Biomedical subjects
Publications and source records attributed to K D Hatch.
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.
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.
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.
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.
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.
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.
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.
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.
Two hundred twelve patients who underwent second-look laparotomy as part of their treatment for epithelial ovarian cancer were evaluated. Factors associated with positive second looks were initial stage, tumor grade, age, and residual disease (P less than 0.05). One factor not of significance was whether adjuvant therapy was platinum based. Initial stage only was associated with recurrence after a negative second look (P less than 0.001). When controlled for volume of disease no difference in survival between various salvage therapies could be demonstrated. Survival between patients with recurrence after negative second look and patients with microscopic residual disease was similar even though the former group was not treated until recurrence (P = 0.75). Second-look laparotomy does not improve survival with currently existing salvage modalities and should primarily be confined to those patients willing to participate in research protocols evaluating new second-line therapy.
A case of primary vaginal tuberculosis is reported. A 62-year-old woman presented with a slightly eroded, granular vaginal lesion 10 months after radiation therapy for Stage II vaginal squamous cell carcinoma. She had previously undergone a total abdominal hysterectomy and left salpingo-oophorectomy at age 37 for abnormal uterine bleeding. This presentation of genital tract tuberculosis is unusual because of the location of the primary lesion, the age at presentation, the occurrence after radiation therapy, and the possible means of infection. We emphasize the need to maintain a high index of suspicion and to biopsy any suspicious vaginal lesions.
We report seven patients who underwent diagnostic laparoscopy and biopsy under local anesthesia using a new optical catheter. Six of these procedures were performed in the office. Four patients had previous malignancies (lung, breast, and fallopian tube), and intraperitoneal recurrences or new primaries were suspected. In two of these patients, laparoscopically directed biopsies confirmed adenocarcinoma similar to their prior malignancies, and in one a new primary was diagnosed. The fourth patient had no evidence of intraperitoneal disease. In the three patients with new intraperitoneal malignancies, biopsies obtained laparoscopically confirmed adenocarcinomas of the ovary in two patients and of the gastrointestinal tract in one patient. We feel that this procedure is a safe, simple, effective, and economical way to evaluate the intraperitoneal cavity and to obtain histologic or cytologic specimens for evaluation in patients with intraperitoneal malignancies. This is an ideal, minimally invasive method for detecting small-volume intraperitoneal disease. In addition, it allows some patients to be spared major operative procedures.
OBJECTIVE: We attempted to evaluate the use of ifosfamide either alone or in combination in patients with refractory malignant gestational trophoblastic disease. STUDY DESIGN: Our study comprised, in part, a phase II multiinstitutional trial of ifosfamide in refractory gynecologic malignancies and, in part, a review of institutional experience with ifosfamide in combination chemotherapy. RESULTS: Single-agent ifosfamide produced a significant response in titer in one of two patients with refractory choriocarcinoma. Ifosfamide with etoposide and cisplatin (also known as VIP) resulted in significant response in human chorionic gonadotropin titers in three patients with highly refractory metastatic gestational trophoblastic disease and one cure in this group of patients. CONCLUSION: Ifosfamide has activity in refractory choriocarcinoma and, when combined with etoposide and cisplatin (VIP), may be curative.
In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose schedule. Response was not an objective of this study, but four partial responses were seen in nine patients with measurable lesions. In general, the therapy was well tolerated, but of the ten patients treated at the first dose level (cisplatin 50 mg/m2 intravenously on day 1 plus mitolactol 180 mg/m2 orally on days 2-6 every 3-4 weeks), 5 required de-escalations and 8 required delays because of toxicity. All three patients treated with cisplatin plus a higher dose of mitolactol (270 mg/m2 x 5) required dose reductions and delays for hematologic toxicity. The first dose level appears tolerable by patients with, and promising in treating, advanced cervix cancer.
Vulvovaginitis is the most common reason for a woman to see her gynecologist. The most common causes are bacterial vaginosis, Candida species, and Trichomonas vaginals, respectively. Human papillomavirus has become a major diagnostic and therapeutic problem. Human papillomavirus DNA testing suggests that exposure to human papillomavirus occurs frequently at birth and intermittently throughout a woman's life after the onset of sexual activity. Interferon has been shown to be effective in treating some forms of human papillomavirus.
