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Biomedical subjects

A Russo

Publications and source records attributed to A Russo.

At least 271 records · Page 15Linked to original sources
PubMed1998

[Cerebrospinal fluid leak after translabyrinthine approach in acoustic neuroma excision].

Cerebrospinal fluid (CSF) leak is one of the most dangerous complications that can arise in cases of acoustic neuroma removal. It increases the risk of meningitis, requires longer postoperative recovery and often requires revision surgery. A retrospective analysis was performed on all cases of acoustic neuromas which had undergone translabyrinthine surgery at the Gruppo Otologico, Piacenza, Italy, between April 1987 and December 1997, in the aim of finding the causes of postoperative CSF leaks. The causes found were high pneumatization of the temporal bone and improper execution of some surgical steps. The technique has presently been modified on the basis of the experience gained from cases of CSF leaks. By scrupulously applying these modifications, from July 1994 to December 1997, a total of 160 patients were consecutively treated using the translabyrinthine approach without a single case of postoperative CSF leak. Routine use of this modified technique can and must lower the percentage of CSF leaks after a translabyrinthine surgery to nearly 0%.

Adolescent↗
PubMed1997

Intake of selected micronutrients and risk of colorectal cancer.

The relationship between various micronutrients and colorectal cancer risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in Italy. Cases were 1,953 incident, histologically confirmed colorectal cancers (1,225 of the colon and 728 of the rectum), admitted to the major teaching and general hospitals in the study areas, and 4,154 controls with no history of cancer, admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases unrelated to the digestive tract and requiring no long-term modifications of the diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratio (ORs) were computed after allowance for age, sex and other potential confounding factors, including physical activity, total energy and fibre intake. For most micronutrients, ORs were below unity with increasing quintile of intake. The most consistent protective effects were for carotene, riboflavin and vitamin C (Multivariate ORs from the continuous model, with unit set as the difference between the upper cut-point of the 4th quintile and that of the 1st one, were 0.65, 0.73 and 0.80, respectively). Inverse relationships were observed also for calcium and vitamin D (ORs of 0.85 and 0.93, respectively). When the combined effect of calcium and vitamin D and selected anti-oxidants was considered, the OR reached 0.46 in subjects reporting high calcium/vitamin D and high anti-oxidant intake compared to those reporting low intake of both groups of micronutrients. Most results were apparently stronger for colon cancer and among females. Our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants.

Adult↗
PubMed1997

Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates. Chemical aspects involved in the balance between oxidative and nitrosative stress.

Thiol-containing proteins are key to numerous cellular processes, and their functions can be modified by thiol nitrosation or oxidation. Nitrosation reactions are quenched by O-2, while the oxidation chemistry mediated by peroxynitrite is quenched by excess flux of either NO or O-2. A solution of glutathione (GSH), a model thiol-containing tripeptide, exclusively yielded S-nitrosoglutathione when exposed to the NO donor, Et2NN(O)NONa. However, when xanthine oxidase was added to the same mixture, the yield of S-nitrosoglutathione dramatically decreased as the activity of xanthine oxidase increased, such that there was a 95% reduction in nitrosation when the fluxes of NO and O-2 were nearly equivalent. The presence of superoxide dismutase reversed O-2-mediated inhibition, while catalase had no effect. Increasing the flux of O-2 yielded oxidized glutathione (GSSG), peaking when the flux of NO and O-2 were approximately equivalent. The results suggest that oxidation and nitrosation of thiols by superoxide and NO are determined by their relative fluxes and may have physiological significance.

Free Radicals↗
PubMed1997

Micronucleus induction in germ and somatic cells of the mouse after exposure to the butadiene metabolites diepoxybutane and epoxybutene.

The genotoxicity of diepoxibutane (DEB) and epoxybutene (EB), two of the main metabolites of 1,3-butadiene, was tested in the germ and somatic cells of the mouse by applying an MN assay in early spermatids, and in peripheral blood reticulocytes of a subgroup of the same animals. DEB (0.17 and 0.35 mmol/kg) and EB (0.35, 0.70 and 1.04 mmol/kg) were administered i.p. In the germ cell assay, significant increases of MN were observed after treatment of premeiotic S-phase cells with both butadiene metabolites, but DEB was shown to be more powerful than EB in the induction of chromosomal damage. A weak effect of the same compounds was also found after treatment of late spermatocytes, approaching the meiotic divisions. From the MN assay in peripheral blood reticulocytes, a statistically significant increase of the frequency of MN was detected at each dose tested for both chemicals. However, the results have again shown that DEB is much more efficient than EB in inducing chromosome damage.

