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Introduction/Background To report on performance of hysteroscopic-injection of tracers (ICG and Tc99m) for sentinel-nodes (SLNs) mapping in endometrial cancer. Methodology A single center retrospective evaluation of Prospectively collected data of Consecutive patients with endometrial cancer underwent SLNs mapping following hysteroscopic-peritumoral-injection of tracer. Evaluation of Detection Rate (DR) (overall-bilateral-aortic) and diagnostic-accuracy (A) among the entire cohort and comparison between tracers. Results 231 procedures were performed. Mean age:60 years (28–84); mean BMI:27.3 Kg/m2 (15–47). In 164 cases (70.9%) hysterectomy and mapping procedure were performed laparoscopically. The overall-DR of the technique was 94.1% (208/221) (10 cases excluded: 9 equipment failure; 1 vagal reaction). Bilateral pelvic mapping was found in 62.5% of cases (130/208) and was more frequent in the ICG group (73.8% vs 53.3%; p:0.001). In 47.6% of cases (99/208) SLNs mapped both to pelvic and aortic nodes, and in 5 cases (2.5%) only in the aortic area. In 8 patients (3.8%) SLNs were found in aberrant (parametrial/pre-sacral) areas. Mean number of detected SLNs was 3.7 (1–8). 26 patients (12.5%) had nodal involvement: 12- (46.2%) macrometastases; 6-(23.1%) micrometastases; 8-(30.7%) ITCs. In 6 cases (23.1%) only aortic nodes were positive; in 6 cases (23.1%) both pelvic and aortic nodes and in 14 cases (53.8%) only pelvic area was involved. Three false-negative results were found, all in the Tc99m group. All had isolated aortic metastases. Overall-sensitivity was 88.5% (95% CI: 71.7–100) and overall-negative-predictive-value (NPV) was 98.4% (95% CI 91.8–100). No differences in terms of overall-DR, overall-sensitivity and overall-NPV were found between the two tracers. Conclusion Hysteroscopic-injection of tracer for SLNs mapping in endometrial cancer is as accurate as cervical injection with a higher DR in the aortic area. ICG improves bilateral DR. Disclosure Nothing to disclose.

Objectives About 30% of Epithelial Ovarian Cancer (EOC) patients present with early-stage disease (FIGO stage I–II). However, in spite of the generally favourable prognosis, eEOC have heterogeneous risk of relapse, ranging from 13% to over 40% in various reports. We previously identified 35 miRNAs that predicted risk of progression or relapse in advanced EOC and used them to create a prognostic model, the 35-miRNA-based predictor of Risk of Ovarian Cancer Relapse or progression (MiROvaR). The aim of the current study is to test MiROvaR performance to predict risk of progression or relapse in patients with eEOC. Methods Patients with eEOC who underwent primary surgery at our Institution between 1994 and 2014 were included. The primary endpoint was progression-free survival. In particular, it was assessed the ability of MiROvaR to predict progression-free survival with Kaplan-Meier curves and the log-rank test. Results A total of 80 patients were included in the study with a median follow-up time of 68.2 months (CI: 61.3–80.7). MiROVaR classified 37 patients (46.3%) at high-risk (14 events, median PFS: 117 months, 95%CI: 62-nyr) and 43 patients (53.7%) at low-risk of relapse (2 events, median PFS time: nyr; 95%CI:nyr). Kaplan-Meier curves confirmed the significantly different PFS time (figure 1) for the two groups with HR=10.13 (95%CI: 2.3–4.4, p=0.00015) for the high-risk patients. Conclusions MiROvaR confirmed as a potential predictor of EOC progression and has prognostic value independent of relevant clinical covariates also in patients with eEOC. MiROvaR warrants further investigation for the development of a clinical-grade prognostic assay.

To investigate the safety, feasibility and effectiveness of laparoscopic approach in the management patients undergoing modified radical hysterectomy for early stage cervical cancer.Consecutive data of 157 women who had class II radical hysterectomy, for stage IA2 and stage IB12 cm cervical cancer, were prospectively collected. Data of patients undergoing surgery via laparoscopy (LRH) were compared with those undergoing open surgical operations (RAH). A propensity-matched comparison (1:1) was carried out to minimize as possible selection biases. Post-operative complications were graded per the Clavien-Dindo classification. Five-year survival outcomes were assessed using Kaplan-Meier model.After the exclusion of 37 (23.5%) patients on the basis of propensity-matching, 60 patients undergoing LRH were compared with 60 patients undergoing RAH. No between-group differences in baseline, disease and pathological variables were observed (p0.05). Patients undergoing surgery via laparoscopy experienced longer operative time than patients undergoing RAH; while LRH correlated whit shorter length of hospitalization and lower blood loss in comparison to RAH. Intra- and post-operative complication rate was similar between groups (p = 1.00). The execution of LRH or RAH did not influence site of recurrence (p0.2) as well as survival outcomes, in term of 5-year disease-free (p = 0.29, log-rank test) and overall survivals (p = 0.50, log-rank test).Laparoscopic approach is a safe procedure, upholds the results of RAH, reducing invasiveness of open surgical operations. Further large prospective investigations are warranted.

Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery.

Aims: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/ recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. Patients: Forty EOC patients were studied. Median age was 52.5 years (range: 30e68) and median follow-up 26.1 months (range: 0.3e 117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. Results: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. Conclusion: Our results suggest that CRS þ IPHP merits further evaluation by a formal prospective trial.

Purpose To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy. Patients and Methods Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group. Results The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 μg/m2 were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption. Conclusion Trabectedin administered as a 3-hour infusion at 1,300 μg/m2 is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.

