Pancreatic Ischemia Research Articles

Clinical implications of intraoperative fluid therapy in pancreatic surgery: it is not “just water”

Background: Recent studies have suggested that intraoperative fluid overload is associated with a worse outcome after major abdominal surgery. However, evidence in the field of pancreatic surgery is still not consistent. The aim of this study was to evaluate whether intraoperative fluid management could affect the outcome of a major pancreatic resection. Methods: Prospective analysis of 350 major pancreatic resections performed in 2016 at The Pancreas Institute, University of Verona Hospital Trust. Patients were dichotomized according to intraoperative fluid volume administration into near-zero fluid balance (NZF - infusion rate 3 mL/kg/h) and liberal fluid balance groups (LF - >3 mL/kg/h). Intraoperative fluid administration was then correlated to the postoperative outcome. Results: Overall, a LF balance was associated with an increased rate of Clavien-Dindo IIIB (50.5% vs. 34.5%; p = 0.02) and delayed gastric emptying (DGE) (8.8% vs. 1.8%; p = 0.05). A NZF balance was associated with a reduced incidence of biliary fistula (0% vs. 7.9%; p = 0.05) and DGE (5% vs. 11.6%; p = 0,04) but an increased rate of post-operative acute pancreatitis (75% vs. 49.2%; p = 0.02) after pancreaticoduodenectomy. Considering patients with a soft pancreatic remnant, a NZF balance was associated with an increased rate of pancreatic fistula (60% vs. 45.2%, p = 0.02). Conclusion: Considering all pancreatic resections, a LF balance is associated with an increased rate of postoperative morbidity. However, in the case of PD with a soft pancreas, a NZF balance could lead to pancreatic stump ischemia and anastomotic failure. Intraoperative fluid management should be managed according to patient's pancreas-specific risk factors.

Clinical Implications of Intraoperative Fluid Therapy in Pancreatic Surgery

BackgroundRecent studies have suggested that intraoperative fluid overload is associated with a worse outcome after major abdominal surgery. However, evidence in the field of pancreatic surgery is still not consistent. The aim of this study was to evaluate whether intraoperative fluid management could affect the outcome of a major pancreatic resection. MethodsProspective analysis of 350 major pancreatic resections performed in 2016 at the Department of General and Pancreatic Surgery—The Pancreas Institute, University of Verona Hospital Trust. Patients were dichotomized according to intraoperative fluid volume administration (near-zero vs. liberal fluid balance) and matched using propensity score. Intraoperative fluid administration was then correlated to the postoperative outcome. ResultsLiberal fluid balance was associated with an increased rate of Clavien-Dindo ≥ IIIB both after pancreaticoduodenectomy (60.3 vs. 30.2%, p < 0.01) and distal pancreatectomy (50 vs. 27.1%, p = 0.03). In case of pancreaticoduodenectomy, liberal fluid balance was also associated with an increased rate of pancreatic fistula (33.3 vs. 19.9%, p = 0.05), but when considering patients with soft remnants, an increase rate of pancreatic fistula (52.8 vs. 23%, p = 0.03) was indeed associated with the near-zero fluid balance. ConclusionConsidering all pancreatic resections, a liberal fluid balance is associated with an increased rate of postoperative morbidity. However, in the case of PD with a soft pancreas, an NZF balance could lead to pancreatic stump ischemia and anastomotic failure. Intraoperative fluid management should be managed according to patient’s pancreas-specific risk factors.

Transcatheter Arterial Embolization for Bleeding Peptic Ulcers: A Multicenter Study.

