Search PubMed⌕ Search

Biomedical subjects

M F Mitchell

Publications and source records attributed to M F Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1993

Relationships between c-Ki-ras mutations, HPV types, and prognostic indicators in invasive endocervical adenocarcinomas.

OBJECTIVE: Ras gene mutations have been identified in squamous cell carcinomas of the cervix and are associated with advanced-stage tumors. The current study was designed to determine the prevalence of c-Ki-ras mutations in invasive endocervical adenocarcinomas and associations between mutations, HPV status, and known prognostic indicators. METHODS: Paraffin-embedded tissue samples from 32 cases of invasive adenocarcinoma of the endocervix were analyzed for the presence of c-Ki-ras mutations by amplification of DNA extracted from paraffin blocks using the polymerase chain reaction (PCR) and subsequent restriction enzyme digestion of the amplimers. This method allows detection of aspartic acid mutations of the c-Ki-ras gene at codons 12 and 13. Samples were also analyzed for the presence of HPV DNA using PCR and either "consensus sequence" primers or "type-specific" primers for HPVs 16 and 18. Patients' charts were reviewed for clinical information and correlations between clinical outcome and known prognostic indicators and the presence of c-Ki-ras mutations was assessed. RESULTS: c-Ki-ras codon 12 mutations were detected in only 4 of the 32 cases (12.5%) of invasive endocervical adenocarcinomas examined. No codon 13 mutations were detected. Fifty-nine percent of the cases were HPV 16 or HPV 18 DNA positive and only 1 of the 4 cases with a codon 12 mutation was associated with HPV 16 or HPV 18. There were no significant associations between stage or grade of tumor or outcome and the presence of codon 12 mutations. However, using the observed survival as computed by the Berkson Gage Method at 12 months, the estimated median survival for patients with c-Ki-ras codon 12 mutations is 29 months compared to 68 months for patients lacking codon 12 mutations. CONCLUSIONS: These results indicate that c-Ki-ras codons 12 and 13 mutations are uncommon in invasive endocervical adenocarcinomas.

Adenocarcinoma↗
PubMed1993

Dedifferentiated extrauterine adenosarcoma responsive to chemotherapy.

Extrauterine adenosarcoma, a low-grade mixed mesodermal tumor, is an uncommon neoplasm. Little information is available regarding the efficacy of treatment of tumors not amenable to surgical resection. Our patient's pelvic adenosarcoma progressed despite multiple attempts at surgical excision over an 8-year period. Hormonal therapy with medroxyprogesterone acetate and tamoxifen did not alter the frequency of recurrence. However, aggressive cisplatin-ifosfamide-based combination chemotherapy produced a dramatic response in the metastatic tumor in the liver. Cisplatinum, doxorubicin, and ifosfamide may thus be active against this tumor. Regional arterial infusion, when feasible, may enhance response.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Aborted exenterative procedures in recurrent cervical cancer.

Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.

Adult↗
PubMed1993

Prognostic factors for patients undergoing simple hysterectomy in the presence of invasive cancer of the cervix.

To identify significant prognostic factors and sites of treatment failure in patients undergoing simple hysterectomy in the presence of invasive cervical cancer, the records of 122 women referred following such a procedure were reviewed retrospectively. All but 2 patients received postoperative megavoltage irradiation. Patients with and without gross disease at the start of posthysterectomy treatment had 5-year survival rates of 39 and 75%, respectively. Factors found to be significantly related to survival were the presence of gross disease (P = 0.0001), retrospectively determined tumor stage (P = 0.0001), and lymphangiogram status (P = 0.007). Patients with adenocarcinoma did not fare worse than those with squamous carcinoma (P = 0.6). By multivariate analysis, factors emerging as significantly detrimental to survival were the presence of gross disease (P = 0.0001) and aortic adenopathy on lymphangiogram (P = 0.004). The most common site of treatment failure was the pelvis. The radiotherapy complication rate was 18%; 7% of patients experienced major morbidity. While survival for patients with no residual cancer after simple hysterectomy is favorable, the treatment complication rate may be higher than that reported for patients undergoing primary irradiation. Survival for patients with gross disease at the start of posthysterectomy treatment is poor.

Adenocarcinoma↗
PubMed1993

Cervical conization as definitive therapy for early invasive squamous carcinoma of the cervix.

Young women who present with stage Ia carcinoma of the uterine cervix may strongly desire preservation of fertility. There is little published information on the outcome of patients treated for early invasive cervical cancer with cervical conization. Patients were considered eligible for conservative management if they had a squamous lesion invading to a depth less than or equal to 3 mm with no lymphatic or vascular space involvement and negative margins. We identified 14 patients who had been treated by cervical conization alone for early invasive carcinoma of the cervix. Pathologic variables were reviewed for all patients. Patient records were retrospectively reviewed for demographic, pathologic, and follow-up information. The mean depth of invasion was 1.6 mm (range, 0.5-2.8 mm). The mean number of cone sections evaluated was nine (range, 6-13 sections). The median follow-up period following conization was 26.5 months (range, 1-170 months). One patient underwent subsequent hysterectomy and was found to have mild dysplasia. Thirteen patients have retained their uteri and none has developed recurrent invasive or preinvasive lesions. We conclude that cervical conization is an acceptable therapy for selected cases of microinvasive squamous carcinoma of the uterine cervix. Larger studies of this patient group are indicated to confirm the safety of conization as definitive therapy in selected cases of early invasive cervical carcinoma.

