Jennifer McCann, PharmD, BCPS, BCCCP

• Assistant Professor of Pharmacy Practice, Butler University College of Pharmacy and Health Sciences, Indianapolis, Indiana

The numbers of patients in each individual study are smaller than in the atomic bomb survivors insomnia 8 weeks pregnant cheap provigil 100 mg with mastercard, but the number of such studies is relatively large insomnia drugs purchase provigil 100 mg without prescription. Because such populations generally receive localized exposures insomnia google purchase provigil 200 mg with amex, these groups generally provide information on cancer risks in specific organs and tissues insomnia xkcd quality 200mg provigil. Such populations also have provided insight into modifying factors, such as age and genetic background. Studies of second cancers after radiation therapy has become an increasingly important source of information. In the past, radiation was used to treat a number of benign disorders, including enlarged thymus glands and tonsils, tinea capitis, ankylosing spondylitis, and peptic ulcers. In general, diagnostic procedures result in very low radiation exposures; however, a few studies have provided evidence for increased cancer risks. One of the most intensively studied of these is a group of tuberculosis patients who were subjected to multiple diagnostic fluoroscopies during their treatment. Although individual doses were low, the number of exposures resulted in the accumulation of relatively large doses. As is the case for other carcinogenic agents, occupational exposures also have been a valuable source of information. Studies of uranium miners and other underground miners have been a particularly valuable source of information on risks of lung cancer after exposure to radon. Most skin cancers are basal cell and squamous cell carcinomas, whereas there is little evidence for the induction of melanomas. In general, bone sarcoma and cancer of connective tissues require relatively high doses before a significant increased risk can be detected. No clear evidence exists for the induction of cancers of the pancreas, prostate, uterine cervix, small intestine, or most childhood cancers (except for acute leukemia). In general, solid cancers do not appear until 10 or more years after the radiation exposure, and it is not unusual for the latent period to exceed 20 years. For example, the appearance of breast cancer is greatly influenced by age at the time of irradiation. The time between radiation exposure and the appearance of breast cancer is quite long for a prepubertal or adolescent girl, whereas for a woman in her late twenties or early thirties, the latent period is generally shorter. A close look at the relationship between age at exposure and time of appearance for breast cancer indicates that these radiation-induced cancers appear at a time when the natural incidence of these cancers is also rising. This is likely a result of host factors that play an important role in breast cancer development and that also appear to strongly influence the expression of radiation-initiated cells. These data have important implications for potential mechanisms of radiation carcinogenesis. These very long latent periods, particularly for younger individuals, are also important to remember when assessing risks associated with specific treatment protocols. Dose-Response Relationships Understanding the relationship between cancer frequency, or risk, and radiation dose is important for providing insight into mechanisms underlying radiation carcinogenesis. It is also important for estimating risks at low doses for which effects cannot be directly determined from experimental or epidemiologic studies. Accurate risk estimates at low doses are essential in regulating environmental and occupational exposures. The question of whether the benefits of this screening outweigh the risks for inducing new breast cancers depends on many complex issues, but central to these issues is the risk of breast cancer from the doses received. It is virtually impossible to observe an increase in risk in an epidemiologic study at the low doses received as a result of a single mammographic procedure (or for that matter any diagnostic procedure) (Table 12-2), so estimates must be based on models of dose-response relationships that allow estimates to be derived. Mainly because of these low-dose risk issues, a substantial amount of effort in epidemiologic studies and in experimental studies of radiation carcinogenesis has been to define dose-response relationships and test predictions of dose-response models. Approximate Doses from Common Diagnostic Procedures From theoretical models of radiation interactions at the cellular and molecular level, and from experimental and epidemiologic studies, two dose-response models are most prominent: the linear model and the linear-quadratic model. With the linear-quadratic model, risk at low doses is linearly related to dose, whereas at higher doses, the risk increases more rapidly as a function of dose. The linear-quadratic model is based on biophysical theories of radiation interactions. The bD 2 component represents effects produced by the interaction of multiple ionization tracks, whereas the aD component represents effects produced by single