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Biomedical subjects

K D Hatch

Publications and source records attributed to K D Hatch.

At least 55 records · Page 3Linked to original sources

Vulvovaginal human papillomavirus infections: clinical implications and management.

The past 2 decades have witnessed an alarming increase in the incidence of human papillomavirus infections. Clinically evident cases represent only a small portion of the infected population, because millions of people have subclinical or latent infection. Human papillomavirus infection is recognized as a precursor to malignancy. Thus it is important to treat clinically evident infection. Treatment is complicated by the ability of the virus to establish latent infection and the lack of an effective antiviral agent. At present treatment is limited to the destruction of obvious and intraepithelial lesions.

Adult↗

Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group.

Between 1984 and 1989, 20 assessable patients with incompletely resected ovarian dysgerminoma were treated on two protocols of the Gynecologic Oncology Group (GOG). All patients received cisplatin, bleomycin, and either vinblastine or etoposide. More recent patients also received consolidation chemotherapy with vincristine, dactinomycin, and cyclophosphamide (VAC). Eleven patients had clinically measurable disease, and 10 responded completely. Fourteen second-look procedures were done, and all were negative. Currently, 19 of 20 patients are disease-free with median follow-up of 26 months. Cisplatin-based chemotherapy is highly effective in patients with advanced dysgerminoma.

Antineoplastic Combined Chemotherapy Protocols↗

Human papillomavirus screening for women with atypical Papanicolaou smears.

A study was undertaken to evaluate the utility of human papillomavirus (HPV) DNA screening and colposcopy in the management of women whose Papanicolaou smears demonstrated atypia less than dysplasia. Fifty patients whose initial Papanicolaou smears were interpreted as showing atypia less than dysplasia were evaluated for the presence of HPV 16 DNA in exfoliated cervicovaginal cells and for histologic findings on biopsy. Those 50 patients were compared to two groups of patients: one consisting of 124 patients with biopsy-documented cervical intraepithelial neoplasia (CIN) and another of 112 patients with normal Papanicolaou smears. The presence of HPV 16 DNA was confirmed with Southern analysis in 46% of patients with atypical Papanicolaou smears, 46% with confirmed CIN and 11.6% with normal Papanicolaou smears. The 50 patients with atypical smears underwent colposcopically directed cervical biopsies, revealing the following results: 14 (28%) had normal histology, 29 (58%) had koilocytosis without dysplasia, and 7 (14%) had CIN. HPV 16 DNA was present in exfoliated cervicovaginal cells from a large percentage of patients from each category (50% of patients with normal histology, 41.2% with koilocytosis and 57% with CIN). HPV 16 DNA screening did not predict which patients with atypical smears had underlying CIN. Colposcopically directed biopsy remains the evaluation method of choice.

Adolescent↗

Phase II study of N-methylformamide (N-MF) (NSC 3051) in patients with advanced squamous cancer of the cervix. A Gynecologic Oncology Group study.

Twenty patients with advanced measurable, squamous carcinoma of the cervix were treated with 25 courses of N-MF at doses ranging from 600-800 mg/m2, intravenously, daily for 5 days every 28 days. Nineteen patients are evaluable for toxicity and 17 for response. All patients had prior radiation and had received one prior chemotherapy regimen while only 10 patients had had prior surgery. All patients were Gynecologic Oncology Group (GOG) performance status 0, 1, or 2. No responses were seen. Hematologic adverse effects were extremely rare as predicted by early clinical trials. One unusual toxicity was a syndrome consisting of pain, anorexia, lethargy, and declining performance status (pain/lethargy syndrome) that was reversible with discontinuation of the drug. This adverse effect was a reason for discontinuation of N-MF in two patients. As reported in previous studies with this drug, hepatic toxicity was also common, usually reversible, and also a cause for discontinuation of the drug. The lack of clinical activity and the unpleasant adverse effects in this population of patients with previously treated cervix cancer makes it unlikely that this drug will play any significant role in treatment.

Adult↗

c-myc amplification in ovarian cancer.

The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer.

Adult↗

Diagnosis and treatment of pulmonary metastases from cervical carcinoma.

The records of 2116 patients treated for cervical malignancy from 1969 to 1984 at the University of Alabama at Birmingham were reviewed and 88 (4.16%) had pulmonary lesions consistent with metastatic cervical cancer. The data were analyzed to characterize risk factors for developing lung metastases, to determine radiographic patterns, to assess methods of documentation, and to determine response to chemotherapy. Platinum-type chemotherapy has a 67.7% response rate on chest X ray, with one-third of the responses being complete. The prognosis is poor with a median survival of 0.69 year (8.3 months); only 2 of these 88 patients were long-term survivors. Although the survival is poor, a few statistically significant factors could be identified as prognostic. Our data do not support use of surveillance chest X rays, as there is no statistically significant survival difference in symptomatic versus asymptomatic patients. The development of more effective salvage therapy may alter this recommendation.

Adult↗

Oncogene alterations in endometrial carcinoma.

