Postoperative pelvic irradiation in early stage uterine mixed mullerian tumors.

PURPOSE OF INVESTIGATION: To review our management experience with uterine mixed mullerian tumors (MMTs) in order to evaluate potential prognostic indicators, and assess the efficacy of various treatment modalities. METHODS: A retrospective, clinicopathologic evaluation of 43 patients presenting for treatment of uterine MMTs between 1982 and 1992 was conducted. Diagnostic criteria for inclusion was the presence of both a malignant glandular or squamous epithelial component, and a homologous or heterologous stromal component. RESULTS: Overall 2- and 5-year cancer related Kaplan-Meier survival estimates with 95% confidence intervals were 44 (.28, .59) and 26% [.12, .39], respectively. Survivals were 83 [.62, .99] and 58% [.31, .85] when disease was confined to the uterus, and 22 [.03, .41] and 7% [.01, .20] when disease extended beyond the uterus. Clinical staging was often inaccurate, with 29% of clinical stage I or II disease being upstaged at laparotomy. A significant survival advantage was found in patients with stage I or II disease treated with surgery plus pelvic irradiation (p = 0.001), as compared to those treated with surgery alone. The prognosis after disease recurrence was poor, irrespective of secondary therapy, with a median survival of 11 months. CONCLUSIONS: A therapeutic advantage may be gained from postoperative pelvic irradiation in the treatment of surgical stage I or II uterine MMT.

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.

Surgical failures in the management of pelvic floor relaxation.

There are a vast number of operations for the correction of symptomatic pelvic floor relaxation, and the pelvic surgeon is faced with a difficult task in selecting the most appropriate procedure(s) for an individual patient. A successful outcome not only depends on the surgeon's skill and operative technique, but also relies heavily on the preoperative recognition and evaluation of factors related to surgical failure. Most importantly, careful attention to all components of the pelvic floor will allow the surgeon to tailor an operation to the individual's particular needs. Awareness of the many pitfalls of pelvic reconstructive surgery should lead to the appropriate preoperative evaluation and patient counseling, thus ensuring the best opportunity for a favorable outcome.

Salvage carboplatin therapy for advanced ovarian cancer after first-line treatment with cisplatin.

From April 1989 to August 1990, 17 patients with Stage 3 or 4 epithelial ovarian cancer (EOC) were treated with intravenous carboplatin (160-400 mg/m2) for refractory or recurrent disease after first-line treatment with cisplatin-based combination chemotherapy. Of fifteen patients evaluable for activity, two complete responses and two partial responses were seen, for a response rate of 27%. The duration of response was 4.5, 5, 8, and 9.2 months, respectively, and responders survived longer than nonresponders. Of the nine evaluable patients receiving carboplatin as the first salvage treatment, four responses were seen. Dose selection for the first cycle of carboplatin was based on previous treatment, and adjustments were made on the basis of myelosuppression. In general, treatment was well tolerated--severe myelosuppression occurred after 6 of 73 cycles. This review confirms previous reports of anti-tumor activity of carboplatin in patients with refractory or recurrent advanced EOC who respond to first-line treatment with cisplatin. Further evaluation may help define the toxicity and efficacy of salvage treatment with carboplatin compared to cisplatin in patients who recur after a prolonged disease-free interval after first-line cisplatin-based therapy.

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.

The role of hexamethylmelamine in the combination chemotherapy of advanced ovarian cancer: a comparison of hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) versus cyclophosphamide, doxorubicin, and cisplatin (CAP).

To evaluate the contribution of hexamethylmelamine (HMM) to the treatment of advanced ovarian cancer with combination chemotherapy, we compared the results of treatment with HMM, cyclophosphamide, doxorubicin, and cisplatin (H-CAP regimen) to treatment results using cyclophosphamide, doxorubicin, and cisplatin (CAP regimen). The treatment regimens were identical in dosage and schedule with the exception of the addition of HMM to one regimen. Fifty-five patients treated with H-CAP at Vanderbilt University Hospital between August 1977 and March 1980 were compared with a subsequent group of 22 patients who received CAP between October 1984 and October 1987. Following six months of therapy, patients were restaged either with second-look laparotomy or with clinical restaging. Fifty-three of 55 patients (96%) had objective responses to H-CAP compared with 14 of 21 patients (67%) treated with CAP (p = 0.001). The pathologic complete response rate was also higher in the patients who received H-CAP (35% versus 19%). The median survival of patients receiving H-CAP is 47 months compared to 21 months for the CAP patients. When patients with limited residual disease (maximum tumor diameter less than or equal to 3 cm) were compared, the median survival also favored the H-CAP treatment (101 months versus 21 months, p = 0.002). The median time to progression was also greater in patients receiving H-CAP versus those receiving CAP (67 months versus 16 months, p = 0.045). Treatment-related toxicity did not differ substantially between the two regimens. Our findings suggest that the addition of HMM to CAP chemotherapy prolongs the median survival in patients with ovarian cancer and limited residual disease following cytoreductive surgery.

Intraoperative guidance for intrauterine procedures with transrectal sonography.

Transrectal sonography was used for intraoperative guidance in intrauterine tandem placement for intracavitary radiation therapy and in dilation and curettage procedures. The authors describe the method and three representative cases in which it was applied. It is concluded that the technique may prevent complications such as uterine perforation or bladder injury in tandem placement, and that it can facilitate dilation and curettage in complicated cases.

High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma in a sigmoid conduit: case report.