ionization tracks. Therefore, any effects observed, such as a double-strand break or a chromosome aberration, must have been a result of effects produced by such single tracks. At higher doses, in which multiple tracks would be traversing a cell, such effects would be expected to be a result of interactions of damage produced by these multiple tracks. Because the probability of inducing a complex type of damage, such as a double-strand break, is greater with multiple events occurring in close proximity, the dose response would be expected to rise more rapidly than at low doses. For densely ionizing radiation, ionization tracks through a cell are few, but the density of the ionization is sufficient to produce complex effects with single tracks with a high probability. As a result, the dose response is expected to be linear over a wide range of doses. Irrespective of the model, the prediction at low doses is that the dose response is linear. This prediction implies that any dose of radiation received has a probability of inducing damage and, therefore, results in some increased risk for cancer development. Although there is some argument about this assumption at very low doses because of the repair and damage response capabilities of cells, current information about underlying mechanisms of cancer induction by ionizing radiation would tend to support the view that any dose of radiation confers some degree of risk. At high dose, the linear quadratic and linear models differ not only in form but also in predictions about risks at low dose rates and fractionated exposures. The linear model in its most simple form predicts that lowering the dose rate or giving many small fractions confers the same cancer risk as the same dose delivered as a single, high dose-rate exposure. The linear-quadratic model predicts that, at high total doses, reducing the rate at which the total dose is received or giving the dose in multiple small fractions reduces the risk. A dose of 4 Gy delivered instantaneously would have the chance of being lethal in a short time, whereas that same dose accumulated over a lifetime would not produce such acutely lethal effects. But whether this same concept holds for the damage that results in increased cancer risk is not certain. Theoretically, because effects are likely to be a result of the interaction of damages produced by independent tracks, lowering the dose rate or fractionating the exposure reduces the probability of the interaction of damage because of cellular repair processes that rapidly respond to such damage. If this theory applies to the damage responsible for radiation-induced cancers, the cancer risk at low dose rates and after low dose fractions would be lower than that predicted from high dose, high dose-rate exposures. At very low dose rates and very low doses per fraction, this results in a predicted dose response that simply is a continuation of the slope of the dose-response curve at low doses [i. Whether this model is appropriate and the degree of the so-called dose-rate effect is a matter of debate and study. Epidemiologic and experimental data are not adequate to resolve the issue at the present time. Analyses of results from epidemiologic studies of the atomic bomb survivors suggest a linear quadratic dose response for the induction of all leukemia, although a simple linear model also fits the data. It must be remembered that the solid tumor data are incomplete at present because of the late onset of these cancers and because a significant fraction of the population who were children and young adults at the time of the bombing are still alive. Studies of radiation-induced breast cancer in the atomic bomb survivors support a linear dose response over a wide range of doses. Although the doses from the individual fluoroscopies were small, relatively large total doses were accumulated. Analysis of these data suggest similar risks for radiation-induced breast cancer in this group compared with those derived from the atomic bomb survivors and other groups who received radiation at a high dose rate. Comparing the risk for lung cancer in the groups receiving fractionated exposures from fluoroscopy to the risk in the atomic bomb survivors indicates that fractionation resulted in a markedly decreased risk for radiation-induced lung cancer. Experimental studies examining dose-response relationships for leukemia and a variety of solid cancers generally support the linear-quadratic model. Interestingly, in mice the dose-rate effect for the induction of lung cancer is greater than that for breast cancer. However, data for mammary tumors in mice, and for transformation in vitro, have shown a so-called inverse dose-rate effect in which doses delivered at low dose rates were seen to be more effective with respect to cancer induction than single acute exposures. Increased risks for thyroid cancer are primarily found after exposure of children to radiation, whereas the risk in adults after exposure to radiation is small. For women older than 45 to 50 years of age, radiation appears to have little influence on breast cancer risk. However, it is generally accepted that an increased risk exists for childhood cancers, including leukemia, from in utero exposure, which should be avoided.