The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor. Amplification of this oncogene in breast carcinoma and ovarian carcinoma is correlated with a poorer prognosis. The c-myc oncogene codes for a DNA binding protein and is believed to regulate cellular proliferation. Sixteen primary endometrial adenocarcinomas were analyzed for c-myc and c-neu amplification. Eleven of sixteen tumor samples exhibited amplification of the neu gene. Four of these eleven patients died of disease an average of 16 months after diagnosis. The five patients without tumor amplification of the c-neu gene have been followed an average of 31.2 months without evidence of recurrent disease. Ten of fifteen tumor samples exhibited amplification of the c-myc gene. Five of the ten patients died of disease an average of 13.4 months after diagnosis. The remaining five patients have been followed for an average of 31.2 months and are free of disease. Six of the sixteen tumor specimens exhibited amplification of the both c-neu and c-myc genes, and four of these patients died of recurrent disease. Amplification of the c-neu or c-myc oncogene correlated with advanced-stage disease and poorly differentiated lesions, suggesting that oncogene amplification may predict biologically aggressive adenocarcinomas of the endometrium.

Adenocarcinoma↗

Pelvic exenteration with low rectal anastomosis: survival, complications, and prognostic factors.

Between July 1979 and January 1989 there were 31 patients who underwent pelvic exenteration with low rectal anastomosis (PE and LRA) at the University of Alabama at Birmingham (UAB). There were no operative deaths; however, 32% of the patients experienced significant postoperative morbidity. Survival (Kaplan-Meier) at 1 year is 86%. Overall survival is 68% with follow-up ranging from 10 months to greater than 9 years. For those patients with disease confined to the cervix and/or vagina (n = 18) the survival is 89% while it is 38% for patients with spread to the bladder, rectum, or parametrium (n = 13). Survival was not influenced by tumor differentiation, time from irradiation to exenteration, or initial stage. Complete healing of the LRA was achieved in 16 patients (52%). However, in the subset of patients with an omental wrap (n = 13) the complete healing rate is 85%. Protective colostomies were utilized in 12 patients; however, this was not shown to improve the healing rate of the LRA. This group of patients is compared to similar patients who had anterior pelvic exenteration at UAB for morbidity and survival. LRA at the time of pelvic exenteration for recurrent cervical cancer is associated with acceptable morbidity and survival and should be attempted in those patients who are appropriate candidates.

Adult↗

Optimal therapy for pelvic recurrence after radical hysterectomy for early-stage cervical cancer.

Forty-eight patients with pelvic recurrence after radical hysterectomy were evaluated. The influence of location of pelvic recurrence (sidewall versus central), histological grade, histological type, and interval from hysterectomy to recurrence had no influence upon curability by radiotherapy. Ten of twenty-eight patients treated by primary radiation therapy for recurrent disease remain without evidence of disease a minimum of 12 months post-therapy, with a projected 5-year disease-free survival in excess of 30%. No patient treated with adjuvant radiation after initial surgery was rendered disease free by subsequent treatment with radiotherapy. Eleven patients were explored for exenterative surgery. Three of six in whom exenteration was technically feasible remain alive without evidence of disease. None of 15 patients treated with chemotherapy remain free of disease. Radiation therapy remains the treatment of choice in post-radical hysterectomy recurrences confined to the pelvis. As exenterative therapy will result in the cure of a small number of patients with disease confined to the pelvis, exenteration should be considered in patients treated previously by radiotherapy. If these efforts fail, chemotherapy is unlikely to result in cure.

Antineoplastic Combined Chemotherapy Protocols↗

Early invasive cervical cancer with pelvic lymph node involvement: to complete or not to complete radical hysterectomy?

The completion of radical hysterectomy in the face of pelvic lymph node involvement presents a dilemma for the surgeon. Some believe it is appropriate to abort the hysterectomy to avoid the excessive morbidity of combined treatment; others believe that completion of the hysterectomy enhances survival. This study was undertaken to define the impact of completing radical hysterectomy followed by adjuvant radiation therapy upon patient survival or pelvic control. Fifteen patients with stage IB and IIA invasive cervical cancer whose radical hysterectomies were aborted solely for reasons of pelvic lymph node involvement were compared to a control group of 15 patients matched for tumor size and number of lymph nodes involved whose radical hysterectomies were completed. Both groups were treated with radiation therapy postoperatively. Survival was not different between groups (P = 0.81). Unexpectedly, local control was slightly improved in the group treated by radiation only (P = 0.127). If radiation therapy is anticipated, completion of radical hysterectomy followed by radiation therapy appears to offer no advantage over radiation therapy with the uterus in place in patients with early-stage invasive cervical cancer and pelvic lymph node involvement.

Combined Modality Therapy↗

Evaluation of the deoxyuridine suppression test by using whole blood samples from folic acid-supplemented subjects.