Animals↗
PubMed1997

Overexpression of folate binding protein in ovarian cancers.

The high affinity folate binding protein (FBP) is overexpressed in ovarian cancers. However, its role in the pathogenesis and biological behaviour of these neoplasms is not clearly understood. Using the monoclonal antibody (MAb) MOv 18 and cytofluorimetric analysis, we investigated FBP expression in frozen neoplastic tissues from 136 patients diagnosed with epithelial ovarian cancer. FBP values were compared with clinico-pathological characteristics (age, stage, histologic grade, histologic type, DNA ploidy, percentage of S-phase cells, and previous chemotherapeutic treatment). Some amount of FBP overexpression was observed in 122 of the 136 tumours examined. The overall mean value of FBP fluorescence index (FBP FI) was 5.6 (median 2.7; min 0.8--max, 78.9). By univariate analysis, FBP FI was overexpressed to a higher degree in ovarian neoplasms with high histologic grade, advanced stage, serous histology, aneuploid status, and high percentage of cells in S-phase. Of the total number (136) of cases, 106 had all the parameters assessed and were thus selected for stepwise selection procedure. The only significant independent variable was the percentage of S-phase cells, which accounted for about 31% of variance of FBP FI. Our results indicate that FBP is associated with parameters of biological aggressiveness in ovarian cancers.

Adenocarcinoma, Mucinous↗
PubMed1997

Health insurance coverage and outcome following acute myocardial infarction. A community-wide perspective.

BACKGROUND: Several studies have suggested that type of medical insurance coverage is associated with hospital utilization rates and receipt of selected diagnostic or treatment approaches. To our knowledge no studies, however, have examined the relation between medical insurance coverage and short-term outcomes following acute myocardial infarction (AMI) from a multihospital, community-wide perspective. OBJECTIVE: To examine the association between medical insurance coverage and in-hospital case-fatality rates as well as length of hospital stay following AMI. METHODS: The study sample consisted of 3735 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI during 1986, 1988, 1990, 1991, and 1993 at all metropolitan Worcester hospitals. Data were obtained from the review of medical records. Patients were stratified into 5 medical insurance groups for purposes of analysis: private or commercial (n = 711), Medicaid (n = 101), Medicare (n = 1991), health maintenance organization (n = 741), and self-pay or other (n = 191). Crude and multivariable-adjusted analyses were used to examine the relation between medical insurance coverage and length of hospital stay and in-hospital case-fatality rates following AMI. RESULTS: In-hospital case-fatality rates during the period under study were 7.7%, 11.9%, 21.4%, 9.3%, and 10.0% in the 5 medical insurance groups, respectively. After adjusting for several factors that may affect in-hospital mortality, relative to the referent group of private or commercial insurance patients (odds ratio, 1.0), the multivariable-adjusted odds for dying during the acute hospitalization were 0.87 (95% confidence interval [CI], 0.56-1.36) for health maintenance organization patients, 1.22 (95% CI, 0.55-2.68) for Medical patients, 1.25 (95% CI, 0.85-1.84) for Medicare patients, and 1.21 (95% CI, 0.60-2.44) for self-pay or other patients. The mean length of hospitalization after excluding patients with a prolonged hospitalization was 10.1 days for private or commercial insurance patients, 9.4 days for health maintenance organization patients, 10.9 days for Medicaid patients, 11.1 days for Medicare patients, and 9.8 days for self-pay or other patients. No significant differences in the average duration of hospitalization were seen between the medical insurance groups after controlling for potential confounding variables. CONCLUSIONS: The results of this population-based study suggest that patient insurance status is not significantly associated with either length of hospital stay or short-term mortality following AMI. Other demographic and clinical prognostic factors appear to be more important predictors of short-term outcome in this patient population.

Adult↗
PubMed1997

Attributable risks for breast cancer in Italy: education, family history and reproductive and hormonal factors.

