Management of gallstone disease in children: a new protocol based on the experience of a single center

Background/purpose: Gallstones and cholelithiasis are being increasingly diagnosed in children owing to the widespread use of ultrasonography. The treatment of choice is cholecystectomy, and routine intraoperative cholangiography is recommended to explore the common bile duct. The objectives of this study were to describe our experience with the management of gallstone disease in childhood over the last 18 years and to propose an algorithm to guide the approach to cholelithiasis in children based on clinical and ultrasonographic findings. Methods: The data for this study were obtained by reviewing the records of all patients with gallstone disease treated between January 1994 and October 2011. The patients were divided into the following 5 groups based on their symptoms: group 1, asymptomatic; group 2, nonbiliary obstructive symptoms; group 3, acute cholecystitis symptoms; group 4, a history of biliary obstructive symptoms that were completely resolved by the time of surgery; and group 5, ongoing biliary obstructive symptoms. Patients were treated according to an algorithm based on their clinical, ultrasonographic, and endoscopic retrograde cholangiopancreatography (ERCP) findings. Results: A total of 223 patients were diagnosed with cholelithiasis, and comorbidities were present in 177 patients (79.3%). The most common comorbidities were hemolytic disorders in 139 patients (62.3%) and previous bariatric surgery in 16 (7.1%). Although symptoms were present in 134 patients (60.0%), cholecystectomy was performed for all patients with cholelithiasis, even if they were asymptomatic; the surgery was laparoscopic in 204 patients and open in 19. Fifty-six patients (25.1%) presented with complications as the first sign of cholelithiasis (eg, pancreatitis, choledocolithiasis, or acute calculous cholecystitis). Intraoperative cholangiography was indicated in 15 children, and it was positive in only 1 (0.4%) for whom ERCP was necessary to extract the stone after a laparoscopic cholecystectomy (LC). Preoperative ERCP was performed in 11 patients to extract the stones, and a hepaticojejunostomy was indicated in 2 patients. There were no injuries to the hepatic artery or common bile duct in our series. Conclusions: Based on our experience, we can propose an algorithm to guide the approach to cholelithiasis in the pediatric population. The final conclusion is that LC results in limited postoperative complications in children with gallstones. When a diagnosis of choledocolithiasis or dilation of the choledocus is made, ERCP is necessary if obstructive symptoms persist either before or after an LC. Intraoperative cholangiography and laparoscopic common bile duct exploration are not mandatory. Published by Elsevier Inc.

Common bile duct stones: analysis of the videolaparoscopic surgical treatment

CONTEXT: About 9% of the Brazilian population has gallstones and the incidence increases significantly with aging. The choledocholithiasis is found around 15% of these patients, and a third to half of these cases presented as asymptomatic. Once the lithiasis in the common bile duct is characterized through intraoperative cholangiography, the laparoscopic surgical exploration can be done through the transcystic way or directly through choledochotomy. OBJECTIVE: To evaluate the results and outcomes of the laparoscopic treatment of common bile duct lithiasis. METHODS: Seventy consecutive patients were evaluated. They prospectively underwent the treatment of the lithiasis in the common bile duct and the exploration ways were compared according to the following parameters: criteria on their indication, success in the clearance, surgical complications. It was verified that about ½ of the choledocholithiasis carriers did not show any expression of predictive factors (clinical antecedents of jaundice and/or acute pancreatitis, compatible sonographic data and the pertaining lab tests). The laparoscopic exploration through the transcystic way is favored when there are no criteria for the practice of primary choledochotomy, which are: lithiasis in the proximal bile duct, large (over 8 mm) or numerous calculi (multiple calculosis). RESULTS: The transcystic way was employed in about 50% of the casuistic and the choledochotomy in about 30%. A high success rate (around 80%) was achieved in the clearance of the common bile duct stones through laparoscopic exploration. The transcystic way, performed without fluoroscopy or choledochoscopy, attained a low rate of success (around 45%), being 10% of those by transpapilar pushing of calculi less than 3 mm. The exploration through choledochotomy, either primary or secondary, if the latter was performed after the transcystic route failure, showed high success rate (around 95%). When the indication to choledochotomy was primary, the necessity for choledochoscopy through choledochotomy to help in the removal of the calculi was 55%. However, when choledochotomy was performed secondarily, in situations where the common bile duct diameter was larger than 6 mm, the use of choledochoscopy with the same purpose involved about 20% of the cases. There was no mortality in this series. CONCLUSION: The laparoscopic exploration of the common bile duct was related to a low rate of morbidity. Therefore, the use of laparoscopy for the treatment of the lithiasis in the common bile duct depends on the criteria for the choice of the best access, making it a safe procedure with very good results.

Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations

Background/Purpose: The mechanisms of increased collagen production and liver parenchyma fibrosis are poorly understood. These phenomena are observed mainly in children with biliary obstruction (BO), and in a great number of patients, the evolution to biliary cirrhosis and hepatic failure leads to the need for liver transplantation before adolescence. However, pediatric liver transplantation presents with biliary complications in 20% to 30% of cases in the postoperative period. Intra-or extrahepatic stenosis of bile ducts is frequent and may lead to secondary biliary cirrhosis and the need for retransplantation. It is unknown whether biliary stenosis involving isolated segments or lobes may affect the adjacent nonobstructed lobes by paracrine or endocrine means, leading to fibrosis in this parenchyma. Therefore, the present study aimed to create an experimental model of selective biliary duct ligation in young animals with a subsequent evaluation of the histologic and molecular alterations in liver parenchyma of the obstructed and nonobstructed lobes. Methods: After a pilot study to standardize the surgical procedures, weaning rats underwent ligation of the bile ducts of the median, left lateral, and caudate liver lobes. The bile duct of the right lateral lobe was kept intact. To avoid intrahepatic biliary duct collaterals neoformation, the parenchymal connection between the right lateral and median lobes was clamped. The animals were divided into groups according to the time of death: 1, 2, 3, 4, and 8 weeks after surgical procedure. After death, the median and left lateral lobes (with BO) and the right lateral lobe (without BO [NBO]) were harvested separately. A group of 8 healthy nonoperated on animals served as controls. Liver tissues were subjected to histologic evaluation and quantification of the ductular proliferation and of the portal fibrosis. The expressions of smooth muscle alpha-actin (alpha-SMA), desmin, and transforming growth factor beta 1 genes were studied by molecular analyses (semiquantitative reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction, a quantitative method). Results: Histologic analyses revealed the occurrence of ductular proliferation and collagen formation in the portal spaces of both BO and NBO lobes. These phenomena were observed later in NBO than BO. Bile duct density significantly increased 1 week after duct ligation; it decreased after 2 and 3 weeks and then increased again after 4 and 8 weeks in both BO and NBO lobes. The portal space collagen area increased after 2 weeks in both BO and NBO lobes. After 3 weeks, collagen deposition in BO was even higher, and in NBO, the collagen area started decreasing after 2 weeks. Molecular analyses revealed increased expression of the alpha-SMA gene in both BO and NBO lobes. The semiquantitative and quantitative methods showed concordant results. Conclusions: The ligation of a duct responsible for biliary drainage of the liver lobe promoted alterations in the parenchyma and in the adjacent nonobstructed parenchyma by paracrine and/or endocrine means. This was supported by histologic findings and increased expression of alpha-SMA, a protein related to hepatic fibrogenesis. (C) 2012 Elsevier Inc. All rights reserved.

Analysis of anti-Mullerian hormone (AMH) and its receptor (AMHR2) genes in patients with persistent Mullerian duct syndrome

Objective: To screen for mutations in AMH and AMHR2 genes in patients with persistent Mullerian duct syndrome (PMDS). Patients and method: Genomic DNA of eight patients with PMDS was obtained from peripheral blood leukocytes. Directed sequencing of the coding regions and the exon-intron boundaries of AMH and AMHR2 were performed. Results: The AMH mutations p.Arg95*, p.Arg123Trp, c.556-2A>G, and p. Arg502Leu were identified in five patients; and p.Gly323Ser and p.Arg407* in AMHR2 of two individuals. In silico analyses of the novel c.556-2A>G, p.Arg502Leu and p.Arg407* mutations predicted that they were harmful and were possible causes of the disease. Conclusion: A likely molecular etiology was found in the eight evaluated patients with PMDS. Four mutations in AMH and two in AMHR2 were identified. Three of them are novel mutations, c.556-2A>G, and p. Arg502Leu in AMH; and p.Gly323Ser in AMHR2. Arq Bras Endocrinol Metab. 2012;56(8):473-8

Exploration time of static images implying different body movements causes time distortions

Studies of subjective time have adopted different methods to understand different processes of time perception. Four sculptures, with implied movement ranked as 1.5-, 3.0-, 4.5-, and 6.0-point stimuli on the Body Movement Ranking Scale, were randomly presented to 42 university students untrained in visual arts and ballet. Participants were allowed to observe the images for any length of time (exploration time) and, immediately after each image was observed, recorded the duration as they perceived it. The results of temporal ratio (exploration time/time estimation) showed that exploration time of images also affected perception of time, i.e., the subjective time for sculptures representing implied movement were overestimated.\

Effect of a propeller duct on AUV maneuverability

A number of autonomous underwater vehicles, AUV, are equipped with commercial ducted propellers, most of them produced originally for the remote operated vehicle, ROV, industry. However, AUVs and ROVs are supposed to work quite differently since the ROV operates in almost the bollard pull condition, while the AUV works at larger cruising speeds. Moreover, they can have an influence in the maneuverability of AUV due to the lift the duct generates in the most distant place of the vehicle's center of mass. In this work, it is proposed the modeling of the hydrodynamic forces and moment on a duct propeller according to a numerical (CFD) simulation, and analytical and semi-empirical, ASE, approaches. Predicted values are compared to experimental results produced in a towing tank. Results confirm the advantages of the symbiosis between CFD and ASE methods for modeling the influence of the propeller duct in the AUV maneuverability. (C) 2012 Elsevier Ltd. All rights reserved.