Epidermolysis bullosa: a spectrum of clinical phenotypes explained molecular heterogeneity insomnia ypsilanti mi buy generic provigil 200mg line. Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 20 polycystic ovary syndrome and 10 control families sleep aid costco order provigil 200 mg with amex. A new contributing factor to polycystic ovary syndrome: the genetic variant of luteinizing hormone sleep aid ar purchase provigil 100 mg amex. Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene insomnia 6 months pregnant cheap provigil 200mg otc. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis. Long-term follow-up of von Recklinghausen neurofibromatosis: survival and malignant neoplasms. A novel moesin-, ezrin-, radaixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor [published erratum appears in Cell 1993 19;75:826]. National Institutes of Health Consensus Development Conference Statement on Acoustic Neuroma, December 1113, 1991. Interstitial del(11p) as a cause of the aniridia-Wilms tumor association: band localization and a heritable basis. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Screening of children with hemihypertrophy, aniridia, and Beckwith-Wiedemann syndrome in patients with Wilms tumour: a report from the National Wilms Tumour Study. Excess risk of breast cancer in the mothers of children with soft tissue sarcomas. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. Detection of novel germ-line p53 mutations in diverse-cancer-prone families identified by selecting patients with childhood adrenocortical carcinoma. Linkage studies in a Li-Fraumeni family with increased expression of p53 protein but no germline mutation in p53. Recommendations on predictive testing for germ line p53 mutations among cancer prone individuals. Meeting report: collaborative interdisciplinary studies of p53 and other predisposing genes in Li-Fraumeni syndrome. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. The relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type 1. Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9. Mutations of the human homologue of Drosophila patched in the nevoid basal cell carcinoma syndrome. Identification and characterization of the familial adenomatous polyposis coli gene. Familial adenomatous polyposis: mutation at codon 1309 and early onset of colon cancer. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. Etiology, natural history, management and molecular genetics of hereditary nonpolyposis colorectal cancer (Lynch syndromes): genetic counseling implications. Through epidemiologic studies, we have learned about changing patterns of cancer incidence and mortality worldwide, risk factors for specific cancers, potential prevention strategies, and the role of genetic variation in cancer etiology. Leads from these studies have formed the basis of many laboratory investigations that have revealed biologic mechanisms for the associations first described in epidemiologic studies. It is beyond the scope of this chapter to detail the complex methodology of epidemiologic studies. Similar to clinical trials, epidemiologic studies are of human populations and, therefore, are frequently multiple years in duration and subject to certain limitations. Epidemiologic studies are usually observational and sometimes opportunistic, to learn as much as possible when humans are unexpectedly exposed to potentially harmful substances. An example is the long-term study of the population of Seveso, Italy, after the 1976 explosion that exposed the local population to high levels of 2,3,7,8-tetrachlorodibenzo-para-dioxin. These studies have greatly enhanced our understanding of cancer biology and have affected treatment. This chapter focuses predominantly on observational studies, since the experimental approach is covered in other chapters on prevention and clinical trials. Descriptive studies are usually large, population-level studies of patterns of disease based on demographic data, such as age, gender, race, geographic residence, calendar year, type of cancer, and possibly other attributes. Descriptive studies provide important information for public health decisions and are often hypothesis-generating. Examples of these studies are the comparison of cancer rates among migrants to a different country, such as the evaluation of breast and colon cancer in Asians after migration to Western countries9,10 and the evaluation of melanoma among individuals of British origin in Australia. Examples would be the resultant investigation of the role of Western diet and lifestyle among Asian migrants to the United States12,13 and the role of sun exposure in the development of melanoma among migrants to Australia. The inference of causation from epidemiologic studies is quite complex; there are no fixed and agreed-on criteria to establish causation. No one analytic study, however large and methodologically robust, is likely to "prove" a causal association. Because epidemiologic studies are largely observational, it is important