Background. The purpose of the work was to determine the feasibility and accuracy of microlaparoscopy as diagnostic method for the reassessment of ovarian cancer patients. Methods. Eight patients scheduled for second-look laparoscopy who had undergone primary surgery for ovarian cancer followed by 6 cycles of chemotherapy were included in the study. Microlaparoscopy was performed using a 2.8 mm laparoscope followed by conventional 10-mm laparoscopy. Three additional 5-mm ancillary trocars were inserted to perform intra-abdominal biopsies. Pelvic washings were performed in all cases. Results. Microlaparoscopy was feasible in all cases and as accurate as conventional laparoscopy in seven cases. In one case the procedure was terminated before conventional laparoscopy because of positive biopsies at frozen section examination. There were no intra-operative complications related to microlaparoscopy. The median time from skin incision to the removal of the microlaparoscope was 47 minutes (range 30-70). Conclusi...

PURPOSE To compare the efficacy of a treatment with cisplatin plus cyclophosphamide given for 5 months and a short treatment with cisplatin alone in advanced ovarian cancer, we conducted a multicenter randomized clinical trial. PATIENTS AND METHODS Eligibility criteria were as follows: first diagnosis of histologically confirmed invasive epithelial ovarian cancer of International Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2 plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS A total of 607 women were entered onto the study. There was no difference in the response to treatment. Pathologic complete response (CR) was documented in 63 of the weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi 1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and 148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms, respectively. Survival curves were similar in the two groups, with a 3-year percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) = 0.004; P = .96). CONCLUSION This study found that 2-month monochemotherapy treatment with cisplatin was as effective as 5-month polychemotherapy including cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

Objective The therapeutic outcomes of patients with advanced vulvar cancer are poor. Multi-modality treatments including concurrent chemoradiation or different regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to reduce the extent of surgery and morbidity. The present single-institution trial aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in locally advanced vulvar cancer. Methods From 2002 to 2009, 10 patients with stage III-IV locally advanced squamous cell carcinoma of the vulva were prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy. Results The clinical response rate of all enrolled patients was 80%, whereas the pathological responses included 1 case with complete remission, 2 with persistent carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than 50%. Four patients had positive nodes. Forty percent of patients experienced grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte-colony stimulating factor, even in cases of elderly patients. Median progression-free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7 recurrent cases were local, and 3 of them were treated with salvage surgery while the other 3 received radiation with or without chemotherapy. After a median follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients remained alive with no evidence of disease, including 2 long-term survivors after recurrence at 5 and 9 years. Conclusion Based on the high response rate and manageable toxicity, NACT with paclitaxel and cisplatin with or without ifosfamide followed by surgery could be considered as a therapeutic option for locally advanced vulvar cancer.

Intestinal obstruction is a common and distressing clinical complication in ovarian cancer. The aim of our study was to assess vomit control in terminal ovarian cancer patients with inoperable gastrointestinal obstruction, using a symptomatic pharmacological treatment with octreotide which obviates the need for nasogastric tube placement. We studied 13 patients, all of whom had advanced ovarian cancer FIGO stage IIIc. Seven patients were treated in the Gynecology Department of S. Raffaele Hospital, at the University of Milan, and 6 were managed in the University of Varese Hospital. Octreotide was administered at doses starting with 0.3 up to 0.6 mg (mean 0.44 mg) a day by subcutaneous bolus or continuous infusion. Octreotide controlled vomiting in all cases to grade 0 on the WHO emesis scale. Complete relief of symptoms was achieved within 3.07 days (range 1-6 days). Vomiting stopped within 2-3 days of starting treatment in most patients. In 8 patients with a nasogastric tube, drainage decreased from 2000 to under 100 ml/day after the start of octreotide treatment. No side effects were reported. All patients died with minimal distress or pain.

BACKGROUND The purpose of the study was to analyze the determinants of long term survival in women with advanced ovarian cancer and negative second-look laparotomy. METHODS A series of 140 advanced (Stage III-IV) ovarian cancer patients (median age, 54 years; range, 22-74 years) with negative second-look laparotomy after primary surgery and chemotherapy is included in the analysis. At first diagnosis, all patients were treated with radical or debulking surgery. After primary surgery, the patients were treated with a chemotherapy regimen based on cisplatin or carboplatin alone or in combination with other drugs. All second-look laparotomies were performed 6-8 months after first surgery. RESULTS The overall survival rates were 76% at 3 years, 66% at 5 years, and 51% at 8 years. The corresponding rates for disease free survival were 57, 50, and 43%, respectively. Survival rates were better for women with a residual tumor 1 cm or less after primary surgery. The 5-year probability of survival was 78% in this group, compared with 55% in women with a residual tumor more than 1 cm (log rank test, P < 0.05). Survival rates for women with tumor Grade 3 tended to be worse than Grades 1-2, but the difference was only of borderline statistical significance. No relationship emerged between survival and age, histotype, and presence of ascites at diagnosis. Women with a residual tumor 1 cm or less and positive lymph nodes had a 66% 5-year probability of survival, compared with 85% for women with a residual tumor 1 cm or less and negative lymph nodes. This difference was significant (log rank test, P = 0.05). The 5-year survival probabilities were 47 and 58%, respectively, in women with a residual tumor more than 1 cm and positive or negative lymph nodes. CONCLUSIONS This analysis shows a favorable long term survival rate for women with advanced ovarian cancer and complete pathologic response after debulking surgery and postoperative chemotherapy. It further suggests that lymph nodal status is a prognostic factor for women with minimal residual tumor after surgery.

