Expression of E-cadherin and ß-catenin in basaloid and conventional squamous cell carcinoma of the oral cavity: are potential prognostic markers?

BACKGROUND: Basaloid squamous cell carcinoma presents with a preference for the head and neck region, and shows a distinct aggressive behavior, with frequent local recurrences, regional and distant metastasis. The alterations in the cadherin-catenin complex are fundamental requirements for the metastasis process, and this is the first study to evaluate the immunostaining of E-cadherin and ß-catenin in oral basaloid squamous cell carcinoma. METHODS: Seventeen cases of this tumor located exclusively in the mouth were compared to 26 cases of poorly differentiated squamous cell carcinoma and 28 cases of well to moderately differentiated squamous cell carcinoma matched by stage and tumor site. The immunostaining of E-cadherin and ß-catenin were evaluated in the three groups and compared to their clinicopathological features and prognosis. RESULTS: For groups poorly differentiated squamous cell carcinoma and basaloid squamous cell carcinoma, reduction or absence of E-cadherin staining was observed in more than 80.0% of carcinomas, and it was statistically significant compared to well to moderately differentiated squamous cell carcinoma (p = .019). A strong expression of ß-catenin was observed in 26.9% and 20.8% of well to moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma, respectively, and in 41.2% of basaloid squamous cell carcinoma. The 5-year and 10-year overall and disease-free survival rates demonstrated no significant differences among all three groups. CONCLUSIONS: The clinical and biological behavior of three groups of the oral cavity tumors evaluated are similar. E-cadherin and ß-catenin immunostaining showed no prognostic value for basaloid and conventional squamous cell carcinomas.

Diagnosis of second primary tumor and long-term survival after single initial triple endoscopy in patients with head and neck cancer.

Patients with squamous cell carcinoma of the upper aerodigestive tract (UADT) have a high risk of developing second primary tumors (SPTs). Most of the studies concerning triple endoscopy (laryngoscopy, digestive tract endoscopy and bronchoscopy) describe the frequency and stage of the SPT, but not its impact on survival. This study is a matched pair analysis that included patients with squamous cell carcinoma of the UADT who were subjected to a triple endoscopy before the first treatment, matched with patients who did not undergo triple endoscopy. One hundred and thirty-five patients were included in each group. The diagnosis of an SPT was more frequent in the initial triple endoscopy group than in the control group (34 and 20 cases, respectively). In the initial triple endoscopy group, 50.0 % of these tumors were diagnosed simultaneously, whereas in the control, only 5.0 %. No significant differences in the survival rates or in clinical stage of the SPTs were found in the two groups. There was no difference in the clinical stage of the SPT and the survival rates of the patient groups who underwent triple endoscopy at the initial evaluation and those subjected to only a routine evaluation and follow-up.

High-risk human papillomavirus in oral squamous cell carcinoma of young patients.

The aim of this study was to investigate a possible relation between oral squamous cell carcinoma (SCC), the presence of high-risk human papillomavirus (HR-HPV) DNA and p16 expression in young patients. Paraffin-embedded tumor blocks from 47 oral SCC of young (≤40-year old) patients were evaluated. The presence of HPV DNA in tumor specimens was analyzed by polymerase chain reaction (PCR) using GP5+/GP6+ generic primers (L1 region) followed by dot blot hybridization for HPV typing. When necessary, the HPV16 positivity was confirmed by PCR HPV16 E7-specific primers. Cases involving young patients were compared with 67 oral SCC from patients ≥50-year old (controls). Demographic and clinical data were collected to analyze patient outcomes. p16(ink4) expression was evaluated by immunostaining of tissue microarrays. HPV16 was detected in 22 (19.2%) cases; 15 (68.2%) young and 7 (31.8%) control patients, a statistically significant difference (p = 0.01). In 1 (1.7%) young group specimen, HPV DNA 16 and 18 was detected. p16 expression was observed in 11 (25.6%) cases from the young group and in 11 (19.6%) controls (p = 0.48). Association between HPV and p16 was verified, and it was statistically significant (p = 0.002). The higher prevalence of high-risk HPV types, especially HPV16, may be a contributing factor to oral carcinogenesis in younger individuals.

Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians.

BACKGROUND: Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. METHODS: A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. RESULTS: Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. CONCLUSIONS: We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.

Primary transpupillary thermotherapy for small choroidal melanoma.

BACKGROUND: The treatment of small choroidal melanoma is controversial. Thermal laser-induced treatment is utilized by some centers but there is still sparse literature about the subject, mainly with short-term follow-up time. The efficacy of transpupillary thermotherapy (TTT) for the treatment of small choroidal melanomas was evaluated. METHODS: A prospective nonrandomized study of transpupillary thermotherapy for small (thickness ≤ 4.0 mm and basal diameter ≤ 12 mm) pigmented choroidal melanomas presenting either growth or risk factors for growth and metastasis. Ophthalmoscopic aspect, tumor control, visual acuity and complications were evaluated. RESULTS: Twenty-seven patients were treated; mean age 61 years; mean tumor thickness before treatment was 2.7 mm and base was 8.52 mm. After a mean of three treatment sessions and 45-month follow-up, mean tumor thickness decreased significantly to 1.34 mm (p < 0.001) and mean tumor base to 5.48 mm (p < 0.001). Complications were observed in 12 patients (44%) and included retinal vascular occlusion, optic disc atrophy, retinal traction, vitreous hemorrhage, rhegmatogenous retinal detachment, and maculopathy. Lesions touching the optic disc were associated with a significantly higher rate of disc atrophy after treatment (60% vs. 40%, p=0.030). Visual acuity remained the same in nine eyes (33%), improved in five (19%) and decreased during the first 6 months after treatment in 13 eyes (48%). Complete tumor control without recurrence was observed in 25 patients (93%). Recurrence at tumor margin was detected in two (7%). All eyes were preserved. One patient had tumor-related death. CONCLUSIONS: TTT is an effective treatment in the management of selected small choroidal melanoma. Decrease in visual acuity occurred early after treatment mainly associated with subfoveal and perifoveal tumors treatment and complications. Long-term randomized studies are still needed in order to better situate this treatment.

Expression of Bcl-2 family proteins and association with clinicopathological characteristics of oral squamous cell carcinoma.

AIMS: To characterize the expression of proteins that inhibit (Bcl-2, Bcl-x, Bcl-xL, Bcl-2-related protein A1, BAG-1) or promote (Bak, Bax, Bim/Bod, Bim-Long, Bad, Bid, PUMA) apoptosis and determine possible correlations between the expression of these proteins and clinicopathological features of oral squamous cell carcinoma (OSCC). METHODS AND RESULTS: Two-hundred and twenty-nine cases of OSCC, arranged in a tissue microarray, were immunohistochemically analysed. The results demonstrated that the absence of vascular invasion was associated with increased expression of Bak, Bax, Bcl-xL, Bcl-2-related protein and PUMA. Increased expression of Bim/Bod and BAG-1 was associated with the presence of perineural infiltration. An increase in Bid and Bim-Long expression was associated with moderately to well-differentiated tumours. Increased expression of the Bcl-2-related protein and PUMA was associated with tumours occurring in the floor of mouth and increased expression of PUMA was also associated with recurrence of the tumour. Multivariate Cox analysis demonstrated that PUMA and Bim-Long were independent factors in prognosis of OSCC. CONCLUSIONS: Our results showed the involvement of the Bcl-2 family of proteins in OSCC tumorigenesis and suggest that the expression of apoptotic molecules might be used as a prognostic indicator for OSCC.

Dietary isoflavone intake, polymorphisms in the CYP17, CYP19, 17beta-HSD1, and SHBG genes, and risk of breast cancer in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians.