One hundred five patients with Stage III or IV epithelial ovarian cancer whose disease had persisted or recurred after primary surgery and first-line chemotherapy were given tamoxifen (20 mg orally twice daily) and evaluated for response. Eighteen percent of the patients responded: 10% demonstrated a complete response (CR) and 8% showed a partial response (PR). Thirty-eight percent of the patients had short-term disease stabilization. CR had a median duration of 7.5 months, with the longest lasting 17 months. For patients with PR or stable disease, the median duration of response was 3 months (maximum duration, 9 months). When estrogen receptors of tumor tissue from patients demonstrating CR were evaluated, eight of nine (89%) had elevated estrogen receptor levels. This contrasts with patients who had stable or progressive disease as only 59% of them had measurable estrogen receptors (P = 0.16).
A case-control study was undertaken to evaluate the roles of obesity and body fat distribution in the etiology of endometrial cancer. The study also included an evaluation of the associations of serum estrone, estradiol, and androstenedione with obesity, body fat distribution, and endometrial cancer risk. The study included 168 cases and 334 control subjects identified at an optometry clinic. A strong, positive relationship between overall obesity and endometrial cancer was found. The relative rate of endometrial cancer for women in the upper 90th percentile of a body mass index compared to those below the median was estimated as 5.5 with 95% confidence limits of 3.2-9.6. There was no association between endometrial cancer and the waist to hip ratio, an index of upper versus lower body fat distribution. A statistical test of trend across the four quartiles of the waist to hip ratio yielded a P value of 0.45 after adjustment for confounding by the body mass index. On the other hand, there was a statistically significant, independent positive effect of a high subscapular to tricep skinfold ratio, a measure of central versus peripheral obesity, on endometrial cancer risk. The relative rates of endometrial cancer for the second, third, or fourth quartile compared to the first quartile of this index were 1.5, 1.9, and 2.7, respectively (P = 0.007), after adjustment for the body mass index. Serum estrone and estradiol, but not androstenedione, were statistically significantly correlated with the body mass index among control subjects (r = 0.37 and 0.40 for estrone and estradiol, respectively). On the other hand, each of the sex hormones was uncorrelated with the waist to hip ratio after adjustment for body mass. The correlations between each of the three hormones and the subscapular to tricep skinfold ratio among controls were weak and were not statistically significant (0.10, 0.10, and 0.14 for estrone, estradiol and androstenedione, respectively). Cases had statistically significantly higher mean serum estrogen and androstenedione levels than did controls and these elevations did not simply reflect a higher prevalence of obesity among them. The findings are equivocal with respect to fat patterns and endometrial cancer. We suggest that future epidemiological studies of cancer and body fat distribution more carefully distinguish among the various types of fat patterns.
From July 1975 through December 1985, 328 patients with ovarian malignancies were treated. Of these, 302 had epithelial invasive malignancies and constitute the study group. The impact of the operative procedure, findings, and subsequent treatment is evaluated. Patients who underwent extensive debulking procedures such as bowel resection and peritoneal stripping did not have improved survival compared with those patients who did not undergo these procedures and yet had residual disease remaining (P = 0.7 and P = 0.34). Reoperating patients felt to be unresectable at the time of referral did not increase survival over reoperating patients after an attempt at chemotherapeutic reduction (P = 0.34).
Between 1969 and 1988, 401 patients were treated by radical hysterectomy and pelvic lymphadenectomy for Stage IB cervical carcinoma at the University of Alabama at Birmingham. In multivariate analysis, pathological tumor diameter (P less than 0.0001) and the presence of lymph node metastasis (P = 0.0005) proved to be the dominant two histopathologic features that significantly correlated with overall survival. Although 5-year survival for the overall group was 85%, 5-year survival in patients with lesions greater than 3.0 cm in diameter and with regional nodal metastasis was less than 30%. This discrepancy in survival in surgically treated early-stage cervical cancer patients supports a need for subcategorization by risk factors such as pathologic tumor dimensions and nodal status and for further investigation of alternative neoadjuvant and adjuvant therapies in those early-stage cervical cancer patients deemed at high risk for poor overall survival.