A case-control study of element levels and cancer of the upper aerodigestive tract

A population-based case-control study was conducted in western Washington state to investigate possible dietary risk factors for laryngeal, esophageal, and oral cancers. Using results from a food frequency questionnaire, past dietary intakes of iron, zinc, and calcium were estimated for 661 cases and 466 controls. Clippings were also taken from the nails of both halluces to determine concentrations of iron, zinc, calcium, chromium, and cobalt in 507 of the cases and 434 of the controls. After adjustment for smoking, alcohol, and dietary beta-carotene and vitamin C intake, individuals who reported dietary intakes of iron and zinc in the upper quartile were less likely to develop cancers of the larynx and esophagus than were individuals with intakes in the lowest quartile [odds ratios (OR), 0.5 for iron and 0.1 for zinc]. However, there were no significant differences in zinc concentrations in nail tissue between subjects with these types of cancer and controls. Esophageal cancer cases had higher nail concentrations of iron and calcium than did controls (OR, 2.9 for high versus low quartiles of iron; OR, 2.6 for high versus low quartiles of calcium). Individuals who developed esophageal or oral cancer were more likely to have elevated cobalt concentrations in their nail tissue than were individuals without cancer (OR, 9.0 and 1.9 respectively, for high versus low quartiles). The results of this study suggest that there may be differences in mineral intake or metabolism between individuals who develop some carcinomas of the upper aerodigestive tract and those who do not.     

Cervical lymph node metastatic patterns of squamous carcinomas in the upper aerodigestive tract

We report a patient with medial medullary infarction who showed deep sensory impairment as his prominent neurological manifestation. A 54-year-old man with a history of hypertension was admitted to our hospital with numbness of the bilateral upper and lower extremities, followed by dysarthria and right hemiparesis. Physical examination revealed no abnormalities except for high blood pressure. He hiccuped continuously. On neurological examination, he exhibited dysarthria, mild dysphagia and right hemiparesis without facial or lingual paresis. Sensitivity to light touch and pinprick was normal, but sensitivity to vibration and joint position was severely decreased in the bilateral upper and lower extremities, predominantly in the lower extremities and on the right side in the upper extremities. He had been treated with antiedema agents and thromboxane synthetase inhibitor. His hiccups stopped within two weeks, and his right hemiparesis gradually improved within one month. However, his deep sensory impairments remained prominent. Blood examinations disclosed positive lupus anticoagulant. MRI showed bilateral infarction at the medial portion of the upper medulla oblongata, extending to both pyramids, especially on the left. Somatosensory evoked potentials (SEP) after median nerve stimulation showed P14 and the later components with prolonged latency. No SEP were recorded after posterior tibial nerve stimulation. The latency of P14 was well correlated with the severity of deep sensory impairments in the upper extremities. Neurological manifestations of our patient are not typical of medial medullary infarction, and are informative about the functional anatomy of the deep sensory tract in the medulla oblongata. We discuss the relation of the intractable hiccups to the bilateral medial medullary lesions, and emphasize the importance of lupus anticoagulant as one of the risk factors in brainstem infarction.     

How tumor stage affects surgeons'' surveillance strategies after surgery for carcinoma of the upper aerodigestive tract

OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA), with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view of their intimate association with intestinal tissue. METHODS: Twenty-five synovial cell lines were generated by interleukin 2 (IL-2) expansion from synovial biopsies of patients with early SpA and RA, obtained from macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44, and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin expression was increased, compared to RA. Furthermore, an inverse relation between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r = +0.84, p < 0.01), as similarly described on a subset of circulating T cells. CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell lines from SpA compared to RA, with discriminative correlations between alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T cells in these diseases.     