We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and Sao Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17beta-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29-0.87; P for trend < 0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06-0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.

Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians.

Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20-74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) (P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk.

Dietary isoflavone intake and breast cancer risk in case-control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians.

Although epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk, little evidence for a dose-response relation is available. We conducted hospital-based case-control studies of patients aged 20-74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from medical checkup examinees in Nagano, Japan and from cancer-free patients in São Paulo, Brazil. A total of 850 pairs (390 Japanese, 81 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. The odds ratio of breast cancer according to isoflavone intake was estimated using a conditional logistic regression model. We found a statistically significant inverse association between isoflavone intake and the risk of breast cancer for Japanese Brazilians and non-Japanese Brazilians. For Japanese, a non-significant inverse association was limited to postmenopausal women. In the three populations combined, breast cancer risk linearly decreased from 'no' to 'moderate' isoflavone intake and thereafter leveled off. Compared to non-consumers, adjusted odds ratios (95% confidence interval) for consumers in increasing quintile intake categories (median intake in each category: 8.7, 23.1, 33.8, 45.7, and 71.3 mg/day) were 0.69 (0.44-1.09), 0.54 (0.31-0.94), 0.45 (0.26-0.77), 0.34 (0.19-0.62), and 0.43 (0.24-0.76), respectively. Overall, we found an inverse association between dietary isoflavone intake and risk of breast cancer. Our finding suggests a risk-reducing rather than risk-enhancing effect of isoflavones on breast cancer within the range achievable from dietary intake alone. In addition, women may benefit from risk reduction if they consume at least moderate amounts of isoflavones.

Genetic polymorphisms in estrogen metabolism and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians.

Although many studies have examined associations between single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2 and CYP1B1 genes and breast cancer risk, no study has examined functional SNPs in the CYP3A5 gene and only a small number of studies have been investigated in Japanese populations. To examine the association between six SNPs, CYP1A1(*)2A, CYP1A1(*)2C, CYP1A2(*)1F, CYP1B1 Arg(48)Gly, CYP1B1 Leu(432)Val and CYP3A5*3 and breast cancer risk, therefore, we conducted hospital-based case-control studies in Nagano, Japan and São Paulo, Brazil including 873 pairs (403 Japanese (JJ), 81 Japanese Brazilians (JB) and 389 non-Japanese Brazilians (NJB)). Although we found no significant association in the three populations combined, subgroup analyses revealed statistically significant associations of CYP1A2*1F in NJB, and CYP1B1 Leu(432)Val and CYP3A5*3 in JJ with breast cancer risk. Compared to women with the AA genotype in CYP1A2*1F, the odds ratio (OR) (95% confidence interval (CI)) for NJB with the CC genotype was 0.54 (0.32-0.90); that for JJ with Leu/Val+Val/Val versus Leu/Leu genotype in CYP1B1 Leu(432)Val was 0.68 (0.48-0.97); and that for JJ with (*)3/(*)1+(*)1/(*)1 versus (*)3/(*)3 genotype in CYP3A5*3 was 1.49 (1.10-2.04). Our findings provide further evidence that genetic polymorphisms related to estrogen metabolism may play a role in the development of breast cancer.

Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women.

BACKGROUND: Several studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated. METHODS: A case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12 were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR A2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Neither dietary intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23-3.83; P trend = 0.010). The MTR 2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01-3.92; P trend = 0.801), and statistically significant interactions with regard to risk were observed between the MTHFR A1298C polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022). CONCLUSION: MTHFR polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12 had no overall association with breast cancer risk. However, increased risk was observed in total women with the MTR 2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions between MTHFR polymorphisms and B vitamins, warrant further investigation.

Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer.

OBJECTIVE: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors. DESIGN: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats as an independent prognostic factor. RESULTS: Patients with alleles

Measuring satisfaction in family members of critically ill cancer patients in Brazil.

