2017-06-01

Survival with advanced pancreatic cancer is less than 12 months. Pancreatic exocrine insufficiency may contribute to pancreatic cancer-related cachexia, via nutrient malabsorption. We aimed to determine the feasibility of prescribing pancreatic extract (Creon®) for patients with advanced pancreatic cancer. Patients with advanced pancreatic cancer, without frank malabsorption, were randomised in this feasibility study to pancreatic extract 50,000 units with meals and 25,000 units with snacks, or placebo. Standardised dietary advice was given. Anti-cancer and supportive care treatments were permitted. Outcomes included weight, body mass index (BMI), quality of life (QLQC30, PAN26), survival and nutritional assessment (PG-SGA). Eighteen patients were randomised before study closure due to slow recruitment. Baseline characteristics were well matched. Weight loss prior to randomisation was numerically greater in the pancreatic extract group (mean 0.7 vs 2.2 kg). Weight loss was numerically greater in the placebo group, however not significantly. No differences in BMI or nutrition score were seen. Quality of life did not differ between study groups. Median overall survival was 17 (95% CI 8.1-48.7) weeks in the control group, and 67.6 (95% CI 14.1-98.4) weeks in the pancreatic extract group (p = 0.1063). Only 17% (18/106) of potentially eligible patients were recruited, related to patient/family reluctance, rapid clinical deterioration and patients already prescribed pancreatic extract. A moderate pill burden was noted. Despite intriguing survival results, this study was not sufficiently feasible to proceed to a fully powered comparative study. A multi-centre study would be required to exclude a significant difference in outcomes.

Conservation of pancreatic tissue by combined gastric, biliary, and pancreatic duct drainage for pain from chronic pancreatitis.

PubMed

Warshaw, A L

1985-04-01

In patients with chronic pancreatitis, the sclerosing process of the pancreas may constrict not only the pancreatic duct for also the bile duct and duodenum. This study analyzes the prevalence of these obstructive lesions in 58 consecutive patients with chronic pancreatitis requiring surgery for either pain (57 patients) or for painless jaundice (1 patient). There was significant biliary obstruction in 21, 4 of whom also had symptomatic duodenal obstruction. All 21 patients with biliary and duodenal obstruction were among the 38 with a dilated pancreatic duct suitable for pancreaticojejunostomy (modified Puestow procedure). None of the 20 patients with small duct pancreatitis had biliary or duodenal obstruction. Pseudocysts were distributed evenly between the two groups (9 of 38 patients with a dilated duct versus 4 of 20 patients with small duct pancreatitis). Pancreaticojejunostomy combined with choledochoenterostomy and gastrojejunostomy in appropriately selected patients provided good to excellent long-term (mean 3.6 years) relief of pain in 30 of 36 patients (83 percent). There was no correlation between successful relief of pain and development of pancreatic exocrine or endocrine insufficiency or calcification. Stenosis of the bile duct developed some years subsequent to pancreaticojejunostomy in four patients and required a second operation for choledochoenterostomy in three. Three other patients required secondary pancreatic resections due to failure of the pancreaticojejunostomy to relieve pain. It is often possible to effect excellent relief of symptoms with maximal conservation of remaining pancreatic functions despite sclerotic obstruction of multiple organ systems.

Update on endoscopic management of main pancreatic duct stones in chronic calcific pancreatitis.

PubMed

Choi, Eun Kwang; Lehman, Glen A

2012-03-01

Pancreatic duct stones are a common complication during the natural course of chronic pancreatitis and often contribute to additional pain and pancreatitis. Abdominal pain, one of the major symptoms of chronic pancreatitis, is believed to be caused in part by obstruction of the pancreatic duct system (by stones or strictures) resulting in increasing intraductal pressure and parenchymal ischemia. Pancreatic stones can be managed by surgery, endoscopy, or extracorporeal shock wave lithotripsy. In this review, updated management of pancreatic duct stones is discussed.