The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer.

Various guidelines recommend that women with triple-negative breast cancer should be tested for BRCA1 mutations, but the prevalence of mutations may vary with ethnic group and with geographic region, and the optimal cutoff age for testing has not been established. We estimated the frequencies of BRCA1 and BRCA2 (BRCA) mutations among 190 women with triple-negative breast cancer, unselected for family history, diagnosed at age 50 or less at a single hospital in Mexico City. Patients were screened for 115 recurrent BRCA mutations, which have been reported previously in women of Hispanic origin, including a common large rearrangement Mexican founder mutation (BRCA1 ex9-12del). A BRCA mutation was detected in 44 of 190 patients with triple-negative breast cancer (23 %). Forty-three mutations were found in BRCA1 and one mutation was found in BRCA2. Seven different mutations accounted for 39 patients (89 % of the total mutations). The Mexican founder mutation (BRCA1 ex9-12del) was found 18 times and accounted for 41 % of all mutations detected. There is a high prevalence of BRCA1 mutations among young triple-negative breast cancer patients in Mexico. Women with triple-negative breast cancer in Mexico should be screened for mutations in BRCA1.

Overweight and obesity as poor prognostic factors in locally advanced breast cancer patients.

Obesity and overweight are established risk factors for the development of breast cancer. They are also associated with poor prognosis for higher risk of disease recurrence and lower overall survival (OS). The aim of this study was to evaluate the influence of overweight and obesity in OS in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy. This is a retrospective analysis that included 819 patients diagnosed with LABC between January 2004 and December 2008. The patients were treated with neoadjuvant chemotherapy (NAT) based on anthracyclines, taxanes, or both, followed by surgery. For comparison, patients were divided into the normal weight (NW) group or the overweight/obesity (OW/OB) group. The prevalence of overweight/obesity was 74 %. General characteristics of the patients, including age, tumor size, clinical stage, nuclear grade, hormone receptors, and HER2 expression, were similar between both groups. At a median follow-up of 28 months, we found a statistically significant difference in OS between the two groups, achieving a 91.5 % in NW patients versus 85.9 % in the OW/OB group (P = 0.050). Cox multivariate analysis demonstrated that obesity was an independent factor for poor prognosis, with a hazard ratio of 1.79 (95 % CI (Confidence Interval) 1.09-2.96; P = 0.022). This is the first Mexican study that confirms the role of OW/OB as a risk factor for poor outcome among patients with LABC. Obesity in our country is a public health problem and requires strong preventive intervention strategies for its control, especially among patients diagnosed with breast cancer.

A Y/15 translocation in a 45,X male with Prader-Willi syndrome.

We report a male neonate with a 45 X karyotype; the long arm of a chromosome 15 was translocated onto the proximal long arm of the Y chromosome. Breakpoints were identified by in situ fluorescence hybridization (FISH) on the proximal 15q13 and Yq11.2. The derivative chromosome has no primary centromere. Clinical features were compatible with Prader-Willi syndrome. This is the first report case ofmonosomy 15q and Yq deletion with Prader-Willi syndrome.

Viruses other than HIV and non-Hodgkin's lymphoma.

There are several viral infections which are known to cause lymphoma among animals; all establish latency in lymphoid cells. The human T-lymphotropic virus type I is a human virus which causes lymphomas among a subset of carriers. However, this virus is very restricted in its distribution and as such, is unlikely to play a role in the increase of non-Hodgkin's lymphoma (NHL). A highly prevalent infection, the Epstein-Barr virus (EBV) is known to play a role in the etiology of NHL among persons with acquired or inherited immune suppression. However, whether it is involved with "spontaneous" NHL is unknown. We have found evidence that among a group of 104 NHL patients with blood samples taken several years before diagnosis, there was an alteration in the antibody profile against the EBV which is quite similar to that seen for immune-suppressed patients prior to their diagnosis. This pattern is most evident in the oldest patients. This suggests that there may be an age-related subclinical immune suppression leading to chronic activation of EBV. If a viral infection is a major factor in the recent increase in NHL in the world, then we should consider the role of immune-suppressive exposures which have become widespread in recent decades.

Dichlorodiphenyltrichloroethane serum levels and breast cancer risk: a case-control study from Mexico.

Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which DDT is still being used to control malaria. In a hospital-based case-control study, we compared 141 histologically confirmed cases of breast cancer with 141 age-matched controls (+/-3 years). All subjects were identified at three referral hospitals of Mexico City between March 1994 and April 1996. Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/- 676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range, 0.004 to 4361.75) for the controls, but this difference was not statistically significant. The age-adjusted odds ratios for breast cancer regarding the serum level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for body mass, accumulated time of breast-feeding and menopause, and other breast cancer risk factors. These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor.

Antimicrobial resistance and characterization of Helicobacter pylori strains isolated from Mexican adults with clinical outcome.

Eradication of Helicobacter pylori infection in Mexico is of great importance due to the elevated seroprevalence, however, there is yet very little information about antibiotic resistance rates in H. pylori isolates in our country. We analyzed susceptibility to three antimicrobials used in therapy of 49 H. pylori strains isolated from patients with active chronic gastritis, active chronic gastritis with lymphoid follicles, intestinal metaplasia and gastric cancer. All isolated strains were susceptible to amoxicillin, 28 (58%) were resistant to metronidazole and 2 (4%) were resistant to both clarithromycin and metronidazole. Sequence analysis of the 23S rRNA of the two clarithromycin-resistant strains showed the A2142G mutation in one and A2143G and T2182C mutations in the other. Metronidazole resistance was associated with cagA negative strains with a frequency of 82% (9/11). No significant correlation was found between vacA s/m alleles and metronidazole resistance.

The spectrum of clinical and pathological manifestations of AIDS in a consecutive series of autopsied patients in Mexico.

OBJECTIVE: Little is known about the clinical profile of AIDS in Latin American populations. This study characterizes the clinical and pathological manifestations of AIDS in a representative series of Mexican AIDS patients at autopsy. DESIGN: The clinical and pathological findings were abstracted retrospectively for a sequential series of autopsied AIDS patients. SETTING: Autopsies were conducted at the four major tertiary level hospitals that serve the majority of AIDS patients in Mexico City. PATIENTS: Subjects included 177 consecutive patients diagnosed with AIDS between March 1984 and January 1989 who subsequently died and were autopsied in the same period in the study hospitals. MAIN OUTCOME MEASURES: Demographic characteristics, including age, gender, residence, socioeconomic status, and risk group; clinical presentation and autopsy findings, including opportunistic infections and malignancies. RESULTS: Sixty per cent of the AIDS patients presented with wasting syndrome. The most common infections were cytomegalovirus (69%), tuberculosis (25%), and Pneumocystis carinii pneumonia (24%). Central nervous system infections were also common and included toxoplasmosis (19%) and cryptococcoses (10%). Kaposi's sarcoma was present in 30% of cases and non-Hodgkin's lymphoma in 9%. CONCLUSION: Clinical manifestation, and types and frequency of opportunistic infections in our Mexican AIDS patients were more similar to those seen in AIDS patients in Africa and Haiti than in the United States and Europe. These findings suggest that the AIDS epidemic in Mexico has an 'intermediate' pattern and may be a prototype for Latin American countries.

A model for the AIDS epidemic in Mexico: short-term projections.

As in many developing countries, the AIDS epidemic in Mexico has become a major public health problem. Given the competition for scarce health resources in Mexico, where hospitals are overcrowded and care for AIDS patients is often unavailable, planning depends on accurate estimates of the incidence of AIDS and the prevalence of HIV-1 infection. This article presents estimates of AIDS incidence in Mexico corrected for delays in reporting and short-term projections based on the corrected AIDS incidence. Trends in incidence cannot be assessed without such correction because only about 50% of AIDS cases are reported within 4 months of diagnosis. In addition to information on AIDS incidence, short-term projections also require estimates of the latency distribution between infection with HIV-1 and onset of AIDS. Latency periods with medians of 8 and 10 years lead to estimates that 22,000 and 24,000 new AIDS cases infected before June 1989 will be diagnosed between 1989 and 1994.

Screening markers for chronic atrophic gastritis in Chiapas, Mexico.