To investigate the outcomes of transcatheter arterial embolization (TAE) for the treatment of peptic ulcer bleeding (PUB). This is a retrospective, multicenter study, which investigated all patients who underwent TAE for the treatment of severe upper gastrointestinal hemorrhage from peptic ulcers in five European centers, between January 1, 2012 and May 1, 2017. All patients had undergone failed endoscopic hemostasis. Forty-four patients (male; mean age 74.0 ± 11.1years, range 49-94), with bleeding from duodenum (36/44; 81.8%) or gastric ulcer (8/44; 18.2%) were followed up to 3.5years (range 2-1354days). In 42/44 cases, bleeding was confirmed by pre-procedural CT angiography. In 50% of the cases, coils were deployed, while in the remaining glue, microparticles, gel foam and combinations of the above were used. The study's outcome measures were 30-day survival technical success (occlusion of feeding vessel and/or no extravasation at completion DSA), overall survival, bleeding relapse and complication rates. The technical success was 100%. The 30-day survival rate was 79.5% (35/44 cases). No patients died due to ongoing or recurrent hemorrhage. Re-bleeding occurred in 2/44 cases (4.5%) and was successfully managed with repeat TAE (one) or surgery (one). The rate of major complications was 4.5% (2/44; one acute pancreatitis and one partial pancreatic ischemia), successfully managed conservatively. According to Kaplan-Meier analysis survival was 71.9% at 3.5years. TAE for the treatment of PUB was technically successful in all cases and resulted in high clinical success rate. Minimal re-bleeding rates further highlight the utility of TAE as the second line treatment of choice, after failed endoscopy.

Evaluation of a single-pass with biphasic intravenous contrast medium injection CT protocol for the assessment of complications post-simultaneous pancreas–kidney transplant

To evaluate the use of a single-pass with biphasic intravenous contrast medium injection computed tomography (CT) protocol to provide diagnostic quality CT studies for the assessment of complications post-simultaneous pancreas-kidney transplant (SPK). This was an audit of practice and the need for informed consent was waived. The protocol was used in consecutive patients undergoing CT to exclude intra-abdominal sepsis post-SPK between June and December 2015. Single CT acquisition of the abdomen and pelvis was initiated 70 seconds after the start of biphasic contrast medium injection (66 ml at 1.2 ml/s, followed by 34 ml at 2.4 ml/s, 370 mg iodine/ml). The named transplant pancreas vessels were identified and the attenuation values of the blood within were measured. Diagnostic quality was confirmed if values were >211 HU and >80 HU in the arteries and veins, respectively. Thirteen CT studies were performed in 10 patients. CT studies were excluded due to complete pancreatic necrosis, and transplant superior mesenteric artery (SMA) thrombus with pancreatic head ischaemia causing effacement of the transplant superior mesenteric vein (SMV). Diagnostic quality of the analysed CT studies were confirmed with mean attenuation value of blood >211 HU in the transplant pancreatic arteries (SMA=259.0±51.4 HU, splenic artery=245.3±37.5 HU), and >80 HU in the pancreatic veins (SMV=195.4±36.2 HU, splenic vein=185.1±54.2 HU). Diagnostic quality CT studies were obtained using the single-pass CT protocol. Radiation exposure to patients may be reduced with this protocol, while permitting simultaneous assessment of parenchymal and vascular complications post-SPK.

Niacin Pretreatment Attenuates Ischemia and Reperfusion of Pancreas-induced Acute Pancreatitis and Remote Lung Injury Through Suppressing Oxidative Stress and Inflammation and Activation of SIRT1

