Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis

Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immun-osorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM en-dotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 μg vs. 0.21 |μg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 μg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = —0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Evaluation of intestinal mucosal permeability function in patients with acute pancreatitis

This study aims to evaluate the intestinal mucosal permeability in patients with acute pancreatitis. The lactulose:mannitol (L:M) ratio was used to assess permeability. It is an inexpensive and quite reliable method. The intestinal permeability was increased in patients with acute pancreatitis compared with the controls. In addition, patients with severe pancreatitis had higher intestinal barrier dysfunction compared with patients with mild pancreatitis, the L:M ratio being .2 and .029, respectively. It was also concluded that the permeability increased gradually over the course of pancreatitis and was maximum at day 7 (P < .01). This provides a window of opportunity for therapeutic intervention to prevent the late observed increase in intestinal permeability.     

Significance of Serum Endotoxin and Antiendotoxin Antibody Levels in Predicting the Severity of Acute Pancreatitis

Abstract. Purpose: A close association between endotoxemia and acute pancreatitis has been reported, and attempts have been made to predict the severity of pancreatitis by estimating the levels of endotoxin. The present study was designed to correlate endotoxemia with the severity and complications of acute pancreatitis as graded by contrast-enhanced computed tomography and Blamey's criteria. Methods: We examined 20 patients with acute pancreatitis, using Blamey's criteria to assess the severity of pancreatitis. The endotoxin level was estimated by the Limulus Amoebocyte Lysate method and the antiendotoxin antibody level was assayed by the enzyme-linked immunoassay technique measuring combined levels of IgG and IgM. Results: Severe pancreatitis was confirmed in 9 of the 20 patients, 17 (85%) of whom were found to have endotoxemia. There was no correlation between the presence and level of endotoxemia and the severity of pancreatitis; however, antiendotoxin antibody titers were significantly lower in patients with severe disease (P < 0.05), those who suffered of major complications (P < 0.01), and those who died of the disease (P < 0.01). Conclusion: The findings of this study demonstrated that the presence of endotoxemia accompanied by a fall in antiendotoxin antibody titer predicts poor outcome in patients with acute pancreatitis. Received: April 26, 2001 / Accepted: November 20, 2001     

Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl-min^−l.cap ⁻¹ [control]; P = NS), whereas mucosal (1.59 _± 0.03 vs. 2.28 ± 0.03 nl.min^−l.cap ⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl-min^−l.cap ^-1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 = 0.03 vs. 1.98 ± 0.04 nl’min^-1.cap ^-1 [control]; P <0.01) and colonic (mucosal: 0.59 = 0.01 vs. 2.28 ± 0.03 nl.min^−l.cap ^-1 [control], P < 0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl.min^−l.cap ^-1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ±19 nmol.hr^−l.cm {−2}2; mild pancreatitis: 158±23 nmol-hr^−l.cm^-2; severe pancreatitis: 181 ±33 nmol.hr^−l.cm^-2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 19–22, 1996. Supported in part by Deutsche Forschungsgemeinschaft (DFG Fo 197/3).     

Early nasogastric feeding in predicted severe acute pancreatitis: A clinical, randomized study

OBJECTIVE: To compare the efficacy and safety of early, nasogastric enteral nutrition (EN) with total parenteral nutrition (TPN) in patients with predicted severe acute pancreatitis (SAP). SUMMARY BACKGROUND DATA: In SAP, the magnitude of the inflammatory response as well as increased intestinal permeability correlates with outcome. Enteral feeding has been suggested superior to parenteral feeding due to a proposed beneficial effect on the gut barrier. METHODS: Fifty patients who met the inclusion criteria were randomized to TPN or EN groups. The nutritional regimen was started within 24 hours from admission and EN was provided through a nasogastric tube. The observation period was 10 days. Intestinal permeability was measured by excretion of polyethylene glycol (PEG) and concentrations of antiendotoxin core antibodies (Endocab). Interleukins (IL)-6 IL-8, and C-reactive protein (CRP) were used as markers of the systemic inflammatory response. Morbidity and feasibility of the nutritional route were evaluated by the frequency of complications, gastrointestinal symptoms, and abdominal pain. RESULTS: PEG, Endocab, CRP, IL-6, APACHE II score, severity according to the Atlanta classification (22 patients), and gastrointestinal symptoms or abdominal pain did not significantly differ between the groups. The incidence of hyperglycemia was significantly higher in TPN patients (21 of 26 vs. 7 of 23; P < 0.001). Total complications (25 vs. 52; P = 0.04) and pulmonary complications (10 vs. 21; P = 0.04) were significantly more frequent in EN patients, although complications were diagnosed dominantly within the first 3 days. CONCLUSION: In predicted SAP, nasogastric early EN was feasible and resulted in better control of blood glucose levels, although the overall early complication rate was higher in the EN group. No beneficial effects on intestinal permeability or the inflammatory response were seen by EN treatment.     

