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Biomedical subjects

J T Chambers

Publications and source records attributed to J T Chambers.

At least 73 records · Page 4Linked to original sources

CA 125 in peritoneal washings and fluid: correlation with plasma CA 125 and peritoneal cytology.

Sixty-four women with ovarian cancer and 46 controls with benign gynecologic conditions underwent cytologic and CA 125 evaluations of peritoneal fluid or peritoneal washings at laparotomy. These parameters were correlated with preoperative disease status, intraoperative findings, and preoperative plasma CA 125 levels to determine their value in assessing occult disease. No false-positive cytology reports were observed. Cytology specimens were positive in 20 of 23 patients (87%) with clinical evidence of disease who had peritoneal fluid present, but in only 18 of 29 (62%) of similar patients with no peritoneal fluid present (P less than .05). CA 125 values were elevated in 16 of 23 (69.5%) and 15 of 29 (52%) of these samples, respectively (P greater than .05). Levels of CA 125 in peritoneal fluid washings correlated poorly with the presence of obvious intraperitoneal cancer and had questionable reliability when used to evaluate patients clinically free of disease. Positive peritoneal cytology reflected the presence of ovarian cancer, but its absence did not mean that an objective response to chemotherapy treatment had occurred. Disease status correlated best with physical examination and circulating levels of CA 125.

Antigens, Tumor-Associated, Carbohydrate↗

Urinary human chorionic gonadotropin free beta-subunit and beta-core fragment: a new marker of gynecological cancers.

Many investigators have shown that a small proportion (13-36%) of subjects with nontrophoblastic gynecological cancers have elevated serum levels of human chorionic gonadotropin (hCG). The low proportion with detectable levels and the accompanying low titers have limited the use of hCG as a tumor marker. hCG is a glycoprotein composed of two noncovalently linked subunits (alpha and beta), which are the products of separate genes. With the intent of expanding the use of hCG as a tumor marker we investigated levels of hCG free beta-subunit and asialo free beta-subunit and its core glycopeptide (composed of beta-subunit residues 6-40 disulfide-linked to 55-92), collectively called urinary gonadotropin fragments (UGF), in healthy and cancer patients. An immunoradiometric assay was developed, using the core glycopeptide-directed antibody B204, that similarly measures the hCG free beta-subunit and the asialo free beta-subunit and its core glycopeptide. Parallel urine and serum samples were collected from 87 women with active gynecological cancer and hCG and UGF were measured. Just 18% of the women tested had detectable serum levels of hCG (greater than 0.2 ng/ml); none had elevated serum levels in the UGF assay (greater than 0.2 ng/ml). Of the same group, 32% had detectable urine hCG levels (mean titer, 0.50 ng/ml) and 74% exhibited elevated urinary levels in the UGF assay (mean titer, 2.0 ng/ml). In a control group (urines from 50 nonpregnant healthy women), 47 negative and three borderline positive results (0.30, 0.35, and 0.48 ng/ml) were observed in the UGF assay. These results suggested a sensitivity of 74% and specificity of 92% for the UGF test for gynecological cancers. By disease, 70% of those with cervical, 73% of those with ovarian, and 77% of those with endometrial cancers had detectable UGF levels (greater than 0.2 ng/ml). By stage, 50, 62, 75, 86, and 100% of those with stage 1, 2, 3, 4, or recurrent disease, respectively, had positive results. UGF is a promising new marker of gynecological malignancies.

Adult↗

Borderline ovarian tumors.

Ninety-four patients with borderline ovarian tumors were retrospectively analyzed for clinical features, treatments, and survival characteristics. There were 46 patients with FIGO stage IA cancer, 7 with stage IB, 20 with stage IC, 4 with stage IIB, 5 with stage IIC, 5 with stage IIIA, 3 with stage IIIB, and 4 with stage IIIC tumors. Seventy patients had at least a total abdominal hysterectomy and bilateral salpingo-oophorectomy, 20 patients had conservative surgery including unilateral salpingo-oophorectomy or ovarian cystectomy, and 4 patients had bilateral salpingo-oophorectomy. Fifteen patients with stage I disease received adjuvant melphalan therapy and 2 received external beam radiation for concomitant gynecologic cancers; 7 with stage II tumors received adjuvant melphalan therapy and 1 received external beam radiation; and 5 with stage III tumors received melphalan therapy and 6 patients received cisplatin-based combination chemotherapy. Follow-up ranged from 1 to 117 months, with a median of 33.5 months. Eighty-seven patients were alive. Seven patients died, two of disease. The overall 5-year survival rate was 83.0%; those treated with adjuvant therapy had a 79.5% survival, whereas the others had 84.6% survival. Second-look surgery was performed in 10 patients; six results were negative after melphalan therapy, one was negative after cisplatin combination therapy, and one was negative after no adjuvant treatment. Two patients had positive second-look surgery, one with stage IIIC disease treated with a cisplatin combination and the other with stage IC disease treated with melphalan. This review did not demonstrate that patients with borderline ovarian tumors benefited from adjuvant therapy.

