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Objective: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC)., Methods: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC)., Results: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%)., Conclusions: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause., (Copyright © 2016. Published by Elsevier Inc.)

Objective: The aim of this review was to analyze the state of the art about HE4 and follow-up in patients treated for ovarian cancer., Methods: A literature search was conducted in the MEDLINE database using the key words "HE4" and "ovarian cancer" and "recurrence" or "relapse" or "follow up.", Results: Seven of 28 clinical studies were selected. Four studies were prospective, and all of them were based on a small number of patients (8-73 women). A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis, thus suggesting the need of a closer follow-up. Moreover, HE4 showed better sensibility and specificity in the diagnosis of ovarian cancer recurrence with respect to CA-125, being also an earlier indicator of the relapse with a lead time of 5 to 8 months. HE4 showed a better performance in this setting if performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an independent predictive factor for the surgical outcome at secondary cytoreductive surgery and to maintain its prognostic role even after the recurrence., Conclusions: These preliminary data start to suggest a superiority of HE4 over CA-125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role of HE4 could help clinicians to personalize the follow-up program, whereas its predictive role could be useful to plan the treatment of the relapse. The role of HE4 in ovarian cancer follow-up deserves to be further investigated in prospective randomized multicentric studies.

Background: Human epididymis protein 4 (HE4), kallikrein 6 (KLK6), osteopontin (OPN) and soluble mesothelin-related peptide (SMRP) are new promising biomarkers that could integrate CA125 in epithelial ovarian cancer (EOC) diagnosis. The autoantibody response to tumor antigens is a potential tool for improving the diagnostic performances of biomarkers. The aim of this study was to assess the diagnostic potential of these biomarkers in the form of free markers and immunocomplexed with immunoglobulin M (IgM). Moreover, we analyzed the association between these markers and clinico-pathological characteristics of EOC patients., Methods: Serum and plasma samples of 60 healthy controls, 60 ovarian benign cysts, 60 endometriosis and 60 EOCs, collected before any treatment, were tested for CICs and free antigens by immunoassays., Results: Immunocomplexes were characterized by poor sensitivity and specificity, since they allowed the detection only of a small number of EOC patients and were increased in patients with benign gynecological pathologies. However, the markers in the form of free antigens showed good diagnostic performances. Of note, CA125 and HE4 showed high sensitivity in the detection of the malignancy and HE4 emerged as a useful biomarker in differential diagnosis between EOC and endometriosis. Finally, elevated KLK6 and OPN, were associated with advanced FIGO stage, high grade disease, suboptimally debulked tumor and ascites., Conclusions: This study confirms the diagnostic role of CA125, HE4, KLK6, OPN and SMRP, and for the first time showed that CA125, HE4, KLK6, OPN and SMRP immunocomplexed with IgM are not a potential tool for EOC diagnosis.

Objectives: Bowel obstruction is a relatively common event (30-40%) in advanced or recurrent ovarian cancer patients. No definitive data are available on the optimal management of this serious complication and treatment is generally limited to adoption of palliative measures. These modalities include both surgical and medical procedures. The aim of this study was to define selection criteria for subjects who would benefit from palliative surgery., Study Design: Out of 270 epithelial ovarian cancer patients treated in the period 1984-2005, 75 (28%) developed bowel obstruction related to progression/recurrence of the disease. Palliative treatment - both medical and surgical - was applied on an individual basis. A new score developed by these authors was retrospectivelly applied to this group of patients with the aim of defining a subgroup that could benefit from surgical treatment., Results: Fifty cases (66.7%) were medically treated whereas 25 patients (33.3%) underwent surgery. Mean and median survival rates were 34 and 28 weeks in the surgical group versus 12 and four weeks in the medical group. Distribution according to score showed 53 cases (71%) in the low score group (< 14) and 22 (29%) in the high score group (> 14). A significantly better survival was observed in the low-score group (p < 0.0001) and in the surgically treated patients (p < 0.001). According to the risk score variables patients treated surgically for obstruction with low scores had a longer survival (p < 0.005) compared to medical treatment but this difference was not found in the high-risk group (p < 0.05)., Conclusions: The prognosis of patients with bowel obstruction in relation to advanced ovarian cancer is best determined by comprehensive assessment of all prognostic parameters to define a subgroup of patients in a low-risk group that may benefit from surgical treatment.

