Advances in classification, prognostication and treatment of immunocholangitis

Immullocholangitis is a collective for chronic inflammatory disorders affecting the biliary tree, presumably with an autoimmune-mediated pathogenesis. Destruction and distortion of bile ducts, leading to impaired bile flmv, are key features of immunocholangitis. In general, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are considered to be the main diseases of immunochoiangitis. PBC, a chronic cholestatic liver disease, is one of the most common vanishing bile duct disorders. Gradual loss of interlobular and septal bile ducts, histologically described as chronic non-suppurative destructive cholangitis, leads to chronic cholestasis, fibrosis and biliary cirrhosis which may ultimately cause liver failure, necessitating transplantation. Since 1988, PBC has been the third leading indication for liver transp

Alteration of postantibiotic effect during one dosing interval of tobramycin, simulated in an in vitro pharmacokinetic model

The kinetics of the postantibiotic effect (PAE) during one dosing interval of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was investigated. We determined the PAE at different time points during this dosing interval of 12 h in an in vitro pharmacokinetic model simulating human pharmacokinetics in which the half-life of tobramycin was adjusted to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h, corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the MIC for the test organism. The PAE decreased significantly from 2.5 h at 1 h to 0 h at 12 h. No change in MIC was observed for the strains during the experiments. We conclude that the PAE decreases with decreasing tobramycin concentrations during a 12-h dosing interval and completely disappears after the concentration has reached the MIC for the test organism. On the basis of these observations, the emphasis that is placed on the PAE in discussions about the optimal dosing interval in aminoglycoside therapy is questionable

Isolation and relative stereochemistry of lippialactone, a new antimalarial compound from Lippia javanica

The aerial parts of Lippia javanica were investigated for biologically active chemical compounds present in them. Chromatographic separation of the ethyl acetate extract of the aerial parts yielded a new antimalarial α-pyrone, lippialactone (2). Lippialactone is active against the chloroquinesensitive D10 strain of Plasmodium falciparum with an IC50 value of 9.1 μg/mL, and is also mildly cytotoxic. The relative stereochemistry of lippialactone was determined by molecular modeling based on the determination of the relative configuration by quantum mechanical GIAO 13C chemical shift calculations.National Research Foundation.http://www.elsevier.com/locate/fitotehb201

Clinical outcomes of biliary drainage of malignant biliary obstruction due to colorectal cancer metastases : a systematic review

Background and aims: Malignant biliary obstruction is an ominous complication of metastatic colorectal cancer (mCRC). Biliary drainage is frequently performed to relieve symptoms of jaundice or enable palliative systemic therapy, but effective drainage can be difficult to accomplish. The aim of this study is to summarize literature on clinical outcomes of biliary drainage in mCRC patients with malignant biliary obstruction.& nbsp; Methods: We searched Medline and EMBASE for studies that included patients with malignant biliary obstruction secondary to mCRC, treated with endoscopic and/or percutaneous biliary drainage. We summarized available data on technical success, clinical success, adverse events, systemic therapy administration and survival after biliary drainage.& nbsp; Results: After screening 3584 references and assessing 509 full-text articles, seven cohort studies were included. In these studies, rates of technical success, clinical success and adverse events varied between 63%-94%, 42%81%, and 19%-39%, respectively. Subsequent chemotherapy was administered in 17%-56% of patients. Overall survival varied between 40 and 122 days across studies (278-365 days in patients who received subsequent chemotherapy, 42-61 days in patients who did not).& nbsp; Conclusions: Successful biliary drainage in mCRC patients can be challenging to achieve and is frequently associated with adverse events. Overall survival after biliary drainage is limited, but is significantly longer in patients treated with subsequent systemic therapy. Expected benefits of biliary drainage should be carefully weighed against its risks

Bacterial cholangitis causing secondary sclerosing cholangitis: A case report

BACKGROUND: Although bacterial cholangitis is frequently mentioned as a cause of secondary sclerosing cholangitis, it appears to be extremely rare, with only one documented case ever reported. CASE PRESENTATION: A 48-year-old woman presented with an episode of acute biliary pancreatitis that was complicated by pancreatic abcess formation. After 3 months she had an episode of severe pyogenic (E. Coli) cholangitis that recurred over the subsequent 7 months on a further two occasions. Initially, cholangiography suggested the presence of extra-biliary intrahepatic abcesses while repeated investigations demonstrated development of multiple segmental biliary duct strictures. After maintenance antibiotic treatment was started, no episodes of cholangitis occurred over a 14-month period. CONCLUSIONS: Sclerosing cholangitis can rapidly develop after an episode of bacterial cholangitis. Extra-biliary involvement of the hepatic parenchyma with abcess formation may be a risk factor for developing this rare but particularly severe complication