Intestinal-type gastric adenocarcinomas usually are preceded by chronic atrophic gastritis. Studies of gastric cancer prevention often rely on identification of this condition. In a clinical trial, we sought to determine the best serological screening method for chronic atrophic gastritis and compared our findings to the published literature. Test characteristics of potential screening tests (antibodies to Helicobacter pyloni or CagA, elevated gastrin, low pepsinogen, increased age) alone or in combination were examined among consecutive subjects enrolled in a study of H. pylori and preneoplastic gastric lesions in Chiapas, Mexico; 70% had chronic atrophic gastritis. English-language articles concerning screening for chronic atrophic gastritis were also reviewed. Sensitivity for chronic atrophic gastritis was highest for antibodies to H. pylori (92%) or CagA, or gastrin levels >25 ng/l (both 83%). Specificity, however, was low for these tests (18, 41, and 22%, respectively). Pepsinogen levels were highly specific but insensitive markers of chronic atrophic gastritis (for pepsinogen I <25 microg/l, sensitivity was 6% and specificity was 100%; for pepsinogen I:pepsinogen II ratio <2.5, sensitivity was 14% and specificity was 96%). Combinations of markers did not improve test characteristics. Screening test characteristics from the literature varied widely and did not consistently identify a good screening strategy. In this study, CagA antibodies alone had the best combination of test characteristics for chronic atrophic gastritis screening. However, no screening test was both highly sensitive and highly specific for chronic atrophic gastritis.

Interobserver variability in application of the revised Sydney classification for gastritis.

The Sydney classification for gastritis provides guidelines for histological grading of gastric biopsies. In an ongoing study of gastric preneoplastic lesions in Chiapas, Mexico, 7 biopsies from 150 patients (4 from the antrum and 3 from the body) were obtained during endoscopy and studied histologically. The first 74 endoscopy specimens were read independently by 2 general surgical pathologists. We assessed diagnostic concordance using kappa statistics. The 2 pathologists then jointly reviewed biopsies about which they had disagreed to reach a final diagnosis. A second group of 76 endoscopies was subsequently evaluated independently by the 2 pathologists, and concordance was again assessed. In the first group of biopsies, we found low concordance rates (Heliobacter pylori 0.59, acute inflammation 0.22, intestinal metaplasia 0.60, and atrophy 0.04). In the second group, of independently reviewed cases, there was better concordance (H pylori 0.77, acute inflammation 0.50, intestinal metaplasia 0.70, and atrophy 0.64). We presumed that use of the Sydney classification would result in minimal interpretational differences achieving ideal kappas greater than 0.80. Because pathology results are based on subjective interpretation of this classification, complete diagnostic agreement is practically impossible. Concordance by general surgical pathologists after joint review of cases was similar to that obtained by gastrointestinal pathologists.

Gastric atrophy and extent of intestinal metaplasia in a cohort of Helicobacter pylori-infected patients.

Atrophy and intestinal metaplasia (IM) are preneoplastic gastric lesions associated with Helicobacter pylori infection. Atrophy and IM are usually found together; however, the association between increasing degrees of severity of both atrophy and IM has not been evaluated completely. Two pathologists graded atrophy and IM using the visual analog scale of the Sydney classification in gastric biopsies from 368 H pylori-infected patients. Extent of IM also included determining the number of specimens affected. We then correlated the degree of atrophy with the degree and number of specimens affected with IM by calculating relative risks (RR) and 95% confidence intervals (95% CI). The mean number of biopsies examined from each patient was 6.5. Atrophy and IM were found more frequently in the antrum (85% and 75% of biopsies, respectively). One hundred thirty-eight patients had a combination of atrophy and IM, 48 had IM only, and 89 had atrophy only. Fifty-three subjects had mild atrophy and IM (RR = 1.57; 95% CI 1.2-2.1), 69 had moderate atrophy and IM (RR = 1.86; 95% CI 1.9-2.4), and 16 had marked atrophy and IM (RR = 2.47; 95% CI 1.8-3.3). The median number of biopsy specimens with IM increased from 0 in subjects with no atrophy to 3 in subjects with severe atrophy. The degree of IM correlated with the degree of atrophy; the median degree was 0.6 in subjects with no atrophy and increased to 2.32 in those with severe atrophy. Our data suggest that higher degrees of IM in an individual specimen and increasing number of specimens with IM are associated with moderate or severe degrees of atrophy.

Surgical site infections at the National Cancer Institute in Mexico: a case-control study.

