Biomedical subjects

J T Chambers

Publications and source records attributed to J T Chambers.

At least 55 records · Page 3Linked to original sources

PubMed1991

Adjuvant whole-abdominal radiation therapy in uterine papillary serous carcinoma.

Nine patients from 34 to 74 years of age (median, 67 years of age) with uterine papillary serous carcinoma (UPSC) were treated with whole-abdominal radiation therapy (WART) on an adjuvant basis after cytoreductive surgery. All patients were treated with megavoltage photons to an abdominopelvic field to a median dose of 2500 cGy, with continued treatment to a whole pelvic field to a median dose of 4500 cGy. Three patients received additional boost to the vaginal apex. Follow-up time ranged from 6 to 31 months (median, 25 months) after completion of WART. Six patients had recurrent disease at 5 to 20 months (median, 7.5 months). Four of these patients died of their disease during the follow-up period. Three of six patients in whom treatment failed had disease at the vaginal apex. None of these patients received boost radiation therapy to that site. In contrast, two of three patients remaining disease free were treated with additional vaginal apex irradiation. Based on these results, the authors do not routinely recommend WART for adjuvant treatment of UPSC. They do, however, recommend vaginal apex irradiation for these patients.

Adult↗

PubMed1991

Sequelae of lateral ovarian transposition in irradiated cervical cancer patients.

Lateral ovarian transposition (LOT) is a useful technique for preserving ovarian function in "high-risk" premenopausal Stage I cervix cancer patients who undergo hysterectomy and subsequent postoperative whole pelvic radiation therapy. From 1978 to 1988, 38 FIGO Stage I cervical cancer patients underwent LOT as part of their initial operative procedure and 14 of these patients (37%) subsequently received pelvic radiation therapy (LOT + RT) because of pathological findings such as metastatic pelvic lymph node involvement or positive surgical margins (13 patients) or recurrent disease (1 patient). Ten (71%) of the 14 (LOT + RT) patients have maintained ovarian function with a median follow-up of 35 months. Preservation of ovarian function was directly related to the estimated scatter dose to the ovaries. For patients whose estimated ovarian dose was 300 cGy or less, only 1 of 9 patients (11%) underwent menopause, whereas 3 of 5 patients (60%) became menopausal if the ovarian dose was more than 300 cGy. The placement of the ovaries was also crucial for preservation of ovarian function, with 100% of the patients developing menopause if the ovaries were placed below the iliac crest. A major side effect of LOT was the development of symptomatic ovarian cysts in 7 (18%) of the 38 Stage I patients who underwent LOT. In the 24 patients who underwent LOT alone without RT, the incidence of symptomatic ovarian cysts was 25% compared to only 7% of the patients who underwent LOT + RT, although this difference was not statistically significant (p = .18).

Combined Modality Therapy↗

PubMed1991

Outpatient surgery in gynecologic oncology.

During the review period, the literature on outpatient gynecologic oncology surgery has focused on two major management problems. The first questions the treatment of cervical dysplasia with local destruction and proposes that excisional biopsy using either the carbon dioxide laser or low voltage loop diathermy is a safe procedure in the outpatient setting with low morbidity and the advantage of histology to exclude microinvasion disease. However, long-term efficacy and complication rates need to be evaluated. The second raises the possibility of extending the role of the laparoscopist to include the management of all pelvic masses using new techniques. These articles represent the beginning of the discussion on the limits that exist (or should exist) in such surgery as many become highly facile endoscopists. Further studies will be needed to determine the necessary parameters to eliminate from this approach women who are at high risk of having a pelvic malignancy.

Ambulatory Surgical Procedures↗

PubMed1990

Urinary gonadotropin fragment, a new tumor marker. III. Use in cervical and vulvar cancers.

