Pancreatic Sepsis Research Articles

Nutritional and Metabolic Status Control and Nutritional Support in Patients with Pancreatic Sepsis (Review)

Acute pancreatitis (AP) is associated with pancreonecrosis in 30% of patients, who may fall at 80% high risk of death when infected pancreatic necrosis progresses to sepsis. Given the catabolic nature of the disease and the significant influence of nutritional status on its course and outcome, these patients require an adequate nutritional support (NS) based on an adequate assessment and control of nutritional and metabolic status.The aim of the study: to identify trends in developing new tools for assessment of nutritional and metabolic status, and provision of NS in patients with pancreatic sepsis (PS).Materials and methods. Keyword search in the PubMed, Scopus and E-library databases for the period from 2018 to 2023 yielded 95 publications, of which 16 meta-analyses and 6 systematic reviews met the requirements.Results. all existing to date scales for assessment of nutritional deficiency in patients with PS have low prognostic value. Of them, mNUTRIC scale seems to be the most appropriate assessment tool. Recommended by EPSEN guidelines tools to assess the risk of nutritional deficiency it is not suitable for ICU patients. Indirect calorimetry should be preferred vs routine calculation formulas in assessing patient’s energy needs in case of PS. It was also found that «standard» anthropometric values, such as BMI, are not always informative and prognostically significant in patients with severe AP in the ICU. Analgesia, infusion therapy, as well as detection and correction of intraperitoneal hypertension are not only integral components of intensive care for PS but are indispensable for supplying adequate NS in PS patients. It was found that early enteral nutrition is the preferred method of NS, although questions concerning choice of tube insertion site, as well as all parameters of tube feeding remain unanswered. The optimal composition of enteral nutrition for patients with PS has not been established, which is indirectly confirmed by the variety of enteral mixtures available on the market. The refeeding syndrome that occurs at initiation of NS was characterized as a life-threatening condition.Conclusion. NS, based on adequate assessment of disorders and control of the nutritional and metabolic status is an integral component of intensive care in PS patients. It can reduce the probability and number of potential complications, time of stay in the ICU, cost of treatment, and improve patient’s prognosis.

Acute Obstructive Suppurative Pancreatic Ductitis Secondary to Intraductal Stones

Pancreatic sepsis secondary to infected necrosis or pancreatic abscess is a well-known clinical entity. Acute obstructive suppurative pancreatic ductitis (AOSPD) in the setting of chronic calcific pancreatitis is a rare complication that is seldom reported. We report two cases of AOSPD who underwent successful pancreatic endotherapy.

Metal stents placement for refractory pancreatic duct stricture in children.

AIMTo evaluate the use of fully covered self-expandable metal stents (FCSEMSs) for pancreatic duct strictures in children with chronic pancreatitis.METHODSEight patients with refractory benign dominant stricture of the main pancreatic duct (MPD) were enrolled through chart reviews between December 2014 and June 2017 in a single center. Endoscopic retrograde cholangiopancreatography (ERCP) with placement of a 6-mm FCSEMS with dual flaps was performed. Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. All procedures were performed by a pediatric gastroenterologist. For the assessment of outcomes, technical and clinical success, adverse events, and stent patency were evaluated retrospectively.RESULTSThe placement and removal of the FCSEMSs were successful in all 8 patients. Five patients were boys and 3 were girls. The median age at initial FCSEMS placement was 12 years (range, 5-18 years). The diameters of all the inserted stents were 6 mm, and the lengths were 4-7 cm. The median indwelling time was 6 mo (range, 3-10 mo). No pancreatic sepsis, pancreatitis, cholestasis, or mortality occurred. There was no proximal and distal migration. All subjects showed a patent stent. On follow-up ERCP, the mean diameter of the stricture improved from 1.1 mm to 2.8 mm (P < 0.05), whereas that of upstream dilation improved from 8.4 mm to 6.3 mm (P < 0.05).CONCLUSIONThis initial experience showed that temporary FCSEMS placement is feasible and safe for the management of refractory benign MPD stricture in children.