The increased risk of developing adenocarcinoma in the sigmoid colon after ureterosigmoidostomy has been acknowledged for some time. Development of adenocarcinoma in colonic conduits isolated from the fecal stream is rare. We report a case of adenocarcinoma arising in a sigmoid conduit that probably represents a metachronous adenocarcinoma of the colon.

Preoperative assessment of myometrial invasion of endometrial adenocarcinoma by sonography (US) and magnetic resonance imaging (MRI).

The presence and/or depth of myometrial invasion of endometrial adenocarcinoma has important prognostic and therapeutic implications. Fifteen patients with histologically proven endometrial cancer underwent preoperative evaluation with sonography (US) and magnetic resonance imaging (MRI) to assess depth of invasion. Using criteria of greater than or equal to 50% of myometrial wall involvement as representing deep invasion, and less than 50% as superficial invasion, US was more accurate than MRI in five cases; in three MRI was more accurate than US; both MRI and US were equally accurate in four; neither was accurate in three. Polypoid lesions caused the greatest number of false positive reports of deep invasion with both MRI and US. Preliminary results indicate that US and MRI have promise as preoperative tests to assess the extent of myometrial invasion.

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.

Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.

The safety and efficacy of a daily combination of micronized estradiol (E2) (0.7-1.05 mg) and progesterone (200-300 mg) were evaluated in ten menopausal women with moderate to severe vasomotor symptoms and/or vaginal atrophy over a 12-month study interval. For comparison, five similar women were placed on conjugated estrogens, 0.625 mg daily, and medroxyprogesterone acetate, 10 mg daily, for the first 10 days of each calendar month for 12 months. Patients were evaluated at 0, 1, 3, 6, and 12 months. Estrogens rose significantly from baseline in both groups (P less than .01). Progesterone increased significantly above baseline in the E2 and progesterone group (P less than .01), but did not change in the conjugated estrogens and medroxyprogesterone acetate users. All women on E2 and progesterone had a decrease in total cholesterol and an increase in high-density lipoprotein cholesterol from baseline (P less than .01). Those on conjugated estrogens and medroxyprogesterone acetate had no significant change from baseline in total cholesterol; however, they did have an increase in high-density lipoprotein cholesterol values (P less than .01). In the E2 and progesterone group, the endometrial histology became completely quiescent and there was no uterine bleeding after 6 months of observation. Four of five women on conjugated estrogens and medroxyprogesterone acetate continued regular withdrawal bleeding throughout the study period, but no endometrial hyperplasia was encountered. This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women.

Occurrence of ovarian malignancy in childhood and adolescence: a community-wide evaluation.

During childhood and adolescence, the rate of malignancy in ovarian enlargement is reported to be high-approximately 35% in many large series from tertiary centers. To assess whether this represents an overestimation because of the referral patterns of these institutions, a retrospective review was conducted at five hospitals in Nashville, Tennessee. In females 21 years of age and under, borderline or malignant ovarian neoplasms were identified in only eight (5.8%) of 137 individuals with ovarian enlargement and eight (9.8%) of 82 females with ovarian neoplasms. All six malignant neoplasms were of germ-cell origin. The borderline neoplasms were of epithelial origin, and occurred in females in their late teens. We conclude that the frequency with which ovarian enlargement represents malignancy in this age group appears to be much smaller than previously suggested. Nevertheless, because of the potential for malignant ovarian neoplasia in young females, the presence of an abdominal-pelvic mass requires prompt and thorough attention.

Gynecologic causes of the acute abdomen.

Acute surgical emergencies of gynecologic origin occur for the most part in women of reproductive age but occasionally in newborn and adolescent patients and rarely in the postmenopausal patient. The most common and most important conditions to be considered include pelvic inflammatory disease (PID) with abscess, ectopic pregnancy, hemorrhage from a functional ovarian cyst, and adnexal or ovarian torsion.

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.

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.

Combination chemotherapy for patients with advanced carcinoma of the cervix: trial of mitomycin-C, vincristine, bleomycin, and cisplatin.

Sixteen patients with metastatic or recurrent carcinoma of the cervix were treated with combination chemotherapy consisting of mitomycin-C, vincristine, bleomycin, and cisplatin. Seven of 14 (50%) evaluable patients responded. In 2 patients all measurable disease resolved. Median duration of response was 4.5 months. Toxicity was severe and consisted of myelosuppression, pulmonary fibrosis, nausea, vomiting, stomatitis, asthenia, and fever. Two treatment-related deaths occurred. This combination chemotherapy regimen appears to have a response rate similar to other cisplatin containing regimens. Response durations were short and toxicity was severe.

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.

Abdominopelvic computed tomography: evaluation in patients undergoing second-look laparotomy for ovarian carcinoma.

Preoperative abdominopelvic computed tomography results and operative findings were compared in 52 patients undergoing second-look laparotomy to confirm tumor status. Seventeen true-negative, 22 false-negative, and 13 true-positive scans were found. The sensitivity was 0.38, specificity was 1.0, and diagnostic accuracy was 0.58. Negative studies were associated with positive findings at laparotomy in 42% of all cases. Fourteen patients were identified who had computed tomography that would have enabled an attempt at the diagnosis of persistent cancer by computed tomography-directed needle aspiration or biopsy, thus avoiding laparotomy. Assuming 80% accuracy of needle aspiration, the cost of computed tomography in all 52 patients is considerably outweighed by the savings that could have been realized by eliminating the need for second-look surgery in these 11 women.