The efficacy of urinary gonadotropin fragment (UGF) and squamous cell carcinoma antigen (SCC) measurements was examined in the management of cervical and vulvar cancers. Of women with benign gynecologic disease (n = 89) 7%, of women with cervical or vulvar intraepithelial neoplasia (n = 25) 8%, and of those with cervical or vulvar malignancies (n = 60) 47% had elevated UGF levels (greater than 3 fmol/ml). SCC at a cutoff of 2.5 ng/ml had a similar sensitivity, 43%, for the same group of cervical and vulvar malignancies. The populations recognized by SCC and UGF, however, only partially overlapped, so that together UGF and SCC were elevated in 62% of women with malignancies. The sensitivity of both markers was stage dependent, so that UGF and SCC detected 26 and 22%, respectively, of early (stage I or II), and 67 and 40%, respectively, of advanced (stage II or IV) cancers. We monitored the progress of 21 women undergoing therapy for cancer with UGF and SCC measurements. Of the 21, 13 (62%) had true-positive UGF levels and 11 (52%) had true-positive SCC levels when cancer was initially detected. The levels of UGF accurately reflected changing clinical observations in 11 of 21 (52%); those of SCC, in 6 of 21 (29%); and levels of either, in 14 of 21 (67%) cases. Recurrences occurred in 7 of the 21 cases. Rising SCC levels predicted (at an earlier clinic visit) the recurrence in 4 of the 7, and rising UGF levels in 5 of the 7 (includes the 4 detected by SCC) patients. While these numbers for UGF and SCC sensitivity are not ideal, until other markers become available, they are seemingly the best achievable. It is suggested that both UGF and SCC be used to monitor therapy and to detect recurrences of cervical and vulvar cancers.

Antigens, Neoplasm↗

PubMed1990

Correlation between measured creatinine clearance and calculated creatinine clearance in ovarian cancer patients.

In 84 patients with advanced ovarian cancer, the measured 24-hr urinary creatinine clearance and a calculated creatinine clearance were compared prior to cis-platinum-based chemotherapy. The overall correlation between the two methods was excellent, using Pearson's coefficient of correlation test, r = 0.508 and P less than 0.000001. In a subset of 59 patients with adequate 24-hr urine collections, analysis showed a correlation of r = 0.526 and P = 0.000018. Furthermore, in this group of patients using a creatinine clearance of 45 ml/min as a threshold for dose adjustment, there was only a 3.3% error in accepting the calculated creatinine clearance for the measured creatinine clearance. In summary, in patients with advanced ovarian cancer, even in the postoperative state, an evaluation of renal function with a calculated creatinine clearance prior to chemotherapy is sufficient.

Adult↗

PubMed1990

Urinary gonadotropin fragment, a new tumor marker. I. Assay development and cancer specificity.

Urinary gonadotropin fragment (synonyms: UGF and human chorionic gonadotropin beta-subunit core fragment) is a small peptide which is present in the urines of pregnant women, of those with trophoblast disease and of those with certain nontrophoblastic malignancies. We developed a new UGF assay with improved specificity and then investigated levels in urines of 493 women: 155 healthy and postmenopause, 79 healthy and premenopause, 89 with benign gynecologic disease, and 170 with active gynecological cancer. A UGF cutoff level of greater than 3 fmole/ml was chosen to monitor the progress of patients during and after cancer therapy. Using this cutoff value, UGF specificity and sensitivity for active cancer were 90 and 66%, respectively. Levels exceeded this cutoff in 74% of women with recurrent disease. For screening purposes and for differentiating benign and malignant disease a cut-off of 8 fmol/ml, was indicated. At this higher cutoff specificity and sensitivity for active cancer were 99 and 46%, respectively.

Biomarkers, Tumor↗

PubMed1990

Urinary gonadotropin fragment, a new tumor marker. II. Differentiating a benign from a malignant pelvic mass.

We examined the efficacy of CA125 and urinary gonadotropin fragment (UGF) measurements for differentiating benign from malignant pelvic masses. CA125, at a cutoff of greater than or equal to 35 U/ml, detected 82% (n = 71) of ovarian malignancies, but also falsely detected 14% of (n = 332) patients with benign pelvic masses. When the CA125 cutoff was raised from greater than or equal to 35 to greater than or equal to 200 U/ml, the number of false-positives decreased to 1.2%, a manageable level. However, using greater than or equal to 200 U/ml only 49% of cancers were detected. We examined levels of UGF and found that they complement those of CA125, detecting false-negatives. Using UGF at a cutoff of greater than 8 fmol/ml and CA125 at greater than or equal to 200 U/ml a combined sensitivity of 86% was achieved for malignant pelvic masses, with minimal false-detection of benign disease (less than 1.2%). We propose that parallel measurements of CA125 and UGF should be used for discriminating benign and malignant pelvic masses.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1990

Urinary gonadotropin fragment, a new tumor marker. IV. Use in endometrial cancers and uterine mixed mullerian tumors.