Adolescent↗

Estrogen and progestin receptor levels as prognosticators for survival in endometrial cancer.

The survival of 213 postmenopausal patients with primary endometrial cancer was analyzed as a function of clinicopathologic features and cytosol steroid receptor levels. Estrogen receptor (ER) levels (P = 0.008) and progestin receptor (PR) levels (P = 0.0001) were negatively correlated with grade. ER and PR levels were positively correlated with each other (P = 0.0001), but neither was correlated with age. In 187 patients with stages I and II, ER positivity (greater than or equal to 20 fmole/mg cytosol protein (cp] was statistically associated with grade (P = 0.007); and PR (greater than or equal to 7 fmole/mg cp) was statistically associated with grade (P = 0.001). Univariant analysis revealed that survival for the early endometrial cancer patients was significantly dependent upon ER status (P = 0.0003), PR status (P = 0.0016), and grade (P = 0.0002). Multivariant analysis of ER status, PR status, age, and grade showed that the ER status was a significant prognostic factor for survival (P = 0.0168), even if the positivity of the PR status was defined at greater than or equal to 50 fmole/mg cp. If ER status was divided at 0-19, 20-100, and greater than 100 fmole/mg cp, survival was significantly different between the low range group and the other two groups. If PR status was divided at 0-6, 7-50, and greater than 50 fmole/mg cp survival was significantly different between the first two groups and the high range group. Thus, survival in these endometrial cancer patients was better predicted by ER status than grade.

Female↗

Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system. II. Initial serial studies.

Levels of UGF, which constitute the free beta-subunit of human chorionic gonadotropin, asialo free beta-subunit, and a core fragment of asialo free beta-subunit, detected by a single immunoradiometric assay, were monitored in the urines of 28 woman undergoing therapy for gynecologic cancer (3 cervical, 8 endometrial, and 17 ovarian). During a 7-month study, 24 of the 28 woman had elevated UGF levels (greater than 0.2 ng/ml). Correlation was observed of UGF levels and changing clinical status during therapy in 23 of these 24. Normal range CA 125 (less than 35 U/ml) was found throughout the study period in 4 of 14 woman undergoing therapy for serous ovarian malignancy. Three of the 4 had elevated UGF levels which accurately followed the course of their disease. These preliminary studies suggest that in monitoring therapy of gynecologic cancers UGF, alone or with CA 125, warrants evaluation.

Calcium↗

High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas.

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.

Adenocarcinoma↗

Evaluation of the role of second-look surgery in ovarian cancer.

The role of second-look surgery in the management of patients with ovarian cancer has come under question. One hundred one patients have undergone the operation at Yale University over the last decade. Of 67 who had epithelial ovarian cancer, 43% had positive and 57% had negative second-look surgery. Multivariate analysis revealed that stage was a significant prognostic factor with regard to second-look surgery findings, as well as absolute and disease-free survival. We found initial tumor size and results of cytology at second-look surgery to be prognostic factors with regard to survival after a positive second-look surgery. Survival after negative second-look surgery was significantly greater than that after a positive operation. However, no improvement in survival accrued to the group of advanced-stage, platinum-treated patients who underwent second-look surgery, compared with a similar group of patients who were eligible but did not undergo the procedure. We conclude that second-look surgery in epithelial ovarian cancer patients should be limited to experimental protocol situations in which precise measurement of tumor size may be important. In ovarian germ cell malignancies, second-look surgery, in the absence of tumor markers, can be justified.

Adolescent↗

Circulating tumor markers in the monitoring of gynecologic malignancies.

