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Sample records for pancreatitis

  1. Pancreatitis

    MedlinePlus

    ... removal is sometimes performed along with a sphincterotomy. Stent placement. Using the endoscope, the doctor places a ... a narrowed pancreatic or bile duct. A temporary stent may be placed for a few months to ...

  2. Hereditary Pancreatitis

    MedlinePlus

    ... meals throughout the day that are high in carbohydrates and low in protein and fat. Pancreatic enzymes ... the Pancreas NPF Centers Pancreatitis Centers Pancreatitis Center Application Pancreatic Cancer Centers Diagnosis of Pancreatic Cancer Pancreas ...

  3. [Chronic pancreatitis, acute pancreatitis].

    PubMed

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  4. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  5. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... hospital for: Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to ...

  6. 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 ...

  7. Pancreatic pseudocyst

    MedlinePlus

    ... More Acute pancreatitis Chronic pancreatitis Pancreatic abscess Shock Review Date 10/27/2015 Updated by: Subodh K. ... gastroenterologist with Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  8. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  9. Chronic Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  10. Acute Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  11. Pancreatic cancer

    MedlinePlus

    ... cancer, cystic pancreatic neoplasms, and other nonendocrine pancreatic tumors. In: Feldman M, Friedman LS, Brandt LJ, ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. ...

  12. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  13. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  14. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. 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 CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  15. Chronic pancreatitis.

    PubMed

    Lindley, Keith J

    2006-10-01

    Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.

  16. Pancreatic Cysts

    MedlinePlus

    ... fluid can be collected from the cyst for analysis in a laboratory for possible signs of cancer. The characteristics and location of the pancreatic cyst, with your age and sex, can help doctors pinpoint the type of cyst ...

  17. Acute pancreatitis

    MedlinePlus

    ... mg/dL Injury to the pancreas from an accident Other causes include: After certain procedures used to ... pressure Rapid heart rate Rapid breathing (respiratory) rate Lab tests that show the release of pancreatic enzymes ...

  18. Pancreatitis - children

    MedlinePlus

    ... an organ or bone marrow transplant Cystic fibrosis Crohn disease and other disorders when the body's immune system ... lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase ...

  19. Pancreatic abscess

    MedlinePlus

    ... high. Possible Complications Complications may include: Multiple abscesses Sepsis When to Contact a Medical Professional Call your ... 2016:chap 144. Read More Abscess Pancreatic pseudocyst Sepsis Review Date 10/27/2015 Updated by: Subodh ...

  20. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  1. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  2. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  3. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%.

  4. Autoimmune pancreatitis mimicking pancreatic tumor

    PubMed Central

    Dede, Kristóf; Salamon, Ferenc; Taller, András; Teknős, Dániel; Bursics, Attila

    2012-01-01

    Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered. PMID:24968399

  5. Is Pancreatic Cancer Hereditary?

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? ...

  6. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation ... the incidence of recurrent attacks minimized. Timothy Gardner, MD is Director of Pancreatic Disorders at Dartmouth-Hitchcock ...

  7. Pancreatic abscesses.

    PubMed

    Shi, E C; Yeo, B W; Ham, J M

    1984-09-01

    This paper presents the clinical features and problems in the management of 34 patients with pancreatic abscesses. In the majority of patients the abscesses developed following an attack of pancreatitis due to alcohol or gallstones. The abscesses were usually multilocular, and often had spread widely in the retroperitoneal space. Invasion into surrounding viscera or the peritoneal cavity occurred in 12 instances, and eight patients developed major bleeding into the abscess cavity. Obstructive complications (affecting bowel, common bile duct and large veins) occurred in eight patients. Twelve of the 34 patients (35 per cent) died, most deaths being due to failure to control sepsis (seven patients) or to massive bleeding from the abscess cavity (three patients). The mortality of this condition is likely to remain high, but may be reduced by better drainage techniques at the initial exploration. The importance of the infra-mesocolic approach for drainage is emphasized.

  8. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    PubMed

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  9. Arterio-Pancreatic Syndrome

    PubMed Central

    Lee, Ser Yee; Ng, Kheng Hong; Sebastian, Mathew George

    2011-01-01

    Acute pancreatitis is a single-organ disorder that has multi-organ sequelae. As a result, it can have varied presentations. Acute pancreatitis presenting as acute limb ischemia is rare. We present a patient with acute pancreatitis presenting with bilateral lower limb ischemia. The episode of acute pancreatitis resolved but the acute lower limb ischemia precipitated as the pancreatitis progressed, and necessitated bilateral above-knee amputations. We review the literature and discuss the pathogenesis of such a phenomenon. PMID:22347150

  10. [External pancreatic fistulas management].

    PubMed

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    2017-01-01

    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.

  11. Pancreatic Cancer Stage 3

    MedlinePlus

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  12. Surgery for pancreatic cancer

    MedlinePlus

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  13. Pancreatic pseudocysts and aneurysms

    PubMed Central

    Andrén-Sandberg, Åke

    2010-01-01

    A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. The author reviewed the most rently reports, and and summarized the latest advances in the pancreatic pseudocysts. PMID:22558566

  14. Pathogenic mechanisms of pancreatitis.

    PubMed

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

    2017-02-06

    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

  15. 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

  16. Experimental Models of Pancreatitis

    PubMed Central

    Hyun, Jong Jin

    2014-01-01

    Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations. PMID:24944983

  17. Chronic pancreatitis: relation to acute pancreatitis and pancreatic cancer.

    PubMed

    Uomo, G; Rabitti, P G

    2000-01-01

    The relationship between chronic pancreatitis (CP) and other pancreatic diseases, such as acute pancreatitis (AP) and pancreatic cancer (PK), remains a fairly debated question. The progression from alcoholic AP to CP is controversial, and some long-term epidemiological studies suggest that alcoholic CP might be the result of recurrent alcoholic AP (necrosis-fibrosis sequence) and a subgroup of alcoholics may present recurrent AP without progression to CP. Other predisposing factors (genetic, nutritional, environmental) seems to be important in inducing different outcomes of pancreatic damage due to alcohol. However, recurrent episodes of AP are clearly involved in pathophysiology of CP in patients with hereditary pancreatitis. A relationship between CP and subsequent PK development has long been suspected, but we actually don't know whether this association is direct or is the result of confounding factors, such as alcohol intake or cigarette smoking. Many issues should be considered as indicators of a causal association, and several of them are not fulfilled. Nonetheless, epidemiological studies (case-control or cohort studies) showed that the risk of PK is increased in patients with CP; the risk is significantly higher in tropical calcifying CP and hereditary pancreatitis. Studies on growth factors, oncogenes, tumor-suppressor genes, and angiogenesis suggest that the sequence PC-KP is plausible from the biological standpoint.

  18. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    PubMed Central

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J.-Matthias

    2017-01-01

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes. PMID:28241470

  19. Pancreatic Cancer Genetics

    PubMed Central

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS). PMID:26929738

  20. Inherited pancreatic cancer syndromes.

    PubMed

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  1. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  2. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  3. Hypermutation In Pancreatic Cancer.

    PubMed

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  4. Lymphoplasmacytic sclerosing pancreatitis (autoimmune pancreatitis): evaluation with multidetector CT.

    PubMed

    Kawamoto, Satomi; Siegelman, Stanley S; Hruban, Ralph H; Fishman, Elliot K

    2008-01-01

    Lymphoplasmacytic sclerosing pancreatitis is a form of chronic pancreatitis characterized by a mixed inflammatory infiltrate that centers on the pancreatic ducts. It is a cause of benign pancreatic disease that can clinically mimic pancreatic cancer. Preoperative detection of lymphoplasmacytic sclerosing pancreatitis is important because patients usually respond to steroid therapy. Patients with lymphoplasmacytic sclerosing pancreatitis are often referred for computed tomography (CT) when they are suspected of having a pancreatic or biliary neoplasm; therefore, it is important to search for potential findings suggestive of lymphoplasmacytic sclerosing pancreatitis when typical findings of a pancreatic or biliary neoplasm are not found. Typical CT findings include diffuse or focal enlargement of the pancreas without dilatation of the main pancreatic duct. Focal enlargement is most commonly seen in the head of the pancreas, and the involved pancreas on contrast material-enhanced CT images may be iso-attenuating relative to the rest of the pancreas, or hypo-attenuating, especially during the early postcontrast phase. Thickening and contrast enhancement of the wall of the common bile duct and gallbladder may reflect inflammatory infiltrate and fibrosis associated with lymphoplasmacytic sclerosing pancreatitis. There are several features seen at CT that may help to differentiate lymphoplasmacytic sclerosing pancreatitis from pancreatic cancer, such as diffuse enlargement of the pancreas with minimal peripancreatic stranding in patients with obstructive jaundice, an absence of significant pancreatic atrophy, and an absence of significant main pancreatic duct dilatation. When these findings are encountered, clinical, other imaging, and serologic data should be evaluated.

  5. Lymphoplasmacytic sclerosing pancreatitis.

    PubMed

    Plaza, Jose Antonio; Colonna, Jorge; Vitellas, Kenneth M; Frankel, Wendy L

    2005-10-01

    Lymphoplasmacytic sclerosing pancreatitis is a rare entity that has been described under many different names and constitutes a diagnostic challenge as it may simulate a neoplastic process. Herein, we report a case of a 61-year-old woman who presented to our institution complaining of left flank pain and was found to have normal levels of amylase and lipase. An abdominal magnetic resonance image showed thickening of the pancreatic tail and compression of the pancreatic duct. The radiographic differential included both chronic pancreatitis and a neoplastic process. She underwent an exploratory laparotomy, during which a pancreatectomy and splenectomy were performed. Grossly, the pancreas contained a yellowish white, firm homogeneous mass measuring 6.5 x 3.3 x 2.9 cm involving the entire pancreatic tail and hilum of the spleen. Histologically, pancreatic sections showed extensive fibrosis admixed with an inflammatory infiltrate. This infiltrate was composed mainly of lymphocytes with multiple germinal centers, as well as plasma cells and eosinophils that surrounded pancreatic ducts and extended into the peripancreatic adipose tissue. No malignancy was identified, and the process was diagnosed as lymphoplasmacytic sclerosing pancreatitis.

  6. Review of idiopathic pancreatitis

    PubMed Central

    Lee, Jason Kihyuk; Enns, Robert

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217

  7. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  8. Epidemiology of pancreatic cancer

    PubMed Central

    Ilic, Milena; Ilic, Irena

    2016-01-01

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease. PMID:27956793

  9. Pancreatic groove cancer

    PubMed Central

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  10. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  11. Pancreatitis following liver transplantation.

    PubMed

    Alexander, J A; Demetrius, A J; Gavaler, J S; Makowka, L; Starzl, T E; Van Thiel, D H

    1988-06-01

    Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.

  12. Diagnosis of autoimmune pancreatitis.

    PubMed

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-11-28

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP).

  13. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

  14. 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

  15. Can Pancreatic Cancer Be Found Early?

    MedlinePlus

    ... Team About Pancreatic Cancer? Pancreatic Cancer Early Detection, Diagnosis, and Staging Can Pancreatic Cancer Be Found Early? Pancreatic cancer is hard to find early. The pancreas is deep inside the body, so early tumors ...

  16. Recurrent acute pancreatitis.

    PubMed

    Khurana, Vishal; Ganguly, Ishita

    2014-09-28

    Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.

  17. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma.

  18. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2015-02-21

    Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

  19. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis.

  20. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  1. Surgery for Pancreatic Cancer

    MedlinePlus

    ... the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy ... pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, ...

  2. Chronic Pancreatitis in Children

    MedlinePlus

    ... years to appear, but this, too, is highly variable; some patients with chronic pancreatitis will develop diabetes ... of modifying factors include other genes or environmental variables, which is a term that scientists use to ...

  3. Pancreatic exocrine function testing

    SciTech Connect

    Goff, J.S.

    1981-11-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

  4. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... would like to unsubscribe/opt out from our communications, please follow this link: http://www.cancer.org/ ...

  5. [Management of postoperative pancreatic fistula].

    PubMed

    Hackert, T; Büchler, M W

    2015-06-01

    The occurrence of a postoperative pancreatic fistula is one of the most important complications following pancreatic resections. The frequency of this complication varies between 3 % after pancreatic head resection and up to 35 % following distal pancreatectomy. In 2005, the international definition of postoperative pancreatic fistula was standardized according to the approach of the International Study Group of Pancreatic Surgery (ISGPS) including an A-C grading system of the severity. Consequently, results from different studies have become comparable and the historically reported fistula rates can be evaluated more critically. The present review summarises the currently available data on incidence, risk factors, fistula-associated complications and management of postoperative pancreatic fistula.

  6. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

  7. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

  8. [Acute pancreatitis due to lupus].

    PubMed

    Hani, Mohamed Aziz; Guesmi, Fethi; Ben Achour, Jamel; Zribi, Riadh; Bouasker, Ibtissem; Zoghlami, Ayoub; Najah, Nabil

    2004-02-01

    Among digestive clinical presentations of systemic lupus erythematosus, acute pancreatitis remains a serious affection with very poor prognosis. To date, pathogenesis is still unclear. We report two cases of fatal acute pancreatitis related to systemic lupus erythematosus.

  9. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  10. Surgery for pancreatic cancer -- discharge

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000820.htm Surgery for pancreatic cancer - discharge To use the sharing features on this ... References Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  11. Genetics Home Reference: hereditary pancreatitis

    MedlinePlus

    ... HEREDITARY Sources for This Page Greer JB, Whitcomb DC. Inflammation and pancreatic cancer: an evidence-based review. ... J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP; European Registry of Hereditary Pancreatitis and ...

  12. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  13. Hepatobiliary and pancreatic ascariasis

    PubMed Central

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  14. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  15. Hepatobiliary and pancreatic ascariasis.

    PubMed

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-07

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

  16. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

    Xue, Jing; Sharma, Vishal; Hsieh, Michael H.; Chawla, Ajay; Murali, Ramachandran; Pandol, Stephen J.; Habtezion, Aida

    2015-01-01

    Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis, we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on IL-4 and IL-13 signaling and we show that mice lacking IL-4Rα, myeloid specific IL-4Rα, and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex-vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage alternative activation. Our study challenges and identifies pathways involved in cross talk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression. PMID:25981357

  17. Incidental isolated pancreatic hydatid cyst.

    PubMed

    Kısaoğlu, Abdullah; Özoğul, Bünyami; Atamanalp, Sabri Selçuk; Pirimoğlu, Berhan; Aydınlı, Bülent; Korkut, Ercan

    2015-03-01

    Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.

  18. Hypertriglyceridaemia-induced pancreatitis.

    PubMed

    Weston, Natasha; Fernando, Upul; Baskar, Varadarajan

    2013-02-27

    Hypertriglyceridaemia is the third most common cause of acute pancreatitis but is relatively rare and therefore requires a high level of clinical suspicion to be diagnosed. We discuss the case of a 46-year-old man who initially presented to the accident and emergency department with suspected first presentation of diabetic ketoacidosis (DKA) and a normal amylase but who did not respond to DKA treatment. Further history revealed significant cardiovascular risk factors, examination showed an evidence of hyperlipidaemia and investigations revealed acute pancreatitis secondary to hypertriglyceridaemia. We discuss the causes of hypertriglyceridaemia, the difficulty in differentiating primary versus secondary hypertriglyceridaemia, possible pathogenesis and current evidence-based treatments.

  19. Enzymatic Debridement in Necrotizing Pancreatitis

    PubMed Central

    Cakir, Murat; Tekin, Ahmet; Kucukkartallar, Tevfik; Vatansev, Husamettin; Kartal, Adil

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis. PMID:26011212

  20. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  1. Diabetes and pancreatic cancer.

    PubMed

    Burney, Saira; Irfan, Khadija; Saif, Muhammad Wasif; Masud, Faisal

    2014-07-28

    Research suggests a possible link between type 2 diabetes and several malignancies. Animal models have shown that hyperinsulinemic state underlying diabetes promotes tumor formation through stimulation of insulin-IGF-1 pathway; a possible role of inflammation is also proposed. One such link which has been under considerable study for years is that between diabetes and pancreatic cancer. Although epidemiological evidence points towards a reciprocal link between the two, the cause-effect relationship still remains unclear. This link was the subject of a large German epidemiological study presented at the American Society of Clinical Oncology Annual Meeting 2014 (Abstract #1604), which underscored the link between diabetes and some cancers. Schmidt et al. performed a retrospective database analysis over a 12 year period and reported an increased risk of certain types of cancer in diabetic patients. The most significant association (HR 2.17) was found for pancreatic cancer. Given the high mortality of pancreatic cancer, prevention through timely screening could play an important role in improving prognosis. Older subjects with recent-onset diabetes represent a high-risk group and hence are potential targets for pancreatic cancer screening thereby enabling its early diagnosis at a curable stage.

  2. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  3. What Are the Key Statistics about Pancreatic Cancer?

    MedlinePlus

    ... Cancer Research? Pancreatic Cancer About Pancreatic Cancer Key Statistics for Pancreatic Cancer How common is pancreatic cancer? ... can be affected by certain risk factors . For statistics related to survival, see Pancreatic Cancer Survival Rates ...

  4. Delayed internal pancreatic fistula with pancreatic pleural effusion postsplenectomy

    PubMed Central

    Jin, Shu-Guang; Chen, Zhe-Yu; Yan, Lu-Nan; Zeng, Yong

    2010-01-01

    The occurrence of pancreatic pleural effusion, secondary to an internal pancreatic fistula, is a rare clinical syndrome and diagnosis is often missed. The key to the diagnosis is a dramatically elevated pleural fluid amylase. This pancreatic pleural effusion is also called a pancreatic pleural fistula. It is characterized by profuse pleural fluid and has a tendency to recur. Here we report a case of delayed internal pancreatic fistula with pancreatic pleural effusion emerging after splenectomy. From the treatment of this case, we conclude that the symptoms and signs of a subphrenic effusion are often obscure; abdominal computed tomography may be required to look for occult, intra-abdominal infection; and active conservative treatment should be carried out in the early period of this complication to reduce the need for endoscopy or surgery. PMID:20845520

  5. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

    PubMed Central

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E.; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L.; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E.; Krenn, Veit; Mayerle, Julia; Lerch, Markus M.; Schett, Georg; Wirtz, Stefan; Neurath, Markus F.; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts. PMID:26964500

  6. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis.

    PubMed

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E; Krenn, Veit; Mayerle, Julia; Lerch, Markus M; Schett, Georg; Wirtz, Stefan; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-03-11

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts.

  7. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  8. Inflammatory pancreatic masses: problems in differentiating focal pancreatitis from carcinoma

    SciTech Connect

    Neff, C.C.; Simeone, J.F.; Wittenberg, J.; Mueller, P.R.; Ferrucci, J.T. Jr.

    1984-01-01

    The authors studied 19 patients with focal inflammatory masses of the pancreas over an 18-month period. In 13 cases, transhepatic cholangiography and/or endoscopic retrograde cholangiopancreatography were unsuccessful in differentiating pancreatitis from carcinoma. Eighteen patients had a history of alcohol abuse, and 12 had had pancreatitis previously. Pre-existing glandular injury appears to be a prerequisite to formation of focal inflammatory pancreatic masses.

  9. Follicular Pancreatitis: A Distinct Form of Chronic Pancreatitis - An Additional Mimic of Pancreatic Neoplasms

    PubMed Central

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-01-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of six patients (male:female = 2:1, mean age = 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis while two presented with abdominal pain, fatigue and elevated liver enzymes. On imaging, three patients had a discrete solid mass while 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2 negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions. IgG4/IgG ratio was <40% in all 6 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  10. Acute Pancreatitis after Kidney Transplantation

    PubMed Central

    Tabakovic, Mithat; Salkic, Nermin N.; Bosnjic, Jasmina; Alibegovic, Ervin

    2012-01-01

    Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient. PMID:23259142

  11. [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.

  12. [Exocrine pancreatic insufficiency (author's transl)].

    PubMed

    Götze, H

    1980-12-01

    Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.

  13. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2013-10-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern knowledge of the etiopathogenesis of the disease, the pharmacological treatment of pain, and knowledge of the natural history of autoimmune pancreatitis. New evidence supports the relatively low prevalence of chronic alcoholic pancreatitis, and the role of tobacco in triggering the etiopathogenic mechanisms of chronic pancreatitis is better understood. Some studies have identified certain factors that are associated with having a positive genetic test in adults with chronic idiopathic pancreatitis, which should help to select those patients who should undergo genetic studies. Antioxidant therapy has been shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Finally, the development of exocrine and endocrine pancreatic insufficiency is a very common finding during the long-term follow-up of patients with autoimmune pancreatitis. Smoking also seems to play a role in this type of pancreatitis.

  14. Acute pancreatitis: The stress factor

    PubMed Central

    Binker, Marcelo G; Cosen-Binker, Laura I

    2014-01-01

    Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340

  15. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2014-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up.

  16. Thromboembolism and pancreatic cancer.

    PubMed

    De Souza, Andre Luiz; Saif, Muhammad Wasif

    2014-07-28

    Venous thromboembolism (VTE) is a frequent event in the clinical course of patients with exocrine pancreatic cancer; studies have been designed to evaluate the role of prophylactic anticoagulation in this ominous disease. Searching for the molecular basis of thrombosis in cancer, Bozkurt et al. present in the Abstract #e22049 the result of their investigation on the frequency of inherited and carcinogenesis-acquired proteins in oncologic patients with and without venous thromboembolism. From the bedside, Muñoz Martin et al. present in the Abstract #e15187 their work on the incidence of venous thromboembolism in patients with exocrine pancreatic cancer and the role of the established Khorana score in predicting symptomatic and incidental venous thromboembolism. At last, Cella et al. in the Abstract #e20625 expand the predictor landscape from the Khorana score to other risk factors for venous thromboembolism, refining the selection of oncologic patients who can benefit from prophylactic anticoagulation.

  17. Pancreatic neuroendocrine tumors

    PubMed Central

    Sun, Jian

    2017-01-01

    Summary Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors including well differentiated pancreatic neuroendocrine tumors (pNETs) and neuroendocrine carcinomas (pNECs). The incidence of pNENs has increased over the past few decades. Although, the understanding and interest for this tumor have also increased significantly, the debate about classification and diagnosis continues. Although the primary treatment for pNENs is surgical resection, there is still a lack of effective therapeutic options for patients with advanced unresectable pNENs. Although many therapeutic methods have proven effective, the choice of treatment and specific programs are still unclear. Our article presents an overview of pNENs, with a focus on their diagnostic work-up, clinical presentation and treatment options. PMID:28357177

  18. Traumatic pancreatic pseudocysts.

    PubMed

    Popoola, D; Lou, M A; Sims, E H

    1983-05-01

    At the Martin Luther King, Jr, General Hospital in Los Angeles, during the period from June 1972 to April 1981, seven patients underwent surgery for traumatic pancreatic pseudocysts. The overall average age was 28 and the average hospital stay was 31 days. Ultrasound was the most useful test for diagnosis and follow-up. Preoperatively, serum amylases were not consistently elevated. Overall recurrences and complications totaled 57 percent. There were no deaths. The authors consider a large cystogastrostomy the treatment of choice for mature cysts that are satisfactorily adherent to the stomach. The second preference is a Roux-en-Y cystojejunostomy. External drainage was employed for acute cysts that required drainage. A distal pancreatectomy was performed for patients with small pancreatic tail pseudocysts. Patients who underwent acute drainage were usually drained externally and had a poorer outcome than patients who were operated on later with internal drainage. When compared with another group of 15 alcoholic patients who were operated on for pancreatic pseudocysts, patients with traumatic pseudocysts had a poorer outcome.

  19. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with (3H)-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with (3H)-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

  20. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    PubMed Central

    Jani, Bharivi; Rzouq, Fadi; Saligram, Shreyas; Nawabi, Atta; Nicola, Marian; Dennis, Katie; Ernst, Carly; Abbaszadeh, Ali; Bonino, John; Olyaee, Mojtaba

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the “groove” of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA) was nondiagnostic. The patient then underwent a Whipple's procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction is present, and

  1. Acute pancreatitis in patients with pancreatic cancer

    PubMed Central

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  2. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    PubMed Central

    Gerloff, Andreas; Singer, Manfred V; Feick, Peter

    2010-01-01

    In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated. PMID:20617020

  3. Canagliflozin-Associated Acute Pancreatitis.

    PubMed

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.

  4. Somatostatin therapy of acute experimental pancreatitis.

    PubMed Central

    Lankisch, P G; Koop, H; Winckler, K; Fölsch, U R; Creutzfeldt, W

    1977-01-01

    Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis. PMID:604191

  5. [Therapeutic attitude in acute necrotizing pancreatitis].

    PubMed

    Leşe, Mihaela; Pop, C; Naghi, Ildiko; Mureşan, Lavinia

    2002-01-01

    The necrosectomy, celiostomy and pancreatic drainage represent the surgical treatment of choice in necrotizing pancreatitis. We present the clinical observation of a patient 59 years old operated in surgical service of Baia Mare for acute necrotizing pancreatitis, discussing the moment of operation, tips of operations, postoperative complications as well as our experience in acute grave pancreatitis treatment.

  6. [Biological aspects of pancreatic cancer].

    PubMed

    Tonel, E; Carbone, A; Scirelli, T; Bellone, G; Emanuelli, G

    2005-04-01

    Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment.

  7. Proteomics studies of pancreatic cancer

    PubMed Central

    Chen, Ru; Pan, Sheng; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States, with 4% survival 5 years after diagnosis. Biomarkers are desperately needed to improve earlier, more curable cancer diagnosis and to develop new effective therapeutic targets. The development of quantitative proteomics technologies in recent years offers great promise for understanding the complex molecular events of tumorigenesis at the protein level, and has stimulated great interest in applying the technology for pancreatic cancer studies. Proteomic studies of pancreatic tissues, juice, serum/plasma, and cell lines have recently attempted to identify differentially expressed proteins in pancreatic cancer to dissect the abnormal signaling pathways underlying oncogenesis, and to detect new biomarkers. It can be expected that the continuing evolution of proteomics technology with better resolution and sensitivity will greatly enhance our capability in combating pancreatic cancer. PMID:18633454

  8. Autoimmune pancreatitis: a surgical dilemma.

    PubMed

    Saavedra-Perez, David; Vaquero, Eva C; Ayuso, Juan R; Fernandez-Cruz, Laureano

    2014-12-01

    Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer.

  9. [Surgical management of chronic pancreatitis].

    PubMed

    Regimbeau, Jean-Marc; Dumont, Frédéric; Yzet, Thierry; Chatelain, Denis; Bartoli, Eacute Ric; Brazier, Franck; Bréhant, Olivier; Dupas, Jean-Louis; Mauvais, François; Delcenserie, Richard

    2007-01-01

    Surgical indications for chronic pancreatitis can be schematically separated into five main groups: pain, effects of fibrosis on adjacent organs, the consequences of main pancreatic duct rupture above an obstruction, and suspected cancer. Finally surgery is also indicated in patients who cannot undergo endoscopic procedures (no accessible papilla) or who have too recently undergone this procedure. Surgical procedures include derivation (pancreatic, cystic, biliary) or mixed procedures combining derivation/resection or pancreatic resection. Finally splanchnicectomy can be discussed. Whatever the indication, surgical treatment must meet several goals: the approach to surgery must be multidisciplinary, surgery must be associated with low morbidity and mortality, preserve as much endocrine function as possible, improve quality of life, and be evaluated in the long term, as well as prospectively if possible. We clarify some important points about the management of patients with chronic pancreatitis before discussing the various treatments in detail.

  10. [Diabetes mellitus in acute pancreatitis].

    PubMed

    Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo

    2002-01-01

    Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.

  11. Blood tests for acute pancreatitis

    PubMed Central

    Basnayake, Chamara; Ratnam, Dilip

    2015-01-01

    Summary The diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria – characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis. Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2–4 times the upper limit of normal is recommended for diagnosis. Serum lipase is now the preferred test due to its improved sensitivity, particularly in alcohol-induced pancreatitis. Its prolonged elevation creates a wider diagnostic window than amylase. Neither enzyme is useful in monitoring or predicting the severity of an episode of pancreatitis in adults. New biomarkers including trypsinogen and elastase have no significant advantage over amylase or lipase. PMID:26648641

  12. New developments in pancreatic cancer.

    PubMed

    Greer, Julia B; Brand, Randall E

    2011-04-01

    Pancreatic adenocarcinoma presents in an advanced stage and has a dismal prognosis. Extensive recent research efforts have provided us with greater insight into the etiology of pancreatic cancer and have also improved our means of prognostication. Molecular analysis demonstrated that specific pathways involved in pancreatic carcinogenesis are perhaps more valuable to study than single genetic aberrations. Previous risk factors, including family history, body mass index, and current cigarette smoking, were validated and novel risks, such as ABO blood group alleles, were identified. Similar to other illnesses, combinations of healthful habits, such as not smoking, adhering to a Mediterranean dietary pattern, and engaging in physical activity, may decrease pancreatic cancer risk. Finally, CA 19-9 levels, the presence of diabetes mellitus, and a six-gene signature provided critical information regarding survival that could help guide treatment of individuals diagnosed with pancreatic adenocarcinoma.

  13. Alcohol consumption on pancreatic diseases.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Bañales, Jesus Maria; Cosme, Angel; Bujanda, Luis

    2013-02-07

    Although the association between alcohol and pancreatic diseases has been recognized for a long time, the impact of alcohol consumption on pancreatitis and pancreatic cancer (PC) remains poorly defined. Nowadays there is not consensus about the epidemiology and the beverage type, dose and duration of alcohol consumption causing these diseases. The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose, type and frequency of alcohol consumption and risk of pancreatitis and PC. The majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis (around 2.5%-3% between heavy drinkers and 1.3% between non drinkers). About 70% of pancreatitis are due to chronic heavy alcohol consumption. Although this incidence rate differs between countries, it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 years. With regard to PC, the role of alcohol consumption remains less clear, and low to moderate alcohol consumption do not appear to be associated with PC risk, and only chronic heavy drinking increase the risk compared with lightly drinkers. In a population of 10%-15% of heavy drinkers, 2%-5% of all PC cases could be attributed to alcohol consumption. However, as only a minority (less than 10% for pancreatitis and 5% for PC) of heavily drinkers develops these pancreatic diseases, there are other predisposing factors besides alcohol involved. Genetic variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.

  14. The clinical significance of pancreatic steatosis.

    PubMed

    Smits, Mark M; van Geenen, Erwin J M

    2011-03-01

    More research is now focused on pancreatic steatosis. Multiple definitions, clinical associations and synonyms for pancreatic steatosis are described in the literature and can be confusing. The integration and comparison of several studies concerning this topic is therefore challenging. In the past, pancreatic steatosis was considered an innocuous condition, a bystander of many underlying diseases (such as congenital syndromes, hemochromatosis and viral infection). However, evidence that pancreatic steatosis (strongly associated with obesity and the metabolic syndrome) has a role in type 2 diabetes mellitus, pancreatic exocrine dysfunction, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula after pancreatic surgery is emerging. This Review focuses on the different etiological factors and the clinical consequences of pancreatic steatosis.

  15. Hereditary pancreatic cancer: a clinical perspective.

    PubMed

    Greer, Julia B; Lynch, Henry T; Brand, Randall E

    2009-01-01

    Pancreatic cancer is an extraordinarily deadly disease and is responsible for over 220,000 deaths worldwide each year. One of the greatest risk factors for developing pancreatic cancer is a positive family history. Hereditary pancreatitis patients have a greatly elevated pancreatic cancer risk and individuals with cystic fibrosis may rarely develop this cancer, but often at very young ages. Various genetically linked cancer syndromes have been associated with pancreatic cancer in mutation-positive family members. Finally, familial pancreatic cancer-defined as families with two or more first-degree relatives who have pancreatic cancer but do not have a known cancer syndrome-is a known entity whose disease-causing mutation remains unidentified. This article describes research to date on hereditary pancreatic cancer, addresses how best clinicians should recognise hereditary forms of pancreatic cancer and explains the emotional burden of discovering a potentially lethal mutation. Many controversies and unanswered questions in hereditary pancreatic cancer remain.

  16. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  17. Venous complications of pancreatitis: a review.

    PubMed

    Aswani, Yashant; Hira, Priya

    2015-01-31

    Pancreatitis is notorious to cause vascular complications. While arterial complications include pseudoaneurysm formation with a propensity to bleed, venous complications can be quite myriad. Venous involvement in pancreatitis often presents with thrombosis. From time to time case reports and series of unusual venous complications associated with pancreatitis have, however, been described. In this article, we review multitudinous venous complications in the setting of pancreatitis and propose a system to classify pancreatitis associated venous complications.

  18. [Ultrasonography of pancreatic neoplasms].

    PubMed

    Innocenti, P; Falchini, M; Stecco, A

    1999-01-01

    Pancreatic tumors are the fourth cause of death in Occident: the 5-year-survival rate is less than 5% because of diagnostic difficulties, low clinical expression at early stage, and complexity of the surgical treatment. The role of ultrasound (US) is in early diagnosis, because also in early cancer there could be lymphatic spread or peritoneal involvement. There are multiple modalities to study the pancreas with US: abdominal US, "contact" US (endosonography and intra-operative or laparoscopic US). The first is not invasive, cheap but limited by extrinsic and intrinsic factors, the latter are respectively characterized by high cost, and need of endoscopic specialists for endosonography, the complementarity to laparoscopy or surgery for the laparoscopic/intraoperative US. Abdominal US is the first diagnostic step for the pancreas, but it is not affordable in 15-25% of patients, because of meteorism. In all the other cases, it represents the pancreas with a good contrast between the normal parenchyma and tumoral tissues. Abdominal US, together with biopsy, can define the resectability. Ecoendoscopy is actually dedicated to small tumors staging, but recent studies demonstrate the same results achieved by spiral TC. Laparoscopic US is a second step imaging in patients already selected for surgery. The first finality in US evaluation of tumor masses is early diagnosis of pancreatic cancer; it can give to some of these patients the opportunity of undergoing to surgical treatment. This could be achieved by a proper use of the moititude of ultrasonic abdominal explorations that are requested in daily practice. US, together with CT and MR, can define the resectability of the tumor, with further supplementar evaluation by mean of laparoscopic US. Intraoperative US is now indicated for planning and guiding the surgeon in resection of the pancreatic cancer.

  19. Combination Chemotherapy With or Without Oregovomab Followed by Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer

    ClinicalTrials.gov

    2017-02-28

    Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  20. Screening for Pancreatic Cancer.

    PubMed

    Ngamruengphong, Saowanee; Canto, Marcia Irene

    2016-12-01

    Pancreatic cancer (PC) is a highly fatal disease that can only be cured by complete surgical resection. However, most patients with PC have unresectable disease at the time of diagnosis, highlighting the need to detect PC and its precursor lesions earlier in asymptomatic patients. Screening is not cost-effective for population-based screening of PC. Individuals with genetic risk factors for PC based on family history or known PC-associated genetic syndromes, however, can be a potential target for PC screening programs. This article provides an overview of the epidemiology and genetic background of familial PC and discusses diagnostic and management approaches.

  1. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    SciTech Connect

    Rossi, R.L.; Braasch, J.W.; O'Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  2. 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

  3. Redox signaling in acute pancreatitis.

    PubMed

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

    2015-08-01

    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.

  4. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

  5. Necrotizing pancreatitis: challenges and solutions

    PubMed Central

    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. PMID:27826206

  6. Recent Progress in Pancreatic Cancer

    PubMed Central

    Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

    2013-01-01

    Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

  7. Pancreatic infection with Candida parapsilosis.

    PubMed

    Ibáñez, R; Serrano-Heranz, R

    1999-01-01

    Candida species other than C. albicans have been implicated as pathogens in intravascular (bloodstream, intravascular devices, endocarditis) and extravascular (arthritis, osteomielitis, endophtalmitis) infections. C. parapsilosis, however, is rarely implicated in intra-abdominal infections (peritonitis during peritoneal dialysis, complicating surgery or solid-organ transplantation). We describe a case of a 48-y-old male with acute pancreatitis who had a pancreatic abscess produced by primary C. parapsilosis infection. Although he received adequate treatment with antifungal medication and surgical drainage, the outcome was fatal. Because the clinical findings are indistinguishable from bacterial abscesses, Candida species should be considered in cases of complicated pancreatitis, in order to establish a prompt adequate treatment.

  8. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    PubMed Central

    Gilliland, Taylor M.; Villafane-Ferriol, Nicole; Shah, Kevin P.; Shah, Rohan M.; Tran Cao, Hop S.; Massarweh, Nader N.; Silberfein, Eric J.; Choi, Eugene A.; Hsu, Cary; McElhany, Amy L.; Barakat, Omar; Fisher, William; Van Buren, George

    2017-01-01

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate

  9. Magnetic resonance imaging of pancreatitis: An update

    PubMed Central

    Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

    2014-01-01

    Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

  10. Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

    PubMed Central

    Macinga, Peter; Pulkertova, Adela; Bajer, Lukas; Maluskova, Jana; Oliverius, Martin; Smejkal, Martin; Heczkova, Maria; Spicak, Julius; Hucl, Tomas

    2017-01-01

    AIM To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic resections performed for focal pancreatic enlargement. METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria. RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was also present in six patients with AIP (40%), all six were men. Patients with AIP + PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

  11. Pancreatic stellate cell: Pandora's box for pancreatic disease biology

    PubMed Central

    Bynigeri, Ratnakar R; Jakkampudi, Aparna; Jangala, Ramaiah; Subramanyam, Chivukula; Sasikala, Mitnala; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-01-01

    Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma. PMID:28210075

  12. Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2014-10-07

    Intraductal Papillary Mucinous Neoplasm of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  13. Drugs Approved for Pancreatic Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  14. Evaluating steatosis in pancreatic transplant.

    PubMed

    Verma, Aneesha Ratan; Papalois, Vassilios

    2011-06-01

    Pancreatic transplant remains the only treatment that cures insulin-dependent diabetes mellitus. It is recognized by transplant surgeons that donor pancreases with excessive fat infiltration have a poorer clinical outcome, resulting in significant recipient morbidity and mortality. However, no objective measure of pancreatic fat infiltration exists, and no study has been done that correlates the level of fat infiltration with clinical outcome. There have been significant radiologic advances that allow assessment of fat content of organs, and these could be used to accurately quantify the extent of pancreatic fat infiltration. We reviewed the literature regarding pancreatic steatosis, and examined ways in which the level of steatosis could be objectively measured before transplant, thereby improving clinical outcome.

  15. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  16. Listeria Vaccines for Pancreatic Cancer

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0411 TITLE: Listeria vaccines for pancreatic cancer...29September2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Listeria vaccines for pancreatic cancer 5b. GRANT NUMBER W81XWH-12-1-0411 5c...explored the capacity of Listeria vaccines to induce anti-tumor T cell immunity in the KPC model. We have found that Listeria vaccines produce

  17. Pancreatic carcinogenesis: apoptosis and angiogenesis.

    PubMed

    Onizuka, Shinya; Kawakami, Shunsuke; Taniguchi, Ken; Fujioka, Hikaru; Miyashita, Kosei

    2004-04-01

    Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future.

  18. Pancreatic cancer, inflammation, and microbiome.

    PubMed

    Zambirinis, Constantinos P; Pushalkar, Smruti; Saxena, Deepak; Miller, George

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Inflammatory conditions such as pancreatitis represent a well-known risk factor for pancreatic cancer development. Yet only in the past 2 decades has pancreatic cancer been recognized as an inflammation-driven cancer, and the precise mechanisms underlying the pathogenic role of inflammation are beginning to be explored in detail. A substantial amount of preclinical and clinical evidence suggests that bacteria are likely to influence this process by activating immune receptors and perpetuating cancer-associated inflammation. The recent explosion of investigations of the human microbiome have highlighted how perturbations of commensal bacterial populations can promote inflammation and promote disease processes, including carcinogenesis. The elucidation of the interplay between inflammation and microbiome in the context of pancreatic carcinogenesis will provide novel targets for intervention to prevent and treat pancreatic cancer more efficiently. Further studies toward this direction are urgently needed.

  19. Pancreatic cancer chemoradiotherapy.

    PubMed

    Brunner, Thomas B; Seufferlein, Thomas

    2016-08-01

    Pancreatic cancer is the most lethal gastrointestinal tumour. Chemotherapy is the mainstay of therapy in the majority of the patients whereas resection is the only chance of cure but only possible in 15-20% of all patients. The integration of radiotherapy into multimodal treatment concepts is heavily investigated. It is now commonly accepted that induction chemotherapy should precede radiotherapy. When fractionated conventionally it should be given as chemoradiotherapy. Recently, stereotactic body radiotherapy emerged as an alternative, but will have to be carefully investigated in clinical trials. This review aims to give an overview of radiotherapeutic strategies with a focus on the latest developments in the field in the context of chemotherapy and surgery.

  20. Pancreatic cancer stem cells.

    PubMed

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.

  1. Capecitabine, Temozolomide and Bevacizumab for Metastatic or Unresectable Pancreatic Neuroendocrine Tumors

    ClinicalTrials.gov

    2016-09-21

    Gastrinoma; Glucagonoma; Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Islet Cell Carcinoma; Recurrent Pancreatic Cancer; Somatostatinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  2. Disconnected pancreatic duct syndrome: complete pancreas transection secondary to acute pancreatitis.

    PubMed

    Gámez-del-Castillo, Juan Manuel; Garcés-Albir, Marina; Fernández-Moreno, María Carmen; Morera-Ocón, Francisco Javier; Villagrasa, Rosana; Sabater-Ortí, Luis

    2016-03-01

    Disconnected pancreatic duct syndrome is a serious complication of acute pancreatitis which is defined by a complete discontinuity of the pancreatic duct, such that a viable side of the pancreas remains isolated from the gastrointestinal tract. This pancreatic disruption is infrequently observed in the clinical practice and its diagnostic and therapeutic management are controversial. We present an extreme case of disconnected pancreatic duct syndrome with complete duct disruption and pancreatic transection following acute pancreatitis, as well as the diagnostic and therapeutic processes carried out.

  3. Lipolysis of Visceral Adipocyte Triglyceride by Pancreatic Lipases Converts Mild Acute Pancreatitis to Severe Pancreatitis Independent of Necrosis and Inflammation

    PubMed Central

    Patel, Krutika; Trivedi, Ram N.; Durgampudi, Chandra; Noel, Pawan; Cline, Rachel A.; DeLany, James P.; Navina, Sarah; Singh, Vijay P.

    2016-01-01

    Visceral fat necrosis has been associated with severe acute pancreatitis (SAP) for over 100 years; however, its pathogenesis and role in SAP outcomes are poorly understood. Based on recent work suggesting that pancreatic fat lipolysis plays an important role in SAP, we evaluated the role of pancreatic lipases in SAP-associated visceral fat necrosis, the inflammatory response, local injury, and outcomes of acute pancreatitis (AP). For this, cerulein pancreatitis was induced in lean and obese mice, alone or with the lipase inhibitor orlistat and parameters of AP induction (serum amylase and lipase), fat necrosis, pancreatic necrosis, and multisystem organ failure, and inflammatory response were assessed. Pancreatic lipases were measured in fat necrosis and were overexpressed in 3T3-L1 cells. We noted obesity to convert mild cerulein AP to SAP with greater cytokines, unsaturated fatty acids (UFAs), and multisystem organ failure, and 100% mortality without affecting AP induction or pancreatic necrosis. Increased pancreatic lipase amounts and activity were noted in the extensive visceral fat necrosis of dying obese mice. Lipase inhibition reduced fat necrosis, UFAs, organ failure, and mortality but not the parameters of AP induction. Pancreatic lipase expression increased lipolysis in 3T3-L1 cells. We conclude that UFAs generated via lipolysis of visceral fat by pancreatic lipases convert mild AP to SAP independent of pancreatic necrosis and the inflammatory response. PMID:25579844

  4. 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.

  5. Blunt pancreatic trauma: A persistent diagnostic conundrum?

    PubMed Central

    Kumar, Atin; Panda, Ananya; Gamanagatti, Shivanand

    2016-01-01

    Blunt pancreatic trauma is an uncommon injury but has high morbidity and mortality. In modern era of trauma care, pancreatic trauma remains a persistent challenge to radiologists and surgeons alike. Early detection of pancreatic trauma is essential to prevent subsequent complications. However early pancreatic injury is often subtle on computed tomography (CT) and can be missed unless specifically looked for. Signs of pancreatic injury on CT include laceration, transection, bulky pancreas, heterogeneous enhancement, peripancreatic fluid and signs of pancreatitis. Pan-creatic ductal injury is a vital decision-making parameter as ductal injury is an indication for laparotomy. While lacerations involving more than half of pancreatic parenchyma are suggestive of ductal injury on CT, ductal injuries can be directly assessed on magnetic resonance imaging (MRI) or encoscopic retrograde cholangio-pancreatography. Pancreatic trauma also shows temporal evolution with increase in extent of injury with time. Hence early CT scans may underestimate the extent of injures and sequential imaging with CT or MRI is important in pancreatic trauma. Sequential imaging is also needed for successful non-operative management of pancreatic injury. Accurate early detection on initial CT and adopting a multimodality and sequential imaging strategy can improve outcome in pancreatic trauma. PMID:26981225

  6. Recurrent pancreatitis in ornithine transcarbamylase deficiency.

    PubMed

    Prada, Carlos E; Kaul, Ajay; Hopkin, Robert J; Page, Kimberley I; Nathan, Jaimie D; Bartholomew, Dennis W; Cohen, Mitchell B; Heubi, James E; Leslie, Nancy D; Burrow, T Andrew

    2012-08-01

    Ornithine transcarbamylase (OTC) deficiency is a urea cycle defect with varying frequency and severity of episodes of hyperammonemia. We report three patients with OTC deficiency with recurrent pancreatitis. The pathogenesis of acute pancreatitis in this patient population requires further elucidation. Pancreatitis significantly affected dietary/metabolic management and increased frequency of hospitalizations.

  7. 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.

