Chronic nausea and vomiting: New insights and approach to treatment

Opinion statement Chronic vomiting of unclear etiology has been given a number of names over time. For many years, it was known as "psychogenic" vomiting because a psychiatric etiology was considered the most likely cause. More recently, the concepts of cyclic vomiting syndrome (CVS) and functional vomiting (FV) have been proposed to better explain this perplexing phenomenon. CVS is a dramatic clinical syndrome characterized by intense episodes of vomiting lasting over a period of days but alternating with periods of intense quiescence. FV, as defined by the Rome II diagnostic criteria, is vomiting of at least 3 months, which need not be consecutive, in the preceding year with at least three separate vomiting episodes in a week. It is found in the absence of obvious metabolic, structural, or psychiatric disorders which could explain the vomiting (Table 1). It will be the purpose of this article to review the history of chronic vomiting from a nomenclature perspective. Methodologic limitations of early studies will be described as well as more contemporary reviews that used updated methodologic approaches to describe this perplexing problem.     

Unexplained nausea and vomiting

Opinion statement Nausea and vomiting are debilitating symptoms for patients, and can be challenging problems in diagnosis and management for physicians. Initial efforts must be made to establish a specific diagnosis that represents the pathophysiological cause of the nausea and vomiting. If a specific diagnosis is made (for example, antral ulceration), then specific therapy for the lesion will usually eradicate the nausea and vomiting associated with the specific disease. When standard gastrointestinal diseases are eliminated as a cause of nausea and vomiting, then gastric neuromuscular disorders (disorders of motility) should be considered as potential causes of these symptoms. Gastric neuromuscular disorders range from gastric dysrhythmias and abnormalities of gastric accommodation to frank gastroparesis. Treatments for nausea and vomiting due to gastric neuromuscular dysfunction include: 1) patient education and dietary counseling; 2) gastrokinetic drugs; 3) visceral, sensory afferent and CNS drugs; 4) gastrostomy for stomach venting; 5) jejunostomy for enteral feeding access; and 6) acustimulation and gastric pacemaker therapies. Treatment approaches based on the pathophysiology of gastric neuromuscular dysfunction(s) and on patient education aid in the successful management of unexplained nausea and vomiting.     

Functional nausea and vomiting

Although functional vomiting (FV), cyclic vomiting syndrome (CVS) and chronic idiopathic nausea (CIN) are fairly rare disorders, it has been increasingly recognized that these conditions can be highly disabling. Traditionally, FV, CVS and CIN have been under-investigated; however, interest in the cause and treatment of these disorders has increased, particularly with regard to their pathophysiology and the evaluation of new treatment approaches. This article presents a literature-based review of the nomenclature, pathophysiology, clinical presentation and management of CIN, CVS and FV. There is a dearth of randomized, controlled trials of treatments for these disorders, owing mainly to their low prevalence. Consequently, referral centers that see a large number of patients with these challenging disorders are working together to share their experience, so that the most productive treatment strategies can be used to help patients. Our knowledge of the treatment of FV, CVS and CIN, as best we know it, is presented here.     

Novel approaches to the treatment of systemic anthrax

Anthrax continues to generate concern as an agent of bioterrorism and as a natural cause of sporadic disease outbreaks. Despite the use of appropriate antimicrobial agents and advanced supportive care, the mortality associated with the systemic disease remains high. This is primarily due to the pathogenic exotoxins produced by Bacillus anthracis as well as other virulence factors of the organism. For this reason, new therapeutic strategies that target events in the pathogenesis of anthrax and may potentially augment antimicrobials are being investigated. These include anti-toxin approaches, such as passive immune-based therapies; non-antimicrobial drugs with activity against anthrax toxin components; and agents that inhibit binding, processing, or assembly of toxins. Adjunct therapies that target spore germination or downstream events in anthrax intoxication are also under investigation. In combination, these modalities may enhance the management of systemic anthrax.     

Management of chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most disturbing side effects of cancer treatment. Research in anti-emetic therapy progressed gradually since the early eighties and the development of anti-emetic agents continues. This review focuses on the current management of CINV based on the most recent guidelines and adherence to the latter is examined more carefully. Setrons (5HT3 receptor antagonists), corticosteroids and NK-1 receptor antagonists are the cornerstones of anti-emetic therapy. The latest developed palonosetron and casopitant proved to be highly promising in clinical trials. Other types include benzodiazepines, cannabinoids and olanzapine. Various risk factors contribute to the overall risk of developing CINV, such as patient characteristics, emetogenic potency of the chemotherapeutic agents and correct prevention of CINV. Current guidelines determine which is the right preventive regimen for each cancer patient at risk for experiencing CINV. Adherence to this guidelines and implementation in daily practice seem to be below the optimal level. In Belgium, authorities use the guidelines as a base for reimbursement and this has increased the level of implementation.     

