PubMed Health⌕ Search

Biomedical subjects

A Malpica

Publications and source records attributed to A Malpica.

At least 19 recordsLinked to original sources
PubMed1998

Near-infrared Raman spectroscopy for in vitro detection of cervical precancers.

In this study, we investigate the potential of near-infrared Raman spectroscopy to differentiate cervical precancers from normal tissues, inflammation and metaplasia and to differentially diagnose low-grade and high-grade precancers. Near infrared Raman spectra were measured from 36 biopsies from 18 patients in vitro. Detection algorithms were developed and evaluated relative to histopathologic examination. Algorithms based on empirically selected peak intensities, ratios of peak intensities and a combination of principal component analysis for data reduction and Fisher discriminant analysis for classification were investigated. Spectral peaks were tentatively identified from measured spectra of potential chromophores. Empirically selected normalized intensities can differentiate precancers from other tissues with an average sensitivity and specificity of 88 +/- 4% and 92 +/- 4%. Ratios of unnormalized intensities can differentiate precancers from other tissues with a sensitivity and specificity of 82% and 88% and high-grade from low-grade lesions with a sensitivity and specificity of 100%. Using multivariate methods, intensities at eight frequencies can be used to differentiate precancers from all other tissues with a sensitivity and specificity of 82% and 92% in an unbiased test. Raman algorithms can potentially separate benign abnormalities such as inflammation and metaplasia from precancers. Comparison of tissue spectra to published and measured chromophore spectra indicate that the most likely primary contributors to the tissue spectra are collagen, nucleic acids, phospholipids and glucose 1-phosphate. These results suggest that near-infrared Raman spectroscopy can be used for cervical precancer diagnosis and may be able to accurately separate samples with inflammation and metaplasia from precancer.

Cervix Uteri↗
PubMed1998

Epidermal growth factor receptor expression in cervical intraepithelial neoplasia and its modulation during an alpha-difluoromethylornithine chemoprevention trial.

Chemoprevention trials designed to prevent progression to invasive cervical cancer will benefit from the identification of biomarkers that assess the risk of developing tumors, predict likelihood of response to treatment, and measure biological response to intervention. The purpose of this study was to examine expression of epidermal growth factor receptor (EGFR) as a marker for progression of cervical intraepithelial neoplasia (CIN) and as a surrogate end point biomarker in a chemoprevention trial with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. To evaluate quantitative and spatial changes in EGFR expression during cervical tumorigenesis, paraffin sections from 42 archival cervical cone biopsies, each containing multiple stages of CIN, were immunohistochemically stained for EGFR, and the level and spatial expression of EGFR were quantitated by image analysis. In the progression from normal epithelium to CIN 1 to CIN 2 to CIN 3 to invasive cancer, EGFR expression showed two types of changes. Normal control epithelium showed EGFR expression predominantly confined to the basal layer, while histologically normal epithelium in specimens containing CIN showed relatively increased EGFR expression in the basal layer and the extension of EGFR expression away from the basal layer. The total EGFR relative staining intensity (RSI) of epithelium increased with the degree of CIN, predominantly due to a progressive expansion of EGFR-expressing cells away from the basal layer rather than an increase in the level of EGFR expression per cell. To determine whether EGFR expression would be modulated by a 1-month chemopreventive intervention with DFMO, pretreatment and posttreatment cervical biopsy specimens from 25 patients (22 evaluable) were examined for EGFR expression. Although the overall levels of EGFR expression were not modulated in either histological responders or nonresponders, responders showed a prominent down-regulation of EGFR expression away from the basal layer after DFMO treatment. Interestingly, pretreatment EGFR expression levels predicted for DFMO response [i.e., eight responses (72.7%) for 11 cases with RSI levels below 0.35 versus one response (9.1%) for 11 cases with RSI levels above 0.35 (P < 0.01)]. These results suggest that CIN progression is associated with a spatial dysregulation of EGFR expression that can be reversed by DFMO treatment, especially in patients whose pretreatment CIN 3 lesions exhibit relatively low EGFR expression.