Plasma from 262 patients with gynecologic malignancies was assayed for levels of circulating tumor markers (CA 125, LSA [lipid associated sialic acid in plasma, LASA-P (Dianon Systems, Inc., Stratford, CT )], Ca 19-9, and carcinoembryonic antigen [CEA]) and correlated with the patients' clinical status. In the patients with ovarian cancer the sensitivities of LSA and CA 125 for patients with clinical evidence of disease were 71% and 76% respectively; the specificities for patients with no clinical evidence of disease were 90% and 86% respectively. Using both tumor markers, a sensitivity of 84% and specificity of 85% was obtained. Additionally, CA 125 was elevated in 59% of patients with clinically advanced or recurrent endometrial cancer, and LSA was elevated in 63% of patients with clinical evidence of cervical cancer. Neither CEA nor CA 19-9 levels correlated with clinical status in patients with ovarian or cervical cancer. The values of Ca 125 and LSA were examined in relation to the findings at second-look surgery in patients with ovarian cancer. Absence of elevated tumor markers does not obviate the need for second-look surgery; the false negative rate for CA 125 was 40% (6/15). However, the finding of two elevated plasma markers 1 month or more apart, in ovarian cancer patients who were clinically free of disease, was strongly suggestive of recurrent cancer; 13 of 14 such patients showed this association. This latter finding may help to identify a group of patients in whom early surgical intervention is indicated.

Antibodies, Monoclonal↗

Etoposide (VP-16-213) plus cis-diamminedichloroplatinum as salvage therapy in advanced epithelial ovarian cancer.

Twenty-two patients with advanced epithelial ovarian cancer were treated with etoposide and cis-platinum. Each had failed one to three regimens of combination chemotherapy including cis-platinum-based combinations. Prior total cis-platinum doses ranged from 50 to 1600 mg/m2 with a median of 440 mg/m2. One of 18 evaluable patients had a complete response lasting 8 months, 1 had a partial response lasting 3 months, 8 had stable disease for a mean of 5.6 months, and 8 had progressive disease. The 4 unevaluable patients had undetectable clinical disease for a mean of 6.7 months. Bone marrow suppression was seen in 4 of 22 patients; two of whom had serious sequelae. The poor objective response rate (9.1%) seen with this combination in patients heavily pretreated with cis-platinum is similar to that seen for single agent etoposide in patients pretreated with alkylating agents. The difficulty of obtaining a good objective response in the face of prior cis-platinum-based combination chemotherapy failure is again verified.

Adult↗

Uterine papillary serous carcinoma.

Reviewed are 37 patients with the diagnosis of uterine papillary serous carcinoma. Clinically, 19 patients presented as stage I, 9 as stage II, 1 as stage III, and 8 as stage IV. Four of 18 patients with clinical stage I disease who underwent surgery had pelvic metastases and five had disease spread beyond the pelvis. Three of nine clinical stage II patients had intraabdominal metastases. At least 50% myometrial invasion was found in 43% of the 30 hysterectomy specimens, and lymphatic invasion in the myometrium was demonstrated in 78% of the specimens. Each of the 15 patients with surgical stage I or II disease received local radiation therapy: 10 are alive and of these 9 are disease-free. Each of nine clinical stage II patients received intense radiation therapy and hysterectomy; seven are alive and of these four are disease free. The five-year survival for combined surgical stages I and II patients was 45%. The three-year survival for combined surgical stages III and IV was 11%. Thirteen patients have been treated with combination chemotherapy, 11 with cis-platinum-based combinations. Nine of these patients are dead; four are alive, with three of these having progressive disease.

Aged↗

CHAP II therapy for epithelial ovarian cancers following primary treatment with platinum-based combination chemotherapy.

Nineteen patients with stage III or IV epithelial ovarian cancer treated on a prospective randomized protocol with either adriamycin and cis-diamminedichloroplatinum or tamoxifen, adriamycin, and cis-diamminedichloroplatinum received a modified "CHAP II" regimen at the time of clinical progression of disease or the finding of occult cancer at second-look surgery. One patient had a clinical complete response lasting 6 months, one had a partial response lasting 23 months, 6 had clinically stable disease for an average of 6.5 months (range 4-15 months), 8 patients had progressive disease, and 3 patients without clinically detectable disease remained disease free for a mean time of 10 months (range 7-16 months). The modified "CHAP II" regimen employed in this study for patients failing prior cis-diamminedichloroplatinum-based regimens appears to have only limited efficacy in inducing objective remissions.

