Long-Term Survival for Platinum-Sensitive Recurrent Ovarian Cancer Patients Treated with Secondary Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. RESULTS: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). CONCLUSIONS: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.

Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study.

OBJECTIVE: Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. PATIENTS AND METHODS: A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. RESULTS: A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96months (range 7-300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. CONCLUSIONS: This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity.

Occurrence of septic shock in a patient submitted to emergency cerclage following a negative amniocentesis: report of a case.

BACKGROUND: Second trimester emergency cerclage is an option for pregnant women presenting bulging fetal membranes. Despite a significant prolongation of pregnancy might be achieved, serious fetal and maternal events have been reported. Exclusion of infections through preprocedure amniocentesis has been proposed. METHODS: A 37-year-old woman, gravida 4 para 1, was admitted at 21 weeks of gestation to our University Hospital due to bulging fetal membranes. An amniocentesis was performed in order to exclude an actual amniotic infection. Our Microbiology Department found a negative amniotic culture for bacteria and Mycoplasma and a normal glucose and interleukin-6 level, so a cervical cerclage was performed. The patient was discharged home on oral erythromycin. RESULTS: After 48 h, the patient complained of hyperpyrexia, shivers and reduced fetal movements. Ultrasound at admission showed absent cardiac activity and after cerclage removal a non-viable fetus was delivered vaginally. Piperacillin and tazobactam were started, but the clinical course of the patient deteriorated and she developed a cold septic shock and was submitted to hysterectomy and transferred to the ICU of our hospital. CONCLUSION: This report heralds that even after negative amniocentesis, a life-threatening infection may not be excluded in women candidate for emergency cerclage due to bulging fetal membranes.

Laparoscopic versus laparotomic approach to endometrial cancer.

OBJECTIVE: The aim of our study was to compare the feasibility, morbidity, long-term safety, disease-free survival, and overall survival of the laparoscopic (LPS) approach to early-stage endometrial cancer (EC) compared to the traditional laparotomic approach. METHODS: We reviewed retrospective data of patients who underwent primary surgery from 1997 to 2009. We recorded clinical parameters, surgical stage, histological type, operative and peri-operative complications, time to resumption of normal functions, conversion to laparotomy, overall survival, and disease-free survival. RESULTS: LPS, did not increase operative risk and peri-operative complications even in obese and older women. The number of pelvic lymph and aortic nodes removed was similar for the two groups. One hundred and eight patients had a follow-up of 60 months. The two groups were similar for disease-free survival and overall survival. CONCLUSIONS: Laparoscopic approach to EC provides a reduction in postoperative complications and hospital stay compared to the laparotomic approach.

[Laparoscopic surgery for endometrial cancer in overweight women]. / Utilizzo della laparoscopia nel trattamento chirurgico delle sovrappese affette da cancro dell' endometrio.

AIM: The aim of this study was to investigate the feasibility and safety of laparoscopic staging of overweight women with endometrial cancer and to compare the surgical outcomes among these patients with those managed by laparotomy. METHODS: This was a retrospective analysis (Canadian Task-force Classification II-3). We reviewed operative and hospital records of 70 patients with a body mass index >25 kg/m2 who underwent surgical treatment for endometrial cancer between 2001 and 2008. Thirty-five patients treated laparoscopically were compared to an equivalent group of patients treated by laparotomy. Operative and postoperative variables were afterwards assessed. RESULTS: Women in laparoscopic group had a significantly lower blood loss (median, 25th-75th percentiles: 1.2, 0.8-2.0 in laparoscopic versus 1.8, 1.0-2.8 in laparotomic group, P<0.05). No differences between both group in terms of operative time (median, 25th-75th percentiles: 165 min, 130-183 in laparoscopic versus 135 min, 110-170 in laparotomic; P>0.05) and mean number of pelvic and para-aortic lymph nodes removed (22 ± 8.4 versus 24 ± 6.2 and 9.2 ± 2.5 versus 9.3 ± 5 respectively; P>0.05). Length of urethral catheter and hospital stay were statistically higher in laparotomic group (two days versus three days; four days versus seven days respectively; P<0.05). CONCLUSION: Laparoscopic surgery in overweight women with endometrial cancer had equivalent surgical staging than women operated by laparotomy. With regard to postsurgical variables, overweight women who underwent laparoscopic surgery had better results than those treated by laparotomy.

Preoperative local staging of endometrial cancer: transvaginal sonography vs. magnetic resonance imaging.

