Leena Kylänpää

Outcome of patients after endoluminal stent placement for benign colorectal obstruction

Abstract Objective. Self-expanding metal stents (SEMS) have been successfully used as a “bridge to surgery” or as palliation for acute malignant colorectal obstruction. Little data on the use of stents for benign obstruction exists and the results vary. The purpose of this study was to evaluate the efficacy and safety of SEMS in benign colorectal obstruction. Material and methods. A total of 21 patients with 23 SEMS procedures between the years 1998 and 2008 were retrospectively studied. Eight patients had an obstruction in the surgical anastomosis. In addition, there were two patients with anastomotic strictures due to Crohns disease. In 10 patients the obstruction was caused by diverticular disease and one patient had a stricture after radiation therapy. Results. Technical success was achieved for all the patients. Clinical success was achieved for 76% (16/21) of the patients. The anastomotic strictures were resolved with SEMS in 5 out of 8 cases (63%). Three patients with diverticular stricture (30%) were eventually resolved with SEMS. Nine (43%) patients in 10 out of 23 procedures (43%) had a complication, the majority being in patients with diverticular stricture. Conclusions. SEMS is a good treatment option for patients with anastomotic stricture of the colon and for patients with benign colonic stricture who are unfit for surgery. SEMS can be used as a bridge to surgery in diverticular obstruction but there seems to be a considerable risk of complications. If a SEMS is placed into a diverticular stricture, the planned bowel resection should be performed within a month.

The Clinical Course of Acute Pancreatitis and the Inflammatory Mediators That Drive It

Acute pancreatitis (AP) is a common emergency condition. In the majority of cases, it presents in a mild and self-limited form. However, about 20% of patients develop severe disease with local pancreatic complications (including necrosis, abscess, or pseudocysts), systemic organ dysfunction, or both. A modern classification of AP severity has recently been proposed based on the factors that are causally associated with severity of AP. These factors are both local (peripancreatic necrosis) and systemic (organ failure). In AP, inflammation is initiated by intracellular activation of pancreatic proenzymes and/or nuclear factor-κB. Activated leukocytes infiltrate into and around the pancreas and play a central role in determining AP severity. Inflammatory reaction is first local, but may amplify leading to systemic overwhelming production of inflammatory mediators and early organ failure. Concomitantly, anti-inflammatory cytokines and specific cytokine inhibitors are produced. This anti-inflammatory reaction may overcompensate and inhibit the immune response, rendering the host at risk for systemic infection. Currently, there is no specific treatment for AP. However, there are several early supportive treatments and interventions which are beneficial. Also, increasing the understanding of the pathogenesis of systemic inflammation and the development of organ dysfunction may provide us with future treatment modalities.

Circulating cytokines in predicting development of severe acute pancreatitis

IntroductionSevere acute pancreatitis (AP) is associated with high morbidity and mortality. Early prediction of severe AP is needed to improve patient outcomes. The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease.MethodsWe performed a prospective study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according to the revised Atlanta criteria. Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels. Admission plasma levels of C-reactive protein (CRP), creatinine and calcium were measured for comparison. In subgroup analyses, we assessed the cytokine profiles of patients with severe AP (n = 14) who did not have organ dysfunction (OD) upon admission (modified Marshall score <2).ResultsOf 14 cytokines elevated in the severe AP group, interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent prognostic markers of severe AP. IL-6, HGF and a combination of them predicted severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive values of CRP, creatinine and calcium were comparable to those of the cytokines. In subgroup analyses of patients with severe AP and without OD upon admission, we found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels predicted the development of severe AP, with G-CSF being the most accurate cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.ConclusionsIL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and HGF, as either single or combined markers, were not perfect in identifying patients at risk for severe AP, the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies.

