Patricia S. Braly

Technical aspects of intraperitoneal chemotherapy in abdominal carcinomatosis

Between November 1983 and July 1985, 41 patients with abdominal carcinomatosis had peritoneal catheters surgically implanted for the purpose of intraperitoneal chemotherapy. Peritoneal fluid distribution was documented by computerized tomography examination prior to chemotherapy and was correlated with the surgical procedure performed and the pathological findings. In this series, peritoneal fluid distribution appeared to be an important prognostic factor in determining tumor response. The catheter-related complication rate was acceptable.

Immediate vaginal reconstruction following resection for malignancy using the gluteal thigh flap

Immediate flap closure of perineal defects following extirpative procedures for gynecologic malignancies is highly desirable. Advantages include more rapid healing, reduced infection rate, decreased nutritional demands, early rehabilitation, greater safety in radiated fields, and more functional results. The posterior thigh flap, deriving its blood supply from the inferior gluteal artery, was used in 7 patients (9 flaps) with excellent results. The flap has proven reliable and quite feasible at the time of resection. While most partial pelvic or vaginal defects can be reconstructed with a single flap, bilateral flaps are recommended for more extensive defects. The major postoperative problem has been discomfort while sitting and paresthesias along the distribution of the posterior cutaneous nerve. To avoid these problems, the flap should be rotated distal to the ischium and, in subtotal reconstruction, the nerve excluded.

A simple method of fetal and neonatal heart rate beat-to-beat variability quantitation: Preliminary report

Good base-line fetal and neonatal heart rate beat-to-beat variability appears to be a reassuring sign of well-being. Conversely, decreased base-line heart rate beat-to-beat variability during the latter part of the intrapartum period is often associated with neonatal acidosis and/or depression. A simple method of quantitation of the beat-to-beat neonatal heart rate is reported here. This method of variability quantitation (VQ) consists of a continuous integration and display of the baseline heart rate beat-to-beat variability on a scale of zero to four, expressed in beats per minute averaged over a one-minute period. Serial variability quantitation in 35 neonates with different clinical conditions appeared to demonstrate a good correlation between the variability quantitation and the outcome of the neonates. Further studies are planned for evaluating the method in the intrapartum period.

The subrenal capsule tumor implant assay as a predictor of clinical response to chemotherapy: 3 Years of experience

The clinical response to chemotherapy of a series of female patients with advanced pelvic malignancies was compared to the response of their tumors to the same agents in the murine subrenal capsule implant assay. A total of 194 different patients were studied in 242 different assays; 89.3% of the assays were evaluable. There were 83 prospective assays (assays performed before the patient received the chemotherapy) of 66 different patients for which clinical correlations were available. In these assays the sensitivity (frequency of positive test results in responding patients) was 85.0%, the specificity (frequency of negative test results in nonresponding patients) was 57.1%, and the efficiency (percentage correctly classified) was 63.9%. There were 100 retrospective assays (assays performed after the patient had been treated with the chemotherapy) of 69 different patients for which clinical correlations were available. In these assays the sensitivity was 66.7%, the specificity 70.7%, and the efficiency 70.0%. Thirty-one of the patients had both prospective and retrospective assays. There were 59 patients for whom the clinical response to chemotherapy could not be determined. It is believed that the clinical utility of the SRC assay has been validated by the good prospective sensitivity of the assay.

Incidence of premature delivery following the oxytocin challenge test

The oxytocin challenge test (OCT) has been used to identify and follow the fetus at risk for uteroplacental insufficiency. Of 389 patients who had at least one OCT prior to 38 weeks gestation, 26 (6.7%) underwent delivery after spontaneous onset of premature labor within 5 days of an OCT. This compares to a 7.5% incidence of spontaneous delivery prior to 38 wk at the University of California Irvine Hospital, and to a 7.6% rate of premature delivery after spontaneous onset of labor in those patients followed with nonstress tests only.

Accurate laboratory predictions of the clinical response of patients with advanced ovarian cancer to treatment with cyclophosphamide, doxorubicin, and cisplatin