Late functional outcome after reconstruction of the upper aerodigestive tract with free transplanted microvascular anastomosed jejunum

Since 1983, 90 autologous jejunal transplantations for reconstruction of the upper digestive tract have been performed in 89 patients (9 females, 80 males, average age 56.3 years). 73 patients were operated primarily, in 16 patients a recurrent tumor had been treated. One patient received a second jejunal graft after necrosis. In these heterogenous patients, the primary tumor was located in the hypopharynx 48 times, in the larynx 21 times, in the oropharynx 19 times and twice in the oral cavity. There was nearly always tumor stage III or IV without distant metastases. Following locoregional tumor resection, speech restoration was achieved 35 times by a siphon-like tube, and the upper digestive tract was reconstructed using a patch 18 times and by a tube 28 times. A combination of tube or patch with a siphon-like tube was employed 9 times. In only two of 16 patients with recurrent tumor, speech reconstruction was performed, in the other 14, the upper digestive tract was reconstructed. In those patients, in whom speech reconstruction (by siphon tube or by combination with tube/patch) was intended, this was achieved in 81.5%. Successful functional reconstruction of the upper digestive tract (by patch, tube, combination) could be achieved in about 60% of these patients.     

Relationship between obesity and risk factors of coronary heart disease in nondiabetics

We analysed the data of 395 nondiabetic obese (BMI 25-42.2, impaired glucose tolerance, IGT, 257 and normal glucose tolerance, NGT, 138) and 482 nonobese subjects (BMI 15.9-24.9, IGT 170 and NGT 312). The blood pressure, plasma glucose, insulin, triglyceride and total cholesterol in obese were higher than that in nonobese, while HDL-c level was lower after controlling for age and sex (P < 0.001). This difference remained to be significant even after the adjustment of age, sex, insulin and 2-hours plasma glucose. Therefore, it was suggested that obesity was easy of access to coronary heart disease risk factors independent of hyperglycemia and hyperinsulinemia.     

Management of thyroid carcinoma invading the aerodigestive tract

OBJECTIVES: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. STUDY DESIGN: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. METHODS: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. RESULTS: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). CONCLUSION: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Four multiple primary malignant neoplasms of the aerodigestive tract

Multiple primary cancers of the head, neck, and upper aerodigestive tract have been documented in patients previously treated for oropharyngeal cancer. There generally is no causal relationship established between the different tumors. Two synchronous or metachronous cancers are common, three are unusual, and four are very unusual. We describe the treatment of a patient with tonsillar and synchronous esophageal and pulmonary cancers followed by a tongue cancer over a 6-year period.     

Effect of various forms of metastatic lymph node involvement on prognosis of squamous epithelial carcinomas of the upper aerodigestive tract

BACKGROUND: Based on a new histo-morphological rating scheme, we assessed the impact on patient prognosis of lymph node metastasis of squamous cell carcinoma (SCC) in the head/neck area. Special attention was given to possible capsular rupture. METHOD: In a retrospective study, 111 patients with squamous cell carcinoma of the head and neck with concomitant cervical lymph node metastases were evaluated to determine the importance of lymph node capsular rupture on the occurrence of disseminated disease, loco-regional recurrence as well as survival rate. To cover the broad morphological spectrum of cervical metastatic disease, a newly developed scheme (differentiating seven different histo-morphological types of lymph node metastasis) was applied. On the basis of this scheme, every single metastatic lymph node received a score from one to seven. These single scores were then added to obtain a total score for every individual patient. These total scores were then divided into four groups. RESULTS: Synthesis of histo-morphological pattern of metastasis in combination with the number of metastatic lymph nodes showed highest concordance/significance in respect of disseminated disease (p = 0.0029), local recurrence (p = 0.0008) and regional lymph node metastasis (p = 0.0000) as well as survival rate (p = 0.0000). CONCLUSION: The newly introduced histological scheme seems to provide more accuiate and detailed information on the prognosis of SCC in the head and neck area.     

Occupational exposure to paint, lacquer and solvents, and cancer risk in the area of the upper aero-digestive tract

So far, only few studies exist that have investigated the influence of occupational exposure to paint and lacquer on the risk of cancer in the upper aerodigestive tract. Based on data from the Heidelberg case control study which enrolled 369 patients with carcinomas of the upper aerodigestive tract and 1476 randomized control subjects, the relative risk of head and neck cancer in patients exposed to paint, lacquer and varnish was analyzed. The relative risk (RR) of squamous cell cancer (after adjustment for possible alcohol and tobacco effects) was significantly increased for the larynx (RR = 2.3) and the oral cavity (RR = 3.6). However, this risk was not increased for the pharynx. Our findings and a critical analysis of the literature provide evidence that chronic exposure to paint, varnish and lacquer is a definite risk factor for cancer of the upper aerodigestive tract. Further studies are required to confirm these findings, and to identify more precisely toxic substances encountered in the workplace.     

