Setup of multidisciplinary team discussions for patients with cholangiocarcinoma: current practice and recommendations from the European Network for the Study of Cholangiocarcinoma (ENS-CCA).

BACKGROUND: Cholangiocarcinomas (CCAs) are a rare group of malignancies characterized by dismal prognosis. There are currently no standardized guidelines for multidisciplinary teams (MDTs) in CCAs. MATERIAL AND METHODS: An online survey was built with the aim of defining the current practice of MDTs in CCAs and identifying possible areas of improvement, providing minimum standards of practice for an ideal CCA MDT. Analysis of the replies regarding current and ideal MDT practice was carried out by calculating weighted average (WA) of likelihood of every item. The survey was shared with members of the European Network for the Study of Cholangiocarcinoma and other medical centers with expertise in biliary tract cancer part of the EURO-CHOLANGIO-NET (European Cholangiocarcinoma Network: https://eurocholangionet.eu/) COST Action CA18122 initiative. RESULTS: The role of the MDT coordinator was a recognized priority in an ideal well-functioning MDT (WA 3.31/4), together with providing minimum clinical information before the meeting to secure adequate case preparation (WA 3.54/4). Optimal frequency of MDT meetings was weekly according to 76.92% of the participants; 73.06% believed that ideally all newly diagnosed patients and each new treatment should be discussed, although that happened only in less than half of the MDTs (46.15%) in current practice. Most participants stated that they always (46.15%) or often (50.00%) used guidelines, mainly international (61.00%) (European and American), followed by national/local (39.00%). We defined the ideal setup of a CCA MDT, identifying specialists whose presence is mandatory with WA >3.0 (oncologist, clinician responsible for patient's care, surgeon, diagnostic and interventional radiologist, hepatologist, pathologist, endoscopist and gastroenterologist) and those whose presence would be recommended with a WA <3.0 (palliative care, nurse, dietitian, basic researcher, psychologist and social worker). CONCLUSIONS: Our identified minimum requirements should be taken into account at the time of CCA MDT setup and quality assessment.

Immediate postoperative and mid-term survival in nonagenarians undergoing non-traumatic emergency surgery.

BACKGROUND: Nonagenarian people are increasingly using the emergency services, however, few studies have addressed this population. The goal of this prospective observational study is to determine relevant factors that independently reduce their immediate postoperative and mid-term survival. METHODS: We included all the nonagenarians who underwent non-traumatic emergency surgery between 2006-2011. The dependent variable, days of postoperative survival, was studied at 2 intervals: 0-30 days and 31 days to 1 year after surgery (immediate and mid-term respectively). Firstly, we calculated the Kaplan-Meier survival curve (KMsc) of the whole population. To analyse the bivariate relationship between each of the pre-, intra-, and postoperative variables and mortality we used c2 and Fischer's test. Finally, we performed a stepwise Cox regression analysis and developed two models -one for each interval. RESULTS: The study included 142 patients. The overall one-year mortality rate was 47.2%, and the 30-day mortality rate was 35.9%. The KMsc showed a steep drop during the first month, and then a more gradual one for the rest of year. The inflection point was at day 26. The variables associated with a reduced immediate postoperative survival were neoplasms and 4 complications: heart failure, pulmonary aspiration, renal impairment and stroke. The factors associated with a reduced mid-term survival were: postoperative arrhythmia, surgical reintervention, and perioperative red blood cell transfusion. CONCLUSION: Postoperative complications are an important predictor of reduced survival both immediately, and in the mid-term. Furthermore, most postoperative mortality occurs within the first 26 days postsurgery; hence the need for an aggressive treatment of such complications during this period.

Anaemia and transfusion in nonagenarians undergoing emergency, non-traumatic surgery: a prospective observational study.

