Pro and contra in minimally invasive oncological surgery. Minimally invasive surgery in lung cancer.
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Humans↗
Biomedical subjects
M Mezzetti
Publications and source records attributed to M Mezzetti.
Influence of selected dietary and lifestyle risk factors on familial propensity to breast cancer.
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Breast Neoplasms↗
Sentinel node localization in primary melanoma: learning curve and results.
Ninety primary melanoma patients were studied to investigate the importance of adopting the simultaneous use of patent blue dye (PBD) and lymphoscintigraphy plus gamma detection probe to locate the sentinel node (SN). In total 135 SNs in 105 basins were visualized preoperatively under a gamma camera after lymphoscintigraphy. When a SN was identified intraoperatively, its radioactivity level and colour were verified and documented. Two of the SNs seen on lymphoscintigraphy were not found. Using PBD 78.52% of the SNs were identified; 95.5% were identified using the gamma detection probe. Using both methods together 98.5% of the SNs were detected. Twenty-two patients (24.4%) had pathologically positive SNs. The surgical learning curve was assessed for the two techniques. The learning curve associated with the methodology was important in finding the SN when using PBD associated with lymphoscintigraphy, but not when the gamma detection probe was used; we found a statistically significant reduction in the percentage of stained SNs found using PBD in the initial 14 SNs biopsied compared with the subsequent 121 nodes. This is important as not all institutions have access to a gamma probe. The time required to identify each SN was documented and analysed. The duration of the procedure was significantly shorter for stained SNs than for non-stained SNs, which support the use of both PBD and the gamma probe. In conclusion, SN biopsy should be performed by surgeons and nuclear medicine doctors in co-operation, both methods being adopted simultaneously to reduce the percentage of procedure failures.
Adolescent↗
Suppression of telomerase activity as an indicator of drug-induced cytotoxicity against cancer cells: in vitro studies with fresh human tumor samples.
Telomerase is a ribonucleoprotein complex with reverse-transcriptase activity responsible for telomere reconstitution. High telomerase activity was found in cancer cells, but not in differentiated homologous nonmalignant tissues. We demonstrated previously that the disappearance of telomerase activity is a reliable marker of tumor cell killing in human cancer cell lines. We have investigated the possibility of evaluating chemosensitivity of neoplastic cells of different origin [ovary, lung, breast, gastrointestinal, skin (melanoma)] obtained from cancer patients, by measuring residual telomerase activity after drug treatment in vitro. Using the classical telomeric repeat amplification protocol ("TRAP") assay based on polymerase chain reaction, we examined telomerase activity of untreated or drug-treated tumor cell suspensions, derived from the processing of surgical specimens. Feasibility and reproducibility of the assay were evaluated according to various parameters, including drug concentration, time of in vitro culture, and type of tumor. The results indicated that the assay is highly sensitive and reproducible, and can be performed using surgical specimens in a reasonable percentage of cases, ranging from 40% (breast cancer) to 100% (ovarian cancer). Moreover, the assay provides comparable results using a wide range of tumor cells, and the presence of normal cells does not interfere with the results. Prolonged tumor cell culture is not required because the assay can be completed within 24 to 72 hours after sample collection. In conclusion, the present investigation provides the technical bases for future studies to evaluate whether this assay would be able to predict patient's response to antitumor agents.
Antineoplastic Agents↗
Sunscreen use, wearing clothes, and number of nevi in 6- to 7-year-old European children. European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.
BACKGROUND: Previous epidemiologic studies have suggested that sunscreen use is associated with an increased risk of melanoma skin cancer. Because high nevi (mole) count in adults is a strong predictor of melanoma, we conducted a study examining the number of nevi in 6- to 7-year-old European children, according to their sunscreen use. METHODS: Whole-body and site-specific counts of nevi 2 mm or larger were performed in 631 children in their first year of primary school in four European cities. Independently, parents were interviewed regarding sun exposure, sunscreen use, and physical sun protection of their child. RESULTS: After adjustment for sun exposure and host characteristics (e.g., skin phototype, eye color), the relative risk for high nevus count on the trunk was 1.68 (95% confidence interval [CI] = 1.09-2.59) for the highest level of sunscreen use and 0.59 (95% CI = 0.36-0.97) for the highest level of wearing of clothes while in the sun. The sun protection factor had no effect on nevus counts despite a high median value of 17.4. Sunburn number was not associated with nevus count. The highest risk associated with sunscreen use was found among children who had never experienced sunburn. CONCLUSIONS: In white, European children, sunscreen use appears to be associated with development of nevi, probably because it allows longer sun exposures. Wearing clothes may be an effective way to prevent proliferation of nevi. Since a high nevus count is a strong predictor of melanoma, sunscreen use may be involved in melanoma occurrence because it may encourage recreational sun exposure.