Feasibility and safety of a fully covered self-expandable metal stent with antimigration properties for EUS-guided pancreatic duct drainage: early and midterm outcomes (with video)

Recently, EUS-guided pancreatic duct drainage (EUS-PD) has been used for patients in whom endoscopic retrograde pancreatography (ERP) has failed. Stent-related adverse events such as stent migrations, failures in stent placement, or pancreatic fluid leakages have been of concern in transmural plastic stenting procedures. The aim of this study is to evaluate the feasibility and safety of EUS-PD with a fully covered self-expandable metal stent (FCSEMS) for patients with obstructive pancreatitis who failed ERP. Twenty-five consecutive patients with painful obstructive pancreatitis underwent EUS-PD with a FCSEMS after failed ERP. Technical and clinical success, adverse events, and stent patency were assessed. EUS-PD was successful in all 25 patients (technical success rate, 100%), and symptoms improved in all patients (clinical success rate, 100%). EUS-guided pancreaticogastrostomy (n = 23), pancreaticoduodenostomy (n = 1), and pancreaticojejunostomy (n = 1) were performed. Pain scores improved significantly after FCSEMS placement (P = .001). Early mild grade adverse events occurred in 5 patients (20%), 4 with self-limited abdominal pain and 1 with minor bleeding. No other adverse events related to FCSEMS, including stent migration, stent clogging, pancreatic sepsis, and stent-induced ductal stricture, were observed during follow-up periods. Mean stent patency duration was 126.9 days during mean follow-up periods (221.1 days). EUS-PD with an FCSEMS may be technically feasible and relatively safe for patients who fail conventional ERP. Further randomized trials comparing EUS-PD with long-term FCSEMS and plastic stents for patients with painful obstructive pancreatitis after failed ERCP should be encouraged.

The Effect of Somatostatin, Ulinastatin and Salvia miltiorrhiza on Severe Acute Pancreatitis Treatment

BackgroundThe aim of this study was to evaluate the efficacy of somatostatin, ulinastatin and Salvia miltiorrhiza for treatment of severe acute pancreatitis. MethodsThree hundred six patients with severe acute pancreatitis were divided randomly into 5 groups: basic treatment, somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza. Amount of time for resolution of abdominal pain/distention, recovery to normal heart and respiratory rates, amylase and blood glucose levels, Acute Physiology and Chronic Health Evaluation II scores, and levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-10 were analyzed and recorded for all 5 subgroups. ResultsTumor necrosis factor-α and IL-6 levels on the fourth and seventh days, and Acute Physiology and Chronic Health Evaluation II scores on the seventh day after treatment showed significant decrease in the somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. IL-10 levels on the fourth and seventh days were significantly improved in the somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. The incidences of pancreatic sepsis, multiple organ dysfunction syndrome and mortality were lower in the somatostatin, somatostatin + ulinastatin, somatostatin + S miltiorrhiza and somatostatin + ulinastatin + S miltiorrhiza subgroups compared with the basic treatment subgroup. ConclusionsSomatostatin is effective for the treatment of acute pancreatitis and both ulinastatin and S miltiorrhiza demonstrate improvement in therapeutic benefits.

Effect of enteral nutrition and ecoimmunonutrition on bacterial translocation and cytokine production in patients with severe acute pancreatitis

BackgroundSevere acute pancreatitis (SAP) with severe complications such as multiple organ failure, necrosis, abscess, and formation of pancreatic pseudocysts often gives rise to a high mortality despite intensive treatment. Parenteral nutrition (PN), elemental enteral nutrition, and ecoimmunonutrition (EIN) hastened the recovery of SAP patients, stimulated gastrointestinal motility, and alleviated the degree of systemic inflammatory response syndrome. This study aimed to examine the effects of enteral nutrition (EN) and EIN on bacterial translocation and cytokine production in patients with SAP. MethodsOne hundred eighty-three SAP patients were randomly divided into three groups receiving PN, EN, or EN + EIN. Acute Physiology and Chronic Health Evaluation II scores, complications (systemic inflammatory response syndrome, multiorgan failure, and infections), intestinal bacterial strains of stool, and plasma concentrations of endotoxin, tumor necrosis factor α (TNF-α), and interleukin (IL) 6 and IL-10 were evaluated. ResultsThe percentage of pancreatic sepsis, multiple organ dysfunction syndrome, and mortality was significantly lower in the EN group and was further lower in the EN + EIN group than that in the PN group. The plasma concentrations of TNF-α and IL-6 and APACHE II scores were significantly decreased in the EN group and were further lowered in the EN + EIN group than those in the PN group. The plasma concentration of IL-10 was higher in the EN group and was further increased in the EN + EIN group than that in the PN group. ConclusionsEN plays effective roles in the treatment of SAP by decreasing the expression of endotoxin, TNF-α, and IL-6 and the bacterial translocation, enhancing the expression of IL-10, and the combination of EIN with EN results in more therapeutic benefits than EN alone.