BackgroundLung injury subsequent to pancreatic ischemia and reperfusion (PIR) due to shock, revascularization, and pancreas transplantation is a major clinical problem. In addition to proteases, massive production and release of reactive oxygen species (ROS) and induction of inflammatory cytokines have been implicated in remote lung injury. Niacin, also known as vitamin B3, is both antioxidative and anti-inflammatory. In this study, we examined the protective effectiveness of niacin pretreatment against PIR-induced pancreatic and remote lung injury. MethodsMale Sprague-Dawley rats were divided into a sham-operated group, a PIR group, and a PIR group pretreated with niacin; the niacin (300 mg/kg per day) was given on 4 consecutive days before the study. Pancreatic ischemia was established by occluding both the gastroduodenal and splenic arteries for 120 minutes, followed by 240 minutes of reperfusion. Lung injury was assessed by pulmonary barrier function via pulmonary filtration coefficient, Kfc, using an isolated-perfused rat lung preparation. Alveolar protein leakage was assessed by protein concentration in the bronchoalveolar lavage fluid (PCBAL). Lung water content was assessed by both wet-weight/dry-weight ratio (W/D) and lung-weight/body-weight ratio (LW/BW). Lung inflammation was evaluated by the lavage differential neutrophil cell count and tissue tumor necrosis-alpha (TNF-α) level. Oxidative stress was assessed by tissue malondialdehyde (MDA) level. Serum lactate dehydrogenase (LDH) and amylase were examined for lung and pancreas injury. We also evaluated lung tissue SIRT1 mRNA expression. ResultsCompared with the sham group, the PIR group had increased serum amylase and LDH, and impaired the pulmonary barrier dysfunction with marked increases in Kfc, PCBAL, W/D, and LW/BW, and augumented oxidative stress and inflammation with elevated tissue MDA and TNF-α and lavage neutrophil count, which correlated with decreased SIRT1 mRNA expression. Conversely, niacin pretreatment reduced pancreatic and remote lung injury and attenuated pulmonary oxidative stress and inflammation, and also protected against PIR-induced pulmonary barrier dysfunction while restoring SIRT1 mRNA expression. ConclusionNiacin pretreatment reduced PIR-induced pancreatic and lung injury and protected against pulmonary barrier function impairment, which was associated with niacin's antioxidative and anti-inflammatory activity and its capacity to increase SIRT1 mRNA expression.

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

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

Hepatic arterial reconstruction using saphenous vein graft interposition for distal pancreatectomy with celiac axis resection

Objective: We report two cases required hepatic arterial reconstruction during distal pancreatectomy with celiac axis resection (DP-CAR). Methods: Case 1, 54 years old male patent underwent DP-CAR for his pancreas cancer. As radical antegrade modular pancreatosplenectomy (RAMPS) approach, Common hepatic artery was resected first then isolation of inferior pancreatoduodenal artery (IPDA) from supra mesenteric artery (SMA) was attempted. However IPDA was injured then hepatic arterial flow was lost. Total pancreatectomy and subtotal gastrectomy was performed to avoid pancreatic fistula and ischemia of the stomach. Then hepatic arterial reconstruction using saphenous vein graft interposition between infra-renal abdominal aorta and proper hepatic artery was performed. Case 2, 75 years old male patient underwent DP-CAR using RAMPS for his pancreas cancer. After lost hepatic arterial flow due to IPDA injury, saphenous vein graft was immediately harvested to minimize ischemia time. DP-CAR was performed and the stomach was preserved, then arterial reconstruction was performed as same as case 1. Results: Case 1, Hemorrhage from stomach stump was remarkable in his postoperative course. The patient is having malnutrition but not suffered from recurrence for 7 months after the surgery. Case 2, The patient developed delayed postoperative pancreatic fistula and bleeding from SMA. The patient died at postoperative day 82. Conclusion: RAMPS for DP-CAR may have a pit fall to keep hepatic arterial flow safe. The hepatic artery reconstruction using saphenous vein graft was feasible in our series. However reconstruction of the gastric arterial flow and minimize ischemia time should be considered for longterm prognosis.

Involvement of a proapoptotic gene (BBC3) in islet injury mediated by cold preservation and rewarming.

Long-term pancreatic cold ischemia contributes to decreased islet number and viability after isolation and culture, leading to poor islet transplantation outcome in patients with type 1 diabetes. In this study, we examined mechanisms of pancreatic cold preservation and rewarming-induced injury by interrogating the proapoptotic gene BBC3/Bbc3, also known as Puma (p53 upregulated modulator of apoptosis), using three experimental models: 1) bioluminescence imaging of isolated luciferase-transgenic ("Firefly") Lewis rat islets, 2) cold preservation of en bloc-harvested pancreata from Bbc3-knockout (KO) mice, and 3) cold preservation and rewarming of human pancreata and isolated islets. Cold preservation-mediated islet injury occurred during rewarming in "Firefly" islets. Silencing Bbc3 by transfecting Bbc3 siRNA into islets in vitro prior to cold preservation improved postpreservation mitochondrial viability. Cold preservation resulted in decreased postisolation islet yield in both wild-type and Bbc3 KO pancreata. However, after culture, the islet viability was significantly higher in Bbc3-KO islets, suggesting that different mechanisms are involved in islet damage/loss during isolation and culture. Furthermore, Bbc3-KO islets from cold-preserved pancreata showed reduced HMGB1 (high-mobility group box 1 protein) expression and decreased levels of 4-hydroxynonenal (4-HNE) protein adducts, which was indicative of reduced oxidative stress. During human islet isolation, BBC3 protein was upregulated in digested tissue from cold-preserved pancreata. Hypoxia in cold preservation increased BBC3 mRNA and protein in isolated human islets after rewarming in culture and reduced islet viability. These results demonstrated the involvement of BBC3/Bbc3 in cold preservation/rewarming-mediated islet injury, possibly through modulating HMGB1- and oxidative stress-mediated injury to islets.