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) recieved endotoxin (10 mg/kg intraperitoneally,n=9), while the control group (CONT,n=8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P<0.05), while the CVP and SMVP increased (P<0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P<0.05). The D-xylose concentration in SMV decreased significantly (P<0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.     

Randomized controlled trial of the effect of early enteral nutrition on markers of the inflammatory response in predicted severe acute pancreatitis

BACKGROUND: Recent evidence suggests that intestinal dysfunction has a role in sustaining the systemic inflammatory response in acute pancreatitis and may be ameliorated by the introduction of enteral nutrition. This study therefore assessed the effect of early enteral nutrition on the systemic inflammatory response in patients with prognostically severe acute pancreatitis. METHODS: Patients with prognostically severe acute pancreatitis within 72 h of disease onset were randomized to receive either enteral nutrition or conventional therapy consisting of a nil-by-mouth regimen. Serum interleukin (IL) 6, soluble tumour necrosis factor receptor I (sTNFRI) and C-reactive protein (CRP) were used as markers of the inflammatory response. Intestinal function was assessed using a differential sugar permeability technique. RESULTS: Of 27 patients, 13 received enteral nutrition. A median of 21 (range 0-100) per cent of calorific requirements was delivered over the first 4 days by enteral nutrition. There were no significant complications of enteral nutrition. The introduction of enteral nutrition did not affect the serum concentrations of IL-6 (P = 0.28), sTNFRI (P = 0.53) or CRP (P = 0.62) over the first 4 days of the study. Although there were no significant differences in intestinal permeability between the two patient groups at admission (chi2 = 2.33, d.f. = 1, P = 0.13), by day 4 abnormal intestinal permeability occurred more frequently in patients receiving enteral nutrition (chi2 = 4.94, d.f. = 1, P = 0.03) CONCLUSION: Early enteral nutrition did not ameliorate the inflammatory response in patients with prognostically severe acute pancreatitis. Furthermore, it did not have a beneficial effect on intestinal permeability. Presented in part to the Pancreatic Society of Great Britain and Ireland in Leeds, UK, November 1998 and at Digestive Disease Week in Orlando, Florida, USA, May 1999     

Altered intestinal morphology and immunity in patients with acute necrotizing pancreatitis

Purpose/Background: Impairment of gut barrier function has been demonstrated in patients with severe acute pancreatitis and may contribute to the development of local and systemic septic complications. The underlying mechanisms, however, remain unclear. Against this background, our aims were to investigate the small intestinal epithelial morphology and mucosal immunity in patients with severe acute pancreatitis. Methods: Segments of terminal ileum from three patients with severe necrotizing acute pancreatitis who underwent pancreatic debridement and ileocolic resection for doubtful or evident segmental colonic viability were available for the study. Control specimens were available from seven patients who underwent gastric bypass and distal ileal resection for morbid obesity. Sections were cut and stained with hematoxylin and eosin for the measurement of villous height and crypt depth, and with toluidine blue for the determination of mucosal mast cell counts. Only adequately oriented specimens were deemed suitable for computer-aided image analysis. Results were expressed as the villous height/crypt depth ratio (VH/CD) and mucosal mast cell index (ratio of mast cell count/length of muscularis mucosa). Results: Microscopy of the small intestine from controls was normal. The villous height and VH/CD were significantly reduced in patients with acute pancreatitis compared with controls (median, 0.47 mm vs 0.68 mm, and 1.9 vs 2.8, respectively; P < 0.00001). The mast cell index was significantly reduced in patients with acute pancreatitis compared with controls (median, 5.88 cells/mm vs 8.58 cells/mm; P = 0.001). A positive correlation was observed between the mast cell index and the height of the villi (r = 0.23; P = 0.027). Conclusions: Patients with necrotizing acute pancreatitis have an altered intestinal morphology and depleted mucosal mast cells. These factors may contribute to the impairment of gut barrier function in patients with severe acute pancreatitis. Received: March 31, 2002 / Accepted: June 14, 2002 Offprint requests to: B. J. Ammori Present address: Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK     