Seventy-six patients with advanced ovarian cancer treated with cyclophosphamide, doxorubicin, and cisplatin (CAP) at 3-week intervals were tested for the response of their tumors to treatment with CAP in the subrenal capsule tumor implant assay. Thirty-four of the patients tumors were assayed prospectively before clinical treatment and 33 were assayed retrospectively, after clinical treatment with CAP. Nine of the patients tumors were assayed both prospectively and retrospectively. All of the patients underwent a tumor debulking laparotomy. Of the patients with clinically measurable residual disease, 17 had a partial response of at least 50% regression of disease, and 11 had a progression of disease. Of the patients with known residual but nonmeasureable disease, 7 had surgically verified complete responses, 8 at least 50% regression, and 23 had progression of disease: 10 had no evidence of disease clinically but had not had surgical confirmation. Twenty-six of the tumors were adenocarcinomas not otherwise specified (2 grade I, 2 grade II, and 22 grade III), 39 were serous adenocarcinomas (7 grade I, 9 grade II, and 23 grade III), 7 were endometrioid adenocarcinoma (all grade III), 3 were mucinous adenocarcinomas (1 each of grade I, II, and III) and 1 was an adenosquamous carcinoma (grade III). Thirty-four of the patients failed the therapy. The subrenal capsule (SRC) assay predicted 21 of these failures (4 prospective and 17 retrospective). Thirty-two of the patients responded to CAP chemotherapy. The SRC assay accurately predicted the clinical regression of the tumors of 22 of the patients (15 prospective and 7 retrospective). Second-look laparotomy confirmed 7 patients with no evidence of disease, 5 patients with minimal disease, and 5 patients with a greater than 50% reduction of their disease. The SRC assay predicted the response of all these patients except 2 with partial responses to chemotherapy. Thus, while the overall positive predictive value of the SRC assay in this study is 65%, it is 100% for those patients whose tumors respond completely and for those who have minimal residual disease after CAP chemotherapy.

Response of human adenocarcinoma to chemotherapy: As sole agents and in combination with sodium ibuprofen

The sensitivity of 12 human tumors to various chemotherapeutic agents was measured in the 6-day subrenal capsule xenograft assay. All of the tumors were adenocarcinomas: 9 ovarian, 2 colon, and one endometrial. Doxorubicin, cisplatin, melphalan, 5- fluorouracil , methotrexate, and vinblastine sulfate were tested for antineoplastic activity on all tumors. In addition, a prostaglandin synthetase inhibitor, sodium ibuprofen, was assayed for cytostatic activity and for the ability to enhance the cytotoxic activity of melphalan and vinblastine sulfate. The response of the tumors to the cytotoxic agents were variable, but 5 of the 12 tumors showed a significant reduction of growth when the animals were treated with sodium ibuprofen alone. The addition of ibuprofen to the chemotherapeutic agents did not significantly alter the therapeutic activity of melphalan, but decreased the effectiveness of vinblastine in one case. When ibuprofen was given in combination with a cytotoxic drug, the primary cytoreductive effect was that of the cytotoxic agent.

Quantitative nuclear DNA analysis of human ovarian adenocarcinoma: Compared before and after chemotherapy and correlated with clinical response

Quantitative DNA measurements on 18 human ovarian adenocarcinomas were made by computerized image analysis. The DNA content of the tumor cells was measured on specimens of tumor obtained at the initial diagnostic surgery and at second-look surgery after treatment with chemotherapy. The mean DNA content of the specimens and the ploidy pattern of the tumor cells were determined. With the exception that borderline tumors had near normal ploidy patterns and mean DNA content, there was no consistent correlation between the stage of disease, grade, or histiologic character of the tumor and either the DNA content or ploidy pattern. But it was noteworthy that all three of the patients who had complete responses (negative second-looks), also had tumors with DNA content and ploidy patterns near triploid. When the ratio of mean DNA content before and after chemotherapy was determined for each ploidy group, there was an apparent correlation between this ratio and clinical status of the patient 10 month after chemotherapy. That is, patients with low ploidy tumors and high DNA content ratio (greater than 1.25) had a better prognosis than patients with high ploidy tumors and lower DNA content ratios (less than 1.25). Thus, although the mean DNA content of the tumor at the initial surgery was not in itself of sufficient prognostic value, when the mean DNA content of the tumor after chemotherapy is also known, an accurate picture of the patients clinical response could be determined.

Depressed natural killer cell activity in tumor-bearing rats: effect of immunotherapy and cytoreductive chemotherapy

A single-cell cytotoxicity assay was used to determine the number of effector cells in the peripheral blood of normal and tumor-bearing Fischer 344 female rats which bound to and lysed K562 target cells. Of the blood leukocytes of normal rats 18.4 +/- 2.6% bound to K562 target cells; one-third of the conjugated target cells were killed as evidenced by trypan blue uptake. Cells isolated from the blood of rats bearing mammary adenocarcinoma R3230 or 13762 bound fewer target cells, 6.3 +/- 1.1 and 7.1 +/- 1.8%, respectively. The proportion of dead conjugated target cells was not different from that of normal rat leukocytes if the leukocytes were from rats bearing 13762 but was reduced by one-half if the leukocytes came from rats bearing R3230. Treatment of the tumor-bearing rats with cytoreductive chemotherapy returned the percentage conjugation to target cells to normal levels if the tumor growth was inhibited more than 70%. Treatment of the tumor-bearing rats with immunomodulating agents did not inhibit the growth of the tumors, but treatment with sodium ibuprofen or muramyl dipeptide increased the percentage conjugation significantly.