Anticarcinogenic Agents↗
PubMed1997

C-met proto-oncogene expression in benign and malignant human renal tissues.

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen to renal epithelial cells in vitro and in vivo. HGF/SF signals through its receptor which is coded by the c-met proto-oncogene. We hypothesized that altered expression of the HGF/SF receptor, c-met, may be involved in the pathogenesis of certain renal cell carcinomas. Our objectives were to 1) assess the presence and localization of c-met protein in benign and malignant human renal tissues, and 2) correlate the presence of c-met protein with renal carcinoma histological subtype, tumor stage and tumor grade. MATERIALS AND METHODS: Immunohistochemical analysis of c-met protein was performed in 41 normal and malignant human renal samples. RESULTS: c-met Immunostaining was detected in the normal kidney tissue in all 41 samples. In the normal kidney c-met immunostaining was limited to the cell membrane and/or cytoplasm of epithelial cells in specific tubular segments, including the proximal convoluted tubule, thin and thick limbs of the loop of Henle, and the collecting duct. The glomeruli, distal convoluted tubule and stroma were consistently negative for c-met staining. c-met Immunostaining was detected in 68% of renal cell carcinomas and was more common in higher nuclear grade cancers (p < 0.034). CONCLUSIONS: The c-met receptor is present in specific tubular segments in the normal kidney and is frequently expressed in higher nuclear grade renal cancers, suggesting a role in renal carcinoma progression. Future studies should evaluate the biological significance of the HGF/ SF-c-met pathway in normal renal physiology, and renal cancer growth and progression.

Carcinoma, Renal Cell↗
PubMed1997

Risk of urethral, vaginal and cervical involvement in patients undergoing radical cystectomy for bladder cancer: results of a contemporary cystectomy series from M. D. Anderson Cancer Center.

PURPOSE: Orthotopic bladder reconstruction in women is the focus of considerable interest. To define suitable candidates for orthotopic reconstruction among women with bladder cancer, we reviewed the risk of secondary urethral, vaginal and cervical involvement by transitional cell carcinoma in patients who underwent radical cystectomy at our institution. MATERIALS AND METHODS: We retrospectively reviewed the charts of women who underwent radical cystectomy for primary transitional cell carcinoma of the bladder between 1985 and 1995. These cases also were reviewed pathologically. RESULTS: Of 115 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder 9 (8%) also had secondary transitional cell carcinoma of the urethra, including 2 with concomitant involvement of the vagina or cervix. In 4 patients (3%) the vagina or cervix was involved but not the urethra. Vaginal and cervical invasion correlated with stages T3b and T4 disease (p = 0.04). By logistic regression analysis the sole significant risk factor for urethral involvement was bladder neck involvement (p = 0.0005). Unlike previous studies 2 of 9 patients with secondary urethral transitional cell carcinoma did not have apparent cancer at the bladder neck. CONCLUSIONS: We report secondary urethral involvement without apparent bladder neck involvement in women with transitional cell carcinoma. Women who are candidates for orthotopic reconstruction should undergo biopsies of the bladder neck and urethra as part of the preoperative evaluation. In patients with palpable masses (stage T3b) on bimanual examination, transvaginal biopsies should also be considered. Intraoperative frozen sections of the urethral and vaginal margins should be obtained.

Adenocarcinoma↗
PubMed1997

Ovarian serous neoplasms of low malignant potential associated with focal areas of serous carcinoma.

This is a study of 12 cases of Stage III ovarian serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma. The purpose of this study was to assess the prognosis of serous tumors that had areas of serous carcinoma but were predominantly of low malignant potential. Eleven serous carcinomas were low grade, and one was high grade. All of the patients underwent surgical resection of the neoplasm and then chemotherapy. Eight patients died of disease after a follow-up of 17 to 94 months (mean, 52 mo). Three patients had no evidence of disease at 60, 69, and 75 months. One patient is alive with progressive disease at 58 months. Serous neoplasms of low malignant potential associated with focal areas (< 50%) of serous carcinoma are aggressive neoplasms that have a prognosis similar to that of serous carcinoma.

