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Biomedical subjects

K D Hatch

Publications and source records attributed to K D Hatch.

At least 19 recordsLinked to original sources

Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report.

There is a critical need to find additional effective therapies in the management of ovarian cancer. A previously reported Gynecologic Oncology Group trial demonstrated that tamoxifen is an active drug when used in the salvage setting in this malignancy. Unfortunately, this original report did not specifically examine the utility of tamoxifen in patients with clinically defined platinum-refractory disease. In this reanalysis of the results of treatment of 102 evaluable patients entered into this multi-institutional trial, an objective response rate of 13% (95% confidence interval, 6.4-22.6%) was observed in patients with cisplatin-refractory ovarian cancer. The median response duration in this patient population was 4.4 months (range 1.2-9.2 months). Although the response rate is modest, this well-tolerated hormonal agent is a reasonable therapeutic option in selected patients with ovarian cancer when salvage therapy is to be considered. A possible role for this hormonal agent in other clinical settings in ovarian cancer will need to be defined through the conduct of carefully designed randomized clinical trials.

Antineoplastic Agents, Hormonal

The role of laparoscopy in gynecologic oncology.

The use of laparoscopy in the management of gynecologic malignancies has significantly increased over the last 5 years. The safety and adequacy of pelvic and para-aortic lymphadenectomy has been established by several investigators. Patients with early carcinoma of the cervix are now undergoing Schauta (radical vaginal) hysterectomy after laparoscopic lymphadenectomy. Patients with carcinoma of the endometrium are treated by laparoscopically assisted vaginal hysterectomy in conjunction with laparoscopic pelvic and para-aortic lymphadenectomy. Staging and second-look procedures are now being performed laparoscopically in patients with carcinoma of the ovary. The Gynecologic Oncology Group is currently investigating the role of laparoscopic surgery for patients with carcinoma of the cervix, endometrium, and ovary in four Phase II trials. A randomized Phase III trial comparing laparoscopy to laparotomy for patients with carcinoma of the endometrium will begin soon.

Clinical Trials as Topic

Phase II study of 13-cis-retinoic acid plus interferon-alpha 2a in heavily pretreated squamous carcinoma of the cervix.

The combination of 13-cis-retinoic acid (13-cRA) and interferon (IFN)-alpha 2a has been reported to be highly active in previously untreated squamous carcinoma of the cervix. In this phase II study, 13-cRA was given at a dose of 1 mg/kg/day and IFN-alpha 2a was given subcutaneously at a dose of 3 million units/m2/day. Thirteen of 14 patients enrolled in this study are evaluable for response and toxicity. There were no complete or partial responses. Ten patients had progressive disease and the remaining three had stable disease. Principle toxicities were fatigue, nausea, and vomiting. This regimen appears cross-resistant with radiotherapy and/or platinum-based cytotoxic therapy in heavily pretreated patients with squamous carcinoma of the cervix.

Adult

Laparoscopic surgical staging of ovarian cancer.

The feasibility of laparoscopic staging in patients with ovarian cancer was undertaken prospectively to determine the ability to adequately evaluate both the intraperitoneal cavity and the retroperitoneal lymph nodes. Two groups of ovarian cancer patients were evaluated: those with optimally debulked advanced disease undergoing second-look procedures and those with presumed stage I disease undergoing surgical staging. Twenty-four of the 44 laparoscopic second-look procedures (56%) were positive for persistent disease. Five of these patients had microscopic disease only, in the omentum, washings, pelvic peritoneum, and in para-aortic lymph nodes (2 patients). In the group of 14 patients undergoing staging for presumed early ovarian carcinoma, metastatic disease was discovered in 8 (57%) patients. Two patients had peritoneal washings positive for adenocarcinoma; 3 had pelvic disease, 1 confined to a fallopian tube and 2 to the pelvic peritoneum; and 3 patients had para-aortic lymph nodes positive for metastatic adenocarcinoma. There were no serious complications in this category. The average hospital stay was 1.6 days. Laparoscopic staging appears to be an accurate staging technique, and further investigation into the validity of this approach is warranted.

Adolescent

An evaluation of human papillomavirus testing for intermediate- and high-risk types as triage before colposcopy.

