Head and neck mucosal melanoma: clinicopathological analysis of 51 cases treated in a single cancer centre and review of the literature.

Head and neck mucosal melanoma (HNMM) is a rare and aggressive malignancy. The objective of this study was to describe the outcomes of patients with HNMM. Clinical and pathological data from 51 patients with primary HNMM were reviewed. All patients were treated at a single cancer centre between 1954 and 2012. Most tumours involved the nasal cavity (35.3%) and upper gingiva (29.4%). The majority of lesions were ulcerated (54.9%) and pigmented (84.3%). Forty-three patients underwent surgical treatment and 21 (41.2%) underwent adjuvant chemotherapy and/or radiotherapy. Eight patients (15.7%) received palliative treatment. The median follow-up period was 21 months. During this period, 30 (58.8%) patients had tumour recurrences. At the last clinical evaluation, only seven (13.7%) patients were alive with no evidence of disease and three (5.9%) were alive with HNMM. There were significant differences in overall survival probability according to the presence of ulceration (P=0.004), metastatic lymph nodes (P=0.003), and treatment including a radical surgical procedure (P<0.001). On multivariate analysis, ulceration was the only variable associated with an increased risk of death. Despite the poor prognosis, there was significant improvement in overall survival in the most recent years in this sample, mainly due to advances in diagnosis and reconstruction techniques.

Fatty acid synthase expression in squamous cell carcinoma of the tongue: clinicopathological findings.

BACKGROUND: Overexpression of fatty acid synthase (FAS), the cytosolic enzyme responsible for the conversion of dietary carbohydrates to fatty acids, has been reported in several human malignancies and pointed as a potential prognostic marker for some tumors. This study investigated whether FAS immunohistochemical expression is correlated with the clinicopathological characteristics of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The clinical features of 102 patients with OSCC of the tongue treated in a single institution were obtained from the medical records and all histopathological diagnoses were reviewed. The expression of FAS was determined by the standard immunoperoxidase technique in formalin-fixed and paraffin-embedded specimens and correlated with the clinicopathological characteristics of the tumors. RESULTS: Eighty-one cases (79.41%) were positive for FAS. Microscopic characteristics such as histological grade (P < 0.05), lymphatic permeation (P < 0.001), perineural infiltration (P < 0.05), and nodal metastasis (P < 0.02) were associated with FAS status. A significantly lower survival probability for patients with advanced clinical stage (log-rank test, P < 0.001), lymph nodes metastasis (log-rank test, P < 0.001), presence of vascular permeation (log-rank test, P = 0.05), and perineural invasion (log-rank test, P = 0.01) was observed in the studied samples. CONCLUSION: The expression of FAS in OSCC of the tongue is associated with the microscopic characteristics that determine disease progression and prognosis.

Low-energy laser therapy for prevention of oral mucositis in hematopoietic stem cell transplantation.

AIM: To evaluate the clinical effects of laser therapy on the prevention and reduction of oral mucositis in patients who underwent hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: From January 2003 to September 2004, 24 patients received prophylactic laser therapy (L+ group). The applications started from the beginning of the conditioning regimen up to day +2. The oral assessment was performed daily until day +30. This group was compared with historical controls, namely 25 patients, who did not receive laser therapy (L- group). RESULTS: All patients developed some grade of mucositis. However, the L- group presented initial mucositis by 4.36 days, whereas the L+ group presented it in 6.12 days (P = 0.01). The maximum mucositis occurred between day +2 and day +6 with healing by day +25 in the L- group and between day +2 and day +7 with healing by day +14 for the L+ group (P = 0.84). Laser therapy also reduced the time of oral pain from 5.64 to 2.45 days (P = 0.04), and decreased the consumption of morphine (P = 0.07). CONCLUSION: This study suggests that laser therapy can be useful in oral mucositis to HSCT patients and improve the patient's quality of life. However, controlled randomized trials should be performed to confirm the real efficacy of laser therapy.

Interobserver perceptual analysis of smokers voice.

The purpose of this study was to investigate variations in the voice by three experienced speech-language therapists. Forty-eight men and nine women from the Associação dos Alcoólicos Anônimos, Santos were studied. Their ages were from 28 to 81 years, with median of 49 years and everyone was a smoker for 60 to 720 months. Most of them used more than 20 cigarettes a day and all of them had stopped alcohol use for 1 to 25 months. The perceptual analysis of the voices was performed by means of the GRBAS scale. The voice sample consisted of a sustained vowel /a/ at a comfortable pitch and loudness level. The three judges were blinded to the opinion of their colleagues and a kappa test was applied. For roughness, the concordance rates were 59.6% for observers 1 and 2 (kappa = 0.234); 47.4% for 1 and 3 (kappa = 0.047) and 52.6% (kappa = 0.016) for 2 and 3. For breathiness, the concordance rates were 80.7% for observers 1 and 2 (kappa = 0.191); 57.9% for 1 and 3 (kappa = 0.147) and 57.9% (kappa = 0.156) for 2 and 3. With regard to asthenic quality, there was concordance of 100% for observers 1 and 2, so kappa could not be applied; the concordance rate was 96.5% for 1 and 3 and for 2 and 3. The evaluation for strained voice revealed concordance rates of 71.9% for observers 1 and 2 (kappa = -0.017); 59.6% for 1 and 3 (kappa = 0.095) and 70.2% (kappa = 0.039) for 2 and 3. The disagreement among the observers was worst for pathological rather than normal voices; when disagreement was present among experienced judges, it was of only one point in the scale used.