OBJECTIVES: To compare the accuracy of transvaginal sonography (TVS) and magnetic resonance imaging (MRI) in the preoperative staging of endometrial carcinoma. METHODS: This was a prospective study in which 74 women consecutively diagnosed with endometrial carcinoma were examined using TVS by physicians trained in gynecological sonography and MRI by radiologists with a special interest in gynecology. All patients underwent surgical-pathological staging after removal of the uterus, adnexa and pelvic lymph nodes. Sensitivity, specificity, and positive and negative predictive values were calculated for each imaging modality with regard to detection of neoplastic invasion of the outer half of the myometrium and cervical involvement. RESULTS: TVS and MRI performed equally well in the preoperative staging of endometrial cancer, with no statistically significant differences between the two techniques. The sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy for TVS in the evaluation of myometrial infiltration were 84%, 83%, 79%, 88% and 84%, respectively. Respective values for MRI were 84%, 81%, 77%, 87% and 82%. The corresponding statistics for detection of cervical involvement were 93%, 92%, 72%, 98% and 92% for TVS; and 79%, 87%, 58%, 95% and 85% for MRI. CONCLUSIONS: When carried out by expert practitioners, TVS shows good accuracy in the local staging of endometrial carcinoma. Because of its high costs, MRI should be offered only to those in whom TVS produces images of poor quality.

Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival.

BACKGROUND: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. METHODS: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). RESULTS: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). CONCLUSIONS: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.

(18)F-FDG PET/CT in the evaluation of recurrent ovarian cancer: a prospective study on forty-one patients.

AIM: Many patients with ovarian cancer are at high risk of recurrence especially in the 2 years following first-line therapy. CA125 serum levels measurement associated to computed tomography (CT), ultrasound (US) and magnetic resonance imaging (MRI) are currently used during follow-up to detect recurrent disease. Unfortunately, in a relevant percentage of cases all of these traditional imaging techniques provide a significant number of doubtful/equivocal results or turn out negative even in presence of elevated Ca125 levels. Aim of our study was to evaluate sensitivity, specificity and accuracy of (18)F-FDG PET/CT in a group of patients with suspicion of ovarian cancer recurrence. METHODS: We prospectively evaluated 41 patients with a mean age of 59.4 years who had been previously treated for ovarian cancer with surgery and radio-chemotherapy or radio-chemotherapy alone. Following the performance of traditional radiologic imaging (US, CT, MRI) and Ca125 measurement, all patients underwent additional (18)F-FDG PET/CT. PET/CT results were compared with histologic findings or clinical, laboratory and repeated traditional imaging techniques during subsequent follow-up data. RESULTS: Of 41 patients 32 had a positive PET-CT (30 true positive, two false positive) whereas nine a negative PET/CT (five true negative, four false negative). Overall, in our experience (18)F-FDG PET/CT provided a good sensitivity (88.2%), specificity (71.4%) and accuracy (85.4%), superior to that reported in literature for traditional radiologic imaging. CONCLUSIONS: It can be concluded that (18)F-FDG PET/CT appears to be a useful and accurate tool in disclosing early recurrent ovarian cancer.

Efficacy of a hyaluronan derivative gel in postsurgical adhesion prevention in the presence of inadequate hemostasis.

BACKGROUND: We previously demonstrated that an auto-cross-linked hyaluronan-based antiadhesion agent (auto-cross-linked polysaccharide [ACP] gel) was effective in postsurgical adhesion prevention after open laparotomy and laparoscopic surgery with adequate hemostasis in animal models. This study assessed the ability of different preparations of ACP gel to prevent adhesions in the presence of bleeding or inadequate hemostasis. METHODS: Ninety-seven female rabbits were subjected to a standardized surgical lesion with subsequent exudative abdominal bleeding (oozing model), and 97 animals were subjected to a standardized surgical lesion with severe abdominal bleeding (bleeding model). After injury, the animals were randomly assigned to 5 groups of treatment: 3 different preparations of ACP gel (20, 40, and 60 mg/mL), a hyaluronan-carboxymethylcellulose film, and no treatment. Three weeks after operation, the animals were killed, and the adhesions were assessed by a blinded observer who measured the length and area of the adhesions and who used the Blauer scoring system. RESULTS: All 3 preparations of ACP gel and the hyaluronan-carboxymethylcellulose film reduced adhesion formation in both models (P <.01) as measured by the number of adhesion-free animals, mean Blauer score, and the mean length and surface area of the adhesions. There were no statistical differences between the different treatment groups. CONCLUSIONS: These data suggest that different hyaluronan based agents in the presence of severe bleeding or exudative abdominal bleeding reduce de-novo postsurgical adhesion formation.