The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols.Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P < 0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and treatment at recurrence (P < 0.0001), and survival after recurrence was related to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P < 0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at recurrence had no prognostic relevance. Cox proportional hazards model showed that residual disease and time to recurrence were the only independent prognostic variables for both survival from initial diagnosis (P < 0.0001) and survival after recurrence (P < 0.0001). In conclusion, there was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.

This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2-IB-IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (45 years: P = 0.0079), FIGO stage (IB1-IIA 4 cm: P = 0.0133), histology (squamous vs nonsquamous, P = 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P = 0.0001), lymphvascular space involvement (present vs absent, P = 0.0007), lymph node status (positive vs negative, P = 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P = 0.0119), FIGO stage (P = 0.011), histology (P = 0.001), and unaffected peripheral stromal thickness (<3 mm: P = 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.

Epithelial ovarian cancer is the leading cause of death from gynecological cancer in the Western countries. Approximately 20%-30% of patients with early-stage disease and 50%-75% of those with advanced disease who obtain a complete response following first-line chemotherapy will ultimately develop recurrent disease, which more frequently involves the pelvis and abdomen. Few formal guidelines exist regarding the surveillance of these patients, and there is no agreement in the literature about the type and timing of examinations to perform. Moreover, the objective of follow-up is unclear as recurrent epithelial ovarian cancer continues to be a therapeutic dilemma and quite all the relapsed patients will eventually die of their disease. The follow-up of asymptomatic patients generally include complete clinical history, serum cancer antigen (CA)125 assay, physical examination, and often ultrasound examination, whereas additional radiologic imaging techniques are usually performed when symptoms or signs appear. (18)Fluoro-2-deoxy-glucose ((18)FDG)-positron emission tomography (PET) has a sensitivity of 90% and a specificity of 85% approximately for the detection of recurrent disease, and this examination appears to be particularly useful for the diagnosis of recurrence when CA125 levels are rising and conventional imaging is inconclusive or negative. Recently, technologic advances have led to novel combined (18)FDG-PET/computed tomography (CT) devices, which perform contemporaneous acquisition of both (18)FDG-PET and CT images. The role of (18)FDG-PET/CT for the detection of recurrent ovarian cancer is very promising, and this technique may be especially useful for the selection of patients with late recurrent disease who may benefit from secondary cytoreductive surgery.

Objective: A rising number of patients affected by ovarian masses suspected of borderline ovarian tumor are operated on primary laparoscopic procedure., Methods: From January 1992 to June 2004, 113 patients affected by low malignant ovarian tumor were followed at the Gynecologic Departments of five Italian Institutions. Fifty-two (46.0%) patients were operated on laparoscopic surgery, whereas traditional laparotomic approach was preferred in 61 cases (54%). In 53 patients (46.9%), a fertility-sparing surgical treatment was chosen., Results: The diameter of the ovarian cysts ranged between 20 and 300 mm; in 20 out 113 patients (17.7%), the borderline tumor was bilateral. In 22/113 (19.5%) cases, we observed tumor rupture or spilling during surgery, and this incidence was greater in the group of patients treated by laparoscopy compared to laparotomy, and this difference is statistically significative. In 13/113 (11.5%) patients, we observed a relapse; the incidence of relapse, however, is not dependent on the type of surgical approach. The progression-free survival is higher for stages IA-IC if compared to stages more than Ist and the difference is statistically significant. Type of surgical approach, laparoscopic versus laparotomic, does not seem to influence the PFS; when cystectomy is performed, the PFS is significantly lower if compared with demolitive surgery or monolateral annessectomy. Eight pregnancies were obtained: in one case, miscarriage was observed, whereas 7 healthy babies were born all but two by vaginal delivery., Conclusions: Conservative laparoscopic surgery may be the treatment of choice; an attractive option is that this surgery should be performed by an oncologist surgeon to obtain correct surgical staging and better results in terms of both relapse-free survival and pregnancies.