OBJECTIVE: Our purpose was to evaluate the role of testing for intermediate- and high-risk human papillomavirus by use of a hybrid capture technique for predicting which patients with abnormal Papanicolaou smears are most likely to have squamous intraepithelial lesions or cancer. STUDY DESIGN: Cervical cytologic studies, hybrid capture tests, and colposcopically directed biopsies were performed on 311 women referred to the colposcopy clinics with abnormal cytologic study results. RESULTS: There was a highly significant correlation (p < 0.0001) between a positive human papillomavirus test and the finding of squamous intraepithelial lesions or invasive cancer. The sensitivity of human papillomavirus testing to detect high-grade squamous intraepithelial lesions was 74% when it was used alone and increased to 91% when coupled with abnormal cytologic study results of low- or high-grade squamous intraepithelial lesions or cancer. In 44 women with atypical squamous cells of undetermined significance on cytologic study, human papillomavirus testing identified six of 10 who had high-grade squamous intraepithelial lesions. For the 96 patients with low-grade squamous intraepithelial lesions, human papillomavirus testing was successful in identifying 29 of the 37 with high-grade squamous intraepithelial lesions (sensitivity 0.76). CONCLUSION: Testing for intermediate- and high-risk human papillomavirus types by hybrid capture improves the detection of high-grade squamous intraepithelial lesions in women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions over cytologic study used alone.

Cervix Uteri

Cryotherapy.

Cryotherapy is as effective as any other therapy for CIN 1 and CIN 2. It can be performed with a minimum of side-effects and long-term sequelae. It is more cost-efficient than other methods since the equipment is inexpensive and it requires little technical training.

Cryosurgery

Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma.

BACKGROUND: Global DNA hypomethylation has been observed in some human neoplasms and has been implicated as an important factor in carcinogenesis. The current study was designed to assess whether DNA hypomethylation occurs in cervical dysplasia and cancer, and to determine the relationship between the degree of DNA hypomethylation and the grade of neoplasia. METHODS: Cervical biopsy specimens were obtained from colposcopically identifiable lesions in 41 patients with abnormal Pap smear results. The extent of global DNA methylation was assessed by incubating the extracted DNA with [3H]-S-adenosylmethionine and Sss1 methyltransferase, an enzyme that specifically catalyzes the transfer of methyl groups to cytosine residues in the cytosine-guanine doublet. The degree of exogenous 3H-methyl group incorporation into the DNA therefore is related reciprocally to the extent of endogenous DNA methylation. These data were compared with the histopathologic classification of the lesions. RESULTS: The extent of 3H-methyl group incorporation was increased threefold and sevenfold in the DNA from cervical dysplasia and cancer, respectively, compared with the DNA from normal cervical tissue (P = 0.006, analysis of variance). Significant incremental increases in DNA hypomethylation were observed in the progression from normal and low grade squamous intraepithelial lesions (SIL) to high grade SIL and to cancer (P < 0.0001, trend). CONCLUSIONS: These data show that global DNA hypomethylation is a significant epigenetic event in cervical carcinogenesis and that the degree of DNA hypomethylation increases with the grade of cervical neoplasia. These data suggest that global DNA methylation may serve as a biochemical marker of cervical neoplasia.

Cervix Uteri

Anti-tumor antibody produced by human tumor-infiltrating and peripheral blood B lymphocytes.

Cell suspensions from 69 human tumor biopsies and malignant effusions depleted of infiltrating T cells were incubated for 10-14 days with mitomycin-C-treated cells of the transformed T cell line MOT as feeder cells. B lymphocytes proliferated and differentiated as indicated by immunoglobulin (Ig) secretion in the culture supernatants (B cell expansion). Ig was present in culture supernatants of tumor cell suspensions incubated without MOT feeder cells (non-expanded cells), but the addition of MOT feeder cells to these cultures invariably resulted in a significant increase in Ig concentration. While IgG, IgA, and IgM isotypes were all detected in supernatants of both expanded- and non-expanded tumor cell suspensions, the increase in total Ig induced by MOT feeder cells was mainly due to an increase in IgG. Peripheral blood B lymphocytes (PBBL) from 15 cancer patients and 4 healthy individuals were also successfully expanded by the same method. In these it was shown that IgA was the predominant Ig isotype. Using a modified enzyme-linked immunosorbent assay, IgG of 25/36 expansions from tumor cell suspensions showed reactivity with autologous tumor targets, and that from 10/13 expansions reacted with allogeneic tumor targets of the same histological diagnosis. No reactivity was found against tumor targets of different histology. IgG of 4/10 expansions of PBBL from cancer patients showed reactivity with allogeneic tumor targets of the same histology, while no reactivity was demonstrated against tumor targets of different histology. IgG of expanded PBBL from healthy individuals showed no reactivity against tumor targets. This method allows detailed study of the specific humoral antitumor immune response of intratumoral and peripheral blood B lymphocytes in cancer.

Antibodies, Neoplasm

Abdominal-wall tumor implantation after laparoscopy for malignant conditions.