Adult↗

Treatment of persistent or recurrent ovarian carcinoma with sequential methotrexate and 5-fluorouracil.

Seventeen patients with persistent or recurrent epithelial cancer of the ovary were treated sequentially with methotrexate 125 mg/m2 or 250 mg/m2 iv followed in 1 hr with 5-fluorouracil 600 mg/m2 iv and in 24 hr with leucovorin rescue factor 10 mg/m2 q 6 hr for 6 doses every 14 days. Sixteen patients had Stage III or IV disease; one patient had Stage IIB disease. There were no complete or partial responders; nine patients had stabilization of disease for at least 1 month and three for greater than 4 months. There was minimal toxicity in the 89 courses given, with 8.9% neutropenia (less than 3000/mm3) and 2.2% thrombocytopenia (less than 100,000/mm3). Two patients developed severe diarrhea; there were no cases of mucositis.

Adult↗

Adjuvant therapy in mixed mullerian tumors of the uterus.

We report 54 patients with mixed mullerian tumors of the uterus treated at Yale-New Haven Hospital from 1962 to 1983. Seven had previous pelvic irradiation. Twenty-five neoplasms were homologous and 29 were heterologous. The mainstay of therapy was surgery and radiation. By FIGO criteria 9 patients had stage IA disease, 31 stage IB, 6 stage II, and 8 patients had clinical extrauterine disease. Ten of forty-six patients (23%) with FIGO stage I and II disease had extrauterine disease found at surgery. No patient with extrauterine disease had prolonged survival. The 2-year disease-free survival with stage IA was 66%, with stage IB surgically confirmed 32%, and for stage II 33%. Surgically advanced disease in clinical stage I and II patients and recurrence were associated more frequently with a heterologous histology (67%). The small uterus with a less than 10-cm cavity had a better prognosis. Among 29 surgically confirmed stage I and II patients, 83% of recurrences appeared within 2 years (mean 16 months +/- 7 months). Patients who received both intracavitary radiation and external beam developed only 17.6% pelvic recurrence but this reduction in local recurrence was not associated with significant improved long-term survival. Six of eight patients treated with cis-platinum, Adriamycin, and dimethyl triazeno imidazole carboximide for persistent disease or for recurrence showed response for 4 to 24 months, none complete. Five patients were treated by radiation, surgery, and adjuvant chemotherapy (4 with Adriamycin-Cytoxan, 1 with Adriamycin-platinum). Four of the five (80%) are disease free from 36 to 60 months. These data and the experience of others support the need for a clinical trial with adjuvant platinum and Adriamycin in this disease.

Adult↗

Splenosis: a complicating factor in total abdominal hysterectomy.

A case of pelvic splenosis is presented to discuss preoperative investigation and to describe surgical difficulties that may be encountered. Surgery should only be undertaken when warranted by troublesome symptoms. Removal of asymptomatic ectopic splenic tissue is contraindicated.

Adult↗

Immediate versus delayed hysterectomy for endometrial carcinoma: surgical morbidity and hospital stay.

Presented is a retrospective review of the intraoperative complications, postoperative morbidity, and length of hospitalization in 138 patients with stage I endometrial carcinoma treated at Yale-New Haven Hospital from January 1, 1977 to December 31, 1981. One group (stage IA, grade 1) was treated with surgery alone; two groups were treated with preoperative intracavitary radium, followed with either an immediate or a delayed hysterectomy. The three groups were comparable in age, weight, and major preoperative medical problems. The mean estimated blood loss during surgery and transfusion requirements during hospitalization were similar for all three groups. The duration of the surgery in the immediate group was longer than the other two groups. The occurrence of febrile morbidity and major postoperative complications in the three groups was similar, except for bacteriuria, which was significantly more common in the immediate group. The length of the postoperative hospitalization was the same for each group; however, the delayed group as compared with the immediate group had a total hospitalization of two days longer. Hence, in the current study, immediate hysterectomy did not significantly increase the surgical or postoperative morbidity rate, compared with delayed hysterectomy. The single hospital stay in the former treatment group represented cost containment.

Brachytherapy↗