Summary Background From 1983 to 1990, 271 consecutive patients with stage I ovarian cancer entered two randomised trials, aimed at assessing the role of adjuvant chemotherapy after radical surgery in early stages of ovarian cancer.Trial I compared cisplatin (50 mg/m2 with repeated courses every 28 days for 6 cycles) to no further therapy in F.I.G.O.stage la & b Grade U-IH patients; trial II compared cisplatin (same dose and schedule) to 32P in Ian & bii and Ic patients Methods Both studies were multicentric and centrally randomized. Treatment was allocated by phone and stratified by center. All patients satisfying major eligibility criteria (histological diagnosis of ovarian carcinoma, correct F.I.G.O. stage and grade, no previous neoplasms) were analysed according to treatment allocated by randomisation. Results With a median observation time of 16 months, cisplatin significantly reduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14–0.89, p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI = 0.19–0.77, p = 0.007; Cox Model) in trial II. Survival was not significantly different (trial I – Kaplan-Meier overall 5-year survival: cisplatin = 88%, control = 82%, HR = 1.15; 95% CI = 0.44 – 2.98; p = 0.773; Cox Model); trial II – overall 5-year survival: cisplatin = 81%, 32P = 79%, HR = 0.72; 95% CI = 0.37–1.43; p = 0.354; Cox model). In both studies the risk of dying after relapse increased for patients originally randomized to the cisplatin arms: in trial I, 6 of 7 patients in the cisplatin relapsed arm and died of tumor compared with 8 of 14 patients in the control arm. In trial II, 11 of 12 patients on cisplatin, and 18 of 26 on 32P succumbed to tumor recurrence. Conclusion Adjuvant cisplatin treatment in early ovarian cancer significantly prevents relapse in comparison to 32P in Stage IC patients or to no immediate treatment in earlier Stage women. The impact of cisplatin adjuvant treatment on survival remains, however, unclear.

Fifty-eight previously untreated patients with gynecological cancer, assigned to cisplatin-based chemotherapy (40-80 mg/m2), received the following antiemetic treatment: day 0, oral ondansetron 8 mg 3 times/day + intravenous dexamethasone 16 mg; days 1-7, oral ondansetron 8 mg twice/day. In cycle 1 complete or major control (0-2 emetic episodes) was achieved in 94.6% of the patients in the acute phase (day 0) and in 89.2% in the delayed phase (day 1-7). In the subgroup receiving cisplatin > or = 75 mg/m2 the effect on acute and delayed emesis decreased significantly with subsequent courses. Reversible side effects were observed in 8.9% of the cases. Oral ondansetron was efficacious, well tolerated and is worth testing further in randomized trials with intravenous therapy.

Objectives The aim of this phase II multicentric study was to evaluate the efficacy and toxicity of neo-adjuvant chemotherapy with weekly topotecan and cisplatin in locally-advanced squamous cervical cancer. Patients and methods From November 2008 to January 2011, 92 patients met the inclusion criteria and were enrolled. Eligibility criteria were: squamous or adenosquamous cervical cancer; clinical stages IB2, IIA, IIB; Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)⩽2; neutrophils⩾1500/μL; platelets⩾100,000/μL, normal renal and liver function. Treatment consisted of six courses of weekly topotecan (2mg/m 2 ) and cisplatin (40mg/m 2 ). All responsive and stable patients were submitted to radical surgery, while progressed cases underwent definitive radiotherapy±chemotherapy. Primary end-point was evaluation of efficacy and toxicity. All patients are evaluable for toxicity and efficacy. Results Ninety-six percent of patients completed the six planned courses of chemotherapy, and 95% of courses were administered at a full dose and without interruption or delay. Mean age was 49years (35–64years). FIGO Stage distribution was 30 IB2, 13 IIA and 49 IIB. Treatment was well tolerated and no death occurred. G3–G4 haematological toxicity was observed in 28% of patients (5% out of cycles). Support therapies (blood transfusions and/or erythropoietin and/or Granocyte-Colony Stimulating Factor) were given to 24% of patients. Clinical response rate was 77%. The nine progressed cases were irradiated, while the remaining 83 patients were submitted to radical surgery. An overall pathologic response was observed in 67% of patients, with an optimal response rate of 32% and a disease downstage in 57% of patients. Nodal metastases occurred in 36% of patients. Adjuvant therapy (radiotherapy and or chemotherapy) was prescribed in 55% of patients, because of lymph node metastases, parametrial or vaginal involvement or cut-through margins. Median follow-up was 18months: 76% of patients are alive and free from recurrence, 24% of patients relapsed and 13% died. Conclusions Weekly topotecan and cisplatin showed an acceptable toxicity profile; the promising response rate warrants further investigation.

Response to a second-line weekly cisplatin chemotherapy in ovarian cancer previously treated with cisplatin- or carboplatin-based regimens was analysed in a clinical series observed between 1984 and 1991. Women who achieved pathological complete response or pathological optimal partial remission after first-line cisplatin- or carboplatin-based regimens were treated at recurrence or progression, occurring at least 4 months after first-line treatment, with second-line chemotherapy. A total of 72 women were included in the analysis. Second-line chemotherapy regimens were: cisplatin 1 mg/kg weekly for seven courses plus epirubicin 70 mg/m2 intravenously (i.v.) every 3 weeks for three courses (28 subjects), cisplatin 1 mg/kg plus etoposide 90 mg/m2 i.v. weekly for a total of seven courses (11 subjects) and cisplatin 1 mg/kg weekly for nine courses plus carboplatin 250 mg/m2 every 3 weeks for three courses (33 subjects). Of the 72 women, 22 (31%, 14 clinical, 8 pathological) had a complete response and 28 (39%), a partial response (24 clinical, 4 pathological). The 24-month cumulative survival probability was 63% in women with complete response, 32% in those who had partial response, but all the 22 non-responders died within 24 months from diagnosis of recurrence (log rank test P0.05). The frequency of complete response and partial response increased with the interval between first diagnosis and recurrence: among the 33 women who had recurrent disease to18 months from first diagnosis, complete response or partial response was obtained in 20 (61%) subjects, this figure was 67% (14 out of 21 women) among subjects who had recurrent disease between 18 and36 months from first diagnosis and 89% (16/18) among those who had recurrenceor = 36 months. In comparison with women who had recurrence 4-18 months from first diagnosis, the OR of response was 1.3 (95% CI 0.4-4.1) for those who had recurrence between 18 and36 and 5.2 (95% CI 1.1-24.3) for those who had recurrenceor = 36 months from surgery (chi 1(2) trend p0.05). Survival rate after the end of second line chemotherapy for women who relapsed 4-18 months, 18-36 or 36 months or more after surgery were, respectively, 24, 20 and 67% (log rank test, P0.05). Age at first diagnosis, histology, stage, and grading of the disease at first diagnosis and site of recurrence were not associated with response to second-line therapy.