The CAG repeat polymorphism in the androgen receptor gene (AR) and its relationship to head and neck cancer.

Sex hormones may play an important role in the tumorigenic process of the head and neck. The aim of our work was to investigate whether the androgen receptor (AR) CAG repeat polymorphism is associated with an increased relative risk for head and neck cancer. Genomic DNA from 103 male patients with head and neck carcinomas and 100 male controls were analyzed for the AR CAG polymorphism by PCR amplification and direct sequencing or denaturing polyacrilamide gel electrophoresis. Logistic regression analysis showed a significant association between CAG repeat length and risk of head and neck cancer in individuals with more than 20 CAG repeats [OR=2.54 (95% CI, 1.3-4.8)]. For the group of individuals with oral and laryngeal cancer the estimated relative risk was increased to 2.79 (95% CI, 1.2-6.3) and 3.06 (95% CI, 1.0-9.6), respectively, in men with CAG repeat length >20. These results suggest, for the first time, that shorter AR CAG repeat alleles have a protective effect for head and neck cancer development.

Presence of ductal carcinoma in situ confers an improved prognosis for patients with T1N0M0 invasive breast carcinoma.

We have retrospectively analyzed a series of 155 sequential cases of T1N0M0 ductal carcinomas of which 51 tumors had a ductal carcinoma in situ (DCIS) component for correlation between the presence of DCIS and clinicopathological variables, recurrence and patient survival. No correlations between the presence of DCIS and age, menopausal status, size, estrogen or progesterone receptors were found. High-grade infiltrative tumors tended not to present a DCIS component (P = 0.08). Patients with tumors associated with DCIS form a subgroup with few recurrences (P = 0.003) and good survival (P = 0.008). When tumors were classified by size, an association between large tumors (>1.0 cm) and increased recurrence and shortened overall survival was found. The presence of DCIS in this subgroup significantly reduced the relative risk of death.

Presence of ductal carcinoma in situ confers an improved prognosis for patients with T1N0M0 invasive breast carcinoma

We have retrospectively analyzed a series of 155 sequential cases of T1N0M0 ductal carcinomas of which 51 tumors had a ductal carcinoma in situ (DCIS) component for correlation between the presence of DCIS and clinicopathological variables, recurrence and patient survival. No correlations between the presence of DCIS and age, menopausal status, size, estrogen or progesterone receptors were found. High-grade infiltrative tumors tended not to present a DCIS component (P = 0.08). Patients with tumors associated with DCIS form a subgroup with few recurrences (P = 0.003) and good survival (P = 0.008). When tumors were classified by size, an association between large tumors (>1.0 cm) and increased recurrence and shortened overall survival was found. The presence of DCIS in this subgroup significantly reduced the relative risk of death

Serological Immunoglobulin G antibody titers to Helicobacter pylori in Japanese Brazilian and Non-Japanese Brazilian gastric cancer patients and controls in São Paulo.

Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer (GC), though evidence for this association is scarce in high-risk areas. Possible case control and/or ethnic differences were investigated as to the presence of H. pylori and its immunogloblin G antibody titer in the multi-ethnic city of São Paulo, where the incidence of GC is relatively high. We performed a cross-sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and non-Japanese Brazilian GC patients and their controls. Japanese Brazilian patients were matched by age, sex and ethnicity with two controls, while non-Japanese Brazilian patients were matched as above with one control. Among Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%) controls were positive for H. pylori-specific antibody (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.47 - 1.36), while among non-Japanese Brazilians, 171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive (OR = 0.84, 95% CI = 0.54 - 1.30). The median serum antibody titer was lower in cases than in controls in both ethnic groups. A high titer (H. pylori titer > or = 50) was associated with less likelihood of GC for both ethnic groups (for Japanese Brazilians, OR = 0.39, 95% CI = 0.16 - 0.92; for non-Japanese Brazilians, OR = 0.56, 95% CI = 0.31 - 1.02). The high titer can be regarded as a sign of the necessity of eradication, and low titer is regarded as a sign of the necessity of close screening for GC in both ethnic groups, because extended atrophy may cause spontaneous disappearance of H. pylori from the stomach.

Prognostic significance of the combined expression of matrix metalloproteinase-9, urokinase type plasminogen activator and its receptor in breast cancer as measured by Northern blot analysis.