Adult↗
PubMed1997

Progressive dysregulation of proliferation during cervical carcinogenesis as measured by MPM-2 antibody staining.

To better characterize the amount and location of loss of proliferation control during cervical carcinogenesis, 44 cervical cone biopsy specimens containing various grades of premalignant and malignant lesions and 12 normal cervix specimens were immunohistochemically examined using MPM-2. This antibody recognizes a phosphorylated epitope on a group of proteins that are preferentially phosphorylated at mitosis. The spatial organization of mitotic figures was determined using a computer-assisted image analysis system. The mitotic figure frequencies/unit of epithelial area were found to increase as the histological type progressed; the numbers of mitoses/square millimeter was 1.7 +/- 0.5 (mean +/- SE) for control normal epithelium (n = 12), 3.1 +/- 1.7 for normal epithelium adjacent to cervical intraepithelial neoplasia (CIN) and cancer (n = 28), 7.9 +/- 1.3 for CIN1 (n = 24), 75.8 +/- 16.3 for CIN2 (n = 11), 127.2 +/- 9.7 for CIN3 (n = 22), 196.9 +/- 33.2 for carcinoma in situ (n = 9), and 156.2 +/- 31.0 for cervical carcinoma (n = 8). The MPM-2 index was higher in high-risk premalignant lesions (i.e., those adjacent to areas of high-grade CIN and carcinoma) than it was in lower risk premalignant lesions (i.e., those with no adjacent higher grade CIN or cervical cancer), even if they exhibited the same histological grade. Moreover, the mean relative distance of the mitotic cells from the basement membrane (i.e., the distance from the basal layer to the surface) also increased as the histological grade progressed. These results suggest that proliferation becomes sequentially dysregulated both quantitatively and spatially during cervical carcinogenesis and that the MPM-2 antibody might be useful as a proliferation biomarker.

Antibodies, Monoclonal↗
PubMed1997

DNA image cytometric measurement as a surrogate end point biomarker in a phase I trial of alpha-difluoromethylornithine for cervical intraepithelial neoplasia.

Cervical intraepithelial neoplasia grade 3 (CIN 3) is considered a high-risk precursor of invasive cervical cancer. alpha-Difluoromethylornithine (DFMO) is a promising antiproliferative chemopreventive agent. The purpose of this study was to evaluate image cytometric measurement of nuclear DNA (ICM-DNA) as a surrogate end point biomarker (SEB) in a Phase I trial of DFMO for CIN. Thirty patients with CIN 3 were treated with DFMO at five doses, ranging from 0.0625 to 1.0 g/m2/day, for 1 month. Half of the patients had histological responses. Twenty-five pre- and posttreatment cervical biopsy specimens (from 11 responders and 14 nonresponders) were available for this analysis. ICM-DNA was performed on 4-micron sections cut from formalin-fixed tissue blocks and stained with a thionin-SO2 Feulgen reaction. ICM-DNAs for each case were expressed as normalized measurements (against the nuclear modal absorbance of lymphocytes) of the absorbance of each cell of interest and were presented in bar histograms. The mean normalized summed absorbance (sigma ODn) was obtained as a mean histogram of the cell population of interest. Nineteen (76%) of 25 patients had a significant decrease in sigma ODn after DFMO treatment. Posttreatment values were significantly lower than pretreatment values in a paired analysis, and responders had significantly lower values than nonresponders. Analyses of different ICM-DNA references, including percentile values of sigma ODn distribution, DNA malignancy grade, and 5c exceeding rate, showed a decrease of mean sigma ODn during DFMO treatment. In addition, the summed posttreatment sigma ODn histograms also showed progressively shorter right shoulders compared with pretreatment histograms in both responders and nonresponders. We concluded that the modulation of sigma ODn reflected the chemoprevention effect of DFMO even before morphological changes appeared, and thus, ICM-DNA may be useful as a SEB in chemoprevention trials of DFMO. Additional reasons for using ICM-DNA as a SEB are the relative simplicity of its use, the high accuracy of the results, the low cost of the reagents, the ability to use small tissue samples, and the objectivity and reproducibility of the procedure.