  8. Management of acute pancreatitis (AP) – Polish Pancreatic Club recommendations

    PubMed Central

    Rosołowski, Mariusz; Lipiński, Michał; Dobosz, Marek; Durlik, Marek; Głuszek, Stanisław; Kuśnierz, Katarzyna; Lampe, Paweł; Małecka-Panas, Ewa; Nowakowska-Duława, Ewa; Nowak-Niezgoda, Magdalena; Radomańska, Barbara; Talar-Wojnarowska, Renata; Wereszczyńska-Siemiątkowska, Urszula

    2016-01-01

    The presented recommendations concern the current management of acute pancreatitis. The recommendations relate to the diagnostics and treatment of early and late phases of acute pancreatitis and complications of the disease taking into consideration surgical and endoscopic methods. All the recommendations were subjected to voting by the members of the Working Group of the Polish Pancreatic Club, who evaluated them every single time on a five-point scale, where A means full acceptance, B means acceptance with a certain reservation, C means acceptance with a serious reservation, D means rejection with a certain reservation and E means full rejection. The results of the vote, together with commentary, are provided for each recommendation. PMID:27350832

  9. The Pancreatic Islet Regulome Browser

    PubMed Central

    Mularoni, Loris; Ramos-Rodríguez, Mireia; Pasquali, Lorenzo

    2017-01-01

    The pancreatic islet is a highly specialized tissue embedded in the exocrine pancreas whose primary function is that of controlling glucose homeostasis. Thus, understanding the transcriptional control of islet-cell may help to puzzle out the pathogenesis of glucose metabolism disorders. Integrative computational analyses of transcriptomic and epigenomic data allows predicting genomic coordinates of putative regulatory elements across the genome and, decipher tissue-specific functions of the non-coding genome. We herein present the Islet Regulome Browser, a tool that allows fast access and exploration of pancreatic islet epigenomic and transcriptomic data produced by different labs worldwide. The Islet Regulome Browser is now accessible on the internet or may be installed locally. It allows uploading custom tracks as well as providing interactive access to a wealth of information including Genome-Wide Association Studies (GWAS) variants, different classes of regulatory elements, together with enhancer clusters, stretch-enhancers and transcription factor binding sites in pancreatic progenitors and adult human pancreatic islets. Integration and visualization of such data may allow a deeper understanding of the regulatory networks driving tissue-specific transcription and guide the identification of regulatory variants. We believe that such tool will facilitate the access to pancreatic islet public genomic datasets providing a major boost to functional genomics studies in glucose metabolism related traits including diabetes. PMID:28261261

  10. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer.

    PubMed

    Du, Juan; Cieslak, John A; Welsh, Jessemae L; Sibenaller, Zita A; Allen, Bryan G; Wagner, Brett A; Kalen, Amanda L; Doskey, Claire M; Strother, Robert K; Button, Anna M; Mott, Sarah L; Smith, Brian; Tsai, Susan; Mezhir, James; Goswami, Prabhat C; Spitz, Douglas R; Buettner, Garry R; Cullen, Joseph J

    2015-08-15

    The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress-induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.

  11. PCMdb: Pancreatic Cancer Methylation Database

    NASA Astrophysics Data System (ADS)

    Nagpal, Gandharva; Sharma, Minakshi; Kumar, Shailesh; Chaudhary, Kumardeep; Gupta, Sudheer; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-02-01

    Pancreatic cancer is the fifth most aggressive malignancy and urgently requires new biomarkers to facilitate early detection. For providing impetus to the biomarker discovery, we have developed Pancreatic Cancer Methylation Database (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated to methylation of genes in pancreatic cancer. Data was collected and compiled manually from published literature. PCMdb has 65907 entries for methylation status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for 3078 tissue samples). Among these entries, 47.22% entries reported a high level of methylation for the corresponding genes while 10.87% entries reported low level of methylation. PCMdb covers five major subtypes of pancreatic cancer; however, most of the entries were compiled for adenocarcinomas (88.38%) and mucinous neoplasms (5.76%). A user-friendly interface has been developed for data browsing, searching and analysis. We anticipate that PCMdb will be helpful for pancreatic cancer biomarker discovery.

  12. Cystic Lesions in Autoimmune Pancreatitis.

    PubMed

    Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán

    2015-01-01

    Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered after corticosteroid therapy. One year later, he presented with a recurrent episode of AIP with elevated IgG4 levels, accompanied by the appearance of multiple intrapancreatic cystic lesions. All but 1 of these cysts disappeared after steroid treatment, but the remaining cyst in the pancreatic head was even somewhat larger 1 year later. Pancreatoduodenectomy was finally performed. Histology showed the wall of the cystic lesion to be fibrotic; the surrounding pancreatic tissue presented fibrosis, atrophy and lymphoplasmacytic infiltration by IgG4-positive cells, without malignant elements. Our case illustrates the rare possibility that cystic lesions can be part of AIP. These pseudocysts appear in the pancreatic segments involved in the autoimmune disease and can be a consequence of the local inflammation or related to ductal strictures. Steroid treatment should be initiated, after which these cysts can completely disappear with recovery from AIP. Surgical intervention may be necessary in some exceptional cases.

  13. Fluid resuscitation in acute pancreatitis

    PubMed Central

    Aggarwal, Aakash; Manrai, Manish; Kochhar, Rakesh

    2014-01-01

    Acute pancreatitis remains a clinical challenge, despite an exponential increase in our knowledge of its complex pathophysiological changes. Early fluid therapy is the cornerstone of treatment and is universally recommended; however, there is a lack of consensus regarding the type, rate, amount and end points of fluid replacement. Further confusion is added with the newer studies reporting better results with controlled fluid therapy. This review focuses on the pathophysiology of fluid depletion in acute pancreatitis, as well as the rationale for fluid replacement, the type, optimal amount, rate of infusion and monitoring of such patients. The basic goal of fluid epletion should be to prevent or minimize the systemic response to inflammatory markers. For this review, various studies and reviews were critically evaluated, along with authors’ recommendations, for predicted severe or severe pancreatitis based on the available evidence. PMID:25561779

  14. Ascariasis of the pancreatic duct.

    PubMed

    Klimovskij, Michail; Dulskas, Audrius; Kraulyte, Zita; Mikalauskas, Saulius

    2015-09-15

    Ascariasis is a common helminthic disease worldwide, although Lithuania and other European countries are not considered endemic areas. The presence of the Ascaris worm in the biliary tree causes choledocholithiasis-like symptoms. We report a case of pancreatic duct ascariasis causing such symptoms. A 73-year-old Lithuanian woman underwent endoscopic retrograde cholangiopancreatography (ERCP) suspecting choledocholithiasis. Contrast injection into the common bile duct demonstrated a slightly dilated biliary tree without any filling defects, and the tail of an Ascaris worm protruding from the opening of the papilla Vater. The worm was captured by a snare but escaped deep into the duct. After a small wirsungotomy the worm was retrieved from the pancreatic duct. The patient received a 150 mg dose of levamisole orally repeated 7 days later and was discharged after complete resolution of symptoms. This first reported sporadic case of pancreatic duct ascariasis in Lithuania was successfully treated with ERCP and Levamisole.

  15. Endoscopic Palliation of Pancreatic Cancer

    PubMed Central

    Coté, Gregory A.; Sherman, Stuart

    2012-01-01

    Endoscopy has an increasingly important role in the palliation of patients with pancreatic ductal adenocarcinoma. Endoscopic biliary drainage is still requested in the majority of patients who present with obstructive jaundice, and the increased use of self-expandable metallic stents has reduced the incidence of premature stent occlusion. First-line use of metallic stents is expected to be utilized more frequently as neoadjuvant protocols are improved. The efficacy of endoscopy for palliating gastroduodenal obstruction has advanced with the development of through-the-scope, self-expandable gastroduodenal stents. There have been advances in pain management, with endoscopic ultrasound-guided celiac plexus neurolysis reducing opiate requirements and pain for patients with unresectable malignancy. Future applications of endoscopy in pancreatic cancer may include fine needle injection of chemotherapeutic and other agents into the lesion itself. This review will summarize the evidence of endoscopy in the management of patients with pancreatic cancer. PMID:23187846

  16. Percutaneous ablation of pancreatic cancer

    PubMed Central

    D’Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

    2016-01-01

    Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review. PMID:27956791

  17. Percutaneous ablation of pancreatic cancer.

    PubMed

    D'Onofrio, Mirko; Ciaravino, Valentina; De Robertis, Riccardo; Barbi, Emilio; Salvia, Roberto; Girelli, Roberto; Paiella, Salvatore; Gasparini, Camilla; Cardobi, Nicolò; Bassi, Claudio

    2016-11-28

    Pancreatic ductal adenocarcinoma is a highly aggressive tumor with an overall 5-year survival rate of less than 5%. Prognosis and treatment depend on whether the tumor is resectable or not, which mostly depends on how quickly the diagnosis is made. Chemotherapy and radiotherapy can be both used in cases of non-resectable pancreatic cancer. In cases of pancreatic neoplasm that is locally advanced, non-resectable, but non-metastatic, it is possible to apply percutaneous treatments that are able to induce tumor cytoreduction. The aim of this article will be to describe the multiple currently available treatment techniques (radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation), their results, and their possible complications, with the aid of a literature review.

  18. Emphysematous pancreatitis predisposed by Olanzapine

    PubMed Central

    Samanta, Sukhen; Samanta, Sujay; Banik, Krishanu; Baronia, Arvind Kumar

    2014-01-01

    A 32-year-old male presented to our intensive care unit with severe abdominal pain and was diagnosed as acute pancreatitis after 2 months of olanzapine therapy for bipolar disorder. His serum lipase was 900 u/L, serum triglyceride 560 mg/dL, and blood sugar, fasting and postprandial were 230 and 478 mg/dL, respectively on admission. Contrast enhanced computed tomography (CECT) of abdomen was suggestive of acute pancreatitis. Repeat CECT showed gas inside pancreas and collection in peripancreatic area and patient underwent percutaneous drainage and antibiotics irrigation through the drain into pancreas. We describe the rare case of emphysematous pancreatitis due to development of diabetes, hypertriglyceridemia and immunosuppression predisposed by short duration olanzapine therapy. PMID:25024479

  19. Hydrocarbon exposure, pancreatitis, and bile acids.

    PubMed Central

    Hotz, P; Pilliod, J; Bourgeois, R; Boillat, M A

    1990-01-01

    The data on hydrocarbon induced pancreatitis are conflicting. This question was therefore studied in a non-selected population exposed to hydrocarbons and in "formerly" exposed workers. Neither the past clinical history nor the pancreatic tests provided any evidence for a causal relation between exposure and pancreatitis. No signs of hydrocarbon induced liver damage were seen either. As a healthy worker effect cannot be totally excluded, however, a case-control study in a group of patients suffering from non-alcohol induced pancreatitis could give useful indications for finally excluding the possibility of pancreatitis being induced by hydrocarbons. PMID:2271391

  20. Notch Signaling in Pancreatic Development

    PubMed Central

    Li, Xu-Yan; Zhai, Wen-Jun; Teng, Chun-Bo

    2015-01-01

    The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways. PMID:26729103

  1. Drug metabolism and pancreatic cancer.

    PubMed

    Flores, John Paul E; Diasio, Robert B; Saif, Muhammad Wasif

    2017-01-01

    Pancreatic cancer remains a fatal disease in the majority of patients. The era of personalized medicine is upon us: customizing therapy according to each patient's individual cancer. Potentially, therapy can be targeted at individuals who would most likely have a favorable response, making it more efficacious and cost effective. This is particularly relevant for pancreatic cancer, which currently portends a very poor prognosis. However, there is much to be done in this field, and more studies are needed to bring this concept to reality.

  2. Adjuvant therapy in pancreatic cancer.

    PubMed

    Jones, Owain Peris; Melling, James Daniel; Ghaneh, Paula

    2014-10-28

    Pancreatic cancer remains one of the leading causes of cancer related death worldwide with an overall five-year survival of less than 5%. Potentially curative surgery, which alone can improve 5-year survival to 10%, is an option for only 10%-20% of patients at presentation owing to local invasion of the tumour or metastatic disease. Adjuvant chemotherapy has been shown to improve 5-year survival to 20%-25% but conflicting evidence remains with regards to chemoradiation. In this article we review the current evidence available from published randomised trials and discuss ongoing phase III trials in relation to adjuvant therapy in pancreatic cancer.

  3. Pancreatic adenocarcinoma pathology: changing “landscape”

    PubMed Central

    Brosens, Lodewijk A. A.; Hackeng, Wenzel M.; Offerhaus, G. Johan; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID:26261723

  4. Three cases of mediastinal pancreatic pseudocysts

    PubMed Central

    Fujihara, Yoshio; Maeda, Kazunori; Okamoto, Masaru; Yanagitani, Atsushi; Tanaka, Kiwamu; Nakamura, Kazuhiko; Ogawa, Toshihide

    2016-01-01

    A rare complication of acute or chronic pancreatitis is the formation of a mediastinal pancreatic pseudocyst (MPP), which is caused by tracking of pancreatic fluids through anatomical openings of the diaphragm into the mediastinum. Herein, we report the imaging characteristics of three cases of this condition. Our results revealed three features in common: (i) the connection between the mediastinum and the pancreatic cystic lesion; (ii) the presence of pleural effusions; and (iii) imaging findings consistent with chronic pancreatitis, such as pancreatic atrophy and calcifications and dilatation and/or stricture of main pancreatic duct (MPD). Serial diameter changes of the MPD and of the adjacent pseudocysts were necessary for the determination of the therapeutic strategy used in each case. PMID:27330827

  5. Ultrasonography in diagnosing chronic pancreatitis: New aspects

    PubMed Central

    Dimcevski, Georg; Erchinger, Friedemann G; Havre, Roald; Gilja, Odd Helge

    2013-01-01

    The course and outcome is poor for most patients with pancreatic diseases. Advances in pancreatic imaging are important in the detection of pancreatic diseases at early stages. Ultrasonography as a diagnostic tool has made, virtually speaking a technical revolution in medical imaging in the new millennium. It has not only become the preferred method for first line imaging, but also, increasingly to clarify the interpretation of other imaging modalities to obtain efficient clinical decision. We review ultrasonography modalities, focusing on advanced pancreatic imaging and its potential to substantially improve diagnosis of pancreatic diseases at earlier stages. In the first section, we describe scanning techniques and examination protocols. Their consequences for image quality and the ability to obtain complete and detailed visualization of the pancreas are discussed. In the second section we outline ultrasonographic characteristics of pancreatic diseases with emphasis on chronic pancreatitis. Finally, new developments in ultrasonography of the pancreas such as contrast enhanced ultrasound and elastography are enlightened. PMID:24259955

  6. Pancreatic Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing pancreatic cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  7. [Pancreatic secretion in domestic sprue].

    PubMed

    Otte, M; Thurmayr, G R; Dageförde, J; Thurmayr, R; Forell, M M

    1985-02-15

    Pancreatic function was determined (using the secretin-pancreozymin test) before the use of gluten-free diet in 22 patients with endemic (celiac) sprue. Water and bicarbonate secretion were within normal limits, if anything there was a trend to high-normal values. Remarkable and apparently characteristic for celiac sprue was the only slight contraction of the gallbladder after intravenous injection of submaximal doses of cholecystokinin-pancreozymin (CCK). Secretion of the 3 enzymes amylase, lipase and trypsin was decreased in about one third of cases, the difference relating both to the concentrations and the amount secreted, compared with normal control values was significant (P greater than 0.01). But in no case was the reduced enzyme secretion so marked that one would expect maldigestion. Multivariate non-linear discriminance analysis demonstrated that pancreatic secretion in sprue is quite distinct from that in healthy subjects and those with chronic pancreatitis. It is assumed that there is a pattern of exocrine pancreatic secretion typical for sprue.

  8. Approaches towards endogenous pancreatic regeneration.

    PubMed

    Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R

    2005-01-01

    The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its beta-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in beta-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this disease. With this view in mind, this article aims to discuss the potential use in clinical strategies of knowledge that we obtained from studies carried out in animal models of diabetes. Approaches to achieve this goal involve the use of biomolecules, adult stem cells and gene therapy. Various molecules, such as glucagon-like peptide-1, beta-cellulin, nicotinamide, gastrin, epidermal growth factor-1 and thyroid hormone, play major roles in the initiation of endogenous islet regeneration in diabetes. The most accepted hypothesis is that these molecules stimulate islet precursor cells to undergo neogenesis or to induce replication of existing beta-cells, emphasizing the importance of pancreas-resident stem/progenitor cells in islet regeneration. Moreover, the potential of adult stem cell population from bone marrow, umbilical cord blood, liver, spleen, or amniotic membrane, is also discussed with regard to their potential to induce pancreatic regeneration.

  9. Regeneration of pancreatic beta cells.

    PubMed

    Jun, Hee-Sook

    2008-05-01

    Diabetes mellitus results from inadequate mass of insulin-producing pancreatic beta cells. Type 1 diabetes is characterized by absolute loss of beta cells due to autoimmune-mediated destruction. Type 2 diabetes is characterized by relative deficiency of beta cells due to lack of compensation for insulin resistance. Restoration of deficient beta cell mass by transplantation from exogenous sources or by endogenous regeneration of insulin-producing cells would be therapeutic options. Mature beta cells have an ability to proliferate; however, it has been shown to be difficult to expand adult beta cells in vitro. Alternatively, regeneration of beta cells from embryonic and adult stem cells and pancreatic progenitor cells is an attractive method to restore islet cell mass. With information obtained from the biology of pancreatic development, direct differentiation of stem and progenitor cells toward a pancreatic beta cell phenotype has been tried using various strategies, including forced expression of beta cell-specific transcription factors. Further research is required to understand how endogenous beta cells differentiate and to develop methods to regenerate beta cells for clinically applicable therapies for diabetes.

  10. Pancreatic function in Crohn's disease.

    PubMed Central

    Hegnhøj, J; Hansen, C P; Rannem, T; Søbirk, H; Andersen, L B; Andersen, J R

    1990-01-01

    We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. PMID:1698692

  11. Pancreatic torsion in a dog

    PubMed Central

    Brabson, Tamera L.; Maki, Lynn C.; Newell, Susan M.; Ralphs, S. Christopher

    2015-01-01

    A 6-month-old male intact Cane Corso mastiff dog was presented for a recent history of vomiting, abdominal pain, and lethargy. A diagnosis of pancreatic torsion was made during abdominal exploratory surgery and was confirmed with histopathology. The dog underwent partial pancreatectomy and recovered with no complications. PMID:25969579

  12. [Perineural pseudoinvasion in chronic pancreatitis].

    PubMed

    Hauptmann, K; Hauptmann, S

    2000-09-01

    The occurrence of perineural epithelial complexes within the pancreas cannot always be regarded as evidence of malignancy. Chronic pancreatitis can induce alterations in the anatomy of the organ with a histological picture comparable to that of neural invasion. The important criteria for differential diagnosis are neuroendocrine differentiation of these cells or their ductular morphology without atypia.

  13. Hepatocyte growth factor attenuates pancreatic damage in caerulein-induced pancreatitis in rats.

    PubMed

    Warzecha, Z; Dembiński, A; Konturek, P C; Ceranowicz, P; Konturek, S J; Tomaszewska, R; Schuppan, D; Stachura, J; Nakamura, T

    2001-10-26

    Hepatocyte growth factor (HGF) overexpression was reported in experimental and clinical acute pancreatitis. These observations prompted us to determine the effect of HGF administration on the development of caerulein-induced pancreatitis in rats. Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. HGF was administrated twice (30 min before caerulein or saline infusion and 3 h later) at the doses: 0.4, 2, 10 or 50 microg/kg s.c. Immediately after cessation of caerulein or saline infusion, the pancreatic blood flow, plasma amylase and lipase activity, plasma cytokines concentration, cell proliferation, and morphological signs of pancreatitis were examined. Caerulein administration induced acute edematous pancreatitis manifested by 41% decrease in DNA synthesis, 53% inhibition of pancreatic blood flow, a significant increase in plasma amylase and lipase activity, plasma interleukin-1beta and interleukin-6 concentration, as well as, the development of the histological signs of pancreatic damage (edema, leukocyte infiltration, and vacuolization). Administration of HGF without induction of pancreatitis increased plasma interleukin-10. Treatment with HGF, during induction of pancreatitis, increased plasma interleukin-10 and attenuated the pancreatic damage, what was manifested by histological improvement of pancreatic integrity, the partial reversion of the drop in DNA synthesis and pancreatic blood flow, and the reduction in pancreatitis evoked increase in plasma amylase, lipase, and interleukin-1beta and interleukin-6 levels. HGF administrated at the dose 2 microg/kg exhibited a similar beneficial effect as administration of HGF at the doses 10 or 50 microg/kg. Treatment with HGF at the dose 0.4 microg/kg was less effective. We conclude that: (1) administration of HGF attenuates pancreatic damage in caerulein-induced pancreatitis; (2) this effect seems to be related to the increase in production of interleukin-10, the reduction in

  14. 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.

  15. Acute pancreatitis in children and adolescents

    PubMed Central

    Suzuki, Mitsuyoshi; Sai, Jin Kan; Shimizu, Toshiaki

    2014-01-01

    In this Topic Highlight, the causes, diagnosis, and treatment of acute pancreatitis in children are discussed. Acute pancreatitis should be considered during the differential diagnosis of abdominal pain in children and requires prompt treatment because it may become life-threatening. The etiology, clinical manifestations, and course of acute pancreatitis in children are often different than in adults. Therefore, the specific features of acute pancreatitis in children must be considered. The etiology of acute pancreatitis in children is often drugs, infections, trauma, or anatomic abnormalities. Diagnosis is based on clinical symptoms (such as abdominal pain and vomiting), serum pancreatic enzyme levels, and imaging studies. Several scoring systems have been proposed for the assessment of severity, which is useful for selecting treatments and predicting prognosis. The basic pathogenesis of acute pancreatitis does not greatly differ between adults and children, and the treatments for adults and children are similar. In large part, our understanding of the pathology, optimal treatment, assessment of severity, and outcome of acute pancreatitis in children is taken from the adult literature. However, we often find that the common management of adult pancreatitis is difficult to apply to children. With advances in diagnostic techniques and treatment methods, severe acute pancreatitis in children is becoming better understood and more controllable. PMID:25400985

  16. Molecular mechanisms of pancreatitis: current opinion.

    PubMed

    Vonlaufen, Alain; Wilson, Jeremy S; Apte, Minoti V

    2008-09-01

    Pancreatitis (necroinflammation of the pancreas) has both acute and chronic manifestations. Gallstones are the major cause of acute pancreatitis, whereas alcohol is associated with acute as well as chronic forms of the disease. Cases of true idiopathic pancreatitis are steadily diminishing as more genetic causes of the disease are discovered. The pathogenesis of acute pancreatitis has been extensively investigated over the past four decades; the general current consensus is that the injury is initiated within pancreatic acinar cells subsequent to premature intracellular activation of digestive enzymes. Repeated attacks of acute pancreatitis have the potential to evolve into chronic disease characterized by fibrosis and loss of pancreatic function. Our knowledge of the process of scarring has advanced considerably with the isolation and study of pancreatic stellate cells, now established as the key cells in pancreatic fibrogenesis. The present review summarizes recent developments in the field particularly with respect to the progress made in unraveling the molecular mechanisms of acute and chronic pancreatic injury secondary to gallstones, alcohol and genetic factors. It is anticipated that continued research in the area will lead to the identification and characterization of molecular pathways that may be therapeutically targeted to prevent/inhibit the initiation and progression of the disease.

  17. Defining the diagnostic algorithm in pancreatic cancer.

    PubMed

    Horwhat, John David; Gress, Frank G

    2004-07-01

    Most patients with pancreatic cancer present with a mass on radiologic studies, however, not every pancreatic mass is cancer. Since radiological studies alone are insufficient to establish the diagnosis of a pancreatic mass and patient management depends on a definitive diagnosis; confirmatory cytology or histology is usually required. As a minimally invasive procedure, EUS and EUS FNA avoid the risk of cutaneous or peritoneal contamination that may occur with CT or US-guided investigations and is less invasive than surgical interventions. As a result, EUS FNA of pancreatic masses is becoming the standard for obtaining cytological diagnosis. This chapter presents an EUS-based diagnostic algorithm for the evaluation of pancreatic lesions and is based upon a review of the pertinent literature in the field of pancreatic endosonography that has been the most influential in helping to guide this evolving field. Realizing there is much overlap among the EUS characteristics of various pancreatic lesions, for the sake of simplicity we have structured our discussion in broad terms of solid versus cystic lesions and discuss various pancreatic lesions within this framework. The additional contributors to this round table discussion have been asked to provide a more dedicated, focused discussion of the various subcategories of pancreatic lesions in greater detail than we could hope to achieve here. We provide this final contribution to the round table as a means of bringing the discussion back to the big picture of pancreatic lesions, rather than trying to hone in on the fine details of any one subclass.

  18. Managing acute and chronic pancreatitis.

    PubMed

    Skipworth, James R A; Shankar, Arjun; Pereira, Stephen P

    2010-10-01

    Pancreatitis may be acute or chronic. Although both can be caused by similar aetiologies, they tend to follow distinct natural histories. Around 80% of acute pancreatitis (AP) diagnoses occur secondary to gallstone disease and alcohol misuse. AP is commonly associated with sudden onset of upper abdominal pain radiating to the back that is usually severe enough to warrant the patient seeking urgent medical attention. Onset of pain may be related to a recent alcohol binge or rich, fatty meal. The patient may appear unwell, be tachycardic and have exquisite tenderness in the upper abdomen. Overall, 10-25% of AP episodes are classified as severe, leading to an associated mortality rate of 7.5%. Disease severity is best predicted from a number of clinical scoring systems which can be applied at diagnosis in association with repeated clinical assessment, measurement of acute inflammatory markers, and CT. All patients with suspected AP should be referred urgently. Chronic pancreatitis (CP) follows continued, repetitive or sustained injury to the pancreas and 70% of diagnoses occur secondary to alcohol abuse. The characteristic presenting feature of CP is insidious progression of chronic, severe, upper abdominal pain, radiating to the back, caused by a combination of progressive pancreatic destruction, inflammation and duct obstruction. Signs and symptoms include weight loss and steatorrhoea and later on diabetes. CP patients may also present with recurrent episodes mimicking AP, both symptomatically and metabolically. Diagnosis of CP should be based on symptom profile, imaging and assessment of exocrine and endocrine pancreatic function. CT should be the first-line imaging investigation.

  19. Recent Advances in Autoimmune Pancreatitis.

    PubMed

    Hart, Phil A; Zen, Yoh; Chari, Suresh T

    2015-07-01

    Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that is characterized clinically by frequent presentation with obstructive jaundice, histologically by a dense lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to corticosteroid therapy. Two distinct diseases, type 1 and type 2 AIP, share these features. However, these 2 diseases have unique pancreatic histopathologic patterns and differ significantly in their demographic profiles, clinical presentation, and natural history. Recognizing the popular and long-standing association of the term "AIP" with what is now called "type 1 AIP," we suggest using "AIP" solely for type 1 AIP and to acknowledge its own distinct disease status by using "idiopathic duct-centric chronic pancreatitis" (IDCP) for type 2 AIP. AIP is the pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). The etiopathogenesis of AIP and IgG4-RD is largely unknown. However, the remarkable effectiveness of B-cell depletion therapy with rituximab in patients with AIP and IgG4-RD highlights the crucial role of B cells in its pathogenesis. IDCP is less commonly recognized, and little is known about its pathogenesis. IDCP has no biomarker but is associated with inflammatory bowel disease in ~25% of patients. Recently, the international consensus diagnostic criteria for AIP identified combinations of features that are diagnostic of both diseases. Both AIP and IDCP are corticosteroid responsive; however, relapses are common in AIP and rare in IDCP. Therefore, maintenance therapy with either an immunomodulator (eg, azathioprine, 6-mercaptopurine, or mycophenolate mofetil) or rituximab is often necessary for patients with AIP. Long-term survival is excellent for both patients with AIP and patients with IDCP.

  20. What's New in Pancreatic Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Pancreatic Cancer About Pancreatic Cancer What’s New in Pancreatic Cancer Research? Research into the causes , ... KRAS oncogene, which affects regulation of cell growth. New diagnostic tests are often able to recognize this ...

  1. Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

    ClinicalTrials.gov

    2016-12-12

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  2. Specific transduction and labeling of pancreatic ducts by targeted recombinant viral infusion into mouse pancreatic ducts.

    PubMed

    Guo, Ping; Xiao, Xiangwei; El-Gohary, Yousef; Criscimanna, Angela; Prasadan, Krishna; Rymer, Christopher; Shiota, Chiyo; Wiersch, John; Gaffar, Iliana; Esni, Farzad; Gittes, George K

    2013-11-01

    Specific labeling of pancreatic ducts has proven to be quite difficult. Such labeling has been highly sought after because of the power it would confer to studies of pancreatic ductal carcinogenesis, as well as studies of the source of new insulin-producing β-cells. Cre-loxp recombination could, in theory, lineage-tag pancreatic ducts, but results have been conflicting, mainly due to low labeling efficiencies. Here, we achieved a high pancreatic duct labeling efficiency using a recombinant adeno-associated virus (rAAV) with a duct-specific sox9 promoter infused into the mouse common biliary/pancreatic duct. We saw rapid, diffuse duct-specific labeling, with 50 and 89% labeling in the pancreatic tail and head region, respectively. This highly specific labeling of ducts should greatly enhance our ability to study the role of pancreatic ducts in numerous aspects of pancreatic growth, development and function.

  3. PanScan, the Pancreatic Cancer Cohort Consortium, and the Pancreatic Cancer Case-Control Consortium

    Cancer.gov

    The Pancreatic Cancer Cohort Consortium consists of more than a dozen prospective epidemiologic cohort studies within the NCI Cohort Consortium, whose leaders work together to investigate the etiology and natural history of pancreatic cancer.

  4. Role of ischemia in acute pancreatitis. Hemorrhagic shock converts edematous pancreatitis to hemorrhagic pancreatitis in rats.

    PubMed

    Kyogoku, T; Manabe, T; Tobe, T

    1992-09-01

    Ischemia has been considered to play a role in the development of acute pancreatitis. The aim of this study was to investigate the effect of ischemia, caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats. Acute pancreatitis was induced by the intravenous infusion of a supramaximally stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock was induced by the removal of blood until the mean arterial blood pressure reached 35 mm Hg. This level was maintained for 30 min, after which time all the blood was reinfused. Hemorrhagic shock alone induced no morphological change in the pancreas. However, after the induction of hemorrhagic shock in animals treated with cerulein, hemorrhage and parenchymal necrosis were frequently observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas none of the rats in the cerulein or shock group died during this experiment. Cathepsin B activity in the pancreas of the cerulein plus shock group was significantly higher than in the other groups at 48 hr. These results suggest that ischemia may be a contributing factor in the pathogenesis of acute pancreatitis.

  5. Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

    ClinicalTrials.gov

    2017-02-24

    BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Metastatic Pancreatic Adenocarcinoma; PALB2 Gene Mutation; Pancreatic Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  6. [On PACAP-aggravated experimental acute pancreatitis].

    PubMed

    Chen, Youdai; Zhou, Zongguang; Chen, Youqin; Wang, Zhao; Gao, Hongkai; Zheng, Xuelian

    2004-12-01

    The role of PACAP (pituitary adenylate cyclase activating polypeptide), a peptidergic transmitter, in the pathogenesis of acute pancreatitis is not yet clear. This experiment was conducted to examine the action of exogenous PACAP on rat pancreas and on the course of experimental acute pancreatitis. The results showed that 5-30 microg/kg of PACAP slightly raised the serum amylase level, induced pancreatic edema (23.88% +/- 2.532%-25.86% +/- 1.974% of experiment groups versus 29.21% +/- 5.657% of control group), inflammatory cell infiltration, vacuolization of acinar cells, and occasionally fatty and parenchymal necroses. 15-30 microg/kg of PACAP aggravated cerulein-induced acute pancreatitis; the pancreatic edema became more marked (13.45% +/- 2.045%-17.66% +/- 4.652% of expreiment groups versus 21.83% +/- 3.013% of cerulein group, P<0.05), the serum amylase level became higher; and ascites, pancreatic bleeding, fatty and parenchymal necroses, and extensive vacuolization of acinar cells appeared. For sodium taurocholate-induced pancreatitis, 5-10 microg/kg of PACAP mildly attenuated the pancreatic edema, reduced the serum amylase level (1986.91 +/- 710.97-2944.33 +/- 1182.47 IU/L vs 3690.87 +/- 2277.99 IU/L, P<0.05), whereas it caused multifocal hemorrhage and prominent necrosis in pancreas. Except the cerulein-induced pancreatitis groups, other groups were found to have reduced pancreatic functional capillary density (FCD); when pancreatic edema was taken into consideration and calibrated FCD was introduced (FCD weighted against pancreatic wet/dry ratio), all groups revealed increases in pancreatic functional capillaries when compared with normal control. In conclusion, PACAP is proinflammatory in the pathogenesis of acute pancreatitis, PACAP plus cerulein can induce acute hemorrhagic/necrotizing pancreatitis, and the action of PACAP on cerulein-induced panceatitis may differ from that on sodium taurocholate-induced one. In this experiment, pancreatic FCD was

  7. Whole-mount imaging demonstrates hypervascularity of the pancreatic ducts and other pancreatic structures.

    PubMed

    El-Gohary, Yousef; Tulachan, Sidhartha; Branca, Maria; Sims-Lucas, Sunder; Guo, Ping; Prasadan, Krishna; Shiota, Chiyo; Gittes, George K

    2012-03-01

    Confocal microscopy in combination with commercial software is frequently used to generate three-dimensional images of tissue architecture. Here we report a novel, whole-mount imaging protocol technique that allows detailed three-dimensional imaging of adult pancreatic structures. This technique provides an improved appreciation of the anatomical detail of pancreatic structures and of the relationship between the pancreatic ducts and islets. In addition, imaging of the pancreatic ducts revealed a previously unappreciated high degree of hypervascularity.

  8. 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.

  9. Pancreatic pseudocyst after acute organophosphate poisoning.

    PubMed

    Kawabe, Ken; Ito, Tetsuhide; Arita, Yoshiyuki; Sadamoto, Yojiro; Harada, Naohiko; Yamaguchi, Koji; Tanaka, Masao; Nakano, Itsuro; Nawata, Hajime; Takayanagi, Ryoichi

    2006-04-01

    Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP.

  10. Acute recurrent pancreatitis: An autoimmune disease?

    PubMed Central

    Pezzilli, Raffaele

    2008-01-01

    In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with “diopathic”pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis. PMID:18286678

  11. Models of acute and chronic pancreatitis.

    PubMed

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  12. Acute pancreatitis as a model of SIRS.

    PubMed

    Bhatia, Madhav

    2009-01-01

    Acute pancreatitis is a common clinical condition. Excessive systemic inflammatory response syndrome (SIRS) in acute pancreatitis leads to distant organ damage and multiple organ dysfunction syndrome (MODS), which is the primary cause of morbidity and mortality in this condition. Development of in vivo experimental models of acute pancreatitis and associated systemic organ damage has enabled us to study the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and associated systemic organ damage. Using these models, recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-a, IL-1b, IL-6, PAF, IL-10, CD40L, C5a, ICAM-1, chemokines, substance P and hydrogen sulfide in acute pancreatitis and the resultant MODS. This chapter intends to present an overview of different experimental animal models of acute pancreatitis and associated MODS and the role of inflammatory mediators in the pathogenesis of this condition.

  13. Cerulein Pancreatitis: Oxidative Stress, Inflammation, and Apoptosis

    PubMed Central

    2008-01-01

    Cerulein pancreatitis is similar to human edematous pancreatitis, manifesting with dysregulation of digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and infiltration of inflammatory cells into the pancreas. Reactive oxygen species are involved in nuclear factor-κB activation, cytokine expression, apoptosis and pathogenesis of pancreatitis. There is recent evidence that cerulein activates NADPH oxidase, which is a major source of reactive oxygen species during inflammation and apoptosis in pancreatic acinar cells. In addition, the Janus kinase/signal transducer and activator of transcription pathway has been suggested as being involved in inflammatory signaling in the pancreas. This review discusses the involvement of oxidative stress in inflammation and apoptosis in pancreatic acinar cells stimulated with cerulein as an in vitro model of pancreatitis. PMID:20485614

  14. Transcatheter Embolization of Pseudoaneurysms Complicating Pancreatitis

    SciTech Connect

    Golzarian, Jafar; Nicaise, Nicole; Deviere, Jacques; Ghysels, Marc; Wery, Didier; Dussaussois, Luc; Gansbeke, Daniel van; Struyven, Julien

    1997-11-15

    Purpose: To evaluate the therapeutic role of angiography in patients with pseudoaneurysms complicating pancreatitis. Methods: Thirteen symptomatic pseudoaneurysms were treated in nine patients with pancreatitis. Eight patients had chronic pancreatitis and pseudocyst and one had acute pancreatitis. Clinical presentation included gastrointestinal bleeding in seven patients and epigastric pain without bleeding in two. All patients underwent transcatheter embolization. Results: Transcatheter embolization resulted in symptomatic resolution in all patients. Rebleeding occurred in two patients, 18 and 28 days after embolization respectively, and was successfully treated by repeated emnbolization. One patient with severe pancreatitis died from sepsis 28 days after embolization. Follow-up was then available for eight patients with no relapse of bleeding after a mean follow-up of 32 months (range 9-48 months). Conclusion: Transcatheter embolization is safe and effective in the management of pseudoaneurysms complicating pancreatitis.

  15. Pancreatic cancer: Pathogenesis, prevention and treatment

    SciTech Connect

    Sarkar, Fazlul H. Banerjee, Sanjeev; Li, Yiwei

    2007-11-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States with a very low survival rate of 5 years. To better design new preventive and/or therapeutic strategies for the fight against pancreatic cancer, the knowledge of the pathogenesis of pancreatic cancer at the molecular level is very important. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways among which the EGFR, Akt, and NF-{kappa}B pathways appear to be most relevant. Therefore, the strategies targeting EGFR, Akt, NF-{kappa}B, and their downstream signaling could be promising for the prevention and/or treatment of pancreatic cancer. In this brief review, we will summarize the current knowledge regarding the pathogenesis, prevention, and treatment of pancreatic cancer.

  16. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs.

    PubMed

    Eisses, John F; Criscimanna, Angela; Dionise, Zachary R; Orabi, Abrahim I; Javed, Tanveer A; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W; Tosun, Akif Burak; Ozolek, John A; Lowe, Mark E; Monga, Satdarshan P; Rohde, Gustavo K; Esni, Farzad; Husain, Sohail Z

    2015-12-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations-that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury-we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury.

  17. Valproic Acid Limits Pancreatic Recovery after Pancreatitis by Inhibiting Histone Deacetylases and Preventing Acinar Redifferentiation Programs

    PubMed Central

    Eisses, John F.; Criscimanna, Angela; Dionise, Zachary R.; Orabi, Abrahim I.; Javed, Tanveer A.; Sarwar, Sheharyar; Jin, Shunqian; Zhou, Lili; Singh, Sucha; Poddar, Minakshi; Davis, Amy W.; Tosun, Akif Burak; Ozolek, John A.; Lowe, Mark E.; Monga, Satdarshan P.; Rohde, Gustavo K.; Esni, Farzad; Husain, Sohail Z.

    2016-01-01

    The mechanisms by which drugs induce pancreatitis are unknown. A definite cause of pancreatitis is due to the antiepileptic drug valproic acid (VPA). On the basis of three crucial observations—that VPA inhibits histone deacetylases (HDACs), HDACs mediate pancreas development, and aspects of pancreas development are recapitulated during recovery of the pancreas after injury—we hypothesized that VPA does not cause injury on its own, but it predisposes patients to pancreatitis by inhibiting HDACs and provoking an imbalance in pancreatic recovery. In an experimental model of pancreatic injury, we found that VPA delayed recovery of the pancreas and reduced acinar cell proliferation. In addition, pancreatic expression of class I HDACs (which are the primary VPA targets) increased in the midphase of pancreatic recovery. VPA administration inhibited pancreatic HDAC activity and led to the persistence of acinar-to-ductal metaplastic complexes, with prolonged Sox9 expression and sustained β-catenin nuclear activation, findings that characterize a delay in regenerative reprogramming. These effects were not observed with valpromide, an analog of VPA that lacks HDAC inhibition. This is the first report, to our knowledge, that VPA shifts the balance toward pancreatic injury and pancreatitis through HDAC inhibition. The work also identifies a new paradigm for therapies that could exploit epigenetic reprogramming to enhance pancreatic recovery and disorders of pancreatic injury. PMID:26476347

  18. Small pancreatic cancer with pancreas divisum preoperatively diagnosed by pancreatic juice cytology.

    PubMed

    Obana, Takashi; Fujita, Naotaka; Noda, Yutaka; Kobayashi, Go; Ito, Kei; Horaguchi, Jun; Takasawa, Osamu; Tsuchiya, Takashi; Sawai, Takashi

    2009-01-01

    We present a case of small pancreatic head cancer with pancreas divisum preoperatively diagnosed by pancreatic juice cytology. A 60-year-old woman was referred to our hospital for evaluation of a dilated main pancreatic duct (MPD). A small and poorly reproducible low-echoic lesion in the pancreas was suspected by ultrasonography (US) and endoscopic ultrasonography (EUS). Magnetic resonance cholangiopancreatography (MRCP) failed to visualize the ventral pancreatic duct, and the upstream dorsal pancreatic duct was dilated. Endoscopic retrograde cholangiopancreatography (ERCP) was indicative of pancreas divisum, and complete obstruction of the MPD in the pancreatic head was seen. Cytology of pancreatic juice obtained from the dorsal pancreas after minor papilla sphincterotomy revealed the presence of adenocarcinoma cells. Pancreatoduodenectomy was performed under the diagnosis of pancreatic head cancer with pancreas divisum. Histological examination revealed moderately-differentiated tubular adenocarcinoma 20 mm in diameter, located in the pancreatic head. Dilatation of the dorsal pancreatic duct is sometimes observed in cases with pancreas divisum without the presence of tumors. When pancreatic duct stenosis also exists in such cases, even if a tumor is not clearly visualized by diagnostic imaging, vigorous examinations such as pancreatic juice cytology are recommended to establish an accurate diagnosis.

  19. Prognostic markers in acute pancreatitis: can pancreatic necrosis be predicted?

    PubMed Central

    Leese, T.; Shaw, D.; Holliday, M.

    1988-01-01

    The value of six prognostic markers was assessed prospectively in 198 attacks of acute pancreatitis with specific attention to their ability to predict pancreatic necrosis. The Imrie Prognostic Score (IPS) was recorded within 48 h of diagnosis. The serum C-reactive protein (CRP) alpha 1 antiprotease (A1AP), alpha 2 macroglobulin (A2M), amylase and white cell count (WCC) were measured on days 1, 3 and 7. When comparing all severe clinical outcomes to mile outcomes, serum CRP concentrations were higher on all three days (P less than 0.02, less than 0.001, less than 0.001), A1AP concentrations were higher on day 3 (P less than 0.05), A2M concentrations were lower on day 7 (P less than 0.01) and WCC was higher on all three days (P less than 0.001, less than 0.001, less than 0.001). Serum amylase concentrations showed no significant differences. None of the measured parameters were helpful in distinguishing patients who subsequently developed pancreatic necrosis from patients who had other severe outcomes. Multivariate analysis revealed that the initial IPS showed greatest independent significance in predicting severe outcome followed by the WCC (days 1 and 7) and CRP (day 3). CRP and WCC may be clinically useful predictors of severe outcome to supplement the initial IPS. These methods are unlikely to distinguish pancreatic necrosis from other severe outcomes, but they may supplement clinical judgment in selecting a high risk group of patients for contrast enhanced computed tomography. PMID:2458063

  20. Pancreatic cancer: from bench to bedside

    PubMed Central

    Ma, Yaokai; Wu, Qing; Li, Xin; Gu, Xiaoqiang; Xu, Jiahua

    2016-01-01

    Pancreatic cancer is recognized as the king of carcinoma, and the gap between basic research and clinical practice is difficult to improve the treatment effect. Translational medicine builds an important bridge between pancreatic cancer basic research and clinical practice from the pathogenesis, early diagnosis of pancreatic carcinoma, drug screening, treatment strategies and metastasis prediction. This article will carry on the concrete elaboration to the above several aspects. PMID:28090514

  1. Approach to acute, recurrent, and chronic pancreatitis.

    PubMed

    Kinney, Timothy P; Freeman, Martin L

    2008-06-01

    Pancreatitis can manifest as a one-time episode, recurring attacks, or chronic pain. It is caused by numerous factors ranging from alcohol consumption to gallstones to subtle obstructive causes and occult autoimmune disorders. As a result, determining the etiology and effectively treating the causes and consequences of pancreatitis can be challenging. This article reviews the diagnosis and management of acute, acute recurrent, and chronic pancreatitis, focusing on more challenging scenarios.

  2. Non-focal enlargement in pancreatic carcinoma

    SciTech Connect

    Wittenberg, J.; Simeone, J.F.; Ferrucci, J.T. Jr.; Mueller, P.R.; van Sonnenberg, E.; Neff, C.C.

    1982-07-01

    Pancreatic adenocarcinoma can appear radiographically as enlargement of the major part of the pancreas. In this series, part or all of three or more pancreatic segments (head, neck, body, and tail) were involved in 27% of patients with adenocarcinoma who had computed tomography. Differentiation from pure pancreatitis may require additional radiographic studies. The varied tissue composition of a pancreas enlarged by adenocarcinoma will often require biopsy of multiple sites for confirmation.

  3. Pancreatic regeneration: basic research and gene regulation.

    PubMed

    Okita, Kenji; Mizuguchi, Toru; Shigenori, Ota; Ishii, Masayuki; Nishidate, Toshihiko; Ueki, Tomomi; Meguro, Makoto; Kimura, Yasutoshi; Tanimizu, Naoki; Ichinohe, Norihisa; Torigoe, Toshihiko; Kojima, Takashi; Mitaka, Toshihiro; Sato, Noriyuki; Sawada, Norimasa; Hirata, Koichi

    2016-06-01

    Pancreatic regeneration (PR) is an interesting phenomenon that could provide clues as to how the control of diabetes mellitus might be achieved. Due to the different regenerative abilities of the pancreas and liver, the molecular mechanism responsible for PR is largely unknown. In this review, we describe five representative murine models of PR and thirteen humoral mitogens that stimulate β-cell proliferation. We also describe pancreatic ontogenesis, including the molecular transcriptional differences between α-cells and β-cells. Furthermore, we review 14 murine models which carry defects in genes related to key transcription factors for pancreatic ontogenesis to gain further insight into pancreatic development.

