Educational workshops with graduates of the University of Cape Town Karl Storz Head and Neck Surgery Fellowship Program: a model for collaboration in outreach to developing countries.

The University of Cape Town Karl Storz Head and Neck Surgery Fellowship is the only head and neck surgery fellowship in Sub-Saharan Africa. This article briefly describes this fellowship and outlines the experience and ongoing collaborative efforts of members of the American Academy of otolaryngology-head and neck surgery with graduates of this program who are now building head and neck surgery programs in East Africa. This educational collaboration avoids many common pitfalls associated with short-term humanitarian outreach and represents a successful model for international collaborative educational efforts with head and neck surgeons in developing countries in Africa.

Octreotide scintigraphy in the head and neck.

OBJECTIVES/HYPOTHESIS: Octreotide is a somatostatin analogue that, when coupled to a radioisotope, produces a scintigraphic image of neuroendocrine tumors (NET) expressing somatostatin type 2 receptors (SSR 2). Octreotide scintigraphy (OS) may be useful in confirming the preoperative diagnosis of certain head and neck NET. Paragangliomas (PG), like many NET, have been found to have a high density of SSR 2 on the cell surfaces. Other NET of the head and neck include merkel cell carcinomas (MCC), medullary thyroid carcinomas (MTC), and esthesioneuroblastomas. STUDY DESIGN: A retrospective study that compared the results of OS with the histopathologic diagnosis in 74 patients with head and neck NET. RESULTS: Of the 60 patients undergoing evaluation for suspected paraganglioma, OS was correctly positive in 36 of the 37 patients with PG. OS was correctly negative in 19 of the 23 patients that did not exhibit PG. For PG, this yielded a sensitivity of 97% and a specificity of 82%. There were 14 patients in the nonparaganglioma group. OS detected or diagnosed all metastases in three patients with MTC, locoregional recurrences in two patients with esthesioneuroblastoma, an extrapituitary adenoma in one patient, and metastasis in two patients with MCC. It failed to detect a paraspinal metastasis in the third patient with MCC. CONCLUSION: On the basis of this series of patients, OS appears to be a reliable test to detect PG and may be helpful in detecting primary and metastatic disease for NET.

Causation in epidemiology.

Causation is an essential concept in epidemiology, yet there is no single, clearly articulated definition for the discipline. From a systematic review of the literature, five categories can be delineated: production, necessary and sufficient, sufficient-component, counterfactual, and probabilistic. Strengths and weaknesses of these categories are examined in terms of proposed characteristics of a useful scientific definition of causation: it must be specific enough to distinguish causation from mere correlation, but not so narrow as to eliminate apparent causal phenomena from consideration. Two categories-production and counterfactual-are present in any definition of causation but are not themselves sufficient as definitions. The necessary and sufficient cause definition assumes that all causes are deterministic. The sufficient-component cause definition attempts to explain probabilistic phenomena via unknown component causes. Thus, on both of these views, heavy smoking can be cited as a cause of lung cancer only when the existence of unknown deterministic variables is assumed. The probabilistic definition, however, avoids these assumptions and appears to best fit the characteristics of a useful definition of causation. It is also concluded that the probabilistic definition is consistent with scientific and public health goals of epidemiology. In debates in the literature over these goals, proponents of epidemiology as pure science tend to favour a narrower deterministic notion of causation models while proponents of epidemiology as public health tend to favour a probabilistic view. The authors argue that a single definition of causation for the discipline should be and is consistent with both of these aims. It is concluded that a counterfactually-based probabilistic definition is more amenable to the quantitative tools of epidemiology, is consistent with both deterministic and probabilistic phenomena, and serves equally well for the acquisition and the application of scientific knowledge.

Measuring the public health burden of cancer in the United States through lifetime and age-conditional risk estimates.