OBJECTIVES: To quantify the surgical infection rate and to identify risk factors associated with surgical site infection. METHODS: We conducted a case-control study of all surgical patients between January 1, 1993, and June 30, 1994. The frequency of surgical site infection per 100 surgeries was calculated. The odds ratio (OR) was estimated by using logistic regression analysis. SETTING: A 130-bed tertiary-care teaching hospital for adult patients with cancer. RESULTS: The study followed 3372 surgeries. Three hundred thirteen patients had a surgical site infection (rate per 100 surgeries: 9. 30). The risk factors associated with surgical site infection were diabetes mellitus (OR = 2.5, 95% confidence interval [CI] = 1.27-4. 91), obesity (OR = 1.76, 95% CI = 1.14-2.7), presence of surgical drains for >5 and <16 days (OR = 1.84, 95% CI = 1.02-3.31), and presence of surgical drains for >/=16 days (OR = 2.14, 95% CI = 1. 0-4.6). The bacteria most frequently isolated were Escherichia coli 38 (21.8% of the total of microorganisms found), Pseudomonas sp 22 (12.6%), Staphylococcus aureus 16 (9.2%), and coagulase-negative Staphylococcus 25 (13.6%). The coexistence of other nosocomial infections was greater among the cases (OR = 1.8, 95% CI = 1.1-3.1) than in the control group. CONCLUSIONS: The surgical site infection rate in our hospital is slightly higher than the rates reported for general hospitals. The risk factors associated with surgical site infection are similar to those previously reported. Diabetes mellitus, obesity, and prolonged presence of a surgical drain increased the risk of infection.

Single-step PCR amplification and enzyme restriction analysis of the entire Helicobacter pylori cytotoxin vacA gene for genetic variability studies.

To monitor changes along the entire Helicobacter pylori vac A gene we carried out full-length single-step PCR amplification in 21 gastritis and gastric cancer isolates. HindIII restriction analysis led us to detect a > 400-bp internal insertion in vacA subsequently shown to be a direct 451-bp gene duplication. We found HindIII profiles for 16 genes that allowed their grouping into two restriction patterns that were related to theoretical profiles for previously sequenced Western genes. Comparisons with theoretical HindIII patterns for Japanese isolates appear suggestive of geographical H. pylori clonality. Full-length single-step PCR amplification seems suitable for quick restriction pattern assignment and detection of gene size changes.

Constitutional translocation (8;13) in a patient with non-Hodgkin's lymphoma.

We report a case of non-Hodgkin's lymphoma in a 16-year-old male, whose peripheral white blood cells have a t(8;13)(q24;q14). There are no previous reports that describe this association. Although the tumor cells were not studied, we discuss the possible link between this finding and the development of the malignant lymphoma.

Intralesional vinblastine vs. 3% sodium tetradecyl sulfate for the treatment of oral Kaposi's sarcoma. A double blind, randomized clinical trial.

In this double-blind, randomized trial, we compared the clinical efficacy of intralesional vinblastine (VNB) and 3% sodium tetradecyl sulfate (STS) in the treatment of oral Kaposi's sarcoma (OKS). Subjects with OKS were randomly assigned to receive a single intralesional injection of either VNB or STS, at a standard dose (0.2 mg/cm(2)). Differences were evaluated by the Mann-Whitney U and Fisher's exact tests. Sixteen HIV-infected patients were included, eight received VNB and eight received STS; clinical response was evaluated at days 7, 14, and 28 following treatment. Tumor size reduction was 0.68 and 0.61 cm in the VNB and STS groups, respectively (P=0.80). Two VNB patients had complete or partial response whereas four STS subjects had partial responses (P=0.61). Patients in both groups experienced minimal toxicity. We conclude that intralesional vinblastine or STS are adequate for the management of OKS. The benefits of STS are its low cost and ease of use.

Combination of radiation therapy and interferon alpha-2b in patients with advanced cervical carcinoma: a pilot study.

Carcinoma of the uterine cervix is the most frequent malignancy in women in developing countries. Based on the possible synergistic effect of the combination of interferon and radiotherapy, a clinical trial was conducted in patients with advanced cervical cancer. The objective was to evaluate the efficacy and security of such a therapeutic approach. This prospective phase II trial was done at the Instituto Nacional de Cancerología in Mexico City. The study included 17 consecutive patients with previously untreated squamous cell cervical cancer, clinical stages III and IV, and tumor mean size of 9.7 cm. The patients received radiotherapy and interferon alpha-2b at a dose of 5 x 106 IU/m2 3 times a week for 6 weeks. Eleven (64%) complete responses were obtained among these patients. Long-term survival was observed in 4 patients (24%) who achieved complete response and are alive after 10 years of follow-up. Immediate toxicity was mild. Late toxicity included the development of proctitis in 13 patients, colostomy was performed in 3 (23%) of them. Our results indicate that the combination of radiotherapy and this cytokine is an active therapy for squamous cell carcinoma of the uterine cervix.

