Surgery as sole treatment for serous borderline tumors of the ovary with noninvasive implants.

OBJECTIVES: The objectives were to describe the clinical characteristics and prognosis of surgically treated patients with stage II and III serous borderline tumors of the ovary with noninvasive implants. MATERIALS AND METHODS: From 1990 to 2000, 16 patients with stage II and III ovarian serous borderline tumors and noninvasive implants were diagnosed and prospectively followed at our center. All patients underwent surgical treatment including staging and their pathology was reviewed. Fifteen patients had thorough surgical staging by laparotomy, while one patient was staged laparoscopically. No patient was treated with adjuvant therapy (radiation or chemotherapy) after surgical treatment and none were lost to follow-up. RESULTS: The mean age at diagnosis was 42 years (range 26-59). Fourteen patients were treated by abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and multiple peritoneal biopsies, while 2 patients were treated conservatively for fertility preservation. Two patients underwent pelvic and para-aortic lymph node dissection. Fifteen of 16 patients had ovarian surface involvement with tumor. All patients but 2 had clinical evidence of extraovarian disease at the time of surgery. The mean duration of follow-up was 60.7 months (range 2-134 months). Thirteen patients (81%) are alive without evidence of disease. Four patients (25%) required subsequent surgery for recurrent disease and all are still alive. Two patients have been treated with chemotherapy (paclitaxel/carboplatin) for progressive borderline disease, while an additional patient was treated after first relapse with chemotherapy for an invasive recurrence. CONCLUSIONS: Carefully staged patients with advanced serous borderline tumors of the ovary and noninvasive implants have a good prognosis without adjuvant therapy.

Incidental malignancy in internal thoracic artery lymph nodes.

The incidental finding of malignant internal thoracic lymph nodes while mobilizing the internal thoracic artery (ITA) for coronary bypass grafting has not to our knowledge been previously reported. The cases of 3 male patients who underwent surgery between January 1990 and January 1993 and in whom malignant lymph nodes were found in the ITA pedicle are reviewed. One individual was found to have metastatic carcinoma of the breast, whereas the other 2 were discovered to have previously undiagnosed lymphomas. After undergoing further relevant investigation and treatment, all 3 patients remain free of recurrent disease 6.8 to 9.8 years after their original cardiac surgery. Primary or metastatic malignancy may be encountered in the course of ITA mobilization for grafting. Abnormally enlarged internal thoracic lymph nodes should be sent for pathologic examination.

DNA content in cervical carcinoma: a flow cytometric assessment of DNA heterogeneity.

The degree of DNA heterogeneity varies between tumors arising in different body sites. Any substantial degree of variability within a given tumor can give rise to significant problems in the interpretation of DNA flow cytometric (FCM) studies. This study was undertaken to evaluate the degree of DNA heterogeneity in cervical carcinomas. A total of 100 3-mm punch biopsies were evaluated from single large cases in 10 sections of cervical carcinoma. Of the 10 tumors, 6 were squamous carcinoma, 1 was an adenocarcinoma, 1 was a mixed small cell and squamous carcinoma, 1 was an adenosquamous cancer, and 1 was a small cell carcinoma with a small area of adenocarcinoma. Adequate histograms were available for 95 (95%) of the samples. Of the 10 cases studied, 9 (90%) revealed homogeneity in the DNA pattern. A solitary case demonstrated heterogeneity in one histogram (nine samples DNA diploid and one sample DNA aneuploid). This case was predominantly small cell undifferentiated carcinoma with focal adenocarcinoma. The area of adenocarcinoma was probably the area that contributed to the heterogeneous FCM pattern. From this study we conclude that for most cervical carcinomas of a specific histologic type there is DNA homogeneity. However, for carcinomas with a mixed morphology, DNA heterogeneity is possible and this must be taken into account in any DNA ploidy studies that include mixed or combined tumors.

Conservative surgery for recurrent or persistent carcinoma of the cervix following irradiation: is exenteration always necessary?