OBJECTIVE: To assess the determinants for satisfaction of cancer patients' family members with the intensive care unit. DESIGN: Prospective cohort study. SETTING: A 13-bed intensive care unit in a tertiary cancer centre. PATIENTS AND PARTICIPANTS: 164 families of consecutive patients with a length of stay greater than 48 h. INTERVENTION: None. MEASUREMENT: A modified version of the Critical Care Family Needs Inventory was applied and compared with the families' perception of prognosis, previous information given to them, and patients' severity of disease (SAPS). RESULTS: The median score of the questionnaire was 11 (2-14), and the cut-off for satisfaction was established at 9 (1st quartile). SAPS >41 was associated with lower satisfaction [(p<0.05, chi-square, OR 2.49 (CI 1.1-5.4)]. When those interviewed surmised a prognosis different from the final outcome [p<0.05, chi-square, OR 2.70 (1.2-6.0)], a significant association with dissatisfaction was found. CONCLUSION: More discussion about prognosis may improve the level of satisfaction of cancer patients' family members with the intensive care unit.

Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients.

PURPOSE: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables. EXPERIMENTAL DESIGN: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis. RESULTS: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer. CONCLUSIONS: The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.

Arterial reconstructions associated with the resection of malignant tumors.

OBJECTIVE: When trunk arteries are affected by malignant neoplasia, and surgical treatment involving tumor and arterial resection is used, the vascular reconstruction must be performed immediately to avoid ischemia in the brain and large tissue masses. The objective of this study was to analyze the results obtained with the treatment of patients with malignant neoplasia who underwent tumor and vascular resection associated with arterial reconstruction. The primary patency of reconstructions, the occurrence arterial complications, and patient survival were assessed. METHODS: Thirty-six patients with cervical, abdominal, or lower limb neoplasias were followed up. These patients underwent elective operations at Hospital do Câncer A.C. Camargo, São Paulo, between September 1997 and September 2004. They were divided into 3 groups according to tumor location: Cervical (14), lower limbs (13), and Abdomen (9). Thirty-eight arterial reconstructions were performed in these 36 patients. RESULTS: There were 5 arterial complications: 2 early- and 3 late-stage. The early complications consisted of 1 symptomatic carotid occlusion with sequelae and 1 femoral graft rupture without sequelae. The late-stage complications consisted of 1 symptomatic carotid occlusion, 1 occlusion of an axillary-carotid graft, and 1 occlusion of a branch of the aortobifemoral graft, all without sequelae. There was no difference between the primary arterial patency rates. All the deaths (22) resulted from progression of neoplasic disease. CONCLUSIONS: Arterial reconstructions associated with resection of malignant neoplasia in cervical, abdominal, or lower limbs can be carried out with low rates of morbidity and mortality. There was no difference in the primary arterial patency rates among the groups studied.

Comparison of low and high dose rate brachytherapy in the treatment of uterine cervix cancer. Retrospective analysis of two sequential series.