The use of urinary gonadotropin fragment (UGF) and CA-125 measurements was examined in the diagnosis and management of endometrial cancers and uterine mixed mullerian tumors. Using a cutoff of 3 fmole/ml for UGF, 37 of 63 (59%) patients with active cancer and 4 of 78 (5%) women with no evidence of disease after successful treatment had elevated levels of UGF. Similar results were obtained for CA-125 (cutoff greater than or equal to 35 U/ml) in the same patients, with elevated levels in 54% of patients with active disease and in 4% of patients with no evidence of disease. Sensitivities and mean values of UGF and CA-125 increased significantly with advancing stage and histologic grade of differentiation. Compared to patients with intrauterine disease only, patients with extra-uterine disease had a significant positivity rate and increased mean values for each tumor marker. The presence of lymph node metastases and levels of UGF showed a significant correlation; there was a significant relationship between CA-125 levels and positive cytology of peritoneal washing. Levels of UGF and CA-125 reflected the clinical courses of disease during therapy. During this study period, 85% of tumor recurrences could be anticipated before the clinical manifestation by elevated UGF and CA-125 levels. All patients who died of advanced or recurrent cancers had elevated levels of UGF and CA-125 before death and the mean values of both markers in these patients were significantly higher than those of both markers in the alive group.

Adenocarcinoma↗

PubMed1990

Neoadjuvant chemotherapy in stage X ovarian carcinoma.

Seventeen patients with presumed advanced ovarian cancer were treated initially with platinum-based chemotherapy. All patients had either cytologic or histologic findings consistent with an ovarian adenocarcinoma. Eight patients subsequently had surgery: one patient had a complete pathological response and one patient had microscopic disease; both are alive without evidence of disease. Five patients were surgically debulked to less than 1 cm, and one patient had large residual disease after surgery. Four of these patients are alive with disease and one died of disease. Nine patients did not have surgery; two patients had no response to chemotherapy and four patients had stabilization of disease. These six patients have died. Two patients had initial partial responses and are alive with disease. One patient with a complete clinical response at autopsy was without evidence of disease. The follow-up ranged from 7 to 109 months; the median survival was 15 months. Comparison of these 17 patients with 21 patients with stage IV disease and 38 suboptimally debulked patients with stage III disease treated during the same period with aggressive surgery followed by chemotherapy revealed no statistical difference in overall survival between these 17 patients and the two groups of patients. The postoperative hospital stay and complication rate were significantly lower for the 9 patients who had surgery than for the 21 patients with stage IV disease. This report suggests that in patients with presumed ovarian cancer and significant medical problems or with a priori nondebulkable tumor, initial chemotherapy and then surgery should be considered.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Sequelae of lateral ovarian transposition in unirradiated cervical cancer patients.

The sequelae of lateral ovarian transposition (LOT) in cervical cancer patients has been examined only in the light of the effect of pelvic radiation therapy on ovarian preservation. Preservation of ovarian function has not been examined in the absence of radiation therapy, and symptomatic ovarian cyst formation in transposed ovaries with the need for subsequent surgery has not been addressed in either radiated or unirradiated cervical cancer patients. We studied 84 premenopausal FIGO stage IA or IB cervical cancer patients treated by primary radical hysterectomy between the years 1978 and 1988. None of these patients received adjuvant radiation therapy. Fifty-nine of eight-four patients had radical hysterectomy (RH) without LOT. These patients were compared to 25 of 84 patients who had LOT in addition to RH. The incidence of symptomatic ovarian cysts, the majority requiring operative intervention, was 24% in the ovarian transposition patients as compared to 7.4% in those who had RH alone. This threefold increase in symptomatic benign ovarian cyst formation in the translocated ovary was significant (P = .048). On the other hand, LOT in these RH patients does not appear to increase the incidence of early menopause (P greater than 0.05). On follow-up of those patients who did not incur additional surgery or radiation, 4.3% became menopausal, as compared to 4.1% of those patients undergoing RH alone, with the mean ages of the two groups being comparable.

Adult↗

PubMed1990

Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part I: Clinical and histologic correlations.