Relationship between dental status and salivary microbiology in adolescents

The authors studied caries prevalence in connection with salivary caries related findings, in 349, 14-16 years old Hungarian adolescents, living in two different cities. DMF.T, DMF-S means, stimulated salivary flow, buffer capacity, Streptococcus mutans, Lactobacillus and Candida albicans counts in saliva were determined. The ratio of cariesfrre adolescents was 4.6% in the total population sample, DMF-T mean values were 7.24 +/- 4.86, DMF-S means 10.50 +/- 8.35. Mean secretion rate of stimulated saliva was 0.84 +/- 0.50, a low buffer capacity was found in 6.3% of the examined children. Ratio of carriers of Streptococcus mutans, Lactobacilli and yeasts in saliva was 89.7%, 73.9% and 47.7% respectively. DMF-T and DMF-S values, as well as S. mutans counts were lower in the capital than in the other city. Statistically significant correlations were found between DMF-S, DMF mean values and salivary microbiological counts.     

Laparoscopic nephroureterectomy for upper tract transitional-cell cancer: technical aspects

OBJECTIVES: The study's objectives were to determine the size and duration of benefits of early versus delayed versus late treatment with zidovudine (ZDV) on disease progression and mortality in HIV-infected patients, and whether patients rapidly progressing before ZDV treatment had a different outcome from those not rapidly progressing before ZDV. DESIGN: The design was an inception cohort of 1003 HIV-infected patients. One hundred and seventy-four of the 1003 patients were treated before CD4 counts fell to <400 x 10(9)/L, ("early treatment"); 183 of 1003 patients were treated after CD4 counts fell to <400 x 10(9)/L but before clinical disease developed ("delayed treatment"); and 646 of the 1003 patients had either been treated after clinical disease developed or had not been treated at all by the end of follow-up ("late treatment"). Outcomes were progression to clinical HIV disease and mortality. RESULTS: The relative risk (RR) of progression for early versus delayed treatment was 0.58 (p < .03), and durability of ZDV benefits on progression was estimated at no more than 2.0 years; however, this estimate had wide confidence intervals. The RR of progression for delayed versus late treatment was 0.54 p < .0001, and durability of ZDV benefits was estimated at 1.74 years; this estimate had narrow confidence intervals. Survival was better for the early versus delayed treatment (RR = 0.55), but this difference was not statistically significant. In the subgroup of patients with more rapid CD4 decline prior to ZDV therapy, significant benefits on progression were observed for early versus delayed ZDV therapy (RR = 0.42, p = .02) and delayed versus late ZDV therapy (RR = 0.51; p = .0004). Duration of benefit was estimated to be 4.5 years (early versus delayed) and 1.7 years (delayed versus late). For patients with less rapid pre-ZDV decline in CD4 levels, a significant progression benefit was observed for delayed versus late therapy (RR = 0.50; p = .02). Duration of benefit in this subgroup was estimated to be 1.8 years. No significant benefit was found for early versus delayed treatment (RR = 1.12) in the less rapid pre-ZDV CD4 cell decline subgroup. CONCLUSIONS: Early treatment compared with delayed treatment was associated with a sizable reduction in HIV progression, but the duration of benefits was estimated to last only about 2 years. Delayed treatment compared with late treatment with ZDV was associated with substantial reduction of progression, but this reduction was also clearly limited in duration. Benefits on progression and mortality for the early treatment group were heavily dependent on the pre-ZDV CD4 slope. In the subgroup of patients with the most rapid pre-ZDV CD4 cell declines, the duration of benefit was much longer, possibly as long as 4 years.     