PURPOSE: Effects of an aging population in the United States on lifetime and age-conditional risk estimates of developing site-specific cancers are identified and the potential role these statistics play in monitoring disease burden discussed. METHODS: Risk estimates were derived by applying cross-sectional population-based incidence rates of cancer and mortality rates from other causes to a hypothetical cohort. The cohort was aged through a double decrement life table to determine the expected proportion of the population that would develop the disease. RESULTS: Despite black men having higher invasive cancer incidence rates than white men, and black and white women having similar rates, because of the better life expectancy among whites lifetime risk estimates of developing cancer are higher for whites than blacks: 45.5% in white men, 40.4% in black men, 39.2% in white women, and 32.4% in black women based on 1995-97 data. White men experience higher 10-year cancer risk than black men in only bladder cancer, non-Hodgkin's lymphomas (NHL), and leukemia. White women tended to show a greater risk than black women for cancers of the breast, corpus uteri, ovary, NHL, and leukemia. For both whites and blacks, the 10-year risk of lung cancer ranks first among men aged 40, ranks second to prostate cancer for men aged 50, 60, and 70, and ranks second to breast cancer for women aged 40, 50, 60, and 70. CONCLUSIONS: Lifetime and age-conditional risk measures reflect both changes in the disease incidence rates and age distribution over calendar time such that they are useful for monitoring the disease burden in the population. Even if cancer rates remain stable or fall, it is possible for the cancer burden, as reflected by lifetime and age-conditional risk estimates, to increase due to the aging population.

Expression and localization of immunoreactive-sialomucin complex (Muc4) in salivary glands.

Sialomucin Complex (SMC; Muc4) is a heterodimeric glycoprotein consisting of two subunits, the mucin component ASGP-1 and the transmembrane subunit ASGP-2. Northern blot and immunoblot analyses demonstrated the presence of SMC/Muc4 in submaxillary, sublingual and parotid salivary glands of the rat. Immunocytochemical staining of SMC using monoclonal antisera raised against ASGP-2 and glycosylated ASGP-1 on paraffin-embedded sections of parotid, submaxillary and sublingual tissues was performed to examine the localization of the mucin in the major rat salivary glands. Histological and immunocytochemical staining of cell markers showed that the salivary glands consisted of varying numbers of serous and mucous acini which are drained by ducts. Parotid glands were composed almost entirely of serous acini, sublingual glands were mainly mucous in composition and a mixture of serous and mucous acini were present in submaxillary glands. Since immunoreactive (ir)-SMC was specifically localized to the serous cells, staining was most abundant in parotid glands, intermediate levels in submaxillary glands and least in sublingual glands. Ir-SMC in sublingual glands was localized to caps of cells around mucous acini, known as serous demilunes, which are also present in submaxillary glands. Immunocytochemical staining of SMC in human parotid glands was localized to epithelial cells of serous acini and ducts. However, the staining pattern of epithelial cells was heterogeneous, with ir-SMC present in some acinar and ductal epithelial cells but not in others. This report provides a map of normal ir-SMC/Muc4 distribution in parotid, submaxillary and sublingual glands which can be used for the study of SMC/Muc4 expression in salivary gland tumors.

A novel CD44 v3 isoform is involved in head and neck squamous cell carcinoma progression.

OBJECTIVES: CD44 comprises a family of isoforms involved in tumorigenesis. Here we investigate the role of CD44 isoforms in head and neck squamous cell carcinoma (HNSCC) progression. MATERIALS AND METHODS: HNSCC specimens underwent reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. After surface biotinylation, FaDu (hypopharyngeal HNSCC) and CD44v3-transfected COS-7 cells were CD44 antibody-precipitated and compared by Western blot analysis. FaDu cells underwent double immunofluorescence staining and growth assays. RESULTS: Southern blot analysis suggested differential CD44v3 isoform expression in tumor and normal tissue. Cloning and sequencing revealed 2 novel CD44v isoforms. Western blot analysis suggested CD44v3 expression in COS-7 transfectants and FaDu. Double immunofluorescence staining revealed co-localization of CD44v3 and actin in FaDu projections. Anti-CD44v3 antibody decreased FaDu growth. CONCLUSION: HNSCC tissue and FaDu appear to express CD44v3 isoforms. These isoforms may promote tumorigenesis. CLINICAL SIGNIFICANCE: CD44v3 isoforms may be effective tumor markers and targets for HNSCC therapy.