Between 1960 and 1988, 47 patients had conservative surgery for postradiation recurrent or persistent cervical carcinoma. Forty-two patients with nonmetastatic disease and available follow-up information were divided into 3 groups based on the extent of disease and type of surgical procedure. Group 1 contained 13 patients with smaller tumors prior to radiation (FIGO Ib and IIa), and recurrent or persistent disease confined to the cervix and/or vaginal vault. Group 2 consisted of 20 patients presenting with more advanced disease than those in Group 1, at the time of either radiation or surgery. Surgical resection of disease was accomplished in both Groups 1 and 2 by either radical vaginal or abdominal hysterectomy. The 8 patients in Group 3 required extended Wertheim operations to encompass locally advanced disease involving the bladder base and/or parametrium. One patient could not be categorized. The 5-year estimated relapse-free survivals for each group were 84, 49, and 25%, respectively. The relapse-free survival of Group 1 was significantly better (P = 0.003) than that of Group 3. Major complications occurred in 4 patients belonging to Group 1 (31%), 10 in Group 2 (50%), and 6 (including two treatment-related deaths) in Group 3 (75%). The most common complication was fistula formation in 11 patients (26%). Radical hysterectomy can be offered as an alternative to exenteration in carefully selected patients.

Necrotic pseudoxanthomatous nodules of the omentum and peritoneum: a peculiar reaction to endometriotic cyst contents.

BACKGROUND: Necrotic pseudoxanthomatous nodules of the ovary, omentum, and peritoneum are rare, and have been described as a late manifestation of endometriosis. CASE: A 39-year-old woman presented with acute abdominal pain and an abdominopelvic mass. Emergency laparotomy revealed a ruptured ovarian neoplasm with several liters of old blood in the abdominal cavity. Left adnexectomy was performed, and exploration of the abdominal cavity revealed no other lesions. Pathologic examination of the neoplasm showed a large endometrioma with an associated endometrioid adenocarcinoma. At surgery 7 weeks later, multiple pseudoxanthomatous peritoneal and omental nodules were found. CONCLUSION: This case suggests that pseudoxanthomatous nodules of the peritoneum and omentum may arise from a peculiar reaction to endometriotic cyst contents and clinically can mimic metastatic ovarian carcinoma.

Surgery without adjuvant chemotherapy for early epithelial ovarian carcinoma after comprehensive surgical staging.

From January 1981 to December 1987, 82 patients with carcinoma of the ovary, Stages 1A, 1B, and 1C (cytology negative) (FIGO 1988), were enrolled in this study following accurate surgical staging. No patient received adjunctive therapy and all were followed from 2 to 6 years with a mean duration of follow-up of 4 years. Sixty-eight patients were eligible for review--thirty-nine Stage 1A, six Stage 1B, and twenty-three Stage 1C (twenty-one with tumor rupture, two with excrescences). The mean age was 48.8 years. Three patients had a recurrence of their disease (one death). Forty patients in this series were Stage 1A or 1B (well or moderately well differentiated, no excrescences, no rupture). Only 1 patient in this group (with clear cell carcinoma) has recurred, suggesting that this patient population can be followed without adjunctive therapy. Adhesions or rupture in this series did not affect outcome. Clear cell tumors may have an ominous prognosis despite apparent local disease.

Reduced incidence of rabbit endometrial neoplasia with levonorgestrel implant.

To test the hypothesis that progestogens protect against the development of endometrial neoplasia, we placed polydimethylsiloxane implants (levonorgestrel or inert) into the right uterine horn at random in 114 old female rabbits. Cross-sectional uterine biopsy specimens were taken from both horns at the time of implantation and at 6, 12, and 24 months thereafter. Twenty-nine levonorgestrel-treated and 33 controls survived to the completion of the study. The incidence of endometrial neoplasia of 17.2% in the group treated with levonorgestrel was significantly less (p less than 0.05) than the 42.4% incidence observed in the control does. Before the completion of the study, one levonorgestrel-treated doe died and was found to have an endometrial tumor. When the findings of this doe are included in the report, the statistical significance is marginally lost. No endometrial neoplasia was found in the eight does with serum levonorgestrel concentrations greater than 0.12 ng/ml. Only one of the five tumors in the levonorgestrel-treated group occurred in the horn containing the levonorgestrel implant, which suggests that a dose effect is likely. Treatment with levonorgestrel decreases the incidence of endometrial neoplasia in rabbits. This finding gives further credence to the use of progestogen supplementation in women at risk for developing endometrial neoplasia.