to replicate findings from one study in other groups or populations to evaluate the consistency of the results. The consistency of results should be interpreted taking into account the relative rigor of both the study designs and the conduct of the investigations and the size and statistical power of the studies. Within appropriately designed and conducted studies, the magnitude of the risks demonstrated and the statistical significance of the risks are important. Evidence of increasing risk of cancer with increasing exposure to a risk factor strengthens a postulated association. Data from studies must be interpreted within the current body of knowledge of that exposure and that cancer. There needs to be sufficient time between the exposure and the development of cancer as well as biologic plausibility of the exposure. Animal studies demonstrating carcinogenicity of an exposure lend credence to the hypothesis. In trying to determine whether an association found in an investigation is plausible and valid, it is important to consider the possibility of bias in the data, confounding factors, and chance associations. Bias can result from a flaw in the design of the study or in the collection of the data. For instance, the study could be designed such that individuals with cancer are identified several months after the cancer is diagnosed. For individuals with a cancer for which there is high survival, this may not be a problem. For individuals with a cancer for which the survival is poor and mortality is rapid, only a subset of better-prognosis individuals would be alive to participate. This subset of individuals may fundamentally differ from those with more aggressive disease in host susceptibility or in risk factor exposures, if either is related to more aggressive disease. If there is differential effort in locating individuals with specific exposures or differential effort in locating individuals who may have become ill, there could be profound effects on the data. If interviewers know who has cancer and who does not, they may be (even unconsciously) more persistent in prompting individuals with cancer for answers to specific questions. These types of difficulties cannot be accommodated well in the data analyses and affect how one can interpret the results. Confounders are variables associated with disease risk and with an exposure under investigation. Confounder variables must demonstrate three characteristics: (1) the confounder must be related to disease risk in individuals with and without the exposure of interest; (2) the confounder variable must be associated with the exposure of interest in the group from which the study participants come; and (3) a confounding variable cannot be an intermediate end point in the development of disease. An example of a confounder would be cigarette smoking in participants in a case-control study that is investigating the role of alcohol consumption in the etiology of oral cancer.

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Carriers are foreign proteins to which small nonimmunogenic antigens sleep aid vs ambien 200 mg provigil fast delivery, or haptens insomnia lyrics generic 100mg provigil visa, can be coupled to render the hapten immunogenic sleep aid pregnant order 200mg provigil fast delivery. In vivo insomnia 2017 buy provigil 200 mg fast delivery, self proteins can also serve as carriers if they are correctly modified by the hapten; this is important in allergy to drugs. Caseation necrosis is a form of necrosis seen in the center of large granulomas, such as the granulomas in tuberculosis. Caspases are a family of closely related cysteine proteases that cleave proteins at aspartic acid residues. They have a far less diverse receptor repertoire than conventional B cells, and since they are the first B cells to be produced they are also known as B-1 cells. They recognize antigens, for example viral antigens, that are synthesized in the cytoplasm of a cell. It is expressed in different isoforms on different cell types, including the different subtypes of T cells. Cell-mediated immunity, or a cell-mediated immune response, describes any adaptive immune response in which antigen-specific T cells have the main role. It is defined operationally as all adaptive immunity that cannot be transferred to a naive recipient with serum antibody. In humans, B lymphocytes develop in bone marrow, whereas T lymphocytes develop within the thymus from bone marrowderived progenitors. Central tolerance is tolerance that is established in lymphocytes developing in central lymphoid organs. Centroblasts are large, rapidly dividing cells found in germinal centers, and are the cells in which somatic hypermutation is believed to occur. Centrocytes are the small B cells in germinal centers that derive from centroblasts. Chediak Higashi syndrome is caused by a defect in a protein involved in intracellular vesicle fusion. Phagocytic cell function is affected as lysosomes fail to fuse properly with phagosomes and there is