Objective To analyze local recurrence rate (LRR), morbidities and oncologic outcome of class III nerve-sparing radical hysterectomy. Patients and methods 170 consecutive class III NSRH cases were performed. Nineteen patients were addressed directly to surgery whilst neoadjuvant chemotherapy was administered in 151 patients. The majority of patients had SCC (75%). The median follow-up was 31months. Results The mean age was 50 [27–78] years. Mean post-operative hospital stay was 7 [3–16] days. 2 intraoperative complications occurred. Operating time and blood loss was similar to the state-of-the-art of conventional radical hysterectomy. Overall G3-4 complication rate was 8.2 % (14/170). Early G3-4 complication rate was 3.5% (6/170). Late G3-4 complication rate was: 4.7%. (8/170). Positive pelvic nodes were noted in 31 patients (18.2%). Vagina and parametrial involvement were present in 38 (22%) and 27 (15.8%) patients, respectively. LRR was 10% (17/170). The sites of relapse were: 12 pelvic, 5 vaginal. There were 9 patients DOD. The 2-year and 5-year DFS rates were 89% and 81%, respectively. Univariate and multivariate analysis identified vagina involvement and postoperative treatment as significant prognostic factors. Conclusions The oncologic results of NSRH were similar to the state-of-the-art of conventional radical hysterectomy. Two years DFS in relation to FIGO stage of disease was 92.3, 89.2 and 86.1 % respectively for IB1, IB2, IIB comparable to literature data. The early and late complications rate related to autonomic injury was significantly lower. The nerve-sparing technique should be considered in all cervical cancer patients addressed to surgery.

Background: To compare quality of life and bladder, intestinal, and sexual dysfunctions in 2 groups of patients undergoing different types of radical hysterectomies (RHs). Methods: Patients with cervical cancer who underwent RH have been enrolled in a questionnaire-based study. Quality of life (QoL) and bladder, intestinal, and sexual dysfunctions were evaluated with the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx). Patients were grouped according to the type of RH: group 1, class II RH and group 2, class III nerve-sparing RH (NSRH). Results: Of 157 women included in the study, 127 filled out the questionnaire. Overall, QoL score assessed with the FACT questionnaire did not differ significantly between the 2 groups. The FACT subscales assessing physical, functional, emotional, and social well-being did not differ significantly between the 2 groups, whereas the FACT-Cx subscales assessing disease-related symptoms in group 2 patients showed a significantly worse score (72 vs 66; P = 0.03). Evaluating singularly the 15 items of the Cx subscales assessing disease-related symptoms, we did not find any significant difference between the 2 groups, but only Cx1 ("I am bothered by discharge or bleeding from my vagina") was significantly worse in group 2 patients. At univariate analysis, we found that NSRH and adjuvant radiotherapy (RT) impact negatively on the FACT-Cx subscales regarding pelvic visceral function. However, at multivariate analysis, only adjuvant RT impact negatively. Conclusions: Patients submitted to class III NSRH did not present worse QoL and pelvic visceral dysfunctions when compared with class II RH. The RT seems to be a factor impacting negatively on bladder and sexual function.

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.

Objectives This paper reviews the evolution of concepts concerning the nerve-sparing radical hysterectomy (NSRH) in cervical cancer. Methods Research studies published between 1991 and 2006 were reviewed. Results Significant progress has been made in understanding the neuroanatomy and the neurophysiology of autonomic pelvic plexus. The ideal surgical management of cervical cancer patients should be tailored on the basis of prognostic factors and quality of life. Within the discussion concerning the optimal level of radicality of hysterectomy, which is still controversial, the new concept of NSRH has to be considered in order to reduce morbidity without compromising the oncological disease control. Surgical strategies have been developed to spare the autonomic functions with promising results. Conclusions To date, there is a growing body of data about NSRH in cervical cancer. However, there is not yet a consensus concerning to which part of uterine support ligaments a NS approach should be directed.

Objectives According to our previous experience, Type III Nerve-sparing Radical hysterectomy (NSRH) for cervical cancer presented an acceptable urologic morbidity, without compromising radicality. The aim of this study was to compare Type NSRH with other types of RH in terms of incidence of early bladder dysfunctions and perioperative complications. Methods One hundred and ten patients with cervical cancer were submitted to Type II RH (group 1), Type III NSRH (group 2) and Type III RH (group 3). We assessed the postoperative early bladder function and complications. The follow-up period was 3 months. Results Group 1 had a significantly shorter duration of the surgery, minor mean blood loss and shorter mean length of postoperative stay when compared to groups 2 and 3. No intraoperative complications were reported in either of the groups. The groups did not differ significantly in terms of GIII/IV morbidity (group 1 = 10%, group 2 = 10% and group 3 = 15%, χ 2 , P value: 0.65). Not even they differed in terms of urologic GI–IV morbidity (group 1 = 13%, group 2 = 15% and group 3 = 10%, χ 2 , P value = 0.88). Groups 1 and 2 presented a prompt recover of bladder function, significantly different from that of group 3. There was a significant difference between the groups regarding the number of patients discharged with self-catheterism (group 1 = 0; group 2 and group 3 = 11; χ 2 , P value ≪ 0.05). Conclusions The Type III NSRH seems to be comparable to Type II RH and superior to Type III RH in terms of early bladder dysfunctions.

Quality control of medical performance requires adequate 'state-of-the-art' data and this is currently not uniformly defined for radical hysterectomy. We have used data from a randomised multicentre clinical trial examining the clinical significance of surgical drains following radical hysterectomy (European Organisation for Research and Treatment of Cancer (EORTC)-55962). Although the study was not designed to analyse the quality of the surgical procedure per se, surgical data during and after the operation were carefully noted. A total of 234 patients from 12 European institutes were included in the study. We reported on the clinical and surgical characteristics, the radicality of surgery and short- and long-term complications of radical hysterectomy: median duration of surgery: 240 min; median number of nodes removed: 26; lymph node metastases: 22%; post-operative mortality

Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC.