Therapeutic Methods Against Insulin Resistance

Clinical, neurosurgical and autopsy findings show that type 2 diabetes mellitus is caused by progressive ischemia in the anterior hypothalamus and endocrine pancreas due to atherosclerosis, and associated with insulin resistance. The hypothalamic ischemia provokes neuroendocrinological disorders through descending projections, and the pancreatic ischemia causes an inappropriate insulin secretion. Both ischemic structures can be improved by means of omental implantation (omental transplantation or transposition) or with anti-inflammatory drugs. Likewise, experimental and clinical observations suggest that insulin resistance is caused by inflammatory action of tumor necrosis factor alpha and resistin in the insulin receptor. Because, in contrast to this, high-dose aspirin or resveratrol can reduce hyperglycemia to normal or near normal in diabetic patients. That is, both drugs are almost specific for the treatment of insulin resistance. Finally, the use of clonazepam at night can have a beneficial effect on glucose homeostasis, because it can reduce the effects of stressful stimuli and normalize the sleep disorders or loss. J Endocrinol Metab. 2016;6(1):1-11 doi: http://dx.doi.org/10.14740/jem333e

Perfusion-CT--Can We Predict Acute Pancreatitis Outcome within the First 24 Hours from the Onset of Symptoms?

PurposeSevere acute pancreatitis (AP) is still a significant clinical problem which is associated with a highly mortality. The aim of this study was the evaluation of prognostic value of CT regional perfusion measurement performed on the first day of onset of symptoms of AP, in assessing the risk of developing severe form of acute pancreatitis.Material and Methods79 patients with clinical symptoms and biochemical criteria indicative of acute pancreatitis (acute upper abdominal pain, elevated levels of serum amylase and lipase) underwent perfusion CT within 24 hours after onset of symptoms. The follow-up examinations were performed after 4–6 days to detect progression of the disease. Perfusion parameters were compared in 41 people who developed severe form of AP (pancreatic and/or peripancreatic tissue necrosis) with parameters in 38 consecutive patients in whom course of AP was mild. Blood flow, blood volume, mean transit time and permeability surface area product were calculated in the three anatomic pancreatic subdivisions (head, body and tail). At the same time the patient's clinical status was assessed by APACHE II score and laboratory parameters such as CRP, serum lipase and amylase, AST, ALT, GGT, ALP and bilirubin were compared.ResultsStatistical differences in the perfusion parameters between the group of patients with mild and severe AP were shown. Blood flow, blood volume and mean transit time were significantly lower and permeability surface area product was significantly higher in patients who develop severe acute pancreatitis and presence of pancreatic and/or peripancreatic necrosis due to pancreatic ischemia. There were no statistically significant differences between the two groups in terms of evaluated on admission severity of pancreatitis assessed using APACHE II score and laboratory tests.ConclusionsCT perfusion is a very useful indicator for prediction and selection patients in early stages of acute pancreatitis who are at risk of developing pancreatic and/or peripancreatic necrosis already on the first day of the onset of symptoms and can be used for treatment planning and monitoring of therapy of acute pancreatitis. Early suspicion of possible pancreatic necrosis both on the basis of scores based on clinical status and laboratory tests have low predictive value.