impaired killing of ingested bacteria. Chemokines are small chemoattractant proteins that stimulate the migration and activation of cells, especially phagocytic cells and lymphocytes. Most lymphoid tumors, and many other tumors, bear chromosomal translocations that mark points of breakage and rejoining of different chromosomes. Chronic granulomatous disease is an immunodeficiency disease in which multiple granulomas form as a result of defective elimination of bacteria by phagocytic cells. The cell-surface receptor called c-Kit is found on many immature hematopoietic cells. The classical pathway of complement activation is the pathway activated by C1 binding either directly to bacterial surfaces or to antibody, that serves as a means of flagging the bacteria as foreign. Clonal deletion is the elimination of immature lymphocytes on binding to self antigens to produce tolerance to self, as required by the clonal selection theory. Clonal deletion is the main mechanism of central tolerance and can also occur in peripheral tolerance. Clonal expansion is the proliferation of antigen-specific lymphocytes in response to antigenic stimulation and precedes their differentiation into effector cells. It is an essential step in adaptive immunity, allowing rare antigen-specific cells to increase in number so that they can effectively combat the pathogen that elicited the response. It states that adaptive immune responses derive from individual antigen-specific lymphocytes that are self-tolerant. These specific lymphocytes proliferate in response to antigen and differentiate into antigenspecific effector cells that eliminate the eliciting pathogen, and memory cells to sustain immunity. The theory was formulated by Sir Macfarlane Burnet and in earlier forms by Niels Jerne and David Talmage. A cloned T-cell line is a continuously growing line of T cells derived from a single progenitor cell. Cloned T-cell lines must be stimulated with antigen periodically to maintain growth. A feature unique to individual cells or members of a clone is said to be clonotypic. Thus, a monoclonal antibody that reacts with the receptor on a cloned T-cell line is said to be a clonotypic antibody and to recognize its clonotype or the clonotypic receptor of that cell. The coagulation system is a proteolytic cascade of plasma enzymes that triggers blood clotting when blood vessels are damaged. The expression of a gene is said to be codominant when both alleles at one locus are expressed in roughly equal amounts in heterozygotes. A coding joint is formed by the imprecise joining of a V gene segment to a (D)J gene segment in immunoglobulin or T-cell receptor genes. Collectins are a structurally related family of calcium-dependent sugar-binding proteins or lectins containing collagen-like sequences. Antigen receptors manifest two distinct types of combinatorial diversity generated by the combination of separate units of genetic information. Receptor gene segments are joined in many different combinations to generate diverse receptor chains, and then two different receptor chains (heavy and light in immunoglobulins; a and b or g and d in T-cell receptors) are combined to make the antigen-recognition site. It plays a key role in the intracellular signaling mediated by these receptors as shown by gene knockout. Common variable immunodeficiency is a relatively common deficiency in antibody production whose pathogenesis is not yet understood. Competitive binding assays are serological assays in which unknowns are detected and quantitated by their ability to inhibit the binding of a labeled known ligand to its specific antibody. When known sources of antibody or antigen are used as competitive inhibitors of antigenantibody interactions, this assay is referred to as a competitive inhibition assay. The complement system is a set of plasma proteins that act together to attack extracellular forms of pathogens. Complement activation can occur spontaneously on certain pathogens or by antibody binding to the pathogen. The pathogen becomes coated with complement proteins that facilitate pathogen removal by phagocytes and can also kill certain pathogens directly. Complement receptors on phagocytes allow them to identify pathogens coated with complement proteins for uptake and destruction. In confocal fluorescent microscopy, it is possible to use optics to produce images at very high resolution by having two origins of fluorescent light that come together only at one plane of a thicker section. Conformational epitopes, or discontinuous epitopes, on a protein antigen are formed from several separate regions in the primary sequence of a protein brought together by protein folding. Each strain is generated by the repetitive back-crossing of mice carrying the desired trait onto a strain that provides the genetic background for the set of congenic strains. Conjugate vaccines are vaccines made from capsular polysaccharides bound to proteins of known immunogenicity, such as tetanus toxoid. The constant region (C region) of