Binding of specific peroxidase-labeled antibody to placental-type phosphatase on tumor-derived membrane fragments.

Monospecific antiserum to human placental alkaline phosphatase was purified by immunoabsorption and labeled with horseradish peroxidase. The binding of this labeled antibody to membrane fragments prepared from placental and tumor tissue was measured using agarose gel filtration to separate bound antibody. The antibody bound only to membrane fragments which contained placental phosphatase, and the amount bound varied in the order ascitic fluid membrane fragments greater than tumor extracts greater than placental extracts. Absorption of the antibody with crude placental membrane yielded a population of antibody which reacted with tumor tissue and pure placental enzyme, but only slightly with placental membranes. These results are interpreted to suggest that some antigenic sites are exposed in tumor tissue membranes which are not in placental membranes.

Adverse effects of intraperitoneal fluorouracil in patients with optimal residual ovarian cancer after second-look laparotomy: a Gynecologic Oncology Group Study.

Twenty-seven patients with ovarian cancer who had failed combination chemotherapy were offered intraperitoneal (IP) fluorouracil (5-FU) as salvage therapy in an attempt to ascertain the efficacy of such a therapeutic method. All patients had minimal residual epithelial cancer. The median number of treatment cycles was six. Major problems with dialysate inflow and egress occurred in ten patients and required discontinuation of therapy. An additional ten patients experienced hematologic toxicity with a median nadir WBC of 2,300/microL. Therapy was altered but not discontinued because of this complication. Other adverse sequelae, such as abdominal pain, were manageable with medication. IP 5-FU is technically feasible on a multiinstitutional basis in residual ovarian cancer, but its therapeutic role remains to be defined.

Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group.

Between 1984 and 1989, 20 assessable patients with incompletely resected ovarian dysgerminoma were treated on two protocols of the Gynecologic Oncology Group (GOG). All patients received cisplatin, bleomycin, and either vinblastine or etoposide. More recent patients also received consolidation chemotherapy with vincristine, dactinomycin, and cyclophosphamide (VAC). Eleven patients had clinically measurable disease, and 10 responded completely. Fourteen second-look procedures were done, and all were negative. Currently, 19 of 20 patients are disease-free with median follow-up of 26 months. Cisplatin-based chemotherapy is highly effective in patients with advanced dysgerminoma.

Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study.

PURPOSE: A phase II trial was conducted to determine the activity of prolonged oral etoposide in platinum-resistant and platinum-sensitive ovarian carcinoma. PATIENTS AND METHODS: Platinum-resistant disease was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. The starting dose was 50 mg/m2/d (30 mg/m2/d for prior radiotherapy) for 21 days, every 28 days. A dose escalation to a maximum dose of 60 mg/m2/d was prescribed. RESULTS: Of 99 patients entered, 97 were assessable for toxicity and 82 were assessable for response. Among 41 platinum-resistant patients a 26.8% response rate (7.3% complete response [CR] and 19.5% partial response [PR] rate) occurred. The median response duration was 4.3 months (range, 1.3 to 8.7), median progression-free interval (PFI) was 5.7 months (range, 0.8 to 30.8+), and median survival time was 10.8 months (range, 1.9 to 45.8). Twenty-five of 41 platinum-resistant patients had also previously received paclitaxel; of which eight (32%) responded. Among 41 platinum-sensitive patients, a 34.1% response rate (14.6% CR and 19.5% PR rate) occurred. The median response duration was 7.5 months (range, 1.9 to 15.2+), median PFI was 6.3+ months (range, 0.9 to 20.4), and median survival time was 16.5+ months (range, 0.9 to 34.8). Of 97 patients assessable for toxicity, grade 3 or 4 hematologic toxicity was common, with leukopenia occurring in 41.2% (grade 3, 29%; grade 4, 12%), neutropenia in 45.4% (grade 3, 20%; grade 4, 25%), thrombocytopenia in 9% (grade 3, 5%; grade 4, 4%), and anemia in 13.4%. Three treatment-related deaths occurred: two from neutropenic sepsis and one from thrombocytopenic bleeding after an overdose. One patient developed leukemia. CONCLUSION: This regimen is active in platinum-resistant and platinum-sensitive ovarian carcinoma. Additionally, the regimen is active in paclitaxel-resistant ovarian carcinoma.

Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study.

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.

Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group.

PURPOSE: Progestins have definite activity against advanced or recurrent endometrial carcinoma. Both parenteral and oral progestins yield similar serum levels and response rates, which range from 18% to 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectively) than previously reported. The present study sought to confirm this earlier study of oral MPA, to assess the importance of prognostic factors such as histologic grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. PATIENTS AND METHODS: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized to receive oral MPA either 200 mg/d or 1, 000 mg/d until unacceptable toxicity intervened or their disease progressed. RESULTS: Among 145 patients receiving the low-dose regimen, there were 25 complete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) complete and 10 (6%) partial responses for an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 months for the low-dose and high-dose regimens, respectively. Median survival durations were 11.1 months and 7.0 months, respectively. The adjusted relative odds of responding to the high-dose regimen compared with the low-dose regimen was 0.61 (90% confidence interval, 0.36 to 1.04). Prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor concentration. Compliance with oral therapy was documented with serum levels 1 month after starting therapy, when possible. MPA levels were commensurate with the assigned dose and schedule. CONCLUSION: Oral MPA is active against endometrial carcinoma. Response to progestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides no evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 mg/d orally. In fact, the trends suggest the opposite. The use of oral MPA 200 mg/d is a reasonable initial approach to the treatment of advanced or recurrent endometrial carcinoma, particularly those lesions that are well-differentiated and/or progesterone receptor-positive (> 50 fmol/mg cytosol protein). Patients with poorly differentiated and/or progesterone receptor levels less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate.

Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities.

PURPOSE: Diethyldithiocarbamate (DDTC) blocks cisplatin-induced toxicities in animal models without inhibiting antitumor effects. DDTC chemoprotection was tested in a randomized, multicenter, double-blind comparison versus placebo (PB) in patients with lung or ovarian cancer. Primary end points were nephrotoxicity, ototoxicity, neuropathy, and completion of therapy. PATIENTS AND METHODS: Between April 1990 and February 1992, 221 patients were registered with small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), or ovarian cancer. Cisplatin (100 mg/m2) and cyclophosphamide (in ovarian cancer) or etoposide (in lung cancer) were administered with either DDTC (1.6 g/m2 over 4 hours) or PB intravenously, every 4 weeks for a planned six cycles. RESULTS: At an interim safety analysis, data were available for 195 patients from the combined lung and ovarian cancer populations (PB, 99 patients; DDTC, 96 patients). Withdrawal for chemotherapy-induced toxicities occurred in 9% of PB-treated patients and 23% of DDTC-treated patients (P = .008). The mean cisplatin delivered dose-intensity (DDI) was 23 mg/m2/wk on both arms. However, the mean cisplatin cumulative dose delivered (CDD) was 379 mg/m2 on the PB arm, compared with 247 mg/m2 on the DDTC arm (P = .0001). At the time of interim analysis, 28% of PB-treated patients had completed all six cycles of therapy, compared with only 6% of DDTC-treated patients (P < .001). Although, clinical hearing loss, neuropathy, emesis, and myelosuppression were equivalent in the two treatment arms, DDTC-treated patients had more nephrotoxicity as determined by changes in serum creatinine concentration. Toxicities related to DDTC infusion included transient hypertension, flushing, and hyperglycemia. DDTC did not compromise response rates in either tumor type. CONCLUSION: This study did not demonstrate a significant chemoprotective effect against cisplatin-induced toxicities with the DDTC dose schedule tested. Patients who received DDTC received lower cumulative doses of cisplatin, but were more likely to be withdrawn from treatment early due to chemotherapy-related toxicities.

Phase II experience with ifosfamide/mesna in gynecologic malignancies: preliminary report of Gynecologic Oncology Group studies.

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Gynecologic Oncology Group experience with ifosfamide.

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study.

PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

Analysis of the relationships of the ploidy and cell cycle kinetics to differentiation and the female sex steroid hormone receptors in adenocarcinoma of the endometrium.

Flow cytometry was used to evaluate proliferative activity and ploidy status in 21 endometrial adenocarcinomas. These data were compared with their histologic and nuclear grades and their estrogen and progesterone receptor contents. Proliferative activity was significantly related to histologic and nuclear grades and the progesterone receptor status but not to the estrogen receptor status. Unlike the majority of solid human malignant neoplasms, only seven tumors were aneuploid, the remainder being diploid. Ploidy was not significantly associated with either grading system, receptor status, or the proliferative index.

Placental-type alkaline phosphatase in ovarian cancer fluids and tissues.

Placental-type alkaline phosphatase was measured in sera, cyst, and ascites fluids, and from tumor extracts obtained from gynecologic cancer patients, particularly those with cancer of the ovary. A modified assay was used that depended on long incubation (20 to 24 hours) to measure the heat-stable, phenylalanine-sensitive placental isoenzyme. The concentration of enzyme in ascites and cyst fluids was markedly higher than in serum. Cyst fluid values were generally higher than ascites fluids from the same individual. The median enzyme levels for malignant cyst fluids were 50 times greater than for benign cyst fluids. When tumor tissue and fluids were available from the same patients, it was observed that the levels in each were proportional. Determination of this isoenzyme in serum did not give a useful index of tumor burden, as metastatic disease did not consistently result in elevated serum enzyme levels. When ovarian cancer patients were divided into two groups--those in whose sera placental-type phosphatase was elevated, and those in whom it was not--the presence of the enzyme in serum at the time of tumor diagnosis appeared to be a negative prognostic indicator, judged from survival data.

Treatment of vaginal intraepithelial neoplasia with the carbon dioxide laser.