Successful Treatment of Primary Sclerosing Cholangitis with a Steroid and a Probiotic

Primary sclerosing cholangitis (PSC) is a serious disease that not only affects quality of life but can also have a significant effect on patient survival. The treatment for PSC is primarily supportive with the aim of controlling cholestatic symptoms and preventing complications. Ursodeoxycholic acid may induce biochemical improvements in affected patients; however, long-term pediatric studies to determine its possible benefits in young patients are lacking. Thus, the treatment of pediatric PSC remains a significant clinical challenge. We describe a patient with PSC and undetermined colitis who was treated with a combination of a steroid, salazosulfapyridine, and a probiotic. This treatment provided benefits both for PSC and the undetermined colitis. These findings suggest that bacterial flora and gut inflammation are closely associated with the pathogenesis of inflammatory bowel disease-related PSC. Suppression of bowel inflammation and maintenance of bacterial homeostasis may be important for treating PSC

Patency of endoscopic ultrasound-guided gastroenterostomy in the treatment of malignant gastric outlet obstruction

Background and study aims Endoscopic ultrasoundguided gastroenterostomy (EUS-GE) with a lumen-apposing metal stent (LAMS) is a novel, minimally invasive technique in the palliative treatment of malignant gastric outlet obstruction (GOO). Several studies have demonstrated feasibility and safety of EUS-GE, but evidence on long-term durability is limited. The aim of this study was to evaluate patency of EUS-GE in treatment of malignant GOO. Patients and Methods An international multicenter study was performed in seven centers in four European countries. Patients who underwent EUS-GE with a LAMS between March 2015 and March 2019 for palliative treatment of symptomatic malignant GOO were included retrospectively. Our main outcome was recurrent obstruction due to LAMS dysfunction; other outcomes of interest were technical success, clinical success, adverse events (AEs), and survival. Results A total of 45 patients (mean age 69.9 ± 12.3 years and 48.9% male) were included. Median duration of followup was 59 days (interquartile range [IQR] 41–128). Recurrent obstruction occurred in two patients (6.1 %), after 33 and 283 days of follow-up. Technical success was achieved in 39 patients (86.7 %). Clinical success was achieved in 33 patients (73.3 %). AEs occurred in 12 patients (26.7 %), of which five were fatal. Median overall survival was 57 days (IQR 32–114). Conclusions EUS-GE showed a low rate of recurrent obstruction. The relatively high number of fatal AEs underscores the importance of careful implementation of EUSGE in clinical practice

Performance of EUS-FNA for mediastinal lymphadenopathy: impact on patient management and costs in low-volume EUS centers

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mediastinal lymphadenopathy has been shown to be a valuable diagnostic tool in high-volume EUS centers (≥ 50 mediastinal EUS-FNA/endoscopist/year). Our goal was to assess the diagnostic accuracy of EUS-FNA and its impact on clinical management and costs in low-volume EUS centers ( <50 mediastinal EUS-FNA/endoscopist/year). METHODS: Consecutive patients referred to two Dutch endoscopy centers in the period 2002-2008 for EUS-FNA of mediastinal lymphadenopathy were reviewed. The gold standard for a cytological diagnosis was histological confirmation or clinical follow-up of more than 6 months with repeat imaging. The impact of EUS-FNA on clinical management was subdivided into a positive impact by providing (1) adequate cytology that influenced the decision to perform surgery or (2) a diagnosis of a benign inflammatory disorder, and a negative impact which was subdivided into (1) false-negative or inconclusive cytology or (2) an adequate cytological diagnosis that did not influence patient management. Costs of an alternative diagnostic work-up without EUS-FNA, as established by an expert panel, were compared to costs of the actual work-up. RESULTS: In total, 213 patients (71% male, median age= 61 years, range = 23-88 years) underwent EUS-FNA. Sensitivity, specificity, and negative and positive predictive values were 89%, 100%, 80%, and 100%, respectively. EUS-FNA had a positive impact on clinical management in 84% of cases by either influencing the decision to perform surgery (49%) or excluding malignant lymphadenopathy (35%), and a negative impact in 7% of cases because of inadequate (3%) or false-negative (4%) cytology. In 9% of cases, EUS-FNA was performed without an established indication. Two nonfatal perforations occurred (0.9%). Total cost reduction was €100,593, with a mean cost reduction of €472 (SD = €607) per patient. CONCLUSIONS: Mediastinal EUS-FNA can be performed in low-volume EUS centers without compromising diagnostic accuracy. Moreover, EUS-FNA plays an important role in the management of patients with mediastinal lymphadenopathy and reduces total diagnostic cost