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Exosomes and pancreatic diseases: status, challenges, and hopes

Exosomes and pancreatic diseases: status, challenges, and hopes

to their functions and mechanisms is an equally important goal. Recently, Zhang et al. classified nanoparticle components of the cellular communication milieu according to particle size via asymmetric flow field fractionation (AF4). Based on the presence of at least two previously reported exosome subgroups, researchers classified small and large exosomes (Exo-S and Exo-L, respectively) and identified a formerly unrecognized nanoparticle called an exomere. Notably, these three nanosized particles exhibited diverse lipophilic, proteomic, DNA and RNA profiles and N-glycosylation patterns, suggesting that they originate via different biogenesis mechanisms.[138] [139] Undoubtedly, this finding represents significant progress in understanding the role of various exosome subtypes in diverse intractable conditions, such as pancreatic diseases. In past studies on pancreatic disease and exosomes in human or animal models, researchers focused on exosomes isolated from biofluids, such as circulating blood, urine, and cerebrospinal fluid. Exosomes in biofluids may in fact derive from multiple organs, and developing approaches to distinguish these exosomes and determine their organ of origination remains a difficult problem. Recently, Vella et al. introduced a rigorous approach for isolating exosomes from brain tissue. Using a novel method, these researchers successfully enriched and characterized exosomes from the human frontal cortex. More importantly, exosomes also maintain their vesicle and cargo integrity via their endosome-derived origin.[140] This novel method will provide significant value in isolating exosomes from the pancreas and facilitate more detailed insight into pancreatic exosomes.
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Ultrasound-guided percutaneous procedures in pancreatic diseases: new techniques and applications

Ultrasound-guided percutaneous procedures in pancreatic diseases: new techniques and applications

Fusion imaging is usually used to assist percutaneous procedures for challenging lesions, especially those char- acterised by low conspicuity on B-mode US [56]; most previous experiences on multimodal fusion imaging (MMFI) were applied to hepatic and prostatic interven- tion. Theoretically, the pancreas could benefit from this technique, since being a retroperitoneal organ it is poorly affected by respiratory movements that could im- pair real-time image fusion and synchronisation of the images. Nevertheless, there are very few literature re- ports on the use of MMFI techniques for US-guided percutaneous intervention in pancreatic diseases. Sofuni et al. [57] and Sumi et al. [58] reported potential useful- ness of fusion imaging for the evaluation of the pancre- atic tail, a well-known “ blind area ” for transabdominal US, and for pancreatic lesions with low conspicuity on B-mode US. Zhang et al. [59] compared the efficacy of US guidance alone and US/CT image fusion guidance in percutaneous drainage of infected walled-off necrosis following acute pancreatitis. The US/CT fusion group achieved a significantly higher imaging effective rate, and significantly lower inflammatory response indexes
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Secretin-stimulated MR cholangiopancreatography: spectrum of findings in pancreatic diseases

Secretin-stimulated MR cholangiopancreatography: spectrum of findings in pancreatic diseases

Chronic asymptomatic pancreatic hyperenzymaemia (al- so called BGullo’s syndrome^) [29, 30] is a persistent abnormal increase in the serum concentrations of the pancreatic enzymes without pancreatic symptoms and evidence at imaging of pancreatic diseases. The medical need in these patients is to differentiate undiagnosed pancreatic disease and other extra-pancreatic conditions that may induce an increase in serum concentrations of amylase and lipase, including chronic viral hepatitis, renal failure, celiac disease, inflammatory bowel disease, hyperparathyroidism and neoplasms [21, 31]. Consistent evidence, however, indicates that asymptomatic subjects with increased pancreatic enzymes lasting for more than 2 years and accompanied by thoroughly negative imag- ing tests (pancreatic CT scan and/or MRCP) are indeed affected by benign pancreatic hyperenzymaemia [30].
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The role of pancreatic polypeptide in pancreatic diseases

The role of pancreatic polypeptide in pancreatic diseases

of pancreatic parenchyma following the resection of this organ causes extreme disturbances in the glucose homeo- stasis, similar to those in pancreatic diabetes. This form of glucose intolerance is different from other forms of dia- betes owing to more frequent episodes of iatrogenic hy- poglycemia. The improvement of postoperative care and a possibility of an early disease diagnosis greatly extend the length and quality of life of patients after pancreatic resection. The pathophysiology of pancreatic diabetes is associated with the deficiency of pancreatic hormones and changes in response of the liver and other organs to lower than normal hormone levels. PP deficiency is associated with hyperglycemia resulting from an un- restrained hepatic glucose production. It is a characteris- tic symptom of diabetes caused by pancreatic resection. Influencing PP release may mitigate the difficulties with glucose concentrations. PP may probably also improve liver cell sensitivity to insulin, thus beneficially influenc- ing the glycemic control system. 36
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CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases

CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases

All CT examinations were performed with the same scanner type (a 64-row multidetector CT) in the three involved cen- tres using the same imaging protocol. Triphasic CT was per- formed with patients in the supine position with the arms extended above the head. The scans included: unenhanced scan from the dome of the liver to the lower level of the pancreas; contrast-enhanced pancreatic parenchymal phase using the bolus-tracking technique (trigger threshold: 200 HU, scan delay after trigger: 15 s) with the same field of view; portal phase (70 s) from the liver dome to the symphy- sis pubis. All patients received 1.5 ml per kilogram of body weight intravenous iodinated contrast agent (Ultravist 370; Bayer Schering Pharma, Leverkusen, Germany) at an injec- tion rate of 4 ml/s using an automatic injector through an antecubital vein and followed by 40 – 50 ml of saline solution chase at the same flow rate. Other scanning parameters were: tube voltage 120 kVp; automatic tube current modulation and slice thickness 2 mm.
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Human pancreatitis associated protein  Messenger RNA cloning and expression in pancreatic diseases

Human pancreatitis associated protein Messenger RNA cloning and expression in pancreatic diseases

characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products. The human protein was therefore named human pancreatitis-associated protein (PAP-H). Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis. In that tissue, the protein could be immunolocalized to the apical regions of acinar cells. An immunoassay was also constructed to quantify the protein in serum. Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis. Values were close to background in healthy subjects and in patients with other abdominal diseases. These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as […]
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Endoscopic treatment of pancreatic diseases via Duodenal Minor Papilla: 135 cases treated by Sphincterotomy, Endoscopic Pancreatic Duct Balloon Dilation (EPDBD), and Pancreatic Stenting (EPS)

Endoscopic treatment of pancreatic diseases via Duodenal Minor Papilla: 135 cases treated by Sphincterotomy, Endoscopic Pancreatic Duct Balloon Dilation (EPDBD), and Pancreatic Stenting (EPS)

occurred, EPS was withdrawn immediately and EPS was re- placed. 52 cases out of 87 cases (52/87=60%), were followed up, for 5 months to 27 years, had EPS-replacement many times and still now EPS(+). We have experienced 3 cases of EPS migration in early period, but after using pig tail type EPS, the migration of EPS doesn’t occur (Figure 4). After treatment via minor papilla, 4 cases had operations-2 pseudocyst case by pancreatic tail resection, 1 which had marked narrowing in the Santorini’s duct by pancreato-duodenal resection. 6 pancreatic and 2 lung cancer occurred and death cases were 3 pancreatic, 1 lung cancer and 6 others (Table 4). Stenosis of the minor papilla after EPS removal occurred in 3 cases in 1 case EPS was re-placed by precutting and balloon dilation method (Figure 15), 2 cases had no therapy without symptoms.
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Multifocal Myocardial Necrosis and Fibrosis in Pancreatic Diseases of Children

Multifocal Myocardial Necrosis and Fibrosis in Pancreatic Diseases of Children

lipomatosis (2 cases), extensive small bowel resection (3 cases, 2 of which were associated with acute interstitial pancreatitis).. To explain these unexpected associations, two hypothes[r]

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The pancreatic stellate cell: a star on the rise in pancreatic diseases

The pancreatic stellate cell: a star on the rise in pancreatic diseases

Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic coun- terparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases.
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A Study of Pancreatic Diseases

A Study of Pancreatic Diseases

Historically, the first description of the pancreas is credited to Herophilus of Chaikaldon around the year 300 B.C. Four centuries later in approximately 100 A.D this abdominal organ was named the pancreas by Rufus of Ephesus. The first operative intervention on the pancreas has been attributed to Le Dentu in the year 1862, involving percutaneous aspiration of a pancreatic mass with an unfavourable outcome. The first successful resection of a periampullary tumour was performed by Halsted in 1899. The tumour was resected locally and reconstruction was performed. The first successful pancreatico duodenectomy was performed by kausch in 1912. In 1935, Whipple done a successful two stage enbloc resection of the head of the pancreas and the duodenum. The first one stage pancreatico duodenectomy was reported in the United States by Trimble in 1941.
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Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition

Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition

It has been reported that malnutrition occurred in 38% to 88% of ICU patients, which was associated with detri- mental clinical outcomes [2]. To provide adequate EN, current studies are focused mostly on the choice of deliv- ery timing, formula selection and route of administration [4]. Little attention has been paid to the potential contri- bution of EPI to malnutrition. In this study, we found that EPI was present in more than 50% of critically ill adult patients without primary pancreatic diseases and nearly 20% of them had severe EPI. If the patients with preexisting EPI had also been included in this study, the proportion of critically ill adult patients with EPI should have been even higher. Hence, the status of exocrine pan- creatic function in ICU patients should be considered seriously when the intention is to prevent undernourish- ment through EN, particularly for those patients with severe EPI or those who have risk factors of EPI. A num- ber of causes other than EPI may also contribute to mal- nutrition, however, such as inadequate or unbalanced diet, reduced absorption of nutrients and increased energy consumption [31]. Moreover, Deane et al. [32] recently reported that absorption at the luminal surface is impaired and small luminal motility may affect lipid absorption in critically ill patients. Therefore, improved digestion of nutrients by pancreatic enzyme supplemen- tation cannot guarantee that the occurrence of malab- sorption and malnutrition will be avoided. Further studies designed to investigate the effects of pancreatic enzyme supplementation on malnutrition in critically ill patients may help to elucidate the underlying association between EPI and malnutrition.
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Evaluation of lipase levels in patients with nephropathia epidemica   no evidence for acute pancreatitis

Evaluation of lipase levels in patients with nephropathia epidemica no evidence for acute pancreatitis

Additionally, increased levels of pancreatic enzymes have been reported in patients with impaired renal function even in the absence of pancreatic diseases although lipase tended to be l[r]

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Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency

Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency

disease, PEI is associated with malnutrition, including low levels of micronutrients and fat-soluble vitamins, particularly vitamin D, and essential fatty acids, coupled with gradual weight loss and steatorrhea as a result of maldigestion. This issue is particularly important in children because malnutrition may affect growth patterns. Therefore, lifestyle (eg, cessation of alcohol and smoking), nutritional (eg, low-fat diet and dietary supplementation with essential minerals and vitamins), and pharmacological interventions are needed to improve the clinical symptoms and pathophysiology of pancreatic diseases. For example, pancreatic enzyme replacement therapy (PERT) not only improves the clinical symptoms and malnutrition caused by PEI, but can also allow the patient to discontinue a low-fat diet.
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Effect of dexmedetomidine in the prophylactic endoscopic injection sclerotherapy for oesophageal varices: a study protocol for prospective interventional study

Effect of dexmedetomidine in the prophylactic endoscopic injection sclerotherapy for oesophageal varices: a study protocol for prospective interventional study

diseases, including upper gastrointestinal bleeding, early gastric cancer, hepatobiliary – pancreatic diseases and oesophageal varices (OVs). 1–4 However, anxiety, pain, fear and adverse gastrointestinal reactions may cause subjects to be less cooperative during endo- scopic procedures, and may even cause harmful cardiovascular adverse events. 5–7 Thus, the role of sedation in endoscopy is therefore very important, with various seda- tive agents commonly used during endo- scopic procedures. 5–7

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The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases

The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases

To ensure that the collected biomaterials are used for high- quality research projects, a workflow for the review process has been established. Research proposals are submitted to the coordi- nator of the Dutch Pancreas Biobank and subsequently evaluated by a dedicated scientific committee. When approved by the scien- tific committee, the Dutch Pancreas Biobank scientific board has to approve the proposal as well. This scientific board consists of one member from all specialties involved in the treatment of pa- tients with pancreatic diseases (surgery, medical oncology, gastro- enterology, pathology, radiology, radiotherapy, and translational research) from each participating center. Hereafter, approval of the IRB from the centers of which samples are used will be acquired. Subsequently, the samples will be provided to the researcher within 4 weeks from the official request to the biobank.
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Role of Endoscopic Retrograde Cholangio Pancreatography in Tropical Calcific Pancreatitis.

Role of Endoscopic Retrograde Cholangio Pancreatography in Tropical Calcific Pancreatitis.

The frequency of steatorrhoea is low because of the low fat intake in the diet.About 20% of patients complain of passing bulky, frothy or frank oily stools. If the fat intake is increased to about 100g day, over 70% of patients have demonstrable steatorrhoea ( Pitchumoni 1984,Geevarghese 1985)[5,90]. Approximately 90% of the exocrine pancreas must be destroyed before significant steartorrhoea, azotorrhoea and creatorrhoea occur[20,21,23]. Fat maldigestion is more severe than protein and carbohydrate maldigestion. This is because lipid depends only on pancreatic lipase and co-lipase for digestion. Bicarbonate insufficiency causes reduced intraduodenal pH which is more injurious to lipase. Steatorrhoea is corrected even if 10% of the normal amount of lipase can be delivered at the proper time. Although maldigestion affects all nutrients, the most clinically significant problem concerns maldigestion of fat and fat-soluble vitamins.
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Chronic diseases, inflammation, and spices: how are they linked?

