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Biomedical subjects

H M Shingleton

Publications and source records attributed to H M Shingleton.

At least 37 records · Page 2Linked to original sources

Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer.

Fifty patients with cervical cancer were treated with radical hysterectomy and lymphadenectomy followed by postoperative radiation therapy for high risk factors (nodal metastases, lymphvascular space invasion, close or involved margins) at the University of Alabama at Birmingham Medical Center from 1969 to 1984. Fifteen (30%) of the patients treated had serious complications, 8 (16%) requiring an operation, and 1 (2%) dying as a result of treatment-related problems. This combined modality approach is associated with significant complications.

Adenocarcinoma

Intraperitoneal chromic phosphate in ovarian cancer: risks and benefits.

Between March 1977 and December 1985, 59 patients were treated with intraperitoneal chromic phosphate at The University of Alabama Birmingham Hospitals and its affiliates. Twenty-seven patients received primary adjuvant therapy. Thirty-two patients were treated "secondarily" after tumor recurrence or after a "positive" second-look laparotomy. Associated morbidity was noted to be 12% with reoperation required in 7%. Early stage and grade tumors demonstrate a good prognosis. Little, if any, benefit was demonstrated in "secondary" therapy of advanced stage and grade tumors.

Chromium

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

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.

Adenocarcinoma

Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay.

Serum samples were collected from 611 gynecologic patients for measurement of squamous cell carcinoma antigen levels using the Abbott Laboratories squamous cell carcinoma antigen radioimmunoassay kit. Sixteen of 83 patients (19.3%) with cervical dysplasia and 72 of 135 (53.3%) with primary or recurrent cervical carcinoma had levels above 2.4 ng/mL. In contrast, only seven of 373 women (1.9%) without genital tract squamous cell intraepithelial neoplasia or carcinoma had squamous cell carcinoma antigen levels above 2.4 ng/mL. Fifty-six patients with cervical cancer were followed for correlation of squamous cell carcinoma antigen levels to disease course, and 20 had persistent or recurrent disease after therapy; rising squamous cell carcinoma antigen levels predicted disease in 15 of these 20 patients with recurrence (13 of 15 with elevated pre-treatment levels and two of five with normal pre-treatment levels). Rising squamous cell carcinoma antigen levels preceded the clinical detection of disease in ten patients by a mean of 4.6 months (range 2-7.5 months); in the remaining five, squamous cell carcinoma antigen levels were elevated only when disease recurrence was documented. Although measurement of squamous cell carcinoma antigen levels is not a sensitive screening method for cervical cancer (sensitivity 53.3%), the test has good specificity (94.3%); the majority of patients with false-positive elevations had other genital tract squamous cell neoplasias. The squamous cell carcinoma antigen assay may be a useful aid for monitoring the disease course of cervical carcinoma.

Antigens, Neoplasm

Amplification of the c-myc proto-oncogene in cervical carcinoma.

Amplification without structural rearrangements of the c-myc proto-oncogene was found in 14 of 44 primary cervical neoplasms. There was no apparent correlation with stage of disease or degree of cellular differentiation. The prognostic significance of c-myc amplification cannot be determined from this study.

Adenocarcinoma

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.

Cell Line

Analysis of prognostic features in adenocarcinoma of the cervix.

Uncertainties regarding the clinical behavior and management of women with primary adenocarcinoma of the cervix persist. A series of 162 patients was evaluated with emphasis on histopathology, clinical features, treatment, and survival. Sixty-seven patients underwent radical hysterectomy alone, 65 patients underwent radiation therapy alone, while the remainder were treated with combined surgery and radiotherapy. When compared to a matched series of squamous cell carcinoma patients, no statistical differences in survival could be demonstrated. Clinical stage (P less than 0.001) and lesion size (P less than 0.001) were the most important prognostic factors for the entire series. Patients with adenocarcinoma of varied histologic patterns were compared to patients with adenosquamous lesions and no statistical difference in survival could be demonstrated. Multivariate analysis of those women with Stage I adenocarcinoma of the cervix identified risk groups based on tumor grade, lesion size, and patient age. Patients in the low risk group had a 5-year survival of 89.5% while patients in the intermediate and high risk groups had 5-year survival rates of 68.4 and 37.3%, respectively. In patients with Stage I well-differentiated lesions survival was excellent, independent of lesion size.

Adenocarcinoma

Adjuvant postoperative radiation therapy following radical hysterectomy in stage IB CA of the cervix--analysis of treatment failure.

Among 240 patients treated by radiation therapy for clinical Stage IB cancer of the cervix between 1969 and 1980, 38 patients received postoperative pelvic radiation therapy after radical hysterectomy because of positive pelvic lymph nodes and/or close surgical margins. The overall recurrence was 45% (17 of 38), and the major complication rate was 15% in minimum 5-year follow-up. In patients with positive pelvic lymph nodes, the pelvic recurrence was 13% (3 of 23). However, distant metastases alone was 26% (6 of 23), which was the most common treatment failure. In 11 patients with close surgical margins, eight patients had paracervical margins and three had vaginal margins. All five patients with paracervical margins treated with vaginal ovoid irradiation only had pelvic recurrence. No local failure occurred in the other three patients treated with whole pelvic irradiation. All patients with vaginal margin alone treated with vaginal ovoid or whole pelvic irradiation had no recurrence of cancer in the pelvis. On the basis of our data, whole pelvic irradiation with or without vaginal ovoid irradiation is necessary in those with a close paracervical margin. In patients with close vaginal margin, whole pelvic irradiation with or without vaginal ovoid irradiation is recommended. The vaginal ovoid irradiation alone should be limited to very selected cases.

Adenocarcinoma

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.