OBJECTIVE: To determine the incidence of abdominal-wall tumor implantation after laparoscopic procedures in patients with known malignancies. METHODS: We reviewed 557 laparoscopic procedures performed by the Gynecologic Oncology Service between November 1990 and February 1994. In 105 procedures, malignancy was documented cytologically or histologically, 88 with intraperitoneal disease and 17 with retroperitoneal disease. Ovarian cancer represented 80% (70 of 88) of the procedures with intraperitoneal malignancy, and the remaining cases consisted of carcinoma of the fallopian tube (two), endometrium (11), cervix (one), breast (three), and stomach (one). Histologically, ovarian carcinomas ranged from low malignant potential to poorly differentiated. Among 88 patients with intraperitoneal disease, 77 had gross disease and 11 had microscopic disease. Four hundred thirty-seven different abdominal-wall puncture sites were used (38 Veress needle sites and 399 laparoscopic ports). RESULTS: One of the 437 (0.2%) abdominal-wall puncture sites developed implantation, a frequency of 1.0% (one in 105) per procedure; this developed after a second-look laparoscopic procedure for ovarian carcinoma in which only microscopic disease was present. If only intraperitoneal disease is considered, the incidence of implantation was 0.3% (one in 363) per abdominal puncture and 1.1% (one in 88) per procedure. CONCLUSION: Tumor implantation at the abdominal-wall puncture site is an infrequent occurrence after laparoscopy in patients with intraperitoneal and retroperitoneal carcinoma.

Abdominal Muscles

Preinvasive cervical neoplasia.

The HPV has been identified as the causative agent for cervical neoplasia. The transforming mechanisms appear to be through inactivation of p105Rb or p53 by the oncoproteins E6 and E7 of HPV types 16 and 18. Because 2% to 24% of normal women test positive for these viral types and the incidence of neoplasia is less than 1%, co-factors must play an important part in carcinogenesis. A search for these co-factors is underway.

Cell Transformation, Neoplastic

Neovaginal reconstruction.

Formation of a neovagina is an important step in restoring a normal self-image for the woman who has had treatment for gynecologic cancer. There are several techniques that the surgeon may select based on the amount of tissue removed or damaged, the surrounding anatomy, and the condition of the patient. The indications, techniques, and results of these procedures will be described in this article.

Female

The rhomboid transposition flap for repair of the perineal defect after radical vulvar surgery.

A detailed account is given of experience at a single institution with the rhomboid transposition flap used to repair the perineal defect after surgery for carcinoma of the vulva. In 13 of 15 assessable cases, the flaps healed completely or had insignificant separation of a segment of the flap. In 2 cases, more major breakdown occurred in association with infection, but in both cases, satisfactory healing occurred without further surgery. In 14 cases, passage of a speculum and inspection of the vagina was possible at follow-up and only 1 patient experienced introital stenosis.

Adult

Laparoscopically assisted surgical staging (LASS) of endometrial cancer.

We report 59 patients who were considered candidates for laparoscopically assisted surgical staging (LASS) to manage their clinical stage I adenocarcinoma of the endometrium. Their ages ranged from 40 to 85 years, with a mean of 69; their weights ranged from 102 to 267 pounds, with a mean of 153 pounds. Patients with intraperitoneal disease were taken off study. Laparoscopic pelvic and para-aortic lymphadenectomies were performed based on the grade of the tumor and the depth of myometrial invasion. Six patients were discovered to have intraperitoneal disease. Of the remaining 53 patients, 29 underwent lymphadenectomy, 1 of whom had positive para-aortic nodes. Of the 24 patients who did not have laparoscopic lymphadenectomy, 2 should have, according to the study criteria; however, obesity precluded this from being performed. Eight patients had grade 3 lesions; of these, 4 lesions had metastasized. The remaining 3 patients with metastatic disease had grade 2 lesions. Complications were related to the laparoscopically assisted vaginal hysterectomy and resulted in two laparotomies: one for a transected ureter and the other for a cystotomy. Estimated blood loss was < 200 cc and the average hospital stay was 2.9 days. We feel that LASS is an attractive alternative to the traditional surgical approach in patients with stage I endometrial carcinoma.

Adenocarcinoma

A phase II trial of medroxyprogesterone acetate in epithelial ovarian cancers. A Gynecologic Oncology Group study.

Twenty-four evaluable patients with advanced or recurrent epithelial ovarian carcinoma who progressed on platinum-containing combination chemotherapy were treated with medroxyprogesterone acetate (C.T. Provera) 50 mg orally three times a day until progression of disease. One patient had a partial response (4.2%), 9 patients had stable disease (37.5%), and 14 (58.3%) had increasing disease. The 95% upper confidence limit for response is less than or equal to 18.3%. There was no toxicity associated with its use. C.T. Provera has limited activity in patients with epithelial ovarian cancer who have failed combination chemotherapy.

