Michele Follen Mitchell

Colposcopy For The Diagnosis of Squamous Intraepithelial Lesions: A Meta-Analysis

Objective To quantify by meta-analysis the performance of colposcopy to set a standard against which new technologies can be compared. Data Sources MEDLINE was searched for articles on colposcopy for diagnosis of squamous intraepithelial lesions (SIL). The search selected articles from 1960 to 1996 combining the key word “colposcopy” with key words “diagnosis,” “positive predictive value,” “negative predictive value,” “likelihood ratio,” and “receiver operating characteristic (ROC) curve.” Methods of Study Selection Articles were selected if the authors studied a population of patients with abnormal screening Papanicolaou smears and presented raw data showing for each cervical lesion type the number of patients judged positive and negative by colposcopic impression versus the standard of colposcopic biopsy results. Nine of 86 studies met these criteria. Tabulation, Integration, and Results Biopsies had been categorized as normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, carcinoma in situ, and invasive cancer; we recalculated performance measures using the Bethesda system. Overall sensitivity, specificity, likelihood ratios, ROC curves, and the corresponding areas under the curves were calculated. The average weighted sensitivity of diagnostic colposcopy for the threshold normal compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL, cancer) was 96% and the average weighted specificity 48%. For the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer, average weighted sensitivity was 85% and average weighted specificity 69%. Likelihood ratios generated small but important changes in probability for distinguishing normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the ROC curve were 0.80 for the threshold normal cervix compared with all abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared with high-grade SIL and cancer. Conclusion Colposcopy compares favorably with other medical diagnostic tests in terms of sensitivity, specificity, and area under the ROC curve. New diagnostic methods for the cervix can be compared with colposcopy using these quantified values.

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

Abstract— 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 un‐normalized 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‐phos‐phate. 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.

Development of a Fiber Optic Probe to Measure NIR Raman Spectra of Cervical Tissue In Vivo

The goal of this study was to develop a compact fiber optic probe to measure near infrared Raman spectra of human cervical tissue in vivo for the clinical diagnosis of cervical precancers. A Raman spectrometer and fiber optic probe were designed, constructed and tested. The probe was first tested using standards with known Raman spectra, and then the probe was used to acquire Raman spectra from normal and precancerous cervical tissue in vivo. Raman spectra of cervical tissue could be acquired in vivo in 90 s using incident powers comparable to the threshold limit values for laser exposure of the skin. Although some silica signal obscured tissue Raman bands below 900 cm‐1, Raman features from cervical tissue could clearly be discerned with an acceptable signal‐to‐noise ratio above 900 cm‐1. The success of the Raman probe described here indicates that near infrared Raman spectra can be measured in vivo from cervical tissues. Increasing the power of the excitation source could reduce the integration time to below 20 s.

A RANDOMIZED CLINICAL TRIAL OF CRYOTHERAPY, LASER VAPORIZATION, AND LOOP ELECTROSURGICAL EXCISION FOR TREATMENT OF SQUAMOUS INTRAEPITHELIAL LESIONS OF THE CERVIX

: Women at least 18 years old with biopsy-provenSIL, negative pregnancy tests, negative findings on endocer-vical curettage, satisfactory colposcopy examinations, andcongruent Papanicolaou smear and biopsy results wereassigned randomly to treatment after stratification by SILgrade, endocervical gland involvement, and lesion size; theywere evaluated 1, 4, 8, 12, 16, 20, and 24 months aftertreatment. Data were analyzed using

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

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.