OBJECTIVES: To characterise transfusion and determine its main predictors in nonagenarians undergoing non-elective, non-traumatic surgery. Simultaneously, we compared nonagenarians to a similar, but younger sample, as far as the transfusional policy is concerned. BACKGROUND: Perioperative anaemia and transfusion are currently topical, but little is known about them in this population. METHODS: In this prospective observational study, we recruited 135 patients older than 90 who underwent a non-elective, non-traumatic procedure, between 2006 and 2011. A descriptive statistical analysis was performed and a logistic regression model developed. As a control sample, we used a similar number of patients in their third age (between 65 and 85 years old), who underwent the same procedure, during the same period. RESULTS: Thirty-five per cent of the nonagenarians were transfused. The main independent factors associated with transfusion were anaemia (OR 6·77, P < 0·01), a coexisting neoplasm (OR 10·99, P < 0·01) and the need for an exploratory laparotomy (OR 3·05, P = 0·01). When comparing the nonagenarians to the younger group, we found a significant difference in their basal health status and the mortality rate (P < 0·01), but the transfusion policy did not differ substantially, except for the haemoglobin threshold (P = 0·01). CONCLUSIONS: The independent transfusion predictors in nonagenarians should be taken into account for cross-matching. Transfusional policy being similar between nonagenarians and third-aged patients; the differences in thresholds were due to the differences in the populations.

Speeding chemical reactions by focusing.

We present numerical results for a chemical reaction of colloidal particles which are transported by a laminar fluid and are focused by periodic obstacles in such a way that the two components are well mixed and consequently the chemical reaction is speeded up. The roles of the various system parameters (diffusion coefficients, reaction rate, and obstacles sizes) are studied. We show that focusing speeds up the reaction from the diffusion limited rate ∼t(-1/2) to very close to the perfect mixing rate, ∼t(-1).

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

Recommendations and expert opinion on the treatment of locally advanced rectal cancer in Spain.

In Spain 22,000 new cases of colorectal cancer are diagnosed each year, with 13,075 deaths resulting from this disease. Around 70% of colorectal cancers are localised in the colon and 30% in the rectum. A group of Spanish experts established recommendations on what would be the best strategy in the treatment of locally advanced rectal cancer (LARC). Adequate assessment of local tumour extension, including high-resolution magnetic resonance imaging and endorectal ultrasound, is essential for successful treatment. The three cornerstones in the treatment of LARC are surgery, radiotherapy and chemotherapy. Most patients will need a total mesorectal excision (TME). Preoperative chemo-radiotherapy (CRT) is preferred for the majority of patients with T3/T4 disease and/or regional node involvement, and adjuvant chemotherapy is recommended after a patient-sharing decision. Capecitabine, after showing a trend in improved downstaging in neoadjuvant stratum and the convenience of its oral administration, represents an alternative to 5-FU as perioperative treatment of LARC.

Recommendations and expert opinion on the treatment of locally advanced rectal cancer in Spain

In Spain 22,000 new cases of colorectal cancer are diagnosed each year, with 13,075 deaths resulting from this disease. Around 70% of colorectal cancers are localised in the colon and 30% in the rectum. A group of Spanish experts established recommendations on what would be the best strategy in the treatment of locally advanced rectal cancer (LARC). Adequate assessment of local tumour extension, including high-resolution magnetic resonance imaging and endorectal ultrasound, is essential for successful treatment. The three cornerstones in the treatment of LARC are surgery, radiotherapy and chemotherapy. Most patients will need a total mesorectal excision (TME). Preoperative chemo-radiotherapy (CRT) is preferred for the majority of patients with T3/T4 disease and/or regional node involvement, and adjuvant chemotherapy is recommended after a patient-sharing decision. Capecitabine, after showing a trend in improved downstaging in neoadjuvant stratum and the convenience of its oral administration, represents an alternative to 5-FU as perioperative treatment of LARC (AU)

Enhancing DNA immunization by targeting ASFV antigens to SLA-II bearing cells.

One of the main criticisms to DNA vaccines is the poor immunogenicity that they confer on occasions, at least in large animals. Confirming this theory, immunization with plasmid DNA encoding two African swine fever virus genes in frame (pCMV-PQ), failed in inducing detectable immune responses in pigs, while it was successful in mice. Aiming to improve the immune responses induced in swine, a new plasmid was constructed, encoding the viral genes fused in frame with a single chain variable fragment of an antibody specific for a swine leukocyte antigen II (pCMV-APCH1PQ). Our results clearly demonstrate that targeting antigens to antigen professional cells exponentially enhanced the immune response induced in pigs, albeit that the DNA vaccine was not able to confer protection against lethal viral challenge. Indeed, a viremia exacerbation was observed in each of the pigs that received the pCMV-APCH1PQ plasmid, this correlating with the presence of non-neutralizing antibodies and antigen-specific SLA II-restricted T-cells. The implications of our discoveries for the development of future vaccines against African swine fever virus and other swine pathogens are discussed.