  4. 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

  5. Exocrine Pancreatic Carcinogenesis and Autotaxin Expression

    PubMed Central

    Kadekar, Sandeep; Silins, Ilona; Korhonen, Anna; Dreij, Kristian; Al-Anati, Lauy; Högberg, Johan; Stenius, Ulla

    2012-01-01

    Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common traits for chemicals inducing pancreatic tumors we studied the National Toxicology Program (NTP) bioassay database. We found that male rats were affected more often than female rats and identified eight chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis generating process we used a text mining tool to analyse published literature for suggested mode of actions (MOA). The resulting MOA analysis suggested inflammatory responses as common feature. In cell studies we found that all the chemicals increased protein levels of the inflammatory protein autotaxin (ATX) in Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive migration were also frequent effects, consistent with ATX activation. Testosterone has previously been implicated in pancreatic carcinogenesis and we found that it increased ATX levels. Our data show that ATX is a target for chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms of action may include stimulated invasive growth and metastasis. ATX may interact with hormones or onco- or suppressor-genes often deregulated in exocrine pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting pancreatic tumor development. PMID:22952646

  6. Reconstruction after pancreatic trauma by pancreaticogastrostomy

    PubMed Central

    Martín, Gonzalo Martín; Morillas, Patricia Jiménez; Pino, José C. Rodríguez; Canis, José M. Morón; Argenté, Francesc X. González

    2015-01-01

    Introduction Pancreatic lesions are very infrequent after closed abdominal trauma (5% of cases) with a complication rate that affects 30–40% of patients, and a mortality rate that can reach 39%. In our experience, closed abdominal traumatisms occurring at typical popular horse-riding festivals in our region constitute a high risk of pancreatic trauma. The purpose of the present paper is to raise awareness about our experience in the diagnosis and treatment of pancreatic lesions secondary to closed abdominal traumatism. Presentation of case We present the clinical cases of two young patients who, after suffering blunt abdominal trauma secondary to the impact of a horse during the celebration of typical horse-riding festival, were diagnosed with pancreatic trauma type III. The treatment was surgical in both cases and consisted in performing a pancreaticogastric anastomosis with preservation of the distal pancreas and spleen. The postoperative period was uneventful and, at present, both patients are asymptomatic. Discussion Signs and symptoms caused by pancreatic lesion are unspecific and difficult to objectify. With some limitations CT is the imaging test of choice for diagnosis and staging in the acute phase. The Wirsung section is indication for surgical treatment. The most extended surgical procedure in these cases is the resection of pancreatic body, tail, and spleen. Conclusion The identification of a pancreatic injury after closed abdominal trauma requires a high suspicion based on the injury mechanism. A safer option may be the distal pancreatic preservation with pancreaticogastric anastomosis in grade III lesions with healthy pancreatic tissue. PMID:25744560

  7. Angiogenesis: a prognostic determinant in pancreatic cancer?

    PubMed

    van der Zee, Jill A; van Eijck, Casper H J; Hop, Wim C J; van Dekken, Herman; Dicheva, Bilyana M; Seynhaeve, Ann L B; Koning, Gerben A; Eggermont, Alexander M M; ten Hagen, Timo L M

    2011-11-01

    Angiogenesis has been associated with disease progression in many solid tumours, however the statement that tumours need angiogenesis to grow, invade and metastasise seems no longer applicable to all tumours or to all tumour subtypes. Prognostic studies in pancreatic cancer are conflicting. In fact, pancreatic cancer has been suggested an example of a tumour in which angiogenesis is less essential for tumour progression. The aim of the present study was therefore to measure angiogenesis in two anatomically closely related however prognostically different types of pancreatic cancer, pancreatic head and periampullary cancer, and investigate its relation with outcome. Vessels were stained by CD31 on original paraffin embedded tissue from 206 patients with microscopic radical resection (R0) of pancreatic head (n=98) or periampullary cancer (n=108). Angiogenesis was quantified by microvessel density (MVD) and measured by computerised image analysis of three randomly selected fields and investigated for associations with recurrence free survival (RFS), cancer specific survival (CSS), overall survival (OS) and conventional prognostic factors. MVD was heterogeneous both between and within tumours. A higher MVD was observed in periampullary cancers compared with pancreatic head cancers (p<.01). Furthermore, MVD was associated with lymph node involvement in pancreatic head (p=.014), but not in periampullary cancer (p=.55). Interestingly, MVD was not associated with RFS, CSS or with OS. In conclusion, angiogenesis is higher in periampullary cancer and although associated with nodal involvement in pancreatic head cancer, pancreatic cancer prognosis seems indeed angiogenesis independent.

  8. Biomarkers and Targeted Therapy in Pancreatic Cancer

    PubMed Central

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers. PMID:27147897

  9. Circumportal pancreas with retroportal main pancreatic duct.

    PubMed

    Hashimoto, Yasushi; Ross, Andrew S; Traverso, L William

    2009-08-01

    There have been 6 cases of circumportal pancreas reported, and 2 of them had the main pancreatic duct in a retroportal dorsal portion. This extremely uncommon anomaly is asymptomatic and therefore incidentally discovered. For the surgeon, it is important to discover this during pancreatic resection so the pancreatic duct can be closed and fistula is avoided. We describe the third case where a circumportal pancreas had its main pancreatic duct passing under the portal vein. The duct was identified and ligated. A fistula did not occur.

  10. Finasteride use and acute pancreatitis in Taiwan.

    PubMed

    Lai, Shih-Wei; Lai, Hsueh-Chou; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-06-01

    The aim of this study was to examine whether there is an association between finasteride use and the risk of acute pancreatitis. This population-based case-control study used the database of the Taiwan National Health Insurance Program. There were 2,530 male subjects aged 40-84 years with a first-attack of acute pancreatitis during the period of 1998-2011 as the case group and 10,119 randomly selected subjects without acute pancreatitis as the control group. Both groups were matched by age and index year of diagnosing acute pancreatitis. Subjects who never had finasteride prescription were defined as "never use." Subjects who at least received 1 prescription for finasteride before the date of diagnosing acute pancreatitis were defined as "ever use." The association of acute pancreatitis with finasteride use was examined by the odds ratio (OR) and 95% confidence interval (CI) using the multivariable unconditional logistic regression model. The crude OR of acute pancreatitis was 1.78 (95%CI 1.33, 2.39) for subjects with ever use of finasteride, when compared with subjects with never use of finasteride. After adjusting for potential confounders, the adjusted OR of acute pancreatitis decreased to 1.25 (95%CI 0.90, 1.73) for subjects with ever use of finasteride, but no statistical significance was seen. No association can be detected between finasteride use and the risk of acute pancreatitis.

  11. Advances in cryoablation for pancreatic cancer

    PubMed Central

    Luo, Xiao-Mei; Niu, Li-Zhi; Chen, Ji-Bing; Xu, Ke-Cheng

    2016-01-01

    Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. At present, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer. PMID:26811625

  12. Contraceptive pills and acute pancreatitis.

    PubMed

    Mehrotra, T N; Mital, H S; Gupta, S K

    1981-06-01

    This article reports a case of acute pancreatitis in a patient taking the oral contraceptive pill. A 32 year old mother had been on combined contraceptive pills since 1975. In 1978 she started having upper abdominal and retrosternal pain. She became critically ill with peripheral circulatory collapse, dyspnoea and cyanosis. A superficial thrombophlebitis was noted on the medial aspect of the right thigh. The diagnosis of pancreatitis was considered with history of recurrent abdominal pain. After several tests and supportive therapy (intravenous fluids, antibiotics, steriods), the woman started showing improvements in 48 hours and recovered in 10 days. This case differs from previously described cases in that the cholesterol and triglyceride levels were normal. The hypoglycemia has not been described previously.

  13. Enteric duplication cyst of the pancreas associated with chronic pancreatitis and pancreatic cancer.

    PubMed

    Chiu, Alexander S; Bluhm, David; Xiao, Shu-Yan; Waxman, Irving; Matthews, Jeffrey B

    2014-05-01

    Pancreas-associated enteric duplication cysts are rare developmental anomalies that communicate with the main pancreatic duct and may be associated with recurrent acute and chronic abdominal pain in children. In adults, these lesions may masquerade as pancreatic pseudocysts or pancreatic cystic neoplasms. An adult patient with a pancreas-associated enteric duplication is described which represents the first reported instance of association with both chronic calcific pancreatitis and pancreatic cancer. The clinical spectrum of pancreas-associated enteric duplication cyst, including diagnostic and therapeutic options, is reviewed.

  14. Prognostic markers in acute pancreatitis.

    PubMed

    Gomatos, Ilias P; Xiaodong, Xu; Ghaneh, Paula; Halloran, Christopher; Raraty, Michael; Lane, Brian; Sutton, Robert; Neoptolemos, John P

    2014-04-01

    Acute pancreatitis has a mortality rate of 5-10%. Early deaths are mainly due to multiorgan failure and late deaths are due to septic complications from pancreatic necrosis. The recently described 2012 Revised Atlanta Classification and the Determinant Classification both provide a more accurate description of edematous and necrotizing pancreatitis and local complications. The 2012 Revised Atlanta Classification uses the modified Marshall scoring system for assessing organ dysfunction. The Determinant Classification uses the sepsis-related organ failure assessment scoring system for organ dysfunction and, unlike the 2012 Revised Atlanta Classification, includes infected necrosis as a criterion of severity. These scoring systems are used to assess systemic complications requiring intensive therapy unit support and intra-abdominal complications requiring minimally invasive interventions. Numerous prognostic systems and markers have been evaluated but only the Glasgow system and serum CRP levels provide pragmatic prognostic accuracy early on. Novel concepts using genetic, transcriptomic and proteomic profiling and also functional imaging for the identification of specific disease patterns are now required.

  15. Saw palmetto-induced pancreatitis.

    PubMed

    Jibrin, Ismaila; Erinle, Ayodele; Saidi, Abdulfattah; Aliyu, Zakari Y

    2006-06-01

    Saw palmetto is a frequently used botanical agent in benign prostatic enlargement (BPH). Although it has been reported to cause cholestatic hepatitis and many medical conditions, Saw palmetto has not been implicated in acute pancreatitis. We report a case of a probable Saw palmetto induced acute hepatitis and pancreatitis. A 55-year-old reformed alcoholic, sober for greater than 15 years, presented with severe non-radiating epigastric pain associated with nausea and vomiting. His only significant comorbidity is BPH for which he intermittently took Saw palmetto for about four years. Physical examination revealed normal vital signs, tender epigastrium without guarding or rebound tenderness. Cullen and Gray Turner signs were negative. Complete blood count and basic metabolic profile were normal. Additional laboratory values include a serum amylase: 2,152 mmol/L, lipase: 39,346 mmol/L, serum triglyceride: 38 mmol/L, AST: 1265, ALT: 1232 and alkaline phosphatase was 185. Abdominal ultrasound and magnetic resonance cholangiography revealed sludge without stones. A hepatic indole diacetic acid scan was negative. Patient responded clinically and biochemically to withdrawal of Saw palmetto. Two similar episodes of improvements followed by recurrence were noted with discontinuations and reinstitution of Saw Palmetto. Simultaneous and sustained response of hepatitis and pancreatitis to Saw palmetto abstinence with reoccurrence on reinstitution strongly favors drug effect. "Natural" medicinal preparations are therefore not necessarily safe and the importance of detailed medication history (including "supplements") cannot be over emphasized.

  16. Alcohol consumption in patients with acute or chronic pancreatitis.

    PubMed

    Sand, J; Lankisch, P G; Nordback, I

    2007-01-01

    Understanding of the relation between the alcoholic consumption and the development of pancreatitis should help in defining the alcoholic etiology of pancreatitis. Although the association between alcohol consumption and pancreatitis has been recognized for over 100 years, it remains still unclear why some alcoholics develop pancreatitis and some do not. Surprisingly little data are available about alcohol amounts, drinking patterns, type of alcohol consumed and other habits such as dietary habits or smoking in respect to pancreatitis preceding the attack of acute pancreatitis or the time of the diagnosis of chronic pancreatitis. This review summarizes the current knowledge. Epidemiological studies clearly show connection between the alcohol consumption in population and the development of acute and chronic pancreatitis. In the individual level the risk to develop either acute or chronic pancreatitis increases along with the alcohol consumption. Moreover, the risk for recurrent acute pancreatitis after the first acute pancreatitis episode seems also to be highly dependent on the level of alcohol consumption. Abstaining from alcohol may prohibit recurrent acute pancreatitis and reduce pain in chronic pancreatitis. Therefore, all the attempts to decrease alcohol consumption after acute pancreatitis and even after the diagnosis of chronic pancreatitis should be encouraged. Smoking seems to be a remarkable co-factor together with alcohol in the development of chronic pancreatitis, whereas no hard data are available for this association in acute pancreatitis. Setting the limits for accepting the alcohol as the etiology cannot currently be based on published data, but rather on the 'political' agreement.

  17. Carbohydrate antigen 19-9 for differential diagnosis of pancreatic carcinoma and chronic pancreatitis

    PubMed Central

    Su, Si-Biao; Qin, Shan-Yu; Chen, Wen; Luo, Wei; Jiang, Hai-Xing

    2015-01-01

    AIM: To evaluate the utility of carbohydrate antigen 19-9 (CA19-9) for differential diagnosis of pancreatic carcinoma and chronic pancreatitis. METHODS: We searched the literature for studies reporting the sensitivity, specificity, and other accuracy measures of serum CA19-9 levels for differentiating pancreatic carcinoma and chronic pancreatitis. Pooled analysis was performed using random-effects models, and receiver operating characteristic (ROC) curves were generated. Study quality was assessed using Standards for Reporting Diagnostic Accuracy and Quality Assessment for Studies of Diagnostic Accuracy tools. RESULTS: A total of 34 studies involving 3125 patients with pancreatic carcinoma and 2061 patients with chronic pancreatitis were included. Pooled analysis of the ability of CA19-9 level to differentiate pancreatic carcinoma and chronic pancreatitis showed the following effect estimates: sensitivity, 0.81 (95%CI: 0.80-0.83); specificity, 0.81 (95%CI: 0.79-0.82); positive likelihood ratio, 4.08 (95%CI: 3.39-4.91); negative likelihood ratio, 0.24 (95%CI: 0.21-0.28); and diagnostic odds ratio, 19.31 (95%CI: 14.40-25.90). The area under the ROC curve was 0.88. No significant publication bias was detected. CONCLUSION: Elevated CA19-9 by itself is insufficient for differentiating pancreatic carcinoma and chronic pancreatitis, however, it increases suspicion of pancreatic carcinoma and may complement other clinical findings to improve diagnostic accuracy. PMID:25892884

  18. 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

  19. The role of pancreatic ducts in the pathogenesis of acute pancreatitis.

    PubMed

    Hegyi, Peter; Rakonczay, Zoltan

    2015-07-01

    Pancreatic ducts secrete 2.5 l of alkaline, HCO3(-)-rich fluid daily which greatly contributes to the homeostasis of the pancreas. Ducts are also important in the pathophysiology of the pancreas; alteration of ductal function can lead to severe diseases such as cystic fibrosis and chronic pancreatitis. The role of pancreatic ducts in the development of acute pancreatitis has only been uncovered recently. Pancreatitis inducing agents like bile acids and ethanol dose-dependently affect pancreatic ductal secretion; low concentrations stimulate, whereas high concentrations inhibit secretion. The majority of the review will focus on the central role of cystic fibrosis transmembrane conductance regulator (CFTR), a critical protein in the regulation of ductal secretion, in the pathogenesis of acute pancreatitis which is highlighted by numerous investigations. Downregulation of CFTR expression results in increased severity of acute pancreatitis in mice. Furthermore, human genetic studies have demonstrated statistically significant association of CFTR mutations with acute recurrent pancreatitis. Overall, the data support the involvement of pancreatic ducts in the pathogenesis of acute pancreatitis.

  20. [Pediatric pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

    PubMed

    Párniczky, Andrea; Czakó, László; Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Morvay, Zita; Oláh, Attila; Pap, Ákos; Sahin-Tóth, Miklós; Szabó, Flóra; Szentkereszti, Zsolt; Szmola, Richárd; Takács, Tamás; Tiszlavicz, László; Veres, Gábor; Szücs, Ákos; Lásztity, Natália

    2015-02-22

    Pediatric pancreatitis is a rare disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has been increased. The management of pediatric pancreatitis requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. In 8 clinical topics (diagnosis; etiology; prognosis; imaging; therapy; biliary tract management; complications; chronic pancreatitis) 50 relevant questions were defined. Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinical statements were accepted with total (more than 95%) agreement. The present Hungarian Pancreatic Study Group guideline is the first evidence based pediatric pancreatitis guideline in Hungary. The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care in pediatric pancreatitis and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

  1. 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

  2. Necrotizing pancreatitis: a review of multidisciplinary management.

    PubMed

    Sabo, Anthony; Goussous, Naeem; Sardana, Neeraj; Patel, Shirali; Cunningham, Steven C

    2015-03-20

    The objective of this review is to summarize the current state of the art of the management of necrotizing pancreatitis, and to clarify some confusing points regarding the terminology and diagnosis of necrotizing pancreatitis, as these points are essential for management decisions and communication between providers and within the literature. Acute pancreatitis varies widely in its clinical presentation. Despite the publication of the Atlanta guidelines, misuse of pancreatitis terminology continues in the literature and in clinical practice, especially regarding the local complications associated with severe acute pancreatitis. Necrotizing pancreatitis is a manifestation of severe acute pancreatitis associated with significant morbidity and mortality. Diagnosis is aided by pancreas-protocol computed tomography or magnetic resonance imaging, ideally 72 h after onset of symptoms to achieve the most accurate characterization of pancreatic necrosis. The extent of necrosis correlates well with the incidence of infected necrosis, organ failure, need for debridement, and morbidity and mortality. Having established the diagnosis of pancreatic necrosis, goals of appropriately aggressive resuscitation should be established and adhered to in a multidisciplinary approach, ideally at a high-volume pancreatic center. The role of antibiotics is determined by the presence of infected necrosis. Early enteral feeds improve outcomes compared with parenteral nutrition. Pancreatic necrosis is associated with a multitude of complications which can lead to long-term morbidity or mortality. Interventional therapy should be guided by available resources and the principle of a minimally invasive approach. When open debridement is necessary, it should be delayed at least 3-6 weeks to allow demarcation of necrotic from viable tissue.

  3. Lack of association between the pancreatitis risk allele CEL-HYB and pancreatic cancer.

    PubMed

    Shindo, Koji; Yu, Jun; Suenaga, Masaya; Fesharakizadeh, Shahriar; Tamura, Koji; Almario, Jose Alejandro Navarro; Brant, Aaron; Borges, Michael; Siddiqui, Abdulrehman; Datta, Lisa; Wolfgang, Christopher L; Hruban, Ralph H; Klein, Alison Patricia; Goggins, Michael

    2017-02-07

    CEL-HYB is a hybrid allele that arose from a crossover between the 3' end of the Carboxyl ester lipase (CEL) gene and the nearby CEL pseudogene (CELP) and was recently identified as a risk factor for chronic pancreatitis. Since chronic pancreatitis is a risk factor for the development of pancreatic cancer, we compared the prevalence of the CEL-HYB allele in patients with pancreatic ductal adenocarcinoma to spousal controls and disease controls. The CEL-HYB allele was detected using Sanger and next generation sequencing. There was no significant difference in the prevalence of the CEL-HYB allele between cases with pancreatic ductal adenocarcinoma compared to controls; 2.6% (22/850) vs. 1.8% (18/976) (p=0.35). CEL-HYB carriers were not more likely to report a history of pancreatitis. Patients with pancreatic cancer are not more likely than controls to be carriers of the CEL-HYB allele.

  4. Pancreatitis-induced Inflammation Contributes to Pancreatic Cancer by Inhibiting Oncogene-Induced Senescence

    PubMed Central

    Guerra, Carmen; Collado, Manuel; Navas, Carolina; Schuhmacher, Alberto J; Hernández-Porras, Isabel; Cañamero, Marta; Rodriguez-Justo, Manuel; Serrano, Manuel; Barbacid, Mariano

    2016-01-01

    Pancreatic acinar cells of adult mice (≥P60) are resistant to transformation by some of the most robust oncogenic insults including expression of K-Ras oncogenes and loss of p16Ink4a/p19Arf or Trp53 tumor suppressors. Yet, these acinar cells yield pancreatic intraepithelial neoplasias (mPanIN) and ductal adenocarcinomas (mPDAC) if exposed to limited bouts of non-acute pancreatitis, providing they harbor K-Ras oncogenes. Pancreatitis contributes to tumor progression by abrogating the senescence barrier characteristic of low-grade mPanINs. Attenuation of pancreatitis-induced inflammation also accelerates tissue repair and thwarts mPanIN expansion. Patients with chronic pancreatitis display senescent PanINs, if they have received anti-inflammatory drugs. These results put forward the concept that anti-inflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC. PMID:21665147

  5. Defining the Accuracy of Secretin Pancreatic Function Testing in Patients With Suspected Early Chronic Pancreatitis

    PubMed Central

    Ketwaroo, Gyanprakash; Brown, Alphonso; Young, Benjamin; Kheraj, Rakhi; Sawhney, Mandeep; Mortele, Koenraad J.; Najarian, Robert; Tewani, Sumeet; Dasilva, Deborah; Freedman, Steven; Sheth, Sunil

    2017-01-01

    OBJECTIVES The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known. METHODS This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as “true positive” or “true negative” for chronic pancreatitis based on follow-up imaging or histologic evidence. RESULTS In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45 %) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1–11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3–11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82 % with a specificity of 86 %. The positive predictive value (PPV) of chronic pancreatitis was 45 % with a negative predictive value (NPV) of 97 %. CONCLUSIONS In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97 %. PMID:23711627

  6. Necrotizing pancreatitis: diagnosis, imaging, and intervention.

    PubMed

    Shyu, Jeffrey Y; Sainani, Nisha I; Sahni, V Anik; Chick, Jeffrey F; Chauhan, Nikunj R; Conwell, Darwin L; Clancy, Thomas E; Banks, Peter A; Silverman, Stuart G

    2014-01-01

    Acute necrotizing pancreatitis is a severe form of acute pancreatitis characterized by necrosis in and around the pancreas and is associated with high rates of morbidity and mortality. Although acute interstitial edematous pancreatitis is diagnosed primarily on the basis of signs, symptoms, and laboratory test findings, the diagnosis and severity assessment of acute necrotizing pancreatitis are based in large part on imaging findings. On the basis of the revised Atlanta classification system of 2012, necrotizing pancreatitis is subdivided anatomically into parenchymal, peripancreatic, and combined subtypes, and temporally into clinical early (within 1 week of onset) and late (>1 week after onset) phases. Associated collections are categorized as "acute necrotic" or "walled off" and can be sterile or infected. Imaging, primarily computed tomography and magnetic resonance imaging, plays an essential role in the diagnosis of necrotizing pancreatitis and the identification of complications, including infection, bowel and biliary obstruction, hemorrhage, pseudoaneurysm formation, and venous thrombosis. Imaging is also used to help triage patients and guide both temporizing and definitive management. A "step-up" method for the management of necrotizing pancreatitis that makes use of imaging-guided percutaneous catheter drainage of fluid collections prior to endoscopic or surgical necrosectomy has been shown to improve clinical outcomes. The authors present an algorithmic approach to the care of patients with necrotizing pancreatitis and review the use of imaging and interventional techniques in the diagnosis and management of this pathologic condition.

  7. Pancreatic cancer screening: state of the art.

    PubMed

    Gemmel, Christian; Eickhoff, Axel; Helmstädter, Lars; Riemann, Jürgen F

    2009-02-01

    Pancreatic cancer is a devastating disease with a median survival of approximately 6 months after diagnosis. Many factors are associated with a worse outcome; examples include late diagnosis, low resection rate, aggressive tumor behavior and a lack of an effective chemotherapy regimen. Owing to the low prevalence of pancreatic cancer relative to the diagnostic accuracy of present detection methods and the absence of promising treatment modalities, even in early stages, it is currently neither advisable nor cost effective to screen the general population. Efforts are focused on early screening of selected high-risk-cohorts, who account for approximately 10% of patients with pancreatic cancer. These include patients with chronic pancreatitis, individuals with a family history of pancreatic cancer, patients with hereditary pancreatitis, Peutz-Jeghers syndrome, cystic fibrosis or familial atypical multiple mole melanoma. At present, a multimodal-screening approach of endoscopic ultrasound, computed tomography and endoscopic retrograde cholangiopancreatography appears to be the most effective method to screen for pancreatic cancer in high-risk patients. Continued efforts are needed to elucidate effective testing to identify patients with nonhereditary risk factors who will benefit from screening protocols. A combined approach of serum markers, genetic markers and specific imaging studies may prove to be the future of pancreatic screening.

  8. [Fulminant pancreatitis--surgical point of view].

    PubMed

    Werner, J

    2006-11-29

    Today, treatment of acute pancreatitis is mainly conservative and surgery is on the retreat. Infection of pancreatic necrosis is still the main risk factor of morbidity and mortality in the course of necrotizing disease. A prophylactic treatment with antibiotics can reduce both infectious complications and mortality. Thus, antibiotics should be administered in severe pancreatitis. If pancreatic infection is suspected, fine needle aspiration should be performed. Today, infected pancreatic necrosis is a well accepted indication for surgery. Aim of the surgical procedure is to remove the septic focus by debridement of the infected pancreatic and peripancreatic necrosis. The optimal timepoint for the surgical intervention is the 3rd to 4th week after onset of the disease. At that time, necrotic tissue is well demarcated. Therefore bleeding complications and removal of vital tissue can be avoided. Today, surgical procedures should combine the necrosectomy with a postoperative method to continuously remove necrosis and debris. This is the case with the following two techniques, the postoperative continuous lavage and the closed packing. In contrast, sterile necrosis is usually treated conservatively. Fulminant acute pancreatitis is a rare subgroup of acute pancreatitis, characterized by a rapidly progressive multiple organ failure in the first days following the onset of the disease with a high probability of death despite ICU therapy. There is poor outcome with both, surgical and conservative therapies. Thus, surgery should only be peformed as an ultima ratio.

  9. Congenital pancreatic anomalies, variants, and conditions.

    PubMed

    Alexander, Lauren F

    2012-05-01

    Understanding pancreatic development and the congenital anomalies and variants that result from alterations in normal development allows for better recognition of these anomalies at diagnostic imaging. This article reviews normal pancreatic embryology and anatomy, and the appearance of the more common developmental anomalies and ductal variants, with emphasis on computed tomography and magnetic resonance imaging. Common mimics of masses are also covered.

  10. Targeting metabolic scavenging in pancreatic cancer.

    PubMed

    Lyssiotis, Costas A; Cantley, Lewis C

    2014-01-01

    Pancreatic tumor metabolism is rewired to facilitate survival and growth in a nutrient-depleted environment. This leads to a unique dependence on metabolic recycling and scavenging pathways, including NAD salvage. Targeting this pathway in pancreatic cancer disrupts metabolic homeostasis and impairs tumor growth.

  11. NSAIDs and Acute Pancreatitis: A Systematic Review

    PubMed Central

    Pezzilli, Raffaele; Morselli-Labate, Antonio Maria; Corinaldesi, Roberto

    2010-01-01

    The resulting pain is the main symptom of acute pancreatitis and it should be alleviated as soon as possible. NSAIDs are the first line therapy for pain and they are generally administered to acute pancreatitis patients upon admission to the hospital. In addition, these drugs have also been used to prevent post-endoscopic cholangiopancreatography (ERCP) acute pancreatitis. On the other hand, there are several reports indicating that NSAIDs may be the actual cause of acute pancreatitis. We carried out a literature search on PubMed/MEDLINE; all full text papers published in from January 1966 to November 2009 on the use of NSAIDs in acute pancreatitis were collected; the literature search was also supplemented by a review of the bibliographies of the papers evaluated. Thus, in this article, we will systematically review the current literature in order to better illustrate the role of NSAIDs in acute pancreatitis, in particular: i) NSAIDs as a cause of acute pancreatitis; ii) their use to prevent post-retrograde ERCP pancreatitis and iii) their efficacy for pain relief in the acute illness of the pancreas. PMID:27713268

  12. Hispanics and Pancreatic Cancer: Things to Know

    MedlinePlus

    ... These include: • What You Need to Know About Cancer of the Pancreas – an online publication about exocrine pancreatic cancer – at www. cancer. gov/ cancertopics/ wyntk/ pancreas • NCI’s summary page about pancreatic cancer – including links ...

  13. Acute Pancreatitis Secondary to Gestational Hypertriglyceridaemia

    PubMed Central

    Cahalane, Alexis M.; Smith, Myles J.; Ryan, James; Maguire, Donal

    2012-01-01

    Gestational hypertriglyceridaemia is a rare cause of acute pancreatitis. Its pathophysiology is incompletely understood. Severity scoring and effective management remain challenging. We report a case of acute pancreatitis secondary to gestational hypertriglyceridaemia. We describe the use of computed tomography to provide an alternative determination of severity, as well as plasmapheresis as a means of treating the condition. PMID:22844296

  14. [Clinico-tomographic correlations in acute pancreatitis].

    PubMed

    Lese, M; Pop, C; Brânduşe, M; Achim, V; Grigorescu, D; Nemeş, S

    1998-01-01

    In the surgery ward from Baia Mare, in the period 1989-1997 have been operated yearly, on an average, 16-17 acute pancreatitis, out of which 8-9 were necrotic-haemorrhagic acute pancreatitis. The possibility of carrying out the computerized tomography allowed a more precise pre-surgery diagnosis and after surgery was improved observation of evolution of the inflammatory phenomena from the pancreatic zone so that the volume, the structure and the outline of the pancreas, the abdominal or pleural liquid collections and the aspect of the neighboring tissues have been correlated in dynamics, with the clinic aspect of the acute pancreatitis and the prognostic indexes. Even if the computerized tomography allowed a more correct evaluation of the patients suffering of acute pancreatitis, there have been 4-6 decreases due to this affection and its complications, the post-surgery death rate remaining at 17-21%.

  15. Pancreatic abscess secondary to Alcaligenes faecalis.

    PubMed

    Ashwath, Mahi Lakshmi; Katner, Harold P

    2005-01-01

    We report a patient with pancreatic abscesses and necrosis secondary to Alcaligenes faecalis infection. He initially presented with alcohol-induced acute pancreatitis. Twenty days after the initial presentation, he re-presented with increasing pain and was found to have pancreatic necrosis and abscesses. Treatment was initiated with meropenem. Because of persistent fevers, computed tomography-guided drainage was performed. The fluid grew A faecalis resistant to meropenem and the patient continued to be febrile. He recovered only after adequate surgical intervention and appropriate antibiotic coverage. Although this is the first case of A faecalis reported to cause pancreatic abscess, we believe selection of this organism occurred because surgical drainage was delayed while the patient was on the recommended treatment with meropenem. This case emphasizes the need for early surgical drainage of pancreatic abscesses to avoid the selection of such resistant pathogens.

  16. Value of Intraoperative Sonography in Pancreatic Surgery.

    PubMed

    Weinstein, Stefanie; Morgan, Tara; Poder, Liina; Shin, Lewis; Jeffrey, R Brooke; Aslam, Rizwan; Yee, Judy

    2015-07-01

    The utility of intraoperative sonography for pancreatic disease has been well described for detection and evaluation of neoplastic and inflammatory pancreatic disease. Intraoperative sonography can help substantially reduce surgical time as well as decrease potential injury to tissues and major structures. Imaging with sonography literally at the point of care--the surgeon's scalpel--can precisely define the location of pancreatic lesions and their direct relationship with surrounding structures in real time during surgery. This article highlights our experience with intraoperative sonography at multiple institutional sites for both open and laparoscopic surgical procedures. We use intraoperative sonography for a wide range of pancreatic disease to provide accurate localization and staging of disease, provide guidance for enucleation of nonpalpable, nonvisible tumors, and in planning the most direct and least invasive surgical approach, avoiding injury to the pancreatic duct or other vital structures.

  17. Computed tomographic appearance of resectable pancreatic carcinoma

    SciTech Connect

    Itai, Y.; Araki, T.; Tasaka, A.; Maruyama, M.

    1982-06-01

    Thirteen patients with resectable pancreatic carcinoma were examined by computed tomography (CT). Nine had a mass, 2 had dilatation of the main pancreatic duct, 1 appeared to have ductal dilatation, and 1 had no sign of abnormality. Resectable carcinoma was diagnosed retrospectively in 8 cases, based on the following criteria: a mass with a distinct contour, frequently containing a tiny or irregular low-density area and accompanied by dilatation of the caudal portion of the main pancreatic duct without involvement of the large vessels, liver, or lymph nodes. Including unresectable cancer, chronic pancreatitis, and obstructive jaundice from causes other than cancer, the false-positive rate was less than 6%. However, a small cancer without change in pancreatic contour is difficult to detect with CT.

  18. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  19. [Pancreatic cancer linked to life style and genome].

    PubMed

    Sand, Juhani; Räty, Sari; Nordback, Isto

    2009-01-01

    Since the prognosis of pancreatic cancer is poor in spite of surgical and drug therapy, the focus should be on the prevention and early detection of the disease. In Europe, smoking accounts for up to 30% of pancreatic cancers, and heavy drinking increases the risk of chronic pancreatitis and pancreatic cancer. Diabetes can be a risk factor for pancreatic cancer and constitute its initial symptom. Obesity and low physical activity are linked to the risk of pancreatic cancer. An increased risk of pancreatic cancer is also associated with a hereditary inflammation, cystic fibrosis, and with part of cystic tumors of the pancreas.

  20. Biliary tract and pancreatic surgery complicated by acute pancreatitis: a clinical analysis

    PubMed Central

    Sun, Chenggang; Li, Xin; Sun, Jintang; Zou, Peng; Gao, Shubo; Zhang, Peixun

    2015-01-01

    Objective: To study the clinical treatment features of biliary tract and pancreatic surgery complicated by acute pancreatitis. Methods: A retrospective analysis of 21 cases of biliary tract and pancreatic surgery complicated by acute pancreatitis in the Department of General Surgery in our hospital during May 2005 to July 2011 was performed; the clinical treatment features were analyzed in terms of surgical option, onset interval of acute pancreatitis after last surgery, length of stay in hospital and Ranson score. Results: There was no statistic difference between the two groups (A: The onset interval of acute pancreatitis after last surgery < 0.5 year. B: The onset interval of acute pancreatitis after last surgery > 0.5 year) in pathogenetic condition and length of stay in hospital. All patients were discharged after treatment, a follow-up of 6-18 months found no recurrence of pancreatitis. Conclusion: There is no relevance between the treatment feature and onset interval of biliary and pancreatic surgery complicated by acute pancreatitis. The disease is still treated meanly with symptomatic and supportive treatment, while the etiological treatment is also particularly important. PMID:26131243

  1. Pancreatic STAT3 protects mice against caerulein-induced pancreatitis via PAP1 induction.

    PubMed

    Shigekawa, Minoru; Hikita, Hayato; Kodama, Takahiro; Shimizu, Satoshi; Li, Wei; Uemura, Akio; Miyagi, Takuya; Hosui, Atsushi; Kanto, Tatsuya; Hiramatsu, Naoki; Tatsumi, Tomohide; Takeda, Kiyoshi; Akira, Shizuo; Takehara, Tetsuo

    2012-12-01

    The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that controls expressions of several genes involved in cell survival, proliferation and differentiation, and tissue inflammation. However, the significance of pancreatic STAT3 in acute pancreatitis remains unclear. We generated conditional STAT3 knockout (stat3(Δ/Δ)) mice by crossing stat3(flox/flox) mice with Pdx1-promoter Cre transgenic mice. Caerulein administration activated pancreatic STAT3 and induced acute pancreatitis as early as 3 hours in wild-type mice, and full recovery from the induced pancreatic injury was observed within 7 days. The levels of serum amylase and lipase and histologic scores of pancreatic necrosis and inflammatory cell infiltration were significantly higher at 3 hours in stat3(Δ/Δ) mice than in stat3(flox/flox) mice. Pancreatic recovery after pancreatitis was significantly delayed in stat3(Δ/Δ) mice compared with stat3(flox/flox) mice. Although stat3(flox/flox) mice had marked production in the pancreas of pancreatitis-associated protein 1 (PAP1), a serum acute phase protein, this induction was completely abrogated in stat3(Δ/Δ) mice. Enforced production of PAP1 by a hydrodynamic procedure in the liver significantly suppressed pancreatic necrosis and inflammation and also promoted pancreatic regeneration and recovery in stat3(Δ/Δ) mice to levels similar to those observed in stat3(flox/flox) mice. In conclusion, pancreatic STAT3 is indispensable for PAP1 production, and this STAT3/PAP1 pathway plays a protective role in caerulein-induced pancreatitis.

  2. Endoscopic naso-pancreatic drainage for the treatment of pancreatic fistula occurring after LDLT.

    PubMed

    Nagatsu, Akihisa; Taniguchi, Masahiko; Shimamura, Tsuyoshi; Suzuki, Tomomi; Yamashita, Kenichiro; Kawakami, Hiroshi; Abo, Daisuke; Kamiyama, Toshiya; Furukawa, Hiroyuki; Todo, Satoru

    2011-08-14

    Pancreatic fistula is a quite rare complication in patients who undergo living donor liver transplantation (LDLT). However, in the cases that show pancreatic fistula, the limited volume of the graft and the resultant inadequate liver function may complicate the management of the fistula. As a result, the pancreatic fistula may result in the death of the patient. We present 2 cases in which endoscopic treatment was effective against pancreatic fistulas that developed after LDLT. In case 1, a 61-year-old woman underwent LDLT for primary biliary cirrhosis. Because of a portal venous thrombus caused by a splenorenal shunt, the patient underwent portal vein reconstruction, and a splenorenal shunt was ligated on postoperative day (POD) 7. The main pancreatic duct was injured during the manipulation to achieve hemostasis, thereby necessitating open drainage. However, discharge of pancreatic fluid continued even after POD 300. Endoscopic naso-pancreatic drainage (ENPD) was performed, and this procedure resulted in a remarkable decrease in drain output. The refractory pancreatic fistula healed on day 40 after ENPD. In case 2, a 58-year-old man underwent LDLT for cirrhosis caused by the hepatitis C virus. When the portal vein was exposed during thrombectomy, the pancreatic head was injured, which led to the formation of a pancreatic fistula. Conservative therapy was ineffective; therefore, ENPD was performed. The pancreatic fistula healed on day 38 after ENPD. The findings in these 2 cases show that endoscopic drainage of the main pancreatic duct is a less invasive and effective treatment for pancreatic fistulas that develop after LDLT.

  3. Role of fibrosis-related genes and pancreatic duct obstruction in rat pancreatitis models: implications for chronic pancreatitis.

    PubMed

    Miyauchi, M; Suda, K; Kuwayama, C; Abe, H; Kakinuma, C

    2007-10-01

    Human chronic pancreatitis is characterized by irreversible fibrosis, whereas pancreatic fibrosis in animal models is reversible. In this study, we compare the development of pancreatic fibrosis in the dibutyltin dichloride (DBTC) model, WBN/Kob rats and bile duct-ligated (BDL) rats. DBTC (8 mg/kg) was administered to LEW rats, and the pancreas was histopathologically investigated sequentially. Male and female WBN/Kob rats aged 4, 6 and 8 months were also examined. BDL rats were prepared by ligation of the bile duct at the duodenal portion and sacrificed at 3 or 7 days after ligation. Fibrosis in the DBTC model peaked after 1 week and was limited to the areas around the pancreatic ducts after 2 weeks, and was composed of both type I and type III collagen. In contrast, fibrosis in male WBN/Kob rats peaked at age 4 months, expanded into intralobular area, and was composed of type III collagen. It exhibited almost no type I collagen and a marked tendency to regress. Pancreatic fibrosis in BDL rats was somewhat difficult to induce and required increased stimulation. This suggests that fibrosis in human biliary pancreatitis may gradually form based on weak, continuous stimulation. We conclude that type I collagen may be involved in the progression of irreversible fibrosis. The imbalance between synthesis and degradation of extracellular matrix molecules or degree of stimulation over a certain period may lead to pancreatic fibrosis. Gene expressions of prolyl hydroxylase and tissue inhibitors of matrix metalloproteinase-2 were elevated.

  4. Depression, cytokines, and pancreatic cancer

    PubMed Central

    Breitbart, William; Rosenfeld, Barry; Tobias, Kristen; Pessin, Hayley; Ku, Geoffrey Y.; Yuan, Jianda; Gibson, Christopher; Wolchok, Jedd

    2014-01-01

    Background To examine the relationships between cytokines, depression, and pancreatic cancer. Method 75 individuals were recruited from two New York City hospitals (a cancer center and a psychiatric hospital) and comprised 4 subgroups: patients with adenocarcinoma of the pancreas who did (n=17) and did not (n=26) have a diagnosis of Major Depressive Episode (MDE), and healthy participants with (n=7) and without (n=25) MDE. All individuals completed a battery of self-report measures. Sera was assayed using Meso Scale Discovery techniques to measure the following pro- and anti-inflammatory cytokines: IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p70, IFN-gamma, TGF-beta, and TNF-alpha; we also calculated the IL-2/IL-4 ratio. Results Pancreatic cancer patients had significantly higher levels of IL-6 and IL-10, and significantly lower TGF-beta levels than healthy participants. When the sample was divided into those with and without MDE, the groups only differed with regard to serum IL-6 levels. No significant cancer×depression interaction effect was observed. Severity of depressive symptoms was also significantly correlated with IL-6, rs=.28, p=.02, while hopelessness was associated with IFN-alpha, rs=.34, p=.006. Pain, fatigue and sleep disturbance were associated with several of the cytokines assayed including IL-1beta (pain intensity), IL-4 (pain intensity and overall sleep quality), IL-12p70 (pain intensity), TGF-beta (fatigue intensity), but anxiety was not associated with any of the cytokines assayed. Conclusions This study demonstrated an association between depression and IL-6, but not with other cytokines. Moreover, IL-6 was not significantly associated with other measures of psychological distress (anxiety, hopelessness) or with symptom distress (pain, fatigue, sleep quality), although some cytokines assayed were associated with specific symptoms. The implications of these findings for the etiology and treatment of depression in pancreatic cancer

  5. Natural History of Pancreatic Cysts.

    PubMed

    Larson, Alexander; Kwon, Richard S

    2017-03-17

    Pancreatic cystic neoplasms are discovered with increasing frequency. Accurate knowledge of the natural history of cystic neoplasms is crucial to develop useful and cost-effective strategies for surveillance and surgical resection. To date, the natural history of cystic neoplasms is still incomplete due to lack of adequate diagnostic accuracy in the absence of surgical pathology. Nevertheless, current evidence points to risk factors for malignant transformation to help clinical management. New biomarkers that accurately distinguish cyst neoplasms and those most likely to progress to cancer would help clarify the natural history of cystic neoplasms.

  6. Influence of high intensity focused ultrasound (HIFU) treatment to the pancreatic function in pancreatic cancer patients.

    PubMed

    Shi, Yulan; Ying, Xiao; Hu, Xiaoye; Zhao, Jing; Fang, Xuefeng; Wu, Minghui; Chen, Tian Zhou; Shen, Hong

    2015-05-01

    Present study was designed to investigate the pancreatic endocrine and exocrine function damage after High Intensity Focused Ultrasound (HIFU) therapy in patients with advanced pancreatic cancer. It was a retrospective analysis of blood glucose and amylase changes in 59 advanced pancreatic cancer patients treated with HIFU from 2010 February to 2014 January. The mean glucose and amylase before HIFU treatment were 6.02mmol/L and 59.17 U/L respectively. After HIFU treatment, it was shown that the mean glucose and amylase levels were 5.66mmol/L and 57.86/L respectively. There was no statistical significance between them. No acute pancreatitis was observed. The endocrine and exocrine function of pancreatic cancer patients was not damaged by HIFU treatment. HIFU treatment for the pancreatic cancer patients seems to be safe.

  7. A Case of Chronic Calcific Nonalcoholic Pancreatitis

    PubMed Central

    Kangas-Dick, Aaron; Khan, Umair; Awoniyi, Oluwafunbi; Waqar, Shanza; Tun, Nu Nwe; Wong, Cynthia

    2016-01-01

    Tropical Calcific Pancreatitis (TCP) is a type of chronic calcific nonalcoholic pancreatitis. Similar to nonalcoholic chronic pancreatitis, it presents in the second and third decades of life; however this type is reported mostly in the developing tropical and subtropical countries. It is associated with the formation of pancreatic calculi and a high probability of developing insulin-dependent diabetes mellitus. Epidemiologic studies have shown that these patients have an increased risk of developing pancreatic carcinoma. The etiology of TCP remains uncertain, with the current consensus suggesting genetics as well as possible toxicity from consuming large amounts of cassava, a tuber. Definite diagnosis of TCP requires younger age of onset, history of malnutrition, and presence of diabetes mellitus along with extensive pancreatic calcification and ductal calculi. When patients meet most but not all of these conditions the term Idiopathic Chronic Pancreatitis (ICP) is used. This is a case of a 44-year-old man who presented with most features seen in TCP, and however, was diagnosed with ICP. PMID:27957355

  8. Acute on chronic pancreatitis causing a highway to the colon with subsequent road closure: pancreatic colonic fistula presenting as a large bowel obstruction treated with pancreatic duct stenting.

    PubMed

    Cochrane, Justin; Schlepp, Greg

    2015-01-01

    Context. Colonic complications associated with acute pancreatitis have a low incidence but carry an increased risk of mortality with delayed diagnosis and treatment. Pancreatic colonic fistula is most commonly associated with walled off pancreatic necrosis or abscess formation and rarely forms spontaneously. Classic clinical manifestations for pancreatic colonic fistula include diarrhea, hematochezia, and fever. Uncommonly pancreatic colonic fistula presents as large bowel obstruction. Case. We report a case of a woman with a history of recurrent episodes of acute pancreatitis who presented with large bowel obstruction secondary to pancreatic colonic fistula. Resolution of large bowel obstruction and pancreatic colonic fistula was achieved with pancreatic duct stenting. Conclusion. Pancreatic colonic fistula can present as large bowel obstruction. Patients with resolved acute pancreatitis who have radiographic evidence of splenic flexure obstruction, but without evidence of mechanical obstruction on colonoscopy, should be considered for ERCP to evaluate for PCF. PCF not associated with walled off pancreatic necrosis or peritoneal abscess can be treated conservatively with pancreatic duct stenting.