Objective: The aim of our work was to assess the diagnostic accuracy of a scoring system versus subjective assessment of the risk of malignancy of pelvic masses achieved by gynecologist/sonologists in the preoperative triage of a busy gynecology department., Methods: One hundred and eighty-two consecutive patients who underwent surgical removal of ovarian neoplasms were examined. In 39 patients pelvic masses were bilateral. The total number of neoplasms analyzed in this series was 221. Lesions were examined and scored according to the sonographic characteristics. Gynecologist/sonologists also recorded a subjective evaluation of the adnexal masses defining them as "probably benign", and "suspicious/probably malignant". Preoperative ultrasound risk assessment was compared to the final pathologic report and diagnostic accuracy was calculated. CA125 was obtained in all patients and its independent and combined accuracy was calculated., Results: The sensitivity of the scoring system and subjective evaluation was 86% and 95% respectively, specificity was 79% and 91% with a positive predictive value of 41% and 53%. The frequency of positive diagnoses for CA125 was 44% due to the high prevalence of endometrosis in this series (48%). In premenopausal patients (75%) the specificity was 93% and 89% for scoring and subjective evaluation, respectively. The combined use of morphological scoring and CA125 achieved higher specificity and positive predictive values both for the whole series and in premenopausal patients., Conclusions: These results confirmed that the experience of gynecological surgeons with ultrasound skills, outperforms the morphological indexing assessment of ovarian masses. Nonetheless an easy sonographic descriptive scoring system is not significantly lower in accuracy than the expertise achieved by gynecologists with sonographic skills.

Objectives: Although cancer is predominantly a disease of aging, an increasing number of women survive malignancies before or during their reproductive years, which may interfere with their fertility potential. Although a variety of studies have tried to document the impact of conservative treatment aimed at preserving ovarian function and reproductive ability, little information has been available regarding survivors' attitudes, emotions, and choices to have children. The aim of this study is to evaluate the reproductive history, experiences, attitudes, and emotions with regard to having children in conservatively treated patients with Stage I epithelial ovarian cancer, any stage LMP tumors, malignant ovarian germ cell tumors (MOGCTs) and Stage I sex cord-stromal tumors (SCSTs)., Study Design: Between 1986 and 2000, a total of 75 patients with primary malignant ovarian tumors underwent conservative treatment. Out of 75 patients in the study, 14 women (19%) presented Stage I epithelial ovarian cancer, 23 (31%) LMP tumors, 33 (43%) MOGCTs, and five (7%) SCSTs. Information was obtained from medical records and from a questionnaire mailed to all patients who were at least 15 years old at the time of the diagnosis (68 subjects). Median time of follow-up was 102 months (35-192 months). There were four (5.2%) clinical recurrences within 35 months. Only 20 patients (49%) had tried to conceive after the completion of their treatment; of these, 15 women (75%) succeeded and delivered 19 healthy children. Seventy percent (32/41) of the respondents claimed that their disease did not have any impact on their desire to have children. Whereas 51% (21/41) fear that their ovarian disease could have damaged their reproductive potential, 76% (31/41) are not concerned about the effects of the treatment they received on offspring. The impact of the disease on the patients' attitudes toward life was reported as positive., Conclusion: The results from our study, in agreement with the data from the literature, confirm that management of Stage I (grade 1, grade 2) epithelial ovarian cancer, any stage LMP tumors, MOGCTs and Stage I SCSTs with fertility-sparing surgery is a safe, practicable treatment option. Though preliminary, this survey provides insight into the attitudes and experiences of young women ovarian cancer survivors regarding fertility.

Objective: The aim of this retrospective multicenter study was to assess whether the pre-chemotherapy hemoglobin levels have any impact on the clinical outcome of patients with advanced epithelial ovarian cancer who received a first-line taxane/platinum-based regimen., Methods: The study was conducted on 315 patients who underwent initial surgery followed by taxane/platinum-based chemotherapy for FIGO stage IIc-IV epithelial ovarian cancer. All the patients had ECOG performance status 0-1 at presentation. The median follow-up of survivors was 36 months (range, 6-120 months)., Results: The 25%, 50%, and 75% quantiles of hemoglobin levels before starting first-line chemotherapy were 10.2, 11.4, and 12.3 g/dl, respectively. Residual disease after initial surgery (>1 cm versus 12.3 g/dl) were inversely related to overall survival at univariate (P = 0.03) but not at multivariate analysis., Conclusions: This investigation showed that hemoglobin levels before starting first-line taxane/platinum-based chemotherapy are not an independent prognostic factor for overall survival in patients with advanced epithelial ovarian cancer.

Purpose: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients., Patients and Methods: The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months)., Results: The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days., Conclusion: The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.