The carbon dioxide laser was used to treat vaginal intraepithelial neoplasia in 24 patients. Initially, partial or complete ablation of vaginal epithelium was performed, the extent of the procedure depending upon the distribution of disease. Later in the series complete ablation was performed routinely because of recurrences among patients treated with only partial ablation. Fifteen patients had severe dysplasia or carcinoma in situ (vaginal intraepithelial neoplasia III), and nine had moderate dysplasia (vaginal intraepithelial neoplasia II). Of the 24 patients, 20 had satisfactory removal of vaginal intraepithelial neoplasia after a single operation. Four patients with vaginal intraepithelial neoplasia III who underwent partial vaginal epithelial ablation had persistence of abnormal tissue detected within six months of treatment. These patients were re-treated successfully with the laser. Average length of hospitalization for vaginal epithelial ablation with the carbon dioxide laser was two days. Excellent postoperative healing occurred and all patients have resumed their pretreatment sexual pattern. Follow-up ranges from six to 27 months, with an average follow-up of 15 months. The carbon dioxide laser can be used cost-effectively to remove vaginal intraepithelial neoplasia.

Ineffectiveness of povidone-iodine irrigation of abdominal incisions.

Two to four percent of uncontaminated surgical wounds become infected; the incidence is increased in contaminated cases. The present study was designed to determine the efficacy of wound irrigation with povidone-iodine in patients not receiving prophylactic antibiotics who were undergoing gynecologic operations. The results revealed no significant difference in the relatively high occurrence of wound infections, morbidity, and elevated fever indices between the povidone-iodine wound irrigation group of patients and the control group. From a review of previous studies of topical antibiotics and antiseptics in contaminated cases as well as from the present findings, providone-iodine wound irrigation without assocaited use of prophylactic antibiotics does not appear to reduce significantly the incidence of wound infections in patients with potential vaginal contamination.

Low-dose carbenicillin prophylaxis for vaginal and abdominal hysterectomy.

A double-blind prospective study of 99 patients undergoing vaginal and abdominal hysterectomy was performed at North Carolina Baptist Hospital of the Bowman Gray School of Medicine at Wake Forest University. The study indicated that low-dose intravenous carbenicillin begun preoperatively and continued for 24 hours resulted in decreased febrile morbidity, postoperative infection rate, and shortened hospital stay in patients undergoing both vaginal and abdominal hysterectomy. The indications for operation, clinical characteristics of patients, and operative and postoperative management were similar for the control and study groups. For the vaginal hysterectomy group, febrile morbidity was reduced from 34.6% in the control group to 7.7% in the group receiving carbenicillin. For patients undergoing abdominal hysterectomy, febrile morbidity was reduced from 54.1% in the control group to 4.0% in the group receiving prophylactic carbenicillin. Similar reductions for the carbenicillin study group in fever index and average total hospital stay were also noted. Urinary tract infections were determined to be present more commonly in the group of patients with febrile morbidity receiving no prophylactic antibiotics. The incidence of pelvic infections were reduced in both carbenicillin-treated groups. This investigation suggests that low-dose carbenicillin prophylaxis is beneficial in reduction of morbidity following both vaginal and abdominal hysterectomy.

Carcinoma of the cervix complicated by a soup spoon.

A case is reported of a large serving spoon discovered in the abdomen after an abdominal hysterectomy. The surgical use of this item is explained.

Menstrual dysfunction following use of oral contraceptives.

PIP: An evaluation of 13 patients with menstrual dysfunction following discontinuation of oral contraceptives is presented. All had normal ovulatory cycles of 26-34 days before beginning oral contraceptive medication. The duration of therapy was 3-42 months with 14 months the mean. Relationship between occurrence of menstrual dysfunction and duration of therapy or type of agent administered was not noted. 9 were classified as amenorrheic (6 months or more of secondary amenorrhea) and their condition lasted from 6 to 36 months. Cervical mucus from 6 demonstrated a 3 to 4+ fern phenomena, indicating significant endogenous estrogen production. Gynecologic endocrine status was evaluated by basal body temperature, endometrial biopsy, and cervical mucus arborization. Total gonadotropins were measured in those demonstrating poor or absent fern phenomenon. Adrenal and thyroid functions were measured by 17-ketosteroid and 17-hydroxysteroid excretion and PBI respectively. Patients were screened for pituitary tumors by X-ray and visual examinations. Clomiphene (Clomid) was administered to 6 patients in 5 day courses of 50 or 100 mg per day. Of these 4 responded with ovulatory cycles. One became pregnant. 2 patients not responding to several such courses, were given human menopausal gonadotropin (HMG Pregova) in doses of 140 I.U. a day until cervical mucus demonstrated 4+ fern phenomenon. Human chorionic gonadotropin (HCG) was then given in a single dose of 5000 I.U. One responded to this treatment and became pregnant. 3 were not treated because they did not desire conception or ovulation induction. The 4 patients who were amenorrheic for less than 6 months were considered oligomenorrheic. 2 responded to clomiphene but the pattern of prolonged follicular phase has recurred in both. Their menstrual dysfunction is thought to be due to delayed recovery from suppression of some hypothalamic-pituitary mechanisms involved in normal gonadotropin regulation. Gonadtropin therapy is the only effective method of ovulation induction in those patients who fail to respond to clomiphene.^ieng