Comparison of information processing technologies.

OBJECTIVE: To examine the type of information obtainable from scientific papers, using three different methods for the extraction, organization, and preparation of literature reviews. DESIGN: A set of three review papers was identified, and the ideas represented by the authors of those papers were extracted. The 161 articles referenced in those three reviews were then analyzed using 1) a formalized data extraction approach, which uses a protocol-driven manual process to extract the variables, values, and statistical significance of the stated relationships; and 2) a computerized approach known as "Idea Analysis," which uses the abstracts of the original articles and processes them through a computer software program that reads the abstracts and organizes the ideas presented by the authors. The results were then compared. The literature focused on the human papillomavirus and its relationship to cervical cancer. RESULTS: Idea Analysis was able to identify 68.9 percent of the ideas considered by the authors of the three review papers to be of importance in describing the association between human papillomavirus and cervical cancer. The formalized data extraction identified 27 percent of the authors' ideas. The combination of the two approaches identified 74.3 percent of the ideas considered important in the relationship between human papillomavirus and cervical cancer, as reported by the authors of the three review articles. CONCLUSION: This research demonstrated that both a technically derived and a computer derived collection, categorization, and summarization of original articles and abstracts could provide a reliable, valid, and reproducible source of ideas duplicating, to a major degree, the ideas presented by subject specialists in review articles. As such, these tools may be useful to experts preparing literature reviews by eliminating many of the clerical-mechanical features associated with present-day scientific text processing.

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract.

OBJECTIVES: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. STUDY DESIGN: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. RESULTS: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. SIGNIFICANCE: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors.

Application of population screening principles to genetic screening for adult-onset conditions.

Recent advances in molecular genetics have highlighted the potential use of genetic testing to screen for adult-onset chronic diseases. Several issues must be addressed, however, before such tests can be recommended for population-based prevention programs. These issues include the adequacy of the scientific evidence, the balance of risks and benefits, the need for counseling and informed consent, and the costs and resources required. Ongoing assessment of the screening program and quality assurance of laboratory testing are also needed. This paper considers the application of general principles for mass screening to genetic testing for susceptibility to adult-onset chronic diseases. Evaluation of proposals for genetic screening in context of these principles reveals that needed evidence is often absent, particularly with respect to the predictive value of tests, efficacy of interventions, and social consequences of testing. The principles of population screening are developed into a framework for public health policy on genetic screening that has three stages: assessment of the screening test and interventions for those who test positive, including assessment of risks and costs, policy development, and program evaluation. Essential elements are identified, including evaluation of evidence and processes for consensus development and program evaluation. The proposed framework for public health policymaking outlined in this commentary, when combined with future efforts that involve an authoritative consensus process, may be useful for the evaluation and planning of genetic screening programs aimed at reducing morbidity and mortality from adult-onset chronic diseases.

Theory and practice in epidemiology.

Scientific and ethical theories are examined in terms of the practice of epidemiology, the study of the determinants and distributions of disease, and the application of the knowledge gained to prevent disease and improve the health of populations. Scientific theories provide explanations and predictions for epidemiologic studies of disease etiology and prevention. Causal theory is the key example for epidemiologic science, although theories of selection processes, theories of health, and theories of probability and statistics are also core. Theories of ethics provide principles, warrants, and methods for acting upon the knowledge gained in the scientific pursuits of epidemiology and for obtaining that knowledge appropriately. Ethical theories guide practitioners in making justified decisions about when and under what conditions public health interventions should be undertaken and how research participants should be treated. Theories of midlevel bioethical principles have received the most attention in epidemiology, but other theories, such as virtue theory and communitarian theory, are also relevant. Many theories matter to the practice of epidemiology: theories of biology, aging, evolution, and medicine; theories of history, religion, law, economics, and politics, as well as the theories of the physical, behavioral, and social sciences. These theories matter because epidemiologists study many different biological and social phenomena, and preventive interventions occur at many different levels of explanation. Development of theory is not a high priority in contemporary epidemiology. Identifying the responsibilities of the discipline to be public health intervention and rigorous science is a first step toward developing and applying theory in epidemiology.