A comprehensive review of the literature and the authors' personal experience on serum determination of tumour markers in epithelial ovarian cancer can be summarised as follows: CA 125 is the most reliable marker for monitoring the course of epithelial ovarian cancer; CA 125 assay is not an adequate screening test for this malignancy but it can represent an useful adjunct to clinical examination and ultrasound in the differential diagnosis of ovarian masses in postmenopausal women; Serial measurements of CA 125 are useful in monitoring the response to chemotherapy and follow-up. In patients with preoperative positive CA 125 assay, the concomitant determination of other tumour markers does not add further information when compared to CA 125 alone. Conversely in patients with preoperative negative assay the measurement of one or more of other antigens could be of clinical relevance.

A continuously growing cultured cell line has been obtained in vitro, starting from a specimen of ascites fluid obtained from a patient with ovarian cancer, in whom a poorly-differentiated adenocarcinoma was diagnosed. This cell line, named OC-A1, is routinely grown in standard, serum-supplemented culture medium and has been fully stabilized to long-term growth and characterized for both cultural and genetic parameters. OC-A1 cells express a set of characteristics, as determined in vitro which, when compared with the in vivo primary tumor, confirm the high malignity of this cancer. In addition, karyotype analysis showed a translocation of chromosome 8 which is correlated with the amplification of c-myc oncogene. However, the expression of this oncogene was found to be significantly inhibited by a new regulatory activity, recently found to be present in a liposarcoma cell line. Conditioned medium from these cells was indeed able to inhibit the growth of OC-A1 cells, arresting their cell cycle in the G1 phase and inducing them to apoptosis. Finally, the cell programmed death appeared to be related to the expression of antioncogene p53.

This multicenter retrospective study is based on 192 patients with advanced ovarian cancer in pathological complete response at second-look surgery. Ninety-four (48.9%) patients developed recurrent disease after a median time of 18 months (range, 4-89 months) from surgical reassessment. The recurrence involved the pelvis in 45 (47.9%) cases, the abdomen in 42 (44.7%), the retroperitoneal lymph nodes in 13 (13.8%), and distant sites in 20 (21.2%). On the whole series, 5- and 7-year disease-free survival rates after negative second-look were 47.4 and 44.5%, respectively. By log-rank test the disease-free survival rate was related to FIGO stage (P = 0.008), tumor grade (P = 0.0021), size of residual disease after initial surgery (P = 0.0038), and type of second-look (laparoscopy vs laparotomy, P = 0.0061), but not to histological type and first-line chemotherapy. Cox proportional hazard model showed that tumor grade, size of residual disease, and type of second-look were independent prognostic variables for disease-free survival. The risk ratio of relapse was 2.386 (95% CI, 1.140-4.990) for grade 2 and 3.118 (95% CI, 1.515-6.416) for grade 3 compared to grade 1 disease. For patients with residual disease 1-2 cm and > 2 cm the risk ratio was, respectively, 1.877 (95% CI, 1.117-3.156) and 2.156 (95% CI, 1.324-3.511) compared to patients with residual disease < 1 cm. The risk ratio was 1.826 (95% CI, 1.121-2.973) for patients who were submitted to a laparoscopic second-look compared to those who underwent a laparotomic reassessment. Poorly differentiated grade and large residual disease after initial surgery are the strongest prognostic variables for recurrence after a negative second-look.

This retrospective study assessed 46 patients with advanced ovarian cancer who had elevated preoperative serum CA 125 (>35 U/ml) and who had another serum CA 125 assay 6-9 days after surgery. Preoperative CA 125 levels were similar in patients with residual disease below 20 mm and in those with larger residuum. The postoperative decline of serum CA 125 was significantly higher in patients with small residual disease at any preoperative serum CA 125 value. By taking 60% as the cutoff of CA 125 decline, the diagnostic accuracy of this parameter in discriminating between patients with residual disease below or above 20 mm improved progressively when we considered patients with increasing preoperative antigen values. However, even in the subset of patients with preoperative serum CA 125 above 400 U/ml, 2 of the 20 patients with less than 20 mm residual disease had a percentage reduction of antigen levels lower than 60%, whereas 5 of the 10 patients with larger than 20 mm residuum had a CA 125 decline higher than 60%. Therefore, we believe that the perioperative changes of CA 125 levels have a limited clinical relevance in the management of patients with ovarian cancer.