  9. [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.

  10. Isolated Pancreatic Uncinate Duct IPMN.

    PubMed

    Maker, Ajay V; Maker, Vijay K

    2017-04-01

    The ventral pancreas originally forms as an evagination of the common bile duct at 32 days gestation and its duct, the uncinate duct, eventually rotates with the ventral anlage to join the dorsal pancreas and fuse with the main pancreatic duct. Thus, though often considered a "branch" duct of the pancreas, embryologically, the uncinate duct is the "main" pancreatic duct of the ventral pancreas. This concept is not fully addressed in the current definitions of intraductal papillary mucinous neoplasms of the pancreas (IPMN) where international consensus guidelines consider the main-duct IPMN as high risk for malignancy and most small branch-duct IPMN as low risk for malignancy. Thus, it is important to recognize that isolated uncinate-duct IPMN can occur and, based on its embryologic origin and increased association with high-grade dysplasia and invasive cancer, may be managed conceptually as a main duct type of disease rather than a branch duct until better biomarkers of malignancy are discovered. The images provide an example of this unique disease process.

  11. Novel strategies for managing pancreatic cancer

    PubMed Central

    Loc, Welley S; Smith, Jill P; Matters, Gail; Kester, Mark; Adair, James H

    2014-01-01

    With the incidence reports of pancreatic cancer increasing every year, research over the last several decades has been focused on the means to achieve early diagnosis in patients that are at a high risk of developing the malignancy. This review covers current strategies for managing pancreatic cancer and further discusses efforts in understanding the role of early onset symptoms leading to tumor progression. Recent investigations in this discussion include type 3c diabetes, selected biomarkers and pathways related to pancreatic intraepithelial neoplasia lesions, drug resistance, and advances in nanomedicine which may provide significant solutions for improving early detection and treatments in future medicine. PMID:25356034

  12. Primary Cilia in Pancreatic Development and Disease

    PubMed Central

    Lodh, Sukanya; O’Hare, Elizabeth A.; Zaghloul, Norann A.

    2014-01-01

    Primary cilia and their anchoring basal bodies are important regulators of a growing list of signaling pathways. Consequently, dysfunction in proteins associated with these structures results in perturbation of the development and function of a spectrum of tissue and cell types. Here, we review the role of cilia in mediating the development and function of the pancreas. We focus on ciliary regulation of major pathways involved in pancreatic development, including Shh, Wnt, TGF-β, Notch, and fibroblast growth factor. We also discuss pancreatic phenotypes associated with ciliary dysfunction, including pancreatic cysts and defects in glucose homeostasis, and explore the potential role of cilia in such defects. PMID:24864023

  13. Biomarkers for early diagnosis of pancreatic cancer.

    PubMed

    Jenkinson, Claire; Earl, Julie; Ghaneh, Paula; Halloran, Christopher; Carrato, Alfredo; Greenhalf, William; Neoptolemos, John; Costello, Eithne

    2015-03-01

    Pancreatic ductal adenocarcinoma is an aggressive malignancy with a 5-year survival rate of approximately 5%. The lack of established strategies for early detection contributes to this poor prognosis. Although several novel candidate biomarkers have been proposed for earlier diagnosis, none have been adopted into routine clinical use. In this review, the authors examine the challenges associated with finding new pancreatic cancer diagnostic biomarkers and explore why translation of biomarker research for patient benefit has thus far failed. The authors also review recent progress and highlight advances in the understanding of the biology of pancreatic cancer that may lead to improvements in biomarker detection and implementation.

  14. Pancreaticoatmospheric fistula following severe acute necrotising pancreatitis

    PubMed Central

    Simoneau, Eve; Chughtai, Talat; Razek, Tarek; Deckelbaum, Dan L

    2014-01-01

    Severe acute necrotising pancreatitis is associated with numerous local and systemic complications. Abdominal compartment syndrome requiring urgent decompressive laparotomy is a potential complication of this disease process and is associated with increased morbidity and mortality. We describe the case of a pancreaticoatmospheric fistula following decompressive laparotomy in a patient with severe acute necrotising pancreatitis. While this fistula was managed successfully using the current standard of care for pancreatic fistulas, the wound care for in this patient with drainage of the fistula through an open abdomen, is a significant challenge. PMID:25519860

  15. [Possibilities of treatment of external pancreatic fistula].

    PubMed

    Cherdantsev, D V; Pervova, O V; Diatlov, V Iu; Kurbanov, D Sh

    2014-01-01

    Evaluation of the efficacy of sekretolitičeskoj therapy with synthetic analogue of somatostatin, a short-acting oktreotid (group 1) and extended oktreotid-depo (group 2) in 24 patients with external pancreatic fistulas after destructive pancreatitis. Results of clinical studies have shown that against the backdrop of an analogue of somatostatin-depo true healing and purulent-necrotic pancreatic external fistula occurs in less time: average 19 ± 1.8, and 16.2 ± 1.2 day observations, respectively.

  16. Contrast‐enhanced ultrasound of pancreatic tumours

    PubMed Central

    D'Onofrio, Mirko; Crosara, Stefano; Dal Corso, Flavia; Barbi, Emilio; Canestrini, Stefano; Mucelli, Roberto Pozzi

    2015-01-01

    Abstract Indication/purpose: To review contrast‐enhanced ultrasound features of the most common pancreatic tumours. Methods: Contrast‐enhanced ultrasound (CEUS) can provide distinctive features of pancreatic tumours that are reported in the present paper, providing radiologic‐pathological correlations and clarifying the main differential diagnosis. Conclusion: Contrast‐enhanced ultrasound plays a well‐established role in the evaluation of pancreatic tumours. When possible, CEUS should be always performed after the initial US diagnosis, in order to improve the accuracy of the first line examination. PMID:28191218

  17. Post-pancreatitis Fat Necrosis Mimicking Carcinomatosis.

    PubMed

    Smith, Joshua P; Arnoletti, J Pablo; Varadarajulu, Shyam; Morgan, Desiree E

    2008-01-01

    Acute pancreatitis can result in retroperitoneal fat necrosis, typically occurring in the peripancreatic region, with extension into the transverse mesocolon, omentum and mesenteric root. When evaluated with contrast enhanced computed tomography (CECT), acute peripancreatic post necrotic collections typically become lower in attenuation over time, and often appear as homogeneous fluid collections. Saponification as a complication of fat necrosis in patients with acute pancreatitis is a well recognized clinical entity. While retroperitonal fat necrosis is commonly seen on CECT, saponification is not a prominent imaging feature. We present a case of acute pancreatitis complicated by extensive saponification of fat throughout the retroperitoneum and peritoneal lining, mimicking carcinomatosis.

  18. Small Bowel Obstruction Secondary to Acute Pancreatitis

    PubMed Central

    Sunkara, Tagore; Etienne, Denzil; Caughey, Megan E.; Gaduputi, Vinaya

    2017-01-01

    While an uncommon occurrence, it is possible for patients diagnosed with acute pancreatitis to develop colonic ileus, obstruction, or perforation. By extension, it is also possible to develop a small bowel obstruction following an episode of acute pancreatitis. Here, we present the case of a 44-year-old male, who after repeated attacks of acute pancreatitis, came to the emergency department with continuous, non-bloody vomiting. This patient also complained of both left upper quadrant and epigastric pain, and was subsequently diagnosed with a small bowel obstruction involving the proximal jejunum. PMID:28270876

  19. Management of Locally Advanced Pancreatic Cancer.

    PubMed

    Martin, Robert C G

    2016-12-01

    The diagnosis for locally advanced pancreatic cancer is based on high-quality cross-sectional imaging, which shows tumor invasion into the celiac/superior mesenteric arteries and/or superior mesenteric/portal venous system that is not reconstructable. The optimal management of these patients is evolving quickly with the advent of newer chemotherapeutics, radiation, and nonthermal ablation modalities. This article presents the current status of initial chemotherapy, surgical therapy, ablative therapy, and radiation therapy for patients with nonmetastatic locally advanced unresectable pancreatic cancer. Surgical resection offers the best chance of long-term disease control and the only chance for cure for patients with nonmetastatic exocrine pancreatic cancer.

  20. Pancreatic cancer stem cells: fact or fiction?

    PubMed

    Bhagwandin, Vikash J; Shay, Jerry W

    2009-04-01

    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  1. Small Bowel Obstruction Secondary to Acute Pancreatitis.

    PubMed

    Sunkara, Tagore; Etienne, Denzil; Caughey, Megan E; Gaduputi, Vinaya

    2017-02-01

    While an uncommon occurrence, it is possible for patients diagnosed with acute pancreatitis to develop colonic ileus, obstruction, or perforation. By extension, it is also possible to develop a small bowel obstruction following an episode of acute pancreatitis. Here, we present the case of a 44-year-old male, who after repeated attacks of acute pancreatitis, came to the emergency department with continuous, non-bloody vomiting. This patient also complained of both left upper quadrant and epigastric pain, and was subsequently diagnosed with a small bowel obstruction involving the proximal jejunum.

  2. Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer.

    PubMed

    Yoshida, Naoki; Masamune, Atsushi; Hamada, Shin; Kikuta, Kazuhiro; Takikawa, Tetsuya; Motoi, Fuyuhiko; Unno, Michiaki; Shimosegawa, Tooru

    2017-04-01

    Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined. SUIT-2 pancreatic cancer cells were subcutaneously injected into nude mice alone or with PSCs and the size of the tumors was monitored. Kindlin-2 expression was observed in PDAC and the peritumoral stroma. Stromal kindlin-2 expression was associated with shorter recurrence-free survival time after R0 resection. Knockdown of kindlin-2 resulted in decreased proliferation, migration, and cytokine expression in PSCs. The PSC-induced proliferation and migration of pancreatic cancer cells were suppressed by kindlin-2 knockdown in PSCs. In vivo, co-injection of PSCs increased the size of the tumors, but this effect was abolished by kindlin-2 knockdown in PSCs. In conclusion, kindlin-2 in PSCs promoted the progression of pancreatic cancer.

  3. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    SciTech Connect

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    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 is 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 altered

  4. Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature.

    PubMed

    Tariq, Hassan; Nayudu, Suresh; Akella, Sai; Glandt, Mariela; Chilimuri, Sridhar

    2016-12-01

    There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome. Pancreatic steatosis can be diagnosed on ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). In addition to a correlation between pancreatic steatosis and metabolic syndrome, pancreatic steatosis may lead to a worse outcome in pancreatitis and may be an etiological factor in pancreatic cancer, but we need further research to examine the associations, pathophysiology, and the impact of pancreatic steatosis and NAFPD on the human health.

  5. Non-Alcoholic Fatty Pancreatic Disease: A Review of Literature

    PubMed Central

    Tariq, Hassan; Nayudu, Suresh; Akella, Sai; Glandt, Mariela; Chilimuri, Sridhar

    2016-01-01

    There is an epidemic of obesity worldwide. The prevalence of obesity has doubled over the last three decades. Obesity, especially abdominal obesity is associated with insulin resistance that can lead to pancreatic steatosis and non-alcoholic fatty pancreatic disease (NAFPD). NAFPD describes a phenotype entity ranging from deposition of fat in the pancreas to pancreatic inflammation, and resultant fibrosis, which is similar to that of non-alcoholic fatty liver disease (NAFLD). NAFPD may represent a meaningful manifestation of metabolic syndrome. Pancreatic steatosis can be diagnosed on ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). In addition to a correlation between pancreatic steatosis and metabolic syndrome, pancreatic steatosis may lead to a worse outcome in pancreatitis and may be an etiological factor in pancreatic cancer, but we need further research to examine the associations, pathophysiology, and the impact of pancreatic steatosis and NAFPD on the human health. PMID:28058076

  6. Implications and Cost of Pancreatic Leak Following Distal Pancreatic Resection

    PubMed Central

    Rodríguez, J. Rubén; Germes, Santos Soto; Pandharipande, Pari V.; Gazelle, G. Scott; Thayer, Sarah P.; Warshaw, Andrew L.; Fernández-del Castillo, Carlos

    2014-01-01

    Objectives Pancreatic stump leak (PL) after elective distal pancreatic resection significantly impacts cost and increases subsequent health care resource utilization. We sought to provide an economic framework for potential interventions aimed at reducing its occurrence. Design Retrospective case series and economic evaluation. Setting University-affiliated, tertiary care referral center. Patients Sixty-six patients undergoing elective distal, pancreatectomy. Main Outcome Measures Postoperative complications; hospital and professional costs. Results Overall postoperative morbidity occurred in 34 patients (52%) with no deaths. The total number of patients with complications directly related to PL was 22 (33%). The mean ± SD number of total hospital days for the no-PL group was 5.2 ± 1.7 days (range, 3–12 days) vs 16.6 ± 14.6 days (range, 4–49 days) for the PL group (P = .001). The average patient with PL-related problems incurred a total cost that was 2.01 times greater than the average patient in the no-PL group. A decision analytic model developed to evaluate threshold costs showed that a hypothetical intervention designed to reduce the complication rate of distal pancreatectomy by one third would be financially justifiable up to a cost of $1418 per patient. Conclusions Complications derived from PL following distal pancreatectomy double the cost and dramatically increase health care resource utilization. There is an urgent need to develop strategies that reduce the incidence of this common complication. Interventions aimed at decreasing the incidence of PL should take into account this cost differential. We provide an economic model to serve as a guide for developing these technologies. PMID:16618893

  7. Hedgehog Signaling in Pancreatic Fibrosis and Cancer.

    PubMed

    Bai, Yongyu; Bai, Yongheng; Dong, Jiaojiao; Li, Qiang; Jin, Yuepeng; Chen, Bicheng; Zhou, Mengtao

    2016-03-01

    The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies.

  8. Mediastinal Pseudocyst in Acute on Chronic Pancreatitis.

    PubMed

    Mishra, Sushil Kumar; Jain, Pawan Kumar; Gupta, Sukhdev

    2016-03-01

    Pseudocyst is a common complication of Acute and chronic pancreatitis. However, its extension into the mediastinum is a rare entity. We present a case of 52 years male with acute on chronic pancreatitis (alcohol related) who presented with dysphagia and dyspnoea and was found to have a pancreatic pseudocyst extending upto the neck. Ultrasound fails to pick up mediastinal pseudocysts and requires additional imaging modalities - CT and MRI. Management of Mediastinal pseudocyst depends upon underlying etiology, ductal anatomy, size of the pseudocyst, and availability of expertise. Small pseudocysts in asymptomatic patients may resolve spontaneously, but requires prolonged conservative therapy with somatostatin or its analogue and Total Parenteral Nutrition. Ruptured pseudocyst in a symptomatic unstable patient requires surgical resection. Endoscopic ultrasound guided drainage (transmural or transpapillary) and Main Pancreatic Duct stenting are safe and effective treatment modality.

  9. Hedgehog Signaling in Pancreatic Fibrosis and Cancer

    PubMed Central

    Bai, Yongyu; Bai, Yongheng; Dong, Jiaojiao; Li, Qiang; Jin, Yuepeng; Chen, Bicheng; Zhou, Mengtao

    2016-01-01

    Abstract The hedgehog signaling pathway was first discovered in the 1980s. It is a stem cell-related pathway that plays a crucial role in embryonic development, tissue regeneration, and organogenesis. Aberrant activation of hedgehog signaling leads to pathological consequences, including a variety of human tumors such as pancreatic cancer. Multiple lines of evidence indicate that blockade of this pathway with several small-molecule inhibitors can inhibit the development of pancreatic neoplasm. In addition, activated hedgehog signaling has been reported to be involved in fibrogenesis in many tissues, including the pancreas. Therefore, new therapeutic targets based on hedgehog signaling have attracted a great deal of attention to alleviate pancreatic diseases. In this review, we briefly discuss the recent advances in hedgehog signaling in pancreatic fibrogenesis and carcinogenesis and highlight new insights on their potential relationship with respect to the development of novel targeted therapies. PMID:26962810

  10. Researchers Identify Early Sign of Pancreatic Cancer

    MedlinePlus

    ... development of pancreatic cancer – an upsurge in certain amino acids that occurs before the disease is diagnosed and ... We found that higher levels of branched chain amino acids were present in people who went on to ...

  11. Pancreatic Adenocarcinoma Complicated by Sinistral Portal Hypertension

    PubMed Central

    Kaley, Kristin; Lamb, Lynne

    2016-01-01

    Pancreatic cancer is known for vague symptoms that lead to a delay in diagnosis, and hence most cases are found at an advanced stage. Many complications can happen secondary to pancreatic cancer including diabetes, malabsorption, and deep venous thrombosis. Sinistral (segmental or left-sided) portal hypertension (SPH) refers to portal hypertension confined to the left-sided segment of the portal venous system namely the splenic side, and the most common etiology is splenic vein thrombosis (SVT). We present here a case of a 66-year-old male with advanced pancreatic cancer who died due to bleeding secondary to SVT. We advise physicians caring for these patients to be aware of this complication, which may also be the manifestation of an undiagnosed pancreatic cancer. PMID:27555987

  12. Immune checkpoint therapy for pancreatic cancer

    PubMed Central

    Johansson, Henrik; Andersson, Roland; Bauden, Monika; Hammes, Sarah; Holdenrieder, Stefan; Ansari, Daniel

    2016-01-01

    Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy. However, due to small sample sizes, major results are not yet identifiable. The present article provides a clinical overview of immune checkpoint inhibition in pancreatic cancer. PubMed, ClinicalTrials.gov and American Society of Clinical Oncology’s meeting abstracts were systematically searched for relevant clinical studies. Four articles, five abstracts and 25 clinical trials were identified and analyzed in detail. PMID:27920468

  13. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Cancer.gov

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  14. An impacted pancreatic stone in the papilla induced acute obstructive cholangitis in a patient with chronic pancreatitis.

    PubMed

    Yoo, Kwang-Ho; Kwon, Chang-Il; Yoon, Sang-Wook; Kim, Won Hee; Lee, Jung Min; Ko, Kwang Hyun; Hong, Sung Pyo; Park, Pil Won

    2012-03-01

    Obstructive jaundice is very rarely caused by impaction of a pancreatic stone in the papilla. We report here on a case of obstructive jaundice with acute cholangitis that was caused by an impacted pancreatic stone in the papilla in a patient with chronic pancreatitis. A 48-year-old man presented with acute obstructive cholangitis. Abdominal computed tomography with the reconstructed image revealed distal biliary obstruction that was caused by a pancreatic stone in the pancreatic head, and there was also pancreatic ductal dilatation and parenchymal atrophy of the pancreatic body and tail with multiple calcifications. Emergency duodenoscopy revealed an impacted pancreatic stone in the papilla. Precut papillotomy using a needle knife was performed, followed by removal of the pancreatic stone using grasping forceps. After additional sphincterotomy, a large amount of dark-greenish bile juice gushed out. The patient rapidly improved and he has remained well.

  15. 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

  16. Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer.

    PubMed

    Wang, Jin; Raimondo, Massimo; Guha, Sushovan; Chen, Jinyun; Diao, Lixia; Dong, Xiaoqun; Wallace, Michael B; Killary, Ann M; Frazier, Marsha L; Woodward, Timothy A; Wang, Jing; Sen, Subrata

    2014-01-01

    Development of sensitive and specific biomarkers, preferably those circulating in body fluids is critical for early diagnosis of cancer. This study performed profiling of microRNAs (miRNAs) in exocrine pancreatic secretions (pancreatic juice) by microarray analysis utilizing pancreatic juice from 6 pancreatic ductal adenocarcinoma (PDAC) patients and two pooled samples from 6 non-pancreatic, non-healthy (NPNH) as controls. Differentially circulating miRNAs were subsequently validated in 88 pancreatic juice samples from 50 PDAC, 19 chronic pancreatitis (CP) patients and 19 NPNH controls. A marked difference in the profiles of four circulating miRNAs (miR-205, miR-210, miR-492, and miR-1427) was observed in pancreatic juice collected from patients with PDAC and those without pancreatic disease. Elevated levels of the four miRNAs together predicted PDAC with a specificity of 88% and sensitivity of 87%. Inclusion of serum CA19-9 level increased the sensitivity to 91% and the specificity to 100%. Enrichment of the four miRNAs in pancreatic juice was associated with decreased OS, as was the combination of miR-205 and miR-210. Higher contents of miR-205 and miR-210 were also associated with lymph node metastasis. Elevated levels of circulating miR-205, miR-210, miR-492, and miR-1247 in pancreatic juice are, therefore, promising candidate biomarkers of disease and poor prognosis in patients with PDAC.

  17. Surgical treatment of the pancreatic stump: preventive strategies of pancreatic fistula after pancreatoduodenectomy for cancer

    PubMed Central

    TERSIGNI, R.; CAPALDI, M.; IALONGO, P.; GRILLO, L.R.; ANSELMO, A.

    2014-01-01

    Background The institutions with high volume of pancreatic surgery report morbidity rate from 30% to 50% and mortality less than 5% after pancreaticoduodenectomy (PD). At the present, the most significant cause of morbidity and mortality is pancreatic fistula (PF). Aim The purpose of the study is to identify the most important clinical factors which may predict PF development and eventually suggest alternative approaches to the pancreatic stump management. Patients and methods A retrospective analysis of a clinical data base of a tertiary care Hospital was performed. From 2002 to 2012 a single Surgeon prospectively performed 150 pancreaticoduodenectomies for cancer. Four different techniques were used: end to end pancreaticojejunostomy, end to side pancreaticojejunostomy, pancreatic duct occlusion and duct to mucosa anastomosis. The intraoperative gland texture was classified as soft, firm and hard. The duct size was preoperatively (CT scan) and intraoperatively recorded and classified: < 3 mm small, 3–6 mm medium, > 6 mm large. The histopathological characteristic of the gland fibrosis was graduate as low 1, moderate 2, high 3. Conclusion Relationships between pre and intraoperative duct size measurement, pancreatic texture and pancreatic fibrosis grading were highly significant. Small duct and soft pancreas with low grade fibrosis are the most important risk factors for pancreatic fistula development. The proper selection of pancreatic stump management or the decision to refer the high risk patients to high volume Center can be suggested by the elevated correspondence of pre and intraoperative duct diameter with the related pancreatic fibrosis grade and gland consistency. Preoperative assessment of the pancreatic duct makes possible to predict the risk of pancreatic fistula. PMID:25419587

  18. Effect of taurine on acinar cell apoptosis and pancreatic fibrosis in dibutyltin dichloride-induced chronic pancreatitis.

    PubMed

    Matsushita, Koki; Mizushima, Takaaki; Shirahige, Akinori; Tanioka, Hiroaki; Sawa, Kiminari; Ochi, Koji; Tanimoto, Mitsune; Koide, Norio

    2012-01-01

    The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC)-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.

  19. [Correlation between hyperamylasemia and acute pancreatitis].

    PubMed

    Monaco, R; Durante, E; Pampolini, M; Tioli, P

    1981-05-31

    It is often difficult to differentiate acute pancreatitis (A.P.) from some other acute abdominal diseases, when there is an elevated serum amylase. In contrast, the renal clearance of amylase, expressed as a percentage of creatinine clearance, can separate patients with A.P. from patients with acute colecistitis, common duct stone without pancreatitis, hyperamylasemia after biliary surgery, acute peptic ulcer and acute salivary diseases.

  20. Minimally invasive surgical approach to pancreatic malignancies

    PubMed Central

    Bencini, Lapo; Annecchiarico, Mario; Farsi, Marco; Bartolini, Ilenia; Mirasolo, Vita; Guerra, Francesco; Coratti, Andrea

    2015-01-01

    Pancreatic surgery for malignancy is recognized as challenging for the surgeons and risky for the patients due to consistent perioperative morbidity and mortality. Furthermore, the oncological long-term results are largely disappointing, even for those patients who experience an uneventfully hospital stay. Nevertheless, surgery still remains the cornerstone of a multidisciplinary treatment for pancreatic cancer. In order to maximize the benefits of surgery, the advent of both laparoscopy and robotics has led many surgeons to treat pancreatic cancers with these new methodologies. The reduction of postoperative complications, length of hospital stay and pain, together with a shorter interval between surgery and the beginning of adjuvant chemotherapy, represent the potential advantages over conventional surgery. Lastly, a better cosmetic result, although not crucial in any cancerous patient, could also play a role by improving overall well-being and patient self-perception. The laparoscopic approach to pancreatic surgery is, however, difficult in inexperienced hands and requires a dedicated training in both advanced laparoscopy and pancreatic surgery. The recent large diffusion of the da Vinci® robotic platform seems to facilitate many of the technical maneuvers, such as anastomotic biliary and pancreatic reconstructions, accurate lymphadenectomy, and vascular sutures. The two main pancreatic operations, distal pancreatectomy and pancreaticoduodenectomy, are approachable by a minimally invasive path, but more limited interventions such as enucleation are also feasible. Nevertheless, a word of caution should be taken into account when considering the increasing costs of these newest technologies because the main concerns regarding these are the maintenance of all oncological standards and the lack of long-term follow-up. The purpose of this review is to examine the evidence for the use of minimally invasive surgery in pancreatic cancer (and less aggressive tumors

  1. Nutritional support in acute and chronic pancreatitis.

    PubMed

    Grant, John P

    2011-08-01

    Nutritional support can have a significant beneficial impact on the course of moderate to severe acute pancreatitis. Enteral nutrition is preferred, with emphasis on establishment of jejunal access; however, parenteral nutrition can also be of value if intestinal failure is present. Early initiation of nutritional support is critical, with benefits decreasing rapidly if begun after 48 hours from admission. Severe malnutrition in chronic pancreatitis can be avoided or treated with dietary modifications or enteral nutrition.

  2. Acute pancreatitis in infants and children.

    PubMed Central

    Hillemeier, C.; Gryboski, J. D.

    1984-01-01

    Acute pancreatitis is being encountered more often in children due to antimetabolite therapy, accidental injury, and traumatic battering. Pancreatitis may occur in the absence of traditionally elevated serum amylase and lipase, and initial diagnosis may depend upon ultrasonography. Traditional therapy of enteric rest with nasogastric suction has been supported by the use of parenteral nutrition. Newer pharmaceutical agents have been ineffective in altering the course of the illness or in preventing complications of pseudocyst or abscess. PMID:6382834

  3. [Pathology and clinical course of pancreatic pseudocyst].

    PubMed

    Giacomelli, L; Brescia, A; Miglietta, A M; Pulcini, A; Finizio, A; Porcelli, C; Manno, A

    1993-01-01

    According to the literature and the personal experience of the authors there seem to exist many controversies on the treatment of pancreatic pseudocysts, partly due to the lack of definitions and to the fact that prognosis is different based upon the pathophysiology of the lesions. We report 4 cases of pancreatic pseudocysts successfully treated with a multidisciplinary approach, stressing the role of pharmacology and of artificial nutrition and endoscopy on the outcome of these lesions.

  4. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  5. Percutaneous catheter drainage of pancreatic pseudocysts.

    PubMed

    Adams, D B; Harvey, T S; Anderson, M C

    1991-01-01

    Pancreatic pseudocysts represent a complication of severe pancreatic inflammatory disease. Although operative drainage is the cornerstone of therapy for pseudocysts, we have undertaken percutaneous catheter drainage in a selected group of 28 patients over a six-year period (1982-88). This represents 42 per cent of pseudocyst patients managed by the senior author and 1.7 per cent of admissions for pancreatitis at the Medical University Hospitals during that period of time. There were 26 men and two women with an age range of 26-66 years (mean = 42.1). Twenty-six patients had alcohol abuse as the cause of pancreatitis; two were due to surgical trauma. Nondilated pancreatic ducts were demonstrated in 25 patients. Six had pancreatic ascites associated with pseudocysts. Four had previous operative drainage (2 internal and 2 external drainage procedures). Five patients received octreotide acetate, a synthetic peptide which mimics the action of somatostatin, in an attempt to aid closure of external fistulas. The mean length of catheter drainage was 48 days (range 7-210 days). Eight (29%) patients developed procedure-related complications (1 pneumothorax, 1 sheared guidewire, six drain tract infections). There was no mortality. Successful resolution of pseudocysts was achieved in 26 patients (93%). Two patients subsequently had elective caudal pancreaticojejunostomy (CPJ), and one lateral pancreaticojejunostomy (LPJ) to drain obstructed pancreatic ducts. One patient has required repeat external drainage. Percutaneous external drainage is successful in pseudocyst eradication. When underlying pancreatic pathology remains uncorrected, elective surgical decompression of obstructed, dilated ducts may be necessary.

  6. Pinealectomy aggravates acute pancreatitis in the rat.

    PubMed

    Jaworek, Jolanta; Zwirska-Korczala, Krystyna; Szklarczyk, Joanna; Nawrot-Porąbka, Katarzyna; Leja-Szpak, Anna; Jaworek, Andrzej K; Tomaszewska, Romana

    2010-01-01

    Melatonin, a pineal indoleamine, protects the pancreas against acute damage; however, the involvement of the pineal gland in the pancreatoprotective action of melatonin is unknown. The primary aim of this study was to determine the effects of pinealectomy on the course of acute caerulein-induced pancreatitis (AP) in rats. AP was induced by a subcutaneous infusion of caerulein (25 μg/kg) into pinealectomized or sham-operated animals. Melatonin (5 or 25 mg/kg) was given via intraperitoneal (ip) injection 30 min prior to the induction of AP. The pancreatic content of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative enzyme, glutathione peroxidase (GSH-Px), were measured in each group of rats. Melatonin blood levels were measured by radioimmunoassay (RIA). In the sham-operated rats, AP was confirmed with histological examination and manifested as pancreatic edema and an increase in the blood lipase level (by 1,500%). In addition, the pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic glutathione peroxydase (GSH-Px) activity was reduced by 40%. Pinealectomy significantly aggravated the histological manifestations of AP, reduced the GSH-Px activity and markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or without AP as compared to sham-operated animals. Melatonin was undetectable in the blood of the pinealectomized rats with or without AP. Treatment with melatonin (25 mg/kg, ip) prevented the development of AP in the sham-operated rats and significantly reduced pancreatic inflammation in the animals previously subjected to pinealectomy. In conclusion, pineal melatonin contributes to the pancreatic protection through the activation of the antioxidative defense mechanism in pancreatic tissue as well as its direct antioxidant effects.

  7. Pancreatic carcinoma: results with fast neutron therapy

    SciTech Connect

    Kaul, R.; Cohen, L.; Hendrickson, F.; Awschalom, M.; Hrejsa, A.F.; Rosenberg, I.

    1981-02-01

    Results of therapy in 31 of 50 patients who were treated for advanced pancreatic carcinoma at Fermi National Accelerator Laboratory are presented here. To date, six patients are alive and four are free of disease. Since the main reason for failure was lack of control of primary tumor, the tumor dose has been increased by 15%. Based on our results, a nationwide study has been launched to assess the effectiveness of neutrons vs photons in the treatment of locally advanced pancreatic carcinoma.

  8. Systemic Therapies for Advanced Pancreatic Neuroendocrine Tumors

    PubMed Central

    Raj, Nitya; Reidy-Lagunes, Diane

    2016-01-01

    SYNOPSIS Pancreatic neuroendocrine tumors are a rare tumor type, and comprise 1-2% of all pancreatic neoplasms. When nonfunctional (i.e. nonhormone secreting), these tumors generally cause few symptoms and often go unnoticed for several years; for this reason, they are rarely localized at presentation, and are typically diagnosed in the presence of metastatic disease, most commonly to the liver. Although pancreatic neuroendocrine tumors can be less aggressive than other tumor types, the management poses a significant challenge because of the heterogeneous clinical presentations and varying degrees of aggressiveness. The therapy of pancreatic neuroendocrine tumors includes a multimodality approach and can often include surgery, liver-directed therapies (i.e. embolization), as well as targeted and cytotoxic systemic treatments. A variety of systemic therapies have been developed for the management of pancreatic neuroendocrine tumors. These therapies include somatostatin analogs (octreotide or lanreotide), a select group of cytotoxic chemotherapy agents (alkylating, fluorouracil and platinum drugs), as well as targeted or biologic agents (everolimus and sunitinib). This chapter will review the available systemic therapy options for advanced pancreatic neuroendocrine tumors. PMID:26614372

  9. L-arginine-induced experimental pancreatitis

    PubMed Central

    Hegyi, Péter; Jr, Zoltán Rakonczay; Sári, Réka; Góg, Csaba; Lonovics, János; Takács, Tamás; Czakó, László

    2004-01-01

    Despite medical treatment, the lethality of severe acute pancreatitis is still high (20%-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et al[1] developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis. Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model. Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis. PMID:15237423

  10. Treatment of Pancreatic Cancer with Pharmacological Ascorbate.

    PubMed

    Cieslak, John A; Cullen, Joseph J

    2015-01-01

    The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.

  11. Antibacterial activity of the pancreatic fluid.

    PubMed

    Rubinstein, E; Mark, Z; Haspel, J; Ben-Ari, G; Dreznik, Z; Mirelman, D; Tadmor, A

    1985-04-01

    The antibacterial activity of canine pancreatic fluid was investigated in an attempt to understand the resistance of this organ, when intact, to ascending bacterial infections. The pancreatic fluid demonstrated bactericidal activity against Escherichia coli, Shigella species, Salmonella species, and Klebsiella pneumoniae; bacteriostatic activity against coagulase-positive and coagulase-negative staphylococci and Pseudomonas aeruginosa; and fungistatic activity against Candida albicans. There was no demonstrable antibacterial activity against Bacteroides fragilis and Streptococcus faecalis. The antibacterial activity was dialyzable and pH dependent, but independent of heat, the activity of several digestive pancreatic enzymes, and the bacterial inoculum. Electron micrographs of Escherichia coli exposed to pancreatic fluid did not demonstrate changes in the bacterial cell wall. Tracer studies of susceptible bacteria demonstrated decreased leucine uptake when briefly exposed to pancreatic fluid. The antibacterial activity was found by column chromatography to be a small molecular peptide. It is likely that pancreatic antibacterial factors protect the pancreas from ascending bacterial infections and operate along with other factors in the homeostasis of the upper small bowel flora.

  12. [Intraductal papillary mucinous neoplasm and recurrent pancreatitis].

    PubMed

    Gálvez, Eduardo; Gálvez, Gustavo; Barboza, Aurelio; Barboza, Eduardo; Combe, Juan Manuel; Combe, Mario R; Combe, Juan; Arias Stella C, Javier; Arias Stella, Javier

    2013-01-01

    Ohashi described for the first time the IPMN on 1982 as a pancreatic neoplasia with mucine cells forming papillae and producing dilatation of the main pancreatic duct or its branches. The IPMN represent the 1% of the pancreatic tumors and 5% of the cystic neoplasias. It is potentially malignant in a period of five years being more frequent in males between 60-70 and clinically these patients' presents as acute, recurrent or chronic pancreatitis, with an incidence of malignancy from 25% to 70%. CT scan and cholangio MRI allows the diagnosis, the variety, localization and possibility of determine malignancy. The treatment is the Whipple resection. We are reporting the case of an obese middle age male, being observed along the last 10 years because of recurrent pancreatitis with a cystic lesion of the head of the pancreas. The CT scan, endoscopic-ultrasound and the analysis of the liquid content suggested a mucinous lesion, reason why the patient underwent a pancreatic-duodenal resection. The histology study confirms the diagnosis of IPMN.

  13. Preclinical fluorescent mouse models of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Bouvet, Michael; Hoffman, Robert M.

    2007-02-01

    Here we describe our cumulative experience with the development and preclinical application of several highly fluorescent, clinically-relevant, metastatic orthotopic mouse models of pancreatic cancer. These models utilize the human pancreatic cancer cell lines which have been genetically engineered to selectively express high levels of the bioluminescent green fluorescent (GFP) or red fluorescent protein (RFP). Fluorescent tumors are established subcutaneously in nude mice, and tumor fragments are then surgically transplanted onto the pancreas. Locoregional tumor growth and distant metastasis of these orthotopic implants occurs spontaneously and rapidly throughout the abdomen in a manner consistent with clinical human disease. Highly specific, high-resolution, real-time visualization of tumor growth and metastasis may be achieved in vivo without the need for contrast agents, invasive techniques, or expensive imaging equipment. We have shown a high correlation between florescent optical imaging and magnetic resonance imaging in these models. Alternatively, transplantation of RFP-expressing tumor fragments onto the pancreas of GFP-expressing transgenic mice may be used to facilitate visualization of tumor-host interaction between the pancreatic tumor fragments and host-derived stroma and vasculature. Such in vivo models have enabled us to serially visualize and acquire images of the progression of pancreatic cancer in the live animal, and to demonstrate the real-time antitumor and antimetastatic effects of several novel therapeutic strategies on pancreatic malignancy. These fluorescent models are therefore powerful and reliable tools with which to investigate human pancreatic cancer and therapeutic strategies directed against it.

  14. Endoscopic management of pain in pancreatic cancer.

    PubMed

    Mekaroonkamol, Parit; Willingham, Field F; Chawla, Saurabh

    2015-01-31

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and one of the leading causes of cancer mortality in the United States. Due to its aggressive behavior and lack of effective therapies, palliation plays a critical role in the management of the disease. Most patients with pancreatic cancer suffer from severe pain, which adversely predicts prognosis and significantly impacts the quality of life. Therefore pain management plays a central role in palliation. Non-steroidal anti-inflammatory drugs and opioid agents are often first line medications in pain management, but they do not target the underlying pathophysiology of pain and their use is limited by adverse effects and dependence. The proposed mechanisms of pain development in pancreatic cancer include neurogenic inflammation and ductal hypertension which may be targeted by endoscopic therapies. Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) and pancreatic duct stent placement are the two primary endoscopic modalities for palliative management in pancreatic cancer patients with refractory pain.  Other endoscopic treatments such as biliary stent placement and enteral stent placement for biliary and duodenal obstruction may also help palliate pain in addition to their role in decompression. This article reviews the existing evidence for these endoscopic interventions for pain management in pancreatic cancer.

  15. Pancreatic Cancer Chemoprevention Translational Workshop: Meeting Report.

    PubMed

    Miller, Mark Steven; Allen, Peter; Brentnall, Teresa A; Goggins, Michael; Hruban, Ralph H; Petersen, Gloria M; Rao, Chinthalapally V; Whitcomb, David C; Brand, Randall E; Chari, Suresh T; Klein, Alison P; Lubman, David M; Rhim, Andrew D; Simeone, Diane M; Wolpin, Brian M; Umar, Asad; Srivastava, Sudhir; Steele, Vernon E; Rinaudo, Jo Ann S

    2016-09-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 10%. The Division of Cancer Prevention of the National Cancer Institute sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10 to 11, 2015. The goal of the workshop was to obtain information regarding the current state of the science and future scientific areas that should be prioritized for pancreatic cancer prevention research, including early detection and intervention for high-risk precancerous lesions. The workshop addressed the molecular/genetic landscape of pancreatic cancer and precursor lesions, high-risk populations and criteria to identify a high-risk population for potential chemoprevention trials, identification of chemopreventative/immunopreventative agents, and use of potential biomarkers and imaging for assessing short-term efficacy of a preventative agent. The field of chemoprevention for pancreatic cancer is emerging, and this workshop was organized to begin to address these important issues and promote multi-institutional efforts in this area. The meeting participants recommended the development of an National Cancer Institute working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer.

  16. HEPATOBILIARY ASCARIASIS COMPLICATED BY PANCREATITIS.

    PubMed

    Azhar, Muhammad; Sheikh, Ali Sibtain Farooq; Khan, Asim; Mustafa, Saqib; Shah, Imran Ali; Hameed, Bilal

    2015-01-01

    Ascaris lumbricoides is the commonest organism causing soil-transmitted helminth infection. It is particularly common in poor sanitary conditions. Nevertheless, involvement of the gallbladder by Ascaris is a rare entity. A lady presented to us with long-standing history of vague abdominal symptoms suggesting dyspepsia. Ultrasound showed a tube like structure invading the biliary channels. Serum amylase was elevated and the patient was managed conservatively, as for acute pancreatitis. She improved clinically, but subsequent imaging with magnetic resonance cholangiopancreatography revealed worm in the gallbladder. Laparoscopic cholecystectomy was done and Ascaris lumbricoides was removed. Ascaris infestation is an important differential diagnosis of patients with upper abdominal symptoms and screening with stool examination and ultrasound is warranted in high-risk population.

  17. [Radiation therapy of pancreatic cancer].

    PubMed

    Huguet, F; Mornex, F; Orthuon, A

    2016-09-01

    Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In adjuvant setting, the standard treatment is 6 months of chemotherapy with gemcitabine and capecitabine. Chemoradiation (CRT) may improve the survival of patients with incompletely resected tumors (R1). This should be confirmed by a prospective trial. Neoadjuvant CRT is a promising treatment especially for patients with borderline resectable tumors. For patients with locally advanced tumors, there is no a standard. An induction chemotherapy followed by CRT for non-progressive patients reduces the rate of local relapse. Whereas in the first trials of CRT large fields were used, the treated volumes have been reduced to improve tolerance. Tumor movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique is not recommended.

  18. [Fluid therapy in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2013-12-01

    Severe acute pancreatitis (AP) is associated with an increased need for fluids due to fluid sequestration and, in the most severe cases, with decreased peripheral vascular tone. For several decades, clinical practice guidelines have recommended aggressive fluid therapy to improve the prognosis of AP. This recommendation is based on theoretical models, animal studies, and retrospective studies in humans. Recent studies suggest that aggressive fluid administration in all patients with AP could have a neutral or harmful effect. Fluid therapy based on Ringer's lactate could improve the course of the disease, although further studies are needed to confirm this possibility. Most patients with AP do not require invasive monitoring of hemodynamic parameters to guide fluid therapy administration. Moreover, the ability of these parameters to improve prognosis has not been demonstrated.

  19. Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery

    ClinicalTrials.gov

    2017-04-13

    Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

  20. Pancreatic protein hypersecretion and elevated plasma CCK: prerequisites for increased pancreatic growth?

    PubMed

    Rivard, N; Guan, D; Maouyo, D; Morisset, J

    1993-09-01

    This study was undertaken to establish if a correlation exists between chronic elevated pancreatic secretion and growth of the pancreas. Rats provided with jugular, pancreatic, biliary, duodenal, or ileal cannulas were fed throughout the experiment with a liquid diet continuously infused into the duodenum. Four days after surgery, control rats and those infused with cerulein (CE) 0.45 microgram/kg/h had their pancreatic juice returned into the duodenum. Two other groups had their pancreatic juice either totally diverted outside (DO) or returned into the ileum (DI). In all groups, bile was returned into the duodenum. Pancreatic juice was collected every 4 h for 4 days with volume and protein determined. After 4 days, rats were killed and their pancreata were evaluated for weight and contents of DNA, RNA, protein, amylase, and chymotrypsinogen. The average volumes/4 h were significantly increased by 259, 241, and 270% in DO, DI, and CE rats, respectively. Protein output remained at control levels in DO rats, whereas increases of 200 and 90% above control values were observed in DI and CE rats, respectively, during the last periods of collection. Constant drainage of pancreatic juice outside (DO) had no effect on pancreatic growth; on the contrary, its reinfusion into the ileum and constant cerulein infusion were associated with impressive growth of the pancreas, with cerulein being the most potent stimulus. In conclusion these data support the hypothesis that increased protein output is associated with pancreatic growth, a phenomenon mediated by endogenous cholecystokinin.

  1. Targeting pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

    PubMed Central

    Madka, Venkateshwar; Brewer, Misty; Ritchie, Rebekah L.; Lightfoot, Stan; Kumar, Gaurav; Sadeghi, Michael; Patlolla, Jagan Mohan R.; Yamada, Hiroshi Y.; Cruz-Monserrate, Zobeida; May, Randal; Houchen, Courtney W.; Steele, Vernon E.; Rao, Chinthalapally V.

    2015-01-01

    Recent development of genetically engineered mouse models (GEMs) for pancreatic cancer (PC) that recapitulates human disease progression has helped to identify new strategies to delay/inhibit PC development. We first found that expression of the pancreatic tumor-initiating/cancer stem cells (CSC) marker DclK1 occurs in early stage PC and in both early and late pancreatic intraepithelial neoplasia (PanIN) and that it increases as disease progresses in GEM and also in human PC. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEM mice revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase-2 (COX-2) decreased DclK1 in GEM. Induction of inflammation/pancreatitis with cerulein in GEM mice increased DclK1, and the novel dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone reduced it. Dietary licofelone significantly inhibited the incidence of PDAC and carcinoma in situ with significant inhibition of pancreatic CSCs. Licofelone suppressed pancreatic tumor COX-2 and 5-LOX activities and modulated miRNAs characteristic of CSC and inflammation in correlation with PDAC inhibition. These results offer a preclinical proof of concept to target the inflammation initiation to inhibit cancer stem cells early for improving the treatment of pancreatic cancers, with immediate clinical implications for repositioning dual COX/5-LOX inhibitors in human trials for high risk patients. PMID:25906749

  2. [Acute pancreatitis. Evidence-based practice guidelines, prepared by the Hungarian Pancreatic Study Group].

    PubMed

    Hritz, István; Czakó, László; Dubravcsik, Zsolt; Farkas, Gyula; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Szücs, Ákos; Takács, Tamás; Tiszlavicz, László; Hegyi, Péter

    2015-02-15

    Acute pancreatitis is one of the most common diseases of the gastrointestinal tract associated with significant morbidity and mortality that requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare evidence based guideline for the medical and surgical management of acute pancreatitis based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and, if it was necessary, complemented and/or modified the international guidelines. All together 42 relevant clinical questions were defined in 11 topics (Diagnosis and etiology, Prognosis, Imaging, Fluid therapy, Intensive care management, Prevention of infectious complications, Nutrition, Biliary interventions, Post-endoscopic retrograde cholangio-pancreatography pancreatitis, Indication, timing and strategy for intervention in necrotizing pancreatitis, Timing of cholecystectomy [or endoscopic sphincterotomy]). Evidence was classified according to the UpToDate® grading system. The draft of the guideline was presented and discussed at the consensus meeting on September 12, 2014. 25 clinical questions with almost total (more than 95%) and 17 clinical questions with strong (more than 70%) agreement were accepted. The present guideline is the first evidence based acute pancreatitis guideline in Hungary. The guideline may provide important help for tuition, everyday practice and for establishment of proper finance of acute pancreatitis. Therefore, the authors believe that these guidelines will widely become as basic reference in Hungary.