Temporary pancreatic stent to prevent post endoscopic retrograde cholangiopancreatography pancreatitis: a preliminary, single-center, randomized controlled trial

Background Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is the most common complication of ERCP, which can occasionally become serious or fatal. This preliminary study was to prospectively evaluate the efficacy of a temporary unflanged pancreatic duct stent (PS) to prevent post-ERCP pancreatitis. Methods A total of 64 patients were randomly divided into a control group, which did not undergo stenting, and a stent group. The stent used was a 5-Fr pigtail PS without an inner flange. Results Placement of an unflanged PS was successful and without complications in all 32 patients. The rates of hyperamylasemia were 50.0% and 34.4% in the control and stent groups, respectively (P > 0.05), and the mean serum amylase levels were 456.2 and 257.9 IU/l, respectively (P = 0.035). The overall rates of post-ERCP pancreatitis diagnosed according to Cotton's criteria were 12.5% and 3.1% in the control and stent groups, respectively (P > 0.05). The severity of pancreatitis was severe in one patient, moderate in one, and mild in two in the control group, whereas in the stent group, the single case of pancreatitis was mild. Conclusions Placement of an unflanged 5-Fr PS may be useful in preventing post-ERCP pancreatitis.     

Increased intestinal permeability during cytomegalovirus infection in renal transplant recipients

Cytomegalovirus (CMV) infections in renal transplant recipients can affect the gastrointestinal tract, but significant clinical manifestations are seldom seen. We hypothesize that subclinical involvement of the gastrointestinal tract may be quite frequent during CMV infection. In order to study this, we measured intestinal permeability by calculating the urinary lactulose mannitol (LM) excretion ratio after oral administration of lactulose and mannitol (normal<0.030) in patients with symptomatic and asymptomatic CMV infection. A total of 111 patients were enrolled in the study, 104 of whom were tested on postoperative day (POD) 10. Twenty-nine patients developed CMV infection, 12 of whom could be studied with the permeability test (median POD 40). Another nine patients without CMV infection were also studied at day 40 and served as controls. The LM ratio increased significantly during CMV infection compared to measurements before active infection (median 0.060 vs. 0.030, P<0.01) and was significantly higher during the infection than in the control group (median 0.007, P<0.01). No correlation could be found between the LM ratio and viral load, humoral response to the virus, or symptomatology of infection. We conclude that an increased intestinal permeability is found in a substantial number of patients with an active, albeit asymptomatic, CMV infection after renal transplantation. Pathophysiological mechanisms and clinical implications remain speculative but will be subject to further study.     

复方大承气汤治疗重症急性胰腺炎所致麻痹性肠梗阻86例

目的：观察复方大承气汤治疗重症胰腺炎（SAP）并发麻痹性肠梗阻的疗效。方法：采用随机分组方法,将149例患者随机分为治疗组和对照组。对照组采用禁食水,持续胃肠减压,抑酶、维持水、电解质及酸碱平衡,完全胃肠外营养,抗生素及温生理盐水500 mL日二次保留灌肠治疗。治疗组在对照组治疗方法的基础上,采用复方大承气汤保留灌肠,比较2组治疗后肠鸣音、排气排便和血淀粉酶恢复时间。结果：治疗组86例患者发生多器官功能障碍综合征共15例,对照组发生共19例,2组比较差异有统计学意义（P〈0.05）。治疗组共治愈82例,死亡4例,对照组治愈44例,共19例死亡。治疗组中的肠鸣音、排气排便和血淀粉酶恢复时间均明显短于对照组,差异有统计学意义（P〈0.05）。结论：早期应用复方大承气汤灌肠治疗SAP并发麻痹性肠梗阻,可促进肠功能的恢复,缩短麻痹性肠梗阻持续时间及减轻其危害,减少住院病程。     

The impact of intestinal ischaemia-reperfusion on caerulein-induced oedematous experimental pancreatitis

BACKGROUND: Intestinal ischaemia is a feature of severe acute pancreatitis. It is not known whether intestinal ischaemia and reperfusion contributes to the progression from mild to severe pancreatitis. AIM: The aim of this study was to examine the impact of intestinal ischaemia-reperfusion on caerulein-induced oedematous experimental pancreatitis. METHOD: Male Wistar rats (n = 48) were randomised to 6 experimental groups: controls (CO), saline infusion (S), saline infusion and intestinal ischaemia-reperfusion (SIR), caerulein infusion (C), caerulein and sham operation (CS), and caerulein infusion with intestinal ischaemia reperfusion (CIR). Caerulein was infused over 6 h to induce mild oedematous pancreatitis. Clamping the superior mesenteric artery for 10 min induced mild intestinal ischaemia. The reperfusion time was 24 h. The primary end point was histology of the pancreas at 24 h. RESULTS: There was no significant difference in histologic severity of pancreatitis at 24 h (Kruskal-Wallis, p = 0.37). CONCLUSION: The severity of acute oedematous pancreatitis was not increased by 10 min of intestinal ischaemia followed by 24 h of reperfusion.     