Fibrin sealant in laparoscopic adhesion prevention in the rabbit uterine horn model.

OBJECTIVE: To assess the effects of fibrin sealant on adhesions after laparoscopic surgery. DESIGN: Standardized surgical trauma was induced in 60 female rabbits. The animals were randomized in three groups for different adhesion prevention treatment. SETTING: University research laboratory. INTERVENTIONS: After standardized trauma was induced, group 1 (n = 20) received no treatment, group 2 animals (n = 20) were injected in the abdominal cavity with 60 mL of Ringer's lactate, and human fibrin sealant was applied on the surgical lesions under laparoscopic vision in group 3 (n = 20). MAIN OUTCOME MEASURES: Five weeks after laparoscopy, a laparotomy was performed, and the adhesions were scored. RESULTS: Fourteen of 20 rabbits in the control group (70%) presented postoperative adhesions, 11 of 20 (55%) in the Ringer's group, and 5 of 20 (25%) in the fibrin sealant group. High-score adhesions were seen in 15% of cases in control and Ringer's group and in 5% of cases in the fibrin sealant group. CONCLUSIONS: When used during laparoscopic surgery, fibrin sealant has a preventive effect on de novo postsurgical adhesions. To assess the efficacy in reproductive surgery, a trial on recurrent postsurgical adhesions is required.

Uterine fistula induced by hysteroscopic resection of an embolized migrated fibroid: a rare complication after embolization of uterine fibroids.

OBJECTIVE: To describe a case in which hysteroscopic removal of a fibroid that had migrated through the uterine wall induced formation of a uterine fistula. DESIGN: After embolization of uterine fibroids, an investigative clinical, sonographic, and hysteroscopic protocol was followed. SETTING: Gynecologic clinic of a university hospital. PATIENT(S): A 38-year-old woman undergoing embolization of uterine arteries for uterine fibroids. INTERVENTION(S): Angiography-guided transcatheter bilateral embolization of uterine arteries, with clinical, sonographic, and hysteroscopic follow-up. MAIN OUTCOME MEASURE(S): Patient morbidity and satisfactory intercourse. RESULT(S): Six months after embolization of the uterine arteries, the patient presented migration of the fibroid through the uterine wall. Hysteroscopic removal of the fibroid induced posthysteroscopic formation of a uterine fistula. CONCLUSION(S): After embolization of the uterine arteries, thorough follow-up examination of the uterine cavity is strictly recommended. Diagnosis of a uterine wall perforation can identify an abnormal source of uterine bleeding, and patients should be counseled to avoid pregnancy until the lesion heals completely.

A novel hyaluronan-based gel in laparoscopic adhesion prevention: preclinical evaluation in an animal model.

OBJECTIVE: To evaluate the effectiveness of a crosslinked hyaluronan solution (ACP gel) in the prevention of postsurgical adhesions in laparoscopic surgery. DESIGN: A randomized blinded study using a rabbit model in laparoscopic surgery. SETTING: A standardized surgical trauma in the rabbit uterine horn to induce adhesion formation. ANIMALS: Sixty-four sexually matured female New Zealand white rabbits weighing 2.5 to 3.0 kg and aged 3-4 months. INTERVENTION(S): After trauma, group 1 (n = 22) received no treatment, group 2 animals (n = 20) received oxidized-regenerated cellulose (Interceed [TC7]) in group 3 (n = 22) 5 mL of ACP gel were applied on the lesion. MAIN OUTCOME MEASURE(S): Six weeks after laparoscopy, a laparotomy was performed and the adhesions were scored according to Blauer's scoring system. RESULT(S): 66% of the untreated animals and 85% of the animals treated with Interceed presented with severe adhesions, whereas only 35% of the ACP gel treatment group had significant adhesions. The mean ( +/- SEM) increased adhesion score was 2.24 +/- 0.26 in the untreated group, 2.45 +/- 0.22 in the Interceed group, and was 1.25 +/- 0.28 in the ACP gel group. CONCLUSION(S): This study revealed that ACP gel holds promise as a novel resorbable biomaterial for the reduction of postoperative adhesions after laparoscopic surgery.