Fully covered self-expanding metal stents for refractory pancreatic duct strictures in chronic pancreatitis

Fully covered self-expanding metal stents (FC-SEMSs), which can be removed from the bile duct, have recently been used in the main pancreatic duct (MPD) in chronic pancreatitis. The aim of this study was to investigate the feasibility, safety, and efficacy of FC-SEMSs in painful chronic pancreatitis with refractory pancreatic strictures. The primary endpoints were technical success and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the dominant pancreatic stricture at endoscopic retrograde pancreatography. Over 5 months, 10 patients with painful chronic pancreatitis and refractory dominant pancreatic duct strictures were treated with FC-SEMSs. All FC-SEMSs were successfully released and removed, although two stents were embedded in the MPD at their distal end and treated endoscopically without complications. Mild abdominal pain was noted in three patients after stent release. During treatment, pain relief was achieved in nine patients, but one continued to take morphine, because of addiction. Cholestasis developed in two patients and was treated endoscopically; no patient developed acute pancreatitis or pancreatic sepsis. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 3.5 mm to 5.8 mm. Patients were followed up for a mean of 19.8 months: two patients who continued drinking alcohol presented with mild acute pancreatitis; one patient developed further chronic pancreatic pain; and one had a transient pain episode. At the end of the study, nine patients no longer had chronic pain and no patients had required surgery. Endoscopic treatment of refractory MPD stricture in chronic pancreatitis by placement of an FC-SEMS appears feasible, safe, and potentially effective.

Antibiotische Therapie von Enterokokken-Infektionen in der Gastroenterologie mit Daptomycin − erste Erfahrungen aus der Registerstudie EU-CORE (European Cubicin® Outcomes Registry and Experience)

Enterococci are a frequent cause of nosocomial infections in gastroenterology. The increase of Enterococcus faecium infections with development of resistance to gentamicin and vancomycin as well as possible linezolid resistance require alternative antibiotic therapies. Study data show that daptomycin, a highly bactericidal antibiotic is effective in enterococcal infections. However, in Germany daptomycin is so far only approved for the treatment of complicated skin and soft tissue infections, bacteremia and infective endocarditis caused by Staphylococcus aureus. In the Department of Internal Medicine I, University Hospital Halle (Saale) from May 2 009 to April 2 010 all gastroenterological patients with evidence of invasive enterococcal infection received intravenous daptomycin treatment at inclusion in the European Cubicin® Outcomes Registry and Experience (EU-CORE). Gastroenterological diseases treated were necrotising pancreatitis, infected pancreatic pseudocysts, abscesses, obstructive cholangitis and sepsis. The clinical outcome was retrospectively detected by protocol-defined criteria. A total of 13 patients (8 male, 5 female, median age 59 years) with microbiologically assured enterococcal infections (10 × E. faecium, including 1 × VRE, 6 × E. faecalis, including double infections) were treated with intravenous daptomycin (6 mg per kg body weight). In the presence of polymicrobial infections (10 of 13 patients), an additional anti-infective therapy was initiated according to sensitivity testing. Concomitantly a direct focus approach with stenting, puncture or drainage was performed. The clinical cure rate was 92 % (12 of 13 patients). One patient died from a non-surgically uncontrollable malignancy (Klatskin tumour Bismuth IIIb). There were no adverse events. These results allow us to conclude that antibiotic therapy with daptomycin in invasive or bacteraemic enterococcal infections leads to high cure rates (up to 90 % and more) when concomitant and adequate focus relief is performed. Larger clinical studies to obtain an extended drug approval are desirable.

Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration

Fully covered self-expandable metal stent (FCSEMS) placement has recently been tried in the management of refractory pancreatic-duct strictures associated with advanced chronic pancreatitis. The major limitation of FCSEMSs was frequent migration. To assess the safety, migration rate, and removability of modified FCSEMSs with antimigration features used for the treatment of benign pancreatic-duct strictures. Prospective study. Tertiary academic center. Thirty-two patients with chronic painful pancreatitis and dominant ductal stricture. Transpapillary endoscopic placement of FCSEMSs in the pancreatic duct with removal after 3 months. Technical and functional success and adverse events associated with the placement of metal stents. FCSEMSs were successfully placed in all patients through the major (n = 27) or minor (n = 5) duodenal papilla. All patients achieved pain relief from stent placement. There was no occurrence of stent-induced pancreatitis or pancreatic sepsis. No stent migrated, and all stents were easily removed. Follow-up ERCP 3 months after stent placement showed resolution of duct strictures in all patients. Pancreatograms obtained at FCSEMS removal displayed de novo focal pancreatic duct strictures in 5 patients, but all were asymptomatic. No long-term follow-up. Temporary 3-month placement of FCSEMSs was effective in resolving pancreatic-duct strictures in chronic pancreatitis, with an acceptable morbidity profile. Modified FCSEMSs can prevent stent migration, but may be associated with de novo duct strictures. Further trials are needed to assess long-term safety and efficacy.