Summary Background In vitro data demonstrated a dose-response relationship for doxorubicin in ovarian cancer cell lines. However, this dose-response question for anthracyclines has never been adequately addressed in ovarian cancer patients. A phase I study with epirubicin gave support to these in vitro findings and recommended a dose of 150 mg/m2 for phase II testing. Patients and methods The present report concerns the final analysis of an EORTC-Gynecological Cancer Cooperative Group (GCCG) phase II study of high-dose epirubicin (HDE) in cisplatin-pretreated patients with epithelial ovarian cancer. A total of 100 eligible patients were included; 34 had progressed during first-line therapy (group 1), 17 had persistent disease after first-line therapy (group 2) and 49 had relapsed following an initial response to first-line therapy (group 3). All patients had measurable or evaluable disease, were aged 2.0 × 109/1 and platelet nadir count was > 75 × 109/1. Results A total of 361 HDE treatment cycles were administered, the median number per patient being 4. Of the 85 patients who received at least two cycles of protocol treatment, 26 (31%) did not have any dose modification, 23 (26%) had dose reduction, while 36 (43%) had the dose increased to 180 mg/m2 at least for one cycle. The response rate in all eligible patients was 20% (95% confidence interval 13%–30%), 15% in group 1, 12% in group 2 and 27% in group 3. Patients with a cisplatin-free interval of > 12 months responded in 41%. The niedian duration of response was nine months (range 19 weeks to 3 years). Main toxicities were myelosuppression (leucopenia, neutropenia), nausea, vomiting, alopecia and mucositis. There were three cases of excessive toxicity leading to early discontinuation of HDE treatment and in one patient this contributed to death. No serious cardiotoxicity was recorded. Conclusions It is concluded that HDE is active in platinum-pretreated patients with epithelial ovarian cancer and should be further studied in first-line in combination with paclitaxel and a platinum compound.

We present the largest multicenter study evaluating whether intraoperative visual estimation can accurately assess the depth of myometrial invasion in patients with endometrial cancer. The study population consisted of 403 consecutive women who underwent total hysterectomy for endometrial cancer. After the uterus was removed, a visual estimate of depth of gross myometrial invasion was recorded. The uterus was opened, the endometrial cavity was inspected, and one or more full-thickness incisions were made through the tumor, myometrium, and serosa. An intraoperative estimation of gross myometrial invasion was made and classified as more or less than 50% of the uterine wall. Gross visual estimation accurately identified the microscopic myometrial invasion in 85.3% (344/403) of cases. Sensitivity, specificity, and positive and negative predictive values of gross estimation in determining a microscopic myometrial invasion greater than 50% were 73.0, 92.5, 85.0, and 85.5%, respectively. Among patients in whom the myometrial invasion was underestimated at gross examination the tumoral invasion was limited to the inner two thirds of the myometrium in 45% (18/40) of cases and the distance from the tumor-myometrial junction to the uterine serosa was greater than 3 mm in 65% (26/40) of cases. We conclude that gross estimation of myometrial invasion is a reliable and inexpensive method for evaluating the invasiveness of uterine carcinomas and that deciding to perform an extensive surgical staging upon gross estimation will be in accordance with the final histopathologic report in about 9 of 10 cases.

The purpose of the work was to determine the feasibility and accuracy of microlaparoscopy as diagnostic method for the reassessment of ovarian cancer patients.Eight patients scheduled for second-look laparoscopy who had undergone primary surgery for ovarian cancer followed by 6 cycles of chemotherapy were included in the study. Microlaparoscopy was performed using a 2.8 mm laparoscope followed by conventional 10-mm laparoscopy. Three additional 5-mm ancillary trocars were inserted to perform intraabdominal biopsies. Pelvic washings were performed in all cases.Microlaparoscopy was feasible in all cases and as accurate as conventional laparoscopy in seven cases. In one case the procedure was terminated before conventional laparoscopy because of positive biopsies at frozen section examination. There were no intra-operative complications related to microlaparoscopy. The median time from skin incision to the removal of the microlaparoscope was 47 minutes (range 30-70).Microlaparoscopy seems to be a safe, accurate, minimally invasive method and therefore we suggest its use as primary approach to the reassessment of ovarian cancer patients.

Objective: To assess the independent contribution of transvaginal ultrasound in identifying women at risk for endometrial disorders, and determine whether a cutoff value identifies women who need endometrial histologic assessment. Methods: Postmenopausal women with breast cancer who were receiving tamoxifen, with ultrasonographic endometrial thickness greater than 4 mm or vaginal bleeding, had hysteroscopy with selective endometrial biopsies. Endometrial thickness, duration of tamoxifen therapy, and endometrial histology were studied. Parametric and nonparametric tests and logistic regression and receiver operating characteristic curves were used for statistical analysis. Results: The study population consisted of 163 women, 46 with vaginal bleeding. The proportion of women with abnormal histologic findings was greater among those with endometrial thicknesses exceeding 9 mm compared with those with endometrial thicknesses 9 mm or less (60% versus 6.1%, P < .001) and among women who received tamoxifen for more than 27 months than those who received it for less time (46% versus 16%, P < .005). Logistic regression showed that endometrial thickness greater than 9 mm and vaginal bleeding were independent predictors of abnormal findings at hysteroscopy. Conclusion: In women taking tamoxifen, sonographic endometrial thickness exceeding 9 mm and the presence of vaginal bleeding are independent predictors of endometrial disease. If either exists, hysteroscopy and biopsy should be done.