Outcome and Reproductive Function After Chemotherapy for Ovarian Dysgerminoma

PURPOSE To review the outcome for all patients with ovarian dysgerminoma treated at the M.D. Anderson Cancer Center who received bleomycin, etoposide, and cisplatin (BEP) and to assess the menstrual and reproductive function of those who received conservative treatment. PATIENTS AND METHODS Clinical information was abstracted from the medical record. Patients completed a detailed questionnaire about menstrual and reproductive function; those who did not return the questionnaire were interviewed by telephone. RESULTS Twenty-six patients were identified as having been treated with BEP chemotherapy for pure ovarian dysgerminoma from January 1984 to January 1998. Their median age was 19.5 years (range, 7 to 32 years). Sixteen patients underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy. At a median follow-up time of 89 months, 25 (96%) of the 26 patients remained continuously disease-free. One patient apparently developed a second primary dysgerminoma in her remaining ovary after BEP and was clinically disease-free after further treatment. Of the 16 patients who underwent fertility-sparing surgery, one was lost to follow-up when she was pregnant, and one was still premenarchal. Of the remaining 14 patients, 10 (71%) maintained their normal menstrual function during and after chemotherapy, and 13 (93%) had returned to their prechemotherapy menstrual pattern at the time of the questionnaire. Five pregnancies have occurred thus far, and two patients have had difficulty conceiving. CONCLUSION Most patients with metastatic dysgerminoma can expect cure with maintenance of normal reproductive function when treated with conservative surgery and BEP chemotherapy.

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

A general multivariate statistical algorithm has been developed to analyze the diagnostic content of cervical tissue fluorescence spectra acquired in vivo.

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.

Youth as a prognostic factor in carcinoma of the cervix: A matched analysis

A matched analysis comparing 250 patients less than 35 years old with squamous cell cancer of the cervix treated between 1971 and 1981 to a randomly selected group matched on treatment who were greater than 35 years old was performed. A chart review that focused on important prognosticators for survival and progression-free interval was performed. The groups were found to be similar for the important prognosticators. Overall survival and progression-free intervals were plotted using Kaplan-Meier curves and demonstrated that for advanced stages, younger patients were less likely to survive and more likely to recur. Cox proportional-hazard analyses were performed, looking at important prognosticators of survival and progression-free interval. Age, stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of survival, while stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of progression-free interval. The plot of relative hazard by stage of younger versus older patients showed an interaction between age and stage that merits further exploration.

Sexual adjustment of patients undergoing gracilis myocutaneous flap vaginal reconstruction in conjunction with pelvic exenteration.

BACKGROUND Although the technique for gracilis myocutaneous vaginal reconstruction was first described in the mid-1970s and has been used in conjunction with pelvic exenteration since that time, there is little available information regarding sexual adjustment after such a procedure. The purpose of this study was to assess the sexual adjustment of women who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution. METHODS In a prospective study design, 95 patients were identified who underwent pelvic exenteration and gracilis myocutaneous vaginal reconstruction at the study institution from 1977 through 1989 and a convenience sample was selected of 44 patients who completed a modified version of the Sexual Adjustment Questionnaire (SAQ) when they returned to the gynecologic oncology outpatient clinic for routine follow-up care. A vaginal assessment was also performed by the attending physician. RESULTS Twenty-one of 40 patients (52.5%) completing the questionnaire reported not resuming sexual activity after surgery; 19 patients reported sexual activity between 1.5 months to 12 years postoperatively. Of the patients who resumed sexual activity, 84% did so within 1 year of surgery. The most common problems noted by patients in adjusting to sexual activity after surgery were self-consciousness about the urostomy or colostomy and being seen in the nude by their partner, vaginal dryness, and vaginal discharge. The mean rank of preexenteration SAQ scores was 66.4, and the mean rank of postexenteration scores was 48.7 (P < 0.0001), demonstrating that sexual adjustment after exenteration was significantly poorer than before the surgery. On the basis of data gathered from a vaginal assessment form, 31 of 44 patients (70.4%) were judged to have a potentially functional neovagina. CONCLUSIONS Based on the findings of this questionnaire study, sexual adjustment is often significantly impaired in women after pelvic exenteration and gracilis myocutaneous vaginal reconstruction. Future modifications in surgical technique, more realistic patient counseling and aggressive postoperative support will hopefully minimize such problems.