ENDOSCOPIC TREATMENT OF MULTIPLE PANCREATIC ABSCESSES CASE REPORT AND REVIEW OF THE LITERATURE

Pancreatic abscesses are treated surgically and the role of endotherapy is still to be established. We describe the case of successful endoscopic management of two pancreatic abscesses in a critically ill patient. A patient was admitted to the hospital for severe acute pancreatitis. One month later the patient developed pancreatic sepsis. CT scan showed two large abscesses. The first was bulging to the posterior wall of the stomach and another at the tail of the pancreas. Parenteral antibiotic therapy was administered. The clinical status of the patient rapidly deteriorated and the patient was unfit for surgical intervention. The endoscopic retrograde cholangiopancreatography was performed. The pancreatic duct communicated with the abscess at the tail of the pancreas. The drainage of this abscess was done transpapillarily. Endoscopic cystogastrostomy was performed to treat the pancreatic abscess that bulged to the posterior gastric wall. A double nasocystic tube was placed for continuous lavage of the abscess. Pseudomonas aeruginosa was cultured and antibiotics were administered according to sensitivity tests. The clinical status returned gradually to normal. A follow-up CT scan 4 months later showed complete resolution of abscesses. The drainage of the abscesses was done by the means of endoscopic cystogastrostomy and transpapillary stent insertion. This was a minimally invasive intervention, by which we avoided surgical intervention that bears significant mortality and morbidity. Endoscopic drainge of pancreatic abscesses may be the therapy of choice in such patients mainly because it does not prevent the chance of subsequent surgical intervention if needed.

Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video)

Painful chronic pancreatitis with main pancreatic ductal strictures is usually managed with endotherapy with a plastic stent. To date, the role of placement of metallic stents, especially uncovered ones in benign pancreatic ductal stricture, has been unsatisfactory as a result of stent dysfunction related to mucosal hyperplasia. We explored the feasibility and safety of temporary placement of a newly designed, fully covered self-expandable metal stent (FCSEMS) in painful chronic pancreatitis and refractory benign pancreatic ductal strictures. A prospective pilot and feasibility study. A tertiary academic center. Thirteen patients with chronic painful pancreatitis of alcoholic (8) or idiopathic (5) etiology. ERCP with temporary FCSEMS placement (2 months). Endoscopic removal of FCSEMSs was performed with a snare or rat-tooth forceps. End points were feasibility, safety, and morbidity. Successful FCSEMS placement was performed in all enrolled patients. After immediate placement of FCSEMS, 2 patients had mild acute pancreatitis related mainly to the stricture dilation procedure (Soehendra stent retriever or balloon dilation). Complications associated with stent placement included 5 migrations (39%, 1 proximal and 4 distal) and 2 incidents of cholestatic liver dysfunction associated with the compression of the bile duct orifice by expansion of FCSEMSs. In 1 patient with proximal migration, the stent was repositioned by an inflated retrieval balloon. Additional endoscopic biliary sphincterotomy with or without biliary stenting was performed in 2 patients with cholestatic liver dysfunction. There was no occurrence of pancreatic sepsis among any patients. FCSEMSs were removed from 9 of 9 patients without stent migration (100% [9/9] as per protocol, and 69% [9/13] as intention to treat, respectively). Improvement or resolution of the pancreatic ductal strictures was confirmed in all 13 patients on follow-up ERCP (2 months after stent placement), regardless of stent migration. Small patient populations without long-term follow-up. Two-month placement of FCSEMSs in patients with refractory benign pancreatic ductal strictures may be feasible and relatively safe. However, stent migration was not uncommon. A further investigation with ideal stent design may therefore be needed before recommending FCSEMSs as a therapeutic option for refractory benign pancreatic ductal strictures.