Acute Gastric Volvulus

Gastric volvulus is characterized by abnormal rotation of the stomach along either its long or short axis, giving rise to acute or chronic gastric outlet obstruction. Rotation beyond 180 degrees can potentially lead to strangulation and ischemia of the stomach, resulting in necrosis and perforation. Thus, it is important to consider it as a differential diagnosis as the outcomes may be deleterious (1). A 75 year old Malay woman with significant past medical history of ischemic heart disease, diabetes mellitus, hypertension and hiatus hernia presented to our unit for acute onset of epigastric pain associated with vomiting. A year prior, she had been diagnosed with a large hiatus hernia on esophagogastroduodenoscopy done for gastro-intestinal evaluation of anemia. Vital signs were stable and cardiac evaluation for an acute myocardial event was unremarkable. A chest x-ray was subsequent performed, revealing air-fluid level in the intra-thoracic portion of the stomach (Figure 1). A computed tomography of the thorax and abdomen was obtained, which demonstrated the same hernia, measuring 14cm at its largest intra-thoracic diameter, compressing on the left lower lobe bronchus and thus leading to left lower lobe partial collapse (Figure 2). A nasogastric (NG) tube was then inserted to decompress the stomach but this was unsuccessful, with the distal tip of the NG tube being restricted only to the intra-thoracic portion of the stomach (Figure 3). The patient underwent laparoscopic repair of the paraoesophageal hernia with anterior 180 degrees partial fundoplication and was discharged well 2 weeks later. Borchardt's triad of pain, vomiting and inability to pass the NG tube is seen in up to 70% of patients with acute gastric volvulus (2). This can be complicated by pancreatic, omental or splenic ischemia secondary to traction, haematemesis due to vomiting or perforation as a result of ischemia. Signs of volume depletion and metabolic disturbances due to vomiting may also be present. Adequate resuscitation and decompression should be followed by surgery in fit candidates, with reduction of the stomach and repair of anatomical defects of the diaphragm (3).

Acute pancreatitis complicated by rupture of abdominal aortic aneurysm.

Acute pancreatitis complicated by rupture of abdominal aortic aneurysm.

Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

ObjectiveSeveral previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.AimThe aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.MethodsAcute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.ResultsTreatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP.ConclusionTreatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

Therapeutic effect of ghrelin in the course of ischemia/reperfusion-induced acute pancreatitis.

Protective effect of pretreatment with ghrelin against different forms of acute pancreatitis (AP) has been recently reported. Moreover, the healing properties of this peptide have been proved in AP evoked by cerulein. However, no studies have investigated whether the administration of ghrelin affects the course of ischemia/reperfusion-induced AP. The aim of this study was to evaluate the impact of ghrelin therapy on the course of necrotizing inflammation of the pancreas and to test its impact on peroxidation of lipids and antioxidant defense system in the acutely inflamed pancreas. Acute inflammation of the pancreas was triggered by pancreatic ischemia which was then followed by reperfusion of the gland. Ghrelin (8 nmol/kg/dose) was administered to intraperitoneally twice daily, 24h after the initiation of AP. The impact of ghrelin on the course of necrotizing pancreatitis was evaluated between 1 and 21 days, and involved histological, functional, and biochemical analyses. Treatment with ghrelin ameliorated morphological signs of pancreatic damage including edema, acinar cells vacuolization, hemorrhages, acinar necrosis, leukocytic infiltration of the gland, and led to its earlier regeneration. These effects were accompanied by an improvement in pancreatic blood flow, enhanced DNA synthesis, reduced serum level of pro- inflammatory interleukin-1β, decreased levels of malondialdehyde and an enhanced superoxide dismutase activity in pancreatic tissue. Ghrelin exerts a pronounced therapeutic effect against ischemia-reperfusion-induced pancreatitis. The mechanisms involved are likely multifactorial and are mediated by its anti-inflammatory, as well as anti-oxidative properties.

