Early precut sphincterotomy and the risk of endoscopic retrograde cholangiopancreatography related complications: An updated meta-analysis

AIM: To study the cannulation and complication rates of early pre-cut sphincterotomy vs persistent attempts at cannulation by standard approach.METHODS: Systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies published up to February 2013. The main outcome measurements were cannulation rates and postendoscopic retrograde cholangiopancreatography(ERCP) complications. A comprehensive systematic search of the Cochrane library, PubMed, Google scholar, Scopus, National Institutes of Health, meta-register of controlled trials and published proceedings from major Gastroenterology journals and meetings until February 2013 was conducted using keywords. All Prospective randomized controlled trials(RCT) studies whichmet our inclusion criteria were included in the analysis. Prospective non-randomized studies and retrospective studies were excluded from our meta-analysis. The main outcomes of interest were post-ERCP pancreatitis, overall complication rates including cholangitis, ERCPrelated bleeding, perforation and cannulation success rates. RESULTS: Seven RCTs with a total of 1039 patients were included in the meta-analysis based on selection criteria. The overall cannulation rate was 90% in the pre-cut sphincterotomy vs 86.3% in the persistent attempts group(OR = 1.98; 95%CI: 0.70-5.65). The risk of post-ERCP pancreatitis(PEP) was not different between the two groups(3.9% in the pre-cut sphincterotomy vs 6.1% in the persistent attempts group, OR = 0.58, 95%CI: 0.32-1.05). Similarly, there was no statistically significant difference between the groups for overall complication rate including PEP, cholangitis, bleeding, and perforation(6.2% vs 6.9%, OR = 0.85, 95%CI: 0.51-1.41). CONCLUSION: This meta-analysis suggests that precut sphincterotomy and persistent attempts at cannulation are comparable in terms of overall complication rates. Early pre-cut implementation does not increase PEP complications.     

Factors predicting adverse short-term outcomes inpatients with acute cholangitis undergoing ERCP: Asingle center experience简

AIM: To identify potential factors that can predict adverse short-term outcomes in patients with acute cholangitis undergoing endoscopic retrograde cholangiopancreatography (ERCP).METHODS: Retrospective analysis of consecutive patients admitted to our center for acute cholangitis and underwent ERCP from 2001 to 2012. Involvement of two or more organ systems was termed as organ failure (OF). Cardiovascular failure was defined based on a systolic blood pressure of < 90 mmHg despite fluid replacement and/or requiring vasopressor treatment; respiratory failure if the Pa0₂/Fi0₂ ratio was < 300 mmHg and/or required mechanical ventilation; coagulopathy if the platelet count was < 80; and renal insufficiency if serum creatinine was > 1.9 mg/dL. Variables associated with short term adverse clinical outcomes defined as persistent OF and/or 30-d mortality was determined.RESULTS: A total of 172 patients (median age 62 years, 56.4% female) were included. The median door to ERCP time was 17 h. Bile duct stones were the most common etiology (n = 67, 39.2%). In multivariate analysis, factors that were independently associated with persistent OF and/or 30-d mortality included American Society of Anesthesiology (ASA) physical classification score > 3 (OR = 7.70; 95%CI: 2.73-24.40), presence of systemic inflammatory response syndrome (OR = 3.67; 95%CI: 1.34-10.3) and door to ERCP time greater than 72 h (OR = 3.36; 95%CI: 1.12-10.20). Door to ERCP time greater than 72 h was also associated with 70% increase in the mean length of stay (P < 0.001). Every one point increase in the ASA physical classification and every 1 mg/dL increase in the pre-ERCP bilirubin level was associated with a 34% and 2% increase in the mean length of hospital stay, respectively. Transfer status did not impact clinical outcomes.CONCLUSION: Higher ASA physical classification and delays in ERCP are associated with adverse clinical outcomes and prolonged length of hospital stay in patients with acute cholangitis undergoing ERCP.     

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte- integrated IL2R for the ligand and thus could suppress host antitumor immunity.     

Reinduction therapy in 297 children with acute lymphoblastic leukemia in first bone marrow relapse: a Pediatric Oncology Group Study

