Cabrini Medical Center

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways—either via mutations or genomic amplification—confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.

BackgroundOne of the key difficulties while managing concussion in sport is that there are few prognostic factors to reliably predict clinical outcome. The aims of the current paper are to review the evidence for concussion modifiers and to consider how the evaluation and management of concussion may differ in specific groups.MethodsA qualitative review of the literature on concussion was conducted with a focus on prognostic factors and specific groups including children, female athletes and elite versus non-elite players. PubMed, MEDLINE and SportsDiscus databases were reviewed.ResultsThe literature demonstrates that number and severity of symptoms and previous concussions are associated with prolonged recovery and/or increased risk of complications. Brief loss of consciousness (LOC) and/or impact seizures do not reliably predict outcomes following a concussion, although a cautious approach should be adopted in an athlete with prolonged LOC or impact seizures (ie, >1 min). Children generally take longer to recover from concussions and assessment batteries have yet to be validated in the younger age group. Currently, there are insufficient data on the influence of genetics and gender on outcomes following a concussion.ConclusionsSeveral modifiers are associated with prolonged recovery or increased risk of complications following a concussion and have important implications for management. Children with concussion should be managed conservatively, with an emphasis on return to learn as well as return to sport. In cases of concussions managed with limited resources (eg, non-elite players), a conservative approach should also be taken. There should be an emphasis on concussion education in all sports and at all levels, particularly in junior and community-based competitions.

A technological explosion has been revolutionizing imaging technology of the heart and lungs over the last decade. These advances have been transforming the health care industry, both preventative and acute care medicine. Ultrasound, nuclear medicine, computed tomography (CT), and magnetic resonance imaging (MRI) are examples of radiological techniques which have allowed for more accurate diagnosis and staging (determination of severity of disease). The most notable advances have occurred in CT and MRI. Most medical subspecialties rely on CT and MRI as the dominant diagnostic tools an exception being cardiology. CT and MRI are able to provide a detailed image of any organ or tissue in the body without the necessity of invasive or painful procedures. Virtually any individual could be tested as long as they are able to remain immobile for the duration of the study. Image generation traditionally has been limited by the perpetual motion of the human body. For example, the human heart is continually contracting and relaxing without a stationary moment during which an image could be obtained. Lung imaging has been more successful than cardiac imaging, but studies were limited to the length of time an ill person is able to hold his or her breath. Historically, imaging technology was limited by inability to take a picture fast enough of a moving object while maintaining a clinically useful level of resolution. Recent technologic innovation, resulting in high speed electrocardiogram- gated CT and MRI imaging, now allows the use of these imaging modalities for evaluation of the heart and lungs. These novel innovations provide clinicians with new tools for diagnosis and treatment of disease, but there are still unresolved issues, most notably radiation exposure. Ultrasound and MRI studies are the safest of the imaging modalities and subjects receive no radiation exposure. Nuclear studies give an approximate radiation dose of 10mSv and as high as 27mSv (Conti, 2005). In CT imaging, radiation dose can vary depending on the organ system being imaged and the type of scanner being used. The average radiation dose for pulmonary studies is 4.2mSv (Conti, 2005). The use of multi-detector CT (MDCT) to evaluate the heart can range from 6.7—13mSv. To put it into perspective, according to the National Institute of Health, an average individual will receive a radiation dose of 360mSv per year from the ambient environment. It is unlikely that the radiation doses received in routine imaging techniques will lead to adverse reactions such as cancer, but patients should be informed of the risks and benefits of each procedure so that they can make informed decisions. It is especially important that patients be informed when radioactive material is to be injected into their bodies. The reasons for this will be discussed later on in the chapter.

It is impossible to pinpoint the exact moment at which computational biology became a discipline of its own, but one could say that it was in 1997 when the society of computational biology was formed. Regardless of its exact birthday, the research community has rapidly adopted computational biology and its applications are being vigorously explored. The study and application of medicine is a dynamic challenge. Changes in medicine usually take place as a result of new knowledge acquired through observation and experimentation. When a tamping rod 1-inch thick went through Phineas Gage’s head in 1848, his survival gave the medical field an unusual opportunity to observe behavior of a person missing their prefrontal cortex. This observation lead to the short-lived psychosurgical procedure known as a lobotomy, which attempted to change a person’s behavior by separating two portions of a person’s brain (Pols, 2001). Countless observations, experiments and mistakes represent how almost all medical knowledge has been acquired. The relatively new field of computational biology offers a nontraditional approach to contribute to the medical body of knowledge. Computational biology is a new field combining biology, computer science, and mathematics to solve problems that are unworkable with traditional biological techniques. It includes traditional areas such as systems biology, molecular biology, biochemistry, biophysics, statistics, and computer science, as well as recently developed disciplines including bioinformatics and computational genomics. Algorithms, which are able to closely model biological behavior, validate the medical understanding of the observed processes and can be used to model scenarios that might not be able to be physically reproduced. The goal of computational biology is to use mathematics and computer science to model biological systems on the molecular level. Instead of taking on large complex systems, computational biology is starting small, literally. Modeling problems in molecular biology and biochemistry is a far less daunting task. At a microscopic level, patient’s characteristics drop out of the equation and all information behavior affecting is known. This creates a deterministic model which, given the same input, will always produce the same output. Some of the major subdisciplines of computational biology are computational genomics, systems biology, protein structure prediction, and evolutionary biology, all of which model microscopic structures.

