Endometrioid carcinoma of the ovary: a retrospective analysis of 106 cases.

AIMS AND BACKGROUND: This report retrospectively analyzes 106 cases of endometrioid carcinoma of the ovary treated at the National Cancer Institute of Milan from 1974 through December 1993. In 12 of the 106 cases (11.3%) a synchronous carcinoma of the uterine body was observed. METHODS AND STUDY DESIGN: Only patients who had previously untreated disease were included in the study. Patients with synchronous tumors were staged according to their ovarian cancer and treated according to the stage of that disease. RESULTS: Thirty-nine patients (36.8%) had stage 1, 17 (16.0%) stage 11, 43 (40.6%) stage III, and 7 (6.6%) stage IV disease. Moderately plus poorly differentiated tumors were present in 76 of the 106 cases (71.7%). Considering the 67 patients with advanced disease, residual tumor was absent in 27 cases (40.3%), < or = 2 cm in 17 (25.4%), and > 2 cm in 23 (34.3%) cases. Systematic pelvic and para-aortic lymphadenectomy was performed in 60 patients (56.6%); selective sampling was carried out in 23 cases (21.7%). After surgery, 77 patients underwent various chemotherapy regimens. CONCLUSION: Using univariate analysis, FIGO stage, tumor grade, residual disease after surgery, lymph node status, and platinum in the chemotherapy regimen significantly influenced 5-year survival. However, when all these variables were included in a multivariate analysis only FIGO stage still had a significant impact on survival. Survival analysis also showed a trend towards longer survival in patients with synchronous tumors.

Systematic pelvic and paraaortic lymphadenectomy at second-look laparotomy for ovarian cancer.

A retrospective review of the medical records of all ovarian cancer patients admitted to our institution from January 1974 to December 1993 was performed. A total of 58 consecutive patients who underwent systematic pelvic and paraaortic lymphadenectomy during second-look surgery was found. Node metastases were found in 15 of 58 patients (25.8%). No significant correlation was found between the variables of disease (e.g., stage of the disease at diagnosis, histology, grade, residual tumor after the first cytoreductive surgery, and the type of chemotherapy administered) and node status at second-look. Node metastases were found in 8 of 45 (17.7%) patients with absence of intraperitoneal disease, compared with 7 of 11 (63.6%) patients with intraabdominal residual disease (P < 0.02). There was no difference in 5-year survival for patients with absence of residual tumor in the peritoneal cavity as well as in the retroperitoneum (5-year survival 80%) and for patients with retroperitoneal disease only (5-year survival 77%). On the contrary, a highly significant difference in survival (P < 0.001) was observed between these two groups of patients and those who had intraabdominal residual tumor. Twelve of 45 (26.6%) patients have recurred. FIGO stage, grade, and residual disease after primary surgery were determinant in predicting recurrence. Notably, no relation emerged between relapse rate and the node status at second-look.

Conservative surgery in high-risk epithelial ovarian carcinoma.

BACKGROUND: In epithelial ovarian cancer, conservative surgery has mainly been adopted for stage Ia disease. The aim of this study is to report on a conservative surgical approach used in selected young patients with ovarian cancer who would usually undergo radical operations. STUDY DESIGN: From 1980 through 1994, 10 patients with invasive epithelial ovarian cancer and with high-grade or limited extraovarian disease were treated with conservative surgery. The mean age was 22.7 years. The stage was Ia grade 3 in 2 patients, Ic in 2 patients, IIIa in 2 patients, and IIIc in 4 patients. Eight patients were given adjuvant therapy (radiotherapy in 1 and chemotherapy in 7). RESULTS: All patients were alive and disease-free at a median followup time of 70 months (range 24-138 months). Nine patients were menstruating regularly and three had become pregnant. CONCLUSIONS: It seems that in selected patients, conservative operations can be used beyond the worldwide accepted criterion of stage Ia. This concept deserves additional investigation in larger series.

Systematic pelvic and paraaortic lymphadenectomy for advanced ovarian cancer: prognostic significance of node metastases.