Adult↗
PubMed1996

Soft tissue sarcoma of the head and neck in children and adolescents.

BACKGROUND: The experience of one institution in treating soft tissue sarcomas of the head and neck in a pediatric population is presented. METHODS: Case materials of 134 patients younger than 20 years who were referred to the University of Texas M. D. Anderson Cancer Center between 1970 and 1989 for treatment of sarcoma of the head and neck were retrospectively reviewed. Patients with rhabdomyosarcoma underwent multimodality treatment consisting of surgery, irradiation, and chemotherapy. Wide resection was the treatment used for patients with nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS). Adjuvant chemotherapy and irradiation were used to treat high grade neoplasms and residual disease. The clinical response to therapy was measured in terms of the disease-specific survival rate. RESULTS: Seventy-nine of 134 patients presented with untreated or biopsy-proven disease. Fifty-six had rhabdomyosarcoma and 23 had NRSTS: At 2 and 5 years, the disease-specific survival rates for patients with rhabdomyosarcoma were 74% and 63%, respectively, and patients with NRSTS had 80% and 75% disease-specific survival rates at 2 and 5 years, respectively. CONCLUSIONS: Rhabdomyosarcoma of the head and neck in children is effectively treated with multimodality therapy. Prognostic indicators for rhabdomyosarcoma include completeness of tumor resection and the development of recurrent disease. Aggressive surgical resection is the treatment of choice for patients with NRSTS: Prognostic indicators for NRSTS include completeness of tumor resection and the development of recurrent disease.

Adolescent↗
PubMed1996

Development of a multivariate statistical algorithm to analyze human cervical tissue fluorescence spectra acquired in vivo.

BACKGROUND AND OBJECTIVE: A general multivariate statistical algorithm has been developed to analyze the diagnostic content of cervical tissue fluorescence spectra acquired in vivo. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess the data to reduce inter-patient and intra-patient variation of tissue spectra within a diagnostic category, without a priori information, (2) dimensionally reduce the preprocessed fluorescence emission spectrum with minimal information loss and use it to select the minimum number of the original emission variables of the fluorescence spectrum required to achieve classification with negligible decrease in predictive ability, and (3) assign a posterior probability to the diagnosis of each sample, so that samples with relative uncertain diagnosis can be reevaluated by a clinician. The algorithm was tested retrospectively and prospectively on cervical tissue spectra acquired from 476 sites from 92 patients at 337 nm excitation. RESULTS: The algorithm based on the entire fluorescence spectrum differentiates squamous intraepithelial lesions (SILs) from normal squamous epithelia and inflammation with an average sensitivity and specificity of 88% +/- 1.4 and 70% +/- 1, respectively. The average sensitivity and specificity of the identical algorithm based on intensity selected at only two emission wavelengths is 88% +/- 1.4 and 71% +/- 1.4, respectively. CONCLUSION: The multivariate statistical algorithm based on both types of spectral inputs at 337 nm excitation has a similar sensitivity and significantly improved specificity relative to colposcopy in expert hands.

Algorithms↗
PubMed1996

Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser-induced fluorescence spectra at multiple excitation wavelengths.