This retrospective multicentric study assessed the prognostic value of the serum CA 125 assay and the common clinicopathological variables in 225 patients with advanced epithelial ovarian cancer. All of these patients had serum CA 125 > or = 35 U/ml before the first cycle of chemotherapy and had had serial antigen determinations during early chemotherapy. By univariate analysis pathological complete response rate was significantly related to stage, size of residual disease after first surgery, serum CA 125 before the first cycle and before the third cycle of chemotherapy, and serum CA 125 half-life. Multiple logistic regression showed that residual disease (P = 0.002), serum CA 125 half-life (P = 0.004), serum CA 125 before the third cycle (P = 0.004), and serum CA 125 before the first cycle (P = 0.03) retained a significant value in predicting second-look findings. By log-rank test survival was significantly related to stage, residual disease, tumor grade, serum CA 125 before the third cycle, and serum CA 125 half-life. Cox proportional hazard model showed that residual disease (P = 0.0001), serum CA 125 half-life (P = 0.007), and tumor grade (P = 0.01) retained a significant value in predicting survival. In conclusion, serum CA 125 half-life during early chemotherapy was an independent prognostic factor for both the achievement of a pathological complete response and the survival of patients with advanced epithelial ovarian cancer.

In the present work the Authors analyse the role and significance of second-look laparotomy in the management of epithelial ovarian cancer. Eighty-three patients with advanced epithelial ovarian cancer (stage III-IV) followed at the Institutes of Gynecology of Padua and Pisa Universities underwent a negative second-look at a median time of 6 months after first surgery. The incidence of relapse after the negative second-look was 45.8% and the mean time of relapse was 27.4 months. Advanced surgical-pathological stage, the presence of residual disease > 2 cm and serous histotype are risk factors for relapse after a negative second-look. These data confirm that, because of its poor prognostic value, a negative second-look laparotomy should not influence the choice of second line chemotherapy and, consequently is no longer routinely performed in our Institutes.

A complete review of case series from 1963 to 1990 allows some considerations and conclusions on the clinical management of epithelial ovarian cancer. In the aim of early diagnosis, the ovarian condition must be evaluated also by ultrasound scans, in every woman, at every gynaecological control, and every ovarian or pelvic mass must be carefully examined and removed. Staging is generally recognized as reliable only by surgical pathological evaluation, (SPS) as in post-surgical FIGO staging. Therapy is based on adequate chemosurgical strategy. Surgery, performed in maximum effort, must aim at radicality or adequate debulking, avoiding, however too heavy mutilations, almost always useless for prognosis. Lymphadenectomy, in advanced cases, should be selectively and not systematically performed. Cyclophosphamide and Cis-Platinum appear to be, today too, the most effective regimens as first line chemotherapy. Neoadjuvant chemotherapy must still be well evaluated in its cost-benefit balance and personalized in particular cases. Second laparotomic look must be personalized in respect to residual disease after primary surgery and tumoral aggressiveness factors.

Surgical re-examination after first line surgery followed by chemotherapy is an absolutely necessary step in the course of integrated treatment of advanced ovarian epithelial tumours. Our personal experience of surgical re-staging and reductive surgery in 48 patients affected by ovarian tumours stage III and IV (FIGO), by laparotomic second look is reported. Repeated surgery succeeds in further reducing the neoplastic deposits or radicalizing the first intervention in 33% of the overall series; in 52% of the cases, the second look was negative for neoplasia; in 16% only, despite tumour finding no reductive surgery was possible. If only the cases presenting residual neoplasia after primary surgery are taken into account, tumour debulking was possible in 44% of the patients. The analysis of this series fully confirms the preliminary statement that the smaller the residual neoplasia after surgery, the greater the chances of success for chemotherapy in ovarian cancer. It confirms as well that the laparotomic second look is the only currently available way to usefully assess the full remission of the disease.

From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.