Chronic diseases, inflammation, and spices: how are they linked?

human non-small cell lung cancer, this potent compound induced apoptosis via the upregulation of micro RNA, miR-192-5p and downregulation  of PI3K/Akt signaling pathway [90]. Also, this compound was reported as a pro- tectant against severe acute pancreatitis via attenuation of NF-κB in vivo [91]. This compound is known to inhibit cancer cell proliferation, survival, invasion, angiogenesis, metastases, chemoresistance, and radiation resistance in different types of cancers via modulation of different sign- aling pathways including NF-κB. Approximately, over 120 clinical trials have proven  its potential to treat different chronic diseases without showing any adverse side effects. Curcumin has been shown to inhibit IBD, colitis, rhini- tis, oral lichen planus, psoriasis, and prostatitis in vari- ous clinical trials. It has also been shown to inhibit cancer alone or in combination with standard chemotherapeutic agents in many clinical trials. So far, curcumin is the most extensively studied spice derived component for the treat- ment of different chronic diseases in both preclinical and clinical settings.
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The Preliminary Approach for the Human Cancer Regression by the Interaction  between Human Bilateral Symmetrical  Parts—Ou MC Decrescendo Phenomenon

The Preliminary Approach for the Human Cancer Regression by the Interaction between Human Bilateral Symmetrical Parts—Ou MC Decrescendo Phenomenon

Ou MC decrescendo phenomenon (OuDP) is induced by interaction between human bilateral fea- tures and has shown to alleviate or cure infectious and non-infectious diseases. The resolution of non-infectious conditions with OuDP indicates to be consistent with restoration of normal tissue function (AJEM, 2012; Proc Physiol Soc, 2014). Ou MC handing remedy (HR) was utilized to induce OuDP by applying the hand to the contralateral body. Four female patients received self-adminis- tered HR separately for their diseases: 1) uterine endometrioid carcinoma stage IIIB, 2) suspicious pancreatic cancer in stage IA with isodense pancreatic nodule, elevated CA199 and dilated tor- tuous main pancreatic duct, 3) uterine leiomyosarcoma stage IB, and 4) suspicious gluteal metas- tatic lesion of chronic myelogenous leukemia. The treatments with HR showed to suppress or ameliorate oncologic changes for these patients: 1) The uterine endometrioid carcinoma regressed from stage IIIB to IA with 5 months treatment. 2) The pancreatic isodense lesion decreased from 1.6 × 1.7 to 1.0 × 1.0 cm in size with CA199 descending from 1090.0 to 136.5 (Unit/ml) associating with the main pancreatic duct diameter decreasing from 0.39 to 0.14 cm with tortuosity disap- pearance after 4 months treatment. 3) The frequent profuse bleeding by uterine leiomyosarcoma prominently decreased immediately with HR and subsequent HR was also effective at minimizing heavy uterine bleeding in the 3 weeks treatment. 4) The gluteal macular lesion of the case with chronic myelogenous leukemia was eliminated with 2 weeks treatment. It reveals OuDP may nor- malize the tumor cells and microenvironment function, which makes tumor cells conform to the
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Original Article Central venous-to-arterial partial pressure of carbon dioxide difference indicates the prognosis of cancer patients with sepsis

Original Article Central venous-to-arterial partial pressure of carbon dioxide difference indicates the prognosis of cancer patients with sepsis

Patients were excluded if they met the follow- ing exclusion criteria: Age < 18 years old; Shock status except septic shock; Chronic diseases (chronic obstructive pulmonary disease and chronic kidney disease) because of the acute exacerbation of organ dysfunction; Taking sali- cylic acid, biguanide hypoglycemic agents and other drugs that can affect blood lactic acid concentration; had undergone a broad spec- trum of antibiotic therapy previously; died in ICU or discharged from ICU within 24 hours. Procedures

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Mikhail V. Blagosklonny 1

Mikhail V. Blagosklonny 1

In summary, the incidence of common cancers such as breast, prostate, colon, lung, pancreatic, gastric, bladder and certain leukemias is increased with age. Conditions that accelerate aging such as obesity also accelerate cancer, whereas slow aging is associated with delayed cancer. One can suggest that pharmacological interventions that slow down organismal aging will delay or prevent cancer. It was demonstrated that mTOR is involved in cellular senescence, converting quiescence into senescence (geroconversion). Importantly, mTOR is involved in organismal aging and its inhibition extends lifespan. Aging can be decelerated by rapamycin.
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