Adriamycin and cisplatin in the treatment of stage III and IV epithelial ovarian carcinoma.

A total of 342 eligible, previously untreated patients with Stage III or IV epithelial ovarian carcinoma were treated with Adriamycin and cisplatin, both at 50 mg/m2, for nine courses. Of the 210 patients who had clinically detectable disease after initial surgery, 85 (41%) had a complete clinical response and 45 (21%) had a partial clinical response. A total of 197 were clinically free of disease at the completion of chemotherapy and 175 of these had a second-look laparotomy; 55 had no macroscopic or microscopic evidence of residual disease after multiple random biopsies were examined histologically (complete surgical/histologic response). The major determinants of complete surgical/histologic response were diameter of largest residual tumor prior to treatment, ECOG performance status, and grade, patients with grade 3 tumors having a higher complete response rate than those with grade 1 or 2 tumors. The major determinants of survival were ECOG performance status and diameter of largest residual tumor prior to treatment. Median survival of the total group was 1.8 years.

A predictive index of cure versus no cure in advanced ovarian carcinoma patients--replacement of second-look laparotomy as a diagnostic test.

Three hundred forty-two Stage III and IV epithelial ovarian carcinoma patients received cytoreductive surgery followed by Adriamycin and cisplatin, 50 mg/m2 each, q 4 weeks for 9 courses. One hundred ninety-seven were clinically NED at completion of treatment and 173 of these 197 had a second-look laparotomy. One hundred twenty had persistent disease. Fifty-three were second-look negative and had no further treatment. Thirty of these latter patients relapsed--all (with one exception) within 2 years. Those not relapsing after negative second-look are considered "cured" (median follow-up 42 months, range 24-68 months) and all others "failures." Stage was a significant predictor of treatment failure--there were no Stage IV "cures." In Stage III patients, age and largest residual tumor diameter post initial surgery were significant predictors of failure. Performance status was marginally significant. In our series, any patient with Stage IV disease or Stage III disease with at least two of the following three poor prognostic factors had a chance of cure of 2.2% (2 "cures" out of 90 patients): age greater than 60 years, macroscopic residual initially, or initial performance status of 2 or 3. Under normal circumstances a second-look procedure to identify persistent disease in this group of patients does not appear justified.

High-dose-intensity regimen of weekly doxorubicin and cisplatin in the treatment of patients with stage III and IV epithelial ovarian carcinoma.

Thirty-seven eligible patients with stage III or IV epithelial ovarian carcinoma were treated with weekly doxorubicin and weekly escalating cisplatin in an attempt to improve outcome by increasing the dose intensity of chemotherapy as compared to more conventional regimens given every 3-4 weeks. There was a 63% clinical response rate, with a median survival time of 18 months. Six patients (16.2%) had a complete surgical/histologic response (negative second-look laparotomy). Two patients had treatment-related deaths, and severe toxicity was responsible for four other patients having to discontinue treatment prematurely. The toxicity of this regimen jeopardized received (as opposed to projected) dose intensity and the regimen therefore offered no improvement compared to other drug combinations and schedules.

Second-line chemotherapy of stage III-IV ovarian carcinoma: a randomized comparison of melphalan to melphalan and hexamethylmelamine in patients with persistent disease after doxorubicin and cisplatin.

A total of 205 women with stage III or IV ovarian cancer who had persistent disease after initial treatment with doxorubicin and cisplatin were randomized to receive melphalan (8 mg/m2 orally for 4 days) or the combination of melphalan (6 mg/m2 for 4 days) and hexamethylmelamine (120 mg/m2 for 14 days) every 4 weeks. Only one of 64 patients with measurable disease had an objective response. The major determinants of survival after randomization were the amount of residual disease after initial chemotherapy and the type of response to initial chemotherapy. There was no overall difference in survival between the two chemotherapy regimens, but the small group of patients whose disease progressed on initial chemotherapy survived significantly longer when treated with the two-drug combination. Neither of these regimens provided effective therapy for women whose disease was not eliminated by first-line treatment. However, the superior results obtained in one subgroup with the addition of hexamethylmelamine suggest that the place of this agent in treating ovarian cancer should be carefully evaluated.