BACKGROUND The aim of this study was to define the clinical relevance of functional biomarkers, prospectively assessed in a randomized clinical protocol, in patients with Stage III-IV epithelial ovarian cancer. The protocol compared cisplatin with polychemotherapy that included cisplatin and cyclophosphamide. METHODS In a subset of 168 patients with invasive epithelial ovarian cancer cell proliferation was determined by the 3H-thymidine labeling index, DNA ploidy was assessed by flow cytometry, and the expression of p53, bcl-2, and glutathione S-transferase-π (GST-π) was evaluated by immunohistochemistry using the antibodies PAb1801, anti-bcl-2, and GST-pi, respectively. RESULTS Cell proliferation, DNA ploidy, and the expression of p53, bcl-2, and GST-π were generally unrelated to one another and unrelated to clinicopathologic features, except for an association between DNA ploidy and the rate of cell proliferation. All biologic variables except bcl-2 were slightly related to tumor grade. DNA ploidy emerged as a predictor of clinical complete response and 3-year overall survival, regardless of treatment type or residual disease. Conversely, except for a favorable outcome for patients with tumors not expressing bcl-2 who were treated with cisplatin, no definitive patterns of predictivity for short term or long term clinical outcomes were observed for the other biomarkers studied. CONCLUSIONS DNA ploidy appears to be the most clinically relevant biomarker for epithelial ovarian cancer. More information is needed to understand the role of the other markers studied in this tumor type. Cancer 1998;82:159-67. © 1998 American Cancer Society.

Approximately 4% of gynecologic cancers are invasive carcinomas of the vulva. This retrospective study was intended to determine the prognostic importance of clinical variables in 389 women seen in the years 1978 through 1995 with squamous cell carcinoma of the vulva. In addition, the prognostic value of tumor characteristics and lymph node metastases was examined in a subgroup of 110 patients with node involvement. They represented approximately one third of patients who underwent lymph node dissection. Surgery consisted of radical vulvectomy modified radical vulvectomy or wide excision of the primary tumor, depending on the extensiveness of the tumor. Follow up averaged nearly 13 years. Overall, 5-year and 10-year survival rates were 66% and 62%, respectively. Univariate analysis identified age, the clinical features of the tumor, lymphovascular space involvement (LVSI), and lymph node status as significant predictors of survival. All patients presenting before age 30 lived 10 years compared with 53% of those older than 60. Patients with ulcerated tumors had a poorer outlook than those with exophytic tumors. A lack of LVSI doubled the chance of living 10 years or longer (61% vs 30%). The most important factor was nodal status; actuarial 10-year survival rates were 76% and 39.5%, respectively, for node-negative and node-positive patients. Neither tumor diameter nor extension of lymphadenectomy to the pelvic chains influenced survival. On multivariate analysis, the most significant independent prognostic factors were the percentage of nodal replacement (hazard ratio [HR], 6.99; 95% confidence interval [CI], 3.51–16.14) and extracapsular spread (HR, 4.88; 95% CI, 2.96–10.14). The investigators conclude that in women with invasive squamous cell carcinoma of the vulva, lymph node status and such nodal features as extracapsular spread and the rate of node replacement can help to identify high-risk patients who may benefit from adjuvant treatment.

We conducted a phase I–II study with escalating paclitaxel doses plus carboplatin at a fixed dose for previously untreated patients with advanced ovarian cancer in order to define the maximum tolerated dose. Eligible for the study were women with a histologically confirmed diagnosis of ovarian cancer stage III–IV according to the FIGO classification. In the first phase of the study, 6 patients were allocated escalating paclitaxel doses with fixed-dose carboplatin in order to establish the maximum tolerated dose. The starting dose of paclitaxel was 150 mg/m2 given after carboplatin (300 mg/m2) every 4 weeks for a total of six courses. The paclitaxel dose step was 25 mg/m2 up to 250 mg/m2. The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase. A total of 27 patients entered phase I and 23 phase II. Neurotoxicity was observed in 47 patients (94%; 29 grade 1, 17 grade 2, 1 grade 3, according to the WHO classification). The intensity of neurotoxicity tended to be dose related: out of the 15 patients who received ⩽ 200 mg paclitaxel, a total of 14 grade 1, but no grade 2 or 3 neurotoxicities, were observed. The frequency of grade 1, 2 and 3 neurotoxicity was 15, 17 and 1, respectively, in the 35 women who received ⩾ 225 paclitaxel + 300 mg carboplatin. There was no clear relationship between median WBC and platelet nadir and dose level. Among other toxicities, alopecia was observed in all 50 cases, hypersensitivity in two (4%) and myalgia in 41 (82%; 34 grade 1 and 7 grade 2). These frequencies tended to increase with the dose, but the relationship was not statistically significant. The overall response rate was 78% ( 39 50 ) with a complete response rate of 62% ( 31 50 ). In conclusion, this study suggests that carboplatin and paclitaxel can be administered safely to patients with advanced ovarian carcinoma. The maximum dose reached was 250 mg/m2 paclitaxel and 300 mg/m2 for carboplatin, but from a clinical point of view the maximum paclitaxel dose we would consider safe is 225 mg/m2.

To compare closure and nonclosure of the peritoneum at radical abdominal hysterectomy and pelvic node dissection with respect to postoperative morbidity.Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned randomly to have a standard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed. Adjuvant radiotherapy was given to patients with risk factors. The postoperative incidence of lymphocysts (within 8 weeks from the operation and after 1 year) and infection-related and non-infection-related complications were analyzed.One hundred twenty subjects were enrolled, of whom 59 had peritoneal closure and 61 did not. Both groups were similar with regard to age, weight, nodes removed, nodal metastases, operative time, type of surgery, need for transfusion, and incidence of postoperative radiotherapy. The median follow-up was 36 months (range 11-72). Eleven patients died, four because of treatment-related complications. The amount of drainage was significantly higher in the closed group than in the unclosed group (median 740 mL, range 50-5980 versus median 340 mL, range 40-4000; P.005). The incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks (17 of 59 versus 15 of 6, respectively), at 8 weeks (eight of 56 versus ten of 61, respectively), and after 1 year (one of 21 versus four of 22, respectively). No difference was found between closed and open groups in terms of symptomatic lymphocysts (one of 59 versus two of 61, respectively), wound and pelvic infection (seven of 59 versus 11 of 61, respectively), febrile morbidity (two of 59 versus 11 of 61, respectively), and obstruction (zero of 59 versus one of 61, respectively).Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications.