Pretreatment with obestatin reduces the severity of ischemia/reperfusion-induced acute pancreatitis in rats

Obestatin, as ghrelin, has been originally extracted from the stomach, which remains its major source. Previous studies have shown that administration of obestatin exhibits protective and healing-promoting effects in several organs, including the stomach and kidney. In pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis and promotes survival of pancreatic beta cells and human islets. The aim of the present study was to check the universality of protective effect of obestatin in the pancreas. For this reason we investigated the influence of obestatin administration on the development of ischemia/reperfusion-induced pancreatitis. Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the gland. Obestatin (4, 8 or 16nmol/kg/dose) was administered intraperitoneally twice: 0.5h before exposure to ischemia, and 3h after the first injection. The effect of obestatin on the course of necrotizing pancreatitis was assessed after 6-h reperfusion, and included histological, functional, and biochemical analyses. Treatment with obestatin reduced morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland. These effects were accompanied by an improvement of pancreatic DNA synthesis and superoxide dismutase activity, and a decrease in serum level of lipase and pro-inflammatory interleukin-1β. Moreover pretreatment with obestatin reduced myeloperoxidase activity and malondialdehyde concentration in pancreatic tissue of rats with acute pancreatitis. Conclusions: Administration of obestatin inhibits the development of ischemia/reperfusion-induced acute pancreatitis. This observation, taken together with previous findings that obestatin protects the pancreas against cerulein-induced pancreatitis, indicates that protective effect of obestatin in the pancreas is universal and independent of the primary cause of acute pancreatitis.

Lazaroid U-74389G Administration in Pancreatic Ischemia-Reperfusion Injury: A Swine Model Encompassing Ischemic Preconditioning.

The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. Twelve pigs, weighing 28-35 kg, were randomized into two experimental groups. Group A (control group, n=6): Two periods of ischemic preconditioning (5 min each) separated by a 5-min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6): the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapy groups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization). In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin) were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705) and tissue malondialdehyde levels (P=0.628) did not differ between the two groups. This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

Therapeutic Efficacy of Spleen-Derived Mesenchymal Stem Cells in Mice with Acute Pancreatitis

Background: Acute pancreatitis (AP), a sudden inflammation of the pancreas, can cause severe complications and high mortality despite treatment. The use of mesenchymal stem cells (MSCs) for the treatment of AP has attracted significant attention in novel treatment strategy; however, the mode of action of spleen-derived MSCs (sp-MSCs) in AP remains unknown. Method: MSCs isolated from mouse spleen (msp-MSCs) were used to investigate the effects in animal models of cerulean-induced acute pancreatitis (CAP) and pancreatic ischemia injury (PII). Results: Msp-MSCs had multipotent differentiation capacities and immunoregulatory functions. A greater number of Qtracker-labeled msp-MSCs were detected in pancreas of mice with CAP than of control mice. Infused msp-MSCs reduced serum levels of amylase, lipase, and myeloperoxidase, and pancreatic edema, necrosis level, expression of inflammation cytokines, and CD3+T cell infiltration. In PII model, infused msp-MSCs promoted cell growth and thus improved pancreatic dysfunction. Conclusion: Msp-MSCs exert protective effects on CAP- and PII-induced pancreatic injury and might be developed as a potential therapeutic agent for pancreatitis treatment.

Effects of intravenous administration of pentoxifylline in pancreatic ischaemia–reperfusion injury

BackgroundTherapeutic strategies to reduce the occurrence of pancreatic ischaemia–reperfusion (I–R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti‐inflammatory effect by inhibiting NF‐κB activation. This group has previously demonstrated that pentoxifylline induces an anti‐inflammatory response in acute pancreatitis and liver I–R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I–R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I–R injury. MethodsPancreatic I–R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I–R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and IL‐10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed. ResultsSignificant reductions in serum TNF‐α, IL‐6 and IL‐10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline‐treated animals, denoting less severe pancreatic histologic damage. ConclusionsPentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I–R injury and may be a useful tool in pancreas and kidney transplantation.