Child↗
Population attributable risk for breast cancer: diet, nutrition, and physical exercise.
BACKGROUND: The percentages of breast cancer cases in a given population attributable to specific risk factors (i.e., the population-attributable risks) can be calculated; determination of such risks associated with potentially modifiable risks factors, such as diet (e.g., levels of consumption of fruits, vegetables, vitamins, etc.), alcohol consumption, exercise, and body weight, are necessary to focus prevention strategies. METHODS: With the use of data from a case-control study conducted in Italy from June 1991 through April 1994 on 2569 breast cancer case subjects and 2588 control subjects, we calculated multivariate odds ratios and population-attributable risks for breast cancer in relation to dietary beta-carotene and vitamin E intake, alcohol consumption, physical activity, and, for postmenopausal women, body mass index. RESULTS: Among all subjects, the following attributable risks for the indicated risk factors were observed: 10.7% (95% confidence interval [CI] = 4.4%-17.0%) for high alcohol intake (i.e., >20 g/day), 15.0% (95% CI = 7.4%-22.9%) for low beta-carotene intake (i.e., <3366 microg/day), 8.6% (95% CI = -0.4%-17.5%) for low vitamin E intake (i.e., <8.5 mg/day), and 11.6% (95% CI = -0.1%-23.3%) for low levels of physical activity. The risks associated with alcohol and beta-carotene intake were larger among premenopausal women, and the risk associated with physical activity was larger among postmenopausal women. Being overweight accounted for 10.2 % (95% CI = 0.2%-20.2%) of breast cancer cases in postmenopausal women. Beta-carotene plus alcohol accounted for 28.1% (95% CI = 16.8-39.4) of the cases. Beta-carotene and physical activity accounted for 32% (95% CI = 14.3-49.8), and these three factors together accounted for 33% (95% CI = 19.9-46.1) of the breast cancer cases in the overall dataset. CONCLUSION: Exposure to a few selected and potentially modifiable risk indicators explained about one third of the cases of breast cancer in this Italian population, indicating the theoretical scope for prevention of the disease.
Adult↗
Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro.
1. Cysteinyl-leukotrienes (cysteinyl-LTs) are important mediators in the pathogenesis of asthma. They cause bronchoconstriction, mucus hypersecretion, increase in microvascular permeability, plasma extravasation and eosinophil recruitment. 2. We investigated the pharmacological profile of the cysteinyl-LT antagonists CGP 45715A (iralukast), a structural analogue of LTD4 and CGP 57698, a quinoline type antagonist, in human airways in vitro, by performing binding studies on human lung parenchyma membranes and functional studies on human isolated bronchial strips. 3. Competition curves vs [3H]-LTD4 on human lung parenchyma membranes demonstrated that: (a) both antagonists were able to compete for the two sites labelled by [3H]-LTD4; (b) as in all the G-protein coupled receptors, iralukast and CGP 57698 did not discriminate between the high and the low affinity states of the CysLT receptor labelled by LTD4 (Ki1=Ki2= 16.6 nM+/-36% CV and Ki1= Ki2 = 5.7 nM+/-19% CV, respectively); (c) iralukast, but not CGP 57698, displayed a slow binding kinetic, because preincubation (15 min) increased its antagonist potency. 4. In functional studies: (a) iralukast and CGP 57698 antagonized LTD4-induced contraction of human bronchi, with pA2 values of 7.77+/-4.3% CV and 8.51+/-1.6% CV, respectively, and slopes not significantly different from unity; (b) the maximal LTD4 response in the presence of CGP 57698 was actually increased, thus clearly deviating from apparent simple competition. 5. Both antagonists significantly inhibited antigen-induced contraction of human isolated bronchial strips in a concentration-dependent manner, lowering the upper plateau of the anti-IgE curves. 6. In conclusion, the results of the present in vitro investigation indicate that iralukast and CGP 57698 are potent antagonists of LTD4 in human airways, with affinities in the nanomolar range, similar to those obtained for ICI 204,219 and ONO 1078, two of the most clinically advanced CysLT receptor antagonists. Thus, these compounds might be useful drugs for the therapy of asthma and other allergic diseases.
Antigens↗
Alcohol intake and risk of cancers of the colon and rectum.