Prognostic factors of primary transitional cell carcinoma of the upper urinary tract

OBJECTIVES: We presented and analyzed our results in order to determine the relationship between patient survival and tumor grade and/or stage. In addition, a retrospective tumor DNA ploidy study was done to evaluate its possible role in predicting future tumor recurrence in the bladder. METHODS: A total of 112 patients with upper urinary tract transitional cell carcinomas (TCCs) were recorded at our hospital. Of these, 68 patients without concurrent bladder tumors (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by nephroureterectomy and bladder cuff resection. They were followed up for 14-79 months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin, cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked tumor specimens was performed on the tumors of 52 patients. RESULTS: Their pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14 at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III. Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a latent period ranging from 2 to 37 months (average 14.9 months). The difference of the tumor DNA ploidy distribution pattern among tumors of high versus low stages and/or grades is not statistically significant (p > 0.05). Overall, the 5-year survival rates for patients with low- and high-stage tumors were 100 and 66.7%, respectively; for patients with grade I-II and III tumors they were 93.6 and 28.3%, respectively. CONCLUSIONS: Patient survival was mainly related to both tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy seems to provide no additional predictive value on subsequent tumor recurrence in the bladder.     

Value of rigid bronchoscopy and cytodiagnosis of bronchial washings in detecting bronchial carcinoma in the presence of a carcinoma of the upper aerodigestive tract

Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v. methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.     

Dietary factors and the risk of endometrial cancer

BACKGROUND: Endometrial cancer is associated with overweight, but little is known on its possible relationship with specific aspects of diet. METHODS: The relationship between dietary factors and the risk of endometrial cancer was investigated in a case-control study conducted in Switzerland and Northern Italy on 274 patients with histologically confirmed endometrial cancers and 572 control subjects admitted to the hospital for acute nongynecologic disorders that were not hormone related, metabolic, or neoplastic. RESULTS: Significant direct associations were observed with (1) the total energy intake (odds ratio [OR] for the highest versus the lowest consumption tertile = 2.7) and, after allowance for energy intake, (2) the frequency of consumption of most types of meats, eggs, beans or peas, added fats (OR for total added fat = 2.5), and sugar (OR = 2.5). Significant protection, of the order of 40-60% reduction in the highest versus the lowest consumption tertile, was conferred by elevated intake of most vegetables and fresh fruit and whole grain bread and pasta. This was reflected in the low OR for the highest tertiles of intake of beta-carotene and ascorbic acid (OR for the highest versus the lowest consumption tertile after allowance for energy intake = 0.5). CONCLUSIONS: The current study suggests that, aside from the predictable adverse effects of overeating and consequent overweight, some qualitative aspects of the habitual diet may also be associated with the risk of endometrial cancer, chiefly, the intake of animal proteins and fat (directly) and of fresh fruit, vegetables, and fibers (inversely).     

Relationship between schistosomiasis and bladder cancer

Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, stimulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem.     

Epidemiology of and risk factors for pancreatic cancer

In the United States, incidence of and mortality from pancreatic cancer increased for several decades earlier in this century but have tended to level off in recent years. Rates increase with age and are higher in blacks than in whites and higher in men than in women. Cigarette smoking increases the risk of pancreatic cancer, while alcohol consumption largely shows no relationship, coffee consumption shows little, if any, association, and a number of occupational exposures seem to be associated but the results are not fully consistent. Finally, human studies have suggested positive associations with meat consumption and carbohydrate intake and a protective effect of dietary fiber and consumption of fruits and vegetables. Thus, much progress has been made in the last two decades in identifying risk factors, but much epidemiologic work is needed to identify and reduce putative exposures.     

Inherited factors and environmental exposures in cancer risk

Carcinogenesis is a multistage process that results from the interaction of carcinogenic exposures, cellular macromolecules (eg, DNA), and endogenous mutational mechanisms. Involved in these processes are metabolic activation and detoxification of chemical carcinogens, genetic sequences of protooncogenes and tumor suppressor genes, and DNA repair, among others. Each of these vary widely among individuals and can be associated with increased cancer risk. Cytochrome P4501A1, P4502E1 and N-acetyl transferase 2 are examples of enzymes involved in the metabolic activation of potential environmental carcinogens such as polycyclic aromatic hydrocarbons, benzene, and aromatic amines, respectively. Germ-line mutations in these genes are common and associated with abnormal enzymatic function that are mechanistically related to quantitative changes in binding of carcinogens to DNA. Allelic frequencies for these mutations vary among different racial and ethnic populations and may explain, in part, differences in cancer rates. Risk assessments attempt to predict cancer rates in humans using mathematical models that are often based upon limited experimental data. They do not generally incorporate the numerous stages of carcinogenesis or interindividual variation. Thus, sensitive and resistant populations are not sufficiently considered. This limits the accuracy of currently applied risk assessment models.