BACKGROUND AND OBJECTIVE: The diagnostic contribution of cervical tissue fluorescence spectra acquired in vivo at 380 and 460 nm excitation were analyzed using a general multivariate statistical algorithm. MATERIALS AND METHODS: The primary steps of the algorithm are to: (1) preprocess data to reduce interpatient and intrapatient variation of tissue spectra from the same diagnostic category, without a priori information, (2) dimensionally reduce the pre-processed spectral data using Principal Component Analysis, and (3) develop a probability based classification scheme based on logistic discrimination using the diagnostically useful principal components. The algorithm was tested on cervical tissue spectra acquired from 165 sites at 380 nm excitation and from 147 sites at 460 nm excitation. A retrospective and prospective estimate of the algorithm's performance was determined. RESULTS: At 460 nm excitation, (1) SILs can be differentiated from normal squamous tissues with an average sensitivity and specificity of 91% +/- 1.3 and 75.5% +/- 1, respectively; furthermore, (2) high grade SILs can be differentiated from low grade SILs with an average sensitivity and specificity of 80% +/- 4 and 76% +/- 5, respectively. In addition, using tissue spectra at 380 nm excitation, SILs can be differentiated from normal columnar epithelia and inflammation with an average sensitivity and specificity of 77% +/- 1 and 72% +/- 9, respectively. CONCLUSIONS: Fluorescence spectra at multiple excitation wavelengths are essential for the detection and differential diagnosis of SILs at colposcopy.

Algorithms↗
PubMed1996

Adenocarcinoma in situ of the cervix: significance of cone biopsy margins.

OBJECTIVE: To evaluate the treatment and outcome of patients with adenocarcinoma in situ of the cervix, with special emphasis on cone biopsy margins. METHODS: Sixty-one women with adenocarcinoma in situ of the cervix treated between April 1984 and December 1993 were identified. Medical records and histologic material were reviewed. Mixed lesions with both adenocarcinoma in situ and squamous cervical intraepithelial neoplasia (CIN) were included. RESULTS: The mean age of the patients was 35.9 years. Fifty-five of the 61 (90%) patients had cone biopsies, and 44 of these 55 (80%) subsequently had hysterectomies. Eight women (13%) had associated invasive cancer. Among 50 patients in whom the status of the margins was confirmed, 23 (46%) had positive margins and 27 (54%) had negative margins. Of 23 women with positive margins, 19 had hysterectomies and ten of the 19 (53%) had residual disease in the uterus. Of 27 patients with negative cone margins, 21 had hysterectomies, and seven of the 21 (33%) had residual disease in the uterus. Two women with negative margins who did not have hysterectomies developed recurrent disease. Fifty-five of the total series of 61 patients followed-up for a median of 57 months (range 17-132) had no evidence of disease at last follow-up. CONCLUSION: Women with adenocarcinoma in situ of the cervix often have residual disease in the uterus, regardless of whether the margins on cone biopsy are positive or negative.

Adenocarcinoma↗
PubMed1996

Cervical precancer detection using a multivariate statistical algorithm based on laser-induced fluorescence spectra at multiple excitation wavelengths.

A portable fluorimeter was developed and utilized to acquire fluorescence spectra from 381 cervical sites in 95 patients at 337, 380 and 460 nm excitation immediately prior to colposcopy. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired in vivo. Two full-parameter algorithms were developed using tissue fluorescence emission spectra at all three excitation wavelengths (161 excitation-emission wavelength pairs) for cervical precancer (squamous intraepithelial lesion [SIL]) detection: a screening algorithm that discriminates between SIL and non-SIL with a sensitivity of 82 +/- 1.4% and specificity of 68 +/- 0.0%, and a diagnostic algorithm that differentiates high-grade SIL from non-high-grade SIL with a sensitivity and specificity of 79 +/- 2% and 78 +/- 6%, respectively. Multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to redevelop algorithms that demonstrate a minimum decrease in classification accuracy. Two reduced-parameter algorithms that employ fluorescence intensities at only 15 excitation-emission wavelength pairs were developed: the screening algorithm differentiates SIL from non-SIL with a sensitivity of 84 +/- 1.5% and specificity of 65 +/- 2% and the diagnostic algorithm discriminates high-grade SIL from non-high-grade SIL with a sensitivity and specificity of 78 +/- 0.7% and 74 +/- 2%, respectively. Both the full-parameter and reduced-parameter screening algorithms discriminate between SIL and non-SIL with a similar specificity (+/-5%) and a substantially improved sensitivity relative to Pap smear screening. A comparison of the full-parameter and reduced-parameter diagnostic algorithms to colposcopy in expert hands indicates that all three have a very similar sensitivity and specificity for differentiating high-grade SIL from non-high-grade SIL.