The relationship between alcohol drinking (mainly wine) and risk of colon and rectal cancer was considered in a case-control study conducted between 1991 and 1996 in six Italian centers. Cases were 1,225 patients < 75 years of age with histologically confirmed cancer of the colon and 728 patients with cancer of the rectum; controls were 4,154 patients admitted to hospital for a wide spectrum of acute, nonneoplastic diseases. Compared with never drinkers, the odds ratios (OR) for current drinkers in the higher quintile of total alcohol intake (> 51.82 g ethanol/day) were 1.01 for colon cancer and 0.90 for rectal cancer, and those for ex-drinkers were 1.20 and 1.07, respectively. The OR for wine drinkers in the highest quartile of intake were 1.07 for colon cancer and 0.97 for rectal cancer. No association was found with duration of the habit, time since starting, or age at starting. Among ex-drinkers, no association appeared with time since stopping. No significant heterogeneity was found across strata of age at diagnosis, sex, education, smoking status, physical activity, family history of colorectal cancer, beta-carotene, vitamin C, coffee, total fiber and folate intake, and number of meals per day. No significant association appeared for various intestinal subsites.
Adult↗
Identification and characterization of two cysteinyl-leukotriene high affinity binding sites with receptor characteristics in human lung parenchyma.
We report the characterization of two distinct binding sites with receptor characteristics for leukotriene (LT)D4 and LTC4 in membranes from human lung parenchyma. The use of S-decyl-glutathione allowed us to characterize a previously unidentified high affinity binding site for LTC4. Computerized analysis of binding data revealed that each leukotriene interacts with two distinct classes of binding sites (Kd = 0.015 and 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites are different entities. LTD4 binding sites displayed features of G protein-coupled receptors, whereas LTC4 binding sites did not show any significant modulation by guanosine-5'-(beta, gamma-imido)triphosphate or stimulation of GTPase activity. The antagonists ICI 198,615 and SKF 104353 were unselective for the high and low affinity states of LTD4 receptor, whereas only SKF 104353 was able to recognize the two [3H]LTC4 binding sites although with different affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4 recognize two different binding sites; these binding sites are different entities; and for LTD4, the two binding sites represent the interconvertible affinity states of a G protein-coupled receptor, whereas for LTC4, the high affinity site is likely to be a specific LTC4 receptor.
Binding Sites↗
Risk factors for high-grade cervical intraepithelial neoplasia in patients with mild cytological dyskaryosis: human papillomavirus testing versus multivariate tree analysis of demographic data.
The objective of this study was to compare the use of molecular hybridization by hybrid capture methodology for human papillomavirus (HPV) with the use of demographic and lifestyle variables as intermediate triage in patients with cytological mild dyskaryosis. The study was designed as a prospective study using regression tree analysis of demographic data in consecutive patients who were subjected to colposcopic evaluation at the colposcopy clinic at the First Department of Obstetrics and Gynaecology, University of Milan (Milan, Italy). A total of 177 women were subjected to colposcopy because of a single routine Pap smear showing mild dyskaryosis. A structured interview, sampling for HPV testing for the detection of viral DNA by hybrid capture methodology, and colposcopic evaluation with cervical biopsies were performed for each subject. The accuracies of molecular hybridization for HPV and of the classification model based on the demographic and lifestyle variables in predicting patients with histologically high-grade cervical intraepithelial lesions were measured. The classification model based on the demographic and lifestyle variables showed comparable results with molecular hybridization for HPV (specificity, 0.75 versus 0.73; sensitivity, 0.61 versus 0.67, respectively). The use of demographic and lifestyle variables appears to be a simple and economic possibility for triaging patients with mild dyskaryotic smears in a screening program.
Adult↗
Impact of inherited polymorphisms in glutathione S-transferase M1, microsomal epoxide hydrolase, cytochrome P450 enzymes on DNA, and blood protein adducts of benzo(a)pyrene-diolepoxide.