  3. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis.

    PubMed

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fábio Payão; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation -, and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients.

  4. The use of pancreatic ductoscopy in the operative management of benign and malignant pancreatic disorders.

    PubMed

    Branum, G D; Pappas, T N; Meyers, W C

    1995-01-01

    Direct visualization of the pancreatic duct was helpful in decision making during complex pancreaticobiliary operations. Two-, 3-, or 5-mm scopes were introduced into the pancreatic ducts of 32 patients with pancreatic disorders. Scopes were passed into the ductal system of: (1) 16 patients undergoing pancreaticojejunostomy; (2) six patients undergoing pancreaticoduodenectomy; (3) four patients with pancreatic pseudocysts or choledochal cysts: (4) two patients undergoing resection of the pancreatic tail; and (5) two patients undergoing accessory ductoplasty for pancreas divism or stricture. Eight patients had calculi removed utilizing the scope, and multiple strictures were identified and filleted. Pancreatic ductoscopy was used in two patients to document successful sphincteroplasty of an accessory duct. In two instances benign pancreatic duct tumors were removed. Pancreatic ductoscopy was used to search for coexistent duct neoplasms in the eight patients who underwent resection. The technique permits intraoperative inspection, biopsy, and removal of lesions intrinsic to the ductal system. Combined with surgical procedures this endoscopic method proved a useful adjunct in difficult cases.

  5. Pancreatitis

    MedlinePlus

    ... Treatment is usually a few days in the hospital for intravenous (IV) fluids, antibiotics, and medicines to ... may also be a few days in the hospital for intravenous (IV) fluids, medicines to relieve pain, ...

  6. Pancreatitis

    MedlinePlus

    ... proteins called enzymes that are important in the digestion of proteins, fats, and sugars. The pancreas also ... occurs it may lead to chronic problems with digestion, dia- betes, and recurrent or persistent pain. In ...

  7. Evaluation of Matrix Metalloproteinase 7 in Plasma and Pancreatic Juice as a Biomarker for Pancreatic Cancer

    PubMed Central

    Kuhlmann, Koert F.D.; van Till, J.W. Olivier; Boermeester, Marja A.; de Reuver, Philip R.; Tzvetanova, Iva D.; Offerhaus, G. Johan A.; ten Kate, Fiebo J.W.; Busch, Olivier R.C.; van Gulik, Thomas M.; Gouma, Dirk J.; Crawford, Howard C.

    2015-01-01

    Differentiating between periampullary carcinoma and chronic pancreatitis with an inflammatory mass is difficult. Consequently, 6% to 9% of pancreatic resections for suspected carcinoma are done inappropriately for chronic pancreatitis. Here, we test if matrix metalloproteinase 7 (MMP-7), a secreted protease frequently expressed in pancreatic carcinoma, can be measured in plasma, pancreatic, and duodenal juice, and if it can distinguish between periampullary carcinoma and chronic pancreatitis. Ninety-four patients who underwent pancreatic surgery for a (peri)pancreatic neoplasm (n = 63) or chronic pancreatitis (n = 31) were analyzed. Median plasma MMP-7 levels were significantly higher in carcinoma (1.95 ng/mL; interquartile range, 0.81–3.22 ng/mL) compared with chronic pancreatitis and benign disease (0.83 ng/mL; interquartile range, 0.25–1.21 ng/mL; P < 0.01). MMP-7 levels in pancreatic juice were higher, although not significantly, in carcinoma (62 ng/mg protein; interquartile range, 18–241 ng/mg protein) compared with chronic pancreatitis and benign disease (23 ng/mg protein; interquartile range, 8.5–99 ng/mg protein; P = 0.17). MMP-7 levels in duodenal juice were universally low. At an arbitrary cutoff of 1.5 ng/mL in plasma, positive and negative predictive values were 83% and 57%, respectively, values comparable to those of today’s most common pancreatic tumor marker, carbohydrate antigen 19-9 (CA19-9; 83% and 53%, respectively). Positive and negative likelihood ratios for plasma MMP-7 were 3.35 and 0.52, respectively. The area under the receiver operating characteristic curve for MMP-7 was 0.73 (95% confidence interval, 0.63–0.84) and for CA19-9, 0.75 (95% confidence interval, 0.64–0.85). Combined MMP-7 and CA19-9 assessment gave a positive predictive value of 100%. Thus, plasma MMP-7 levels discriminated between patients with carcinoma and those with chronic pancreatitis or benign disease. The diagnostic accuracy of plasma MMP-7 alone is not

  8. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma.

    PubMed

    Mazur, Pawel K; Einwächter, Henrik; Lee, Marcel; Sipos, Bence; Nakhai, Hassan; Rad, Roland; Zimber-Strobl, Ursula; Strobl, Lothar J; Radtke, Freddy; Klöppel, Günter; Schmid, Roland M; Siveke, Jens T

    2010-07-27

    Pancreatic cancer is one of the most fatal malignancies lacking effective therapies. Notch signaling is a key regulator of cell fate specification and pancreatic cancer development; however, the role of individual Notch receptors and downstream signaling is largely unknown. Here, we show that Notch2 is predominantly expressed in ductal cells and pancreatic intraepithelial neoplasia (PanIN) lesions. Using genetically engineered mice, we demonstrate the effect of conditional Notch receptor ablation in KrasG12D-driven pancreatic carcinogenesis. Deficiency of Notch2 but not Notch1 stops PanIN progression, prolongs survival, and leads to a phenotypical switch toward anaplastic pancreatic cancer with epithelial-mesenchymal transition. By expression profiling, we identified increased Myc signaling regulated by Notch2 during tumor development, placing Notch2 as a central regulator of PanIN progression and malignant transformation. Our study supports the concept of distinctive roles of individual Notch receptors in cancer development.

  9. Focal autoimmune pancreatitis and chronic sclerosing sialadenitis mimicking pancreatic cancer and neck metastasis.

    PubMed

    Sun, Li; Zhou, Qiang; Brigstock, David R; Yan, Su; Xiu, Ming; Piao, Rong-Li; Gao, Yan-Hang; Gao, Run-Ping

    2014-12-14

    Type 1 autoimmune pancreatitis (AIP) or chronic sclerosing sialadenitis (Küttner's tumour) is an uncommon disorder that has recently been confirmed as an IgG4-related disease. Here, we describe a rare case of a 53-year-old male patient who primarily presented with pancreatic body mass, left neck mass and several lumps in his lower lip mimicking pancreatic cancer (PC) and neck metastasis. The patient underwent pancreatic body mass and labial gland lumps resection as well as an ultrasound-guided biopsy of the left neck mass. He was diagnosed with IgG4-related focal type of AIP (f-AIP) and Küttner's tumour by immunohistochemistry. The patient responded well to corticosteroid therapy and remains healthy with no signs of recurrence at one year follow-up. The differentiation of f-AIP from PC is very important to avoid unnecessary pancreatic resection.

  10. Timing of cholecystectomy in biliary pancreatitis treatment

    PubMed Central

    Demir, Uygar; Yazıcı, Pınar; Bostancı, Özgür; Kaya, Cemal; Köksal, Hakan; Işıl, Gürhan; Bozdağ, Emre; Mihmanlı, Mehmet

    2014-01-01

    Objective: Gallstone pancreatitis constitutes 40% of all cases with pancreatitis while it constitutes up to 90% of cases with acute pancreatitis. The treatment modality in this patient population is still controversial. In this study, we aimed to compare the results of early and late cholecystectomy for patients with biliary pancreatitis. Material and Methods: Patients treated with a diagnosis of acute biliary pancreatitis in our clinics between January 2000 and December 2011 were retrospectively reviewed. Patients were divided into two groups: Group A, patients who underwent cholecystectomy during the first pancreatitis attack, Group B, patients who underwent an interval cholecystectomy at least 8 weeks after the first pancreatitis episode. The demographic characteristics, clinical symptoms, number of episodes, length of hospital stay, morbidity and mortality data were recorded. All data were evaluated with Statistical Package for the Social Sciences (SPSS) 13.0 for windows and p <0.05 was considered as statistically significant. Results: During the last 12 years, a total of 91 patients with surgical treatment for acute biliary pancreatitis were included into the study. There were 62 female and 29 male patients, with a mean age of 57.9±14.6 years (range: 21–89). A concomitant acute cholecystitis was present in 46.2% of the patients. Group A and B included 48 and 43 patients, respectively. The length of hospital stay was significantly higher in group B (9.4 vs. 6.8 days) (p<0,05). More than half of the patients in Group B were readmitted to the hospital for various reasons. No significant difference was observed between the two groups, one patient died due to heart failure in the postoperative period in group B. Conclusion: In-hospital cholecystectomy after remission of acute pancreatitis is feasible. It will not only result in lower recurrence and complication rates but also shorten length of hospital stay. We recommend performing cholecystectomy during the

  11. Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

    PubMed

    Treiber, Matthias; Schulz, Hans-Ulrich; Landt, Olfert; Drenth, Joost P H; Castellani, Carlo; Real, Francisco X; Akar, Nejat; Ammann, Rudolf W; Bargetzi, Mario; Bhatia, Eesh; Demaine, Andrew Glenn; Battagia, Cinzia; Kingsnorth, Andrew; O'Reilly, Derek; Truninger, Kaspar; Koudova, Monika; Spicak, Julius; Cerny, Milos; Menzel, Hans-Jürgen; Moral, Pedro; Pignatti, Pier Franco; Romanelli, Maria Grazia; Rickards, Olga; De Stefano, Gian Franco; Zarnescu, Narcis Octavian; Choudhuri, Gourdas; Sikora, Sadiq S; Jansen, Jan B M J; Weiss, Frank Ulrich; Pietschmann, Matthias; Teich, Niels; Gress, Thomas M; Ockenga, Johann; Schmidt, Hartmut; Kage, Andreas; Halangk, Juliane; Rosendahl, Jonas; Groneberg, David Alexander; Nickel, Renate; Witt, Heiko

    2006-12-01

    Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

  12. Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis

    PubMed Central

    Mews, P; Phillips, P; Fahmy, R; Korsten, M; Pirola, R; Wilson, J; Apte, M

    2002-01-01

    Background: It is now generally accepted that chronic pancreatic injury and fibrosis may result from repeated episodes of acute pancreatic necroinflammation (the necrosis-fibrosis sequence). Recent studies suggest that pancreatic stellate cells (PSCs), when activated, may play an important role in the development of pancreatic fibrosis. Factors that may influence PSC activation during pancreatic necroinflammation include cytokines known to be important in the pathogenesis of acute pancreatitis, such as tumour necrosis factor α (TNF-α), and the interleukins 1, 6, and 10 (IL-1, IL-6, and IL-10). Aim: To determine the effects of these cytokines on PSC activation, as assessed by cell proliferation, α smooth muscle actin (α-SMA) expression, and collagen synthesis. Methods: Cultured rat PSCs were incubated with cytokines for 24 hours. Cell proliferation was assessed by measuring 3H thymidine incorporation into cellular DNA, α-SMA expression by western blotting, and collagen synthesis by incorporation of 14C proline into collagenase sensitive protein. mRNA levels for procollagen α1(1) in PSCs were determined by northern and dot blotting methods. Results: Expression of α-SMA by PSCs was increased on exposure to each of the cytokines used in the study. Stellate cell proliferation was stimulated by TNF-α but inhibited by IL-6, while IL-1 and IL-10 had no effect on PSC proliferation. Collagen synthesis by PSCs was stimulated by TNF-α and IL-10, inhibited in response to IL-6, and unaltered by IL-1. Changes in collagen protein synthesis in response to TNF-α, IL-10, and IL-6 were not regulated at the mRNA level in the cells. Conclusion: This study has demonstrated that PSCs have the capacity to respond to cytokines known to be upregulated during acute pancreatitis. Persistent activation of PSCs by cytokines during acute pancreatitis may be a factor involved in the progression from acute pancreatitis to chronic pancreatic injury and fibrosis. PMID:11889076

  13. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    SciTech Connect

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- 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 is 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. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  14. The role of transpapillary drainage in management of patients with pancreatic fluid collections and pancreatic duct disruption as a consequences of severe acute pancreatitis.

    PubMed

    Jagielski, Mateusz; Smoczyński, Marian; Adrych, Krystian

    In last thirty years we have been observing significant development of an endoscopic treatment of pancreatic fluid collections, including transmural drainage of walled-off pancreatic necrosis. Simultaneously, the use of endotherapy in treatment of main pancreatic ducts disruptions has increased. Despite many publications available in current literature, concerning the endoscopic treatment of consequences of acute necrotizing pancreatitis, the role of transpapillary drainage in management of patients with pancreatic fluid collections and pancreatic duct disruption as an after-effect of severe acute pancreatitis remains unclear and is still a current problem. This publication includes comment on the article entitled 'Early dual drainage combining transpapillary endotherapy and percutaneous catheter drainage in patients with pancreatic fistula associated with severe acute pancreatitis' published by Yokoi et al. in the July-August 2016 issue of Pancreatology together with questions to the authors. Furthermore, in the article we did pay particular attention to the role of transpapillary drainage in management of pancreatic fluid collections, especially of walled-of pancreatic necrosis.

  15. Pancreatic Cancer Screening of High-Risk Individuals in Arkansas

    ClinicalTrials.gov

    2016-12-08

    Pancreatic Neoplasms; Peutz-Jegher's Syndrome; BRCA1 Gene Mutation; BRCA2 Gene Mutation; Ataxia Telangiectasia; Familial Atypical Mole-Malignant Melanoma Syndrome; Colorectal Neoplasms, Hereditary Nonpolyposis; Hereditary Pancreatitis

  16. Optical spectroscopy for clinical detection of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Chandra, Malavika; Wilson, Robert H.; Scheiman, James; Simeone, Diane; McKenna, Barbara; Purdy, Julianne; Mycek, Mary-Ann

    2009-07-01

    A prototype clinical fluorescence and reflectance spectrometer was developed and employed to detect human pancreatic adenocarcinoma. For the first time, quantitative pancreatic tissue models and chemometric algorithms were applied to successfully distinguish among tissue types.

  17. Is There a Link Between Diabetes and Pancreatic Cancer?

    MedlinePlus

    ... html Is There a Link Between Diabetes and Pancreatic Cancer? Type 2 diabetes onset or worsening may be ... 2 diabetes could be an early sign of pancreatic cancer, new research suggests. Researchers analyzed data from nearly ...

  18. Acute pancreatitis : complication of chicken pox in an immunocompetent host.

    PubMed

    Roy, Pinaki; Maity, Pranab; Basu, Arindam; Dey, Somitra; Das, Biman; Ghosh, U S

    2012-12-01

    Chicken pox is a benign self limited disease. But it may rarely be complicated with acute pancreatitis in otherwise healthy patient. We present a case of varicella pancreatitis and its marked recovery with acyclovir.

  19. The Relation of Pancreatic Disease to Weber-Christian Disease

    PubMed Central

    Moore, Sean

    1963-01-01

    A case of acute Weber-Christian disease is reported, in which pancreatitis was accompanied by evidence of dissemination of pancreatic enzymes causing necrosis of fat and vessels. There is clinical and experimental evidence in the literature to suggest that widespread vascular dissemination of lipase occurs in cases of pancreatitis or pancreatic carcinoma. Review of the autopsy literature of cases of Weber-Christian disease shows that a majority had pancreatitis and systemic involvement of fat. A minority showed lesions confined to the panniculus, which tended to ulcerate; these lesions were in other ways not typical of Weber-Christian disease. In this group none had autopsy evidence of pancreatitis. The opinion is expressed that Weber-Christian disease results from disruption of pancreatic tissue and subsequent vascular dissemination of pancreatic enzymes. PMID:20327582

  20. Pancreatic schwannoma: Report of a case and review of literature.

    PubMed

    Kinhal, Vidyadhar A; Ravishankar, T H S; Melapure, Ashok I; Jayaprakasha, G; Range Gowda, B C; Manjunath

    2010-07-01

    Connective tissue tumors of pancreas are uncommon, among them pancreatic schwannoma is very rare tumor, very few cases were reported in literature. Aggressive resections like whipple's procedure, or distal pancreatectomy are not necessary for pancreatic schwannoma as it rarely goes to malignant change and simple enuclation is sufficient.In our patient pancreatic schwannoma is associated with simple cyst in liver and absence of one kidney. Here, we are presenting a case of pancreatic schwannoma treated by simple enucleation.

  1. Pancreatic Secretion in Response to Jejunal Feeding of Elemental Diet

    PubMed Central

    Cassim, M. M.; Allardyce, D. B.

    1974-01-01

    The instillation of elemental diet into the proximal jejunum of dogs results in a brisk pancreatic secretory response, but the fluid is watery and “enzyme-poor.” The administration of the caloric equivalent in a standard blenderized ward diet induces pancreatic enzyme secretion. Although elemental diet does not “rest” the pancreas, the failure of these preparations to stimulate pancreatic enzyme secretion gives them a theoretical advantage as a nutritional source in the convalescent phase of acute pancreatitis. PMID:4210477

  2. Endoscopic ultrasonography in the management of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Trowers, Eugene A.

    2001-05-01

    Pancreatic cancer diagnosis and management has been enhanced with the application of endoscopic ultrasound. The close proximity of the pancreas to the stomach and duodenum permits detailed imaging with intraluminal ultrasonography and staging of pancreatic tumors. EUS directed fine needle aspiration and injection may be successfully employed with patients with pancreatic cancer. Expandable metal stents can palliate patients with obstruction of the pancreaticobiliary tract as well as the gastroduodenum. The efficacy of EUS in the management of pancreatic cancer is critically reviewed.

  3. Pancreatic tumor of mesenchymal origin--an unusual surgical finding.

    PubMed

    Peskova, M; Fried, M

    1994-04-01

    Recently, a patient with an unusual pancreatic tumor of smooth muscle origin, presented at the First Surgical Clinic, Charles University Hospital, Prague. Leiomyosarcoma, a malignant smooth muscle tumor, may arise almost anywhere in the body. Pancreatic localization is very unusual. A number of authors have surveyed the literature on pancreatic tumors of mesenchymal origin. As many as fifty cases have been reported in autopsy studies since 1882. Only six operated cases of pancreatic sarcomas were found in surgical series.

  4. Inhibition of Pancreatic Cancer Cell Proliferation by LRH-1 Inhibitors

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-12-1-0396 TITLE: INHIBITION OF PANCREATIC CANCER CELL...DATES COVERED 15September2012–14September2013 4. TITLE AND SUBTITLE INHIBITION OF PANCREATIC CANCER CELL PROLIFERATION BY LRH-1 INHIBITORS 5a...of pancreatic cancer is devastating, with mortality rates nearing its incidence rates. To date, there are no effective targeted anti-pancreatic

  5. Pancreatic Heterotopia of Small Intestine with Tubercular Ileitis

    PubMed Central

    Srivastava, Romi; Prakash, Jay; Varma, Kachnar; Misra, Vatsala

    2015-01-01

    Pancreatic heterotopia is defined as pancreatic tissue outside the boundary of pancreas that lacks an anatomic and vascular connection to it. Till today, no case of pancreatic heterotopia along with tubercular ileitis has been reported. We report one such case that presented in our institution. PMID:25737997

  6. Peripheral fat necrosis after penetrating pancreatic trauma: a case report.

    PubMed

    Adams, D B

    1993-11-01

    Peripheral fat necrosis (PFN), a rare complication of pancreatitis, has been reported previously in association with blunt pancreatic trauma. A patient who developed peripheral fat necrosis after penetrating pancreatic trauma and needed bilateral above-the-knee amputations to treat complications of lower extremity fat necrosis is reported.

  7. Alcoholic pancreatitis: New insights into the pathogenesis and treatment

    PubMed Central

    Clemens, Dahn L; Schneider, Katrina J; Arkfeld, Christopher K; Grode, Jaclyn R; Wells, Mark A; Singh, Shailender

    2016-01-01

    Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis. PMID:26909228

  8. Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice

    PubMed Central

    Li, Ning; Wu, Xuefeng; Holzer, Ryan G.; Lee, Jun-Hee; Todoric, Jelena; Park, Eek-Joong; Ogata, Hisanobu; Gukovskaya, Anna S.; Gukovsky, Ilya; Pizzo, Donald P.; VandenBerg, Scott; Tarin, David; Atay, Çiǧdem; Arkan, Melek C.; Deerinck, Thomas J.; Moscat, Jorge; Diaz-Meco, Maria; Dawson, David; Erkan, Mert; Kleeff, Jörg; Karin, Michael

    2013-01-01

    Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss of pancreatic function. We investigated the role of IκB kinase α (IKKα) in pancreatic homeostasis. Pancreas-specific ablation of IKKα (IkkαΔpan) caused spontaneous and progressive acinar cell vacuolization and death, interstitial fibrosis, inflammation, and circulatory release of pancreatic enzymes, clinical signs resembling those of human chronic pancreatitis. Loss of pancreatic IKKα causes defective autophagic protein degradation, leading to accumulation of p62-mediated protein aggregates and enhanced oxidative and ER stress in acinar cells, but none of these effects is related to NF-κB. Pancreas-specific p62 ablation prevented ER and oxidative stresses and attenuated pancreatitis in IkkαΔpan mice, suggesting that cellular stress induced by p62 aggregates promotes development of pancreatitis. Importantly, downregulation of IKKα and accumulation of p62 aggregates were also observed in chronic human pancreatitis. Our studies demonstrate that IKKα, which may control autophagic protein degradation through its interaction with ATG16L2, plays a critical role in maintaining pancreatic acinar cell homeostasis, whose dysregulation promotes pancreatitis through p62 aggregate accumulation. PMID:23563314

  9. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    PubMed Central

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  10. Exocrine pancreatic insufficiency following esophagectomy.

    PubMed

    Huddy, J R; Macharg, F M S; Lawn, A M; Preston, S R

    2013-08-01

    Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 μg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 μg/g (EPI) as well as those in the 200-500 μg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 μg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in

  11. Diagnosis of pancreatic disease in feline platynosomosis.

    PubMed

    Köster, Liza S; Shell, Linda; Ketzis, Jennifer; Rajeev, Sreekumari; Illanes, Oscar

    2017-01-01

    Objectives Platynosomum species are cat-specific parasitic trematodes that parasitize the biliary ducts and gall bladder. Due to the common connection to the major duodenal papilla of the pancreas and common bile ducts in addition to the periductal proximity of the pancreas, it is possible that platynosomosis could cause pancreatitis. The objective of this study was to determine whether platynosomosis, a commonly diagnosed parasitic disease in cats on St Kitts, has any association with pancreatic disease. Methods To investigate this possibility, the pancreas of free-roaming cats with naturally acquired platynosomosis were evaluated via ultrasound, serum concentrations of feline pancreatic lipase (fPL), cobalamin, folate and feline trypsin-like immunoreactivity (fTLI) and histopathology. Twenty free-roaming, young adult, feral cats, positive for feline immunodeficiency virus, and diagnosed with Platynosomum species infection via fecal analysis were recruited. The liver, biliary system and pancreas were evaluated via ultrasonography during a short duration anesthesia. Serum concentrations of fPL, fTLI, folate and cobalamin were measured. Sections of the right limb, left limb and body of the pancreas were evaluated histopathologically using hematoxylin and eosin (H&E) stain. Results None of the cats had sufficient criteria to fulfill the ultrasonographic diagnosis of pancreatitis. One cat had an elevated fPL concentration in the range consistent with pancreatitis. Four cats had cobalamin deficiencies and 11 had abnormal folate concentration. The fTLI concentration was equivocal for the diagnosis of exocrine pancreatic insufficiency in one cat. With a single exception, histopathology changes, when present (n = 12), were mild, non-specific and predominantly characterized by lymphocytic infiltrates and fibrosis. The exception was a cat that presented a chronic interstitial and eosinophilic pancreatitis of slightly increased severity, likely the result of platynosomosis

  12. Adjuvant and neoadjuvant treatment in pancreatic cancer.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-04-14

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  13. Surgical management of necrotizing pancreatitis: an overview.

    PubMed

    Kokosis, George; Perez, Alexander; Pappas, Theodore N

    2014-11-21

    Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15% that reach 30% in case of infection. Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity. This approach is however associated with poor outcomes. Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches. Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds: Delay, Drain and Debride. Patients can be managed in the intensive care unit and any intervention should be delayed. Percutaneous drainage can be utilized first and early in the course of the disease, followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary. Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach. The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease.

  14. Surgical management of necrotizing pancreatitis: An overview

    PubMed Central

    Kokosis, George; Perez, Alexander; Pappas, Theodore N

    2014-01-01

    Necrotizing pancreatitis is an uncommon yet serious complication of acute pancreatitis with mortality rates reported up to 15% that reach 30% in case of infection. Traditionally open surgical debridement was the only tool in our disposal to manage this serious clinical entity. This approach is however associated with poor outcomes. Management has now shifted away from open surgical debridement to a more conservative management and minimally invasive approaches. Contemporary approach to patients with necrotizing pancreatitis and/or infectious pancreatitis is summarized in the 3Ds: Delay, Drain and Debride. Patients can be managed in the intensive care unit and any intervention should be delayed. Percutaneous drainage can be utilized first and early in the course of the disease, followed by endoscopic drainage or video assisted retroperitoneoscopic drainage if necrosectomy is deemed necessary. Open surgery is now less frequently performed and should be reserved for cases refractory to any other approach. The management of necrotizing pancreatitis therefore requires a multidisciplinary dynamic model of approach rather than being a surgical disease. PMID:25473162

  15. Proteomics as a Systems Approach to Pancreatitis

    PubMed Central

    Williams, John A.

    2013-01-01

    Proteomics is an approach to looking at the identity, amount, proteolysis, compartmentalization and post-translational modification of a large number of proteins simultaneously in a cell or tissue. Recently, proteomics has begun to be applied to the study of pancreatitis to ascertain mechanisms of disease and search for biomarkers of disease. Most mechanistic work has been carried out in animal models of acute pancreatitis. In eight studies, 97 proteins have been reported to increase, 55 to decrease and 23 to undergo proteolysis. Proteins showing increases are most often related to stress, inflammation or the cytoskeleton while decreases are seen in digestive enzymes and proteins related to metabolism. Many protein changes however, are not consistent between studies and only the most recent studies are rigorous and quantitative. By contrast, biomarker studies have focused on pancreatic juice and plasma of humans with disease and often are directed at distinguishing chronic pancreatitis from cancer. Chronic pancreatitis has also been investigated in tissue sections of histological samples. In this review the results of studies to date are described as well as coverage of the methods used and special issues that must be considered. Areas are pointed out that are worthy of future study. PMID:23851428

  16. Pancreatic cancer, treatment options, and GI-4000

    PubMed Central

    Hartley, Marion L; Bade, Najeebah A; Prins, Petra A; Ampie, Leonel; Marshall, John L

    2015-01-01

    Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year, which is reduced to 6% after 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors—RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials. PMID:25933185

  17. Pancreatic cancer, treatment options, and GI-4000

    PubMed Central

    Hartley, Marion L; Bade, Najeebah A; Prins, Petra A; Ampie, Leonel; Marshall, John L

    2015-01-01

    Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year and only 6% will make it past 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors—RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials. PMID:25585100

  18. Severe hypertriglyceridemia-related acute pancreatitis.

    PubMed

    Stefanutti, Claudia; Labbadia, Giancarlo; Morozzi, Claudia

    2013-04-01

    Acute pancreatitis is a potentially life-threatening complication of severe hypertriglyceridemia. In some cases, inborn errors of metabolism such as lipoprotein lipase deficiency, apoprotein C-II deficiency, and familial hypertriglyceridemia have been reported as causes of severe hypertriglyceridemia. More often, severe hypertriglyceridemia describes various clinical conditions characterized by high plasma levels of triglycerides (>1000 mg/dL), chylomicron remnants, or intermediate density lipoprotein like particles, and/or chylomicrons. International guidelines on the management of acute pancreatitis are currently available. Standard therapeutic measures are based on the use of lipid-lowering agents (fenofibrate, gemfibrozil, niacin, Ω-3 fatty acids), low molecular weight heparin, and insulin in diabetic patients. However, when standard medical therapies have failed, non-pharmacological approaches based upon the removal of triglycerides with therapeutic plasma exchange can also provide benefit to patients with severe hypertriglyceridemia and acute pancreatitis. Plasma exchange could be very helpful in reducing triglycerides levels during the acute phase of hyperlipidemic pancreatitis, and in the prevention of recurrence. The current evidence on management of acute pancreatitis and severe hypertriglyceridemia, focusing on symptoms, treatment and potential complications is reviewed herein.

  19. MRI of pancreatic metastases from renal cancer

    SciTech Connect

    Kelekis, N.L.; Semelka, R.C.; Siegelman, E.S.

    1996-03-01

    Our goal was to describe the MR features of pancreatic metastases from renal cancer. Five patients with pancreatic metastases from renal cancer were imaged with MR. Imaging was performed on a 1.5 T MR imager using excitation-spoiled fat-suppressed T1-weighted SE images (all patients), T1-weighted spoiled GE images (all patients), T2-weighted fast SE (one patient) and excitation-spoiled fat-suppressed T2-weighted fast SE (one patient) images, serial postgadolinium spoiled GE images (all patients), and postcontrast excitation-spoiled fat-suppressed T1-weighted SE images (two patients). Multiple pancreatic lesions (n = 6) were present in two patients, solitary tumors in two patients, and diffuse micronodular pancreatic enlargement in one patient. All lesions were hypointense compared to normal pancreas on T1-weighted fat-suppressed SE images. Lesions were high in ST on T2-weighted images in two of two patients. All lesions demonstrated enhancement on the immediate postgadolinium spoiled GE images with the smaller tumors (<1.5 cm, three individual and the micronodular tumors) showing diffuse enhancement and the larger tumors (>1.5 cm, five tumors) showing pre-dominantly rim enhancement. Pancreatic metastases from renal cell carcinoma have distinctive MR features that include diffuse enhancement in small lesions and rim enhancement in large lesions on immediate postgadolinium images and high SI on T2-weighted images. 20 refs., 4 figs.

  20. Loss of Ifnar1 in Pancreatic Acinar Cells Ameliorates the Disease Course of Acute Pancreatitis

    PubMed Central

    Miller, Katharina J.; Raulefs, Susanne; Kong, Bo; Steiger, Katja; Regel, Ivonne; Gewies, Andreas; Kleeff, Jörg; Michalski, Christoph W.

    2015-01-01

    Type I interferon constitutes an essential component of the combinational therapy against viral disease. Acute pancreatitis is one side effect of type I interferon-based therapy, implying that activation of type I interferon signaling affects the homeostasis and integrity of pancreatic acinar cells. Here, we investigated the role of type I interferon signaling in pancreatic acinar cells using a caerulein-induced murine model of acute pancreatitis. Pancreas-specific ablation of interferon (alpha and beta) receptor 1 (Ifnar1) partially protected animals from caerulein-induced pancreatitis, as demonstrated by reduced tissue damage. Profiling of infiltrating immune cells revealed that this dampened tissue damage response correlated with the number of macrophages in the pancreas. Pharmacologic depletion of macrophages reversed the protective effect of Ifnar1 deficiency. Furthermore, expression of chemokine (C-C motif) ligand 2 (Ccl2), a potent factor for macrophage recruitment, was significantly increased in the Ifnar1-deficient pancreas. Thus, type I interferon signaling in pancreatic acinar cells controls pancreatic homeostasis by affecting the macrophage-mediated inflammatory response in the pancreas. PMID:26618925

  1. Altered Gene Expression in Cerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis

    PubMed Central

    Yu, Ji Hoon; Lim, Joo Weon

    2009-01-01

    Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with 10-8 M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis. PMID:20054485

  2. Analysis of the pancreatic low molecular weight proteome in an animal model of acute pancreatitis.

    PubMed

    Lassout, Olivier; Pastor, Catherine M; Fétaud-Lapierre, Vanessa; Hochstrasser, Denis F; Frossard, Jean-Louis; Lescuyer, Pierre

    2010-09-03

    We used a peptidomic approach for the analysis of the low molecular weight proteome in rat pancreatic tissue extracts. The goal was to develop a method that allows identifying endogenous peptides produced in the pancreas in the course of acute pancreatitis. The workflow combines peptides enrichment by centrifugal ultrafiltration, fractionation by isoelectric focusing, and LC-MS/MS analysis without prior enzymatic digestion. The method was assessed on pancreatic extracts from 3 rats with caerulein-induced pancreatitis and 3 healthy controls. A qualitative analysis of the peptide patterns obtained from the different samples was performed to determine the main biological processes associated to the identified peptides. Comparison of peptidomic and immunoblot data for alpha-tubulin, beta-tubulin and coatomer gamma showed that the correlation between the number of identified peptides and the protein abundance was variable. Nevertheless, peptidomic analysis highlighted inflammatory and stress proteins, which peptide pattern was related to acute pancreatitis pathobiology. For these proteins, the higher number of peptides in pancreatitis samples reflected an increase in protein abundance. Moreover, for murinoglobulin-1 or carboxypeptidase B, peptide pattern could be related to protein function. These data suggest that peptidomic analysis is a complementary approach to proteomics for investigating pathobiological processes involved in acute pancreatitis.

  3. Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

    PubMed

    Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

    2013-06-01

    Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

  4. [Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

    PubMed

    Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Takács, Tamás; Tiszlavicz, László; Szücs, Ákos; Czakó, László

    2015-02-22

    Autoimmune pancreatitis is a rare disease which can even mimic pancreatic tumor, however, unlike the latter, it requires not surgical but conservative management. Correct diagnosis and differential diagnosis of autoimmune pancreatitis and treatment of these patients requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 29 relevant clinical questions in 4 topics were defined (Basics; Diagnosis; Differential diagnostics; Therapy). Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinial questions were accepted with almost total (more than 95%) agreement. The present guideline is the first evidence based autoimmune pancreatitis guideline in Hungary. The guideline may provide very important and helpful data for tuition of autoimmune pancreatitis, for everyday practice and for establishing proper finance. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

  5. Pancreatic Satellite Cells Derived Galectin-1 Increase the Progression and Less Survival of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Gao, Jun; Wang, Sen; Ye, Nianyuan; Li, Ping; Gao, Sujun; Miao, Yi; Wang, Daorong; Jiang, Kuirong

    2014-01-01

    Background Galectin-1, a member of carbohydrate-binding proteins with a polyvalent function on tumor progression, was found strongly expressed in pancreatic satellite cells (PSCs), which partner in crime with cancer cells and promote the development of pancreatic ductal adenocarcinoma (PDAC). We evaluated the effects of PSCs derived Galectin-1 on the progression of PDAC, as well as the tumor establishment and development in mouse xenografts. Methods The relationship between immunohistochemistry staining intensity of Galectin-1 and clinicopathologic variables were assessed in 66 PDAC tissues, 18 chronic pancreatitis tissues and 10 normal controls. The roles of PSCs isolated from PDAC and normal pancreas on the proliferative activity, MMP2 and MMP9 expression, and the invasion of CFPAC-1 in the co-cultured system, as well as on the tumor establishment and development in mouse xenografts by mixed implanting with CFPAC-1 subcutaneously were evaluated. Results Galectin-1 expression was gradually increased from normal pancreas (negative), chronic pancreatitis (weak) to PDAC (strong), in which Galectin-1 expression was also increased from well, moderately to poorly differentiated PDAC. Galectin-1 staining intensity of pancreatic cancer tissue was associated with increase in tumor size, lymph node metastasis, perineural invasion and differentiation and UICC stage, and served as the independent prognostic indicator of poor survival of pancreatic cancer. In vitro and in vivo experiments indicated that TGF-β1 upregulated Galectin-1 expression in PSCs, which could further promotes the proliferative activity, MMP2 and MMP9 expression, and invasion of pancreatic cancer cells, as well as the tumor establishment and growth. Conclusion Galectin-1 expression in stromal cells of pancreatic cancer suggests that this protein plays a role in the promotion of cancer cells invasion and metastasis and provides a therapeutic target for the treatment of pancreatic cancer. PMID:24595374

  6. Involvement of endogenous cholecystokinin in pancreatic regeneration after cerulein-induced acute pancreatitis.

    PubMed

    Jurkowska, G; Grondin, G; Morisset, J

    1992-01-01

    This study was undertaken to determine the involvement of endogenous cholecystokinin (CCK) in the regeneration of pancreatic tissue after cerulein-induced acute pancreatitis treated by the CCK receptor antagonist L364,718. Acute pancreatitis was induced in rats by s.c. injections of cerulein in gelatin (12 micrograms/kg) three times a day for 2 days with controls receiving saline in gelatin. Rats were then divided into four treatment groups: saline-dimethyl sulfoxide (DMSO) (SD), saline-L364,718 (SA), cerulein-pancreatitis-DMSO (CD), and cerulein-pancreatitis-L364,718 (CA). In the first experiment, rats were treated for 3 or 10 days with DMSO or L364,718 (0.1 mg/kg, twice a day). In the second experiment, rats were treated for 13 days with DMSO or L364,718 (1.0 mg/kg, twice a day). After the rats were killed, pancreata were weighed and evaluated for their total protein, amylase, chymotrypsin, RNA, and DNA. We found that destruction of the pancreatic tissue occurred after cerulein-induced pancreatitis and that regeneration of the tissue was in progress but incomplete after 10 days; the low dose of L364,718 did not prevent regeneration. After 13 days, regeneration was still incomplete but the 1-mg dose of L364,718 strongly inhibited spontaneous regeneration. These data suggest that endogenous CCK is an important and potent trophic factor in the regeneration process of pancreatic tissue following an episode of acute pancreatitis.

  7. APC promoter is frequently methylated in pancreatic juice of patients with pancreatic carcinomas or periampullary tumors

    PubMed Central

    Ginesta, Mireia M.; Diaz-Riascos, Zamira Vanessa; Busquets, Juli; Pelaez, Núria; Serrano, Teresa; Peinado, Miquel Àngel; Jorba, Rosa; García-Borobia, Francisco Javier; Capella, Gabriel; Fabregat, Joan

    2016-01-01

    Early detection of pancreatic and periampullary neoplasms is critical to improve their clinical outcome. The present authors previously demonstrated that DNA hypermethylation of adenomatous polyposis coli (APC), histamine receptor H2 (HRH2), cadherin 13 (CDH13), secreted protein acidic and cysteine rich (SPARC) and engrailed-1 (EN-1) promoters is frequently detected in pancreatic tumor cells. The aim of the present study was to assess their prevalence in pancreatic juice of carcinomas of the pancreas and periampullary area. A total of 135 pancreatic juices obtained from 85 pancreatic cancer (PC), 26 ampullary carcinoma (AC), 10 intraductal papillary mucinous neoplasm (IPMN) and 14 chronic pancreatitis (CP) patients were analyzed. The methylation status of the APC, HRH2, CDH13, SPARC and EN-1 promoters was analyzed using methylation specific-melting curve analysis (MS-MCA). Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations were also tested with allele-specific quantitative polymerase chain reaction amplification. Out of the 5 promoters analyzed, APC (71%) and HRH2 (65%) were the most frequently methylated in PC juice. APC methylation was also detected at a high frequency in AC (76%) and IPMN (80%), but only occasionally observed in CP (7%). APC methylation had a high sensitivity (71–80%) for all types of cancer analyzed. The panel (where a sample scored as positive when ≥2 markers were methylated) did not outperform APC as a single marker. Finally, KRAS detection in pancreatic juice offered a lower sensitivity (50%) and specificity (71%) for detection of any cancer. APC hypermethylation in pancreatic juice, as assessed by MS-MCA, is a frequent event of potential clinical usefulness in the diagnosis of pancreatic and periampullary neoplasms. PMID:27602165

  8. Gene therapy in pancreatic cancer.

    PubMed

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-10-07

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

  9. Perineural Mast Cells Are Specifically Enriched in Pancreatic Neuritis and Neuropathic Pain in Pancreatic Cancer and Chronic Pancreatitis

    PubMed Central

    Wang, Kun; Kehl, Timo; Giese, Nathalia A.; Algül, Hana; Friess, Helmut; Ceyhan, Güralp O.

    2013-01-01

    Background Pancreatic neuritis is a histopathological hallmark of pancreatic neuropathy and correlates to abdominal neuropathic pain sensation in pancreatic adenocarcinoma (PCa) and chronic pancreatitis (CP). However, inflammatory cell subtypes that compose pancreatic neuritis and their correlation to the neuropathic pain syndrome in PCa and CP are yet unknown. Methods Inflammatory cells within pancreatic neuritis lesions of patients with PCa (n = 20) and CP (n = 20) were immunolabeled and colorimetrically quantified with the pan-leukocyte marker CD45, with CD68 (macrophages), CD8 (cytotoxic T-lymphocytes), CD4 (T-helper cells), CD20 (B-lymphocytes), NCL-PC (plasma cells), neutrophil elastase, PRG2 (eosinophils), anti-mast cell (MC) tryptase and correlated to pain sensation. Perineural mast cell subtypes were analyzed by double immunolabeling with MC chymase. Expression and neural immunoreactivity of protease-activated receptor type 1 (PAR-1) and type 2 (PAR-2) were analyzed in PCa and CP and correlated to pain status of the patients. Results In PCa and CP, nerves were predominantly infiltrated by cytotoxic T-lymphocytes (PCa: 35% of all perineural inflammatory cells, CP: 33%), macrophages (PCa: 39%, CP: 33%) and MC (PCa: 21%, CP: 27%). In both entities, neuropathic pain sensation was associated with a specific increase of perineural MC (PCa without pain: 14% vs. PCa with pain: 31%; CP without pain: 19% vs. CP with pain: 34%), not affecting the frequency of other inflammatory cell subtypes. The vast majority of these MC contained MC chymase. PAR-1 and PAR-2 expression did not correlate to the pain sensation of PCa and CP patients. Conclusion Pancreatic neuritis in PC and CP is composed of cytotoxic T-lymphocytes, macrophages and MC. The specific enrichment of MC around intrapancreatic nerves in neuropathic pain due to PCa and CP suggests the presence of MC-induced visceral hypersensitivity in the pancreas. Therefore, pancreatic and enteric neuropathies seem

  10. Gastrointestinal Hemorrhage Due to Splenic Artery Aneurysm Pancreatic Duct Fistula in Chronic Pancreatitis

    PubMed Central

    Blumgart, Leslie H.

    1993-01-01

    Gastrointestinal hemorrhage due to splenic artery aneurysm pancreatic duct fistula in chronic pancreatitis is rare. It is, however, important to diagnose this condition particularly in patients having chronic pancreatitis, since it may result in a life-threatening situation. The diagnosis is usually difficult to establish and it may take repeated admissions for intermittent gastrointestinal bleeding until the real source is recognized. Clinical attacks of epigastric pain followed by GI-bleeding 30–40 minutes later are characteristic. Occasionally these attacks are followed by transient jaundice. The present case report describes this rare complication and reviews the current literature. PMID:8268107

  11. Microbiota, oral microbiome, and pancreatic cancer.

    PubMed

    Michaud, Dominique S; Izard, Jacques

    2014-01-01

    Only 30% of patients with a diagnosis of pancreatic cancer survive 1 year after the diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest that the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease susceptibility, should shed light on how to better tackle prevention, early detection, and treatment of this highly fatal disease.

  12. Pancreatic Adenocarcinoma, Version 2.2012

    PubMed Central

    Tempero, Margaret A.; Arnoletti, J. Pablo; Behrman, Stephen W.; Ben-Josef, Edgar; Benson, Al B.; Casper, Ephraim S.; Cohen, Steven J.; Czito, Brian; Ellenhorn, Joshua D. I.; Hawkins, William G.; Herman, Joseph; Hoffman, John P.; Ko, Andrew; Komanduri, Srinadh; Koong, Albert; Ma, Wen Wee; Malafa, Mokenge P.; Merchant, Nipun B.; Mulvihill, Sean J.; Muscarella, Peter; Nakakura, Eric K.; Obando, Jorge; Pitman, Martha B.; Sasson, Aaron R.; Tally, Anitra; Thayer, Sarah P.; Whiting, Samuel; Wolff, Robert A.; Wolpin, Brian M.; Freedman-Cass, Deborah A.; Shead, Dorothy A.

    2013-01-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. PMID:22679115

  13. Pancreatic function in chronic inflammatory bowel disease.

    PubMed

    Angelini, G; Cavallini, G; Bovo, P; Brocco, G; Castagnini, A; Lavarini, E; Merigo, F; Tallon, N; Scuro, L A

    1988-03-01

    This study was prospectively carried out to evaluate the frequency and clinical significance of pancreatic impairment in the course of chronic inflammatory bowel disease (CIBD). Twenty-seven patients affected by ulcerative colitis or Crohn's disease were submitted to a secretin-cerulein test, oral glucose test (OGT) and to indirect immunofluorescence (IFL) for detection of autoantibodies against exocrine and endocrine tissue. A bicarbonate plus enzyme or only an enzyme insufficiency was found in 11/27 patients, whereas isolated lipase decrease was observed in 18 subjects. In the results of the OGT and the indirect IFL test there was no difference between patients and controls. These data demonstrate that pancreatic impairment is a far more frequent occurrence than generally recognized in clinical practice. The decrease of lipase secretion could worsen the consequences of malabsorption in Crohn's disease of the small intestine. Therefore we think that a pancreatic assessment is advisable, at least in Crohn's disease patients with steatorrhea.

  14. Exocrine pancreatic insufficiency in the cat.

    PubMed

    Steiner, Jörg M

    2012-08-01

    Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient amount of pancreatic digestive enzymes in the small intestine. Clinical signs most commonly reported in cats with EPI are weight loss, loose and voluminous stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair coat in the perianal region. Serum feline trypsin-like immunoreactivity concentration is the diagnostic test of choice for the diagnosis of affected cats. Treatment of cats with EPI consists of enzyme supplementation with either a powdered pancreatic extract or raw pancreas. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require lifelong parenteral cobalamin supplementation. Most cats respond well to therapy and can have a normal life expectancy and quality of life.

  15. Stereotactic Body Radiation Therapy for Pancreatic Cancer.

    PubMed

    Goodman, Karyn A

    2016-01-01

    The role of radiation therapy in the management of pancreatic cancer represents an area of some controversy. However, local disease progression remains a significant cause of morbidity and even mortality for patients with this disease. Stereotactic body radiotherapy (SBRT) is an emerging treatment option for pancreatic cancer, primarily for locally advanced (unresectable) disease as it can provide a therapeutic benefit with significant advantages for patients' quality of life over standard conventional chemoradiation. There may also be a role for SBRT as neoadjuvant therapy for patients with borderline resectable disease to allow conversion to resectability. The objective of this review is to present the data supporting SBRT in pancreatic cancer as well as the potential limitations and caveats of current studies.