This study evaluates the possible use of computed tomography not as an alternative diagnostic method but, rather, as a supplement to laparotomy in patients treated for ovarian cancer. The following conclusions can be drawn: in patients presenting no clinical evidence of persistent or relapsing disease C.T. Scan is not a mandatory but, rather, an optional test since it entails 25% false negatives, a 66.6% predictive value and because the involved patients will need, in any case, a further intervention. Conversely, C.T. Scan is clearly indicated in patients presenting clinical evidence of disease. It can prove helpful in detecting metastases in areas that prove difficult to be clinically examined; in assessing whether the retroperitoneal areas conceal neoplastic tissue or in planning the right operation for masses that have been palpated only before chemotherapy, and then in regression. When, despite chemotherapy, tumour progresses, surgery may became useless, and the C.T. Scan may therefore prove helpful in defining the condition and guiding non surgical treatment. Therefore, in the follow up of ovarian cancer the C.T. Scan may be performed on the basis of clinical course, instead than on a rigid aprioristic planning.

The Authors refer their own experience on a planned prospective study of integrated chemosurgical treatment in advanced epithelial ovarian cancer. Repetitive surgery interspersed with non cross resistant schedules of chemotherapy can achieve more than 60% of complete responses with an expected five years survival rate dependent on the residual disease after primary and especially second operation. In particular residual neoplasia larger than five centimeters after the first laparotomy or larger than two centimeters left behind at second laparotomy constitutes the worst prognostic index.

In a planned prospective study 39 consecutive patients with stage III ovarian cancer have been admitted in two years. All patients have received initial extensive surgery followed on as out patients basis by 5 courses of A-Cy chemotherapy and by a second operation and further non cross resistant chemotherapy with Platinum, Hexamethyl-Melamine, Polymelphalan; 24 have been found pathologically free of disease at second surgery, and 34/39 are clinically free of disease while reporting. These data, exactly collected and evaluated are consistent with our (previously reported) empyrical observation that adjuvant surgery interspersed with courses of aggressive chemotherapy may render free of disease the majority of patients, prolong survival, and possibly cure a portion of this population.

Fifty-four patients were referred to Medical Oncology after operation for "limited" ovarian cancer; 7 were excluded because immediate restaging showed evidence of macroscopic spread to structures outside the true pelvis, and 10 will be considered separately because of microscopic spread shown only by cytology. Thirty-seven patients (31 stage I and 6 stage II) were accordingly accepted as "localized", because peritoneal cytology and diaphragm and omental plus parietal peritoneum histology could rule out the spread to the large abdominal cavity. Some of the referred patients had been operated in nearby hospitals; the Padua GYN Cin. performed 14 of the 37 first surgery operations and 30 of the 37 second look operations. All patients soon after surgery underwent first-line chemotherapy with 5 courses of high dose adriamycin plus cyclophosphamide for 4 months, then surgical second look, and second-line non-cross-resistant chemotherapy for 3 months. During the second look the organ and tissue removal was completed in those 21 patients having received "limited" first surgery. Two patients died within 5 years from admission, so that the overall 5 year actuarial survival from referral is 93% for the entire group with 11 patients still at risk; 87% are disease free 5 years after the second look with 7 at risk. Subdivision of the patients according to "adequate" vs. "limited" first surgery, may select a group (the "adequate" one, composed of 16 patients) completely free from relapses, up to now. The complex therapeutic program described seems to offer long term relapse-free survival to the majority of patients, while the few failures seem closely related with inadequacies of the initial surgical procedure.

Coagulation disorders, including thromboembolic phenomena and disseminated intravascular coagulation are recognised as a complication of neoplastic disease. In the present study the Fibrinogen Degradation Products (F.D.P.) were determined in 26 patients with Advanced Ovarian Cancer (stage III and IV FIGO) (mean = 38.1; S.D. = 37.6) and in ten healthy patients considered as controls (mean = 2.7; S.D. = 13). The significative difference (p less than 0.05) between the two groups points in evidence an increasing activation of Ffibrynolytic processes. The F.D.P. determination has revealed a good correlation (p less than 0.001) with the tumor extension as showed by the difference between third stage with large tumor masses (late) (mean = 44.5; S.D. = 24.5) and third stage with minimal residual disease after reductive surgery (early) (mean = 6.7; S.D. = 5.7).

The Authors have evaluated the diagnostic contribution offered by the serum dosage of the antigen CA-125 in the diagnostics of pelvic masses. This method has been compared with the objective and echographic evaluation, as a noninvasive method of enquiry in the diagnosis of malignant neoplasias of the ovary. The Authors endorse the increase in diagnostic sensitivity brought about by the evaluation of this marker, above all if it is inserted into an integrated diagnosis.