Vicki V. Baker

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.

Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix

&NA; Between September 1969 and January 1, 1986, 143 pelvic exenterations for recurrent cervical cancer were performed by the gynecologic oncologists at the University of Alabama at Birmingham. Of this group, 78 patients underwent total pelvic exenteration, 63 patients had anterior exenteration, and two had posterior exenteration. The overall operative mortality rate was 6.3%, mostly associated with total pelvic exenteration. The 5‐year survival rates were 50% overall, 63% with anterior exenteration and 42% with total exenteration. Univariate and multivariate analyses were performed to identify clinical and histopathologic factors predictive of prolonged survival. Using three clinical factors (duration from initial radiation therapy to exenteration, size of the central mass, and presence of preoperative sidewall fixation), low‐, intermediate‐, and high‐risk groups were constructed; the 5‐year survival rates for these groups were 82, 46, and 0%, respectively. Inclusion of one histopathologic factor (margin status of the surgical specimen) added to the ability to predict 2‐ and 5‐year survival rates. The best candidates for cure by pelvic exenteration were those with recurrent small (less than 3 cm), mobile central masses who were a year or longer from the time of their previous radiation therapy. Attempts to resect bulky pelvic recurrences that impinge on the pelvic sidewall, especially in the case of persistent or early recurrent disease (within 6 months), or continuation of exenterative procedures in women known to have nodal metastases or extrapelvic spread, are generally futile. For those women falling between the two extremes, sound clinical and operative judgment is imperative in regard to selecting the treatment offering the best quality of life. (Obstet Gynecol 73:1027, 1989)

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.

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.

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

Abstract 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 >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.

Amniotic fluid embolism. Three case reports with a review of the literature.

Amniotic fluid embolism is a catastrophic event of the intra- and early postpartum period which may also be seen with cesarean delivery and during abortions. Presenting symptomatology includes respiratory distress with cyanosis, shock, and possibly tonic-clonic seizures. DIC frequently occurs. The pathogenesis may include entry of amniotic fluid through lacerations or ruptures of the uterus or cervix, through endocervical veins and through abnormal uteroplacental sites, such as with placental abruption, placenta previa, or placenta accreta. Amniotic fluid probably causes cardiovascular-respiratory symptoms by pulmonary vascular obstruction and through a vasoactive substance causing pulmonary vascular constriction. The lethality of amniotic fluid may be enhanced by a high particulate content or meconium staining. The diagnosis of amniotic fluid embolism may be made ante mortem by demonstrating amniotic fluid debris in central blood samples or expectorated sputum. Postmortem diagnosis often requires meticulous examination of the pulmonary microvasculature with the utilization of special stains. Treatment is directed towards symptoms of shock, arterial hypoxemia, and DIC. Acute renal failure may complicate the picture after shock. If the patient survives the embolic and coagulative problems, recovery is usually complete without long-term sequelae.

Low rectal resection and anastomosis at the time of pelvic exenteration

Twenty patients underwent a supra levator total pelvic exenteration with low rectal anastomosis for recurrent or persistent cervical carcinoma following radiotherapy. Fourteen (70%) had complete healing. Five of 9 patients with protective colostomies had complete healing while 9 of 11 without protective colostomies healed. Three of 7 patients with a rectal stump length of less than 6 cm healed while 11 of 13 whose rectal stump was 6 cm or greater experienced complete healing. Overall, 13 of the 20 patients are clinically free of disease and 8 (61%) of those enjoy life with excellent bowel continence. A low rectal anastomosis should be attempted in those patients undergoing a supralevator total pelvic exenteration.

Selective inhibition of c-myc expression by the ribonucleic acid synthesis inhibitor mithramycin☆

Expression of the c-myc proto-oncogene has been shown to correlate with the rate of cellular proliferation and malignant transformation in a number of cell types. JEG-3 choriocarcinoma cells demonstrate c-myc transcript levels that are greater than those of nonmalignant trophoblastic tissue at any stage of gestation. Southern blot analysis documents c-myc gene amplification in JEG-3 cells, with a gene copy number of approximately 20. The methylation pattern and genomic structure of the amplified c-myc oncogene in JEG-3 choriocarcinoma cells are identical to those of normal placenta. Treatment of JEG-3 cells with mithramycin, a ribonucleic acid synthesis inhibitor, results in a dramatic decrease in c-myc expression relative to that of the c-Ha-Ras gene. The apparent selectivity of mithramycin for c-myc expression represents the only example, to date, of the selective pharmacologic modulation of oncogene expression.

Review: Basic Mechanisms of Metastasis

ABSTRACT Metastatic disease is responsible for the majority of deaths caused by cancer. The process of metastasis is an orderly, stepwise process that results in the selection of cells that possess the capability to establish viable metastases. These cells must be locally invasive and be able to survive the physical traumas of dissemination and normal host defenses. Once metastatic cells have been arrested in a capillary bed, they must be able to invade the host organ parenchyma and survive in that milieu. Studies in a number of model systems have documented the phenotypic alterations in cells that have “metastatic potential.” These differences may stem from normal tumor cell heterogeneity and surprisingly reflect only minor differences in gene expression. The role of activated oncogenes in metastasis is unclear, but a number of laboratories have documented that transfection with activated Ha-Ras results in increased metastatic potential. An increased understanding of the genetic basis of metastatic potential may suggest new directions for intervening in this deadly process.

Neurofibrosarcoma complicating pregnancy

Sarcomatous degeneration of a neurofibroma during pregnancy is exceedingly rare. Prompt diagnosis followed by surgical resection is recommended.