The percent population attributable risk (AR) for breast cancer was estimated in relation to education, family history of the disease and some reproductive and hormonal factors, using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centres on 2,569 histologically confirmed incident breast cancer cases and 2,588 controls, admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. On the basis of multivariate odds ratios, a high level of education accounted for 20% of cases, elevated age at first birth and nulliparity for 38% and a family history of breast cancer in first-degree relatives for 7%. Education and nulliparity and age at first birth together explained 47% of all breast cancer cases, and the combination of these 2 factors plus a family history of the disease explained 50% of cases. In pre-menopausal women a high level of education accounted for 31% of all breast cancer cases, older age at first birth for 44% and the combination of the 2 factors for 49%. In post-menopausal women the corresponding values were 13%, 31% and 42%; further addition of risk associated with family history of the disease explained 52% of pre-menopausal cases. In post-menopausal women older age at menopause and the use of hormone replacement therapy accounted for 15% and 2% of breast cancer cases, respectively. The combination of risks associated with a high level of education, old age at first birth and nulliparity and older age at menopause accounted for 51% of cases; further inclusion of risk associated with use of hormone replacement therapy explained 52%, and the AR resulting from these 4 risk factors combined plus a family history of breast cancer was 56%. Thus, a few selected and well-identified risk factors explain about one-half the breast cancer cases in this Italian population.

Age Factors↗
PubMed1997

In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy.

Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 microsecond, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10-50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques.

Animals↗
PubMed1997

Nitric oxide and some nitric oxide donor compounds enhance the cytotoxicity of cisplatin.

A major emphasis in cancer therapy research is finding mechanisms to enhance the effectiveness of clinically used chemotherapeutic agents. In this report, we show the effects of direct NO exposure or NO delivery agents such as NONOate NO donors, DEA/NO ((C2H5)2N[N(O)NO]-Na+) and PAPA/ NO (NH2(C3H6)(N[N(O)NO]C3H7)), or S-nitrosothiol NO donors (GSNO, S-nitrosoglutathione, and SNAP, S-nitroso-N-acetylpenicillamine) on the cytotoxicity of cisplatin with Chinese hamster V79 lung fibroblast cells. Cells pretreated with bolus NO or NO delivered from NONOate NO donors were markedly sensitized to subsequent cisplatin treatment, whereas S-nitrosothiol NO donors exerted little effect. The enhancement in cisplatin cytotoxicity from pretreatment with DEA/NO and PAPA/ NO persisted for approximately 180 and 240 min, respectively; thereafter cytotoxicity returned to a level consistent with cisplatin treatment alone. Pretreatment of cells with GSNO or SNAP did not enhance cisplatin cytotoxity. To discern why there were differential effects among the different NO donors, formation of NO over the time course of the experiment was assessed by the nitrosation of 2,3-diaminonaphthylene. Bolus NO, DEA/NO, and PAPA/NO produced more reactive nitrogen oxide species (RNOS) than did treatment with GSNO or SNAP. Previously reported electrochemical studies revealed that temporal NO concentrations measured from DEA/NO and PAPA/NO (1 mM) were greater than 5 microM. It appears that the flux of NO, as well as the amount of RNOS, is important in the NO-mediated enhancement of cisplatin cytotoxicity. Our results demonstrate the importance of NO delivery systems in the enhancement of cisplatin cytotoxicity and may provide insights into strategies for participation of NO donors and nitric oxide synthase with cisplatin therapy.

Animals↗
PubMed1997

Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence of survival. METHODS: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology. RESULTS: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. CONCLUSIONS: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM.

Adult↗
PubMed1997

Pathological and immunophenotypic features of adult non-Hodgkin's lymphomas by age group.

To elucidate age-related differences in non-Hodgkin's lymphoma (NHL), the authors evaluated 950 consecutive, human immunodeficiency virus-negative patients (age range, 15 to 96 years) observed between July 1988 and June 1995 in the same Italian cancer institute. Patients were grouped into six age groups and cross-tabulated by Working Formulation (WF) categories and other newly recognized entities according to the Revised European American Lymphoma (REAL) classification, cell immunophenotype, and nodal or extranodal location. There was a tendency of the low-grade category to increase with increasing age (16.8% in the age group 15 to 34 years to 32.4% in the age group 65 to 74 years), although a subsequent decline was seen at age 75 years or older (23.2%). Also the intermediate-grade category was more frequent in the elderly (46.6% and 49.4% at 65 to 74 years and at 75 years or older, respectively). High-grade category showed compared with low and intermediate grade ones, a significant downward trend with age (X2 for trend = 25.31; P < .001), interrupted in only the oldest age group. The relative excess of low-grade NHL in patients older than 55 years. of age was accounted for by the high proportion of small lymphocytic lymphomas, which, however, somewhat declined at age 75 years or older. Conversely, the relative excess of high-grade NHL below age 35 years chiefly derived from the high percentage (28.4%) of CD30-positive anaplastic large cell lymphomas. B- and T-cell lymphomas accounted for 85.9% and 9.0% of all cases, respectively. B- and T- and non-B, non-T-cell and histiocytic NHL accounted for the remaining 5.1%. A highly significant trend of increase in the proportion of B-cell lymphomas with age increase was noted (X2 for trend = 21.90; P < .001); chiefly attributable to the excess of T-cell (15.1%) and undetermined phenotype (18.6%) in patients younger than 35 years of age. Extranodal location was not significantly related to age groups. Thus, the present study showed some interesting differences in NHL morphology and cell phenotype according to age, avoiding, at the same time, the arbitrariness of patients' dichotomization into elderly and nonelderly.

