Can bile duct injuries be prevented? "A new technique in laparoscopic cholecystectomy"

BACKGROUND: Over the last decade, laparoscopic cholecystectomy has gained worldwide acceptance and considered to be as "gold standard" in the surgical management of symptomatic cholecystolithiasis. However, the incidence of bile duct injury in laparoscopic cholecystectomy is still two times greater compared to classic open surgery. The development of bile duct injury may result in biliary cirrhosis and increase in mortality rates. The mostly blamed causitive factor is the misidentification of the anatomy, especially by a surgeon who is at the beginning of his learning curve. Biliary tree injuries may be decreased by direct coloration of the cystic duct, ductus choledochus and even the gall bladder. METHODS: gall bladder fundus was punctured by Veress needle and all the bile was aspirated. The same amount of fifty percent methylene blue diluted by saline solution was injected into the gall bladder for coloration of biliary tree. The dissection of Calot triangle was much more safely performed after obtention of coloration of the gall bladder, cystic duct and choledocus. RESULTS: Between October 2003 and December 2004, overall 46 patients (of which 9 males) with a mean age of 47 (between 24 and 74) underwent laparoscopic cholecystectomy with methylene blue injection technique. The diagnosis of chronic cholecystitis (the thickness of the gall bladder wall was normal) confirmed by pre-operative abdominal ultrasonography in all patients. The diameters of the stones were greater than 1 centimeter in 32 patients and calcula of various sizes being smaller than 1 cm. were documented in 13 cases. One patient was operated for gall bladder polyp (our first case). Successful coloration of the gall bladder, cystic duct and ductus choledochus was possible in 43 patients, whereas only the gall bladder and proximal cystic duct were visualised in 3 cases. In these cases, ductus choledochus visibility was not possible. None of the patients developed bile duct injury. CONCLUSION: The number of bile duct injuries related to anatomic misidentification can be decreased and even vanished by using intraoperative methylene blue injection technique into the gall bladder fundus intraoperatively

Serum microrna biomarkers for detection of non-small cell lung cancer

Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73-0.91), sensitivity of 100% (95% CI; 0.93-1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results. © 2012 Hennessey et al

Hormone withdrawal-associated symptoms with ethinylestradiol 20 µg/drospirenone 3 mg (24/4 regimen) versus ethinylestradiol 20 µg/desogestrel 150 µg (21/7 regimen)

Johannes Bitzer,1 Maria Jesusa Banal-Silao,2 Hans-Joachim Ahrendt,3 Jaime Restrepo,4 Marion Hardtke,5 Ulrike Wissinger-Graefenhahn,6 Dietmar Trummer7 1Department of Obstetrics and Gynecology, University Hospital of Basel, Basel, Switzerland; 2University of the Philippines College of Medicine, Manila, Philippines; 3Praxis für Frauenheilkunde, Klinische Forschung und Weiterbildung (Clinical Research and Further Education), Magdeburg, Germany; 4Centro de Investigación Clínica, Clinica Medellin Poblado, Medellin, Colombia; 5Global Clinical Development Operations, Bayer Pharma AG, Berlin, Germany; 6Global Medical Affairs Women’s Healthcare, Bayer Pharma AG, Berlin, Germany; 7Clinical Statistics Europe, Bayer Pharma AG, Berlin, Germany Objective: To assess whether the combined oral contraceptive (COC) ethinylestradiol (EE) 20 µg/drospirenone 3 mg taken in a 24/4-day regimen (ie, 4-day hormone-free interval) is more effective than an EE 20 µg/desogestrel (DSG) 150 µg COC taken in a 21/7-day regimen (ie, 7-day hormone-free interval) in reducing hormone withdrawal-associated symptoms (HWAS).Methods: This double-blind, randomized study (NLM identifier: NCT01076582) was conducted at 34 centers in 12 countries. Otherwise healthy women who experienced ≥2 HWAS of headache, pelvic pain, and/or bloating when using their current COCs in a 21/7-day regimen were recruited. Subjects rated the severity of their HWAS daily on a seven-point Likert scale during a baseline cycle and during four 28-day cycles with EE/drospirenone 24/4 (n=290) or EE/DSG 21/7 (n=304). The primary variable was the mean change from baseline to cycle 4 in the composite HWAS score (sum of scores for all three symptoms) during cycle days 22–28.Results: In the EE/drospirenone 24/4 group, the mean (standard deviation) composite HWAS score during cycle days 22–28 was reduced from 42.2 (24.8) at baseline to 12.8 (13.4) at cycle 4 (change from baseline: -30.3 [22.9]). In the EE/DSG 21/7 group, the corresponding value was reduced from 41.9 (25.8) to 14.3 (13.2) (change from baseline: -27.7 [24.8]), not significantly different versus EE/drospirenone 24/4. Bleeding pattern, treatment response, rescue medication use, compliance, quality of life, and tolerability were similar between treatments.Conclusion: Both EE/drospirenone 24/4 and EE/DSG 21/7 reduced the composite HWAS score from baseline to cycle 4 in otherwise healthy women. The differences between treatments were too small to be statistically significant.Keywords: combined oral contraceptives, ethinylestradiol, drospirenone, desogestrel, hormone withdrawa

Development of a UC781 releasing polyethylene vinyl acetate vaginal ring

UC781 is potent, hydrophobic, non-nucleotide reverse transcriptase inhibitor (NNRTI) against the human immunodeficiency virus (HIV). UC781 is currently being investigated for use as a potential HIV microbicide. A study in rhesus macaques demonstrated that a 100-mg UC781-loaded silicone elastomer vaginal ring released limited amounts of UC781 into the vaginal fluid and tissue after 28 days. The reason for this was due to the hydrophobic nature and limited aqueous solubility of UC781. This study describes the manufacture of UC781-loaded polyethylene vinyl acetate (PEVA) vaginal rings, which have an improved in vitro release rate of UC781 when compared to UC781-loaded silicone elastomer vaginal rings. The study demonstrates that the UC781 in the PEVA rings is mostly in its amorphous form due to the rings being manufactured above UC781’s melting point. Furthermore, the rings do not show any signs of UC781 degradation, such as the presence of UC22