Using Northern blot analysis we have measured the co-expression of the matrix metalloprotease MMP-9, plasminogen activator urokinase type (uPA) and its receptor (uPAR) mRNAs in 81 biopsies of breast carcinomas with the objective of analyzing the impact of these factors on the overall survival probability of the patients (median follow-up time: 4 years). Individual mRNA levels of either uPA or uPAR showed parallel variations with MMP-9 mRNA, suggesting a coordinate transcription of these markers. When median values were used as cutoff points to discriminate between high and low factor expression, no association was found with patient outcome and MMP-9 or uPA mRNA distribution. However, increased uPAR mRNA levels were associated with poor prognosis (p = 0.01). The combination of MMP-9 and uPAR mRNA measurements has not enhanced prognostic information compared to information supplied by the receptor alone (p = 0.01). The combination of MMP-9 and high levels of uPA mRNA led to a significant association with poor outcome (p = 0.03). Multivariate analysis supported the notion that increased uPAR mRNA production in primary breast cancer may be a predictor of overall survival.

Hypomagnesemia in critically ill cancer patients: a prospective study of predictive factors.

Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6%) patients had hypomagnesemia and 123 (54.4%) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 +/- 0.14 mmol/l compared with 0.66 +/- 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1. 17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations.

Hypomagnesemia in critically ill cancer patients: a prospective study of predictive factors

Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6 percent) patients had hypomagnesemia and 123 (54.4 percent) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 ± 0.14 mmol/l compared with 0.66 ± 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1.17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations

Cytochrome P450 2E1 polymorphism in gastric cancer in Brazil: case-control studies of Japanese Brazilians and non-Japanese Brazilians.

Cytochrome P450 2E1 (Cyp2E1) is involved in the metabolic oxidation of carcinogenic nitroso compounds, including N-nitrosoamines. There is an RsaI polymorphism in the transcriptional regulatory region of this gene, and in vitro evidence suggests that the variant type of this polymorphic site has higher transcriptional activity but less chlorzoxazone-metabolizing activity. Interindividual differences in the metabolic capacity of Cyp2E1 are assumed to be associated with cancer susceptibility, but the results of the previous studies on the relation between Cyp2E1 RsaI polymorphism and cancer susceptibility have been inconsistent. Two case-control studies of gastric cancer in Japanese Brazilians (96 cases, 192 controls) and Brazilians not of Japanese ancestry (non-Japanese Brazilians; 236 cases, 236 controls) in São Paulo were designed to clarify the role of the Cyp2E1 RsaI genotype in susceptibility to gastric cancer after considering multifactorial environmental influences. The subjects with variant RsaI genotypes amounted to 47% (28 of 59) and 48% (64 of 133), respectively, of the Japanese cases and controls, and 6% (11 of 187) and 10% (19 of 192), respectively, of the non-Japanese cases and controls. As expected, a difference in the distributions of the two groups was observed. The odds ratio of the RsaI variant genotype of Cyp2E1 was 0.46 (95% confidence interval, 0.21-1.04) in the non-Japanese Brazilian population and 0.98 (95% confidence interval, 0.50-1.90) in the Japanese Brazilian population after adjusting for sex, age, tobacco use, and meat consumption. Additional adjustment for potential confounding factors did not change the odds ratio substantially. No significant interactions were observed between the polymorphism and environmental factors. In regard to the histological type of gastric cancer, the variant genotype was significantly more prevalent than the common genotype in Japanese subjects with diffuse type gastric cancer. Our study suggests that the Cyp2E1 RsaI polymorphism is associated with a reduced risk of gastric cancer, although how the assumed increase in Cyp2E1 expression produced by this polymorphism is related to a reduced risk of cancer remains unclear. The observations in this study are consistent with the recent observations of esophageal cancer in endemic areas of China.

Ethnic differences in serum pepsinogen levels among Japanese and non-Japanese Brazilian gastric cancer patients and controls.

A low level of serum pepsinogen I (Pg I) is a risk factor for gastric cancer (GC); low levels of Pg I and the pepsinogen ratio (Pg I:Pg II) are correlated with chronic atrophic gastritis. We report serum Pg levels and compare the degree of association with GC among Japanese and non-Japanese Brazilians. Sera were cross-sectionally ascertained from 93 Japanese Brazilian patients category matched by age and sex with 110 controls, and 228 non-Japanese Brazilian patients individually matched by age and sex with one control. Among non-Japanese Brazilians, GC was associated with a Pg I level <30 ng/ml (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.8) and a Pg I:Pg II ratio < 3.0 (OR, 3.4; 95% CI, 2.2-5.3). However, among Japanese Brazilians, the association was present with a level of Pg I < 30 ng/ml (OR, 3.5; 95% CI, 1.9-6.3), and was weak with a Pg I:Pg II ratio < 3.0 (OR, 1.3; 95% CI, 0.73-2.4). Serum Pg I may be preferred to the Pg I:Pg II ratio to study the association between Pg and GC among Japanese Brazilians.

Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations.

The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an aggressive form of the disease.