Silent ischemic pancreatitis following urosepsis

Pancreatic ischemia is an uncommon cause of acute pancreatitis. Ischemia with resultant pancreatitis has been reported in vasculitis, atheroembolism, intraoperative hypotension, survivors of cardiac arrest and hemorrhagic shock. Ischemic acute pancreatitis is difficult to recognize clinically. In this report we present a 63 year old woman with painless ischemic pancreatitis following urosepsis. We suggest that if a critically ill patient is hypotensive for more than 24-48 hours, amylase levels must be monitored to establish ischemic acute pancreatitis (AP) even if the patient remains asymptomatic. J. Exp. Clin. Med., 2013; 30:63-66

From SDD to a risk- and CIRCO-diagnosis-based approach for treatment and prophylaxis of intestinal bacterial overgrowth in critically ill patients

Dear Editor, With great interest, I read Silvestri and coworkers’ review article [1] introducing the concept of ‘‘critical illness–related carriage in overgrowth concentrations (CIRCO)’’ as the leading mechanism behind what is called selective digestive tract decontamination (SDD). The authors don’t put much weight on the risk of resistance development shown in the Oostdijk study [2], however in an age when colistin is the only available antibiotic to treat some multiresistant Gram-negative organisms, some questions about the general use of the original SDD strategy with the entry criteria of ‘‘ventilatory support for more than 48 h’’ should be raised. De Smet’s [3] large multicenter trial also questions the necessity of the systemic antibiotic component, especially as third-generation cephalosporines are strongly associated with ESBL development [4]. Recently, Razazo and co-workers [4] demonstrated that many patients admitted to the medical ICU from the community are colonized with ESBL E. coli, but in the majority of cases nosocomial infections occur by other Gram-negative organisms in longer term ICU patients after a median of 9 days, and are mostly already found in rectal swabs. This study supports the concept of CIRCO and indicates that its diagnosis by regular surveillance cultures seems possible before infection occurs. In my clinical experience, a number of nonventilated patients show the described overgrowth patterns and develop nosocomial infections associated to these organisms, but many ventilated patient do not. Moreover, since the original introduction of SDD, the ventilatory support regimen has dramatically changed, including the intense utilization of noninvasive ventilation. Ventilatory care bundles including the use of oral care with antiseptic solutions have reduced the incidence of VAP. Early enteral nutrition has been the accepted standard promoting the integrity of the mucosal barrier, and most likely of the intestinal flora as well. Concepts have been introduced utilizing probiotics for the latter purpose [5]. This might be a reason why many practitioners, not only in the US, are still SDD skeptics. To translate the available evidence into the daily life of clinical practice, and as a concept for further clinical studies, I would like to introduce the following risk and CIRCO-diagnosisbased modified SDD concept in which patients with an anticipated ICU stay longer than 72 h need to be screened on admission and then once or twice a week, depending on unit characteristics: The modified SDD regimen, with enteral (given orally or via a feeding tube) tobramycin, colistin, and amphotericin B (add vancomycin if rectal swab is positive for MRSA) only, is used for critically ill patients after 72 h in the ICU if CIRCO (which would be defined as the presence of Klebsiella spp., Enterobacter spp., Citrobacter spp., Proteus mirabilis, Morganella morganii, Serratia marcescens, Acinetobacter baumannii or Pseudomonas aeruginosa in relevant quantity in the nasopharyngeal or rectal screening swabs) is already present on admission, or a change towards CIRCO evolves in continuous surveillance swabs, independently of whether they are receiving ventilatory support or not. In high-risk patients for early infections admitted to the ICU, e.g., patients with severe burns, severely immunocompromised patients defined as groups 2 and 3 by KRINKO [6], anastomotic leakage after esophageal, gastric, intestinal and pancreatic surgery, ileus, bowel ischemia, neurological or neurosurgical disease with increased ICP (especially when treated with hypothermia or barbiturate sedation), and those with femoral lines for ECMO, IABP or renal replacement therapy, the modified SDD regimen can be started on admission prophylactically without CIRCO diagnosis. The indication for continuous treatment should be evaluated weekly. With such a diagnosis-based concept we could utilize the benefits of SDD in those patients who are most likely profit from it, while avoiding unnecessary treatment in others, and also reduce the risk of unwanted ecological changes and resistance development.