The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Orofacial pain in cancer: part I--mechanisms.

The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poorly understood. The aim of the first of this two-part series is to review the involved pathophysiological mechanisms and explore their possible roles in the orofacial region. However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.

Orofacial pain in cancer: part II--clinical perspectives and management.

Cancer-associated pain is extremely common and is associated with significant physical and psychological suffering. Unfortunately, pain associated with cancer or its treatment is frequently under-treated, probably due to several factors, including phobia of opioids, under-reporting by patients, and under-diagnosis by healthcare workers. The most common etiology of cancer pain is local tumor invasion (primary or metastatic), involving inflammatory and neuropathic mechanisms; these have been reviewed in Part I. As malignant disease advances, pain usually becomes more frequent and more intense. Additional expressions of orofacial cancer pain include distant tumor effects, involving paraneoplastic mechanisms. Pain secondary to cancer therapy varies with the treatment modalities used: Chemo-radiotherapy protocols are typically associated with painful mucositis and neurotoxicity. Surgical therapies often result in nerve and tissue damage, leading, in the long term, to myofascial and neuropathic pain syndromes. In the present article, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. As a presenting symptom of orofacial cancer, pain is often of low intensity and diagnostically unreliable. Diagnosis, treatment, and prevention of pain in cancer require knowledge of the presenting characteristics, factors, and mechanisms involved.