Exploration of the parameter space in an agent-based model of tuberculosis spread: emergence of drug resistance in developing vs developed countries

In this work we present an agent-based model for the spread of tuberculosis where the individuals can be infected with either drug-susceptible or drug-resistant strains and can also receive a treatment. The dynamics of the model and the role of each one of the parameters are explained. The whole set of parameters is explored to check their importance in the numerical simulation results. The model captures the beneficial impact of the adequate treatment on the prevalence of tuberculosis. Nevertheless, depending on the treatment parameters range, it also captures the emergence of drug resistance. Drug resistance emergence is particularly likely to occur for parameter values corresponding to less efficacious treatment, as usually found in developing countries.

Exploration of the Antiplatelet Activity Profile of Betulinic Acid on Human Platelets

Betulinic acid, a natural pentacyclic triterpene acid, presents a diverse mode of biological actions including antiretroviral, antibacterial, antimalarial, and anti-inflammatory activities. The potency of betulinic acid as an inhibitor of human platelet activation was evaluated, and its antiplatelet profile against in vitro platelet aggregation, induced by several platelet agonists (adenosine diphosphate, thrombin receptor activator peptide-14, and arachidonic acid), was explored. Flow cytometric analysis was performed to examine the effect of betulinic acid on P-selectin membrane expression and PAC-1 binding to activated platelets. Betulinic acid potently inhibits platelet aggregation and also reduced PAC-1 binding and the membrane expression of P-selectin. Principal component analysis was used to screen, on the chemical property space, for potential common pharmacophores of betulinic acid with approved antithrombotic drugs. A common pharmacophore was defined between the NMR-derived structure of betulinic acid and prostacyclin agonists (PGI2), and the importance of its carboxylate group in its antiplatelet activity was determined. The present results indicate that betulinic acid has potential use as an antithrombotic compound and suggest that the mechanism underlying the antiplatelet effects of betulinic acid is similar to that of the PGI2 receptor agonists, a hypothesis that deserves further investigation.

Analog circuit synthesis performing fast Pareto frontier exploration and analysis through 3D graphs

This paper presents a technique for performing analog design synthesis at circuit level providing feedback to the designer through the exploration of the Pareto frontier. A modified simulated annealing which is able to perform crossover with past anchor points when a local minimum is found which is used as the optimization algorithm on the initial synthesis procedure. After all specifications are met, the algorithm searches for the extreme points of the Pareto frontier in order to obtain a non-exhaustive exploration of the Pareto front. Finally, multi-objective particle swarm optimization is used to spread the results and to find a more accurate frontier. Piecewise linear functions are used as single-objective cost functions to produce a smooth and equal convergence of all measurements to the desired specifications during the composition of the aggregate objective function. To verify the presented technique two circuits were designed, which are: a Miller amplifier with 96 dB Voltage gain, 15.48 MHz unity gain frequency, slew rate of 19.2 V/mu s with a current supply of 385.15 mu A, and a complementary folded cascode with 104.25 dB Voltage gain, 18.15 MHz of unity gain frequency and a slew rate of 13.370 MV/mu s. These circuits were synthesized using a 0.35 mu m technology. The results show that the method provides a fast approach for good solutions using the modified SA and further good Pareto front exploration through its connection to the particle swarm optimization algorithm.

Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection

PURPOSE: To present a review about a comparative study of bile duct ligation versus carbon tetrachloride Injection for inducing experimental liver cirrhosis. METHODS: This research was made through Medline/PubMed and SciELO web sites looking for papers on the content "induction of liver cirrhosis in rats". We have found 107 articles but only 30 were selected from 2004 to 2011. RESULTS: The most common methods used for inducing liver cirrhosis in the rat were administration of carbon tetrachloride (CCl4) and bile duct ligation (BDL). CCl4 has induced cirrhosis from 36 hours to 18 weeks after injection and BDL from seven days to four weeks after surgery. CONCLUSION: For a safer inducing cirrhosis method BDL is better than CCl4 because of the absence of toxicity for researches and shorter time for achieving it.