an immunoglobulin or T-cell receptor is that part of the molecule that is relatively constant in amino acid sequence between different molecules. In an antibody molecule the constant regions of each chain are composed of one or more C domains. A contact hypersensitivity reaction is a form of delayed-type hypersensitivity in which T cells respond to antigens that are introduced by contact with the skin. Poison ivy hypersensitivity is a contact hypersensitivity reaction due to T-cell responses to the chemical antigen pentadecacatechol in poison ivy leaves. Continuous epitopes, or linear epitopes, are antigenic determinants on proteins that are contiguous in the amino acid sequence and therefore do not require the protein to be folded into its native conformation for antibody to bind. A convertase is an enzymatic activity that converts a complement protein into its reactive form by cleaving it. Red blood cells that are coated with antibody are agglutinated if they are exposed to an anti-immunoglobulin antibody. The Coombs test is important in detecting the nonagglutinating antibodies against red blood cells produced by Rh incompatibility in pregnancy. Two binding sites are said to demonstrate cooperativity in binding to their ligand when the binding of ligand to one site enhances the binding of ligand to the second site. A co-receptor is a cell-surface protein that increases the sensitivity of the antigen receptor to antigen by binding to associated ligands and participating in signaling for activation. Corticosteroids are a family of drugs related to steroids that are naturally produced in the adrenal cortex, such as cortisone. Corticosteroids can kill lymphocytes, especially developing thymocytes, inducing apoptotic cell death.

Tumors of the nasal septum can be approached through a lateral rhinotomy or by a midface degloving technique sleep aid apps purchase 200 mg provigil visa. Wong and Cummings have pointed out that most patients presented with lesions that are less than or equal to 5 cm sleep aid tablets buy provigil 100mg without prescription, and less than 10% present with lymph node metastases sleep aid safe for breastfeeding provigil 200mg with mastercard. Given the high propensity for local recurrence insomnia yoga nidra buy cheap provigil 100mg on line, combined modality therapy consisting of surgery and radiation should be used in most circumstances. Treatment of Paranasal Sinus Cancers For cancers of the maxillary sinus, maxillectomy is the procedure of choice and generally is combined with postoperative radiation. For most lesions, maxillectomy entails a standard Weber-Fergusson incision through skin of the anterior face. The bone cuts used depend on the decision to preserve or resect the orbital floor and orbital contents. It should be recognized that multiple procedures are encompassed by the term maxillectomy dependent on the extent or resection of the bony framework. Furthermore, the management of the eye in patients with paranasal sinus cancer remains controversial. Surgeons would advocate resection of orbital contents in patients whose tumors transgress the orbital floor and infiltrate orbital contents. In certain circumstances, however, invasion of orbital floor by maxillary sinus cancers cannot be determined preoperatively. However, ocular motion may be impaired and diplopia can result from such a procedure secondary to loss of structural support of orbital contents. This complication has led to numerous procedures for reconstructing the resected orbital floor including median galeal pericranial flaps. This fascial plane is rarely involved in their series, even in the presence of periorbital involvement. The authors note radiographic assessment cannot discriminate involvement of this fascial plane. The authors go on to note that ocular function with preservation of this fascial plane, even when combined with postoperative radiation, is good. With advances in surgical technique and cumulative experience, factors that classically are considered to preclude surgical excision are continually evolving. Disease involving dura, although associated with an adverse outcome, in selected instances can be controlled surgically. Survival of patients with olfactory neuroblastoma is far superior to those with adenocarcinoma. Involvement of brain parenchyma and extensive involvement of the infratemporal fossa from tumors of the maxillary sinus has not been considered amenable to surgical resection for cure. Each of the decisions regarding resectability should be tempered by the skill of the primary surgeon and availability of neurosurgical and reconstructive expertise. A major decision in the treatment of paranasal sinus involves reconstruction of the surgical defects. Multiple methods of reconstruction have been advocated including temporal muscle slings, skin grafts, and even composite flaps containing bone. In general, elective treatment of regional lymph nodes in patients without clinical evidence of lymph node metastases is not indicated. The