Anastomosis, Surgical

Incisions.

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Abdominal Muscles

CA125 as a serum marker for poor prognosis in ovarian malignancies.

In cancer of the ovary, a tumor marker is much needed to assist the conventional methods for monitoring the disease course. All published reports of the CA125 serum immunoassay to date have indicated that rising or falling CA125 levels correlated with disease progression or regression in patients with ovarian malignancies. Our experience with CA125 at the University of Alabama at Birmingham shows that rising CA125 levels are highly suggestive of progressive disease. However, the significance of our findings with CA125 is that, contrary to other reports, falling CA125 levels are not a reliable indicator for regressive disease. Thus, falling CA125 levels are not clinically useful whereas rising CA125 levels may be interpreted as indicative of poor tumor response to therapy, and of the presence of persistent or recurrent disease either prior to second-look laparotomy or during post-treatment follow-up.

Antigens, Neoplasm

The adverse effects of cervical cancer treatment on bladder function.

Bladder dysfunction is a recognized complication following radical hysterectomy, however, the effect of radiation alone or in combination with surgery on bladder function has received little attention. Thirty patients who underwent radical hysterectomy with postoperative whole pelvis radiation (RH + RT) were matched for age, stage of disease, and time interval since therapy, with 30 patients who had radical hysterectomy alone (RH) and 30 patients who were treated with pelvic radiotherapy (RT). Bladder function was assessed by symptoms and urodynamic evaluation. Altered bladder sensation and voiding problems were associated with surgery, and were more frequent after RH or RH + RT than RT (P = 0.002). fifty percent of RH patients voided by abdominal straining compared to 10% who had only RT. No greater problem was seen after RH + RT compared to RH. Urinary incontinence was present in 15% of patients prior to therapy. After treatment, incontinence requiring protection developed in 23% of RT patients, 26% of RH patients, and 63% of RH + RT patients. The severity of the incontinence was greater after RH + RT. Bladder neck and urethral function was similar in all groups, however, bladder compliance was reduced in RT patients and significantly (P = 0.0001) reduced after RH + RT compared to RH alone. This reduction was related to the bladder dose of external radiation and was a factor in the etiology of the urinary incontinence seen in RH + RT patients.

Adult

Treatment of nonmetastatic gestational trophoblastic disease with oral methotrexate.

Fifteen patients with nonmetastatic gestational trophoblastic disease were treated solely with methotrexate given orally rather than intramuscularly. Remission, defined as a beta-human chorionic gonadotropin titer of less than 5 mIU/ml for 3 consecutive weeks, was attained in 13 (87%) of the 15 patients. Level of toxicity was acceptable. Patient comfort, convenience, and less time off work and in the physician's office are significant advantages to this efficacious, well-tolerated method of therapy.

Administration, Oral

The short-term effect of radical hysterectomy on urethral and bladder function.

To investigate bladder neck and urethral function after radical hysterectomy, 21 patients were investigated before and 3 months after the operation. Each patient had an excretory urogram, CO2 cystoscopy, uroflowmetry, water cystometry and a urethral pressure profile, using a dual sensor microtransducer catheter, at rest and during stress. Postoperatively there was a significant reduction in urethral length and urethral closure pressure; however, pressure transmission ratios were maintained, indicating no loss of bladder neck support with stress. Of the six patients with pre-operative bladder neck weakness, two (33%) had stress urinary incontinence at the 3 months assessment. No patient with a normal pre-operative assessment developed this complication. Fifteen (71%) voided by abdominal straining and this manoeuvre emptied the bladder effectively. These data suggest that patients with pre-operative evidence of an incompetent bladder neck may be predisposed to develop stress urinary incontinence after radical hysterectomy because of a reduction in the urethral closure pressure.

Adult

The short-term effect of pelvic irradiation for gynecologic malignancies on bladder function.

Urinary symptoms and urodynamic studies were evaluated prospectively in 33 women undergoing radiation therapy for cervical cancer. Patients were evaluated during treatment, after one to two months, and after five to six months. Significant reductions in peak urinary flow, volume at first desire to void, cystometric capacity, and bladder compliance were evident during and immediately after therapy. Bladder symptoms and urodynamic alteration did not correlate with age, race, or stage of disease. Bladder compliance was significantly reduced in those patients receiving more than 3000 rads to the entire bladder from external beam irradiation.

Adult

Metastatic tumors mimicking gynecologic cancer.

Review of the admissions to the Gynecologic Oncology Service at the University of Alabama Medical Center over a 12-year period reveals that 1% of all referrals had nongynecologic malignancies. Duration of symptoms was short; of 40 patients with adequate follow-up, 31 (77%) were dead from their cancer, with a median survival of eight months. The value of diagnostic radiologic procedures was assessed and, while these procedures proved helpful, most patients required a surgical procedure (often a reoperation) to establish the diagnosis.

Adenocarcinoma

Immunohistochemistry of the blood group A,B,H isoantigens and Oxford Ca antigen as prognostic markers for stage IB squamous cell carcinoma of the cervix.

Currently, there is lack of a histologic classification of squamous cell carcinoma of the cervix that correlates significantly with patient survival. This study investigated the survival predictive value of two immunohistochemical markers, the blood group A,B,H isoantigens and the Oxford Ca antigen, on conventional histologic sections of tumor tissues from 85 surgically treated patients with Stage IB squamous cell cervical cancer. The results indicated that the two antigens are two distinct markers, neither of which correlates with tumor grade. The expression of the A,B,H isoantigens is significantly related to patient survival after adjustment for the depth of stromal invasion of the tumor, whereas the Oxford Ca antigen has no survival predictive value.

ABO Blood-Group System