  16. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  17. Tumor antigens as related to pancreatic cancer.

    PubMed

    Chu, T M; Holyoke, E D; Douglass, H O

    1980-01-01

    Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

  18. Simultaneous pancreatic-renal transplant scintigraphy

    SciTech Connect

    Shulkin, B.L.; Dafoe, D.C.; Wahl, R.L.

    1986-12-01

    99mTc-DTPA scintigraphy was evaluated in seven patients as a technique to assess perfusion of the transplanted pancreas and kidney. Such scans provide high-quality images of both organs in both the flow phase and later phases. The radionuclide is readily available and its brief effective half-life allows repeated evaluations at short intervals. /sup 131/I-hippuran, the major radiopharmaceutical for renal transplant scintigraphy, does not allow visualization of the transplanted pancreas or evaluation of its blood supply. Although the blood glucose is a gross indicator of the function of the pancreatic allograft, pancreatic scintigraphy with 99mTc-DTPA in one case was capable of detecting graft dysfunction before elevation of the blood glucose occurred. While additional studies will be necessary to determine the predictive value of this test, 99mTc-DTPA is valuable for pancreatic-renal transplant evaluation.

  19. Glycoproteins and glycoproteomics in pancreatic cancer

    PubMed Central

    Pan, Sheng; Brentnall, Teresa A; Chen, Ru

    2016-01-01

    Aberrations in protein glycosylation and polysaccharides play a pivotal role in pancreatic tumorigenesis, influencing cancer progression, metastasis, immuno-response and chemoresistance. Abnormal expression in sugar moieties can impact the function of various glycoproteins, including mucins, surface receptors, adhesive proteins, proteoglycans, as well as their effectors and binding ligands, resulting in an increase in pancreatic cancer invasiveness and a cancer-favored microenvironment. Recent advance in glycoproteomics, glycomics and other chemical biology techniques have been employed to better understand the complex mechanism of glycosylation events and how they orchestrate molecular activities in genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A variety of strategies have been demonstrated targeting protein glycosylation and polysaccharides for diagnostic and therapeutic development. PMID:27895417

  20. Pathophysiology of pulmonary complications of acute pancreatitis

    PubMed Central

    Browne, George W; Pitchumoni, CS

    2006-01-01

    Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines. PMID:17131469

  1. Chronic pancreatitis in India and Asia.

    PubMed

    Garg, Pramod Kumar

    2012-04-01

    Chronic pancreatitis (CP) is widely prevalent in Asian countries much more so in India and Japan. The phenotype of CP is somewhat similar to that reported from western countries. The prevalent types of CP are mainly idiopathic and alcohol related. Current evidence suggests that the term "tropical pancreatitis" used for idiopathic CP from India is a misnomer. Gallstones' association with CP reported from China remains controversial. There has been ample evidence that mutations in the SPNIK1 and CFTR genes are strongly associated with idiopathic CP in patients from different ethnic backgrounds. Oxidative stress is important in the pathophysiology and antioxidants have been shown to result in significant pain relief with CP. Home-made balanced diet is effective for treating malnutrition in patients with CP. Endoscopic therapy combined with ESWL may provide significant relief in patients with pancreatic ductal calculi/stricture. Surgery is quite effective in CP and may be better than endotherapy.

  2. Gall stones and chronic pancreatitis: the black box in between.

    PubMed

    Yan, M-X; Li, Y-Q

    2006-04-01

    The relation between gall stones and chronic pancreatitis is uncertain; there are differing opinions on this issue. Firstly, gall stones are the most common reason for acute pancreatitis, but it cannot cause chronic pancreatitis. Secondly, a connection between gall stones and chronic inflammation of the pancreas might exist. Numerous studies or investigations have shown that changes associated with chronic pancreatitis are common in gallstone patients. Although it seems that gall stones might be a cause of chronic pancreatitis according to these findings, clinical and experimental studies are still needed for confirmation, and further studies are required to determine the mechanisms involved.

  3. Intravital characterization of tumor cell migration in pancreatic cancer

    PubMed Central

    Beerling, Evelyne; Oosterom, Ilse; Voest, Emile; Lolkema, Martijn; van Rheenen, Jacco

    2016-01-01

    ABSTRACT Curing pancreatic cancer is difficult as metastases often determine the poor clinical outcome. To gain more insight into the metastatic behavior of pancreatic cancer cells, we characterized migratory cells in primary pancreatic tumors using intravital microscopy. We visualized the migratory behavior of primary tumor cells of a genetically engineered pancreatic cancer mouse model and found that pancreatic tumor cells migrate with a mesenchymal morphology as single individual cells or collectively as a stream of non-cohesive single motile cells. These findings may improve our ability to conceive treatments that block metastatic behavior. PMID:28243522

  4. Benign pancreatic hyperenzymemia (Gullo syndrome), histamine intolerance, and carbohydrate malabsorption

    PubMed Central

    Enko, Dietmar; Mangge, Harald; Schenk, Michael; Lackner, Sonja; Holasek, Sandra J.

    2017-01-01

    Benign pancreatic hyperenzymemia (Gullo syndrome) is characterized by a more than threefold increase of the pancreatic enzymes lipase and amylase in the absence of a pancreatic disease over a period of more than 1 year, with elevations and significant undulations of pancreatic enzyme serum concentrations occurring on a day-to-day basis for 5 consecutive days. Nonspecific abdominal complaints may be caused by carbohydrate and/or protein malabsorption. We report a patient with benign pancreatic hyperenzymemia with lactose and histamine malabsorption; the symptoms of gastrointestinal malabsorption were treated successfully with an individually tailored lactose- and histamine-free diet.

  5. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  6. Vascular Complications of Pancreatitis: Imaging and Intervention

    SciTech Connect

    Kirby, John M. Vora, Parag; Midia, Mehran; Rawlinson, John

    2008-09-15

    The objective of this study was to highlight technical challenges and potential pitfalls of diagnostic imaging, intervention, and postintervention follow-up of vascular complications of pancreatitis. Diagnostic and interventional radiology imaging from patients with pancreatitis from 2002 to 2006 was reviewed. We conclude that biphasic CT is the diagnostic modality of choice. Catheter angiography may (still) be required to diagnose small pseudoaneurysms. Endovascular coiling is the treatment of choice for pseudoaneurysms. Close clinical follow-up is required, as patients may rebleed/develop aneurysms elsewhere.

  7. [Laparoscopic abdominal drainage by sterile destructive pancreatitis].

    PubMed

    Kuznetsov, N A; Rodoman, G V; Shalaeva, T I; Trefilova, O I; Sosikova, N L

    2009-01-01

    90 patients with acute pancreatitis were observed, in 60 of them laparoscopic drainage was performed. The procedure by sterile pancreatonecrosis is indicated only in presence of extent amount of exudate in abdominal cavity. Duration of draining the abdominal cavity should be strictly limited because of the high risk of septic complications. Contraindications for the abdominal drainage by acute necrotic pancreatitis are not only adhesions in the abdomen and shock state of the patient at the moment of procedure necessity, but also unstable hemodynamics in anamnesis and even by the arterial pressure downtrend.

  8. A giant pancreatic pseudocyst treated by cystogastrostomy

    PubMed Central

    Wang, Grace C; Misra, Subhasis

    2015-01-01

    We report a case of a giant pancreatic pseudocyst in a 65-year-old man presenting with abdominal pain, loss of appetite and abdominal distension. CT scans demonstrated a giant pancreatic pseudocyst measuring 25.7 cm×15.3 cm×10.9 cm anteroposteriorly, with significant compression of surrounding organs. An open cystogastrostomy was performed through a midline incision, and 3 L of fluid was drained from the giant pseudocyst. Recovery has been uneventful. PMID:25804943

  9. Moving Into Stage IV: Pancreatic Cancer.

    PubMed

    Waxler, Robert P

    2016-12-01

    Living with pancreatic cancer is always an adjustment, an attempt to find balance and direction in a world of the sick and the healthy. It is also a journey into unknown territory, a search for beauty, a battle of life against death, eros struggling with thanatos. In this narrative, you will find personal details of the life of a pancreatic cancer patient, his daily struggles, his treatments, his medications, but you will also find his search for the meaning of life itself embedded in his unfolding story, his attempt to come to terms with the questions of why we live and what we might consider to be a genuinely fortunate life.

  10. Novel adjuvant therapies for pancreatic adenocarcinoma

    PubMed Central

    Oyasiji, Tolutope

    2015-01-01

    Contemporary adjuvant therapy for pancreatic cancer patients following surgical resection includes chemotherapy and chemoradiotherapy. However, the median survival remains approximately 20 months despite multi-modality treatment using gemcitabine or fluoropyrimidine systemic chemotherapy. Adjuvant randomized trials are currently underway to evaluate cytotoxic combinations found to be active in advanced disease including FOLFIRINOX, gemcitabine/nab-paclitaxel and gemcitabine/capecitabine. Immunotherapy using genetically engineered cell-based vaccines had shown promise in resected pancreatic cancer patients during early phase trials, and algenpantucel-L vaccine is currently being evaluated in adjuvant setting in a randomized trial. This review focuses on novel adjuvant therapies currently in clinical evaluation. PMID:26261729

  11. Unraveling pancreatic islet biology by quantitative proteomics

    SciTech Connect

    Zhou, Jianying; Dann, Geoffrey P.; Liew, Chong W.; Smith, Richard D.; Kulkarni, Rohit N.; Qian, Weijun

    2011-08-01

    The pancreatic islets of Langerhans play a critical role in maintaining blood glucose homeostasis by secreting insulin and several other important peptide hormones. Impaired insulin secretion due to islet dysfunction is linked to the pathogenesis underlying both Type 1 and Type 2 diabetes. Over the past 5 years, emerging proteomic technologies have been applied to dissect the signaling pathways that regulate islet functions and gain an understanding of the mechanisms of islet dysfunction relevant to diabetes. Herein, we briefly review some of the recent quantitative proteomic studies involving pancreatic islets geared towards gaining a better understanding of islet biology relevant to metabolic diseases.

  12. Dantrolene mitigates caerulein-induced pancreatitis in vivo in mice.

    PubMed

    Orabi, Abrahim I; Shah, Ahsan U; Ahmad, Mahwish U; Choo-Wing, Rayman; Parness, Jerome; Jain, Dhanpat; Bhandari, Vineet; Husain, Sohail Z

    2010-07-01

    Acute pancreatitis is a painful, inflammatory disorder for which adequate treatments are lacking. An early, critical step in its development is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. This Ca(2+) release is modulated by the intracellular Ca(2+) channel the ryanodine receptor (RYR). We have previously shown that RYR inhibition reduces pathological intra-acinar protease activation, an early marker of pancreatitis. In this study, we examined whether pretreatment with the RYR inhibitor dantrolene attenuates the severity of caerulein-induced pancreatitis in mice. Immunofluorescent labeling for RYR from mouse pancreatic sections showed localization to the basolateral region of the acinar cell. After 1 h of caerulein hyperstimulation in vivo, dantrolene 1) reduced pancreatic trypsin activity by 59% (P < 0.05) and 2) mitigated early ultrastructural derangements within the acinar cell. Eight hours after pancreatitis induction, dantrolene reduced pancreatic trypsin activity and serum amylase by 61 and 32%, respectively (P < 0.05). At this later time point, overall histological severity of pancreatitis was reduced by 63% with dantrolene pretreatment (P < 0.05). TUNEL-positive cells were reduced by 58% (P < 0.05). These data suggest that the RYR plays an important role in mediating early acinar cell events during in vivo pancreatitis and contributes to disease severity. Blockade of Ca(2+) signals and particularly RYR-Ca(2+) may be useful as prophylactic treatment for this disease in high-risk settings for pancreatitis.

  13. THE PANC 3 SCORE PREDICTING SEVERITY OF ACUTE PANCREATITIS

    PubMed Central

    BEDUSCHI, Murilo Gamba; MELLO, André Luiz Parizi; VON-MÜHLEN, Bruno; FRANZON, Orli

    2016-01-01

    Background : About 20% of cases of acute pancreatitis progress to a severe form, leading to high mortality rates. Several studies suggested methods to identify patients that will progress more severely. However, most studies present problems when used on daily practice. Objective : To assess the efficacy of the PANC 3 score to predict acute pancreatitis severity and its relation to clinical outcome. Methods : Acute pancreatitis patients were assessed as to sex, age, body mass index (BMI), etiology of pancreatitis, intensive care need, length of stay, length of stay in intensive care unit and mortality. The PANC 3 score was determined within the first 24 hours after diagnosis and compared to acute pancreatitis grade of the Revised Atlanta classification. Results : Out of 64 patients diagnosed with acute pancreatitis, 58 met the inclusion criteria. The PANC 3 score was positive in five cases (8.6%), pancreatitis progressed to a severe form in 10 cases (17.2%) and five patients (8.6%) died. Patients with a positive score and severe pancreatitis required intensive care more often, and stayed for a longer period in intensive care units. The PANC 3 score showed sensitivity of 50%, specificity of 100%, accuracy of 91.4%, positive predictive value of 100% and negative predictive value of 90.6% in prediction of severe acute pancreatitis. Conclusion : The PANC 3 score is useful to assess acute pancreatitis because it is easy and quick to use, has high specificity, high accuracy and high predictive value in prediction of severe acute pancreatitis. PMID:27120730

  14. Dantrolene mitigates caerulein-induced pancreatitis in vivo in mice

    PubMed Central

    Orabi, Abrahim I.; Shah, Ahsan U.; Ahmad, Mahwish U.; Choo-Wing, Rayman; Parness, Jerome; Jain, Dhanpat; Bhandari, Vineet

    2010-01-01

    Acute pancreatitis is a painful, inflammatory disorder for which adequate treatments are lacking. An early, critical step in its development is the aberrant signaling of Ca2+ within the pancreatic acinar cell. This Ca2+ release is modulated by the intracellular Ca2+ channel the ryanodine receptor (RYR). We have previously shown that RYR inhibition reduces pathological intra-acinar protease activation, an early marker of pancreatitis. In this study, we examined whether pretreatment with the RYR inhibitor dantrolene attenuates the severity of caerulein-induced pancreatitis in mice. Immunofluorescent labeling for RYR from mouse pancreatic sections showed localization to the basolateral region of the acinar cell. After 1 h of caerulein hyperstimulation in vivo, dantrolene 1) reduced pancreatic trypsin activity by 59% (P < 0.05) and 2) mitigated early ultrastructural derangements within the acinar cell. Eight hours after pancreatitis induction, dantrolene reduced pancreatic trypsin activity and serum amylase by 61 and 32%, respectively (P < 0.05). At this later time point, overall histological severity of pancreatitis was reduced by 63% with dantrolene pretreatment (P < 0.05). TUNEL-positive cells were reduced by 58% (P < 0.05). These data suggest that the RYR plays an important role in mediating early acinar cell events during in vivo pancreatitis and contributes to disease severity. Blockade of Ca2+ signals and particularly RYR-Ca2+ may be useful as prophylactic treatment for this disease in high-risk settings for pancreatitis. PMID:20448143

  15. Energetic etiologies of acute pancreatitis: A report of five cases

    PubMed Central

    Shmelev, Artem; Abdo, Alain; Sachdev, Sarina; Shah, Urvi; Kowdley, Gopal C; Cunningham, Steven C

    2015-01-01

    There are several common causes of acute pancreatitis, principally excessive alcohol intake and gallstones, and there are many rare causes. However, cases of pancreatitis still occur in the absence of any recognizable factors, and these cases of idiopathic pancreatitis suggest the presence of unrecognized etiologies. Five cases of acute pancreatitis in four patients came to attention due to a strong temporal association with exposure to nerve stimulators and energy drinks. Given that these cases of pancreatitis were otherwise unexplained, and given that these exposures were not clearly known to be associated with pancreatitis, we performed a search for precedent cases and for mechanistic bases. No clear precedent cases were found in PubMed and only scant, weak precedent cases were found in public-health databases. However, there was a coherent body of intriguing literature in support of a mechanistic basis for these exposures playing a role in the etiology of pancreatitis. PMID:26600983

  16. Scrotal Abscess: A Rare Presentation of Complicated Necrotizing Pancreatitis.

    PubMed

    Mirhashemi, Seyyedhadi; Soori, Mohsen; Faghih, Gholamhossein; Peyvandi, Hassan; Shafagh, Omid

    2017-02-01

    Acute pancreatitis is characterized by activation of digestive enzymes inside the pancreas. In severe pancreatitis, necrosis of pancreas and surrounding tissues may occur. Acute necrotizing pancreatitis commonly presents as pancreatic abscess occasionally with systemic complications. Rarely, necrotic tissue may be drained from scrotum due to retroperitoneal extension of necrotic process. Here, we report a case of acute necrotizing pancreatitis in a 29-year-old man who presented with severe abdominal pain, nausea and vomiting. A computerized tomography (CT) scan confirmed necrotizing pancreatitis with multiple abscesses spreading bilaterally in the pelvic cavity. Several surgical operations were performed, including necrosectomy and drainage. Subsequently, the patient developed a scrotal abscess, which was drained surgically. The patient's condition was complicated by pleural effusion, acute respiratory distress syndrome, colocutaneous and scrotal fistulas, and incisional hernia. It seems that the scrotal abscess is a very rare complication of necrotizing pancreatitis.

  17. Acute pancreatitis: Manifestation of acute HIV infection in an adolescent

    PubMed Central

    Bitar, Anas; Altaf, Muhammad; Sferra, Thomas J.

    2012-01-01

    Summary Background: Pancreatitis in the pediatric age group is not as common as in adults. Etiologies are various and differ from those in adults. Although infectious etiology accounts for a significant number of cases of pancreatitis, acute infection with Human Immunodeficiency Virus (HIV) was rarely reported as a possible etiology for acute pancreatitis in adults. Acute pancreatitis has never been reported as a presenting manifestation of acute HIV infection in children. Case Report: We describe a pediatric patient who presented with acute pancreatitis that revealed acute HIV infection. Conclusions: Acute pancreatitis as a primary manifestation of HIV infection is very rare. It may represent an uncommon aspect of primary HIV infection. We suggest that acute HIV infection should be considered in the differential diagnosis of acute pancreatitis at all ages. PMID:23569476

  18. A Minimally Invasive Approach for Postoperative Pancreatic Fistula

    SciTech Connect

    Yamazaki, Shintaro Kuramoto, Kenmei; Itoh, Yutaka; Watanabe, Yoshika; Ueda, Toshisada

    2003-11-15

    Pancreas fistula is a well-known and severe complication of pancreaticoduodenectomy. It is difficult to control with conservative therapy, inducing further complications and severe morbidity. Until now, re-operation has been the only way to resolve pancreatic fistula causing complete dehiscence of the pancreatic-enteric anastomosis (complete pancreatic fistula). Percutaneous transgastric fistula drainage is one of the treatments for pancreatic fistula. This procedure allows both pancreas juice drainage and anastomosis re-construction at the same time. This is effective and minimally invasive but difficult to adapt to a long or complicated fistula. In particular, dilatation of the main pancreatic duct is indispensable. This paper reports the successful resolution of a postoperative pancreatic fistula by a two-way-approach percutaneous transgastric fistula drainage procedure. Using a snare catheter from the fistula and a flexible guidewire from the transgastric puncture needle, it can be performed either with or without main pancreatic duct dilatation.

  19. Endoscopic ultrasound in the diagnosis and treatment of pancreatic disease

    PubMed Central

    Teshima, Christopher W; Sandha, Gurpal S

    2014-01-01

    Endoscopic ultrasound (EUS) is an important part of modern gastrointestinal endoscopy and now has an integral role in the diagnostic evaluation of pancreatic diseases. Furthermore, as EUS technology has advanced, it has increasingly become a therapeutic procedure, and the prospect of multiple applications of interventional EUS for the pancreas is truly on the near horizon. However, this review focuses on the established diagnostic and therapeutic roles of EUS that are used in current clinical practice. In particular, the diagnostic evaluation of acute pancreatitis, chronic pancreatitis, cystic pancreatic lesions and solid masses of the pancreas are discussed. The newer enhanced imaging modalities of elastography and contrast enhancement are evaluated in this context. The main therapeutic aspects of pancreatic EUS are then considered, namely celiac plexus block and celiac plexus neurolysis for pain control in chronic pancreatitis and pancreas cancer, and EUS-guided drainage of pancreatic fluid collections. PMID:25110426

  20. Overexpression of ankyrin1 promotes pancreatic cancer cell growth

    PubMed Central

    Omura, Noriyuki; Mizuma, Masamichi; MacGregor, Anne; Hong, Seung-Mo; Ayars, Michael; Almario, Jose Alejandro; Borges, Michael; Kanda, Mitsuro; Li, Ang; Vincent, Audrey; Maitra, Anirban; Goggins, Michael

    2016-01-01

    The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity. PMID:27144336

  1. [Chronic elevation of enzymes of pancreatic origin in asymptomatic patients].

    PubMed

    Quílez, C; Martínez, J; Gómez, A; Trigo, C; Palazón, J M; Belda, G; Pérez-Mateo, M

    1998-05-01

    Chronic asymptomatic elevation of pancreatic enzymes is a well known entity although little has been reported. In most cases chronic asymptomatic elevation of amylase is due to a salival isoamylase increase or macroamylasemia. However, we have studied 10 cases with an increase in amylases due to pancreatic isoamylase and an increase in the remaining pancreatic enzymes which remained elevated during the follow up period ranging from 2 to 60 months. The amylase values ranged from 186 to 1,600; the lipase from 176 to 3,989, trypsin from 476 to 2,430 and pancreatic isoamylase from 122 to 1,263. In all patients CT and echography were carried out, which discarded structural damage. Nonetheless, an indirect test of pancreatic function presented unexplained pathologic values in 4 out of 10 patients. In conclusion, we suggest that chronic asymptomatic elevation of pancreatic enzymes is of unknown etiology with no associated structural pancreatic pathology demonstrable by the usual study methods.

  2. Chronic Pancreatitis: Landmark Papers, Management Decisions, and Future.

    PubMed

    DiMagno, Eugene P; DiMagno, Matthew J

    2016-01-01

    On May 16, 2015 at the invitation of the American Gastroenterological Association Institute Council E.P.D. presented a state-of-the-art lecture at Digestive Disease Week 2015. The aims were to discuss a selection of landmark papers in chronic pancreatitis (CP) that influence modern management and to conclude by suggesting some future directions. This is based on that presentation. We will specifically review the following: duct anatomy and pancreas divisum, description of chronic relapsing pancreatitis and its differentiation from recurrent acute pancreatitis and established CP (ECP), natural histories and gene discoveries of alcoholic, idiopathic and hereditary pancreatitis, development of pancreatic cancer in CP, exocrine pancreatic insufficiency and calculation of dose and delivery of enzymes, endoscopic ultrasonography, and autoimmune pancreatitis. With some exceptions, we exclude basic science and surgery.

  3. Irreversible electroporation for the treatment of pancreatic neuroendocrine tumors

    PubMed Central

    Papamichail, Michail; Ali, Amir; Pizanias, Michail; Peddu, Praveen; Karani, John

    2016-01-01

    Backgrounds/Aims Resection or enucleation is currently the treatment of choice for small pancreatic neuroendocrine tumors (NETs). Irreversible electroporation is a novel ablative method that is used for locally advanced pancreatic adenocarcinoma, but little data exists for its use for pancreatic NETs. We report an early experience of IRE for early pancreatic NETs. Methods Between April 2014 and March 2015, 3 patients with small (<2 cm) pancreatic NETs were treated with percutaneous IRE. Results There were no adverse effects during the procedure. Mean hospital stay was 2.6 days. All patients remained disease free on 12-19 months follow up. One patient developed recurrent pancreatitis with pseudocyst formation. Conclusions IRE for small tumors of the pancreas is practical and may offer advantages over other thermal ablative techniques, since it preserves vital structures such as blood vessels, bile and pancreatic ducts. Further data regarding the long term disease free interval is required to establish efficacy. PMID:27621748

  4. Timing of cholecystectomy after acute severe pancreatitis in pregnancy

    PubMed Central

    TALEBI-BAKHSHAYESH, Mousa; MOHAMMADZADEH, Alireza; ZARGAR, Ali

    2015-01-01

    Acute pancreatitis is one of the most common diseases of the gastrointestinal tract and is usually caused by gallstones; its occurrence in pregnancy is rare. Cholecystectomy for biliary pancreatitis during pregnancy is unavoidable, but its timing is controversial. We herein present the case of a patient who underwent termination of pregnancy due to deteriorated acute severe pancreatitis during the 27th week of gestation. Cholecystectomy was performed because of the relapse of acute biliary pancreatitis 10 days after being discharged. The interval from pancreatitis to cholecystectomy varies with its severity; in mild pancreatitis the interval may be one week, but in severe cases it maybe up to three weeks. Because pancreatitis may relapse during this interval, as occurred in the present case, a better solution for the timing of cholecystectomy must be sought. PMID:26715899

  5. Amylase, lipase, pancreatic isoamylase, and phospholipase A in diagnosis of acute pancreatitis.

    PubMed

    Clavé, P; Guillaumes, S; Blanco, I; Nabau, N; Mercé, J; Farré, A; Marruecos, L; Lluís, F

    1995-08-01

    To determine the utility of serum amylase (AMY), lipase (Lp), pancreatic isoamylase (isoA), phospholipase A (PLA), and urine AMY in the diagnosis of acute pancreatitis, samples of serum and urine were obtained on admission and every day thereafter for 5 days from 384 patients with acute abdominal pain. Diagnostic accuracy, determined as the area under the receiver operating characteristic curve, was > 0.975 for serum AMY, Lp, isoA, and urine AMY. For each of these enzymes, a threshold value (twice to sixfold the upper limit of the reference values) offering diagnostic efficiency > 95% could be determined. In contrast, accuracy and efficiency of serum PLA were low. The profiles of these enzymes in acute pancreatitis decreased in a parallel fashion over 5 days except for PLA. We conclude that diagnostic utilities are similar for serum AMY, Lp, isoA, and urine AMY for acute pancreatitis, provided that an appropriate threshold is established.

  6. Meandering Main Pancreatic Duct as a Relevant Factor to the Onset of Idiopathic Recurrent Acute Pancreatitis

    PubMed Central

    Gonoi, Wataru; Akai, Hiroyuki; Hagiwara, Kazuchika; Akahane, Masaaki; Hayashi, Naoto; Maeda, Eriko; Yoshikawa, Takeharu; Kiryu, Shigeru; Tada, Minoru; Uno, Kansei; Ohtsu, Hiroshi; Okura, Naoki; Koike, Kazuhiko; Ohtomo, Kuni

    2012-01-01

    Background Meandering main pancreatic duct (MMPD), which comprises loop type and reverse-Z type main pancreatic duct (MPD), has long been discussed its relation to pancreatitis. However, no previous study has investigated its clinical significance. We aimed to determine the non-biased prevalence and the effect of MMPD on idiopathic pancreatitis using non-invasive magnetic resonance (MR) technique. Methods and Findings A cross-sectional study performed in a tertiary referral center. The study enrolled 504 subjects from the community and 30 patients with idiopathic pancreatitis (7 acute, 13 chronic, and 10 recurrent acute). All subjects underwent MR scanning and medical examination. MMPD was diagnosed when the MPD in the head of pancreas formed two or more extrema in the horizontal direction on coronal images of MR cholangiopancreatography, making a loop or a reverse-Z shaped hairpin curves and not accompanied by other pancreatic ductal anomaly. Statistical comparison was made among groups on the rate of MMPD including loop and reverse-Z subtypes, MR findings, and clinical features. The rate of MMPD was significantly higher for all idiopathic pancreatitis/idiopathic recurrent acute pancreatitis (RAP) (20%/40%; P<0.001/0.0001; odds ratio (OR), 11.1/29.0) than in the community (2.2%) but was not higher for acute/chronic pancreatitis (14%/8%; P = 0.154/0.266). Multiple logistic regression analysis revealed MMPD to be a significant factor that induces pancreatitis/RAP (P<0.0001/0.0001; OR, 4.01/26.2). Loop/reverse-Z subtypes were found more frequently in idiopathic RAP subgroup (20%/20%; P = 0.009/0.007; OR, 20.2/24.2) than in the community (1.2%/1.0%). The other clinical and radiographic features were shown not associated with the onset of pancreatitis. Conclusions MMPD is a common anatomical variant and might be a relevant factor to the onset of idiopathic RAP. PMID:22655061

  7. Crohn's disease and acute pancreatitis. A review of literature.

    PubMed

    Jasdanwala, Sarfaraz; Babyatsky, Mark

    2015-03-20

    Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.

  8. Radiotherapy for Pancreatic Neuroendocrine Tumors

    SciTech Connect

    Contessa, Joseph N.; Griffith, Kent A.; Wolff, Elizabeth; Ensminger, William; Zalupski, Mark; Ben-Josef, Edgar

    2009-11-15

    Purpose: Pancreatic neuroendocrine tumors (PNTs) are rare malignant neoplasms considered to be resistant to radiotherapy (RT), although data on efficacy are scarce. We reviewed our institutional experience to further delineate the role of RT for patients with PNTs. Methods and Materials: Between 1986 and 2006, 36 patients with PNTs were treated with RT to 49 sites. Of these 36 patients, 23 had radiographic follow-up data, which were used to determine the tumor response rate and freedom from local progression. Long-term toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: The overall response rate to RT was 39% (13% complete response, 26% partial response, 56% stable disease, and 4% progressive disease). A significant difference in the freedom from local progression between the groups receiving either greater than or less than the median 2 Gy/fraction biologically equivalent dose of 49.6 Gy was found, with all radiographic progression occurring in patients who had received <=32 Gy. The actuarial 3-year local freedom from progression rate was 49%. Palliation was achieved in 90% of patients, with either improvement or resolution of symptoms after RT. Of 35 patients, 33 had metastatic disease at their referral for RT, and the median overall survival for this patient population was 2 years. Three long-term Grade 3 or greater toxicities were recorded. Conclusion: RT is an effective modality for achieving local control in patients with PNTs. RT produces high rates of symptomatic palliation and freedom from local progression. Prospective trials of radiotherapy for PNTs are warranted.

  9. Pancreatic β Cell Mass Death

    PubMed Central

    Marrif, Husnia I.; Al-Sunousi, Salma I.

    2016-01-01

    Type two diabetes (T2D) is a challenging metabolic disorder for which a cure has not yet been found. Its etiology is associated with several phenomena, including significant loss of insulin-producing, beta cell (β cell) mass via progressive programmed cell death and disrupted cellular autophagy. In diabetes, the etiology of β cell death and the role of mitochondria are complex and involve several layers of mechanisms. Understanding the dynamics of those mechanisms could permit researchers to develop an intervention for the progressive loss of β cells. Currently, diabetes research has shifted toward rejuvenation and plasticity technology and away from the simplified approach of hormonal compensation. Diabetes research is currently challenged by questions such as how to enhance cell survival, decrease apoptosis and replenish β cell mass in diabetic patients. In this review, we discuss evidence that β cell development and mass formation are guided by specific signaling systems, particularly hormones, transcription factors, and growth factors, all of which could be manipulated to enhance mass growth. There is also strong evidence that β cells are dynamically active cells, which, under specific conditions such as obesity, can increase in size and subsequently increase insulin secretion. In certain cases of aggressive or advanced forms of T2D, β cells become markedly impaired, and the only alternatives for maintaining glucose homeostasis are through partial or complete cell grafting (the Edmonton protocol). In these cases, the harvesting of an enriched population of viable β cells is required for transplantation. This task necessitates a deep understanding of the pharmacological agents that affect β cell survival, mass, and function. The aim of this review is to initiate discussion about the important signals in pancreatic β cell development and mass formation and to highlight the process by which cell death occurs in diabetes. This review also examines the

  10. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    PubMed

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

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  11. Isolated Pancreatic Histoplasmosis: An Unusual Suspect of Pancreatic Head Mass in an Immunocompetent Host.

    PubMed

    Aggarwal, Avin; Garg, Shashank

    2015-01-01

    Histoplasmosis is endemic to the Mississippi and Ohio River valley regions in the US. It usually affects patients with underlying immunodeficiency but can also be seen in immunocompetent hosts. Although gastrointestinal involvement is common in the setting of disseminated histoplasmosis, isolated gastrointestinal involvement is uncommon. We report a case of isolated pancreatic histoplasmosis in an immunocompetent patient, presenting as painless jaundice and pancreatic head mass.

  12. BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

    PubMed

    Petrovic, I; Dobric, I; Drmic, D; Sever, M; Klicek, R; Radic, B; Brcic, L; Kolenc, D; Zlatar, M; Kunjko, K; Jurcic, D; Martinac, M; Rasic, Z; Boban Blagaic, A; Romic, Z; Seiwerth, S; Sikiric, P

    2011-10-01

    Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 μg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure.

  13. Chronic stress accelerates pancreatic cancer growth and invasion: a critical role for beta-adrenergic signaling in the pancreatic microenvironment.

    PubMed

    Kim-Fuchs, Corina; Le, Caroline P; Pimentel, Matthew A; Shackleford, David; Ferrari, Davide; Angst, Eliane; Hollande, Frédéric; Sloan, Erica K

    2014-08-01

    Pancreatic cancer cells intimately interact with a complex microenvironment that influences pancreatic cancer progression. The pancreas is innervated by fibers of the sympathetic nervous system (SNS) and pancreatic cancer cells have receptors for SNS neurotransmitters which suggests that pancreatic cancer may be sensitive to neural signaling. In vitro and non-orthotopic in vivo studies showed that neural signaling modulates tumour cell behavior. However the effect of SNS signaling on tumor progression within the pancreatic microenvironment has not previously been investigated. To address this, we used in vivo optical imaging to non-invasively track growth and dissemination of primary pancreatic cancer using an orthotopic mouse model that replicates the complex interaction between pancreatic tumor cells and their microenvironment. Stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells. Pharmacological activation of β-adrenergic signaling induced similar effects to chronic stress, and pharmacological β-blockade reversed the effects of chronic stress on pancreatic cancer progression. These findings indicate that neural β-adrenergic signaling regulates pancreatic cancer progression and suggest β-blockade as a novel strategy to complement existing therapies for pancreatic cancer.

  14. The gastric/pancreatic amylase ratio predicts postoperative pancreatic fistula with high sensitivity and specificity.

    PubMed

    Jin, Shuo; Shi, Xiao-Ju; Sun, Xiao-Dong; Zhang, Ping; Lv, Guo-Yue; Du, Xiao-Hong; Wang, Si-Yuan; Wang, Guang-Yi

    2015-01-01

    This article aims to identify risk factors for postoperative pancreatic fistula (POPF) and evaluate the gastric/pancreatic amylase ratio (GPAR) on postoperative day (POD) 3 as a POPF predictor in patients who undergo pancreaticoduodenectomy (PD).POPF significantly contributes to mortality and morbidity in patients who undergo PD. Previously identified predictors for POPF often have low predictive accuracy. Therefore, accurate POPF predictors are needed.In this prospective cohort study, we measured the clinical and biochemical factors of 61 patients who underwent PD and diagnosed POPF according to the definition of the International Study Group of Pancreatic Fistula. We analyzed the association between POPF and various factors, identified POPF risk factors, and evaluated the predictive power of the GPAR on POD3 and the levels of serum and ascites amylase.Of the 61 patients, 21 developed POPF. The color of the pancreatic drain fluid, POD1 serum, POD1 median output of pancreatic drain fluid volume, and GPAR were significantly associated with POPF. The color of the pancreatic drain fluid and high GPAR were independent risk factors. Although serum and ascites amylase did not predict POPF accurately, the cutoff value was 1.24, and GPAR predicted POPF with high sensitivity and specificity.This is the first report demonstrating that high GPAR on POD3 is a risk factor for POPF and showing that GPAR is a more accurate predictor of POPF than the previously reported amylase markers.

  15. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

    PubMed Central

    Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  16. Follicular pancreatitis, report of a case clinically mimicking pancreatic cancer and literature review.

    PubMed

    Mizuuchi, Yusuke; Aishima, Shinichi; Hattori, Masami; Ushijima, Yasuhiro; Aso, Akira; Takahata, Shunichi; Ohtsuka, Takao; Ueda, Junji; Tanaka, Masao; Oda, Yoshinao

    2014-02-01

    We herein present a 71-year-old man who underwent pancreatoduodenectomy with the diagnosis of follicular pancreatitis. We could not completely deny malignancy by a preoperative imaging study. Endoscopic ultrasonography-guided fine needle aspiration biopsy demonstrated clusters of benign acinar cells and no proliferation of atypical lymphoid cells or rich plasma cells. Histologically, the prominent lymphoid follicle formation was seen in an ill-defined mass, 15 mm in size, in the pancreatic parenchyma. Duct-centered fibrotic rims were seen in the pancreatic ducts accompanied by mild fibrotic change between the follicles and obliterative phlebitis. No neoplastic epithelial cells were observed in the resected specimen, and infiltrating lymphocytes did not show any morphological atypia and monoclonal proliferation by immunohistochemical staining with B and T cell markers. In addition, we could exclude IgG4-related disease, because plasmacytic cells were rarely positive for IgG4. Although follicular pancreatitis is rare, this mass-forming inflammatory disease (pancreatitis) should be included in the preoperative differential diagnosis of pancreatic cancer.

  17. [Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

    PubMed

    Takács, Tamás; Czakó, László; Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Patai, Árpád; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Tiszlavicz, László; Szücs, Ákos

    2015-02-15

    Chronic pancreatitis is an inflammatory disease associated with structural and functional damage of the pancreas. In most cases pain, maldigestion and weight loss are the leading symptoms, which significantly worsen the quality of life. Correct diagnosis and differential diagnosis of chronic pancreatitis and treatment of these patients requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 123 relevant clinical questions in 11 topics were defined. Evidence was classified according to the UpToDate® grading system. The draft of the guidelines were presented and discussed at the consensus meeting in September 12, 2014. All clinical questions were accepted with total or strong agreement. The present guideline is the first evidence based guideline for chronic pancreatitis in Hungary. This guideline provides very important and helpful data for tuition, everyday practice and proper financing of chronic pancreatitis. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

  18. Early Detection of Sporadic Pancreatic Cancer

    PubMed Central

    Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

    2015-01-01

    Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

  19. Common bile duct involvement in chronic pancreatitis.

    PubMed

    Angelini, G; Sgarbi, D; Castagnini, A; Cavallini, G; Bovo, P

    1994-03-01

    The features of the common bile duct (CBD) have been checked in 78 chronic pancreatitis patients in order to evaluate the frequency of extrahepatic bile duct changes, possible associated factors and effects on the outcome of the disease. Fifty of the 78 patients had an intrapancreatic stricture of the CBD and 24 of them also showed an upstream dilatation. No relationship was found between the features of the CBD and the severity of the pancreatitis, the presence of calcifications and the length of the disease. Humoral signs of impaired bile flow were found in 20 subjects, 19 of whom had an intra-pancreatic stricture of the CBD. Sixteen of these 19 patients also showed an upstream dilatation and five of them had overt jaundice. A surgical intervention on the biliary tree was carried out in 7 patients, all with a biliary stricture. Six of them also had a CBD dilatation over the stricture (p < 0.02 versus patients without CBD stricture). In conclusion CBD involvement during chronic pancreatitis is quite frequent but poorly predictable and should be checked in all patients with humoral cholestasis in order to prevent further complications.

  20. 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.

  1. Polyphenolic Compounds as Pancreatic Lipase Inhibitors.

    PubMed

    Buchholz, Tina; Melzig, Matthias F

    2015-07-01

    Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion.

  2. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    PubMed

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  3. [Significance of prognostic parameters in acute pancreatitis].

    PubMed

    Guastella, T; Scuderi, M; Di Stefano, A; Scala, R; Rapisarda, D; Succi, L; Russello, D

    1993-07-01

    The diagnostic and therapeutic approach to Acute Pancreatitis (A.P.) is directly related to the clinical presentation. The Authors reviewed the data of 66 patients, hospitalized between October 1989 and December 1991, to verify the effectiveness of the prognostic criteria suggested by Ranson (1974), Mercadier (1977) and Imrie (1978). A.P. was of biliary origin in the majority of the patients (63.5%); five patients (7.5%) had an acute alcoholic pancreatitis, while the aetiology was traumatic or unknown in the remaining cases. A complicated clinical course was defined by the development of pseudocyst, pancreatic abscess, digestive haemorrhage, death or prolonged hospitalization (more than 20 days). The 28.8% of the patients developed complications during hospitalization. There were seven pancreatic pseudocysts, six pulmonary complications, three renal insufficiencies, two vascular complications, two sepsies and a gastrointestinal haemorrhage. The mean hospitalization period was 15.1 days (range 1-112). The Authors conclude that the three different prognostic criteria are equally useful to test the severity of A.P. attacks allowing to identify patients with the higher risk to develop complications during hospitalization.

  4. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

    PubMed Central

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-01-01

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. PMID:24084722

  5. Duodenal leiomyosarcoma mimicking a pancreatic pseudocyst.

    PubMed

    Sperti, C; Pasquali, C; Di Prima, F; Baffa, R; Pedrazzoli, S

    1994-01-01

    A case of duodenal leiomyosarcoma presenting as a cystic mass is reported. Amylase, tumour markers levels in the cyst fluid and radiological findings suggested an inflammatory pancreatic pseudocyst. Exploratory laparotomy and frozen section examination showed a smooth muscle tumour of the duodenum. Pancreatoduodenectomy with pylorus-preser vation was performed and the patient remained symptom-free at 8 months follow-up.

  6. Tamoxifen-induced hypertriglyceridemia causing acute pancreatitis

    PubMed Central

    Singh, Hemant Kumar; Prasad, Mahendranath S.; Kandasamy, Arun K.; Dharanipragada, Kadambari

    2016-01-01

    Tamoxifen has both antagonistic and agonistic tissue-specific actions. It can have a paradoxical estrogenic effect on lipid metabolism resulting in elevated triglyceride and chylomicron levels. This can cause life-threatening complications like acute pancreatitis. To our knowledge, very few cases of tamoxifen-induced pancreatitis have been reported in the literature. We report a case of severe hypertriglyceridemia and acute pancreatitis following tamoxifen use. A 50-year-old diabetic lady was on tamoxifen (20mg/day) hormonal therapy for breast cancer. Within 3 months of starting therapy, she developed hypertriglyceridemia and acute pancreatitis. Laboratory values include: Serum amylase 778 IU/L, total cholesterol 785 mg/dL, triglycerides 4568 mg/dL and high-density lipoproteins (HDL) 12 mg/dL. Tamoxifen was substituted with letrozole and atorvastatin started. There was a prompt reversal of the adverse effects. Effects on lipid profile must be considered while initiating tamoxifen in predisposed individuals as the consequences are life threatening. PMID:27127396

  7. Clinical practice guideline: management of acute pancreatitis

    PubMed Central

    Greenberg, Joshua A.; Hsu, Jonathan; Bawazeer, Mohammad; Marshall, John; Friedrich, Jan O.; Nathens, Avery; Coburn, Natalie; May, Gary R.; Pearsall, Emily; McLeod, Robin S.

    2016-01-01

    There has been an increase in the incidence of acute pancreatitis reported worldwide. Despite improvements in access to care, imaging and interventional techniques, acute pancreatitis continues to be associated with significant morbidity and mortality. Despite the availability of clinical practice guidelines for the management of acute pancreatitis, recent studies auditing the clinical management of the condition have shown important areas of noncompliance with evidence-based recommendations. This underscores the importance of creating understandable and implementable recommendations for the diagnosis and management of acute pancreatitis. The purpose of the present guideline is to provide evidence-based recommendations for the management of both mild and severe acute pancreatitis as well as the management of complications of acute pancreatitis and of gall stone–induced pancreatitis. Une hausse de l’incidence de pancréatite aiguë a été constatée à l’échelle mondiale. Malgré l’amélioration de l’accès aux soins et aux techniques d’imagerie et d’intervention, la pancréatite aiguë est toujours associée à une morbidité et une mortalité importantes. Bien qu’il existe des guides de pratique clinique pour la prise en charge de la pancréatite aiguë, des études récentes sur la vérification de la prise en charge clinique de cette affection révèlent des lacunes importantes dans la conformité aux recommandations fondées sur des données probantes. Ces résultats mettent en relief l’importance de formuler des recommandations compréhensibles et applicables pour le diagnostic et la prise en charge de la pancréatite aiguë. La présente ligne directrice vise à fournir des recommandations fondées sur des données probantes pour la prise en charge de la pancréatite aiguë, qu’elle soit bénigne ou grave, ainsi que de ses complications et de celles de la pancréatite causée par un calcul biliaire. PMID:27007094

  8. MicroRNA Targeted Therapeutic Approach for Pancreatic Cancer

    PubMed Central

    Li, Yiwei; Sarkar, Fazlul H.

    2016-01-01

    Pancreatic cancer remains the fourth leading cause of cancer-related death in the US and is expected to be the second leading cause of cancer-related death by 2030. Therefore, it is important to better understand the molecular pathogenesis, phenotypes and features of pancreatic cancer in order to design novel molecularly targeted therapies for achieving better therapeutic outcome of patients with pancreatic cancer. Recently, the roles of microRNAs (miRNAs) in the development and progression of pancreatic cancer became a hot topic in the scientific community of pancreatic cancer research. By conducting miRNA expression profiling, the aberrant expression of miRNAs was revealed in the serum and in cancer tissues from patients with pancreatic cancer. These aberrantly expressed miRNAs are critically correlated with the disease stage, drug resistance, and survival of pancreatic cancer patients. Hence, targeting these tiny molecules, the specific miRNAs, could provide an efficient and optimal approach in the therapy of pancreatic cancer. Indeed, the pre-clinical and in vivo experiments showed that nanoparticle delivery of synthetic oligonucleotides or treatment with natural agents could be useful to modulate the expression of miRNAs and thereby inhibit pancreatic cancer growth and progression, suggesting that targeting miRNAs combined with conventional anti-cancer therapeutics could be a novel therapeutic strategy for increasing drug sensitivity and achieving better therapeutic outcome of patients diagnosed with pancreatic cancer. PMID:26929739

  9. 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.