A retrospective study of 488 patients with untreated advanced ovarian cancer is presented. Systematic pelvic and paraaortic lymphadenectomy was performed in 248 cases (50.8%). Selective sampling and node biopsy was performed in 33 (6.7%) and 47 (9.6%) patients, respectively. Node metastases were found in 194 of 328 patients (59.1%). The incidence of metastatic nodes significantly increased with more advanced stages, with serous histology, and with a greater amount of residual tumor. Node status appeared to be related to pathology findings at second-look. A complete pathologic response was documented in 26 of 31 (83.8%) patients with negative nodes and in 38 of 59 (64.6%) with positive nodes at first surgery. Patients with negative nodes survived significantly longer (5-year survival, 46%; median, 60 months) than those who had node metastases (5-year survival, 25%; median, 36 months). Using multivariate analysis, lymph node status, together with the stage of disease and residual tumor, still had a significant impact on 5-year survival. Moreover, among patients with optimal cytoreduction, 5-year survival was 46% (median, 56 months) and 30% (median, 41 months) for patients who did and did not undergo lymphadenectomy, respectively (P = 0.05). Likewise, when suboptimal cytoreduction was considered, a median 5-year survival of 24 months was obtained in patients who underwent lymphadenectomy compared with 14 months in patients who did not (P < 0.005).

Fallopian tube cancer: incidence and role of lymphatic spread.

Lymphatic spread pattern in 17 cases of adenocarcinoma of fallopian tube is reported. Median age of the patients was 48 years. All patients underwent surgical staging including total abdominal hysterectomy, bilateral salpingo-oopherectomy omentectomy, and appendectomy. Systematic pelvic and paraaortic lymphadenectomy was feasible in 15 cases. Majority of the patients (11 of 17 cases, 64%) had advanced disease and showed serous adenocarcinoma (83%). Lymph nodes were involved in 10 of 17 cases (59%). Node metastases rate increased significantly (P < 0.01) with intraperitoneal stage of disease and with grading. Interestingly, positive nodes were also found in 2 cases (33%) of 6 patients with disease still limited to fallopian tube. Overall, patients with negative nodes had a median survival of 76 months, compared with only 33 months if node metastases were found. In conclusion, combined pelvic and para-aortic lymphadenectomy seems to be necessary for staging and perhaps for prognosis of this disease.

Malignant degeneration in leiomyomatosis peritonealis disseminata.

Leiomyomatosis peritonealis disseminata (LPD) is a rare clinico-pathologic entity typically observed in women of reproductive age. Its malignant degeneration has been reported in literature in only three cases. In this report we describe the clinical course of two more cases with proved malignant transformation of LPD; both cases were treated with combined chemotherapy.

Regression of advanced ovarian carcinoma by intraperitoneal treatment with autologous T lymphocytes retargeted by a bispecific monoclonal antibody.

BACKGROUND: The high frequency of relapse after induction chemotherapy of advanced ovarian carcinoma calls for new therapeutic approaches. Lysis of ovarian carcinoma cells can be achieved by retargeting of T lymphocytes using F(ab')2 fragments of the bispecific monoclonal antibody (MAb) OC/TR, which is directed to the CD3 molecule on T lymphocytes and to the folate receptor on ovarian carcinoma cells. PURPOSE: Our purpose was to assess in ovarian carcinoma patients the antitumor activity of in vitro-activated autologous peripheral blood T lymphocytes retargeted with OC/TR. METHODS: Patients with epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages III and IV) meeting specific criteria were eligible to enter a phase II immunotherapy trial. Before immunotherapy, the 28 patients who entered the trial underwent laparotomy to reduce their tumor load and to allow measurement of all indicator lesions. They then received two cycles of five daily intraperitoneal infusions of autologous in vitro activated peripheral blood T lymphocytes retargeted with OC/TR plus recombinant interleukin 2 (IL-2) with (n = 11) or without (n = 17) a second daily infusion of OC/TR F(ab')2 and IL-2. Response to treatment could be assessed in 26 patients following explorative laparotomy; time to progression could be assessed in 27 patients. RESULTS: Seven patients had clinical evidence of progressive disease after treatment and therefore did not undergo laparotomy. Of the 19 patients evaluated by surgery and histology, three showed complete response, one showed complete intraperitoneal response with progressive disease in retroperitoneal lymph nodes, three showed partial response, seven had stable disease, and five had progressive disease. The overall intraperitoneal response rate was 27% (95% confidence interval [CI] = 10%-44%). The complete responses seen in three patients lasted 26 months in one patient, 23 months in the second, and 18 months in the third. Two patients were not assessable for response. One of these patients had bowel perforation during catheter removal, which precluded further evaluation. The second patient was positive only by cytologic examination before immunotherapy, was tumor free at laparotomy after immunotherapy, and remained so for the entire 21 months of follow-up, as determined by cytologic examination of random biopsy specimens. The median time to disease progression in the 15 assessable patients plus those who had stable disease was 11 months (95% CI = 6-18 months). Immunotherapy-related toxic effects included mild to moderate fever, nausea, emesis, and fatigue. Anti-mouse antibodies were detectable by the end of the treatment in 21 of 25 patients tested. CONCLUSIONS: Locoregional immunotherapy of ovarian cancer with bispecific MAb-retargeted T lymphocytes can result in tumor regression. Toxicity was mild to moderate and only transient. IMPLICATIONS: Improvement in systemic antitumor responses is needed before this approach can prove useful as adjunctive treatment following induction chemotherapy in patients with minimal residual disease.