Cisplatin, radiation, and amifostine in carcinoma of the uterine cervix.

A pilot, open, comparative study was performed on patients with locally advanced cervical cancer to investigate the efficacy and safety of amifostine. Twenty patients with a histologic diagnosis of squamous cervical cancer were treated with radiotherapy and randomized in two groups. Group A received cisplatin at 20 mg/m2 for five days in two cycles during intracavitary radiotherapy and 100 mg/m2 x 2 cycles during external radiotherapy, and amifostine 825 mg/m2 15 min before the cisplatin infusion. Patients in group B received cisplatin in the same doses without amifostine. All patients had complete responses during a median follow-up of 20 months. Grade three neutropenia was present in two patients in group A and in four of the control group, P = 0.31; grade 2 neurologic toxicity was seen in four patients in group B and in one of the patients in group A, P = 0.15. One patient needed temporary interruption of amifostine due to hypotension. Eight of 10 patients in group A developed hypocalcemia during the treatment with amifostine. Our findings indicate that amifostine was well tolerated. In this series a mild neurologic and hematologic protection was found in patients that received amifostine, although this was not statistically significant. No differences in disease-free survival response and overall survival was seen between the two groups.

Synthesis of terminal disaccharide elements corresponding to the Ogawa and Inaba antigenic determinant from Vibrio cholerae O1.

Vibrio cholerae O1 LPS terminal mono- and disaccharide elements were synthesized by reduction of the azido group in several 4-amino-4,6-dideoxy-D-mannose mono- and disaccharide derivatives, followed by coupling with 2, 4-di-O-acetyl-3-deoxy-L-glycero-tetronic acid in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. This compound represents a useful model in order to elucidate the size of the epitopes which define Ogawa and Inaba serotypes from Vibrio cholerae O1.

Hippocampal involvement associated with human immunodeficiency virus encephalitis in Mexico.

The objective of the present study was to review the alterations of the central nervous system (CNS) in a group of deceased Mexican patients with acquired immunodeficiency syndrome; autopsies were reviewed with a special emphasis on the damage to the hippocampal formation. Of these 19 deceased patients with acquired immunodeficiency syndrome, nine (47%) had opportunistic infections in the CNS that were accompanied by human immunodeficiency virus encephalitis (HIVE), three (16%) had evidence of opportunistic infections in the brain without HIVE, and two (11%) had HIVE alone. All of the patients who had presented with neurological and neurobehavioral alterations had evidence of HIVE and/or opportunistic infections in the CNS. Of these 19 patients, 11 (58%) had presented with evidence of HIVE (with or without opportunistic CNS infections), as evidenced by the presence of gp41-positive microglial cells in the basal ganglia, neocortex, and hippocampus. The subiculum was the region that displayed the most abundant infiltration by gp41-positive microglial cells. The percentage of cases of acquired immunodeficiency syndrome with HIVE and/or CNS opportunistic infections in our series was similar when compared with that of other series in which similar methods of detection of human immunodeficiency virus in the CNS were used. We conclude that evidence of human immunodeficiency virus-associated lesions in the hippocampal formation might in part explain the selective neuronal alterations in this limbic structure, and we suggest that damage to this circuitry might be in part involved in the cognitive alterations in HIVE.

Prognostic factors on 45 cases of phyllodes tumors.

The authors, in order to obtain a diagnostic index for phyllodes tumors and identified histological parameters that will predict the clinical course of this neoplasm, developed a histological degree of aggressiveness based on specific histological parameters, including: stromal:gland ratio, tumor margins, mitotic index and degree of stromal pleomorphism. Three categories were established: benign, intermediate and malignant. The probability of recurrence was estimated by the relative risk and by a multivariate Cox analysis. A strong and significant association was observed between this histological index and recurrence. The relative risk was 6.0 for intermediate lesions and 11.4 for malignant lesions when compared with the benign category. The microscopic examination of all axillary lymph nodes was negative for metastatic disease. In the multivariate analysis, the stroma:gland ratio was the strongest predictor for recurrence. These results indicate that by assigning a numerical value to certain histopathologic variables a better correlation with the clinical outcome of the patient can be obtained.