Risk factors for complications of ERCP in primary sclerosing cholangitis

BACKGROUND AND STUDY AIMS Endoscopic retrograde cholangiographic pancreatography (ERCP) is the most accurate technique for surveillance of patients with primary sclerosing cholangitis (PSC). Our aim was to evaluate risk factors for complications of ERCP in patients with PSC. PATIENTS AND METHODS In 2007 - 2009 we performed 441 ERCPs in patients with PSC. The primary tools for ERCP were a guide wire and papillotomy knife to gain access into the biliary duct. If the primary cannulation failed, and the wire went only into the pancreatic duct, pancreatic sphincterotomy was performed. If necessary, a further oblique cut with a needle knife was done in order to expose the biliary duct. RESULTS Primary cannulation was successful in 389 patients (88.2 %). Of these, 147 (37.8 %) had had biliary sphincterotomy performed previously. In the group with failed primary cannulation, access into the biliary duct was achieved after pancreatic sphincterotomy in 52 patients. In 11 of these, a further cut with a needle knife was performed. Post-ERCP pancreatitis (PEP) was diagnosed in 31 patients (7.0 %). Factors predicting PEP were female sex (odds ratio [OR] 2.6, P = 0.015) and a guide wire in the pancreatic duct (OR 8.2, P < 0.01). Previous biliary sphincterotomy was a protective factor (OR 0.28, P = 0.02). The risk of PEP increased with the number of times the wire accidentally passed into the pancreatic duct (P < 0.001). Cholangitis developed in 6 patients (1.4 %). CONCLUSIONS In patients with PSC the incidence of ERCP complications remained relatively low. The complication risk increased with the complexity of cannulation. In a patient with PSC in whom follow-up ERCP is planned, biliary sphincterotomy should be considered, as it may protect against PEP.

Patient-controlled sedation with propofol and remifentanil for ERCP: a randomized, controlled study

BACKGROUND Deep sedation with propofol and an opioid is commonly used for ERCP but is associated with increased risk and may require the presence of an anesthesiologist. Delivery of propofol and a short-acting, potent opioid analgesic remifentanil by patients to themselves (patient-controlled sedation, PCS) could be another option. Comparative studies with propofol PCS for ERCP are lacking. OBJECTIVE To compare PCS with propofol/remifentanil to anesthesiologist-managed propofol sedation. DESIGN Prospective, randomized, controlled human trial. SETTING University hospital. PATIENTS This study involved 80 patients presenting for elective ERCP. INTERVENTION Patients were randomized to PCS with propofol/remifentanil (PCS group) or anesthesiologist-managed propofol sedation (propofol infusion group). Sedation level was estimated every 5 minutes throughout the procedure by using Ramsay and Gillham sedation scores. The total amount of propofol was calculated at the end of the procedure. Endoscopist and patient satisfaction with the procedures was evaluated with a structured questionnaire. MAIN OUTCOME MEASUREMENTS Patient vital signs, amount of consumed propofol, sedation levels, and degree of endoscopist and patient satisfaction. RESULTS PCS was successful with 38 of 40 (95%) ERCP patients. In the PCS group, the mean (±standard deviation) level of sedation was markedly lighter and propofol consumption significantly smaller (175±98 mg) than in the propofol infusion group (249±138 mg) (P<.01). Degrees of patient and endoscopist satisfaction were equally high in both groups. All of the patients preferred the same sedation method should a repeat ERCP be required. LIMITATIONS Single-center study. CONCLUSION PCS with propofol/remifentanil is a suitable and well-accepted sedation method for ERCP. Anesthesiologist-managed propofol sedation with constant propofol infusion is associated with unnecessary deep sedation without any impact on the degree of patient or endoscopist satisfaction. Further larger-scale studies are needed to assess the safety of PCS in ERCP patients. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01079312.).

Randomized multicenter study of multiple plastic stents vs. covered self-expandable metallic stent in the treatment of biliary stricture in chronic pancreatitis

BACKGROUND AND STUDY AIMS The use of covered self-expandable metallic stents (cSEMS) in benign biliary indications is evolving. The aim of the study was to assess the safety and feasibility of cSEMS compared with multiple plastic stents in the treatment of benign biliary stricture (BBS) caused by chronic pancreatitis. PATIENTS AND METHODS This was a prospective, multicenter, randomized study of 60 patients with BBS caused by chronic pancreatitis. All patients received an initial plastic stent before randomization. At randomization, the stent was replaced either with a single cSEMS or three plastic stents. After 3 months, the position of the cSEMS was checked or another three plastic stents were added. At 6 months after randomization, all stents were removed. Clinical follow-up including abdominal ultrasound and laboratory tests were performed at 6 months and 2 years after stent removal. RESULTS Two patients dropped out of the cSEMS group before stent removal. In April 2014, the median follow-up was 40 months (range 1 - 66 months). The 2-year, stricture-free success rate was 90 % (95 % confidence interval [CI] 72 % - 97 %) in the plastic stent group and 92 % (95 %CI 70 % - 98 %) in the cSEMS group (P = 0.405). There was one late recurrence in the plastic stent group 50 months after stent removal. Stent migration occurred three times (10 %) in the plastic stent group and twice in the cSEMS group (7 %; P = 1.000). CONCLUSION A 6-month treatment with either six 10-Fr plastic stents or with one 10-mm cSEMS produced good long-term relief of biliary stricture caused by chronic pancreatitis.Study registered at ClinicalTrials.gov (NCT01085747).