OUTCOME OF OPEN NECROSECTOMY IN THE ERA OF MINIMALLY INVASIVE PANCREATIC SURGERY

Introduction: Minimally invasive approaches to debridement of pancreatic sepsis are increasingly reported but their adoption is as yet unsupported by randomized trial evidence. This report provides data on contemporary outcome of pancreatic necrosis managed by a protocol of fine-needle-aspiration (FNA) guided management and open necrosectomy. Methods: 124 patients with clinically severe acute pancreatitis were admitted to critical care over the period January 2000 to January 2006. Of these, 26 patients who underwent open necrosectomy constitute the dataset. The median (range) age was 50 (20-77) years. Aetiology was biliary in 13 and alcohol in 13. The median logistic organ dysfunction score-predicted mortality on admission was 4.8% which increased to 7.1% immediately prior to surgery. All patients received antibiotics and 19 (73%) had antifungal treatment. FNA was undertaken prior to surgery in 19 (73%) with positive results in 14. Results: Surgery was via midline in 16 and transverse in 10. No patients had additional mobilisation of colonic flexure, t-tube drainage of common bile duct or decompressing gastrostomy. Synchronous cholecystectomy was undertaken in 11 (48%). All patients had abdominal drains. Lesser sac irrigation was not employed. In-hospital stay was 84 (28-193) days and there were 5 (19%) deaths. Discussion: Open necrosectomy has evolved and is now a lesser procedure targeted at draining the focus of infection and blunt debridement. Acceptable outcomes in critically ill patients suggest that this is the standard to which minimally invasive operations should be compared.

Acute Pancreatitis Presenting as Sudden, Unexpected Death

Acute pancreatitis represents a spectrum of disease, ranging from a mild, transitory illness to a severe, rapidly progressive hemorrhagic form, with massive necrosis and mortality rates of up to 24%. The reported incidence of acute pancreatitis diagnosed first at clinicopathologic autopsy ranges between 30% and 42%. To better describe outpatient fatalities due to acute pancreatitis that present as sudden, unexpected death, we retrospectively reviewed the autopsy files at the Institute of Legal Medicine, University of Hamburg, Germany, from 2000-2004. Individual cases were analyzed for sex, age, race, circumstances of death, social background of the deceased and previous medical history, seasonal occurrence of the disease, blood alcohol concentration at the time of death, body mass index, autopsy findings, histopathology, and etiology of acute pancreatitis. Among the 6178 autopsies carried out during the 5-year period evaluated, there were 27 cases of acute pancreatitis that presented as sudden, unexpected death. In all cases, the diagnosis was first made at autopsy. The male:female ratio was 1.7:1 and the mean age was 52 years (range, 30-91 years). Etiologies of acute pancreatitis included alcohol (n=19), gall stones (n=2), other identified etiologic factors (n=3), and idiopathic (n=3). Complications of acute pancreatitis included lung edema and/or acute respiratory distress syndrome, peritonitis, disseminated intravascular coagulation, and sepsis. At least 20 subjects (74%) had lived isolated, with no social contacts. Contrary to the clinical observations of a clear seasonal variation in the onset of acute pancreatitis, we found no correlation between death due to acute pancreatitis and a specific month or season. Many prior studies have suggested that the majority of deaths in severe acute pancreatitis occur in the late phase of the disease as a result of pancreatic sepsis. Conversely, in the present study, the majority of affected individuals died during the very early phase of the disease. While gallstones represent the main etiologic factor in most larger clinical series, biliary etiology seems to play only a minor role in outpatient deaths undergoing medicolegal autopsies. Data derived from medicolegal autopsy studies should be included in future population-based studies of acute pancreatitis.

Endoscopic pancreatic-stent placement and sphincterotomy for relief of pain in tropical pancreatitis: results of a 1-year follow-up

Tropical chronic pancreatitis frequently presents with intractable abdominal pain. Surgical treatment has its own morbidity and mortality, and long-term results may not be satisfactory. To analyze the results of endoscopic pancreatic-stent placement and sphincterotomy for the pain of tropical pancreatitis. Retrospective review. Tertiary-referral hospital. Twenty-four patients with tropical pancreatitis with severe, persistent pain not responding to standard medical therapy over a period of 30 months beginning January 1998. Stent placement of the pancreatic duct, along with sphincterotomy. At least 80% global improvement in pain as reported by the patient during follow-up after the procedure. In the 19 evaluable patients, the intended procedure, pancreatic stent placement along with sphincterotomy, was successful in 14 (73.7%); 3 others had sphincterotomy alone. Over a follow-up period of 6 to 38 months, 12 of the 14 patients (85.7%) who underwent stent placement plus sphincterotomy and 2 of the 3 patients who had sphincterotomy alone responded. Twelve of these were completely free of pain, and the remaining 2 patients had mild infrequent pain that occurred once in 2 to 4 months, lasting a few hours at a time and never needing hospitalization. The only major complication was the development of pancreatic sepsis, which required stent removal in 1 patient. Eight patients were stent free at the end of 6 months, and, over a further follow-up of 6 to 20 months, the pattern of pain relief persisted in them. The retrospective nature of the study, the limited numbers studied, and the lack of assessment of pain on a standard visual analog scale. Stent placement of the pancreatic duct with pancreatic sphincterotomy constitutes an important nonsurgical therapeutic option for the intractable pain of tropical pancreatitis.