PURPOSE: This retrospective analysis aims to report on the comparative outcome of cervical cancer patients treated with low dose rate (LDR) and high dose rate (HDR) brachytherapy. METHODS AND MATERIALS: From 1989 to 1995, 190 patients were treated with low dose rate (LDR) brachytherapy (LDR group) and from 1994 to 2001, 118 patients were treated with high dose rate (HDR) brachytherapy (HDR group). FIGO stage distribution for the LDR group was Stage I: 6.3%; Stage II: 57.4%; and Stage III: 36.3% and for the HDR group Stage I: 9.3%; Stage II: 43.2%; and Stage III: 47.4%. All patients were treated with telecobalt external-beam radiotherapy (EBR). Median doses of LDR brachytherapy at Point A were 40 Gy and 50 Gy for patients treated with 1 and 2 implants, respectively. All patients from the HDR group were treated with 24 Gy in 4 fractions of 6 Gy to Point A. Survival, disease-free survival, local control, and late complications at 5 years, were endpoints compared for both groups. RESULTS: Median follow-up time for LDR and HDR groups was 70 months (range, 8-127 months) and 33 months (range, 4-117 months), respectively. For all stages combined, overall survival, disease-free survival, and local control at 5 years were better in the LDR group (69% vs. 55%, p = 0.007; 73% vs. 56%, p = 0.002; and 74% vs. 65%; p = 0.04, respectively). For clinical Stages I and II, no differences was seen in overall survival, disease-free survival, and local control at 5 years between the two groups. For clinical Stage III, overall survival and disease-free survival at 5 years were better in the LDR group than in the HDR group (46% vs. 36%, p = 0.04 and 49% vs. 37%, p = 0.03, respectively), and local control was marginally higher in the LDR group than in the HDR group (58% vs. 50%, p = 0.19). The 5-year probability of rectal complications was higher in the LDR group than in the HDR group (16% vs. 8%, p = 0.03) and 5-year probability of small bowel and urinary complications was not statistically different between the the LDR group and the HDR group (4.6% vs. 8.9%, p = 0.17 and 6% vs. 3%, p = 0.13, respectively). CONCLUSIONS: This comparative series suggests similar outcome for Stages I and II patients treated with either HDR or LDR brachytherapy. Lower overall and disease-free survival and marginally lower local control were observed for Stage III patients treated with HDR brachytherapy. Less late rectal complications were observed in the HDR group patients. These findings were probably the result of the relatively low HDR brachytherapy dose delivered at Point A.

[Swallowing after chemotherapy and radiotherapy for laryngeal and hypopharyngeal carcinomas]. / Deglutição após quimioterapia e radioterapia simultânea para carcinomas de laringe e hipofaringe.

UNLABELLED: The main goals of the larynx preservation protocol are eradication of cancer and preservation of a functional larynx with maintenance of respiration, phonation and swallowing. Few studies, however have addressed functional outcomes. OBJECTIVE: Functional evaluation of oropharyngeal swallowing in patients enrolled in a larynx preservation protocol at the Hospital do Câncer AC Camargo. METHODS: Evaluation of swallowing was performed by videofluoroscopy in 31 patients, focusing on: oropharyngeal motility disorders, stasis, laryngeal penetration, aspiration and severity of dysphagia. RESULTS: Swallowing analysis: 5 patients showed inefficient bolus preparation, 14 had changes in the bolus propulsion; 23 patients had a reduced laryngeal elevation, 26 presented with stasis in the vallecula and 14 with stasis in hypopharynx. Nine patients presented silent aspiration. We detected functional swallowing in 11 patients; mild dysphagia in 7; mild/moderate in 7; moderate in 3 and severe dysphagia in 3. CONCLUSION: Larynx preservation results in changes of swallowing, ranging in their majority from discrete to moderate. Some patients, however, developed severe dysphagia, and oral feeding was not possible.

TP53 mutations in primary breast carcinomas from white and African-Brazilian patients.

We have attempted to determine the incidence, nature and clinical significance of TP53 mutation in a group of white (242 cases) and African-Brazilian (52 cases) patients with breast cancer. The interethnic admixture as estimated by STR markers showed that white subjects displayed 67.9+/-0.4%, 25.0+/-1.7% and 7.0%+/-1.6% and the black populations had 34.4+/-1.9%, 56.2+/-1.9 and 9.4+/-2.2% respectively of European, African and Amerindian genes. Clinical parameters such as age, lymph node status and steroid receptors were similar in both groups. African-Brazilian patients presented more advanced lesions. Mutation screening was performed using polymerase chain reaction-single strand conformation analysis followed by sequencing. Compared to whites (13.6%), a relatively high frequency of TP53 mutation was found in blacks (32.7%) (p=0.001). African-Brazilian women have a larger proportion of mutations in exons 5 and 7, whereas white women have more mutations in exon 8. Mutations within exon 4 were found only in tumors of white patients. The spectra of TP53 mutations show that A:T-->G:C nucleotide transversion and G:C-->C:G transition were more common in African-Brazilian women whereas G:C-->T:A transversion occurs very frequently in whites. A high prevalence of G:C-->A:T nucleotide transitions and deletions was detected in both groups. No association was found between p53 gene mutation and tumor or clinical parameters independently of the ethnic group. With a median follow-up of 35.6 months for whites and 43.4 months for the blacks, no differences in overall survival were found. If white patients were stratified according to the type and location of TP53 mutations, patients with mutations affecting amino acids directly involved in DNA or Zn binding displayed a poor prognosis. The pattern of mutations found in our population seems to reflect a base line pattern observed in populations with similar ethnic profile with some modifications, which might be derived from specific etiological factors.