Management of gallstone pancreatitis in Auckland: progress and compliance

Background: Recent advances in the management of acute gallstonepancreatitis include the introduction of laparoscopic cholecystectomy,defining the role of endoscopic retrograde cholangiopancreatography(ERCP) and early cholecystectomy to prevent recurrent pancreatitis.The aim of the present study was to review the current managementof gallstone pancreatitis in Auckland Hospital, compare findingswith a similar study published a decade ago and to determine theextent to which the management is compliant with recently publishedconsensus guidelines. Methods: A retrospective review of consecutive patients admittedwith acute pancreatitis during a 39‐month study period was undertaken.Data were recorded regarding demographics, diagnosis, predictedand actual severity of gallstone pancreatitis (index and recurrentattacks), the role of ERCP and computed tomography scanning, thetiming of cholecystectomy (open and laparoscopic), intraoperativecholangiography, duration of hospital stay, complications and mortality. Results : There were 216 patients admitted with acute pancreatitis,106 of whom had proven gallstones. An ERCP was performed in 62(59%) patients with gallstone pancreatitis but not morecommonly in patients with severe pancreatitis, and common bile duct stoneswere identified in 26% of these patients. Of the 70 (66%)patients who had a cholecystectomy, 56 (80%) had it within3 weeks of admission. Although the proportion of patientswith gallstone pancreatitis who had a cholecystectomy is similarto the earlier study, there has been a significant increase in theproportion of patients having a cholecystectomy during the indexadmission (χ² = 3.83; P = 0.05).This has resulted in a reduction in recurrent pancreatitis (P < 0.001).Although the overall mortality from gallstone pancreatitis has notsignificantly decreased, it has for patients with predicted severegallstone pancreatitis (P = 0.02). Conclusion : There has been reasonable compliance with publishedguidelines and some progress in the management of gallstone pancreatitis,particularly in relation to performing timely laparoscopic cholecystectomywith a reduction in the incidence of recurrent pancreatitis. Concernsremain regarding the overuse of diagnostic ERCP in patients withmild pancreatitis.     

谷氨酰胺对腹部手术后肠通透性及细菌易位影响的临床研究

目的观察外源性谷氨酰胺（Gln）对腹部手术后病人肠道通透性的影响,继而探讨其与肠细菌易位的关系。方法将暨南大学附属第一医院2004年5月至2007年5月收治的76例腹部大中型手术病人随机分成Gln治疗组（n=38）和对照组（n=38）。两组均于术后第2d开始给予肠外营养支持,持续7d。Gln治疗组于肠外营养中加入Gln。两组分别于术前、术后检测血谷氨酰胺水平、尿乳果糖/甘露醇（L/M）比值、外周血肠源性细菌DNA。结果术后7d治疗组Gln与术前相比差异无统计学意义［(61614±4213) μmol/L vs (611354±3981)μmol/L］,P﹥005。与对照组比较Gln显著升高,差异具有统计学意义, P﹤001。术后L/M比值对照组较术前显著升高,P﹤005;治疗组与术前比较无升高,P﹥005。两组术后相比较对照组高于治疗组,差异具有统计学意义,P﹤001。外周血细菌DNA行PCR扩增后阳性率为1053%（8/76）,PCR阳性组Gln水平较PCR阴性组显著降低,P﹤005;L/M则显著增高,P﹤001。结论外源性Gln的补充可以有效的提高腹部手术后病人Gln水平,保护肠黏膜屏障功能,减少细菌易位的发生。     

Intestinal protein loss in patients with haemorrhagic fever with renal syndrome.