group of patients who had a grossly complete operation, leaving only microscopic residual, enjoyed 79% local control. Local failure remains the most frequent site of failure in the treated surgery, occurring at rates ranging from 10% to more than 40%, emphasizing the need for effective multimodality therapy. Results were dependent on histology, with only a 17% local control in patients with adenoid cystic carcinoma. Although these data support using radiation alone for the occasional stage I patient, the results with more advanced stages are clearly suboptimal. Only two patients had T1 lesions, 12 patients had T2 lesions, 117 had T3 lesions, and 198 had T4 lesions. It is clear that the reported local control rates for paranasal sinus tumors are suboptimal. A patient with squamous cell carcinoma of the right maxillary antrum, with disease extension toward the medial portion of the right eye. The target volume is seen, and the isodose curve shows that the isodose line covers the target volume well. The anterior field has a block for the lateral aspect of the orbit, thereby protecting the lacrimal gland. The left lateral field has blocking for the spinal cord, optic chiasm, and left eye. B: the same patient, with a cut through a level below the orbits but through the maxillary antrum. Chemotherapy for Cancer of the Paranasal Sinuses Information on the role of chemotherapy in treating paranasal sinus cancer is limited because these patients are usually reported as a subset of a larger series of head and neck cancer patients. One form of chemotherapy that is specific to paranasal sinus cancer is intraarterial drug delivery. The rationale is based on the steep dose-response curve exhibited by most cytotoxic drugs. The rationale for using this method of drug delivery for maxillary sinus cancers in particular is to increase local control and to preserve the orbit. In 19 cases of residual tumor after therapy, partial resection of the maxilla and intracavitary irradiation were effective in eradicating the tumor. In question, however, as cisplatin-based combination chemotherapy regimens evolved, was whether the intraarterial route afforded any advantage over intravenous administration. More recent trials used intraarterial cisplatin alone or combined with other agents in sequence or simultaneously with radiotherapy. Of 18 patients who were initially judged to need orbital exenteration, only 7 required it. The complete response rate was 32% and partial response rate was 50%, which is comparable with that reported for combination chemotherapy administered intravenously. The median survival of untreated patients who achieved complete response was 21 months; for those achieving partial response it was 13 months, and for those achieving no response it was 3 months. For patients treated for recurrent disease who achieved a complete response, the median survival was 16 months; for those who achieved a partial response it was 13. These results compared favorably with a 40% survival rate for historic controls treated with surgery and radiotherapy. None of the complete responders have had a local recurrence, although median follow-up is only 1 year. These encouraging results for unresectable paranasal sinus cancer raise the issue as to whether this combined modality approach could be successful in earlier stage disease. Interesting results have come from Robbins and colleagues using their Rad-Plat protocol of 150 to 200 mg/m2 of cisplatin weekly for up to four doses through a microcatheter placed angiographically to selectively encompass the dominant tumor supply. This intraarterial regimen is continuing to be studied by this group in patients with locally advanced head and neck cancer, and high complete response rates have been achieved. For patients with paranasal sinus cancer who need orbital exenteration or major craniofacial resection, the option of intraarterial chemotherapy as induction therapy to preserve the eye should be considered as an alternative treatment. The population diets of these regions are what contributes a link to disease development. The cooking of such food releases volatile nitrosamines that are distributed over nasopharyngeal mucosa when carried by steam. An increased odds ratio of disease was also demonstrated in individuals who carry the B17 antigen. Anteriorly it is in continuity to the nasal cavity by way of the posterior choanae. The roof is formed by the basisphenoid, the basiocciput, and the anterior arch of the atlas. The lateral walls of the nasopharynx contain the eustachian tube openings, which lie within the elevations of the torus tubarii. Lymphatic drainage from the nasopharynx encompasses all levels within the neck as it proceeds along the jugular vein and spinal accessory nerve. Extensive lymphatics within the nasopharynx also drain into the retropharyngeal nodes medial to the carotid artery. It characteristically is associated with a lymphoid infiltrate that accounts for its more familiar description, lymphoepithelioma.