Cyclin D1 gene polymorphism as a risk factor for squamous cell carcinoma of the upper aerodigestive system in non-alcoholics.

Squamous cell carcinoma of the upper aerodigestive tract (UADT) is associated with environmental factors, especially tobacco and alcohol consumption. Genetic factors, including cyclin D1 (CCND1) polymorphism have been suggested to play an important role in tumorigenesis and progression of UADT cancer. To investigate the relationship between CCND1 polymorphism on susceptibility for UADT cancers, 147 cancer and 135 non-cancer subjects were included in this study. CCND1 genotype at codon 242(G870A) in exon 4 was undertaken using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. Significant odds ratio (OR) of the AA+GA genotypes [OR=7.5 (95% CI: 1.4-39.7)] was observed in non-drinkers but for non-smokers a non-significant [OR=5.4 (95% CI: 0.9-31.4)] was found in the adjusted model. These results suggest that allele A may be a risk factor for UADT cancer, especially in non-alcoholics. However, further epidemiological studies are needed to establish the exact role of CCND1 polymorphism and the development of UADT cancers.

Voice and swallowing in patients enrolled in a larynx preservation trial.

BACKGROUND: The main goals of larynx preservation protocols are preservation of a functional larynx with intact voice and maintenance of normal deglutition. However, few studies have addressed functional outcomes. OBJECTIVES: To evaluate voice and swallowing in patients enrolled in a larynx preservation protocol. DESIGN AND SETTING: Acoustic analysis of 15 patients and videofluoroscopic evaluation of 14 patients who underwent chemoradiotherapy in an attempt to preserve the larynx. PATIENTS: Forty-three patients with larynx or hypopharynx squamous cell carcinomas were treated with weekly paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) concurrent to radiotherapy (180-rad/d fraction [1.8 Gy] to 7040 rad [70.4 Gy]). Voice was analyzed perceptually and acoustically in 15 patients. Videofluoroscopic evaluation of swallowing was performed in 14 patients, focusing on oropharyngeal motility disorders, stasis, laryngeal penetration, aspiration, and dysphagia severity. RESULTS: Vocal analysis produced normal results in 1 patient, mild dysphonia in 4, moderate dysphonia in 6, and severe dysphonia in 4. The mean fundamental frequency for acoustic analysis was 131.4 Hz for men and 109.8 Hz for women. Acoustic measures of perturbation and noise were above the reference limits, indicating changes in the voice signal. Swallowing analysis showed inefficient bolus preparation in 13 patients and changes in the bolus propulsion in 12. Stasis was observed in all areas of the oropharynx. Five patients had reduction in laryngeal elevation, and 12 had stasis in the hypopharynx. Five patients presented with silent aspiration. We detected functional swallowing in 3 patients, mild dysphagia in 7, mild or moderate dysphagia in 2, and severe dysphagia in 2. CONCLUSIONS: Laryngeal preservation resulted in voice and swallowing abnormalities, but they tend to be mild to moderate, allowing intelligible communication and efficient swallowing in most patients.