Novel treatment approaches to fibrosis in scleroderma

The molecular mechanisms leading to tissue fibrosis were only poorly understood in the past, and even today the cause or trigger of systemic sclerosis is still unknown. Remarkable breakthrough findings have been obtained regarding the identification of key molecules, key cellular mechanisms, and key intracellular signaling cascades, which mediate the perpetuation of fibrosis rather than trigger it. These findings have true translational implications, because modifiers of these key mediators and key mechanisms are often in clinical use in other disease indications, such as cancer. This article summarizes the clinical and preclinical evidence of examples of these novel antifibrotic treatment approaches in systemic sclerosis, including stem cell transplantation, modifiers of transforming growth factor-beta1 signaling, intravenous immunoglobulins, tyrosine kinase inhibitors, and histone deacetylase inhibitors.     

Mechanisms and management of chemotherapy-induced nausea and vomiting

Only in recent years has serious attention been given to the control of chemotherapy-induced emesis (CIE) which is to the patient a most obnoxious side-effect. Important advances in the understanding of the mechanisms of CIE have led to the scientific appraisal of potential anti-emetics whilst additional, useful anti-emetics have appeared by serendipity. CIE has largely been studied in trials separating either cis-platinum (severely emetic) or non-cis-platinum(moderately emetic)-induced emesis. In the evolution of these trials the difficulty and importance of accurate evaluation of emesis has been revealed and the whole area of psychogenic emesis opened to investigation and treatment. Phenothiazines and butyrophenones have a definite modest anti-emetic role against moderately emetogenic chemotherapy but increasingly corticosteroids, benzodiazepines, high dose metoclopramide and cannabinoids are being used with great effect even with severely emetic drugs. Combination anti-emesis has further improved control rates and new schedules of currently available anti-emetics are now proving their worth. Major advances in anti-emetic control have been achieved recently and every patient at risk of CIE should have good control, if not total abolition, of emesis with appropriate use of anti-emetics.     

Managing nausea and vomiting in thoracic oncology

Nausea and vomiting are frequent symptoms that deteriorate the quality of life of lung cancer patients. They are most often iatrogenic and related to chemotherapy based on platinum salts; they can also be evidence of metastasis to the brain or hypercalcemia. Understanding the physiopathological mechanisms at work can make it possible to adopt effective therapeutic measures that are specific to each etiological context.     

Helicobacter pylori infection and postoperative nausea and vomiting

BACKGROUND/AIMS: The aim of this study was to identify factors most relevant to postoperative nausea and vomiting (PONV) and determine the association of Helicobacter pylori with PONV. METHODOLOGY: A cross-sectional analytic survey was conducted on 127 elective patients who underwent general and urological surgery at Sina Hospital in Tehran between March 2005 and March 2006. Related factors considered to have a possible effect on the prevalence of PONV events were evaluated by using a special questionnaire and serological laboratory test of H. pylori. Data was analyzed using t test and chi2 test and logistic regression analysis for comparing the variables. RESULTS: Prevalence of PONV was 54.7% in patients having H. pylori infection. There was no relationship between H. pylori infection and PONV (p>0.05). Prior history of PONV was a significant risk factor for increasing the prevalence of PONV (p<0.05). Also, history of PONV beside female gender, overweighting/obesity and operation type (urologic surgery) could increase the severity of PONV (p<0.05). But, administration of opioids could decrease the severity of PONV (p<0.05). CONCLUSIONS: It was found that PONV had a high prevalence among patients undergoing urologic and general surgery. H. pylori infection cannot affect the prevalence of PONV. More surveys are needed to develop effective protocols for preventing this common and unpleasant problem.     

Novel approaches to the treatment of non-small cell lung cancer.

Prognosis of non-small cell lung carcinomas (NSCLC) remains poor, especially in advanced disease. The introduction of new cytotoxic agents in the past decade did only attain minor improvements in survival. It is rather clear that chemotherapy may have reached a plateau, and that it will be difficult to obtain better results in advanced NSCLC by chemotherapy alone. Novel treatment modalities are urgently needed in advanced NSCLC. Backed-up by advances in the understanding of tumor cell biology, a new generation of anticancer agents specifically directed at targets such as tyrosine kinases, farnesyl transferase, angiogenesis factors, matrixmetalloproteinases and oncogenes has been developed in recent years. In this review, we give a brief summary of the state-of-the-art treatment of NSCLC, highlighting its limitations. Novel systemic approaches are then discussed in detail with focus on their mechanistic rationale, stage of clinical development and possible drawbacks. Finally, perspectives of future applications and impact on the treatment of NSCLC are also discussed.