Algorithms↗
PubMed1996

Vulvar intraepithelial neoplasia and vulvar cancer.

Vulvar carcinoma is a rare cancer. It is more frequent among older women, but the incidence is increasing among younger women. The incidence of VIN may be rising in younger women as well. Different factors have been associated with an increased risk for vulvar cancer (HPV, age, smoking, education, diet, genital infections, infrequent pelvic examinations, socioeconomic status, immunosuppressive diseases); however, conclusive epidemiologic evidence is lacking. More studies with larger sample sizes are needed to understand more fully the role of these and other as yet unknown factors in the etiology of vulvar cancer. At present, studies of the molecular risk assessment for VIN and vulvar cancer focus mostly on HPV. The treatments for VIN are painful, and the disease has a high risk of recurrence. The treatments for vulvar cancers are morbid, even though radical vulvectomy is being replaced by the less morbid wide local excision and unilateral groin lymph node dissection. Therefore, VIN and vulvar cancer benefit from early detection, and their morbidity is decreased by early treatment. Screening should be performed by the primary care practitioner and should focus on women with HPV; women who smoke; and women who have other preinvasive disease of the cervix, vagina, or perianal area. Chemoprevention and an HPV vaccine may eventually be promising, but no studies have yet been performed. Patients should be educated about performing vulvar self-examination stopping smoking, being persistent about insisting on a biopsy if symptoms persist, and avoiding exposure to HPV.

Biomarkers, Tumor↗
PubMed1996

Vaginal intraepithelial neoplasia and vaginal cancer.

Vaginal cancer is infrequent, but the morbidity associated with treatment is high. Delays in diagnosis account for presentations in advanced stages. Screening is probably not warranted given the low incidence, but inspection of the vagina should be performed at the time of Pap smear screening. No molecular markers are currently promising. Chemoprevention with retinoids may be feasible.

Carcinoma in Situ↗
PubMed1996

Cervical intraepithelial neoplasia and cervical cancer.

Cervical cancer remains an important health problem for women worldwide, despite its decline in countries where organized screening programs are in place. The morbidity of treatment and the mortality for advanced lesions are high, a frustrating situation because the cervix is accessible and a good screening test, the Pap smear, exists. HPV is an important risk factor, and the molecular evidence for its role is overwhelming. Molecular markers may soon help us decide which lesions are at highest risk of progression to invasion and which invasive lesions are likely to recur. Chemoprevention of precursor lesions is promising. An HPV vaccine could be effective in eradicating this cancer.

Biomarkers, Tumor↗
PubMed1996

Endometrial hyperplasia and endometrial cancer.

Endometrial cancer is the most frequently seen gynecologic neoplasm, but it fortunately has low mortality, which is due largely to its presentation with abnormal bleeding and its subsequent early diagnosis. The morbidity associated with therapy for early lesions is moderate. Hyperplasia with atypia should be treated as early cancers. Many molecular markers are currently under study. Markers may soon help us identify invasive lesions at higher risk of recurring and thus more suitable for adjunct therapy. Screening in the general population is not recommended, but a high-risk group that is more suitable for screening could be identified, including obese and nulliparous women, those treated with unopposed estrogen or tamoxifen, or those with family or past histories of breast or colon cancer. Development of chemoprevention with an oral contraceptive during the reproductive years is under way, and there may be a role for chemoprevention in the reversal of hyperplasias.

Biomarkers, Tumor↗
PubMed1996

Uterine sarcoma.

Sarcomas are rare tumors with unpredictable prognosis. They are treated similarly to endometrial cancers. Little is known of epidemiologic risk factors for sarcoma; similarly, little work has been performed assessing molecular alterations in sarcomas. Because of their rarity, uterine sarcomas are not suitable for screening. Chemoprevention studies might target those at risk for recurrence or a second neoplasm.

Biomarkers, Tumor↗