Capecitabine as second-line treatment for metastatic cholangiocarcinoma: A report of two cases

Background: The management of recurrent, metastatic cholangiocarcinoma still remains a problem since this tumor entity is classified as chemotherapy-resistant. When advanced or metastatic disease is diagnosed, the therapeutic efforts are essentially directed toward palliation. Patients and Methods: We report on 2 patients suffering from metastatic cholangiocarcinoma. Both had received previous chemotherapy for metastatic disease, including hepatic artery infusion {[}5-fluorouracil (5-FU)/folinic acid (FA) and oxaliplatin] and a combination therapy consisting of 5-FU/FA and gemcitabine. Since a progression of the disease was diagnosed, both patients were started on oral capecitabine at a daily dose of 2,500 mg/m(2) in 2 divided doses for 2 weeks, followed by 1 week rest. Results: Capecitabine was tolerated well and severe side effects were not observed. A stop of progression, documented by imaging procedures and tumor marker kinetics, was achieved in both patients. Conclusion: Capecitabine could potentially be used for second-line treatment in patients with progressive metastatic cholangiocarcinoma

Are you in or out? Recruitment of adolescent smokers into a behavioral smoking cessation intervention.

IntroductionEven though many adolescent smokers want to quit, it is difficult to recruit them into smoking cessation interventions. Little is known about which adolescent smokers are currently reached by these measures. In this study we compare participants of a group-based, cognitive behavioral smoking cessation intervention with adolescent smokers who decided against participating.MethodsWithin a non-randomized controlled trial, data of 1053 smokers (aged 11-19) from 42 German secondary schools were analyzed. Of these smokers, 272 were recruited into 47 courses of the intervention. An in-class information session, individually addressing potential participants, and incentives were used as means of recruitment. Personal predictors of participation were analyzed using regression analyses and multivariate path analyses to test for mediation.ResultsIn the path analysis model, nicotine dependence, quit motivation, and a previous quit attempt were directly positively related to participation. Heavier smoking behavior was indirectly positively associated with participation through nicotine dependence and negatively through quit motivation, yielding an overall positive indirect effect. The positive effect of a previous quit attempt on participation was partially mediated through nicotine dependence and quit motivation. The proportion of smoking friends were indirectly positively related to participation, mediated through nicotine dependence.ConclusionsSince adolescents with heavier smoking behavior and stronger nicotine dependence are less likely to undertake a successful unassisted quit attempt, the reach of these young smokers with professional cessation interventions is desirable. Further measures to improve the recruitment of those currently not motivated to quit have to be examined in future studies

Automated optimization of a reduced layer 5 pyramidal cell model based on experimental data.

The construction of compartmental models of neurons involves tuning a set of parameters to make the model neuron behave as realistically as possible. While the parameter space of single-compartment models or other simple models can be exhaustively searched, the introduction of dendritic geometry causes the number of parameters to balloon. As parameter tuning is a daunting and time-consuming task when performed manually, reliable methods for automatically optimizing compartmental models are desperately needed, as only optimized models can capture the behavior of real neurons. Here we present a three-step strategy to automatically build reduced models of layer 5 pyramidal neurons that closely reproduce experimental data. First, we reduce the pattern of dendritic branches of a detailed model to a set of equivalent primary dendrites. Second, the ion channel densities are estimated using a multi-objective optimization strategy to fit the voltage trace recorded under two conditions - with and without the apical dendrite occluded by pinching. Finally, we tune dendritic calcium channel parameters to model the initiation of dendritic calcium spikes and the coupling between soma and dendrite. More generally, this new method can be applied to construct families of models of different neuron types, with applications ranging from the study of information processing in single neurons to realistic simulations of large-scale network dynamics

Re-evaluation of HER2 status in metastatic breast cancer and tumor-marker guided therapy with vinorelbine and trastuzumab

Background: HER2 is overexpressed in 20 - 30% of breast cancers. Compared to chemotherapy alone, chemotherapy with trastuzumab improves clinical outcome in patients with HER2- positive metastatic breast cancer ( MBC). In general, HER2 status in a primary lesion predicts the status of metastases, so that biopsy of metastatic lesions appears unnecessary. Case Report: A 39- year old woman was diagnosed with primary breast cancer in November 2000. Using the method and scoring system of the DAKO Hercep Test, the tumor has shown low HER2 expression ( DAKO score 1+). After failure of several chemotherapy regimens for metastatic disease ( liver, skeletal), the patient underwent CT- guided needle biopsy of the liver which showed HER2 positive adenocarcinoma ( DAKO score 3+). In consequence, the patient was treated with vinorelbine ( 30 mg/ m(2) d1,8,15 q4w) and trastuzumab ( 4 mg/ kg loading dose, 2 mg/ kg weekly). During a treatment period of 4 months imaging results as well as tumor marker kinetics indicated an excellent response with sustained decrease of tumor markers. A retrospective analysis of the HER2 shed antigen in metastatic stage revealed excessively increased serum levels and supports HER2 overexpression observed in liver metastasis. The kinetics of the HER2 shed antigen during therapy for metastatic disease were found to be in phase with the kinetics of CEA and CA15- 3. Conclusion: This case report demonstrates that re- evaluation of the HER2 status may be helpful in single patients not sufficiently responding to treatment of metastatic disease. Determination of HER2 overexpression may be facilitated by a determination of the HER2 shed antigen level in peripheral blood