Weak disorder: anomalous transport and diffusion are normal yet again.

We carry out a detailed study of the motion of particles driven by a constant external force over a landscape consisting of a periodic potential corrugated by a small amount of spatial disorder. We observe anomalous behavior in the form of subdiffusion and superdiffusion and even subtransport over very long time scales. Recent studies of transport over slightly random landscapes have focused only on parameters leading to normal behavior, and while enhanced diffusion has been identified when the external force approaches the critical value associated with the transition from locked to running solutions, the regime of anomalous behavior had not been recognized. We provide a qualitative explanation for the origin of these anomalies, and make connections with a continuous time random walk approach.

Observational study of nonogenarians undergoing emergency, non-trauma surgery.

BACKGROUND: Nonagenarian population is growing, and so is the number of them needing emergency surgery. Yet, their treatment is often based on the outcomes of younger patients: although old age is known to be a risk factor for surgery, its level is not clear. This is a prospective, observational study to describe the population. It is aimed at providing quantified scientific evidence of the current procedures and their outcomes. METHODS: All non-traumatic nonagenarians who underwent surgery between July 2006 and September 2010 in our University Hospital were recruited and followed up over a month after discharge. A descriptive statistical analysis was performed. RESULTS: Of the approximately 12 660 surgical emergencies, 102 were nonagenarians: 69.6% were women, who mostly had an ASA score III (62.7%). Perioperative morbidity and mortality rates of 61.6% [95% confidence interval (CI): 52.33-71.19%] and 35.3% (95% CI: 26.01-44.57%), respectively, were found statistically associated with preoperative neoplasms. The most frequent causes of surgery were acute limb arterial thrombosis (20), incarcerated hernia (17), and bowel occlusion (14). Confusion, renal failure, and abdominal problems accounted for the most frequent causes of morbidity. Among them, abdominal complications, cardiogenic pulmonary oedema, aspiration, stroke, and renal failure were associated with mortality. CONCLUSIONS: The study gave scientific support and actual figures to many intuitive beliefs: morbidity and mortality are high and are associated with many preoperative comorbidities. All this, combined with an already reduced life expectancy, and a presumably low physiological reserve makes these patients particularly vulnerable to emergency surgery.

Controlling chaotic transport in two-dimensional periodic potentials.

We uncover and characterize different chaotic transport scenarios in perfect two-dimensional periodic potentials by controlling the chaotic dynamics of particles subjected to periodic external forces in the absence of a ratchet effect (i.e., with no directed transport by symmetry breaking of zero-mean forces). After identifying relevant symmetries of the equations of motion, analytical estimates in parameter space for the occurrence of different transport scenarios are provided and confirmed by numerical simulations. These scenarios are highly sensitive to variations of the system's asymmetry parameters, including the eccentricity of the two-dimensional periodic potential and the direction of dc and ac forces, which could be useful for particle sorting purposes in those cases where chaos is unavoidable.

Diffusion coefficient in periodic and random potentials.

Transport and diffusion of particles on modulated surfaces is a nonequilibrium problem which is receiving a great deal of attention due to its technological applications, but analytical calculations are scarce. In earlier work, we developed a perturbative approach to begin to provide an analytic platform for predictions about particle trajectories over such surfaces. In some temperature and forcing regimes, we successfully reproduced results for average particle velocities obtained from numerical simulations. In this paper, we extend the perturbation theory to the calculation of higher moments, in particular the diffusion tensor and the skewness. Numerical simulations are used to check the domain of validity of the perturbative approach.

Numerical study of A+A-->0 and A+B-->0 reactions with inertia.