The response rate and the determinants of response to a cisplatin-based regimen of neodjuvant chemotherapy (NACT) in women with a histologically confirmed first-diagnosis of invasive bulky stage IB-IIB cervical cancer are analyzed. A total of 79 cases were treated with cisplatin (40 mg/m2) each 7 days for seven courses. During the first, fourth, and seventh cycles, ifosfamide (3.5 g/m2) was given by infusion for 24 hr. At the end of the seven cycles, 51 had a partial response (64.5%) and 4 a complete pathological response (5.1%). The overall 24-month cumulative survival was 80%, being 93% in responders and 43% in nonresponders (log-rank test, P0.05). With respect to the 66 subjects for whom pretreatment status of pelvic lymph nodes was available, complete or partial response was obtained in 35 of 42 subjects with negative pelvic lymph nodes at computed tomography, but in only 13 of 24 with positive lymph nodes. The corresponding odds ratios of response was 0.2 for women with positive status in comparison with those with negative status (95% confidence interval, 0.1-0.4). With respect to the 66 women who underwent surgery after NACT, of the 24 women with pretreatment positive lymph nodal status, 15 had positive nodes at surgery, but in 9 cases the histological analysis of nodes showed negative findings. Positive nodes at surgery were observed in 2 of the 42 subjects with negative nodes before treatment.

The objective of this study was to test the accuracy of transabdominal color Doppler imaging in the prediction of malignancy of adnexal tumors when integrated in combination with CA 125 levels and two-dimensional ultrasound.We considered 129 consecutive patients with a suspected adnexal mass at clinical examination and transabdominal and transvaginal two-dimensional ultrasound. Serum CA 125 was measured in all cases. All the patients underwent color Doppler imaging to measure the Resistance index of the tumor associated blood flow profile and then surgery and histologic diagnosis.The median age of the patients was 44 years (range 12-91), 64.3% were premenopausal and the prevalence of malignancy was 28.7%. The sensitivity of color Doppler mapping was 75.7%, specificity 71.7%, positive predictive value 68.3% and negative predictive value 93.0%, compared with 75.7%, 68.5%, 49.1% and 87.5% for CA 125 and 83.8%, 83.7%, 67.4% and 92.8% for two-dimensional ultrasound. Blood flow was undetectable by color Doppler imaging in 17 of the 129 cases (13.2%). In 55 patients with three concordant tests, the positive and negative predictive values were 100%. When CA 125 values and two dimensional ultrasound results were discordant (35 patients), the color Doppler diagnosis was correct in 88.6% of the cases (93% in premenopausal women).Color Doppler imaging alone is not better than two-dimensional ultrasound in predicting malignancy of pelvic masses. Its use together with CA 125 and two-dimensional ultrasound may improve the accuracy of predictions when the three tests are concordant or when the other two are discordant.

5096 Background: NACT followed by surgery is a different therapeutic approach to locally advanced cervical cancer that seems to offer specific advantages over chemoradiation such as potential activity against distant micrometastases, a debulking effect improving subsequent surgical outcome, less toxicity, and an easier management of salvage therapy. This phase II trial was designed to evaluate the toxicity and activity of NACT with TAP in patients with LACA. Methods: Patients (pts) with FIGO stage IB2 (9 pts)- II (21 pts) uterine adenocarcinoma were treated with cisplatin 70 mg/mq, doxorubicin hydrochloride 45 mg/mq and paclitaxel 150 mg/mq day 1 every 21 days for 3 cycles. Eight pts (26.6%) presented with positive lymphnodes ( +LY) at diagnosis (5 pelvic and 3 pelvic+paraortic). After the last cycle of chemotherapy patients underwent radical surgery with lymphnode dissection. Clinical responses to chemotherapy was evaluated according to Recist criteria. Pathological response was classified as no residual tumor (pCR), residual disease with 3 mm stromal invasion (pR2). Due to the slow accrual the trial was closed before the target population of 45 pts was reached. Results: Between 2003 to 2010, 30 women were enrolled. Two complete clinical responses (6.7%), 21 partial responses (70%) and 7 stabilizations of disease (23.3%) were registered. All the patients underwent radical surgery and were assessable for pathologic responses. Five patients (16.6%) achieved a pCR , 8 (26.6 %) a pR1 response; 17 patients (56.7%) a pR2 response. At pathological assessment 10 pts (33.3%) presented with +LY (7 pelvic, 1 paraortic, 2 pelvic+paraortic). At a median follow up of 45 months progression free survival and overall survival were 37 months (95% CI 1-98) and 45 months (95% CI 9-101+) respectively. Hematologic toxicity was the most relevant side effect with 13 pts (43 %) reporting grade 3-4 neutropenia. Conclusions: The TAP combination seems to be feasible with an acceptable toxicity profile and a promising response rate for the treatment of LACA. The effect of NACT on lymphnodes status warrant further investigation.

16520 Background: Brostallicin is a DNA minor groove binder showing a covalent interaction with DNA in the presence of glutathione/glutathione S-transferase (GSH/GST). Ovarian tumors previously tre...

16500 Background: Concomitant chemoradiation is the treatment of choice for locally advanced cervical cancer. Neoadjuvant chemotherapy has been proposed as an alternative, and a 14% absolute improv...