We performed the deoxyuridine suppression test (dUST) along with assessment of folate and vitamin B-12 status in blood specimens from 136 normal women and 109 women with cervical dysplasia. All tests were repeated at 2, 4, and 6 mo in subjects with dysplasia during a randomized, double-blind intervention trial in which 50 received a 10-mg daily oral folic acid supplement (F group) and 59 received a placebo (P group). Median folate concentration increased fivefold in plasma and threefold in erythrocytes of F group beginning at the second months and remained elevated whereas concentrations of the P group remained unchanged. Vitamin B-12 values did not vary significantly in either group. The dUST value decreased from 10.4 +/- 4.6% (means +/- SD) pretreatment to 4.5 +/- 4.7% in F group after 2 mo (p less than 0.001). The dUST values had significant negative correlation with plasma and erythrocyte folate concentrations. However, erythrocyte folate had the greatest power to distinguish P group from F group.

Adult↗

Methotrexate in advanced endometrial carcinoma. A phase II trial of the Gynecologic Oncology Group.

Thirty-three patients with advanced or metastatic endometrial carcinoma were entered in a Phase II trial utilizing methotrexate, 40 mg/m2 intravenously on a weekly basis. Almost all patients had prior total abdominal hysterectomy and almost two-thirds prior pelvic irradiation. No patient had prior chemotherapy. There was one complete and one partial response, for a complete and partial response rate of 6% (95% confidence intervals for a response of 1.7 to 19.6%). Toxicity was mild, with major adverse effects being nausea and vomiting and myelosuppression. One death may have been drug related. Methotrexate displays minimal clinical activity in patients with advanced or recurrent endometrial carcinoma who have received no prior chemotherapy.

Adult↗

Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin.

From June 1977 to June 1987 74 patients were treated with cisplatin for recurrent squamous cell carcinoma of the cervix as the primary chemotherapeutic agent. Sixty-eight patients were evaluable for response or survival. Patients with disease confined to the chest had a 53% complete response rate with an overall response rate of 73%. Patients with localized pelvic recurrences or persistence demonstrated no complete responses and a 21% overall response rate. Isolated chest metastases are more likely to respond to cisplatin than pelvic recurrences (P = 0.0007); however, location of recurrence did not significantly alter survival (mean 22.7 months versus 14.1 months; P = 0.24.). Concomitant disease in other locations reduced the likelihood of response in the chest (P less than 0.05) by virtue of lack of response in those other sites. Lesion size, clinical stage, patient age, and duration from primary treatment to recurrence were not of significance with regard to response or survival. When evaluating response to chemotherapy in recurrent cervical cancer, location of metastasis and effect on survival must be considered.

Adult↗

Radioimmunoassay of free beta-subunit of human chorionic gonadotropin in diagnosis of high-risk and low-risk gestational trophoblastic disease.

A radioimmunoassay was performed with monoclonal antibody 1E5, which distinguishes free beta-subunit of human chorionic gonadotropin in the presence of intact human chorionic gonadotrophin. Serum samples were obtained from 68 pregnant women, 9 with hydatidiform mole who underwent spontaneous remission, 12 with hydatidiform mole who developed gestational trophoblastic disease, 5 with metastatic gestational trophoblastic disease of high-risk category, and 1 with choriocarcinoma concomitant with pregnancy. The concentrations of free beta-subunit of human chorionic gonadotropin and total beta-subunit were determined on the sera. The assay data were expressed as a ratio of nanograms of free beta-subunit per 1000 mIU of total beta-subunit. The ratios, analyzed by the Wilcoxon two-sample test, indicated a highly significant correlation between high ratios and the eventual diagnosis of high-risk gestational trophoblastic disease (p = 0.0019). This study suggests that the excessive production of free beta-subunit of human chorionic gonadotrophin may identify patients with high-risk gestational trophoblastic disease much earlier and identify gestational trophoblastic disease in patients during pregnancy.

Adult↗

Value of serum 125Ca levels: does the result preclude second look?

Forty-five women with known histories of ovarian cancer underwent reoperative surgery. Thirty-seven patients underwent routine second-look laparotomy and eight patients were reexplored with clinical evidence of disease with the intent of re-resection. Preoperative CA 125 levels were obtained. Evaluation as to the predictive value of the CA 125 level and operative findings show a positive predictive value of 100% and a negative predictive value of 54%. Twenty of the forty-five patients had gross disease present on reoperation. Twenty patients were found to have persistent disease at reoperation. Twenty-five percent of patients with CA 125 levels less than or equal to 35 U/ml and 37% of these with CA 125 levels greater than 35 U/ml were resectable to no gross disease at the completion of the reoperation. CA 125 levels greater than or less than 35 U/ml were not predictive of the potential for re-resectability of the tumor.

Antigens, Tumor-Associated, Carbohydrate↗

Treatment of nonmetastatic gestational trophoblastic disease with sequential intramuscular and oral methotrexate.

Thirty-seven patients with nonmetastatic gestational trophoblastic disease (NMGTD) were treated with one or more cycles of oral methotrexate following intramuscular methotrexate as part of induction chemotherapy. Remission was achieved in 31 patients (83.8%). All failures were readily cured with alternate regimens. Prospective studies using this safe, easily administered modality are needed to verify its apparent efficacy.

Administration, Oral↗