Abigail Stocker

Clinical Efficacy and Toxicity of Anti-EGFR Therapy in Common Cancers

Epidermal growth factor receptor (EGFR) is a cell surface molecule and member of the ErbB family of receptor tyrosine kinases. Its activation leads to proliferation, antiapoptosis, and metastatic spread, making inhibition of this pathway a compelling target. In recent years, an increasing number of clinical trials in the management of solid malignancies have become available indicating the clinical efficacy of anti-EGFR monoclonal antibodies and oral small molecule tyrosine kinase inhibitors (TKIs). This review addresses frequently used EGFR inhibitors, summarizes clinical efficacy data of these new therapeutic agents, and discusses their associated toxicity and management.

Autonomic Evaluation of Patients With Gastroparesis and Neurostimulation: Comparisons of Direct/Systemic and Indirect/Cardiac Measures.

Background Disorders of nausea, vomiting, abdominal pain, and related problems often are manifestations of gastrointestinal, neuromuscular, and/or autonomic dysfunction. Many of these patients respond to neurostimulation, either gastric electrical stimulation or electroacupuncture. Both of these therapeutic techniques appear to influence the autonomic nervous system which can be evaluated directly by traditional testing and indirectly by heart rate variability. Methods We studied patients undergoing gastric neuromodulation by both systemic autonomic testing (39 patients, six males and 33 females, mean age 38 years) and systemic autonomic testing and heart rate variability (35 patients, seven males and 28 females, mean age 37 years) testing before and after gastric neuromodulation. We also performed a pilot study using both systemic autonomic testing and heart rate variability in a small number of patients (five patients, all females, mean age 48.6 years) with diabetic gastroparesis at baseline to compare the two techniques at baseline. Systemic autonomic testing and heart rate variability were performed with standardized techniques and gastric electrical stimulation was performed as previously described with electrodes implanted serosally in the myenteric plexus. Results Both systemic autonomic testing and heart rate variability measures were often abnormal at baseline and showed changes after gastric neuromodulation therapy in two groups of symptomatic patients. Pilot data on a small group of similar patients with systemic automatic nervous measures and heart rate variability showed good concordance between the two techniques. Conclusions Both traditional direct autonomic measures and indirect measures such as heart rate variability were evaluated, including a pilot study of both methods in the same patient group. Both appear to be useful in evaluation of patients at baseline and after stimulation therapies; however, a future full head-to-head comparison is warranted.

Intravenous immunoglobulin in drug and device refractory patients with the symptoms of gastroparesis—an open-label study

Gastroparesis is a complex clinical entity; many aspects of which remain unknown. Although most patients have idiopathic, diabetic, or postsurgical gastroparesis, many are thought to have measurable neuromuscular abnormalities. Immunotherapy has recently been utilized to treat suspected autoimmune gastrointestinal dysmotility.

A Novel System and Methodology for Continuous Ambulatory Monitoring of Gastric Slow Waves

Fig. 1. Left: The block diagram of the system is composed of a front-end, back-end, and a computer. The system can record gastric slow waves from 3 channels, and stimulate the stomach through one channel. Right: The flow chart shows the front-end function, consisting of wireless data transmission to the backend module, as well as storing data to a micro SD memory card for off-line analysis. Gastric contractions are initiated and coordinated by an underlying bioelectrical activity, termed slow waves (SWs). Dysrhythmias of SWs have been associated with gastroparesis (Gp). Gastric electrical stimulation (GES) is an option to alleviate the Gp symptoms. However, various researchers have reported conflicting therapeutic effects, and the mechanisms of action are not fully understood. As a result a novel methodology to objectively document the GES effect is required. We have developed a system and methodology to chronically monitor SWs. Introduction

Endoscopic aspects of temporary gastric electrical stimulator lead placement in patients with gastroparesis and gastroparesis-like syndromes