Review: Antibiotic prophylaxis of pancreatic necrosis in acute pancreatitis reduces mortality and sepsis

Source Citation Villatoro E, Larvin M, Bassi C. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2004;(2):CD002941. 145...

Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.

Acute pancreatitis is a common acute abdominal emergency which lacks specific therapy. In severe attacks, areas of the pancreas may become necrotic. The mortality risk rises to >40% if sterile necrosis becomes superinfected, usually with gut derived aerobic organisms. Experimental and clinical studies indicate a window of opportunity of 1-2 weeks, when superinfection, and thus high-risk surgical debridement, may be prevented by administering systemic antibiotics to 'sterilise' tissues adjacent to necrotic areas. There are theoretical risks of encouraging antibacterial resistance and opportunistic fungal infections. To determine the effectiveness and safety of prophylactic antibiotic therapy in patients with severe acute pancreatitis who have developed pancreatic necrosis. MEDLINE, EMBASE, and the Cochrane Library were searched. We also examined other sources including Conference Abstracts (published and unpublished data). Randomised controlled trials (RCT) were sought using the search strategy detailed below. No linguistic limitations were applied. RCTs were selected in which antibacterial therapy was evaluated in patients with severe acute pancreatitis associated with pancreatic necrosis proven by intravenous contrast-enhanced computed tomography (CT). No linguistic limitations were applied. Searching was undertaken initially in November 2001 and updated in March 2003. Two reviewers extracted data from trial publications independently, concerning rates for the primary end-points: with respect to: all cause mortality and rates of infection of pancreatic necrosis (proven by microbiological examination of fine needle aspirate or operative specimens). In addition, secondary end-points included peri-pancreatic sepsis, remote sepsis (respiratory, urinary, central venous line sources), operative rates, length of hospital stay, adverse events including the incidence of drug resistant microorganisms and opportunistic fungal infection. It was possible to evaluate mortality in all four included studies, and it demonstrated a survival advantage for antibiotic therapy (Odds ratio 0.32, p=0.02). Pancreatic sepsis (infected necrosis) was also measurable in all four studies and showed an advantage for therapy (Odds ratio 0.51, p=0.04). Extra-pancreatic infection could be evaluated in three studies, but showed no significant advantage for therapy (Odds ratio 0.47, p=0.05).Operative treatment data was available in three studies, but surgery rates were not significantly reduced (Odds ratio 0.55, p=0.08). Fungal infections showed no strongly increased preponderance with therapy (Odds ratio 0.83, p=0.7), but there were no data on infection with resistant organisms. Length of hospital stay could only be evaluated in two studies and was not significantly different. Sub-group analyses planned for the influence on outcome measures of the antibiotic regimen, the time of commencement of therapy in relation to symptom onset and/or hospitalisation, duration of therapy, and aetiology could not be performed as no data were available. Despite variations in drug agent, case mix, duration of treatment and methodological quality (especially the lack of double blinded studies), there was strong evidence that intravenous antibiotic prophylactic therapy for 10 to 14 days decreased the risk of superinfection of necrotic tissue and mortality in patients with severe acute pancreatitis with proven pancreatic necrosis at CT. Further studies are required to confirm all of the benefits suggested (in particular the need for operative debridement), to provide more adequate data on adverse effects, to address the choice of antibacterial agents and effects of varying duration of therapy, and whether outcome is related to aetiology.

Do Pancreatic Duct Stents Cause or Prevent Pancreatic Sepsis?