Many children with acute lymphoblastic leukemia (ALL) develop a marrow relapse during or shortly following initial continuation chemotherapy. Achievement of a second complete remission is the initial step in a successful retreatment effort. Reinduction results using two or three drugs have been unsatisfactory, and previous reports of four-drug reinduction programs have included relatively small numbers of patients. Pediatric Oncology Group protocol 8303 was designed for patients with ALL in first marrow relapse during or within 6 months after cessation of chemotherapy. The results of reinduction therapy in 297 study patients are described here. Four-drug reinduction therapy consisted of daily oral prednisone, weekly vincristine and daunorubicin, and asparaginase three times weekly for 4 weeks (PVDA). CNS retreatment consisted of two doses of triple intrathecal chemotherapy. Of the 297 patients receiving reinduction, 245, or 82%, entered second complete remission, six died of infection or progressive disease, and 46 others still had M2 or M3 bone marrow status. Forty of these latter patients received four doses (during a 2-week period) of teniposide and cytarabine, after which 13 (32%) achieved complete remission status. Thus, the overall second complete remission rate with PVDA with or without teniposide/cytarabine was 258 of 297, or 87%. The treatment program was generally well tolerated. Among the numerous factors analyzed by using logistic regression, only female sex (P = .035), the presence of blasts on the blood smear at the time of relapse (P = .0002), and a length of initial complete remission less than 12 months (P = .021) were independent predictors of failure to enter second remission. We conclude that the intensive reinduction program described here is a highly effective first step in the delivery of salvage therapy to patients with ALL in first marrow relapse. The current challenge is to develop improved continuation treatment for these children.     

Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event- free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.     

Systematic review and stratified meta-analysis of the efficacy of carnosine in animal models of ischemic stroke

Carnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies. We included publications describing in vivo models of ischemic stroke where the neuroprotective efficacy of carnosine was being evaluated through the reporting of infarct volume and/or neurological score as outcomes. Overall efficacy was evaluated using weighted mean difference random effects meta-analysis. We also evaluated for study quality and publication bias. We identified eight publications that met our inclusion criteria describing a total of 29 comparisons and 454 animals. Overall methodological quality of studies was moderate (median = 4/9). Carnosine reduced infarct volume by 29.4% (95% confidence interval (CI), 24.0% to 34.9%; 29 comparisons). A clear dose-response effect was observed, and efficacy was reduced when carnosine was administered more than 6 h after ischemia. Our findings suggest that carnosine administered before or after the onset of ischemia exhibits robust efficacy in experimental ischemic stroke. However, the methodological quality of some of the studies was low and testing occurred only in healthy young male animals.     

Chloramphenicol-induced bone marrow injury: possible role of bacterial metabolites of chloramphenicol

To explore the potential role of some bacterial metabolites of chloramphenicol (CAP) in CAP-induced hematotoxicity, we examined their cytotoxic effects on bone marrow cells in vitro using a number of cytotoxicity parameters. Among the metabolites tested, dehydro-CAP (DHCAP) and p-nitrophenyl-2-amino-3 hydroxypropanone-HCI (NPAP) were more toxic than CAP. DHCAP was at least as toxic as nitroso-CAP. At concentrations of less than or equal to 10(-4) mol/L, DHCAP caused total irreversible inhibition of myeloid colony (CFU-GM) growth and 80% inhibition of DNA synthesis in human bone marrow. Incubation of human bone marrow cells with 10(-4) mol/L nitroso-CAP or DHCAP for 24 hours resulted in 75% and 65% cell death respectively. Although DHCAP was 10- to 20-fold more cytotoxic than CAP, it was only one third as effective in inhibiting mitochondrial protein synthesis, indicating that DHCAP exerts its toxic effect by alternate mechanisms. The cytotoxicity of DHCAP and its relative stability, compared to the unstable nitroso CAP, suggest that this bacterial metabolite of CAP, and possibly others, may play a significant role in CAP-induced hematotoxicity.     

Persistence of circulating blasts after 1 week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia

Early response to therapy, typically assessed by bone marrow status, is predictive of outcome in childhood acute lymphoblastic leukemia (ALL). Less is known about the significance of early clearance of blast cells in peripheral blood. We reviewed medical records of all patients with ALL enrolled on St Jude Total Therapy Study XI (February 1984 to September 1988) to determine the presence of blast cells in peripheral blood at diagnosis and after 1 week of intensive induction therapy. Of the 358 patients, 59 lacked evidence of circulating blast cells at diagnosis, and data were unavailable for 2 patients. The prognostic significance of persistent circulating blast cells in the remaining 297 patients was assessed in a multivariate analysis that included known adverse prognostic factors. Persistent circulating leukemic blasts were present at day 8 in 41 patients (14%). Compared with the "blast- negative" group, these patients had a significantly higher frequency of several adverse clinical features (leukocyte count > 50 x 10(9)/L, mediastinal mass, central nervous system leukemia, T-cell phenotype, lack of CD10 expression, and L2 morphology) and a significantly poorer 5-year event-free survival (34% +/- 8% [SE] v 77% +/- 3%, P < .01). By multivariate analysis, blast cell persistence at week 1 was the most significant adverse feature in the overall cohort (relative risk, 2.9; 95% confidence interval, 1.8 to 4.8) and in an analysis limited to B- lineage cases (relative risk, 3.6; 95% confidence interval, 1.9 to 7.1). Patients identified by this simple, noninvasive measure may benefit from early modification of therapy.