BACKGROUND: In haemorrhagic fever with renal syndrome (HFRS) vascular dysfunction has been observed in various organs, but the involvement of the intestine has not yet been reported. This study was performed to evaluate the association of intestinal protein loss in this disease with other clinical parameters reflecting vascular permeability or disease severity. METHODS: Twenty patients with HFRS were included in this study. Intestinal protein loss was measured by (99m)Tc-human serum albumin ((99m)Tc-HSA) scintigraphy in the acute stage, and quantitative analysis of protein loss was measured by the faecal clearance of alpha 1-antitrypsin (C(AT)) in the acute and the recovery stages. C(AT) was then compared with clinical parameters reflecting disease activity and vascular permeability. RESULTS: (99m)Tc-HSA scintigraphy was positive in 13 (65%) patients, and C(AT) in the acute stage was significantly increased as compared with C(AT) in the recovery stage (40.5+/-24.1 vs 9.2+/-4.2 ml/day, P<0.001). C(AT) was associated with serum albumin levels, frequency of hypotensive episodes, severity of acute renal failure, and degree of thrombocytopenia. CONCLUSIONS: Our data suggest that the increased vascular permeability of HFRS is associated with the increased intestinal loss of plasma proteins, which might represent one of the parameters of disease severity in HFRS.     

腹腔镜联合十二指肠镜早期治疗轻型急性胆源性胰腺炎57例报告

目的 探讨运用腹腔镜联合十二指肠镜早期治疗胆囊结石继发细径胆总管结石和轻型急性胆源性胰腺炎的手术方法及疗效.方法 分析在发病7 d内(早期手术组)同期行腹腔镜胆囊切除术(LC)联合十二指肠镜下乳头切开术(EST)40例患者资料,并与在胰腺炎治疗2周后(延期手术组)同期行LC联合EST 17例患者资料,观察两组的疗效.结果 同期行LC联合EST手术成功率早期手术组为92.5%,延期手术组为94.1%,两组差异无统计学意义(P>0.05).两组术后均无胆管残留结石、胰腺炎加重.无胃肠穿孔、胆管穿孔、胆漏、大出血等手术并发症,无死亡.但延期手术组的住院时间和住院费用明显高于早期手术组.(P<0.05).结论 只要选择合适的轻型急性胆源性急性胰腺炎病例,于发病7 d内同期行腹腔镜胆囊切除术及十二指肠镜下乳头切开术是安全、有效的.     

Serum amyloid A is a better early predictor of severity than C-reactive protein in acute pancreatitis

BACKGROUND: Serum amyloid A (SAA) is an early and sensitive marker of the extent of tissue trauma and inflammation. The aim of this study was to compare the early prognostic accuracy of SAA with that of serum C-reactive protein (CRP) in acute pancreatitis. METHODS: In a prospective multicentre trial, plasma SAA and CRP levels were measured in patients with severe and mild acute pancreatitis, and in a control group with acute abdominal pain. Plasma samples were collected on admission and at 6-h intervals for 48 h, every 12 h between 48 and 72 h, then daily for 5 days. Plasma SAA was measured by a new enzyme-linked immunosorbent assay and CRP was measured by immunoturbidometry. RESULTS: There were 137 patients with mild and 35 with severe acute pancreatitis, and 74 control patients. SAA levels were significantly higher in patients with severe acute pancreatitis than in those with mild acute pancreatitis, on admission, at 24 h or less after symptom onset, and subsequently. Whereas plasma CRP concentration was also significantly higher in patients with severe acute pancreatitis on admission, it failed to distinguish mild from severe acute pancreatitis until 30-36 h after symptom onset. SAA levels predicted severity (sensitivity 67 per cent, specificity 70 per cent, negative predictive value 89 per cent, mean(s.d.) area under curve 0.7(0.05)) significantly better than CRP (57 per cent, 60 per cent, 84 per cent, 0.59(0.06) respectively) on admission (P = 0.02) and at 24 h following symptom onset (area under curve 0.65(0.09) versus 0.58(0.09) respectively; P < or = 0.02). CONCLUSION: Plasma SAA concentration is an early marker of severity in acute pancreatitis and is superior to CRP estimation on hospital admission and at 24 h or less after symptom onset. This study suggests that plasma SAA concentration is clinically useful, with the potential to replace CRP in the management of acute pancreatitis.     