Background Pancreatic sepsis can occur after contrast injection into an obstructed or disrupted pancreatic duct. Whether stents cause or prevent pancreatic sepsis is unknown. Accordingly, the pancreatic duct bacteriology in patients with pancreatic duct stents was retrospectively reviewed and contrasted with biliary cultures taken from patients at the time of bile duct stent retrieval and/or exchange. Methods Of 61 patients (29 men, 32 women; 72 stents; mean age 51 [16] years, range 14–88 years), 36 with pancreatic duct stents had pancreatic duct cultures obtained at the time of stent exchange and/or retrieval. The results of these cultures were compared with bile duct cultures taken from 36 patients at the time of biliary stent exchange/retrieval. Eleven of the 36 patients with pancreatic duct stents also had bile duct stents. Data collected included stent patency, clinical sepsis at initial stent placement or retrieval, administration of antibiotics before the procedure, indication for stent placement, stent duration, and culture results. Results At stent retrieval and/or exchange, all 61 patients with pancreatic and/or biliary stents had contamination of the respective ducts with multiple enteric bacteria (mean 3.4 organisms in patients with pancreatic duct stents vs. 3.3 in those with bile duct stents). Clostridium perfringens was found in 17% and 0% of patients with, respectively, bile duct and pancreatic duct stents. Among the most common indications for pancreatic duct stent placement were stricture (28), sphincterotomy (9), leak (7), stones (3), and dilated pancreatic duct (1). Indications for a biliary stent included benign stricture (29), malignancy (6), stones (2), cholangitis (1), chronic pancreatitis (1), and dilated common bile duct (1). Pancreatic cultures were taken at a median of 85 days (interquartile range 60–126; range 13–273) and biliary cultures at a median of 87 days (interquartile range 45–149; range 19–927) after stent placement. Eleven patients, 6 with a bile duct stent, 4 with a pancreatic duct stent, and one with dual stents, developed pre-exchange/retrieval clinical sepsis; 3 had pancreatic sepsis. All had received antibiotics at initial placement. In the 11 patients with sepsis (12 stents), 8 stents were completely occluded at exchange/retrieval, 3 were partially occluded, and one was patent. In 50 patients (60 stents), no clinical sepsis developed; 7 stents were patent, 31 partially occluded, and 22 completely obstructed. Conclusions (1) Comparable to patients with biliary stents, all patients with pancreatic stents had contamination of the pancreatic ductal system by enteric flora. (2) In contrast to the 17% of patients with bile duct stents who had intraductal Clostridium perfringens, there were no instances ofcontamination with this organism in patients with pancreatic stent ( p = 0.025), although, after adjusting for multiple comparisons, statistical significance was lost. (3) There was a tendency for stent occlusion to predispose to pancreatic sepsis, but occlusion by itself was insufficient ( p = 0.106). (4) Further investigation is required to define the additional variables that are associated with the development of pancreatic sepsis.

Clinical outcomes in patients who undergo extracorporeal shock wave lithotripsy for chronic calcific pancreatitis

Background: There is controversy as to whether extracorporeal shock wave lithotripsy fragmentation and ERCP retrieval of pancreatic stones are associated with relief of chronic pain or relapsing attacks of pancreatitis. Our most recent experience with this technology is reviewed. Methods: Forty patients with chronic calcific pancreatitis who required extracorporeal shock wave lithotripsy between 1995 and 2000 to facilitate pancreatic duct stone removal were retrospectively reviewed. Data collected included patient presentation, number of lithotripsy and ERCP sessions required, complications, and outcomes measures to include pre- and post-ESWL pain scale, monthly oxycodone (5 mg)-equivalent pills ingested, yearly hospitalizations, and need for subsequent surgery. Results: A single extracorporeal shock wave lithotripsy session was required for 35 patients who underwent a total of 86 ERCPs to achieve complete stone extraction from the main pancreatic duct. Minor complications occurred in 20%. There was one episode of pancreatic sepsis that was treated with antibiotics and removal of an occluded pancreatic prosthesis. At a mean [SD] follow-up of 2.4 (0.6) years, 80% of patients had avoided surgery and there was a statistically significant decrease in pain scores (6.9 [1.3] vs. 2.9 [1.1]; p = 0.001), yearly hospitalizations for pancreatitis (3.9 [1.9] vs. 0.9 [0.9]; p = 0.001), and oxycodone-equivalent narcotic medication ingested monthly (125 [83] vs. 81 [80]; p = 0.03). Conclusions: Extracorporeal shock wave lithotripsy fragmentation of pancreatic duct calculi in conjunction with endoscopic clearance of the main pancreatic duct is associated with significant improvement in clinical outcomes in most patients with chronic pancreatitis. (Gastrointest Endosc 2002;56:496-500.)

Pancreatic sepsis: prevention and therapy

Except for a minority of early fatalities most deaths in acute pancreatitis occur after the first 7 to 10 days due to infective complications, particularly infected necrosis. Hence, preventing this risk factor seems to represent a major step forward in the clinical management of severe pancreatitis. Consequently, antibiotics emerged as a cornerstone of the treatment of severe acute pancreatitis. The duration of such treatment, the route of administration and the substance(s) of choice need to be carefully selected. Surgical debridement is the treatment of choice of infected necrosis, while percutaneous drainage is successful in some patients.