  10. Familial pancreatic cancer: Concept, management and issues

    PubMed Central

    Matsubayashi, Hiroyuki; Takaori, Kyoichi; Morizane, Chigusa; Maguchi, Hiroyuki; Mizuma, Masamichi; Takahashi, Hideaki; Wada, Keita; Hosoi, Hiroko; Yachida, Shinichi; Suzuki, Masami; Usui, Risa; Furukawa, Toru; Furuse, Junji; Sato, Takamitsu; Ueno, Makoto; Kiyozumi, Yoshimi; Hijioka, Susumu; Mizuno, Nobumasa; Terashima, Takeshi; Mizumoto, Masaki; Kodama, Yuzo; Torishima, Masako; Kawaguchi, Takahisa; Ashida, Reiko; Kitano, Masayuki; Hanada, Keiji; Furukawa, Masayuki; Kawabe, Ken; Majima, Yoshiyuki; Shimosegawa, Toru

    2017-01-01

    Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish > Caucasian) and a younger onset are common also in FPC. In European countries, “anticipation” is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-ras mutations, similar to colorectal polyposis seen in the FAP patients. As with HBOC patients, a patient who is a BRCA mutation carrier with unresectable pancreatic cancer (accounting for 0%-19% of FPC patients) demonstrated better outcome following platinum and Poly (ADP-ribose) polymerase inhibitor treatment. Western countries have established FPC registries since the 1990s and several surveillance projects for high-risk individuals are now ongoing to detect early PCs. Improvement in lifestyle habits, including non-smoking, is recommended for individuals at risk. In Japan, the FPC study group was initiated in 2013 and the Japanese FPC registry was established in 2014 by the Japan Pancreas Society. PMID:28246467

  11. Pancreatic cancer surgery: past, present, and future

    PubMed Central

    Poruk, Katherine E.

    2015-01-01

    The history of pancreatic cancer surgery, though fraught with failure and setbacks, is punctuated by periods of incremental progress dependent upon the state of the art and the mettle of the surgeons daring enough to attempt it. Surgical anesthesia and the aseptic techniques developed during the latter half of the 19th century were instrumental in establishing a viable setting for pancreatic surgery to develop. Together, they allowed for bolder interventions and improved survival through the post-operative period. Surgical management began with palliative procedures to address biliary obstruction in advanced disease. By the turn of the century, surgical pioneers such as Alessandro Codivilla and Walther Kausch were demonstrating the technical feasibility of pancreatic head resections and applying principles learned from palliation to perform complicated anatomical reconstructions. Allen O. Whipple, the namesake of the pancreaticoduodenectomy (PD), was the first to take a systematic approach to refining the procedure. Perhaps his greatest contribution was sparking a renewed interest in the surgical management of periampullary cancers and engendering a community of surgeons who advanced the field through their collective efforts. Though the work of Whipple and his contemporaries legitimized PD as an accepted surgical option, it was the establishment of high-volume centers of excellence and a multidisciplinary approach in the later decades of the 20th century that made it a viable surgical option. Today, pancreatic surgeons are experimenting with minimally invasive surgical techniques, expanding indications for resection, and investigating new methods for screening and early detection. In the future, the effective management of pancreatic cancer will depend upon our ability to reliably detect the earliest cancers and precursor lesions to allow for truly curative resections. PMID:26361403

  12. Nanoparticle formulation of ormeloxifene for pancreatic cancer

    PubMed Central

    Khan, Sheema; Chauhan, Neeraj; Yallapu, Murali M.; Ebeling, Mara C.; Balakrishna, Swathi; Ellis, Robert T.; Thompson, Paul A.; Balabathula, Pavan; Behrman, Stephen W.; Zafar, Nadeem; Singh, Man Mohan; Halaweish, Fathi T.; Jaggi, Meena; Chauhan, Subhash C.

    2015-01-01

    Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery. Therefore, we have developed a novel ORM encapsulated poly(lactic-co-glycolic acid) nanoparticle (NP) formulation (PLGA-ORM NP). This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). Because of its facile composition, this novel formulation is compatible with antibody/aptamer conjugation to achieve tumor specific targeting. The particle size analysis of this PLGA-ORM formulation (~ 100 nm) indicates that this formulation can preferentially reach and accumulate in tumors by the Enhanced Permeability and Retention (EPR) effect. Cellular uptake and internalization studies demonstrate that PLGA-ORM NPs escape lysosomal degradation, providing efficient endosomal release to cytosol. PLGA-ORM NPs showed remarkable anti-cancer potential in various pancreatic cancer cells (HPAF-II, BxPC-3, Panc-1, MiaPaca) and a BxPC-3 xenograft mice model resulting in increased animal survival. PLGA-ORM NPs suppressed pancreatic tumor growth via suppression of Akt phosphorylation and expression of MUC1, HER2, PCNA, CK19 and CD31. This study suggests that the PLGA-ORM formulation is highly efficient for the inhibition of pancreatic tumor growth and thus can be valuable for the treatment of pancreatic cancer in the future. PMID:25890768

  13. Pancreatic Panniculitis in an 18-Month-Old with Complete DiGeorge Syndrome.

    PubMed

    Aivaz, Ohara; Radfar, Arash; Kirkorian, Anna Yasmine

    2016-05-01

    Pancreatic panniculitis, characterized by tender, erythematous subcutaneous nodules occurring most commonly on the lower extremities, occurs in 2% of cases of pancreatic disease. We present a rare case of pancreatic panniculitis in a child with complete DiGeorge syndrome.

  14. Alisertib and Gemcitabine Hydrochloride in Treating Patients With Solid Tumors or Pancreatic Cancer

    ClinicalTrials.gov

    2017-01-19

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  15. Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis

    PubMed Central

    Apte, M; Haber, P; Darby, S; Rodgers, S; McCaughan, G; Korsten, M; Pirola, R; Wilson, J

    1999-01-01

    BACKGROUND—The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress. 
AIMS—To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor β (TGF-β). 
METHODS—Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-β. 
RESULTS—Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of 3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-β showed a dose dependent increase in α smooth muscle actin expression and increased collagen synthesis. In addition, TGF-β increased the expression of PDGF receptors on stellate cells. 
CONCLUSIONS—Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-β by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis. 

 Keywords: pancreatic fibrosis; stellate cell activation; cytokines PMID:10075961

  16. Duodenal acidity may increase the risk of pancreatic cancer in the course of chronic pancreatitis: an etiopathogenetic hypothesis.

    PubMed

    Talamini, Giorgio

    2005-03-10

    Chronic pancreatitis patients have an increased risk of developing pancreatic cancer. The cause of this increase has yet to be fully explained but smoking and inflammation may play an important role. To these, we must now add a new potential risk factor, namely duodenal acidity. Patients with chronic pancreatitis very often present pancreatic exocrine insufficiency combined with a persistently low duodenal pH in the postprandial period. The duodenal mucosa in chronic pancreas patients with pancreatic insufficiency has a normal concentration of s-cells and, therefore, the production of secretin is preserved. Pancreatic ductal cells are largely responsible for the amount of bicarbonate and water secretion in response to secretin stimulation. When gastric acid in the duodenum is not well-balanced by alkaline pancreatic secretions, it may induce a prolonged secretin stimulus which interacts with the pancreatic ductal cells resulting in an increased rate of ductular cell activity and turnover. N-Nitroso compounds from tobacco, identified in human pancreatic juice and known to be important carcinogens, may then act on these active cells, thereby increasing the risk of cancer. Duodenal acidity is probably of particular concern in patients who have undergone a duodenum-preserving pancreatic head resection, since, in this anatomic situation, pancreatic juice transits directly via the jejunal loop, bypassing the duodenum. Patients undergoing a Whipple procedure or side-to-side pancreaticojejunostomy are probably less critically affected because secretions transit, at least in part, via the papilla. If the duodenal acidity hypothesis proves correct, then, in addition to stopping smoking, reduction of duodenal acid load in patients with pancreatic insufficiency may help decrease the risk of pancreatic cancer.

  17. Duct Drainage Alone is Sufficient in the Operative Management of Pancreatic Pseudocyst in Patients With Chronic Pancreatitis

    PubMed Central

    Nealon, William H.; Walser, Eric

    2003-01-01

    Objective To test a hypothesis that definitive management of pseudocyst associated with chronic pancreatitis is predicated on addressing pancreatic ductal anatomy. Summary Background Data The authors have previously confirmed the impact of pancreatic ductal anatomic abnormalities on the success of percutaneous drainage of pancreatic pseudocyst. The authors have further defined a system to categorize the pancreatic ductal abnormalities that can be seen with pancreatic pseudocyst. The authors have published, as have others, the usefulness of defining ductal anatomy when managing pancreatic pseudocysts associated with chronic pancreatitis. Methods Beginning in 1985, all patients with pseudocyst who were candidates for intervention (operative, percutaneous, or endoscopic) have undergone endoscopic retrograde cholangiopancreatography (ERCP). An associated diagnosis of chronic pancreatitis was established by means of ERCP findings. Patients were candidates for longitudinal pancreaticojejunostomy (LPJ) if they had a pancreatic ductal diameter greater than 7 mm. In a nonrandomized fashion, patients were managed with either combined simultaneous LPJ and pseudocyst drainage or with LPJ alone. Results Two hundred fifty-three patients with pseudocyst have been evaluated. Among these there have been 103 patients with chronic pancreatitis and main pancreatic duct (MPD) dilatation (>7 mm). Among these 103 patients, 56 underwent combined LPJ/pseudocyst drainage and 47 had LPJ alone. Compared to combined LPJ/pseudocyst drainage, the patients undergoing LPJ alone had a shorter operative time, slightly less transfusion requirement, slightly reduced length of hospital stay, and slightly reduced complication rate. Long-term pain relief was achieved in 90%, and pseudocyst recurrence was less than 1%. Rates of each of these long-term outcomes were nearly incidental among the two groups. Conclusions Ductal drainage alone (LPJ) is sufficient in patients with chronic pancreatitis (MPD > 7

  18. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    ClinicalTrials.gov

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  19. RON is not a prognostic marker for resectable pancreatic cancer

    PubMed Central

    2012-01-01

    Background The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. Methods RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. Results RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Conclusions Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer. PMID:22958871

  20. Synchronous anterior celiotomy and posterior drainage of pancreatic abscess.

    PubMed

    Berne, T V; Donovan, A J

    1981-05-01

    Pancreatic abscess has been characterized by a high rate of reoperation for persistent sepsis and by a high mortality. Nine patients with pancreatic abscess have undergone synchronous anterior celiotomy and posterior drainage following resection of the 12th rib. Pancreatic abscess was secondary to acute pancreatitis in seven of the cases. In two cases, the combined procedure was a secondary operation to treat abscess that developed following surgery for pancreatic trauma. All of these nine patients survived. One patient required reoperation for drainage of a left retrocolic abscess. A synchronous approach permits adequate exploration of the abdomen, provides the exposure necessary to remove necrotic tissue, and allows dependent drainage of the left subphrenic space without fear of splenic, pancreatic, or vascular injury.

  1. Early laparoscopic approach to pancreatic injury following blunt abdominal trauma.

    PubMed

    Vijay, Adarsh; Abdelrahman, Husham; El-Menyar, Ayman; Al-Thani, Hassan

    2014-12-04

    The incidence of pancreatic injury following blunt abdominal trauma is rare. A timely accurate diagnosis of such injury is difficult and also the management remains controversial. Here, we reported the successful use of laparoscopy to diagnose, characterize and treat blunt pancreatic trauma in a 28-year-old male patient involved in a motor vehicle crash. An abdominal computed tomography scan showed peripancreatic fat stranding suggestive of pancreatic injury. With persistent clinical signs of peritonitis and laboratory investigations suggestive of pancreatitis, the patient underwent laparoscopic drainage of the lesser sac. The patient had an uneventful postoperative course. The management of patients with blunt pancreatic injuries should be tailored to individual situations. Our experience suggests that a timely laparoscopic management of traumatic pancreatic injury is safe approach in selected cases.

  2. Genetics of Alcoholic and Non-Alcoholic Pancreatitis

    PubMed Central

    Whitcomb, David C

    2013-01-01

    Purpose of review To provide an expert review and expert perspective on important advances related to the genetics of acute and chronic pancreatitis. Recent findings Provocative new reports highlight the interplay between genetic, developmental and environmental factors. Key findings include the relationship between pancreas divisum and CFTR mutations, the role of trypsin in acute and recurrent acute pancreatitis and the discovery of a pancreatitis modifier gene on the X chromosome that provides new clues to why the vast majority of patients with alcoholic pancreatitis are men. Summary Pancreatic genetics is complex, linked to the multiplicative and modifying effects of multiple interacting genetic, structural and environmental factors. Clinical interpretation will require disease modeling and simulation to understand the combined effect of risk factors that alone are neither sufficient or necessary to cause disease, and to design treatment strategies that prevent the develop of advanced chronic pancreatitis – which by definition is irreversible. PMID:22885947

  3. Proteomics analysis of bodily fluids in pancreatic cancer

    PubMed Central

    Pan, Sheng; Brentnall, Teresa A.; Chen, Ru

    2015-01-01

    Proteomics study of pancreatic cancer using bodily fluids emphasizes biomarker discovery and clinical application, presenting unique prospect and challenges. Depending on the physiological nature of the bodily fluid and its proximity to pancreatic cancer, the proteomes of bodily fluids, such as pancreatic juice, pancreatic cyst fluid, blood, bile and urine, can be substantially different in terms of protein constitution and the dynamic range of protein concentration. Thus, a comprehensive discovery and specific detection of cancer-associated proteins within these varied fluids is a complex task, requiring rigorous experiment design and a concerted approach. While major challenges still remain, fluid proteomics studies in pancreatic cancer to date have provided a wealth of information in revealing proteome alterations associated with pancreatic cancer in various bodily fluids. PMID:25780901

  4. Pancreatic rupture in four cats with high-rise syndrome.

    PubMed

    Liehmann, Lea M; Dörner, Judith; Hittmair, Katharina M; Schwendenwein, Ilse; Reifinger, Martin; Dupré, Gilles

    2012-02-01

    Pancreatic trauma and rupture are rare after feline high-rise syndrome; however, should it happen, pancreatic enzymes will leak into the abdominal cavity and may cause pancreatic autodigestion and fatty tissue saponification. If not diagnosed and treated, it can ultimately lead to multiorgan failure and death. In this case series, 700 records of high-rise syndrome cats that presented between April 2001 and May 2006 were analysed, and four cats with pancreatic rupture were identified. Clinical signs, diagnosis using ultrasonography and lipase activity in blood and abdominal effusion, and treatment modalities are reported. Three cats underwent surgical abdominal exploration, one cat was euthanased. Rupture of the left pancreatic limb was confirmed in all cases. Two of the operated cats survived to date. High-rise syndrome can lead to abdominal trauma, including pancreatic rupture. A prompt diagnosis and surgical treatment should be considered.

  5. Keratinocyte growth factor induces pancreatic ductal epithelial proliferation.

    PubMed

    Yi, E S; Yin, S; Harclerode, D L; Bedoya, A; Bikhazi, N B; Housley, R M; Aukerman, S L; Morris, C F; Pierce, G F; Ulich, T R

    1994-07-01

    Keratinocyte growth factor (KGF) causes a proliferation of pancreatic ductal epithelial cells in adult rats after daily systemic administration for 1 to 2 weeks. Even before the proliferation of intralobular ducts is histologically evident, KGF also induces proliferating cell nuclear antigen expression within the ductal epithelium of intercalated, intralobular, and interlobular ducts. KGF also causes incorporation of 5-bromodeoxyuridine in ductal epithelial cells. Epithelial cell proliferation is histologically most prominent at the level of the intralobular ducts adjacent to and within the islets of Langerhans. Pancreatic ductal proliferation is not histologically apparent in rats sacrificed 7 to 10 days after the cessation of KGF administration. The pancreatic hormones insulin, glucagon, somatostatin, and pancreatic polypeptide are normally distributed within islets that demonstrate intrainsular ductal proliferation. The proliferating ductal epithelium does not show endocrine differentiation as evidenced by the lack of immunoreactivity for pancreatic hormones. KGF is a potent in vivo mitogen for pancreatic ductal epithelial cells.

  6. Staining Protocols for Human Pancreatic Islets

    PubMed Central

    Campbell-Thompson, Martha L.; Heiple, Tiffany; Montgomery, Emily; Zhang, Li; Schneider, Lynda

    2012-01-01

    Estimates of islet area and numbers and endocrine cell composition in the adult human pancreas vary from several hundred thousand to several million and beta mass ranges from 500 to 1500 mg 1-3. With this known heterogeneity, a standard processing and staining procedure was developed so that pancreatic regions were clearly defined and islets characterized using rigorous histopathology and immunolocalization examinations. Standardized procedures for processing human pancreas recovered from organ donors are described in part 1 of this series. The pancreas is processed into 3 main regions (head, body, tail) followed by transverse sections. Transverse sections from the pancreas head are further divided, as indicated based on size, and numbered alphabetically to denote subsections. This standardization allows for a complete cross sectional analysis of the head region including the uncinate region which contains islets composed primarily of pancreatic polypeptide cells to the tail region. The current report comprises part 2 of this series and describes the procedures used for serial sectioning and histopathological characterization of the pancreatic paraffin sections with an emphasis on islet endocrine cells, replication, and T-cell infiltrates. Pathology of pancreatic sections is intended to characterize both exocrine, ductular, and endocrine components. The exocrine compartment is evaluated for the presence of pancreatitis (active or chronic), atrophy, fibrosis, and fat, as well as the duct system, particularly in relationship to the presence of pancreatic intraductal neoplasia4. Islets are evaluated for morphology, size, and density, endocrine cells, inflammation, fibrosis, amyloid, and the presence of replicating or apoptotic cells using H&E and IHC stains. The final component described in part 2 is the provision of the stained slides as digitized whole slide images. The digitized slides are organized by case and pancreas region in an online pathology database

  7. Staining protocols for human pancreatic islets.

    PubMed

    Campbell-Thompson, Martha L; Heiple, Tiffany; Montgomery, Emily; Zhang, Li; Schneider, Lynda

    2012-05-23

    Estimates of islet area and numbers and endocrine cell composition in the adult human pancreas vary from several hundred thousand to several million and beta mass ranges from 500 to 1500 mg. With this known heterogeneity, a standard processing and staining procedure was developed so that pancreatic regions were clearly defined and islets characterized using rigorous histopathology and immunolocalization examinations. Standardized procedures for processing human pancreas recovered from organ donors are described in part 1 of this series. The pancreas is processed into 3 main regions (head, body, tail) followed by transverse sections. Transverse sections from the pancreas head are further divided, as indicated based on size, and numbered alphabetically to denote subsections. This standardization allows for a complete cross sectional analysis of the head region including the uncinate region which contains islets composed primarily of pancreatic polypeptide cells to the tail region. The current report comprises part 2 of this series and describes the procedures used for serial sectioning and histopathological characterization of the pancreatic paraffin sections with an emphasis on islet endocrine cells, replication, and T-cell infiltrates. Pathology of pancreatic sections is intended to characterize both exocrine, ductular, and endocrine components. The exocrine compartment is evaluated for the presence of pancreatitis (active or chronic), atrophy, fibrosis, and fat, as well as the duct system, particularly in relationship to the presence of pancreatic intraductal neoplasia. Islets are evaluated for morphology, size, and density, endocrine cells, inflammation, fibrosis, amyloid, and the presence of replicating or apoptotic cells using H&E and IHC stains. The final component described in part 2 is the provision of the stained slides as digitized whole slide images. The digitized slides are organized by case and pancreas region in an online pathology database creating a

  8. Small amounts of tissue preserve pancreatic function

    PubMed Central

    Lu, Zipeng; Yin, Jie; Wei, Jishu; Dai, Cuncai; Wu, Junli; Gao, Wentao; Xu, Qing; Dai, Hao; Li, Qiang; Guo, Feng; Chen, Jianmin; Xi, Chunhua; Wu, Pengfei; Zhang, Kai; Jiang, Kuirong; Miao, Yi

    2016-01-01

    Abstract Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear. The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP. From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires. Our case series included 3 women and 2 men, with median age of 50 (37–81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250–615) min and 800 (400–5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4

  9. Tuberculous pancreatic abscess: an unusual manifestation of HIV infection.

    PubMed Central

    Desmond, N M; Kingdon, E; Beale, T J; Coker, R J; Tanner, A G; Harris, J W

    1995-01-01

    Pancreatic tuberculosis is unusual occurring in only 2.7% of autopsy studies of persons with miliary disease. Reports of focal pancreatic tuberculosis are rare, even in patients with the acquired immunodeficiency syndrome (AIDS) in whom abdominal tuberculosis is a frequent feature. We describe two patients infected with the human immunodeficiency virus (HIV) who developed tuberculous pancreatic abscesses. In both this was their AIDS-defining illness. Images Figure 1 PMID:7769586

  10. What Have We Learned About Acute Pancreatitis in Children?

    PubMed Central

    Bai, Harrison X.; Lowe, Mark E.; Husain, Sohail Z.

    2012-01-01

    Pediatric pancreatitis has received much attention during the past few years. Numerous reports have identified an increasing trend in the diagnosis of acute pancreatitis in children and key differences in disease presentation and management between infants and older children. The present review provides a brief, evidence-based focus on the latest progress in the clinical field. It also poses important questions for emerging multicenter registries to answer about the natural history and management of affected children with pancreatitis. PMID:21336157

  11. From acute to chronic pancreatitis: the role of mutations in the pancreatic secretory trypsin inhibitor gene.

    PubMed

    Hirota, Masahiko; Kuwata, Kinuko; Ohmuraya, Masaki; Ogawa, Michio

    2003-03-01

    Pancreatic secretory trypsin inhibitor (PSTI) is a potent natural inhibitor of trypsin. We proposed the hypothesis that, if the function of the PSTI is impaired by its genetic mutation, trypsin may easily promote autodigestion causing pancreatitis and we performed a mutational analysis of the PSTI gene in patients with pancreatitis. Two exonic mutations (N34S and R67C) were thought to be associated with a predisposition to pancreatitis. The N34S mutation was co-segregated with two intronic mutations, IVS1-37T>C and IVS3-69insTTTT. Although we analyzed the function of the recombinant N34S protein, we could not demonstrate the loss of function of this protein. Intronic mutations, rather than N34S itself (IVS1-37T>C + N34S + IVS3-69insTTTT complex), may be associated with the decreased function of the PSTI. Alternatively, increased digestion of N34S in vivo may be applicable. As for R67C, the conformational alteration of the protein by forming intra-molecular or inter-molecular disulfide bonds with 67Cys was strongly suggested. These results, along with the brand-new findings in PSTI knockout mice, suggest that the genetic mutation of the PSTI is one of the important mechanisms for predisposition to pancreatitis by lowering the trypsin inhibitory function.

  12. Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis

    PubMed Central

    Charrier, Alyssa; Brigstock, David R.

    2010-01-01

    Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is due to excessive collagen deposition by activated pancreatic stellate cells (PSC). The aim of this study was to establish a model of ACP in mice, a species that is usually resistant to the toxic effects of alcohol, and to identify the cell type(s) responsible for production of connective tissue growth factor (CTGF), a pro-fibrotic molecule. C57Bl/6 male mice received intraperitoneal ethanol injections for three weeks against a background of cerulein-induced acute pancreatitis. Peak blood alcohol levels remained consistently high in ethanol-treated mice as compared to control mice. In mice receiving ethanol plus cerulein, there was increased collagen deposition as compared to other treatment groups as well as increased frequency of α-smooth muscle actin and desmin-positive PSC which also demonstrated significantly enhanced CTGF protein production. Expression of mRNA for collagen α1(I), α-smooth muscle actin or CTGF were all increased and co-localized exclusively to activated PSC in ACP. Pancreatic expression of mRNA for key profibrotic markers were all increased in ACP. In conclusion, a mouse model of ACP has been developed that mimics key pathophysiological features of the disease in humans and which shows that activated PSC are the principal producers of collagen and CTGF. PSC-derived CTGF is thus a candidate therapeutic target in anti-fibrotic strategies for ACP. PMID:20368699

  13. Melatonin reduces pancreatic prostaglandins production and protects against caerulein-induced pancreatitis in rats.

    PubMed

    Chen, Han-Ming; Chen, Jih-Chang; Ng, Chip-Jin; Chiu, De-Fa; Chen, Miin-Fu

    2006-01-01

    Melatonin has been used to treat experimental pancreatitis, although not all the drug's therapeutic mechanisms of melatonin have been defined. Prostaglandins (PGs) are proinflammatory mediators that exert their effects mainly locally during inflammatory diseases. The present study was undertaken to examine whether treatment with melatonin influences local PG production. An acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by continuously infusing caerulein (15 mg/kg/hr). Mean arterial pressure and pancreatic perfusion were monitored continuously. Melatonin was delivered via the intraperitoneal route at doses of either 2 or 10 mg/kg, 30 min after caerulein injection. Malondialdehyde and glutathione levels of the pancreas and liver and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hr after infusion of caerulein). Intraperitoneal injection of melatonin (2 and 10 mg/kg) reduced the reduction in systemic arterial pressure and decreased pancreatic perfusion in the rat model of caerulein pancreatitis. Moreover, melatonin treatment changed local PG production toward control level. Higher dose of melatonin was somewhat more effective in preventing the caerulein-induced alterations than was the lower dose.

  14. 4-Phenylbutyric Acid Attenuates Pancreatic Beta-Cell Injury in Rats with Experimental Severe Acute Pancreatitis

    PubMed Central

    Guo, Wen-yi; Zhao, Liang; Xiang, Ming-wei; Mei, Fang-chao; Abliz, Ablikim; Hu, Peng; Deng, Wen-hong; Yu, Jia

    2016-01-01

    Endoplasmic reticulum (ER) stress is a particular process with an imbalance of homeostasis, which plays an important role in pancreatitis, but little is known about how ER stress is implicated in severe acute pancreatitis (SAP) induced pancreatic beta-cell injury. To investigate the effect of 4-phenylbutyric acid (4-PBA) on the beta-cell injury following SAP and the underlying mechanism, twenty-four Sprague-Dawley rats were randomly divided into sham-operation (SO) group, SAP model group, and 4-PBA treatment group. SAP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. 4-PBA or normal saline was injected intraperitoneally for 3 days in respective group before successful modeling. Results showed that 4-PBA attenuated the following: (1) pancreas and islet pathological injuries, (2) serum TNF-α and IL-1β, (3) serum insulin and glucose, (4) beta-cell ultrastructural changes, (5) ER stress markers (BiP, ORP150, and CHOP), Caspase-3, and insulin expression in islet. These results suggested that 4-PBA mitigates pancreatic beta-cell injury and endocrine disorder in SAP, presumably because of its role in inhibiting excessive endoplasmic reticulum stress. This may serve as a new therapeutic target for reducing pancreatic beta-cell injury and endocrine disorder in SAP upon 4-PBA treatment. PMID:27656209

  15. 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

  16. Interventional Therapy for Pancreatic Cancer

    PubMed Central

    Zhu, Jianwei; Jin, Zhendong

    2016-01-01

    Background Palliative therapy and primarily chemoradiotherapy are the mainstream treatments in patients with locally advanced or metastatic pancreatic cancer (PC). Conventional endoscopy and endoscopic ultrasound (EUS)-guided interventional therapy has emerged as an important procedure for PC management. In this review, the progress in conventional endoscopy and EUS for PC management is discussed. Summary For local palliative therapy against PC, EUS-guided fine needle injection (FNI) could deliver different kinds of agents, such as radioactive seeds and fiducials. Although their feasibility and safety have been proven, the long-term efficiency of EUS-FNI is still not established. For pain, EUS-celiac plexus neurolysis (CPN) is effective. However, CPN can only relieve the pain to a limited degree, with short duration. Endoscopy-guided stent placement is the preferred strategy for biliary and duodenal obstruction. Plastic and metal stents are equally effective for the relief of obstructive jaundice. The functional times of metal stents are longer than those of a plastic stent. Key Message For biliary obstruction, a metal stent is the first choice. The long-term efficiency of EUS-FNI still needs further study. Practical Implications Endoscopy and EUS-guided interventions have gradually become the mainstream method for local treatment of PC due to mini-invasiveness and real-time observation. PC is the second most common gastrointestinal malignancy and the sixth leading cause of cancer mortality in the United States, leading to about 4.0% of all cancer deaths [Siegel et al: CA Cancer J Clin 2014;64:9-29]. The only curative approach for patients with PC is surgical resection, but unfortunately 80-90% of patients have a surgically inoperable disease, with 53% having local metastases at the time of diagnosis [Weinberg et al: Oncology (Williston Park) 2015;29:809-820, 886]. Therefore, palliative therapy and primarily chemoradiotherapy are the mainstream of treatment in

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

    SciTech Connect

    Yu, Ge; Wan, Rong; Hu, Yanling; Ni, Jianbo; Yin, Guojian; Xing, Miao; Shen, Jie; Tang, Maochun; Chen, Congying; Fan, Yuting; Xiao, Wenqin; Zhao, Yan; Wang, Xingpeng; and others

    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 of 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.

  18. [Chronic pancreatitis or pancreatic malignancy: clinical and radiological differential diagnosis of pancreas head space-occupying mass].

    PubMed

    Nieß, H; Albertsmeier, M; Thomas, M; Kleespies, A; Angele, M; Bruns, C J

    2013-02-01

    Chronic pancreatitis can be complicated both by an inflammatory benign mass and by the development of pancreatic cancer. The distinction of these complications is not only difficult but also crucial as patients suffering from either of the two have significantly different prognoses. This article describes typical clinical and radiological findings, which may help the physician in differentiating these two maladies. Furthermore, we conducted a retrospective study where we evaluated the clinical patterns in patients with chronic pancreatitis who underwent resection for a pancreatic mass. Although certain findings may be indicative for benign tumors, none of the diagnostic tools available offers a sufficient degree of certainty. In cases of tumors secondary to autoimmune pancreatitis the diagnostic error is exceptionally high. Because of the poor prognosis related to untreated pancreatic cancer, the general recommendation is to perform resection of the tumor when technically possible and when carcinoma cannot be ruled out completely.

  19. Pancreatic injury revealed in abdominal ultrasound: a case report.

    PubMed

    Papadoliopoulos, Ioannis; Bourikos, Panagiotis; Chloptsios, Christos; Ilias, Georgios; Moustakis, Elias; Karanasiou, Vasilissa; Stamatiou, Kostantinos

    2009-07-01

    Pancreatic laceration due to blunt trauma is relatively uncommon and it is less likely to accompany injury of a retroperitoneal organ. While renal injuries are easily detectable in both clinical and radiographic imaging examination, pancreatic injuries are difficult to diagnose clinically and in several cases remain occult. Although ultrasonography is not generally recommended for initial assessment of the trauma patient and its role is limited in the follow-up of contained intra- or perihepatic bilomas that are treated conservatively, it was demonstrated to be capable for exploration of pancreatic injuries as well. We present a case of a 23-year-old male with pancreatic injury found in ultrasonography.

  20. [Prognostic significance of helical CT in patients with destructive pancreatitis].

    PubMed

    Bulanova, T V

    2000-01-01

    Spiral scanning computed tomography (CT) is able not only to image the pancreas and to evaluate its structure, but to interpret the status of the adjacent organs and tissues. CT symptoms of pancreatic necrotic changes and multiorgan failure were studied in the prospective follow-up of 47 patients with prior destructive pancreatitis (158 studies). CT differentially substantiated indications for choosing treatment policy for different forms of pancreatic lesions. The paper gives a quantitative assessment of necrotic pancreatic parencymatous areas and shows its prognostic value.

  1. Obesity, autophagy and the pathogenesis of liver and pancreatic cancers.

    PubMed

    Aghajan, Mariam; Li, Ning; Karin, Michael

    2012-03-01

    Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor-κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma.

  2. The new revised classification of acute pancreatitis 2012.

    PubMed

    Sarr, Michael G; Banks, Peter A; Bollen, Thomas L; Dervenis, Christos; Gooszen, Hein G; Johnson, Colin D; Tsiotos, Gregory G; Vege, Santhi Swaroop

    2013-06-01

    This study aims to update the 1991 Atlanta Classification of acute pancreatitis, to standardize the reporting of and terminology of the disease and its complications. Important features of this classification have incorporated new insights into the disease learned over the last 20 years, including the recognition that acute pancreatitis and its complications involve a dynamic process involving two phases, early and late. The accurate and consistent description of acute pancreatitis will help to improve the stratification and reporting of new methods of care of acute pancreatitis across different practices, geographic areas, and countries.

  3. [Autophagy contributes to the initiation of pancreatic cancer].

    PubMed

    Iovanna, Juan L

    2017-03-01

    The pancreatic adenocarcinoma initiation results from the interaction of genetic events combined with multiple other factors. Among the genetic alterations that contribute to the pathogenesis of this disease, the mutation of the KRAS oncogene is required but not sufficient to trigger this cancer. Pancreatitis, an inflammatory disease, facilitates and accelerates the transformation of pancreatic cells when the KRAS oncogene is mutated. Of note, the repertoire of molecular mediators of pancreatitis which are responsible of the promotion of KRAS-mediated transformation is not completely defined. Importantly, autophagy has been proposed as one of the cellular mechanisms contributing to pancreatic carcinogenesis, especially in the initial phases, in which the oncogene KRAS appears to play its leading role. In addition, autophagy is strongly induced during pancreatitis. Although some aspects of autophagy in pancreatic cancer development are not completely established, we can affirm that overexpression of VMP1, an inducer of autophagy which is specifically activated in pancreas during pancreatitis, improves the development of pancreatic precancerous lesions PanINs when the oncogene KRAS is mutated. In addition, inhibition of the autophagic flux with chloroquine inhibits the KRAS pro-tumor effect in the pancreas. In conclusion, activation of expression of VMP1 improves the pro-tumor role of KRAS in pancreas.

  4. Application of glycoscience to the early detection of pancreatic cancer.

    PubMed

    Miyoshi, Eiji; Kamada, Yoshihiro

    2016-10-01

    The prognosis of pancreatic cancer is extremely poor compared to other cancers. One of the reasons for this is the difficulty of early diagnosis. Surveillance using cancer biomarkers and image diagnosis can enable early detection and has improved the prognosis of hepatocellular carcinoma in Japan. However, it is very difficult to detect pancreatic cancer at an early stage using cancer biomarkers and image diagnosis alone. Fucosylation is one of the most important types of glycosylation involved in cancer and inflammation. We have developed a novel glycocancer biomarker, fucosylated haptoglobin (Fuc-Hpt), and have investigated its usefulness for the diagnosis of pancreatic cancer over approximately 10 years. Recently, we also found that most pancreatic tissues surrounding pancreatic cancer exhibit chronic pancreatitis with fibrosis and/or fatty degeneration. Certain forms of chronic pancreatitis might indicate high risk for the development of pancreatic cancer. In this review, we provide a historical summary of our research on Fuc-Hpt as a cancer biomarker, and discuss a potential early detection system for pancreatic cancer.

  5. Pancreatoduodenectomy for groove pancreatitis Report of two cases.

    PubMed

    Fregoli, Lorenzo; Palmeri, Matteo; De Napoli, Luigi; De Marco, Salvatore; Pelosini, Marco; Bertolucci, Andrea; Galatioto, Christian; Cengeli, Ismail; Chiarugi, Massimo

    2016-01-01

    Groove pancreatitis is a rare condition with patients having clinical characteristics similar to those of chronic pancreatitis. Differentiating on clinical and radiological basis between groove pancreatitis and paraduodenal head cancer can be extremely challenging. Due to diagnostic uncertainty and to poor response to medical treatment surgery may offer these patients the best chance of cure. As the main localization of the inflammatory process is at the groove between the duodenum and the head of the pancreas, pancreato-duodenectomy is proposed as the most reliable surgical procedure. We report about two patients presenting with clinical and radiological features suggesting a groove pancreatitis in which control of symptoms was achieved by pancreatoduodenectomy.

  6. Acute Pancreatitis: The Role of Imaging and Interventional Radiology

    SciTech Connect

    Maher, Michael M.; Lucey, Brian C.; Gervais, Debra A.; Mueller, Peter R.

    2004-09-15

    Acute pancreatitis can manifest as a benign condition with minimal abdominal pain and hyperamylasemia or can have a fulminant course, which can be life-threatening usually due to the development of infected pancreatic necrosis, and multisystem organ failure. Fortunately, 70-80% of patients with acute pancreatitis have a benign self-limiting course. The initial 24-48 hours after the initial diagnosis is usually the period that determines the subsequent course, and for many of the 20-30% of patients who subsequently have a fulminant course, this becomes apparent within this time frame. With reference to long-term outcome following acute pancreatitis, most cases recover without long-term sequelae with only a minority of cases progressing to chronic pancreatitis. In the initial management of acute pancreatitis, assessment of metabolic disturbances and systemic organ dysfunction is critical. However, the advent and continued refinement of cross-sectional imaging modalities over the past two decades has led to a prominent role for diagnostic imaging in assessing acute pancreatitis. Furthermore, these cross-sectional imaging modalities have enabled the development of diagnostic and therapeutic interventional techniques in the hands of radiologists. In this article we review the diagnostic features of acute pancreatitis, the clinical staging systems, complications and the role of imaging. The role of interventional radiology techniques in the management of acute pancreatitis will be discussed as well as potential complications associated with these treatments.

  7. Prevention and management of post-ERCP pancreatitis.

    PubMed

    Sahakian, Ara B; Buxbaum, James L; Van Dam, Jacques

    2014-11-28

    Pancreatitis remains as one of the most frequent and serious complications of ERCP. Research has identified several patient-related and procedural risk factors, which help guide the endoscopist in prophylaxis and management of pancreatitis. Recent studies have had a major impact on both procedural techniques and pharmacological methods for prophylaxis of post-ERCP pancreatitis. The purpose of this article is to review the relevant literature and describe the most recent and effective approaches in prevention and management of post-ERCP pancreatitis.

  8. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

    PubMed Central

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans. PMID:27302647

  9. Distribution of pancreatic elastase and metalloproteinase in vertebrates.

    PubMed

    Yoshinaka, R; Sato, M; Tsuchiya, N; Ikeda, S

    1986-01-01

    Elastase-like enzymes were detected as zymogens in all of the pancreatic extracts from the gummy shark, bullhead shark, angel shark, smooth hammerhead, bestel, rainbow trout, carp, eel, Japanese mackerel, yellowtail, sea bass, parrotfish, bullfrog, chicken, bluewhite dolphin, hog, rat, cat, and dog. The distribution of pancreatic elastase and metalloproteinase was examined on the basis of the effect of specific inhibitors on elastase like-activity in each extract. The results indicate that pancreatic elastases are present in all the species examined and pancreatic metalloproteinases are present only in the teleost fishes.

  10. Diabetes mellitus and pancreatitis--cause or effect?

    PubMed

    Davison, L J

    2015-01-01

    Diabetes mellitus and pancreatitis are two distinct diseases encountered commonly in small animal practice. Whilst the clinical signs of diabetes mellitus are usually unmistakeable, a firm diagnosis of pancreatitis can prove more elusive, as clinical signs are often variable. Over the past 10 to 15 years, despite the fact that the clinical signs of diabetes mellitus are remarkably consistent, it has become more apparent that the underlying pathology of diabetes mellitus in dogs and cats is heterogeneous, with exocrine pancreatic inflammation accompanying diabetes mellitus in a number of cases. However, the question remains as to whether the diabetes mellitus causes the pancreatitis or whether, conversely, the pancreatitis leads to diabetes mellitus--as there is evidence to support both scenarios. The concurrence of diabetes mellitus and pancreatitis has clinical implications for case management as such cases may follow a more difficult clinical course, with their glycaemic control being "brittle" as a result of variation in the degree of pancreatic inflammation. Problems may also arise if abdominal pain or vomiting lead to anorexia. In addition, diabetic cases with pancreatitis are at risk of developing exocrine pancreatic insufficiency in the following months to years, which can complicate their management further.

  11. Autoimmune Pancreatitis: A Case of Atypical Radiographic Findings

    PubMed Central

    Karimi, Shawhin; Bharill, Parth

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare pancreatic disorder that can present as a manifestation of a broader systemic inflammatory disease known as immunoglobulin G4-related systemic disease (IGG4-RSD). AIP is divided into two subtypes based on clinical, radiological, and histological findings. The disease can be mistaken for pancreatic cancer because of overlapping clinical and radiological findings, but early recognition can help avoid unnecessary surgery. We present a case of a 65-year-old female with suspected acute gallstone pancreatitis found to have AIP based on serology, radiological findings, and response to steroids. PMID:27920645

  12. Induction of chronic pancreatitis by pancreatic duct ligation activates BMP2, apelin, and PTHrP expression in mice.

    PubMed

    Rastellini, Cristiana; Han, Song; Bhatia, Vandanajay; Cao, Yanna; Liu, Ka; Gao, Xuxia; Ko, Tien C; Greeley, George H; Falzon, Miriam

    2015-10-01

    Chronic pancreatitis (CP) is a devastating disease with no treatments. Experimental models have been developed to reproduce the parenchyma and inflammatory responses typical of human CP. For the present study, one objective was to assess and compare the effects of pancreatic duct ligation (PDL) to those of repetitive cerulein (Cer)-induced CP in mice on pancreatic production of bone morphogenetic protein-2 (BMP2), apelin, and parathyroid hormone-related protein (PTHrP). A second objective was to determine the extent of cross talk among pancreatic BMP2, apelin, and PTHrP signaling systems. We focused on BMP2, apelin, and PTHrP since these factors regulate the inflammation-fibrosis cascade during pancreatitis. Findings showed that PDL- and Cer-induced CP resulted in significant elevations in expression and peptide/protein levels of pancreatic BMP2, apelin, and PTHrP. In vivo mouse and in vitro pancreatic cell culture experiments demonstrated that BMP2 stimulated pancreatic apelin expression whereas apelin expression was inhibited by PTHrP exposure. Apelin or BMP2 exposure inhibited PTHrP expression, and PTHrP stimulated upregulation of gremlin, an endogenous inhibitor of BMP2 activity. Transforming growth factor-β (TGF-β) stimulated PTHrP expression. Together, findings demonstrated that PDL- and Cer-induced CP resulted in increased production of the pancreatic BMP2, apelin, and PTHrP signaling systems and that significant cross talk occurred among pancreatic BMP2, apelin, and PTHrP. These results together with previous findings imply that these factors interact via a pancreatic network to regulate the inflammation-fibrosis cascade during CP. More importantly, this network communicated with TGF-β, a key effector of pancreatic pathophysiology. This novel network may be amenable to pharmacologic manipulations during CP in humans.

  13. Evaluation of serum feline pancreatic lipase immunoreactivity and helical computed tomography versus conventional testing for the diagnosis of feline pancreatitis.

    PubMed

    Forman, M A; Marks, S L; De Cock, H E V; Hergesell, E J; Wisner, E R; Baker, T W; Kass, P H; Steiner, J M; Williams, D A

    2004-01-01

    Serum feline trypsinogen-like immunoreactivity (fTLI) concentrations and abdominal ultrasound have facilitated the noninvasive diagnosis of pancreatitis in cats, but low sensitivities (33% and 20-35%, respectively) have been reported. A radioimmunoassay has been validated to measure feline pancreatic lipase immunoreactivity (fPLI), but the assay's sensitivity and specificity have not been established. In human beings, the sensitivity of computed tomography (CT) is high (75-90%), but in a study of 10 cats, only 2 had CT changes suggestive of pancreatitis. We prospectively evaluated these diagnostic tests in cats with and without pancreatitis. In all cats, serum was obtained for fTLI and fPLI concentrations, and pancreatic ultrasound images and biopsies were acquired. Serum fPLI concentrations (P< .0001) and ultrasound findings (P = .0073) were significantly different between healthy cats and cats with pancreatitis. Serum fTLI concentrations (P = .15) and CT measurements (P = .18) were not significantly different between the groups. The sensitivity of fTLI in cats with moderate to severe pancreatitis was 80%, and the specificity in healthy cats was 75%. Feline PLI concentrations were both sensitive in cats with moderate to severe pancreatitis (100%) and specific in the healthy cats (100%). Abdominal ultrasound was both sensitive in cats with moderate to severe pancreatitis (80%) and specific in healthy cats (88%). The high sensitivities of fPLI and abdominal ultrasound suggest that these tests should play an important role in the noninvasive diagnosis of feline pancreatitis. As suggested by a previous study, pancreatic CT is not a useful diagnostic test for feline pancreatitis.

  14. Preclinical models of pancreatic ductal adenocarcinoma.

    PubMed

    Hwang, Chang-Il; Boj, Sylvia F; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA.

  15. Pancreatic Differentiation from Murine Embryonic Stem Cells.

    PubMed

    Sakano, Daisuke; Shiraki, Nobuaki; Kume, Shoen

    2016-01-01

    Pluripotent stem cells are considered as a cell source for replacement therapies for pancreatic beta cells and other organs.We identified tetrabenazine (TBZ), vesicular monoamine transporter 2 (VMAT2) inhibitor as a promoter of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Ngn3-positive endocrine progenitor cells. A cell-permeable cAMP analog, dBu-cAMP promotes beta cell maturation in late stage of differentiation. The induced beta cells can secrete insulin in a glucose-dependent manner.Our protocol consists of a three -step differentiation process. ES cell recapitulate embryonic developmental processes in vitro. Therefore, the ES cell differentiation system is a useful model for the understanding of molecular mechanism of beta-cell differentiation and are useful for application for future regenerative medicine.

  16. Enteral Nutrition and Acute Pancreatitis: A Review

    PubMed Central

    Spanier, B. W. M.; Bruno, M. J.; Mathus-Vliegen, E. M. H.