Adolescent↗
PubMed1997

Prevalence of anxiety disorders comorbidity in bipolar depression, unipolar depression and dysthymia.

Eighty-seven patients with current episode of depression were assessed by the SCID-P and subdivided in bipolar depressives (N = 24), unipolar depressives (n = 38) and dysthymics (n = 25). Anxiety disorders comorbidity in these three groups was investigated by means of the SCID-P. Panic disorder comorbidity was found in 36.8% of bipolar depressives, 31.4% of unipolar depressives and 13% of dysthymics. Prevalence of obsessive-compulsive disorder was 21.1% in bipolars, 14.3% in unipolars and 8.7% in dysthymics. Generalized anxiety disorder resulted in being much more associated with dysthymia (65.2%) than with bipolar (31.6%) or unipolar depression (37.1%). Social phobia comorbidity was exhibited mainly by unipolars (11.4%), while no cases were detected in the bipolar group. Odds ratios revealed that generalized anxiety disorder is significantly more likely to co-occur with dysthymia. Panic disorder showed a higher trend to be associated with bipolar and unipolar depression. Social phobia was more frequent among unipolar depression.

Adult↗
PubMed1997

Mastoidectomy in noncholesteatomatous chronic suppurative otitis media: is it necessary?

Chronic suppurative otitis media (CSOM) without cholesteatoma, the surgical treatment of which is still controversial, is a common diagnosis in otologic practice. A retrospective analysis of 323 patients who underwent surgery for noncholesteatomatous chronic otitis media in the Gruppo Otologica, Piacenza, Italy, between April 1983 and December 1993 is presented. Cases were separated into three groups according to different surgical treatment modalities and conditions of the ears at the time of operation. Group I (n = 53) consisted of cases of CSOM treated by tympanoplasty without mastoidectomy (TLWOM). Group II (n = 28) included cases of CSOM treated by tympanoplasty with mastoidectomy (TLWM). Intact canal wall technique was used in these cases. The ears in both these groups were discharging severely at the time of surgery. Group III (n = 242) included patients whose ears were dry at the time of surgery but who had had previous recurrent episodes of suppuration and who were treated by TLWOM. At the last follow-up, graft success rates for groups I, II, and III were 90.5%, 85.7%, and 89.2%, respectively, and mean residual gaps were 17.2 dB, 20.1 dB, and 19.4 dB, respectively. There was no statistically significant difference between the three groups either on graft success rates (p > 0.05) or on final functional hearing outcome (p > 0.05). TLWM is the preferable treatment modality for most surgeons in noncholesteatomatous CSOM. Nevertheless, in our experience TLWOM yields comparable results for this group of patients. In addition, we could not find any significant difference in results of graft success and final functional hearing rates between dry and discharging ears (p > 0.05).

Adolescent↗
PubMed1997

Clinical observations on coexistence of sudden hearing loss and vestibular schwannoma.

It has long been recognized that sudden hearing loss (SHL) may be a harbinger of vestibular schwannoma (VS). Among 192 VS patients who underwent operation in the Gruppo Otologico, Piacenza, Italy, from April 1987 to October 1995, the charts of 14 (7.3%) cases with a history of SHL were examined. SHL was the first symptom in 8 (4.2%) patients. Eight (57.1%) of 14 VS cases with SHL anamnesis had reported recovery of their previous hearing either totally or partially before establishment of tumor diagnosis. Five (35.7%) cases had recurrent bouts of SHL. SHL was observed less frequently in cases with large tumors (>3 cm). However, the frequency of SHL in patients with small tumors did not differ from that of medium-sized tumors. Awareness about coexistence of SHL and VS, as well as concomitant use of auditory brain stem response and magnetic resonance imaging, is crucial to rule out the diagnosis of VS in a patient with SHL.

