Lonnie S. Burnett

Advanced Ovarian Cancer: Long-Term Results of Treatment with Intensive Cisplatin-Based Chemotherapy of Brief Duration

STUDY OBJECTIVE To determine the efficacy of a 6-month course of combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) in the treatment of advanced ovarian carcinoma. DESIGN Prospective, non-randomized, single-institution trial with a 6-month course of chemotherapy, followed by second-look laparotomy for restaging. Minimum follow-up after completion of therapy is 83 months. PATIENTS Fifty-five patients with advanced (stage III or IV), intermediate- or high-grade epithelial carcinoma of the ovary. Twenty patients had limited residual tumor (3 cm or less maximal tumor diameter) after initial cytoreductive surgery; 35 had extensive residual disease. INTERVENTIONS All patients received chemotherapy with hexamethylmelamine (150 mg/m2 body surface area orally on days 1 to 14), cyclophosphamide (350 mg/m2 intravenously on days 1 and 8), doxorubicin (20 mg/m2 intravenously on days 1 and 8), and cisplatin (60 mg/m2 intravenously on day 1). Courses were repeated at 4-week intervals; 41 patients (75%) received six courses; 10 patients received five courses, 3 patients received four courses, and 1 patients received three courses. Forty-seven patients underwent second-look laparotomy after completion of therapy; 8 had their disease restaged clinically. RESULTS Fifty-three of fifty-five patients (96%) had either partial or complete response to treatment. Nineteen of forty-seven patients who had a second-look laparotomy had a surgically documented complete response; 17 of these 19 patients began chemotherapy with limited residual tumor. Ten patients (18%) remain disease-free 83 to 108 months after therapy, whereas three additional patients died of other diseases without clinical evidence of recurrent ovarian cancer. Nine of twenty patients who began chemotherapy with limited residual tumor remain disease-free, as compared to only 1 of 35 patients with more extensive tumor (P less than 0.001). All long-term, disease-free survivors had surgically documented complete response at second-look laparotomy. CONCLUSIONS Treatment with cisplatin-based combination chemotherapy after aggressive cytoreductive surgery should be considered standard treatment for advanced ovarian carcinoma. Our intensive, 6-month course of treatment produced results comparable to those previously reported with prolonged treatment.

Peritoneal Carcinomatosis of Unknown Primary Site in Women: A Distinctive Subset of Adenocarcinoma

STUDY OBJECTIVE To define the clinical features and results of systemic treatment in women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surfaces. DESIGN Retrospective analysis of 18 patients treated at a single institution between 1978 and 1984. PATIENTS All 18 women had abdominal carcinomatosis and had no primary site identified at laparotomy. Nine patients had limited residual tumor (maximal tumor diameter, 3 cm or less) after initial cytoreductive surgery, and 9 patients had extensive residual disease. INTERVENTIONS In general, patients were treated according to standard guidelines for treatment of advanced ovarian carcinoma. All patients had initial laparotomy with attempted cytoreduction; of these 18 patients, 16 subsequently received cisplatin-based chemotherapy. Patients were restaged either clinically (10 patients) or with second-look surgery (8 patients). RESULTS The median survival for all patients was 23 months. Five patients had complete response to chemotherapy, and three patients remain disease-free 41, 59, and 77 months after diagnosis. Patients with limited residual disease had longer median survival than did those with extensive residual disease (31 months compared with 11 months). CONCLUSIONS Women with adenocarcinoma of unknown primary site involving predominantly the peritoneal surface should be distinguished from other patients with adenocarcinoma of unknown primary site because they have a more indolent disease course, a higher response rate to systemic therapy, and a chance for long-term, disease-free survival after therapy. Although optimal treatment is undefined, we recommend that these patients be treated using the guidelines established for therapy of advanced ovarian carcinoma, including initial surgical cytoreduction followed by cisplatin-based combination chemotherapy.