Soluble thrombomodulin plasma levels are an early indication of a lethal course in human acute pancreatitis

BACKGROUND: The potential to predict severe disease and lethality by using plasma soluble thrombomodulin (sTM) and C-reactive protein (CRP) levels in 73 patients with acute pancreatitis was analyzed in a prospective 5-year investigation performed at a single institution. METHODS: According to the Atlanta criteria, pancreatitis was classified as mild in 23 patients and as severe in 50 patients. Blood was collected on days 1, 3, 5, 7, 10, 14, 21, and 28 after the onset of pain and analyzed for sTM and CRP. RESULTS: During the period between days 3 and 10 of acute pancreatitis when most of the admissions occurred, sTM levels at a cutoff of 75 ng/mL on day 3 (sensitivity, 100%; specificity, 77%; positive predictive value, 38%; negative predictive value, 100%) and 71 ng/mL on day 10 (sensitivity, 100%; specificity, 77%; positive predictive value, 41%; negative predictive value, 100%) were predictive of a lethal outcome. With sTM levels, it was not possible to differentiate patients with mild pancreatitis from those with severe pancreatitis (Atlanta classification). In contrast, CRP levels at a cutoff of 113 mg/L on day 3 differentiated severe from mild courses with a diagnostic sensitivity of 84%, a specificity of 60%, a positive predictive value of 78%, and a negative predictive value of 69%. CRP levels at a cutoff of 122 mg/L on day 10 differentiated mild from severe courses (nonsurvivors) with a diagnostic sensitivity of 72%, a specificity of 72%, a positive predictive value of 86%, and a negative predictive value of 53%. In contrast, differentiation of mild forms of acute pancreatitis from severe pancreatitis (survivors) on day 10 was not possible. CONCLUSIONS: CRP is a valuable marker of disease severity in acute pancreatitis especially in the first period of pancreatitis, whereas sTM identifies early those patients with the most severe courses and a high risk of dying (negative predictive value, 100%). Determination of sTM in addition to CRP offers the opportunity of identifying early those patients who require intensive care most urgently. Of course, further investigations of sTM in acute pancreatitis are indicated to confirm our results.     

Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal permeability in experimental severe acute pancreatitis

BACKGROUND: Bacterial translocation plays an important role for infectious complications in severe acute pancreatitis (SAP). Breakdown of intestinal mucosal integrity may increase intestinal permeability and may be implicated in bacterial translocation. It is suggested that increase in intestinal permeability is correlated with the changes of tight junction and/or apoptosis in intestinal epithelial cells. The aim of this study was to investigate the changes of intestinal mucosa and its permeability in SAP. METHODS: SAP was induced by injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. Permeability of intestinal wall was assayed ex vivo by measuring the leaked amount of FITC-dextran from the ileum pouch. Alteration of tight junction proteins such as zonula occludens (ZO)-1 and Occludin was evaluated by Western blotting and immunofluorescence staining. Apoptotic change of intestinal mucosa was detected by TUNEL staining and DNA fragmentation ELISA. In vitro, apoptosis-inducing effect of pancreatitis-associated ascitic fluid (PAAF) was examined using T84 cells. Integrity of monolayer cells was assessed by transepithelial electric resistance (TEER). RESULTS: Permeability of ileum was significantly increased 6 h after induction of SAP. Blood endotoxin level was significantly elevated and bacterial translocation occurred 18 h after induction of SAP. Six hours after induction of SAP, expressions of ZO-1 and Occludin were not altered, but apoptosis of ileum mucosa was significantly accelerated. Addition of PAAF to T84 cells did not affect expressions of ZO-1 or Occludin, but significantly increased the apoptosis and significantly decreased TEER. CONCLUSIONS: These results suggest that breakdown of intestinal mucosa via accelerated apoptosis may increase in intestinal permeability in SAP and that PAAF contains factor(s) that accelerates the apoptosis of intestinal epithelial cells.     

HLA-DR expression in acute pancreatitis.

OBJECTIVE: To investigate the role of the monocyte/macrophage system in acute pancreatitis DESIGN: Prospective clinical study SETTING: University clinic, Germany SUBJECT: 37 consecutive patients who presented with acute pancreatitis. MAIN OUTCOME MEASURE: Correlation between function of monocytes measured by HLA-DR expression and outcome RESULTS: Patients were divided into three groups according to outcome: those with severe pancreatitis who died (n = 10), those with severe pancreatitis who survived (n = 15), and those with mild pancreatitis who survived (n = 12). There was a clear and significant difference between those with severe and those with mild disease. HLA-DR expression was initially depressed in both groups, but after the third day of treatment it started to recover significantly in those with mild disease (p < 0.05). The difference was also significant from day 7 onwards between those with severe disease who died and those with severe disease who survived (p < 0.05). CONCLUSION: Monocyte function as measured by HLA-DR expression (CD14+DR+) is reduced in patients with acute pancreatitis and does not recover in patients who are going to die (median < 20 relative antigen density units; RU).