Adult↗
PubMed1993

Transitional cell carcinoma of the ovary: a matched control study of advanced-stage patients treated with cisplatin-based chemotherapy.

OBJECTIVE: The purpose of this study was to compare patients with advanced-stage transitional cell carcinoma of the ovary with those who had poorly differentiated serous carcinoma for surgical response and survival. STUDY DESIGN: Sixty-two patients with transitional cell carcinoma were identified through a retrospective review and were matched with serous carcinoma patients for stage and residual disease. All patients received cisplatin-based chemotherapy. End points selected for analysis were surgical response, progression-free survival time, and survival time. Univariate and multivariate regression analyses were also performed. RESULTS: The surgical complete response rate for patients with transitional cell carcinoma was 37%, compared with 11% for those with serous carcinoma (p < 0.001). The survival time was significantly longer for the patients with transitional cell carcinoma (median 52.3 vs 22.0 months) (p < 0.001). Multivariate analyses strengthened these findings. CONCLUSION: Transitional cell carcinoma of the ovary is significantly more chemosensitive and associated with a better prognosis than the more common serous carcinoma.

Adult↗
PubMed1993

Second genital primary squamous neoplasms in vulvar carcinoma: viral and histopathologic correlates.

OBJECTIVE: To determine whether vulvar squamous cell carcinomas associated with certain morphologic features and/or human papillomavirus (HPV) nucleic acids were more likely to be associated with other genital primary squamous neoplasms. METHODS: We surveyed 169 invasive squamous cell carcinomas of the vulva and correlated associated vulvar intraepithelial neoplasia (VIN), invasive growth patterns resembling VIN (intraepithelial-like or basaloid), and the presence of HPV nucleic acids by in situ hybridization with a history of a second primary squamous neoplasm of the genital tract. RESULTS: Twenty-two patients (13%) had a history of a second primary. An intraepithelial growth pattern or an associated VIN correlated significantly with HPV, at P = .0005 and P = .007, respectively, and with a second primary, at P = .077 and P = .009, respectively. When HPV-positive, the same histologic variables correlated with a second primary at P = .099 and P = .25, respectively. Compared with cases lacking both these histologic features and HPV, they correlated with multifocal disease at P = .01 and P = .003. CONCLUSIONS: The findings of HPV nucleic acids, tumor growth patterns, and associated VIN are interrelated and confer risk of other genital primary neoplasms in women with vulvar carcinoma. This supports the concept that subsets of vulvar carcinoma may be distinguished not only by morphology and HPV DNA, but also by a distinctly different risk of a second genital primary neoplasm.

Aged↗
PubMed1992

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.

Adolescent↗
PubMed1992

The effect of prolonged cisplatin-based chemotherapy on progression-free survival in patients with optimal epithelial ovarian cancer: "maintenance" therapy reconsidered.

From 1978 until 1988, 116 patients with epithelial ovarian cancer were entered onto one of three consecutive prospective clinical trials involving cisplatin-based combination chemotherapy. They had the following characteristics: (1) stage III or IV disease, (2) grade 2 or 3 tumors, and (3) optimally debulked tumors (residual disease < or = 2 cm). The purpose of the study was to investigate the influence of duration of chemotherapy on survival. The treatment plans were as follows: Trial 1, 12 cycles of cisplatin/melphalan (43 patients); Trial 2, 12 cycles of cisplatin/cyclophosphamide (24 patients); and Trial 3, 6 cycles of cisplatin/cyclophosphamide (49 patients). The total dose of cisplatin was 60 mg/m2 in the first trial and 50 mg/m2 in the second and third trials. Median survival times for the three groups were 58, 29, and 35 months, respectively (NS). Median progression-free survival (PFS) times were 37, 23, and 15 months, respectively (P = 0.0008). Combining patients from the first two trials, the median PFS for patients receiving 12 planned cycles of chemotherapy was 30 months versus 15 months for patients receiving 6 planned cycles (P = 0.0004). Using a forward stepwise Cox proportional hazard model, the use of 12 cycles of therapy and melphalan predicted increased PFS (P = 0.0001 and P = 0.0002, respectively). In view of these results, the lack of published data supporting the superiority of 6 over 12 cycles of chemotherapy, and the rather recent availability of less toxic maintenance therapy (i.e., carboplatin), we believe that a multiinstitutional trial comparing the 6-cycle regimen with more prolonged chemotherapy is justifiable.

Adult↗
PubMed1992

Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide.

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) on Day 1 and etoposide (75 mg/m2) on Days 1-3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2-6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.

Adult↗
PubMed1991

The long-term effects of radiation therapy on patients with ovarian dysgerminoma.