A series of 183 cases of primary endometrial carcinomas were immunohistochemically stained for estrogen receptors (ERs) and progesterone receptors (PRs) using formalin-fixed, paraffin-embedded sections. All specimens were obtained from uterine curettages performed at the time of the initial diagnosis or initial therapy. The ER and PR content in the malignant and benign components (benign epithelium, stroma, and myometrium) was evaluated separately for positivity and divided into three groups according to the percentage of positive cells and the intensity of the nuclear stain. Endometrioid-type adenocarcinoma had the highest degree of positivity for both receptors, followed by adenosquamous carcinoma, serous carcinoma, and clear cell carcinoma. The positivity for ERs and PRs of the malignant component was statistically correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P less than 0.01), FIGO grade (P less than 0.001), and nuclear grade (P less than 0.0001) of the tumors. The degrees of ER and PR positivity of the malignant component correlated with each other (P less than 0.0001). There was no association between the depth of myometrial tumor invasion and either receptor status of the malignant component. There was a significant association between the presence of lymph vessel invasion and the positivity for PR. Positivity for PR correlated negatively with the patients' ages (P less than 0.004). The results of this study indicate that immunohistochemical analysis of sex steroid receptor status on formalin-fixed, paraffin-embedded tissue offers an excellent alternative to the standard biochemical procedure.

Adenocarcinoma↗

PubMed1990

Immunohistochemical evaluation of estrogen and progesterone receptor content in 183 patients with endometrial carcinoma. Part II: Correlation between biochemical and immunohistochemical methods and survival.

One hundred eighty-three patients with endometrial carcinoma had both immunohistochemical and biochemical analysis of estrogen receptor (ER) and progesterone receptor (PR) content of the tumor. Biochemical analysis was done on a homogenate of uterine curettings; immunohistochemical stainings were done on formalin-fixed, paraffin-embedded sections. The biochemical method was scored quantitatively and the immunohistochemical, in a semiquantitative way. There was a significant correlation between the immunohistochemical categories of the malignant component of the tumor and the biochemical levels of receptor content (P = 0.0001). The sensitivity of the immunohistochemical method for the ER content was 78.5% and the specificity was 58.2%. The sensitivity for the PR was 52.5% and the specificity was 92.8%. Changing cut-off levels for positivity of the biochemical analysis changed the sensitivity and specificity. Survival was predicted by the immunohistochemical status of the ER (P = 0.001) and PR (P = 0.01). Similarly, it was predicted by the biochemical receptor status. Multivariate analysis of the immunohistochemical receptor status and the biochemical receptor status showed that the immunohistochemically determined estrogen status was the most significant predictor of survival (P = 0.001). The immunohistochemical analysis of sex steroid receptor status on formalin-fixed, paraffin-embedded tissue is not only possible and practical, but also predicts survival.

Adult↗

PubMed1989

Development of leukemia after doxorubicin and cisplatin treatment for ovarian cancer.

Alkylating agents have been the major group of chemotherapeutic agents associated with an increased incidence of secondary leukemias. In ovarian cancer alkylating agents have resulted in a lesser, although still increased, risk of secondary malignancies. This paper reports two cases of ovarian cancer treated with cisplatin and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), and the subsequent development of an acute nonlymphocytic leukemia and a preleukemia syndrome. This regimen does not contain alkylating agents, and has not been associated with leukemia in patients with ovarian cancer. In these two cases, abnormalities of chromosomes 5, 7, 11, and 17 are reported which have been shown to occur in therapy-related leukemia.

Adenocarcinoma↗

PubMed1989

Tamoxifen in combination with cytotoxic chemotherapy in advanced epithelial ovarian cancer. A prospective randomized trial.

One hundred patients with Stage III and IV epithelial ovarian cancer participated in a prospective randomized study to determine whether the addition of tamoxifen, an estrogen agonist-antagonist, to standard cytotoxic chemotherapy (doxorubicin, cis-diamminedichloroplatinum) would significantly improve survival. Fifty-one patients received the standard cytotoxic chemotherapy and 49 received tamoxifen as well. No significant difference in overall or progression-free survival between these two patient groups was observed. Cytosol steroid receptor determinations were performed on tumor samples from 72 patients. No correlation was evident between therapy and cytosol estrogen and progestin receptor content of the tumors. This study suggests that the strategy of combining an antiproliferative, hormonally active agent with cytotoxic chemotherapy for management of advanced ovarian cancer may be inappropriate.

Adult↗

PubMed1989

Bleomycin, vincristine, mitomycin C, and cis-platinum in gynecologic squamous cell carcinomas: a high incidence of pulmonary toxicity.

Twenty-three patients with gynecologic squamous cell carcinomas (20 cervical, 2 vulvar, 1 ovarian) were treated with bleomycin, vincristine, mitomycin-C, and cis-platinum. Twenty-one patients had prior radiation therapy. Of the 21 evaluable patients, the response rate was 48% with a median duration of 4 months. Toxicity in the 23 patients was high, with the most significant being that of pulmonary toxicity. Eight patients had pulmonary toxicity with 5 of 8 dying a respiratory death while free of disease. Bleomycin is excreted primarily by the kidneys, and its half-life is known to increase in patients with renal insufficiency. Patients with advanced, recurrent cervical cancer who have failed radiation therapy often have underlying renal compromise. Extreme caution should be exercised when administering bleomycin with nephrotoxic chemotherapeutic agents in this setting.