Cushing's syndrome with small cell carcinoma of the uterine cervix

A 28 year old white women was found to have a cervical tumor in the 25th week of pregnancy. Pathologic examination revealed a nonkeratinizing small cell carcinoma. After delivery by cesarean section, pelvic lymph node exploration was carried out, and all 15 nodes were free of tumor. Her condition was staged as II-A, and she was treated with local radiation. Metastatic disease became manifest almost a year later and was histologically similar to her primary disease. A Cushingoid appearance was noticed and plasma cortisol levels were elevated. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) and 17-ketosteroid (17-KS) levels were elevated and failed to suppress with dexamethasone. Plasma adrenocorticotropin (ACTH) level was elevated. Electron microscopic examination of the tumor tissue revealed neurosecretory granules. Immunoperoxidase stains for ACTH were positive. The patients course was one of progressive decline and eventual death. A literature review revealed two other cases in which carcinoma of the uterine cervix was considered to be the source of ectopic ACTH. Some small cell carcinomas of the cervix may arise from cells of the APUD series. Small cell carcinoma of the uterine cervix may behave differently from the more commonly encountered keratinizing and large cell nonkeratinizing carcinomas of the cervix and may not respond as well to standard therapy. Ectopic hormone production, production of abnormal peptides or of vasoactive amines may be more common in small cell carcinoma of the cervix than is currently recognized, and these products may be clinically useful as tumor markers.

Transvaginal sonography of postmenopausal ovaries with pathologic correlation.

The sonographic appearance of 67 ovaries in 34 postmenopausal women who underwent preoperative transvaginal sonography (TVS) was correlated to findings on pathologic examination. Both ovaries were detected by TVS in 60% of the women examined; in 85%, at least one ovary was detected. The size of the normal, sonographically visualized postmenopausal ovary was 2.2 +/‐ 0.7 cm in transverse, 1.2 +/‐ 0.3 cm in anteroposterior, and 1.1 +/‐ 0.6 cm in longitudinal axes, with an average volume of 2.6 +/‐ 2.0 cm3. The average size of ovaries that were not detected by TVS was 0.7 x 0.4 cm (range, 0.3 to 1.3 cm); most of these (five of six) were atrophic on pathologic exam. The difference between actual and sonographically measured size was negligible (TVS overestimated by 0.3 cm). Four simple cysts that ranged from 0.5 to 3.5 cm were found by TVS and confirmed pathologically, as were three benign serous cystadenomas that ranged from 2.5 to 3.5 cm, one 3 x 6‐cm tubal carcinoma, and one 1 X 4‐cm paratubal cyst. TVS missed a 6‐cm dermoid, a 2.5‐cm cystadenoma, a 0.8‐cm Sertoli cell tumor, and a 0.5‐cm fibrothecoma that were nonpalpable but that were found on pathologic examination. None of the missed lesions were palpable preoperatively. The positive predictive value was 94% for detection of an ovarian mass; the negative predictive value for exclusion of an ovarian lesion was 92%. It is concluded that TVS can accurately delineate the ovaries in most, but not all, postmenopausal women and that only rarely will pathologic lesions not be detected by TVS.

Preservation of anal function after total excision of the anal mucosa for Bowen's disease.

Six women with Bowens disease of the anogenital area were treated by total excision of the anal mucosa, perianal skin and, in some cases, partial vulvectomy. Two patients had foci of microinvasive squamous carcinoma. Adequate tumor margins were determined by frozen sections. The resulting mucosal and cutaneous defects were grafted with medium split-thickness skin grafts applied to the anal canal and sutured circumferentially to the rectal mucosa. Grafts were held in place by a finger cot inserted in the anal canal and stuffed with cotton balls. Patients were constipated five or six days with codeine. The skin grafts healed per primam. One additional patient was similarly treated for a chronic herpetic ulceration of the anus and healed. Contrary to dire predictions, all patients were able to distinguish between gaseous and solid rectal contents and sphincter function was preserved. In one patient, Bowens disease has recurred in the grafted perianal skin.