A retrospective chart review and questionnaire study was undertaken to look at the long-term effects of radiation therapy in ovarian dysgerminoma patients. Forty-three patients and 55 controls responded to a questionnaire that detailed bowel, bladder, thyroid, menstrual, reproductive, sexual, and growth function. Statistically significant differences in the number of bowel movements were noticed when comparing patients with controls. The authors noticed no significant differences between cases and controls in bladder function. No thyroid disorders were attributable to mediastinal radiation therapy. Most patients with intact uteri bleed monthly on hormonal replacement. Three patients with a remaining ovary and uterus resumed menstrual function after substantial doses of abdominopelvic radiation therapy. No patients have conceived. The authors noticed a slight increase in dyspareunia in the treated group, but most patients were satisfied with their sexual function. One premenarchal patient exhibited a growth disorder.

Adolescent↗
PubMed1991

Unsuspected invasive squamous cell carcinoma of the vulva in young women.

Although the incidence of preinvasive vulvar lesions seems to be rising in the younger population, invasive squamous cell carcinoma remains exceedingly rare. As a result, diagnostic biopsy is often delayed and ablative therapy frequently instituted without an adequate histologic diagnosis. We recently treated three women aged 25 or less who had invasive squamous cell carcinoma of the vulva. In no case was the correct diagnosis initially suspected. All three patients had T2 lesions at the time of diagnosis and were treated by radical wide excision. One patient developed a second ipsilateral vulvar cancer which has recurred in the contralateral groin; the other two patients are free of disease 8 months and 4 years after resection. An awareness of the possibility of invasive vulvar carcinoma, even in the relatively young patient, should lead to prompt and thorough histologic evaluation of any vulvar lesion. Pretreatment evaluation is particularly important when ablation of extensive lesions is planned.

Adolescent↗
PubMed1991

Prognostic indicators for invasive carcinoma of the vulva.

Three hundred sixty-five patients with invasive squamous cell carcinoma of the vulva have been treated at M.D. Anderson Cancer Center between 1944 and 1990. We undertook a rigorous review of the medical records, and a Cox proportional hazards model was applied to examine predictors of both failure to survive and recurrence. Significant predictors of both failure to survive and recurrence included tumor size, clinical stage, therapy aim, pelvic or inguinal nodal metastases, and positive margins. We then undertook an analysis of Stage I and II lesions treated with a curative aim to see if there was a difference in survival or in disease-free interval between those patients treated with radical vulvectomy and those treated with radical wide local excision. There was no survival advantage from the radical vulvectomy procedure. We conclude that careful selection may allow us to choose some patients for less radical procedures.

Carcinoma↗
PubMed1991

Medical record review in an employee cancer screening clinic.

Documentation was evaluated through a series of chart reviews in the University of Texas M.D. Anderson Cancer Center's employee cancer screening clinic. One hundred charts were reviewed for three periods: 1987, before a QA program was established; 1988, during the QA program's introduction; and 1989, when chart review elements were identified. Documentation increased across these periods, with a significant increase for 10 of the 32 elements across at least two periods. However, mean follow-up time (initial examination to referral and communication of test results) did not vary across time, averaging 14 days. A new computer-based data system should help reduce follow-up time and facilitate access to data on patient compliance regarding tests and referrals.

Adolescent↗
PubMed1991

Risk profiles of women with cervical neoplasia.

Risk-factor profiles were compared in M.D. Anderson Cancer Center patients with various uterine cervix histologic diagnoses. Intraepithelial neoplasia (n = 171) and condyloma (n = 82) were associated with significantly lower patient age (mean 23.6 and 25.8 years, respectively). In addition, these two groups were lowest in annual income, age at beginning intercourse and at first pregnancy, and highest in percentages of black and Hispanic patients, number of sexual partners, and history of gonorrhea. Women with squamous carcinoma in situ (n = 47), who were about a decade older, exhibited a similar socioeconomic distribution and sexual history. All three groups also reported high prevalences of current smokers, were most likely to use oral contraceptives, and were least likely to use diaphragms or condoms. Patients with invasive squamous cell carcinoma (n = 77) had a mean age of 46.3 years, a large lowest-income constituency, and the highest mean number of pregnancies; they were least likely to have used oral contraceptives. Adenocarcinoma (n = 21) was epidemiologically distinct: a predominance of white woman characterized by high socioeconomic status, elevated body mass index, and non of the liberal sexual practices of the other groups. Primary and secondary prevention strategies must be tailored to the unique needs and socioeconomic status of the young at-risk populations.

Adult↗
PubMed1983

Popular medical concepts in Jamaica and their impact on drug use.

Universally, popular medical concepts form the basis of lay understanding of health, disease and cure. In Jamaica these concepts first developed in association with traditional herbal medicine. Now they are applied to the most common forms of primary care: over-the-counter and prescribed drugs. Research findings suggest that where there is disagreement between popular and professional medical models, as is the case in Jamaica, the effect of popular concepts is to increase self-medication and reduce adherence to prescribed medical regimens. To ameliorate this situation and the attendant potential risks for drug consumers, methods for providing needed drug information and improving physician-patient communication are suggested. These suggestions apply not only to Jamaicans living in Jamaica and the United States, but also to members of any group whose ethnomedical concepts differ from the biomedical training of physicians.

Adolescent↗