    2011-01-01

    Introduction. In patients with acute pancreatitis (AP), nutritional support is required if normal food cannot be tolerated within several days. Enteral nutrition is preferred over parenteral nutrition. We reviewed the literature about enteral nutrition in AP. Methods. A MEDLINE search of the English language literature between 1999–2009. Results. Nasogastric tube feeding appears to be safe and well tolerated in the majority of patients with severe AP, rendering the concept of pancreatic rest less probable. Enteral nutrition has a beneficial influence on the outcome of AP and should probably be initiated as early as possible (within 48 hours). Supplementation of enteral formulas with glutamine or prebiotics and probiotics cannot routinely be recommended. Conclusions. Nutrition therapy in patients with AP emerged from supportive adjunctive therapy to a proactive primary intervention. Large multicentre studies are needed to confirm the safety and effectiveness of nasogastric feeding and to investigate the role of early nutrition support. PMID:20811543

  17. The Pancreatic Expression database: 2011 update

    PubMed Central

    Cutts, Rosalind J.; Gadaleta, Emanuela; Hahn, Stephan A.; Crnogorac-Jurcevic, Tatjana; Lemoine, Nicholas R.; Chelala, Claude

    2011-01-01

    The Pancreatic Expression database (PED, http://www.pancreasexpression.org) has established itself as the main repository for pancreatic-derived -omics data. For the past 3 years, its data content and access have increased substantially. Here we describe several of its new and improved features, such as data content, which now includes over 60 000 measurements derived from transcriptomics, proteomics, genomics and miRNA profiles from various pancreas-centred reports on a broad range of specimen and experimental types. We also illustrate the capabilities of its interface, which allows integrative queries that can combine PED data with a growing number of biological resources such as NCBI, Ensembl, UniProt and Reactome. Thus, PED is capable of retrieving and integrating different types of -omics, annotations and clinical data. We also focus on the importance of data sharing and interoperability in the cancer field, and the integration of PED into the International Cancer Genome Consortium (ICGC) data portal. PMID:20959292

  18. The Pancreatic Expression database: 2011 update.

    PubMed

    Cutts, Rosalind J; Gadaleta, Emanuela; Hahn, Stephan A; Crnogorac-Jurcevic, Tatjana; Lemoine, Nicholas R; Chelala, Claude

    2011-01-01

    The Pancreatic Expression database (PED, http://www.pancreasexpression.org) has established itself as the main repository for pancreatic-derived -omics data. For the past 3 years, its data content and access have increased substantially. Here we describe several of its new and improved features, such as data content, which now includes over 60,000 measurements derived from transcriptomics, proteomics, genomics and miRNA profiles from various pancreas-centred reports on a broad range of specimen and experimental types. We also illustrate the capabilities of its interface, which allows integrative queries that can combine PED data with a growing number of biological resources such as NCBI, Ensembl, UniProt and Reactome. Thus, PED is capable of retrieving and integrating different types of -omics, annotations and clinical data. We also focus on the importance of data sharing and interoperability in the cancer field, and the integration of PED into the International Cancer Genome Consortium (ICGC) data portal.

  19. Intraportal endovascular ultrasonography for pancreatic cancer.

    PubMed

    Kaneko, T; Nakao, A; Takagi, H

    1998-01-01

    Intraportal endovascular ultrasonography (IPEUS) is a new diagnostic procedure for pancreatic cancer. In portal invasion, subtle invasion and compression are difficult to differentiate with conventional imaging techniques such as computed tomography and angiography. IPEUS is performed with an 8-French, 20-MHz intravascular ultrasound catheter. IPEUS provides high-resolution, real-time images perpendicular to the portal vein axis. With IPEUS, the portal vein wall is visualized as an echogenic band. A subtle portal invasion can be detected by observing this portal vein wall. Moreover, the segment II of the extrapancreatic nerve plexus is visualized as an echogenic area around the inferior pancreaticoduodenal artery (IPDA). The extrapancreatic nerve plexus invasion can be diagnosed as low echoic infiltration of the area around the IPDA. In the diagnosis of portal vein and extrapancreatic nerve plexus invasion, IPEUS provides a good diagnostic value and important information for the staging of local extension of the pancreatic cancer.

  20. Surgical management of pancreatic cancer--pancreaticoduodenectomy.

    PubMed

    Donahue, Timothy R; Reber, Howard A

    2015-02-01

    Pancreaticoduodenectomy, the Whipple resection, is a complex operation that is commonly performed for patients with pancreatic ductal adenocarcinoma and other malignant or benign lesions in the head of the pancreas. It can be done with low morbidity and mortality rates, particularly when performed at high-volume hospitals and by high-volume surgeons. While it has been conventionally reserved for patients with early-stage malignant disease, it is being used increasingly for patients with locally extensive tumors who have undergone neoadjuvant therapy and downstaging. This article summarizes the role of pancreaticoduodenectomy for the treatment of patients with pancreatic cancer. It highlights the surgical staging of disease, the technical aspects of the operation and perioperative care, and the oncologic outcome.

  1. Radiological description of cystic pancreatic tumors.

    PubMed

    Rodríguez Torres, C; Larrosa López, R

    2016-01-01

    Although most cystic pancreatic lesions are pseudocysts, it is important to do a thorough differential diagnosis with true cystic tumors because cystic tumors are potentially malignant. Sometimes computed tomography and magnetic resonance imaging cannot establish the definitive diagnosis, making it necessary to perform other imaging tests such as endoscopic ultrasound, which in addition to morphological information, can also enable cytologic and biochemical analysis of the lesion through puncture and aspiration of its contents. Combining all these findings nearly always provides enough diagnostic information to allow the appropriate approach in each case. This article describes the specific morphological characteristics for each cystic pancreatic tumor on computed tomography, magnetic resonance imaging, and endoscopic ultrasound and reviews the guidelines for managing these types of lesions.

  2. Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein.

    PubMed Central

    Montalto, G; Bonicel, J; Multigner, L; Rovery, M; Sarles, H; De Caro, A

    1986-01-01

    Pancreatic stone protein (PSP) is the major organic component of human pancreatic stones. With the use of monoclonal antibody immunoadsorbents, five immunoreactive forms (PSP-S) with close Mr values (14,000-19,000) were isolated from normal pancreatic juice. By CM-Trisacryl M chromatography the lowest-Mr form (PSP-S1) was separated from the others and some of its molecular characteristics were investigated. The Mr of the PSP-S1 polypeptide chain calculated from the amino acid composition was about 16,100. The N-terminal sequences (40 residues) of PSP and PSP-S1 are identical, which suggests that the peptide backbone is the same for both of these polypeptides. The PSP-S1 sequence was determined up to residue 65 and was found to be different from all other known protein sequences. Images Fig. 1. PMID:3541906

  3. Hereditary pancreatitis of 3 Chinese children

    PubMed Central

    Dai, Li-Na; Chen, Ying-Wei; Yan, Wei-Hui; Lu, Li-Na; Tao, Yi-Jing; Cai, Wei

    2016-01-01

    Abstract Background: Hereditary pancreatitis (HP) is quite rare and is distinguished by incomplete penetrance presentation as early-onset relapsing pancreatitis, usually beginning in childhood. HP is now known to be commonly relevant to mutations in the PRSS1 (gene-encoding cationic trypsinogen), SPINK1 (serine protease inhibitor, Kazal type 1), CFTR (cystic fibrosis), carboxypeptidase A1 (CPA1), and chymotrypsin C (CTRC) genes as reported in some Caucasian studies. HP has a variable spectrum of severity and may develop complications. Methods & Results: We describe the clinical course of 3 preschool children, hospitalized with postprandial abdominal pain, whose laboratory tests showed high serum amylase. Similar episodes of abdominal pain led to readmission, and the patients recovered quickly after using symptomatic therapy. The condition of the first boy, who developed a pancreatic tail pseudocyst and splenic infarction, was especially complicated. The boy underwent 2 endoscopic retrograde cholangiopancreatographies and stenting, along with a surgical procedure that completely relieved his symptoms for 3 months. The 3 patients and their parents were given genetic testing. All of the patients carried 1 or more gene mutations inherited from their mothers, fathers, or both parents; however, none of the parents were affected. Conclusion: For children with repeated pancreatitis, clinicians should consider HP in the differential diagnosis. It is reliable to perform gene sequencing on suspicious patients and their parents. Multidisciplinary and comprehensive treatment should be recommended to manage HP and its complications. Cholangiopancreatography and stenting is a relatively minimally invasive approach when compared with surgery and can be tried as an early intervention. Surgical procedures should be reserved for patients with complications. PMID:27603351

  4. Pancreatic cytology: standardised terminology and nomenclature.

    PubMed

    Perez-Machado, M A

    2016-06-01

    Pancreatic cytology can make a real difference to the management of patients. However it is a challenge in those cases where a definitive diagnosis of malignancy cannot be made with confidence. This creates the need for a unified terminology and nomenclature system that provides intra- and interdepartmental guidance for diagnosis. The Papanicolaou Society of Cytopathology (PSC) has published new guidelines for pancreaticobiliary cytology, addressing indications, techniques, terminology and nomenclature, ancillary studies, and postprocedure management.

  5. Molecular Imaging of Pancreatic Cancer with Antibodies

    PubMed Central

    2015-01-01

    Development of novel imaging probes for cancer diagnostics remains critical for early detection of disease, yet most imaging agents are hindered by suboptimal tumor accumulation. To overcome these limitations, researchers have adapted antibodies for imaging purposes. As cancerous malignancies express atypical patterns of cell surface proteins in comparison to noncancerous tissues, novel antibody-based imaging agents can be constructed to target individual cancer cells or surrounding vasculature. Using molecular imaging techniques, these agents may be utilized for detection of malignancies and monitoring of therapeutic response. Currently, there are several imaging modalities commonly employed for molecular imaging. These imaging modalities include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance (MR) imaging, optical imaging (fluorescence and bioluminescence), and photoacoustic (PA) imaging. While antibody-based imaging agents may be employed for a broad range of diseases, this review focuses on the molecular imaging of pancreatic cancer, as there are limited resources for imaging and treatment of pancreatic malignancies. Additionally, pancreatic cancer remains the most lethal cancer with an overall 5-year survival rate of approximately 7%, despite significant advances in the imaging and treatment of many other cancers. In this review, we discuss recent advances in molecular imaging of pancreatic cancer using antibody-based imaging agents. This task is accomplished by summarizing the current progress in each type of molecular imaging modality described above. Also, several considerations for designing and synthesizing novel antibody-based imaging agents are discussed. Lastly, the future directions of antibody-based imaging agents are discussed, emphasizing the potential applications for personalized medicine. PMID:26620581

  6. Genetic predispositions to acute and chronic pancreatitis.

    PubMed

    Whitcomb, D C

    2000-05-01

    Advances in molecular genetics have provided the powerful tools necessary to identify the key molecules and mechanisms that underly the disease process. Continued work in this area promises to reveal new insights as new disease genes are discovered. This article focuses on the insights into the cause of acute and chronic pancreatitis gained by investigation of the HP genes, the diagnosis of the known mutations, the fascinating observation of nonpenetrance, and a look at future directions.

  7. A novel in vitro pancreatic carcinogenesis model

    PubMed Central

    Kang, Hyo Jin; Hong, Young Bin; Kim, Hee Jeong; Yi, Yong Weon; Nath, Raghu G.; Chang, Young Soo; Cho, Ho-Chan; Bae, Insoo

    2011-01-01

    Environmental factors (e.g., BaP) have been pointed out as one of the etiologies of pancreatic cancer. However, very limited experimental assays are available to identify pancreatic specific environmental mutagens or susceptibility genes. In this study, we have developed a simple in vitro cell culture model system that can be used to study the molecular and biochemical aspects of carcinogenesis in a near-normal immortalized pancreatic ductal epithelial cell lines. In order to demonstrate that xenobiotic stress response is intact in these cells we employed standard molecular biology techniques. For examples, luciferase reporter and/or real-time quantitative PCR assays were used to determine stress-induced CYP1A1 and CYP1B1 gene expression. Western blotting and immunocytochemistry assays were used to demonstrate that TCDD or BaP could activate AhR signaling. For exploring the carcinogenesis mechanism, we incubated cells with [3H]BaP and determined BaP-DNA binding activity by measuring its radioactivity. BaP-DNA adduct formation was further confirmed by [32P]-postlabeling assay. Finally, we demonstrated the effects of endogenous AhR or BRCA1 in BaP-DNA adduct accumulation in our cell system: As results, no apparent BaP-DNA adduct accumulation by [32P]-postlabeling assay was found in either control-siRNA or AhR-siRNA pretreated cells. On the other hand, a significant increase of BaP-DNA adduct accumulation was found in BRCA1 knockdown cells. In conclusion, we suggest that this in vitro model may provide the feasibility for future studies on the molecular basis of pancreatic ductal cell carcinogenesis caused by dietary mutagens. PMID:21256203

  8. CT guided interstitial therapy of pancreatic carcinoma

    SciTech Connect

    Haaga, J.R.; Owens, D.B.; Kellermeyer, R.W.; Shina, D.; Pilai, K.; Began, N.

    1987-11-01

    We describe the use of percutaneous CT guidance for localization and placement of /sup 192/Ir sources into a patient with pancreatic carcinoma. We have shown the feasibility of this procedure and the lack of complications which are probably due to minimal damage to tissue involved. Computed tomography is ideally suited for percutaneous implantation because it provides the most accurate method for needle placement within the abdomen.

  9. [DIAGNOSIS OF VASCULAR INVASION BY PANCREATIC TUMORS].

    PubMed

    Dronov, O I; Zemskov, S V; Bakunets, P P

    2016-02-01

    Basing on analysis of own material (84 patients) and data of literature there was established, that vascular invasion by pancreatic tumors constitutes the main obstacle for conduction of the patients' radical treatment. Early diagnosis permits radical resectability of the patients, what constitutes the only one effective method of treatment. In vascular invasion by tumor a surgeon experience and professional preparation determines possibility of the extended operation performance with intervention on affected main vessel, enhancing the treatment radicalism.

  10. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  11. Autoimmune pancreatitis in Japan: overview and perspective.

    PubMed

    Shimosegawa, Tooru; Kanno, Atsushi

    2009-01-01

    Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.

  12. Mouse Model of Human Hereditary Pancreatitis

    DTIC Science & Technology

    2016-09-01

    cause hereditary pancreatitis in humans. Previous attempts to introduce these mutant forms of human trypsinogen into mice have failed to produce...mutations in mouse trypsinogen isoform T7. Under this aim, we had two major tasks in our SOW: Major Task 1 was the design and construction of mutant forms...of the T7 mouse trypsinogen gene and expression and purification of these mutant enzymes. Major Task 2 was to analyze autoactivation of the T7

  13. Serum markers and clinical data in diagnosing pancreatic cancer: a contrastive approach.

    PubMed

    Fabris, C; Del Favero, G; Basso, D; Piccoli, A; Meggiato, T; Angonese, C; Plebani, M; Leandro, G; Burlina, A; Naccarato, R

    1988-05-01

    In order to assess the value of serum markers and simple clinical data in the differential diagnosis of pancreatic cancer, we studied 32 control subjects and 28 patients with pancreatic cancer, 26 with chronic pancreatitis, and 37 with extra-pancreatic diseases. CA 19-9 was found to be the best marker in detecting pancreatic cancer. Among the clinical data, presence and onset of pain attacks, age, and weight loss were selected as the most informative in assessing chronic pancreatic disease. Clinical data correctly classified 88.5% of chronic pancreatitis and 75.0% of pancreatic cancer; serum markers identified pancreatic tumor in 67.9% of the patients. The adjunct of serum markers to clinical data did not improve accuracy in diagnosing chronic pancreatic disease. Since clinical data and serum markers generally become positive at an advanced stage of the disease, early diagnosis of pancreatic cancer is a goal still to be attained.

  14. Endoscopic pancreatic and biliary manometry in pancreatic, biliary, and papillary disease, and after endoscopic sphincterotomy and surgical sphincteroplasty.

    PubMed Central

    Gregg, J A; Carr-Locke, D L

    1984-01-01

    Endoscopic manometry was used to measure pancreatic duct, common bile duct, pancreatic duct sphincter and bile duct sphincter pressures in 43 healthy volunteers and 162 patients with a variety of papillary, pancreatic and biliary disorders. Common bile duct pressure was significantly raised after cholecystectomy, with common bile duct stones and papillary stenosis but pancreatic duct pressure only in papillary stenosis. After endoscopic sphincterotomy mean common bile duct pressure fell from 11.2 to 1.1 mmHg and pancreatic duct pressure from 18.0 to 11.2 mmHg. Distinct pancreatic duct sphincter and bile duct sphincter zones were identified as phasic pressures of 3-12 waves/minute on pull-through from pancreatic duct and common bile duct to duodenum. Pancreatic duct sphincter pressures were higher with common bile duct stones and stenosis whereas bile duct sphincter pressures were higher in pancreatitis and stenosis. Bile duct sphincter activity was present in 60% of patients after surgical sphincteroplasty but 21% of patients after endoscopic sphincterotomy. Endoscopic manometry facilitated the diagnosis of papillary stenosis, has allowed study of papillary pathophysiology and has shown a functional inter-relationship between the two sphincteric zones. PMID:6500363

  15. Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma

    PubMed Central

    Mathur, Abhishek; Hernandez, Jonathan; Shaheen, Fawad; Shroff, Miloni; Dahal, Sujat; Morton, Connor; Farrior, Thomas; Kedar, Raj; Rosemurgy, Alexander

    2011-01-01

    Background Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD). Objectives We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma. Methods High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm. Results Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01). Conclusions In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies. PMID:21609373

  16. Pancreatic Candidiasis That Mimics a Malignant Pancreatic Cystic Tumor on Magnetic Resonance Imaging: A Case Report in an Immunocompetent Patient.

    PubMed

    Seong, Minjung; Kang, Tae Wook; Ha, Sang Yun

    2015-01-01

    Candida is a commensal organism that is frequently found in the human gastrointestinal tract. It is the most common organism that causes pancreatic fungal infections. However, magnetic resonance imaging findings of Candida infection in the pancreas have not been described. We report imaging findings of pancreatic candidiasis in a patient in immunocompetent condition. It presented as a multi-septated cystic mass with a peripheral solid component in the background of pancreatitis and restricted diffusion on diffusion-weighted image that mimicked a malignant pancreatic cystic tumor.

  17. Necrotizing pancreatitis: A review of the interventions.

    PubMed

    Bugiantella, Walter; Rondelli, Fabio; Boni, Marcello; Stella, Paolo; Polistena, Andrea; Sanguinetti, Alessandro; Avenia, Nicola

    2016-04-01

    Acute pancreatitis may have a wide range of severity, from a clinically self-limiting to a quickly fatal course. Necrotizing pancreatitis (NP) is the most dreadful evolution associated to a poor prognosis: mortality is approximately 15% and up to 30-39% in case of infected necrosis, which is the major cause of death. Intervention is generally required for infected pancreatic necrosis and less commonly in patients with sterile necrosis who are symptomatic (gastric or duodenal outlet or biliary obstruction). Traditionally the most widely used approach to infected necrosis has been open surgical necrosectomy, but it is burdened by high morbidity (34-95%) and mortality (11-39%) rates. In the last two decades the treatment of NP has significantly evolved from open surgery towards minimally invasive techniques (percutaneous catheter drainage, per-oral endoscopic, laparoscopy and rigid retroperitoneal videoscopy). The objective of this review is to summarize the current state of the art of the management of NP and to clarify some aspects about its diagnosis and treatment.

  18. Pancreatic Cancer Epidemiology, Detection, and Management

    PubMed Central

    Zhang, Qiubo; Zeng, Linjuan; Chen, Yinting; Lian, Guoda; Qian, Chenchen; Chen, Shaojie; Li, Jiajia; Huang, Kaihong

    2016-01-01

    PC (pancreatic cancer) is the fourth most common cause of death due to cancer worldwide. The incidence and mortality rates have been increasing year by year worldwide, and this review has analyzed the most recent incidence and mortality data for pancreatic cancer occurrence in China. Several possible risk factors have been discussed here, involving known established risk factors and novel possible risk factors. The development of this cancer is a stepwise progression through intraepithelial neoplasia to carcinoma. Though early and accurate diagnosis is promising based on a combination of recent techniques including tumor markers and imaging modalities, lacking early clinical symptoms makes the diagnosis late. Correct staging is critical because treatment is generally based on this parameter. Treatment options have improved throughout the last decades. However, surgical excision remains the primary therapy and efficacy of conventional chemoradiotherapy for PC is limited. Recently, some novel new therapies have been developed and will be applied in clinics soon. This review will provide an overview of pancreatic cancer, including an understanding of the developments and controversies. PMID:26941789

  19. Acute necrotizing pancreatitis: a multicenter study.

    PubMed

    Fernández-Cruz, L; Navarro, S; Valderrama, R; Sáenz, A; Guarner, L; Aparisi, L; Espi, A; Jaurietta, E; Marruecos, L; Gener, J

    1994-04-01

    A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

  20. Oncogenic KRAS signalling in pancreatic cancer.

    PubMed

    Eser, S; Schnieke, A; Schneider, G; Saur, D

    2014-08-26

    Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal. The annual number of deaths equals the number of newly diagnosed cases, despite maximal treatment. The overall 5-year survival rate of <5% has remained stubbornly unchanged over the last 30 years, despite tremendous efforts in preclinical and clinical science. There is unquestionably an urgent need to further improve our understanding of pancreatic cancer biology, treatment response and relapse, and to identify novel therapeutic targets. Rigorous research in the field has uncovered genetic aberrations that occur during PDAC development and progression. In most cases, PDAC is initiated by oncogenic mutant KRAS, which has been shown to drive pancreatic neoplasia. However, all attempts to target KRAS directly have failed in the clinic and KRAS is widely assumed to be undruggable. This has led to intense efforts to identify druggable critical downstream targets and nodes orchestrated by mutationally activated KRAS. This includes context-specific KRAS effector pathways, synthetic lethal interaction partners and KRAS-driven metabolic changes. Here, we review recent advances in oncogenic KRAS signalling and discuss how these might benefit PDAC treatment in the future.

  1. Pancreatic Islet Cell Development and Regeneration

    PubMed Central

    Romer, Anthony I.; Sussel, Lori

    2015-01-01

    Purpose This review will discuss recent advances in understanding mouse and human pancreatic islet cell development, novel concepts related to β cell dysfunction and improved approaches for replenishing β cells to treat diabetes. Recent Findings Considerable knowledge about pancreatic islet development and function has been gained using model systems with subsequent validation in human tissues. Recently, several rodent studies have revealed that differentiated adult islet cells retain remarkable plasticity and can be converted to other islet cell types by perturbing their transcription factor profiles. Furthermore, significant advances have been made in the generation of β-like cells from stem cell populations. Therefore, the generation of functionally mature β cells by the in situ conversion of non-β cell populations or by the directed differentiation of human pluripotent stem cells could represent novel mechanisms for replenishing β cells in diabetic patients. Summary The overall conservation between mouse and human pancreatic development, islet physiology and etiology of diabetes encourages the translation of novel β cell replacement therapies to humans. Further deciphering the molecular mechanisms that direct islet cell regeneration, plasticity and function could improve and expand the β cell replacement strategies for treating diabetes. PMID:26087337

  2. Ultrasound-enhanced nanotherapy of pancreatic cancer

    NASA Astrophysics Data System (ADS)

    Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

    2010-03-01

    The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

  3. Tackling pancreatic cancer with metronomic chemotherapy.

    PubMed

    Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Marchetti, Paolo

    2017-05-28

    Pancreatic tumours, the majority of which arise from the exocrine pancreas, have recently shown an increasing incidence in western countries. Over the past few years more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to significant improvements. However, despite such advances in therapy, prognosis of pancreatic cancer remains disappointing. Metronomic chemotherapy (MCT), which consists in the administration of continuous, low-dose anticancer drugs, has demonstrated the ability to suppress tumour growth. Thus, it may provide an additional therapeutic opportunity for counteracting the progression of the tumour. Here we discuss evidence arising from preclinical and clinical studies regarding the use of MCT in pancreatic cancer. Good results have generally been achieved in preclinical studies, particularly when MCT was combined with standard dose chemotherapy or antinflammatory, antiangiogenic and immunostimolatory agents. The few available clinical experiences, which mainly refer to retrospective data, have reported good tolerability though mild activity of metronomic schedules. Further studies are therefore awaited to confirm both preclinical findings and the preliminary clinical data.

  4. Necrolytic migratory erythema and pancreatic glucagonoma.

    PubMed

    Rodríguez, Gerzaín; Vargas, Elga; Abaúnza, Claudia; Cáceres, Sergio

    2016-06-03

    Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma.

  5. New targeted therapies in pancreatic cancer.

    PubMed

    Seicean, Andrada; Petrusel, Livia; Seicean, Radu

    2015-05-28

    Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

  6. Molecular Targeted Intervention for Pancreatic Cancer

    PubMed Central

    Mohammed, Altaf; Janakiram, Naveena B.; Pant, Shubham; Rao, Chinthalapally V.

    2015-01-01

    Pancreatic cancer (PC) remains one of the worst cancers, with almost uniform lethality. PC risk is associated with westernized diet, tobacco, alcohol, obesity, chronic pancreatitis, and family history of pancreatic cancer. New targeted agents and the use of various therapeutic combinations have yet to provide adequate treatments for patients with advanced cancer. To design better preventive and/or treatment strategies against PC, knowledge of PC pathogenesis at the molecular level is vital. With the advent of genetically modified animals, significant advances have been made in understanding the molecular biology and pathogenesis of PC. Currently, several clinical trials and preclinical evaluations are underway to investigate novel agents that target signaling defects in PC. An important consideration in evaluating novel drugs is determining whether an agent can reach the target in concentrations effective to treat the disease. Recently, we have reported evidence for chemoprevention of PC. Here, we provide a comprehensive review of current updates on molecularly targeted interventions, as well as dietary, phytochemical, immunoregulatory, and microenvironment-based approaches for the development of novel therapeutic and preventive regimens. Special attention is given to prevention and treatment in preclinical genetically engineered mouse studies and human clinical studies. PMID:26266422

  7. Management of pancreatic cancer in the elderly

    PubMed Central

    Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

    2016-01-01

    Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care. PMID:26811623

  8. [Use of plasmapheresis in hypertriglyceridemic pancreatitis].

    PubMed

    Jerkovich, Fernando; Remón, Javier A; Barretto, Mariano; Ciocchini, Cleto; Speroni, Gerardo

    2014-01-01

    Hypertriglyceridemia is reported as cause of 1 to 4% of the episodes of acute pancreatitis. We report the case of a 42-year-old woman with a history of obesity, type 2 diabetes mellitus, hypertriglyceridemia and hypercholesterolemia, with triglycerides of 9365 mg/dl, total cholesterol of 1822 mg/dl, one month prior to the consultation. She presented at the emergency unit with a 5 day history of abdominal pain, which progressed in intensity in the last 48 hours. Abdominal computed tomography revealed pancreatic and peripancreatic inflammation. Thirty-six hours after admission, a first session of plasmapheresis was conducted with a plasma triglyceride and cholesterol reduction of 25 and 30%, respectively. A second session was performed the next day, with a further reduction of triglycerides to 996 mg/dl and cholesterol to 238 mg/dl. During hospitalization the patient presented fever and Klebsiella pneumoniae bacteremia with no pancreatic collection or necrosis in tomography and, later on, nosocomial pneumonia, both infections with adequate response to antibiotic therapy. At the time of discharge, triglycerides and cholesterol levels were 652 mg/dl and 167 mg/dl respectively, no abdominal pain was present and the patient resumed oral nutrition. We observed a 90% reduction of triglycerides and 87% of cholesterol after 2 sessions of plasmapheresis, compared to 70% in average of reduction in most of the studies reviewed. We did not find the presence of bacteremia or nosocomial pneumonia as complications in the reported cases.

  9. Clinical approach to incidental pancreatic cysts

    PubMed Central

    Chiang, Austin L; Lee, Linda S

    2016-01-01

    The approach to incidentally noted pancreatic cysts is constantly evolving. While surgical resection is indicated for malignant or higher risk cysts, correctly identifying these highest risk pancreatic cystic lesions remains difficult. Using parameters including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines have sought to identify the higher risk patients who would benefit from further evaluation using endoscopic ultrasound (EUS). Not only can EUS help further assess the presence of solid component and nodules, but also fine needle aspiration of cyst fluid aids in diagnosis by obtaining cellular, molecular, and genetic data. The impact of new endoscopic innovations with novel methods of direct visualization including confocal endomicroscopy require further validation. This review also highlights the differences between the 2012 IAP and 2015 AGA guidelines, which include the thresholds for sending patients for EUS and surgery and methods, interval, and duration of surveillance for unresected cysts. PMID:26811661

  10. Management of Pancreatic Calculi: An Update

    PubMed Central

    Tandan, Manu; Talukdar, Rupjyoti; Reddy, Duvvur Nageshwar

    2016-01-01

    Pancreatolithiasis, or pancreatic calculi (PC), is a sequel of chronic pancreatitis (CP) and may occur in the main ducts, side branches or parenchyma. Calculi are the end result, irrespective of the etiology of CP. PC contains an inner nidus surrounded by successive layers of calcium carbonate. These calculi obstruct the pancreatic ducts and produce ductal hypertension, which leads to pain, the cardinal feature of CP. Both endoscopic therapy and surgery aim to clear these calculi and decrease ductal hypertension. In small PC, endoscopic retrograde cholangiopancreatography (ERCP) followed by sphincterotomy and extraction is the treatment of choice. Large calculi require fragmentation by extracorporeal shock wave lithotripsy (ESWL) prior to their extraction or spontaneous expulsion. In properly selected cases, ESWL followed by ERCP is the standard of care for the management of large PC. Long-term outcomes following ESWL have demonstrated good pain relief in approximately 60% of patients. However, ESWL has limitations. Per oral pancreatoscopy and intraductal lithotripsy represent techniques in evolution, and in current practice their use is limited to centers with considerable expertise. Surgery should be offered to all patients with extensive PC, associated multiple ductal strictures or following failed endotherapy. PMID:27784844

  11. Pancreatic panniculitis as a paraneoplastic phenomenon of a pancreatic acinar cell carcinoma.

    PubMed

    Naeyaert, Charlotte; de Clerck, Frederik; De Wilde, Vincent

    2016-12-01

    We present the case of a 59-year-old patient admitted with extreme painful erythematous subcutaneous nodules of the lower extremities in association with arthritis and peripheral eosinophilia. Upon skin biopsy, the diagnosis of pancreatic panniculitis was made. On further investigation, an underlying acinar cell type pancreas carcinoma was revealed. This clinical case does illustrate how a seemingly innocuous skin condition may herald an underlying malignant disease. The presence of pancreatic panniculitis should trigger clinicians to undertake further thorough diagnostic investigation of the pancreas.

  12. Jejunum or Stomach for the Pancreatic Anastomosis After Pancreaticoduodenectomy

    PubMed Central

    1997-01-01

    Objective: The authors hypothesized that pancreaticogastrostomy is safer than pancreaticojejunostomy after pancreaticoduodenectomy and less likely to be associated with a postoperative pancreatic fistula. Summary Background Data: Pancreatic fistula is a leading cause of morbidity and mortality after pancreaticoduodenectomy, occurring in 10% to 20% of patients. Nonrandomized reports have suggested that pancreaticogastrostomy is less likely than pancreaticojejunostomy to be associated with postoperative complications. Methods: Between May 1993 and January 1995, the findings for 145 patients were analyzed in this prospective trial at The Johns Hopkins Hospital. After giving their appropriate preoperative informed consent, patients were randomly assigned to pancreaticogastrostomy or pancreaticojejunostomy after completion of the pancreaticoduodenal resection. All pancreatic anastomoses were performed in two layers without pancreatic duct stents and with closed suction drainage. Pancreatic fistula was defined as drainage of greater than 50 mL of amylase-rich fluid on or after postoperative day 10. Results: The pancreaticogastrostomy (n=73) and pancreaticojejunostomy (n=72) groups were comparable with regard to multiple parameters, including demographics, medical history, preoperative laboratory values, and intraoperative factors, such as operative time, blood transfusions, pancreatic texture, length of pancreatic remnant mobilized, and pancreatic duct diameter. The overall incidence of pancreatic fistula after pancreaticoduodenectomy was 11.7% (171145). The incidence of pancreatic fistula was similar for the pancreaticogastrostomy (12.3%) and pancreaticojejunostomy (11.1%) groups. Pancreatisc fistula was associated with a significant prolongation of postoperative hospital stay (36±5 vs. 15±1 days) (p<0.001). Factors significantly increasing the risk of pancreatic fistula by univariate logistic regression analysis included ampullary or duodenal disease, soft pancreatic

  13. The Timing of Biliary Surgery in Acute Pancreatitis

    PubMed Central

    Ranson, John H. C.

    1979-01-01

    The timing of biliary surgery remains controversial in patients with acute pancreatitis associated with cholelithiasis. Eighty hospital admissions for acute pancreatitis, occurring in 74 patients with cholelithiasis, have therefore been reviewed. Among 22 patients who underwent abdominal surgery during the first week of treatment, there were five deaths (23%) and four patients (18%) who required more than seven days of intensive care. Fifty-eight episodes of pancreatitis were managed nonoperatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. Biliary surgery was undertaken later during the same admission in 37 patients, with no deaths. Twenty-one patients were discharged without biliary operation, but seven (33%) developed further pancreatitis. Previously reported prognostic signs were used to divide pancreatitis into 57 “mild” episodes (1.8% mortality) and 23 “severe” episodes (17% mortality). Early (day 0-7) definitive biliary surgery was undertaken in 11 patients with “mild” pancreatitis, with one death (9%), and in six patients with “severe” pancreatitis, with four deaths (67%). In three recent patients with “severe” pancreatitis, early biliary surgery was limited to cholecystostomy, with no deaths. These findings suggest that although early correction of associated biliary disease may be undertaken safely in many patients with “mild” acute pancreatitis, early definitive surgery is hazardous in “severe” pancreatitis and should, if possible, be deferred until pancreatitis has subsided. In most patients biliary surgery should precede hospital discharge. PMID:443917

  14. Protein Kinase D Regulates Cell Death Pathways in Experimental Pancreatitis

    PubMed Central

    Yuan, Jingzhen; Liu, Yannan; Tan, Tanya; Guha, Sushovan; Gukovsky, Ilya; Gukovskaya, Anna; Pandol, Stephen J.

    2012-01-01

    Inflammation and acinar cell necrosis are two major pathological responses of acute pancreatitis, a serious disorder with no current therapies directed to its molecular pathogenesis. Serine/threonine protein kinase D family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple physiological and pathophysiological effects. We recently reported that PKD/PKD1, the predominant PKD isoform expressed in rat pancreatic acinar cells, mediates early events of pancreatitis including NF-κB activation and inappropriate intracellular digestive enzyme activation. In current studies, we investigated the role and mechanisms of PKD/PKD1 in the regulation of necrosis in pancreatic acinar cells by using two novel small molecule PKD inhibitors CID755673 and CRT0066101 and molecular approaches in in vitro and in vivo experimental models of acute pancreatitis. Our results demonstrated that both CID755673 and CRT0066101 are PKD-specific inhibitors and that PKD/PKD1 inhibition by either the chemical inhibitors or specific PKD/PKD1 siRNAs attenuated necrosis while promoting apoptosis induced by pathological doses of cholecystokinin-octapeptide (CCK) in pancreatic acinar cells. Conversely, up-regulation of PKD expression in pancreatic acinar cells increased necrosis and decreased apoptosis. We further showed that PKD/PKD1 regulated several key cell death signals including inhibitors of apoptotic proteins, caspases, receptor-interacting protein kinase 1 to promote necrosis. PKD/PKD1 inhibition by CID755673 significantly ameliorated necrosis and severity of pancreatitis in an in vivo experimental model of acute pancreatitis. Thus, our studies indicate that PKD/PKD1 is a key mediator of necrosis in acute pancreatitis and that PKD/PKD1 may represent a potential therapeutic target in acute pancreatitis. PMID:22470346

  15. Autoimmune pancreatitis: Multimodality non-invasive imaging diagnosis

    PubMed Central

    Crosara, Stefano; D'Onofrio, Mirko; De Robertis, Riccardo; Demozzi, Emanuele; Canestrini, Stefano; Zamboni, Giulia; Pozzi Mucelli, Roberto

    2014-01-01

    Autoimmune pancreatitis (AIP) is characterized by obstructive jaundice, a dramatic clinical response to steroids and pathologically by a lymphoplasmacytic infiltrate, with or without a pancreatic mass. Type 1 AIP is the pancreatic manifestation of an IgG4-related systemic disease and is characterized by elevated IgG4 serum levels, infiltration of IgG4-positive plasma cells and extrapancreatic lesions. Type 2 AIP usually has none or very few IgG4-positive plasma cells, no serum IgG4 elevation and appears to be a pancreas-specific disorder without extrapancreatic involvement. AIP is diagnosed in approximately 2%-6% of patients that undergo pancreatic resection for suspected pancreatic cancer. There are three patterns of autoimmune pancreatitis: diffuse disease is the most common type, with a diffuse, “sausage-like” pancreatic enlargement with sharp margins and loss of the lobular contours; focal disease is less common and manifests as a focal mass, often within the pancreatic head, mimicking a pancreatic malignancy. Multifocal involvement can also occur. In this paper we describe the features of AIP at ultrasonography, computed tomography, magnetic resonance and positron emission tomography/computed tomography imaging, focusing on diagnosis and differential diagnosis with pancreatic ductal adenocarcinoma. It is of utmost importance to make an early correct differential diagnosis between these two diseases in order to identify the optimal therapeutic strategy and to avoid unnecessary laparotomy or pancreatic resection in AIP patients. Non-invasive imaging plays also an important role in therapy monitoring, in follow-up and in early identification of disease recurrence. PMID:25493001

  16. Inhibition of pancreatic protein secretion by ghrelin in the rat

    PubMed Central

    Zhang, Weizhen; Chen, Min; Chen, Xuequn; Segura, Bradley J; Mulholland, Michael W

    2001-01-01

    The role of ghrelin in the regulation of pancreatic protein secretion was investigated in vivo using anaesthetized rats with pancreatic ductal cannulas, and in isolated pancreatic acinar cells and pancreatic lobules in vitro. In vivo, pancreatic protein output stimulated by CCK-8 (400 pmol kg−1 h−1) was dose-dependently inhibited by continuous ghrelin infusion (1.2 and 12 nmol kg−1 h−1) by 45 ± 8 and 84 ± 7 %, respectively. In rats with acute subdiaphragmatic vagotomy, ghrelin (12 nmol kg−1 h−1) significantly inhibited CCK-stimulated pancreatic protein secretion by 75 ± 18 %. Infusion of ghrelin (12 nmol kg−1 h−1) abolished pancreatic protein secretion caused by the central vagal stimulant 2-deoxy-d-glucose (75 mg kg−1), whereas bethanechol-stimulated pancreatic protein output was inhibited by only 59 ± 7 %. In vitro, ghrelin (10−11–10−7m) produced no change in basal amylase release from dispersed, purified acinar cells. Co-incubation of ghrelin (10−11−10−7m) with CCK−8 (10−10m) demonstrated no inhibition of CCK-stimulated amylase release from dispersed acini. In contrast, ghrelin (10−9−10−7m) dose-dependently inhibited amylase release from pancreatic lobules exposed to 75 mm potassium. Our results show that (1) ghrelin is a potent inhibitor of pancreatic exocrine secretion in anaesthetized rats in vivo and in pancreatic lobules in vitro; and (2) the actions of ghrelin are indirect and may be exerted at the level of intrapancreatic neurons. PMID:11711576

  17. Impact of Global Fxr Deficiency on Experimental Acute Pancreatitis and Genetic Variation in the FXR Locus in Human Acute Pancreatitis

    PubMed Central

    Nijmeijer, Rian M.; Schaap, Frank G.; Smits, Alexander J. J.; Kremer, Andreas E.; Akkermans, Louis M. A.; Kroese, Alfons B. A.; Rijkers, Ger. T.; Schipper, Marguerite E. I.; Verheem, André; Wijmenga, Cisca; Gooszen, Hein G.; van Erpecum, Karel J.

    2014-01-01

    Background Infectious complications often occur in acute pancreatitis, related to impaired intestinal barrier function, with prolonged disease course and even mortality as a result. The bile salt nuclear receptor farnesoid X receptor (FXR), which is expressed in the ileum, liver and other organs including the pancreas, exhibits anti-inflammatory effects by inhibiting NF-κB activation and is implicated in maintaining intestinal barrier integrity and preventing bacterial overgrowth and translocation. Here we explore, with the aid of complementary animal and human experiments, the potential role of FXR in acute pancreatitis. Methods Experimental acute pancreatitis was induced using the CCK-analogue cerulein in wild-type and Fxr-/- mice. Severity of acute pancreatitis was assessed using histology and a semi-quantitative scoring system. Ileal permeability was analyzed in vitro by Ussing chambers and an in vivo permeability assay. Gene expression of Fxr and Fxr target genes was studied by quantitative RT-PCR. Serum FGF19 levels were determined by ELISA in acute pancreatitis patients and healthy volunteers. A genetic association study in 387 acute pancreatitis patients and 853 controls was performed using 9 tagging single nucleotide polymorphisms (SNPs) covering the complete FXR gene and two additional functional SNPs. Results In wild-type mice with acute pancreatitis, ileal transepithelial resistance was reduced and ileal mRNA expression of Fxr target genes Fgf15, SHP, and IBABP was decreased. Nevertheless, Fxr-/- mice did not exhibit a more severe acute pancreatitis than wild-type mice. In patients with acute pancreatitis, FGF19 levels were lower than in controls. However, there were no associations of FXR SNPs or haplotypes with susceptibility to acute pancreatitis, or its course, outcome or etiology. Conclusion We found no evidence for a major role of FXR in acute human or murine pancreatitis. The observed altered Fxr activity during the course of disease may be a

  18. Human pancreatic cancer fusion 2 (HPC2) 1-B3: a novel monoclonal antibody to screen for pancreatic ductal dysplasia.

    PubMed

    Morgan, Terry K; Hardiman, Karin; Corless, Christopher L; White, Sandra L; Bonnah, Robert; Van de Vrugt, Henry; Sheppard, Brett C; Grompe, Markus; Cosar, Ediz F; Streeter, Philip R

    2013-01-01

    BACKGROUND.: Pancreatic ductal adenocarcinoma is rarely detected early enough for patients to be cured. The objective of the authors was to develop a monoclonal antibody to distinguish adenocarcinoma and precancerous intraductal papillary mucinous neoplasia (IPMN) from benign epithelium. METHODS.: Mice were immunized with human pancreatic adenocarcinoma cells and monoclonal antibodies were screened against a panel of archived pancreatic tissue sections, including pancreatitis (23 cases), grade 1 IPMN (16 cases), grade 2 IPMN (9 cases), grade 3 IPMN (13 cases), and various grades of adenocarcinoma (17 cases). One monoclonal antibody, human pancreatic cancer fusion 2 (HPC2) 1-B3, which specifically immunostained adenocarcinoma and all grades of IPMN, was isolated. Subsequently, HPC2 1-B3 was evaluated in a retrospective series of 31 fine-needle aspiration (FNA) biopsies from clinically suspicious pancreatic lesions that had long-term clinical follow-up. RESULTS.: HPC2 1-B3 was negative in all 31 cases of chronic pancreatitis that were tested. In contrast, HPC2 1-B3 immunostained the cytoplasm and luminal surface of all 16 well- to moderately differentiated pancreatic ductal adenocarcinomas. It demonstrated only weak focal staining of poorly differentiated carcinomas. All high-grade IPMNs were found to be positive for HPC2 1-B3. The majority of low-grade to intermediate-grade IPMNs were positive (66% of cases). Immunostaining a separate series of pancreatic FNA cell blocks for HPC2 1-B3 demonstrated that the relative risk for detecting at least low-grade dysplasia (2.0 [95% confidence interval, 1.23-3.26]) was statistically significant (P = .002 by the Fisher exact test). CONCLUSIONS.: To reduce the mortality of pancreatic cancer, more effective early screening methods are necessary. The data from the current study indicate that a novel monoclonal antibody, HPC2 1-B3, may facilitate the diagnosis of early pancreatic dysplasia.

  19. Utility of preoperative dynamic magnetic resonance imaging of the pancreas in diagnosing tumor-forming pancreatitis that mimics pancreatic cancer: report of a case.

    PubMed

    Kuroki, Tamotsu; Tajima, Yoshitsugu; Tsuneoka, Noritsugu; Adachi, Tomohiko; Kanematsu, Takashi

    2010-01-01

    The differential diagnosis of pancreatic carcinoma and tumor-forming pancreatitis remains difficult, and this situation can cause serious problems because the management and prognosis of these two focal pancreatic masses are entirely different. We herein report a case of tumor-forming pancreatitis that mimics pancreatic carcinoma in an 80-year-old woman. Computed tomography showed a solid mass in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed a complete obstruction of the main pancreatic duct in the head of the pancreas. Dynamic contrastenhanced magnetic resonance imaging (MRI) demonstrated a time-signal intensity curve (TIC) with a slow rise to a peak (1 min after the administration of the contrast material), followed by a slow decline at the pancreatic mass, indicating a fibrotic pancreas. Under the diagnosis of tumor-forming pancreatitis, the patient underwent a segmental pancreatectomy instead of a pancreaticoduodenectomy. The histopathology of the pancreatic mass was chronic pancreatitis without malignancy. The pancreatic TIC obtained from dynamiccontrast MRI can be helpful to differentiate tumor-forming pancreatitis from pancreatic carcinoma and to avoid any unnecessary major pancreatic surgery.

  20. Techniques for prevention of pancreatic leak after pancreatectomy

    PubMed Central

    Schoellhammer, Hans F.; Fong, Yuman

    2014-01-01

    Pancreatic resections are some of the most technically challenging operations performed by surgeons, and post-operative pancreatic fistula (POPF) are not uncommon, developing in approximately 13% of pancreaticoduodenectomies and 30% of distal pancreatectomies. Multiple trials of various operative techniques in the creation of the pancreatic ductal anastomosis have been conducted throughout the years, and herein we review the literature and outcomes data regarding these techniques, although no one technique of pancreatic ductal anastomosis has been shown to be superior in decreasing rate of POPF. Similarly, we review the literature regarding techniques of pancreatic closure after distal pancreatectomy. Again, no one technique has been shown to be superior in preventing POPF; however the use of buttressing material on the pancreatic staple line in the future may be a successful means of decreasing POPF. We review adjunctive techniques to decrease POPF such as pancreatic ductal stenting, the use of various topical biologic glues, and the use of somatostatin analogue medications. We conclude that future trials will need to be conducted to find optimal techniques to decrease POPF, and meticulous attention to intra-operative details and post-operative care by surgeons is necessary to prevent POPF and optimally care for patients undergoing pancreatic resection. PMID:25392839