Adult

Laparoscopic para-aortic lymphadenectomy in gynecologic malignancies.

OBJECTIVE: To determine the feasibility, safety, limiting factors, and advantages of laparoscopic para-aortic lymphadenectomy in a series of patients with gynecologic malignancies. METHODS: During a 2-year period, 61 women underwent laparoscopic para-aortic lymph node dissection as part of their management for invasive gynecologic malignancies. A transperitoneal incision directly over the aorta was used. Initially, only the right-side infra-inferior mesenteric artery nodes were removed. The technique of removal of left-side low para-aortic nodes was then developed, followed by the technique for removal of right- and left-side nodes above the transverse duodenum. A total of 52 right para-aortic lymphadenectomies were performed, 12 of which were combined with left-side lymphadenectomies. A total of 17 left-side lymphadenectomies were performed, 12 of which were bilateral. Four patients had nodes removed above the inferior mesenteric artery. RESULTS: The procedure could not be performed in four instances because of obesity or adhesions. Twenty-four patients had their laparoscopic surgery combined with another procedure, which increased their hospital stays: radical hysterectomy (five), laparoscopy-assisted vaginal hysterectomy (17), transperineal interstitial irradiation (one), and anterior-posterior colporrhaphy (one). The remaining 33 patients had laparoscopic surgical staging only. One patient required laparotomy to control bleeding from the vena cava; however, the others had no short- or long-term complications, and the average hospital stay was 1.3 days. CONCLUSION: Laparoscopic para-aortic lymphadenectomy is a safe, effective procedure that allows a shorter hospitalization than traditional laparotomy.

Adolescent

Comparison of Doppler with two-dimensional sonography and CA 125 for prediction of malignancy of pelvic masses.

OBJECTIVE: To assess the validity of Doppler flow sonography for the prediction of malignancy in adnexal masses and to compare the results with two-dimensional ultrasonographic examination and CA 125 levels. METHODS: In a cross-sectional study, 55 patients with adnexal masses were examined using Doppler sonography to measure the resistance index of tumor-associated blood flow profiles. In addition, abdominal and transvaginal ultrasound examinations were performed and preoperative CA 125 serum levels were assessed. RESULTS: Sixteen patients had malignant tumors and 39 had benign tumors. A resistance index cutoff of less than or equal to 0.8 showed the highest sensitivity (93.8%), with a specificity of 56.4%, a positive predictive value of 46.8%, and a negative predictive value of 95.7%. Compared with two-dimensional sonographic evaluation using either a scoring system or subjective assessment, and with CA 125 levels, the resistance index showed higher sensitivity and negative predictive value but lower specificity and positive predictive value. False-positive resistance index values were prevalent with endometriosis, leiomyomata, and mucinous cystadenoma. The combination of the resistance index with either the sonographic features or CA 125 increased the sensitivity and negative predictive value to 100%, with only a slight decrease in specificity and positive predictive value, but was not superior to the combination of two-dimensional sonography and CA 125. CONCLUSION: Doppler sonographic evaluation of resistance indexes in the vessels of adnexal masses increased the sensitivity of two-dimensional sonography and CA 125. However, 46% of positive Doppler results were false and 37.5% of the benign tumors had low resistance indexes, thus limiting the validity of this technique for screening programs.

Adnexal Diseases

Oral folic acid supplementation for cervical dysplasia: a clinical intervention trial.

OBJECTIVE: We attempted to evaluate the effect of oral folic acid supplementation on the course of cervical dysplasia. STUDY DESIGN: A total of 235 subjects with grade 1 or 2 cervical intraepithelial neoplasia were randomly assigned to receive either 10 mg of folic acid or a placebo daily for 6 months. Clinical status, human papillomavirus type 16 infection, and blood folate levels were monitored at 2-month intervals. Outcome data were subjected to chi 2 analysis. RESULTS: The prevalence of human papillomavirus type 16 infection initially was 16% among subjects in the upper tertile of red blood cell folate versus 37% in the lower tertile (trend p = 0.035). After 6 months no significant differences were observed between supplemented and unsupplemented subjects regarding dysplasia status, biopsy results, or prevalence of human papillomavirus type 16 infection. CONCLUSION: Folate deficiency may be involved as a cocarcinogen during the initiation of cervical dysplasia, but folic acid supplements do not alter the course of established disease.

Administration, Oral