BackgroundPancreaticoduodenectomy is the procedure of choice for tumors of the head of the pancreas and periampulla. Despite advances in surgical technique and postoperative care, the procedure continues to carry a high morbidity rate. One of the most common morbidities is delayed gastric emptying with rates of 15%–40%. Following two prolonged cases of delayed gastric emptying, we altered our reconstruction to avoid this complication altogether. Subsequently, our patients underwent a classic pancreaticoduodenectomy with an undivided Roux-en-Y technique for reconstruction.MethodsWe reviewed the charts of our last 13 Whipple procedures evaluating them for complications, specifically delayed gastric emptying. We compared the outcomes of those patients to a control group of 15 patients who underwent the Whipple procedure with standard reconstruction.ResultsNo instances of delayed gastric emptying occurred in patients who underwent an undivided Roux-en-Y technique for reconstruction. There was 1 wound infection (8%), 1 instance of pneumonia (8%), and 1 instance of bleeding from the gastrojejunal staple line (8%). There was no operative mortality.ConclusionUse of the undivided Roux-en-Y technique for reconstruction following the Whipple procedure may decrease the incidence of delayed gastric emptying. In addition, it has the added benefit of eliminating bile reflux gastritis. Future randomized control trials are recommended to further evaluate the efficacy of the procedure.

M. Poon, C. Learra prevalence of Afib in patients over the age of 80 is greater than 6% (Fuster 2001). As the population of developed countries ages in the next 50 years, it is expected that Afib will become a major healthrelated issue and a contributor to rising health-care costs (Wolf 1991, Flegel 1987). The increased rate of death due to Afib is mainly attributed to cardiacrelated rather than due to thromboembolism (Dries 1998). In patients examined by nuclear myocardial perfusion studies, the presence of Afib is a poor prognosticator. Furthermore, Abidov et al. recently reported that, in these patients, the finding of Afib independently increases the risk of adverse cardiac events to an extent greater than perfusion and function variables (Abidoy 2004). The treatment of Afib has evolved greatly in the last decade. Nonetheless, the pharmacological approach has not been optimal due to a myriad of drug-related side effects, and surgical treatment is effective but not practical. As catheter ablation of Afib continues to gain popularity and wider acceptance in the medical community, advanced tomographic imaging of the heart, particularly using multi-slice CT, begins to take on a more important role in the planning and follow-up of patients undergoing this procedure.

Previous studies have demonstrated a decrease in intestinal healing in intra‐abdominal infection. Currently, the effect of localized intra‐abdominal infection on anastomotic healing and strength is not known. This study was designed to evaluate anastomotic wound healing in the presence of intra‐abdominal abscess.30 male Sprague Dawley rats weighing 270–300 grams were used for this experiment. 20 animals underwent cecal ligation and puncture (CLP) with 16 gauge needle. They were followed for 14 days. 9 of them died in the first week. The CLP animals had an initial 20% weight loss; however by day 10 they had a gradual return toward control weight. At the end of 14 days, rats from CLP group (n = 11) and control group (n = 10) underwent laparotomy and single‐layer left colonic anastomosis. Blood cultures and abdominal swab cultures were sent from both groups. Post‐operatively, animals were allowed to recover, food and water were offered ad libitum. At post‐operative day five, animals were euthanized by thiopental overdose. Following anastomotic bursting pressure measurements, two samples were taken from the anastomotic line for subsequent determination of hydroxyproline content. Groups were compared with Students’t test. Data were expressed as means ± SEM.In the post‐operative period, all rats lost 10% to 12% of their body weight. No bacterial growth was detected in cultures. Hydroxyproline content measurements were significantly higher in the CLP group (11.2 ± 0.3 vs. 9.8 ± 0.5 ug HPO/mg dry tissue weight. P < 0.05). On the other hand, no significant difference was observed in bursting pressure measurements between the groups (177 ± 6.3 vs. 164 ± 10.4 mmHg. P > 0.05).These findings suggest that localized intra‐abdominal infection without sepsis doesn’t inhibit intestinal anastomotic healing.Supported by a grant from Turkish Scientific and Technical Research Council.