Diffuse uterine leiomyomatosis: a case study with pregnancy complicated by intrapartum hemorrhage.

Diffuse leiomyomatosis of the uterus is a rarely reported condition which has been implicated as a cause of infertility and menorrhagia. We report the first documented case of pregnancy in the presence of this disorder. The course was complicated by cervical incompetence, spontaneous premature rupture of membranes, delivery by cesarean section, and intrapartum hemorrhage necessitating hysterectomy. The literature is reviewed and the clinical significance of this lesion discussed. Finally, speculations are made on the nature of this disorder.

Cholesterol granulomas in lymph nodes draining a benign ovarian neoplasm.

A 69-year-old woman underwent a hysterectomy and bilateral salpingo-oophorectomy for a 20-cm right ovarian tumor. Multiple peritoneal and lymph node biopsy specimens were obtained to determine the clinical stage. Despite the surgeon's concern of malignancy, pathologic examination demonstrated a benign mucinous cystadenoma. Periaortic and external iliac lymph nodes showed an unusual granulomatous reaction, with multinucleated giant cells surrounding cholesterol-like clefts. Analysis of cyst fluid from the ovarian tumor revealed high concentrations of protein and lipid; the lipid component was predominantly free cholesterol (0.61 mumole/mL) and phospholipid (0.225 mumole/mL). We speculate that fluid from the ovarian neoplasm drained into regional lymph nodes, causing this unusual granulomatous response.

Aggressive angiomyxoma of pelvic soft parts: a clinicopathologic study of nine cases.

Nine cases of aggressive angiomyxoma (AAM) of the pelvic soft parts were studied by light and electron microscopy and immunohistochemistry. The tumors were confined to the vulva, vagina, pelvic floor, and perineum in the seven women. The perineum and the para-anal region were involved in the two men. The patients ranged in age from 18 to 63 years. Aggressive angiomyxoma presented as a slowly growing, polypoid or cyst-like tumor. Six of the nine cases were followed up; all of the tumors recurred within nine to 84 months, and one recurred for the second time at 144 months. Recurrences were attributed to incomplete tumor excision. None of the six patients died or had metastases. The aggressive angiomyxomas had infiltrative borders and rubbery, white or soft, gelatinous cut surfaces. Histologically, the lesions were composed of stellate and spindle-shaped neoplastic cells embedded in a collagenous and hyaluronic acid-containing stroma. Nuclear atypia and mitoses were absent. Typically, the lesions had an important vascular component, often displaying medial hypertrophy and vascular grouping. Ultrastructurally, the neoplastic cells resembled fibroblasts rather than myofibroblasts. They showed strong immunoreactivity for actin but were negative for S-100 protein, Factor VIII, carcinoembryonic antigen, and keratin. The morphoimmunocytochemical characteristics of AAM cells favor a fibroblastic origin and differentiation. Aggressive angiomyxoma should be distinguished from the more common benign and malignant myxoid neoplasms or tumor-like conditions of the pelvic soft parts. Recurrence of AAM may be avoided by wide, local excision.

Microbiological and histological findings in the fallopian tubes of women using various contraceptive methods.

The oviducts of seventy-three women undergoing sterilization by partial salpingectomy were submitted for microbiological and histologic studies. Twenty women were intrauterine device users, twenty-five women were oral contraceptive pill users and twenty-eight women used natural or barrier methods of contraception. Among intrauterine device users, there was an excess of mild and severe acute inflammatory histologic changes involving both the lumen and the tubal mucosa. Five of the eight intrauterine device users with acute inflammatory change had sterile tubal cultures.