Pharmacodynamic effects on blood coagulation of a new low molecular weight heparin (alfa-LMWH) in healthy volunteers and gynecological surgery patients.

The pharmacodynamic properties of a new LMWH (alfa-LMWH) were investigated in 8 healthy volunteers after single subcutaneous administrations of 7,500, 15,000 and 30,000 anti-XaU doses at weekly intervals. Anti-Xa and anti-IIa heparin activities were monitored together with aPTT, thrombin time, bleeding time and euglobulin lysis time. No relevant changes in bleeding time or major side-effects were ever recorded. A group of 26 patients submitted to gynaecological surgery were then investigated to determine the dosage schedule for prophylaxis of post-operative deep vein thrombosis. Two subgroups received daily subcutaneous doses of 7,500 and 15,000 anti-XaU alfa-LMWH respectively, beginning 2 h before surgery; the third subgroup received 5,000 IU calcium heparin three times daily over the seven postoperative days. The following tests were peri-operatively monitored: anti-Xa heparin activity, aPTT, PT, fibrinogen, Antithrombin III. No differences in intra-operative bleeding or side-effects were recorded. On the basis of the levels of anti-Xa heparin activity and the negligible effects on aPTT, the dose of 7500 anti-XaU was selected at single daily administration for thromboprophylaxis in gynecological surgery.

Extensive cytoreductive surgery in advanced ovarian carcinoma.

From June 1985 to June 1993, 152 patients with advanced ovarian cancer were treated with maximum cytoreductive surgery, and six to nine cycles of platinum-based chemotherapy. Six patients had stage IIIA-B disease, 101 stage IIIC, and 45 stage IV. Twenty-two tumors were grade 1. 58, grade 2. and 72, grade 3. Eighty-four patients (55%) presented with bulky tumors (> 10 cm in diameter). Optimal cytoreductive surgery (diameter of largest residual mass < 2 cm) was performed in 138 patients (91%). Fifty patients (33%) developed postoperative complications; 38 patients (25%) required a second laparotomy within a few days. Two postoperative deaths occurred. Overall 2-year and 4-year survival rates were 56% and 28%, respectively. There was a clear relationship between residual tumor and survival: the 2-year survival rate was 80% in the absence of residual tumor vs. 22% when the residuum exceeded 2 cm in diameter. The 2-year survival rate was 49% for tumor nodules < 2 cm in diameter. In a multivariate analysis of various risk factors (grade, stage, lymph node metastases, residual tumor, and age), the one that correlated most with survival was residual tumor. Despite a high morbidity rate, this modality of treatment, with the presence of optimal and aggressive perioperative measures in terms of intensive care unit and post-operative follow-up, offers an encouraging if not promising strategy for increased chances of survival in advanced ovarian cancer.

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Behaviour of ovarian tumors of low malignant potential treated with conservative surgery.

OBJECTIVE: Fertility-sparing surgery has been proposed for the treatment of borderline ovarian tumors. The aim of this study was to evaluate the outcome of patients submitted to cystectomy (CYS) compared with patients treated by unilateral salpingo-oophorectomy (USO) or bilateral salpingo-oophorectomy with/without total hysterectomy (radical surgery, RS). METHODS: We reviewed retrospectively the data of patients treated in 3 institutions for borderline ovarian tumors. One hundred and sixty-eight patients underwent laparoscopic or laparotomic surgical treatment from 1985 to 2006. Tumor recurrence rate, disease-free survival and site of recurrences were evaluated. Specific prognostic factors, such as stage, histology, micropapillary subtype, exophytic tumor growth, intraoperative spillage, endosalpingiosis, staging procedures, and route of surgery were analysed. RESULTS: Thirty-five patients underwent cystectomy, 50 unilateral salpingo-oopohorectomy, and 83 radical surgery. Twelve patients in the CYS group (34.3%), 10 in the USO group (20.0%), and 5 (6.0%) in RS group relapsed. Five-year progression-free survival (PFS) was 59.6%, 78.4%, and 93.5% in CYS, USO and RS groups, respectively. None of the relapsed patients died of disease. CONCLUSIONS: Cystectomy is an effective surgical strategy for patients with borderline ovarian tumor. The higher risk of local relapses is not associated with a reduction in the overall survival. The procedure should be offered to young patients with bilateral tumors and to very young ones, considering the higher risk of local relapse.