3799 Pancreatic sepsis as a late complication of endoscopic pancreatic duct stone removal.

INTRODUCTION: Multiple authors have reported success in removing pancreatic duct stones using endoscopic techniques. To date, there has been little recognition of late pancreatic sepsis (PS) following such treatments. PATIENTS & METHODS: From April 1991 to July 1999, 70 patients underwent endoscopically directed efforts to remove pancreatic duct stones at our center. TREATMENTS: 43 males, 27 females, age 3 to 90 (median 62) were treated with pull type pancreatic sphincterotomy,then variably with mechanical lithotripsy, electro-hydraulic intraductal lithotripsy, ESWL, PD stents, and fragment extraction using balloons or baskets. RESULTS: In follow-up there were 7 episodes of PS in 6 patients from 1 month to 20 months following initial intervention. In 4 of the 6 cases, complete stone clearance was felt to have been accomplished.In 2, partial removal or stenting led to resolution of symptoms. All 6 patients presented with upper abdominal pain and fever. All 6 were found to have recurrent PD stone obstruction. In 3 cases, these appeared to be sidebranch stones, as the patients had multiple calcifications at the completion of previous endoscopic RX. In the remaining cleared patient, the recurrent stone was of unclear source suggesting an incorrect assumption of clearance or new stone formation. In 3 episodes, ERCP documented purulent pancreatic ductal discharge above the impacted stone without leakage or pseudocyst formation. In 3, infected pseudocysts were documented by percutaneous drainage in 1 and surgery in 2. The final episode was prompt recurrence of sepsis 1 month after an episode of sepsis treated with ERCP and recurrent stone extraction. 1 patient developed a septic fistula at the tip of a PD stent, which was placed around an incompletely fragmented stone. This resolved with a longer stent at repeat ERCP. 2 patients have undergone elective surgery after clearance of their PS with repeat stent placement at ERCP. CONCLUSIONS: Late pancreatic sepsis following pancreatic sphincterotomy for pancreatic duct stone clearance has been little recognized. Bacterial colonization of the duct following pancreatic sphincterotomy likely predisposes to significant pancreatic sepsis following reobstruction. This late complication needs better documentation, particularly in patients with incomplete stone clearance. These patients may well require more definitive surgical drainage on an elective basis. INTRODUCTION: Multiple authors have reported success in removing pancreatic duct stones using endoscopic techniques. To date, there has been little recognition of late pancreatic sepsis (PS) following such treatments. PATIENTS & METHODS: From April 1991 to July 1999, 70 patients underwent endoscopically directed efforts to remove pancreatic duct stones at our center. TREATMENTS: 43 males, 27 females, age 3 to 90 (median 62) were treated with pull type pancreatic sphincterotomy,then variably with mechanical lithotripsy, electro-hydraulic intraductal lithotripsy, ESWL, PD stents, and fragment extraction using balloons or baskets. RESULTS: In follow-up there were 7 episodes of PS in 6 patients from 1 month to 20 months following initial intervention. In 4 of the 6 cases, complete stone clearance was felt to have been accomplished.In 2, partial removal or stenting led to resolution of symptoms. All 6 patients presented with upper abdominal pain and fever. All 6 were found to have recurrent PD stone obstruction. In 3 cases, these appeared to be sidebranch stones, as the patients had multiple calcifications at the completion of previous endoscopic RX. In the remaining cleared patient, the recurrent stone was of unclear source suggesting an incorrect assumption of clearance or new stone formation. In 3 episodes, ERCP documented purulent pancreatic ductal discharge above the impacted stone without leakage or pseudocyst formation. In 3, infected pseudocysts were documented by percutaneous drainage in 1 and surgery in 2. The final episode was prompt recurrence of sepsis 1 month after an episode of sepsis treated with ERCP and recurrent stone extraction. 1 patient developed a septic fistula at the tip of a PD stent, which was placed around an incompletely fragmented stone. This resolved with a longer stent at repeat ERCP. 2 patients have undergone elective surgery after clearance of their PS with repeat stent placement at ERCP. CONCLUSIONS: Late pancreatic sepsis following pancreatic sphincterotomy for pancreatic duct stone clearance has been little recognized. Bacterial colonization of the duct following pancreatic sphincterotomy likely predisposes to significant pancreatic sepsis following reobstruction. This late complication needs better documentation, particularly in patients with incomplete stone clearance. These patients may well require more definitive surgical drainage on an elective basis.