The role of appendectomy in surgical procedures for ovarian cancer.

To assess the role of appendectomy in the surgical procedures for ovarian cancer, we evaluated retrospectively the clinical charts of 435 patients who underwent surgery after diagnosis of ovarian cancer. The appendix was removed in 160 cases and pathological examination revealed 37 with metastatic implants (23%). All the patients with appendiceal metastases showed advanced disease (stages III-IV) with an incidence of 43%. Ninety-one percent (31/34) of the tumors with appendiceal involvement at the staging operation were of the serous cell type and grade II or III. No case with early stage, right ovary carcinoma showed appendiceal metastatic foci, denying the existence of a preferential lymphatic pathway. Microscopic involvement was found only in 4 patients with advanced disease (11.7%). No intra- or postoperative complication directly related to the appendectomy was recorded. We conclude, with these results, that appendectomy should be part of the cytoreductive operation for ovarian cancer.

Potentials of cell kinetics in the management of patients with ovarian cancers.

The relevance of 3H-thymidine labeling index (3H-dt LI) on clinical outcome was evaluated on 85 patients with advanced ovarian cancers treated with carboplatin or cisplatin alone (39 cases) or cisplatin in association with doxorubicin and/or cyclophosphamide (46 cases). 3H-dT LI of the primary tumour was significantly related to the 3-year probability of survival in patients treated by monochemotherapy (low LI, 63%; high LI, 21%; P = 0.013) but not in those treated with polychemotherapy. Analysis of the relation between cell kinetics and clinical outcome as a function of treatment showed that in patients with rapidly proliferating tumours the 3-year survival was significantly higher following polychemotherapy than monochemotherapy (51 vs. 21%; P = 0.04). In patients with slowly proliferating tumours no significant difference in survival was observed following the two types of treatment for the overall series, whereas in patients not achieving a complete response survival was significantly higher following monochemotherapy than polychemotherapy (61 vs. 9%; P = 0.008).

Adoptive immunotherapy of ovarian carcinoma with bs-MAb-targeted lymphocytes: a multicenter study.

A bispecific monoclonal antibody (bs-MAb) (OC/TR) was produced in large quantities for the intraperitoneal (i.p.) treatment of ovarian cancer. The bs-MAb recognizes the folate-binding protein on ovarian cancer cells on the one hand and the CD3 activation site on T lymphocytes on the other. T lymphocytes were expanded ex vivo, targeted with OC/TR in vitro and administered to the i.p. cavity in the presence of soluble OC/TR. All patients developed human anti-mouse-antibodies (HAMA). In the Dutch study, 2 complete remissions (CR) were seen, 2 partial regressions (PR), I stable disease (SD) and I progressive disease (PD). In the Italian study 3 CR, I PR, I SD and 2 PD were seen.

Radioimmunoscintigraphy of ovarian cancer with the MOv18 monoclonal antibody.

The monoclonal antibody (Mab) 131I-MOv18 was administered to 30 patients with ovarian carcinoma intravenously (n = 20) and intraperitoneally (n = 10). After intraperitoneal administration, higher tumour uptake (mean values 1.3% vs. 0.8%) and a better tumour/background ratio (mean values 2.8 vs. 1.9) than after intravenous injection were obtained. Moreover, after intraperitoneal administration the uptake in non-affected organs, such as liver and spleen, was lower. However, occasionally the favourable results of the intraperitoneal route were cancelled by persistent pelvic non-specific accumulations of 131I-MOv18. The possibility to change the biodistribution pattern in the latter cases with peritoneal washing was evaluated. 3 patients were submitted to this procedure and an improvement in the radiotracer biodistribution was obtained in 1 case. With regard to tumour detection, the average sensitivity (73%) showed a significant difference from the sensitivities for abdominal (61%) and pelvic lesions (90%). No false positive results were noted.

Quadrantectomy versus lumpectomy for small size breast cancer.

Between 1985 and 1987 quadrantectomy plus external radiotherapy and lumpectomy plus external and interstitial radiotherapy were compared in a randomized trial of patients with small carcinomas of the breast. Quadrantectomy involves excision of 2-3 cm of normal tissue around the tumour plus the removal of a sufficiently large portion of overlying skin and underlying fascia whilst lumpectomy removes only the tumour mass with a narrow margin of normal tissue. Patients in both groups also received total axillary dissection. 705 cases were evaluable, 360 quadrantectomies and 345 lumpectomies. No differences in distant metastases and survival were observed in the two groups. However, lumpectomy patients had a much higher frequency of local recurrences (7.0 vs. 2.2%). Since a local recurrence needs a second operation and creates severe psychological distress to the patient, conservative surgical procedures should include generous excision of normal tissue around the primary carcinoma plus intensive postoperative radiotherapy.