The Ovarian Remnant Syndrome and Ureteral Obstruction: Medical Management

The ovarian remnant syndrome represents the development of symptoms due to residual ovarian tissue after bilateral salpingo-oophorectomy. Treatment generally consists of surgical resection but recurrence after resection is common. A case is reported in which a postoperative recurrent ovarian remnant was successfully managed by using a luteinizing hormone-releasing hormone agonist. In addition, this report includes a survey of gynecologists to determine the frequency of this syndrome and of ureteral involvement.

Simultaneous radiation and chemotherapy for advanced carcinoma of the cervix

Six patients with poor prognosis carcinoma of the cervix were treated with external radiation therapy simultaneously with cisplatin, bleomycin, and vincristine. Toxicity was very mild with nausea and vomiting and mild myelosuppression being the major toxicities. At a median of 36 months follow-up, four of six patients are alive, three with no evidence of disease. The median survival after diagnosis is 25+ months. The data suggest that radiation therapy and cytotoxic therapy administered together in patients with advanced cervix carcinoma is well tolerated. Further study to determine therapeutic efficacy is warranted.

Malignant mixed mesodermal tumors of the uterus and ovary treated with cisplatin-based combination chemotherapy

Twelve patients with malignant mixed mullerian tumors were treated with combination chemotherapy at Vanderbilt University Hospital from 1977 through 1981. Nine patients, all of whom received combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (HCAP), were evaluable for response. Objective responses (all partial responses) were noted in 3 (33.3%) (response rate greater than 10% and less than 55% with 90% confidence limits), a minimal response was noted in one patient, and stable disease in four (50%) patients. Responders survived longer (calculated from the initiation of HCAP) than nonresponders (median 112 vs 19 weeks). These results are not at present statistically different from previous studies utilizing doxorubicin alone, cisplatin alone, the combination of doxorubicin and DTIC, or the combination of vincristine, actinomycin D, and cyclophosphamide.

Sonographic features of ovarian remnants

Ovarian remnants occur after a portion of ovarian tissue is left behind unintentionally after oophorectomy. The ovarian remnant may be functional and cystic, producing pelvic pain and, in some patients, extrinsic compression of the distal ureter. Ovarian remnants frequently are associated with adhesions from previous pelvic surgery for endometriosis or pelvic inflammatory disease. Ovarian remnants also may be included within pelvic peritoneal inclusion cysts. In this retrospective study, the sonographic features of ovarian remnants in 10 patients with surgical proof or clinical follow‐up data are described. Most ovarian remnants were simple cysts (seven of 10), three had multiple septations, and six had a rim of presumably ovarian tissue with arterial and venous flow. Three patients with ovarian remnant masses that were aspirated had symptomatic relief without recurrence. In one patient, guided aspiration was unsuccessful, probably owing to the presence of organized hemorrhage within the mass. Extrinsic compression of the distal ureter was observed in one patient, who was treated with gonadotropin releasing hormone agonist (Lupron). The sonographic findings of a completely cystic or multiseptated pelvic mass with a rim of vascularized solid tissue in a postoophorectomy patient, although such cases are rare, suggest the diagnosis of an ovarian remnant. If the diagnosis can be established with a high degree of certainty, sonographically guided aspiration may be attempted in an effort to provide symptomatic relief. Otherwise, sonography is useful in serial assessment of these masses in patients receiving medical treatment.

Transrectal and transperineal sonography during guided intrauterine procedures

Transrectal sonography was used to provide intraoperative guidance for dilatation and curettage and placement of intrauterine tandem apparatus in 20 patients in whom the external cervical os could not be visualized adequately. Transrectal sonography was found to be useful in providing guidance for these procedures and at the same time helped avoid uterine perforation. This method also was used during cerclage placement in two patients who had undergone several conizations. Transperineal sonography was used in three patients whose area of abnormality was best approached transperineally. These cases included transvaginal biopsy of a metastatic trophoblastic tumor and one guided aspiration of a perirectal abscess after pelvic exenteration. The potential advantages and pitfalls in the intraoperative use of transrectal and transperineal sonography for guided intrauterine procedures are discussed and illustrated.