The benzo(a)pyrene (BaP) metabolite benzo(a)pyrenediolepoxide (BPDE) is strongly implicated as a causative agent of lung cancer. To assess the risk of exposure to BaP, we made a combined analysis of levels of BPDE adducts to hemoglobin (Hb), serum albumin (SA), and lymphocyte DNA in 44 patients with incident lung cancer, as a prototype of a population mainly exposed to tobacco-derived BaP. We also investigated whether genetic polymorphisms of cytochrome P450IA1 (CYPIA1), microsomal epoxide hydrolase (mEH), and glutathione S-transferase M1 (GSTM1), which are involved in BaP metabolism, can be determinants of adduct formation. BPDE-Hb, BPDE-SA, and BPDE-DNA adducts were quantified as BaP tetrols released from hydrolysis of macromolecules and measured by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry to achieve high specificity and sensitivity. Individuals with detectable Hb adducts were positive for SA adducts but not vice versa, suggesting that BPDE-Hb adducts are less informative indicators of BaP exposure. Using PCR methods on DNA, we characterized GSTM1 deletion, CYPIA1 MspI and exon 7 valine variants, and mEH polymorphisms at amino acid positions 113 (EH3) and 139 (EH4). Levels of BPDE adducts were no different among CYPIA1, mEH, and GSTM1 genotypes. However, individuals with measurable BPDE-SA adducts were CYPIA1 variant carriers more frequently (P = 0.03). There was a slightly higher percentage of DNA detectable adducts in subjects with CYPIA1 exon 7 valine polymorphism. When subjects were classified by both polymorphisms on the mEH gene, those with two slow alleles (EH3 homozygous mutated) and no fast alleles (EH4 homozygous wild type) had a lower frequency of BPDE-SA adducts and no DNA adducts (P = 0.06). These results are based on a small number of observations thus far, but this exploratory study suggests that CYPIA1 and mEH variants might have an impact on BPDE exposure markers such as BPDE-SA adducts. Chemical specificity in adduct measurements is important to identify the biomarkers that reflect BaP exposure more accurately.
Aged↗
Non-selective impairment of Wisconsin Card Sorting Test performance in patients with schizophrenia.
Sixty-two schizophrenic patients and 26 healthy volunteers were administered the Wisconsin Card Sorting Test (WCST) a task putatively specific for frontal functions and the Wechsler Adult Intelligence Scale (WAIS). The purpose of this study was to evaluate the presence of specific frontal lobe deficits in the course of schizophrenia and the capacity of these tasks to discriminate between patients and controls. Schizophrenic patients showed a poorer performance than control subjects in both tests. No evidence emerged to support a higher discriminant power for the WCST in identifying schizophrenic subjects from healthy controls compared with the WAIS. Our data suggest that the deficit in WCST performance is not selective, but rather part of a more generalized neuropsychological impairment in schizophrenic patients.
Adult↗
Fibers and breast cancer risk.
Data from a multicenter case-control study on breast cancer conducted in Italy were used to analyze the relationship between various types of fibers and breast cancer risk. Cases were 2,569 women with histologically confirmed, incident breast cancer; controls were 2,588 women admitted to the same network of hospitals for acute, nonneoplastic, non-hormone-related diseases. Cases and controls were interviewed between 1991 and 1994 using a validated food frequency questionnaire. The data were modeled through multiple logistic regression, controlling for demographic and reproductive breast cancer risk factors. The continuous odds ratios for the difference between the upper cut point of the fourth and the first quintile of intake were 0.90 [95% confidence interval = 0.82-0.98, p (for trend) < 0.05] for cellulose and 0.94 (95% confidence interval = 0.86-1.02) for soluble fibers. The protection tended to be stronger in premenopausal women. No material association was found for noncellulose polysaccharides and lignin. This study, based on a large data set from various Italian regions, suggests that fiber intake may confer some protection against breast cancer, particularly for cellulose and also for soluble fibers, i.e., those of vegetable origin. This possible protection has been related to an influence of fibers on levels and availability of estrogens and other steroid hormones in breast carcinogenesis.
Adult↗
Attributable risks for colorectal cancer in northern Italy.
Using data from a case-control study conducted between 1985 and 1992 in northern Italy on 828 cases of colon cancer, 498 cases of rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract disorders, we estimated the percent population attributable risk (PAR) for colorectal cancer in relation to beta-carotene, vitamin C (as markers of a diet rich in fruit and vegetables), red meat and seasoning fat intake, daily meal frequency and family history of the disease. On the basis of multivariate odds ratios, adjusted for total calorie intake, a low intake of beta-carotene accounted for 39% of all the cases and a low intake of vitamin C for 14%. These two micronutrients together explained 43% of all colorectal cancer cases in this population. A high frequency of intake of red meat consumption explained 17% of all cases, and a high score of seasoning fats 4%. A higher daily meal frequency was responsible for 13% of the cases, and these 5 dietary factors together explained 63% of colorectal cancer cases in this population. Family history of colorectal cancer accounted for 4% of all cases. These estimates were similar for colon and rectal cancers separately, in males and females, and in younger and elderly subjects, except for seasoning fats and family history, whose PARs were apparently greater for colon cancer and at younger age. Thus, even though available dietary data were limited in several aspects, and the PAR estimates were based on somewhat arbitrary assumptions regarding the exposure distribution, about two-thirds of all colorectal cancers in this population could be explained in terms of a few risk factors or risk indicators considered. This would correspond to the avoidance of a large proportion of the over 18,000 deaths from colorectal cancer registered per year in the whole of Italy.