Using numerical methods the authors study the annihilation reactions A+A-->0 and A+B-->0 in one and two dimensions in the presence of inertial contributions to the motion of the particles. The particles move freely following Langevin dynamics at a fixed temperature. The authors focus on the role of friction.

Dispersionless transport in a washboard potential.

We study and characterize a new dynamical regime of underdamped particles in a tilted washboard potential. We find that for small friction in a finite range of forces the particles move essentially nondispersively, that is, coherently, over long intervals of time. The associated distribution of the particle positions moves at an essentially constant velocity and is far from Gaussian-like. This new regime is complementary to, and entirely different from, well-known nonlinear response and large dispersion regimes observed for other values of the external force.

Analytical approach to sorting in periodic and random potentials.

There has been a recent revolution in the ability to manipulate micrometer-sized objects on surfaces patterned by traps or obstacles of controllable configurations and shapes. One application of this technology is to separate particles driven across such a surface by an external force according to some particle characteristic such as size or index of refraction. The surface features cause the trajectories of particles driven across the surface to deviate from the direction of the force by an amount that depends on the particular characteristic, thus leading to sorting. While models of this behavior have provided a good understanding of these observations, the solutions have so far been primarily numerical. In this paper we provide analytic predictions for the dependence of the angle between the direction of motion and the external force on a number of model parameters for periodic as well as random surfaces. We test these predictions against exact numerical simulations.

Exported oscillator competition: a concept to analyze complex rhythms.

We study the interaction between two independent nonlinear oscillators competing through a neutral excitable element. The first oscillator, completely deterministic, acts as a normal pacemaker sending pulses to the neutral element which fires when it is excited by these pulses. The second oscillator, endowed with some randomness, though unable to make the excitable element to beat, leads to the occasional suppression of its firing. The missing beats or errors are registered and their statistics analyzed in terms of the noise intensity and the periods of both oscillators. This study is inspired in some complex rhythms such as a particular class of heart arrhythmia.

Physical analysis of a processive molecular motor: the conventional kinesin.

We present a model that allows for the derivation of the experimentally accessible observables: spatial steps, mean velocity, stall force, useful power, efficiency and randomness, etc. as a function of the [adenosine triphosphate] concentration and an external load F. The model presents a minimum of adjustable parameters and the theoretical predictions compare well with the available experimental results.

Sorting on periodic surfaces.

Particles moving on crystalline surfaces and driven by external forces or flow fields can acquire velocities along directions that deviate from that of the external force. This effect depends upon the characteristics of the particles, most notably particle size or particle index of refraction, and can therefore be (and has been) used to sort different particles. We introduce a simple model for particles subject to thermal fluctuations and moving in appropriate potential landscapes. Numerical results are compared to recent experiments on landscapes produced with holographic optical tweezers and microfabricated technology. Our approach clarifies the relevance of different parameters, the direction and magnitude of the external force, particle size, and temperature.

From subdiffusion to superdiffusion of particles on solid surfaces.

We present a numerical and partially analytical study of classical particles obeying a Langevin equation that describes diffusion on a surface modeled by a two-dimensional potential. The potential may be either periodic or random. Depending on the potential and the damping, we observe superdiffusion, large-step diffusion, diffusion, and subdiffusion. Superdiffusive behavior is associated with low damping and is in most cases transient, albeit often long. Subdiffusive behavior is associated with highly damped particles in random potentials. In some cases subdiffusive behavior persists over our entire simulation and may be characterized as metastable. In any case, we stress that this rich variety of behaviors emerges naturally from an ordinary Langevin equation for a system described by ordinary canonical Maxwell-Boltzmann statistics.

Modelization of surface diffusion of a molecular dimer.

A simple model for a dimer molecular diffusion on a crystalline surface, as a function of temperature, is presented. The dimer is formed by two particles coupled by a quadratic potential. The dimer diffusion is modeled by an overdamped Langevin equation in the presence of a two-dimensional periodic potential. Numerical simulation's results exhibit some dynamical properties observed, for example, in Si2 diffusion on a silicon [100] surface. They can be used to predict the value of the effective friction parameter. Comparison between our model and experimental measurements is presented.