Adult↗

PubMed1989

Radiation treatment of FIGO stage IVA carcinoma of the cervix.

Forty-eight patients with FIGO stage IVA cervix cancer were treated with radiation therapy at the Hunter Radiation Therapy Center, Yale--New Haven Hospital from 1966 to 1985. Nine of the 48 patients are alive without recurrence (NED) and the 5-year actuarial survival rate is 18% (+/- 6%, standard error). There was a substantial difference in outcome based on treatment technique. Thirty-five patients were treated with external beam (EB) plus intracavitary (IC) and 8 of these patients (23%) are NED. None of the 12 patients treated with EB alone are alive. One patient treated with preoperative EB plus exenteration is NED. The severe complication rate was 22% and most complications were vesicovaginal fistulas due to successful treatment for bladder involvement. There was a significant difference in survival for patients with minimal parametrial disease (stage IVA1) versus patients with significant parametrial disease (stage IVA2) which was defined as fixation to one or both pelvic sidewalls or hydronephrosis on IVP. The 5-year survival for stage IVA1 disease was 46% (+/- 14%) versus only 5% (+/- 4%) for stage IVA2 disease. Our results indicate that superior survival for stage IVA cervix cancer patients is associated with two factors: minimal parametrial disease and radiation treatment which combines EB plus IC.

Adenocarcinoma↗

PubMed1989

Circulating levels of CSF-1 (M-CSF) a lymphohematopoietic cytokine may be a useful marker of disease status in patients with malignant ovarian neoplasms.

We have previously reported our observations of epithelial tumor cell expression of transcripts and protein antigens of CSF-1 and transcripts of a protein closely related--if not identical--to the CSF-1 receptor in ovarian and endometrial neoplasms in vivo and in vitro. In the present communication, we extend these investigations to analyze the clinical utility of determinations of plasma CSF-1 concentrations in 125 samples from 33 patients with ovarian neoplasms and one patient with benign endometriosis. We observed that plasma CSF-1 levels in patients with active and recurrent neoplastic disease were markedly elevated and follow changes in disease status in individual patients. These and other results presented in this communication suggest that not only could CSF-1 be a useful circulating tumor marker in ovarian carcinoma patients, but also that in combination with measurements of other markers--such as CA-125--determinations of plasma CSF-1 levels might actually improve the accuracy of "tumor marker"-based assessments of disease status in patients with malignant ovarian neoplasms.

Adenocarcinoma↗

PubMed1989

CA 125, NB/70K, and lipid-associated sialic acid in monitoring uterine papillary serous carcinoma.

Ninety-four plasma samples from 18 women with uterine papillary serous carcinoma were analyzed for three circulating tumor markers: CA 125, NB/70K, and lipid-associated sialic acid. Tumor marker values were correlated with the patients' clinical status. Preoperatively, CA 125, NB/70K, and lipid-associated sialic acid were elevated in 62, 64, and 67%, respectively. The distribution of clinical stages was I -- 56%, II -- 28%, III -- 6%, and IV -- 11%. The distribution of surgical stages was I -- 28%, II -- 17%, III -- 0%, and IV -- 56%. Nine of ten patients with an elevated tumor marker had extrauterine disease confirmed surgically. Eight of nine patients with elevated levels of two markers had extrauterine disease. Four of four patients with three elevated markers had extrauterine disease. There were two false-positive elevations, both in patients who had occult surgical stage II disease. Rising and falling tumor marker levels correlated with progression and regression of disease, respectively. A doubling of CA 125 predicted clinical recurrence in four of six women an average of 17 weeks before clinical confirmation. Lipid-associated sialic acid levels that increased by 25% or by five units predicted recurrence or rapid progression in three of six patients in an average of 5 weeks, and a 50% elevation in NB/70K predicted recurrence in two of three patients by 5 and 3 weeks before clinical confirmation. Although the number of patients in this series is small, preoperative elevated tumor markers in patients known to have uterine papillary serous carcinoma correlate closely with the presence of extrauterine disease. This information should influence surgical management and may be useful in postsurgical treatment assessment.

Aged↗