Between March 1982 and March 1987, 26 patients with minimal residual epithelial ovarian cancer after cisplatin-based chemotherapy were treated with whole-abdomen irradiation [moving-strip technique (MST)] with or without pelvic boost. Prior to radiation residual disease was macroscopic (less than or equal to 0.5 cm) in 8 cases and microscopic (positive random biopsies) in 18 cases (8 diffuse, 10 localized). Eighty percent of patients completed the planned therapy, 34% with interruptions secondary to hematologic or gastrointestinal toxicity. With a median follow-up time from completion of radiotherapy of 24 months, 34.6% of patients remain alive. The 3-year survival rates (from the second-look procedure) are 50% for the patients with microscopic tumor and 25% for those with macroscopic residual disease. Progression-free intervals are statistically different in the two groups: 16.9 months for microscopic residuals and 6.16 months for macroscopic tumors (P = 0.037). All but two of the recurrences were in the irradiated field (pelvis and/or abdomen); one was distant (pleural) and one only retroperitoneal. Small bowel injury was the most limiting complication: 3.8% was registered as fatal acute enteritis and 19% as late obstruction or malabsorption syndrome, necessitating surgical intervention in 10% of treated cases.

The purpose of the study was to analyze the determinants of long term survival in women with advanced ovarian cancer and negative second-look laparotomy.A series of 140 advanced (Stage III-IV) ovarian cancer patients (median age, 54 years; range, 22-74 years) with negative second-look laparotomy after primary surgery and chemotherapy is included in the analysis. At first diagnosis, all patients were treated with radical or debulking surgery. After primary surgery, the patients were treated with a chemotherapy regimen based on cisplatin or carboplatin alone or in combination with other drugs. All second-look laparotomies were performed 6-8 months after first surgery.The overall survival rates were 76% at 3 years, 66% at 5 years, and 51% at 8 years. The corresponding rates for disease free survival were 57, 50, and 43%, respectively. Survival rates were better for women with a residual tumor 1 cm or less after primary surgery. The 5-year probability of survival was 78% in this group, compared with 55% in women with a residual tumor more than 1 cm (log rank test, P0.05). Survival rates for women with tumor Grade 3 tended to be worse than Grades 1-2, but the difference was only of borderline statistical significance. No relationship emerged between survival and age, histotype, and presence of ascites at diagnosis. Women with a residual tumor 1 cm or less and positive lymph nodes had a 66% 5-year probability of survival, compared with 85% for women with a residual tumor 1 cm or less and negative lymph nodes. This difference was significant (log rank test, P = 0.05). The 5-year survival probabilities were 47 and 58%, respectively, in women with a residual tumor more than 1 cm and positive or negative lymph nodes.This analysis shows a favorable long term survival rate for women with advanced ovarian cancer and complete pathologic response after debulking surgery and postoperative chemotherapy. It further suggests that lymph nodal status is a prognostic factor for women with minimal residual tumor after surgery.

Serum CA 125 was measured in 100 patients with ovarian epithelial carcinoma at diagnosis and in follow-up. Levels over 35 U/ml were found in 43 (75.4%) of 57 cases at diagnosis and in 21 (48.8%) of 43 cases in follow-up. A correlation was found between tumor burden and marker positivity: advanced Stages (III and IV) and recurrences had 84.2 and 91% of positivity, compared to 59.1% in early disease (Stages I and II). Analysis by histotype and FIGO grade revealed a difference between the mucinous type and the others and a positive association with less differentiated tumors. In the 30 patients submitted to second-look laparotomy a correlation was found between CA 125 levels and pathological response in 86.7% of cases. This ovarian cancer marker may thus be more useful in monitoring the response to treatment and in long-term follow-up than in diagnosis.

Peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) were isolated from 36 patients with advanced ovarian adenocarcinoma and peritoneal effusions for study of lymphokine-activated killer activity. PBLs and TALs cultured in vitro for 3-5 days in the presence of interleukin-2 (IL-2, supernatant of the MLA 144 gibbon cell line, or human recombinant IL-2) expressed higher levels of cytotoxicity as compared to cells cultured in medium alone, against natural killer (NK)-susceptible (K562) or NK-resistant targets (Daudi and the human ovarian carcinoma cell line SW626). When ovarian tumor cells, freshly isolated from carcinomatous ascites or surgical specimens, were used as target cells in the cytotoxicity assay, 8 of 14 PBLs and 5 of 7 TAL preparations lysed the autologous tumor after treatment with IL-2, while no spontaneous reactivity was observed in any of the 14 patients tested. Although levels of lysis were usually relatively low, these data demonstrate that PBLs and TALs from ovarian cancer patients (TALs usually exhibiting low NK activity) when stimulated in vitro by IL-2 acquire some cytotoxic potential against the autologous tumor.

Objectives: The aimof this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. Methods: Twenty patients received a 30–60-min infusion of gemcitabine a week for 2 weeks, followed by 120–180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m2, respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. Results: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9–51%). Conclusion: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.

Nerve-sparing radical hysterectomy has increasingly been used for cervical cancer, with less morbidity. We aimed with this study: i) to describe an alternative technique of nerve-sparing radical Piver III hysterectomy, using the CUSA®, in which attention was given to the uterosacral ligament and cardinal ligament; ii) to evaluate the feasibility of this new nerve-sparing technique; iii) to describe the surgical anatomy of the autonomic nervous system; iv) to assess the early incidence of bladder dysfunction. Twelve consecutive patients with local-regional advanced cervical cancer were enrolled in the study on nerve-sparing radical hysterectomy with extended pelvic lymphadenectomy. The mean age was 44 years (range, 30–59), mean body mass index was 24 kg/m2 (range, 18–30), mean operating time was 217 mins (range, 195–240), and mean blood loss was 437 cc (range, 200–750). The average hospitalization time was 9 days (range, 5–15 days). Two patients presented pathologically positive parametrium. Two of 12 (17%) patients were discharged with self-catheterism. In the first outpatient follow-up, 1 patient had recovered spontaneous voiding. The nerve-sparing technique with CUSA® can be an option to reduce radical hysterectomy-related morbidity. The technique proved to be feasible, with promising results in terms of preventing bladder dysfunction. An elevated body mass index and large tumors can impair the performance of the technique. Further studies clarifying neuroanatomy and neurophysiology of autonomic nervous structures, as well as a prospective controlled trial on nerve-sparing radical hysterectomy should be carried out to confirm our data.