Management of difficult bile duct cannulation in ERCP

In Encoscopic Retrograde Cholangiopancreatography (ERCP), the main concern is to gain access into the bile duct while avoiding the pancreatic duct because of the risk of post-ERCP pancreatitis. Difficult cannulation is defined as a situation where the endoscopist, using his/her regularly used cannulation technique, fails within a certain time limit or after a certain number of unsuccessful attempts. Different methods have been developed to manage difficult cannulation. The most common solution is to perform a precut papillotomy either with a needle knife or with a sphincterotome with or without a guide wire. This review describes different methods to overcome cases of difficult cannulation. We will discuss the success rate and complication rates associated with different methods of reaching the biliary tract.

Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis

IntroductionDisturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF.Patients and methodsThirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC.ResultsDuring the initial two weeks of hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13 (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r = 0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC pathway was associated with systemic inflammation-triggered immune suppression.ConclusionPC deficiency and decreased APC generation in severe AP probably contributed to a compromised anticoagulant and anti-inflammatory defence. The PC pathway defects were associated with the development of MOF. The data support feasibility of testing the use of APC or PC to improve the clinical outcome in AP.

Patient-controlled sedation for ERCP: a randomized double-blind comparison of alfentanil and remifentanil.

BACKGROUND AND STUDY AIMS Self-administration of a propofol and opioid mixture by patients (patient-controlled sedation, PCS) could offer a practical alternative for individual sedation during endoscopic retrograde cholangiopancreatography (ERCP). However, what would be the most suitable sedative mixture for PCS is unknown. The aim of this study was to compare remifentanil and alfentanil in the PCS during ERCP. PATIENTS AND METHODS Eighty-one patients undergoing elective ERCP received PCS with propofol and opioid in three different regimens. The concentrations of opioids in the sedative mixture were 0.02 mg/mL in the remifentanil group (R) and 0.04 mg/mL and 0.08 mg/mL in the alfentanil 1 (A1) and alfentanil 2 (A2) groups, respectively. The infusion pump was adjusted to deliver a 1 mL single dose with zero lockout time. We considered PCS as successful if no procedure interruption due to sedation-related complications occurred or if additional propofol was not needed. The consumption of propofol was registered, and sedation levels and vital signs were monitored. Endoscopist and patient satisfaction with sedation were assessed using structured questionnaires. RESULTS The consumption (SD) of propofol was 177 (105)mg in group R, 197 (88) mg in group A1 and 162 (70)mg in group A2. PCS was successful in 74 /81 (91 %) of sedations, without differences between the groups in terms of propofol consumption, sedation success rate, sedation levels, vital signs, postprocedural pain, and endoscopist and patient satisfaction. Respiratory depression and nausea were observed more frequently with remifentanil than with alfentanil (P < 0.05). CONCLUSIONS PCS is an acceptable method of sedation for ERCP. The combination of propofol and alfentanil should be recommended because a remifentanil - propofol mixture depresses spontaneous respiration more and produces nausea more frequently.

A randomized comparison of target-controlled propofol infusion and patient-controlled sedation during ERCP

BACKGROUND AND STUDY AIMS Propofol is widely used during endoscopic retrograde cholangiopancreatography (ERCP) but high doses are recognized as a risk factor for sedation-related complications. The aim of this study was to compare target-controlled infusion (TCI) with patient self-administration (patient-controlled sedation, PCS) of propofol during ERCP. Propofol consumption, the ease of ERCP performance, and speed of recovery were recorded. PATIENTS AND METHODS A total of 82 patients undergoing elective ERCP were randomized 1:1 to receive propofol 10 mg/mL using TCI (initial targeted effect-site concentration 2 μg/mL) or PCS (single bolus 1 mL, lockout time set at zero). Alfentanil was administered if signs of insufficient analgesia occurred. Consumption of propofol and alfentanil was recorded, sedation levels and vital signs were monitored, the ease of ERCP performance, speed of recovery, and satisfaction with sedation were evaluated. RESULTS All procedures were performed without interruptions or major sedation-related complications. The mean (± SD) consumption of propofol was 306 ± 124 mg in the TCI group and 224 ± 101 mg in the PCS group (P = 0.002). Patients in the PCS group recovered faster (P = 0.035). The mean (± SD) consumption of alfentanil was 0.5 ± 0.4 mg in both groups. The combination of propofol and alfentanil was associated with an increased risk of sedation-related adverse events (P = 0.031). CONCLUSIONS No benefits of TCI over PCS could be demonstrated in this study. We recommend considering PCS as a feasible option for propofol administration during ERCP because of its ease of use, high success rate, reduced consumption of propofol, and faster recovery.