Adult↗
Software for attributable risk and confidence interval estimation in case-control studies.
The increasing interest in obtaining model-based estimates of attributable risk (AR) and corresponding confidence intervals, in particular when more than one risk factor and/or several confounding factors are jointly considered, led us to develop a program based on the procedure described by Benichou and Gail for case-control data. This program is structured as an SAS-macro. It is suited to analysis of the relationship between risk factors and disease in case-control studies with simple random sampling of controls, in terms of relative risks and ARs, by means of unconditional logistic regression analysis. The variance of the AR is obtained by the delta method and is based on three components, namely, (i) the variance-covariance matrix of the vector of the estimated probabilities of belonging to joint levels of the exposure and confounding factors conditional on being a case, (ii) the variance-covariance matrix of the odds ratio parameter estimates from the logistic model, and (iii) the covariances between these probability and parameter estimates. Only a limited number of commands is requested from the user (i.e., the name of the work file and the names of the variables considered). The estimated relative risks for all the factors included in the model, the attributable risk for the exposure factor under consideration, and the corresponding 95% confidence intervals are given as outputs by the macro. Computational problems, if any, may arise for large numbers of covariates because of the resulting large size of vectors and matrices. The macro was tested for reliability and consistency on published data sets of case-control studies.
Age Factors↗
Video-assisted thoracoscopic resection of pulmonary sequestration in an infant.
Pulmonary sequestration is a congenital anomaly of lung parenchyma that can be definitively treated only with surgical resection. We report a case of an intralobar sequestration of the right lower pulmonary lobe in an infant successfully treated with video-thoracoscopic surgical removal of the involved lobe at 6 months of age.
Bronchopulmonary Sequestration↗
Prospective study of surgical treatment of lung cancer in the elderly patient.
BACKGROUND: In 1986 the authors began a prospective study to investigate operative mortality and long-term survival after surgery of patients in their seventh decade of life suffering from non-small cell lung cancer in Stages I and II. METHODS: From 1986 to 1991, 519 lung cancer patients underwent radical surgery. Of this number, 54 were aged 70 years and older (Group A), while 465 fell within the 40-69 age range (Group B). The most widely applied operation in absolute terms was lobectomy (no difference between the two groups). Pneumonectomies were performed in greater number in Group B (p < .025), whereas minor resections were more numerous in Group A (p < .0005). RESULTS: Operative mortality, i.e., within 30 days of operation, was higher in the elderly patients, but without any significant difference between the two groups (A, 5.5%; B, 1.3%). Morbidity presented a very similar pattern: Group A, 7.4%; Group B, 6.9%. Actuarial survival at 2 and 5 years for the patients in Stage I was distributed as follows: Group A, 78.2% and 52.1%; Group B, 80.0% and 57.8%. CONCLUSIONS: No statistically significant difference exists between the survival rates of the two groups. The data gathered suggest that patients in their seventh decade of life can receive surgical treatment exactly as younger patients in the case of non-small cell lung cancer in Stages I and II.
Adult↗
Videothoracoscopy versus thoracotomy for the diagnosis of the indeterminate solitary pulmonary nodule.
The solitary pulmonary nodule often presents a diagnostic challenge to the specialist because the nature of the nodule is often indeterminate at the end of the usual diagnostic process, and operation frequently is required before a definite diagnosis can be made. We have conducted a randomized, prospective trial to evaluate the diagnostic efficacy of video-assisted thoracic surgery versus muscle-sparing lateral thoracotomy. Between January 1991 and May 1994, 44 patients suffering from solitary pulmonary nodule were divided at random into two groups: the nodule was removed in 22 cases by video-assisted thoracic surgery and in 22 cases by lateral thoracotomy. Nineteen wedge resections, 1 segmentectomy, and 2 lobectomies were performed in the first group and 13 wedge resections, 8 segmentectomies, and 1 lobectomy in the second group. An "access" thoracotomy had to be performed in 5 patients in the video-assisted thoracic surgery group. The operating room time was 97.2 +/- 32.9 minutes in the video-assisted thoracic surgery group and 130.5 +/- 14 minutes in the lateral thoracotomy group (p > 0.05). In both groups a final diagnosis was made in 100% of cases. The postoperative hospital stay was 4.6 +/- 1.08 days in the video-assisted thoracic surgery group and 7.8 +/- 0.89 days in the lateral thoracotomy group (p < 0.01). Pain was evaluated on a visual analogue scale; the scores were 26.5 +/- 11.6 in the video-assisted thoracic surgery group and 48.3 +/- 12.8 in the lateral thoracotomy group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