PIP: The oviducts of 7o women undergoing sterilization by partial salpingectomy were subjected to microbiologic and histologic study. The objective was to determine whether there is a link between the histologic evidence of salpingitis and microbiological findings in the fallopian tubes of IUD users. Of the 73 subjects, 20 had been IUD users, 25 used oral contraceptives (OCs), and 28 were natural or barrier mehtod users. Microscopic examination revealed no significant differences between user groups with respect to edema, fibrosis, chronic inflammation, or granulomatous inflammation. However, acute inflammatory cells were found in the lumen and the mucosa of the right or left tube in an excess of IUD users. 5 of the 8 IUD users with acute inflammatory change had sterile tubal cultures. There were no differences between user groups with respect to the microbiologic organisms found in cervical or oviductal cultures, supporting the concept that inflammatory changes do not necessarily reflect the presence of infection. Further studies of the links between IUD use, sterile acute inflammation, and pelvic infection are recommended.

Peritoneal epithelial lesions associated with proliferative serous tumours of ovary.

The peritoneal epithelial lesions in 40 cases of proliferating ovarian serous tumour are described. The lesions were varied and of both neoplastic and non-neoplastic form. The most common was serous tumour similar to that in the associated ovarian neoplasm. Tumour of this type was present in some or all of the peritoneal lesions in 77.5% of cases. In nearly two-thirds, the tumour was superficial; in the rest it invaded omentum. Occasionally, the infiltrating tumour was poorly differentiated. Benign tubular lesions resembling endosalpingiosis occurred in 16 (40%) of the 40 cases, but in seven it was associated with serous tumour. Psammoma bodies frequently accompanied serous tumour and endosalpingiosis and in occasional cases the majority of lesions consisted of psammomatous foci. The duration of follow up is too short to adequately assess the biological significance of these findings but it is clear that the peritoneal tumour occasionally may kill the patient within a few years. 'Serous tumour of low malignant potential' is the most appropriate term to describe the general group of ovarian serous tumours of so-called 'borderline malignant' type.

Combination v. sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer.

The results of a national clinical trial to compare combination and sequential chemotherapy for stage III or IV ovarian cancer are reported. Of the 253 patients from 16 centres across Canada who were admitted to the trial 13 were excluded from the analysis. All the patients were observed for 2 to 5 years from entry into the trial. There were no differences in response to therapy or in survival between the patients treated with melphalan followed by 5-fluorouracil and then by methotrexate in high dosage and the patients treated with the same agents in combination. Patients with minimal residual disease after resection of stage III ovarian cancer had a good prognosis. Other favourable prognostic factors were age (less than 55 years), performance status (90% or 100% on the Karnofsky scale) and histologic grade of the tumour.

Left atrial myxoma: false negative echocardiographic findings in a tumor demonstrated by coronary arteriography.

A report of left atrial myxoma discovered at coronary arteriography by virtue of unusual tumor "vascularity" is presented in which establishing the diagnosis by means of echocardiography proved difficult. The difficulty may have been due to the highly vascular nature of the tumor with resultant loss of the acoustic reflectivity required for echocardiographic demonstration. Previous cases in which left atrial myxomas have shown arteriographically demonstrable "tumor vascularity" are reviewed.

Tumorigenic aspects.

This report presents a review of tumors, except those of pituitary, that have been reported to occur in women taking combined oral contraceptive preparations. Pathologic features, both gross and microscopic, and differential diagnosis are emphasized. Particular attention is given to tumors of the liver: focal nodular hyperplasia (hepatic hamartoma) and liver cell adenoma (benign hepatoma). The characteristic features of these usually distinctive lesions are illustrated, and an attempt is made to evaluate the significance of each with respect to oral contraceptives. Tumorigenic aspects relating to the uterus and the breast are briefly discussed.

Hodgkin's disease following thorium dioxide angiography.

Hodgkin's disease occurred in a 53-year-old man who, 25 years previously, had undergone cerebral angiography, for which thorium dioxide suspension (Thorotrast) was used. Deposits of throium dioxide were noted in reticuloendothelial cells in various locations. An association between thorium dioxide administration and the subsequent development of malignant tumours and neoplastic hematologic disorders has previously been reported.