Gastric electrical stimulation (GES) is an accepted form of therapy for gastroparesis and is considered for compassionate therapy in patients with refractory nausea and vomiting. The U. S. Food and Drug Administration has approved GES for treatment of drug-refractory idiopathic gastroparesis and diabetic gastroparesis, but it has also been used off label for related conditions. Although GES has been shown to improve the frequency of nausea and vomiting in patients with idiopathic and diabetic gastroparesis, it has also shown benefit in patients affected by the symptoms of gastroparesis, ie, nausea, vomiting, and abdominal pain, but with nondelayed gastric emptying, referred to as gastroparesis-like syndrome or unexplained nausea and vomiting. Because not all patients with gastroparesis and gastroparesis-like syndrome benefit from GES, a trial of temporary gastric stimulation (Fig. 1) can help determine those who would benefit from placement of a permanent gastric stimulator, which requires surgery. The techniques for endoscopic and surgical placement of gastric electrical stimulators are not widely known or performed. The purpose of this video (Video 1, available online at www.VideoGIE.org). is to highlight the important aspects of temporary gastric electrical

Clinical Efficacy of Serum-Derived Bovine Immunoglobulin in Patients With Refractory Inflammatory Bowel Disease

Background: Inflammatory bowel disease (IBD) can have autoimmunity and/or intestinal barrier dysfunction as part of pathophysiology and may be refractory to all available treatment options. Serum‐derived bovine immunoglobulin (SBI) binds microbial components with postulated downstream effects of normalized gut immune and barrier function, which may be useful for managing IBD. The purpose of our study was to evaluate the effectiveness of SBI in the management of refractory IBD, particularly symptoms of chronic diarrhea and loose stools. Methods: We retrospectively analyzed charts for patients diagnosed with IBD (n = 40) who were refractory to standard treatment. Patients received oral SBI 5 g daily for a period of at least 6 weeks. Twelve patients with IBD fulfilled study inclusion criteria. Each patient graded the severity and frequency of gastrointestinal symptoms before starting SBI and at 6 weeks of treatment using a standardized patient assessment form. Means and standard deviations for all symptom scores at baseline and week 6 of treatment were analyzed. Results: Mean symptom scores decreased significantly for nausea (P = 0.02 for severity and P = 0.03 for mean symptom score) and diarrhea (P = 0.0006, P = 0.0001 and P = 0.0001 for severity, frequency and mean symptom score, respectively). Conclusions: Therapy with SBI alleviated some refractory gastrointestinal symptoms in patients with IBD, including nausea and diarrhea. Increased duration, dosage and/or frequency of SBI might provide additional symptom improvement and could be tested through controlled clinical trials with larger sample sizes and longer follow‐up.

Ambulatory gastric mucosal slow wave recording for chronic experimental studies

Dysrhythmic bioelectric slow wave activity have been implicated in major functional motility disorders such as gastroparesis and chronic unexplained nausea and vomiting, but its correlation to symptoms is still unclear. For patients with severe gastroparesis, high-frequency gastric stimulation is offered as a therapy in some centers. Temporary gastric electrical stimulation has also been proposed an approach to screen patients who would benefit from the implantation of a permanent stimulator. In this study we introduced novel methods for recording slow wave activity from the gastric mucosa during the entire temporary stimulation phase of 5 days, in 3 patients. An ambulatory recording system was applied to record 3 channels of mucosal slow wave activity, as well as three axis accelerometer data to monitor when the patient was mobile. Techniques were developed to detect large movements and these time periods were excluded from analyses of mucosal slow waves. The frequency and amplitude of the slow waves was calculated in a 5 min segment, with 75% overlap, for the entire duration. In feasibility studies, the slow wave frequency and amplitude for the patients were 3.0±0.96 cpm and 1.43±1.75 mV. Large variations in slow wave amplitude were seen in comparsion to slow wave frequency, which were concordant with previous studies. The use of the ambulatory system will allow for investigation of pathophysiology, correlation of electrophysiology data to patient symptoms and to determine the effects of post-prandial and noctural slow wave patterns. We anticipate that future use of slow wave information alongside patient symptoms may allow improved selection of patients for stimulaton techniques.