Adult↗
PubMed1997

Direct evidence for in vivo nitroxide free radical production from a new antiarrhythmic drug by EPR spectroscopy.

The new Class I anti-arrhythmic agent 2,2,5,5-tetramethyl-3-pyrroline-1-carboxamide derivative, is currently being evaluated in clinical trials in patients with a high risk for cardiac arrhythmias. In this study we show that this antiarrhythmic drug can be chemically converted to the nitroxide free radical analog. Further, using an in vivo Electron Paramagnetic Resonance (EPR) spectroscopy model by detecting free radicals in the distal portion of the tail of an anesthetized mouse, we demonstrate that the drug is oxidized to the corresponding nitroxide. In vitro studies using Chinese hamster V79 cells suggest that the oxidation products of the drug, namely, the hydroxylamine and the nitroxide protect against oxidative damage induced by hydrogen peroxide (H2O2). Taken together, our results suggest that, in addition to the antiarrhythmic effects of the parent drug, sufficient levels of nitroxides may accumulate from the parent drug in vivo to provide antioxidant defense to cardiac tissue that may be subject to ischemia and oxidation-driven injury.

Animals↗
PubMed1997

Evaluation of tempol radioprotection in a murine tumor model.

Tempol, a stable nitroxide free radical compound, is an in vitro and in vivo radioprotector. Previous studies have shown that Tempol protects C3H mice against whole-body radiation-induced bone marrow failure. In this study, the radioprotection of tumor tissue was evaluated. RIF-1 tumor cells were implanted in female C3H mice 10 d prior to radiation. Groups of mice were injected intraperitoneally with Tempol (275 mg/kg) or PBS followed 10 min later by a single dose of radiation to the tumor bed. Tumor growth curves generated after 10 and 33.3 Gy doses of radiation showed no difference in growth between the Tempol- and PBS-treated animals. A full radiation dose-response experiment revealed a tumor control dose in 50% of the animals in 30 d (TCD(50/30)) value of 36.7 Gy for Tempol-treated mice and 41.8 Gy for saline-treated mice suggesting no protection of the RIF-1 tumor by Tempol. Tumor pharmacokinetics were done to determine why Tempol differentially protected bone marrow and not tumor cells. Differential reduction of Tempol in the RIF-1 tumor and bone marrow was evaluated with EPR spectroscopy 10, 20, and 30 min after injection. Bioreduction of Tempol to its corresponding hydroxylamine (which is not a radioprotector) occurred to a greater extent in RIF-1 tumor cells compared to bone marrow. We conclude that the differences in radioprotection may result from enhanced intratumor bioreduction of Tempol to its nonradioprotective hydroxylamine analogue. The nitroxides as a class of compounds may provide a means to exploit the redox differences between normal tissues and tumors.

Animals↗
PubMed1997

Changes in lung cancer histological types in Varese Cancer Registry, Italy 1976-1992.

Shifts in histological tumour type distribution, chiefly an increase in adenocarcinoma, have been reported to accompany changes in lung cancer incidence in the last two decades in the United States and several other developed countries. To elucidate this phenomenon further, we analysed population-based lung cancer incidence rates in the period 1976-1992 from the Varese province, an area with 788,000 inhabitants in Northern Italy. Rates were age-standardised on the world standard population. Overall, lung cancer had stopped increasing in males since the late 1980s, and had started declining in middle-aged men. Conversely, upward trends persisted in females up to 1991-1992. Although it decreased from 13 to 9, the male-to-female incidence ratio was, in 1991-1992 still substantially higher than in the U.S. and North Europe. Specific trends emerged according to histological type(s), with declines (males) or stabilisation (females) for squamous-cell carcinoma and gradual increases for small-cell carcinoma in males. Adenocarcinoma was the only lung cancer type whose incidence rates increased similarly (2.5-fold) in males and females thus approaching, in 1991-1992, in the two sexes combined, the rate for squamous-cell carcinoma. Although advances in diagnostic techniques may have played a role, the absolute and relative increases in the adenocarcinoma rate reflect changes in cigarette manufacture (i.e. spread of filter tips and low-nicotine low-tar cigarettes) and the decrease in smokers.

Adenocarcinoma↗