Pelvic and para-aortic lymphadenectomy in cancer of the ovary.

The role of the lymphadenectomy in ovarian carcinoma is widely discussed. The natural history of disease, its tendency to spread to peritoneal cavity and the lack of any reported series of careful node dissections undertaken during surgical exploration has made it difficult to establish the real significance of nodal metastatization and the optimal therapeutic approach for patients with positive nodes. At the Istituto Nazionale Tumori, Milan, 341 patients with ovarian carcinoma have been subjected to lymph node dissection. In 253 cases in which lymphadenectomy has been carried out during first surgery, the lymphonodal diffusion has been evaluated by stage, grading and histology. The incidence of lymphonodal metastases increased with the diffusion of the primitive tumour and this is particularly evident for the serous adenocarcinoma. From our data (as shown in our series of 173 cases Stage III with peritoneal and retroperitoneal diffusion) the lymphonodal involvement has to be considered as a negative prognostic factor, influencing survival in a statistically significant way. In the 88 patients subjected to radical lymphadenectomy during second-look surgery, after chemotherapy, a smaller percentage of positive nodes was observed as compared to untreated cases but, on the other hand, we documented a portion of positive nodes not sterilized by sistemic therapy. All this data confirm the necessity to perform radical lymphadenectomy not only as a staging procedure (because of low sensitivity of lymphangiography) but also as a therapeutic one for some patients.

[Sequelae of radiosurgical treatment in patients having undergone Wertheim radical hysterectomy]. / Sulle sequele del trattamento radiochirurgico nelle pazienti operate di isterectomia radicale alla Wertheim.

The sequelae from therapeutic treatment in a series of 361 patients subjected to Wertheim's hysterectomy, 125 of whom had a lumbo-aortic lymphadenectomy, have been studied. All these patients underwent postoperative external beam irradiation and intracavitary radium or caesium. Twenty-six cases of functional vesical disturbance, 12 of iliac lymphocele, 24 of parametritis, 4 of bladder vaginal fistula, 35 of ureteral fistula, 16 of ureteral fibrosis, 6 of lymphedema of the lower limbs and 1 of rectal ulcer were found. In some types of sequelae, the most important cause was surgery, with greater evidence if the operation was more extensive. For other types of sequelae the most important cause was radiotherapy for dystrophy and fibrosis of the irradiated tissues, leading to occlusion of lymphatic vessels, and intestinal and ureteral fibrosis. Recovery was easier with better results if the causes of sequelae were prevalently from surgery. The clinical findings were later and recovery more difficult if the causes were prevalently from radiotherapy.

Changes in receptor status after treatment with tamoxifen in endometrial cancer.

Estrogen (ER) and progesterone receptor (PgR) status was determined in 41 women with operable endometrial cancer before and after administration of tamoxifen (TAM). The first sample was obtained by hysteroscopy to ensure a precise biopsy of neoplastic tissue; the second was done on the surgical specimen. PgR content was significantly increased after TAM treatment and this data was compared with the degree of tumor differentiation.

Immunohistochemical study of ten cases of argyrophilic carcinoma (carcinoid) of the breast.

The significance of argyrophilia in human breast cancer is still a controversial issue. We tested immunohistochemically 10 cases of argyrophilic carcinomas of the breast and found evidence of immunoreactivity with neuroendocrine markers: chromogranin, NSE, gastrin, insulin and bombesin. Argyrophilia was demonstrated in breast cancers of the usual types and was found to be related to the secretory activity of neoplastic cells. Unfortunately, no adequate follow-up data are available to clarify the natural history of argyrophilic breast cancer. A clinical treatment different from that of conventional breast cancer is not at present justified.

Usefulness and potential pitfalls of sialic acid determination in sera of patients with ovarian tumors.

Increasing evidence in the literature indicates that serum sialic acid is increased in cancer patients suggesting a possible usefulness of its determination as a tumor marker. However there are many discrepancies in the data reported, probably due to methodological errors, mainly in lipid bound sialic measurement. In this paper we illustrate the results obtained when we applied a method worked out in our laboratory for the determination of total and fractionated sialic acid (lipid and protein bound) to the analysis of sera from patients with ovarian tumors and the preliminary data on the follow up of selected cases. The potential pitfalls in using this relatively new tumor marker will be critically evaluated.