Advocacy in epidemiology and demography.

This paper is a summary of a panel discussion at the Conference on Epidemiology and Demography held at Georgetown University, in Washington D.C. on February 8-9, 2001. The participants were Al Hermalin, Linda Martin, Mike Stoto, Robert Wallace, Douglas Weed, and Rose Li (who chaired the session). A list of questions similar to the section headings in this paper was prepared in advance of the conference, and each of the participants was asked to address specific issues, although the presentations typically covered a range of topics. This summary also includes comments from the floor.

Epidemiologic evidence and causal inference.

Preventing cancer depends on the ability to recognize and remove causal factors. In current practice, the methods used to judge cause from epidemiologic, clinical trials and biologic evidence include systematic narrative reviews, criteria-based inference methods, and meta-analysis. Subjectivity and values play a key role in the practice of causal inference, especially in selecting criteria and assigning rules of evidence to those criteria. Judging cause is a central concern of physicians, epidemiologists, and other public health professionals committed to cancer prevention.

Investigation of design and bias issues in case-control studies of cancer screening using microsimulation.

Using a microsimulation approach, the authors examined design and bias issues in case-control studies of cancer screening. Specifically, they looked at the impact on the odds ratio of the way in which exposure to screening is defined, the type of age matching, the time scale used, and the criteria used to determine control eligibility. The results showed that defining exposure as "ever/never" screened produced, as expected, a serious bias in favor of screening. Defining exposure as being screened no later than the time the case's cancer is diagnosed has a serious bias against screening. An alternative exposure definition--screening can occur no later than the time the case would have been clinically diagnosed--eliminates the bias against screening. Further, the results showed that the type of age matching and the time scale used can produce a bias against screening and that this bias can be quite strong when case-control studies are performed in populations with a periodic screening program that is the only source of screening. Finally, control eligibility criteria had little effect.

Interpreting epidemiological evidence: how meta-analysis and causal inference methods are related.

Interpreting observational epidemiological evidence can involve both the quantitative method of meta-analysis and the qualitative criteria-based method of causal inference. The relationships between these two methods are examined in terms of the capacity of meta-analysis to contribute to causal claims, with special emphasis on the most commonly used causal criteria: consistency, strength of association, dose-response, and plausibility. Although meta-analysis alone is not sufficient for making causal claims, it can provide a reproducible weighted average of the estimate of effect that seems better than the rules-of-thumb (e.g. majority rules and all-or-none) often used to assess consistency. A finding of statistical heterogeneity, however, need not preclude a conclusion of consistency (e.g. consistently greater than 1.0). For the criteria of strength of association and dose-response, meta-analysis provides more precise estimates, but the causal relevance of these estimates remains a matter of judgement. Finally, meta-analysis may be used to summarize evidence from biological, clinical, and social levels of knowledge, but combining evidence across levels is beyond its current capacity. Meta-analysis has a real but limited role in causal inference, adding to an understanding of some causal criteria. Meta-analysis may also point to sources of confounding or bias in its assessment of heterogeneity.

Sensory recovery in melolabial flaps used for oral cavity reconstruction.

Current literature advocates the use of complex reinnervated free flaps to re-establish oral sensation after resection of oral cavity cancers. It has been demonstrated that noninnervated flaps can also re-establish sensation. We assessed the return of sensation in local melolabial flaps used in oral reconstruction. Seven patients underwent sensory testing at intervals from 12 to 18 months after surgery. The ability to distinguish differences in temperature was present in all patients. Spontaneous return of sensitivity to touch was documented by clinical testing in 71% of the patients. Less return of sensation was seen in flaps used for defects of the buccal mucosa relative to the floor of mouth. We conclude that spontaneous return of flap sensation does occur with local melolabial flaps. Given the simplicity of these procedures, melolabial flaps represent a reasonable alternative in floor-of-mouth reconstruction for selected patients.