Efficacy and safety of robotic-assisted surgery in challenging hysterectomies - a single institutional experience.

OBJECTIVE: An increasing number of robotic hysterectomies are being performed and the most common indication is fibroids. Fibroid uterus is common indication for hysterectomy for enlarged uteri. The role of robotic approach for complex pathologies as enlarged uterus is still debatable. The study aimed to analyze the feasibility of robotic hysterectomy in patients with enlarged uteri and the impact of uterine weight on surgical outcomes and on operative time length. PATIENTS AND METHODS: One hundred and thirty-eight patients who underwent robotic hysterectomy for benign indications at the 2nd Division of Obstetrics and Gynecology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa were consecutively enrolled. RESULTS: Data of patients undergoing robotic surgery for benign indications were collected. Patients were stratified in two groups based on their uterine weight, to analyze the effective impact of uterine weight and dimension on surgical performance, operative time and postoperative outcomes. Conversion rate was 0%. Median uterine weight was 615 g (range 400-1900 g). Median total operating time was 131 minutes (range 70-255 minutes). Increase in uterine weight significantly increased operative times (p=0.003) and morcellation time (p=0.001). On the other hand, operative time was just partially influenced by route for removal of the uterus (p=0.085) but significantly affected by uterine weight (p=0.008), previous surgeries (p=0.003) and BMI of the patient (p=0.005). CONCLUSIONS: Robotic hysterectomy is feasible and safe for challenging cases as large uteri. This technique could enable patients with outsized uteri, not suitable for vaginal hysterectomy, to undergo minimally invasive surgery with excellent results. Larger studies to investigate and compare robotic with other surgical approaches for difficult hysterectomies are needed to confirm these data.

Safety and efficacy of tigecycline in complicated and uncomplicated pelvic inflammatory disease.

OBJECTIVE: Tigecycline is a glycylcycline antimicrobial structurally related to minocycline, with a wide spectrum of activity that includes anaerobes and typical and atypical microorganisms causing pelvic inflammatory disease (PID). This study aimed to evaluate efficacy and safety of tigecycline in complicated PID and un-complicated PID after the failure of first-line antibiotic therapy. PATIENTS AND METHODS: Between May 2014 and April 2016 at the 2nd Unit of Obstetrics and Gynecology, Santa Chiara Hospital of Pisa a pilot study on 20 women with mild/moderate PID after the failure of first-line antibiotic therapy and on 8 women with complicated PID was conducted. The treatment protocol was 10-day course of tigecycline, with a loading dose of 100 mg intravenously (i.v.) at day one and then 50 mg IV twice daily. The primary endpoint was to evaluate tigecycline's efficacy in terms of clinical response to test-of-cure (TOC) at the end of therapy and 30 days after the last dose. Clinical response during therapy and safety were analyzed as well. RESULTS: A total of 28 women were enrolled, and 25 patients completed the study protocol, because 3 patients reported adverse drug effects resulting in treatment interruption. PID was mainly caused by Chlamydia, Gardnerella, Mycoplasma/Ureaplasma. Tigecycline showed a 100% remission of signs and symptoms in patients resistant to first-line antibiotic regimen and in patients with complicated PID. Moreover, tigecycline showed good tolerability and compliance. CONCLUSIONS: Despite the limited sample size, tigecycline seemed an effective and safe treatment for women with complicated/resistant PID. Nevertheless, further clinical trials are needed to confirm these results.

Elderly and very elderly advanced ovarian cancer patients: does the age influence the surgical management?

BACKGROUND: To examine the surgical treatment and clinical outcome of elderly and very elderly advanced epithelial ovarian cancer patients. METHODS: We retrospectively analyzed FIGO stage IIIC-IV ovarian cancer patients, divided in elderly (Group A, >65 and <75 years) and very elderly patients (Group B, ≥ 75 years) treated by primary debulking surgery (PDS) or by interval debulking surgery (IDS) at the Catholic University at Rome and Campobasso, Italy. RESULTS: 164 patients were included: 123 (Group A) and 41 (Group B). Complete cytoreduction was achieved in 60 patients (60.6%) in Group A and in 20 patients (62.5%) in Group B (p = 0.75). In the remaining cases, optimal cytoreduction was performed (39 cases (39.4%) in Group A and 12 (37.5%) in Group B; p = 0.75). In Group A complete/optimal debulking was achieved in 53 patients (53.5%) at PDS and in 46 patients (46.5%) at IDS (p = 0.55). In the Group B a higher rate of patients was debulked at IDS with respect to PDS (10 (31.3%) vs. 22 patients (68.7%); p = 0.02). In Group A patients debulked at PDS showed better DFS (p = 0.007) and OS (p = 0.003) with respect to patients submitted to successful IDS, whereas in group B we did not observed any survival difference according to time of cytoreduction. CONCLUSIONS: Our data suggest that elderly and very elderly patients may tolerate radical and ultra-radical surgery. These patients should be managed in a gynecologic oncology unit, with prudent but complete approach.

Robotic treatment of colorectal endometriosis: technique, feasibility and short-term results.

BACKGROUND: Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Since a medical approach is often insufficient, a minimally invasive approach is considered the gold standard for complete disease excision. Robotic-assisted surgery is a revolutionary approach, with several advantages compared with traditional laparoscopic surgery. METHODS: From March 2010 to May 2011, we performed 22 consecutive robotic-assisted complete laparoscopic excisions of DIE endometriosis with colorectal involvement. All clinical data were collected by our team and all patients were interviewed preoperatively and 3 and 6 months post-operatively and yearly thereafter regarding endometriosis-related symptoms. Dysmenorrhoea, dyschezia, dyspareunia and dysuria were evaluated with a 10-point analog rating scale. RESULTS: There were 12 patients, with a median larger endometriotic nodule of 35 mm, who underwent segmental resection, and 10 patients, with a median larger endometriotic nodule of 30 mm, who underwent complete nodule debulking by colorectal wall-shaving technique. No laparotomic conversions were performed, nor was any blood transfusion necessary. No intra-operative complications were observed and, in particular, there were no inadvertent rectal perforations in any of the cases treated by the shaving technique. None of the patients had ileostomy or colostomy. No major post-operative complications were observed, except one small bowel occlusion 14 days post-surgery that was resolved in 3 days with medical treatment. Post-operatively, a statistically significant improvement of patient symptoms was shown for all the investigated parameters. CONCLUSIONS: To our knowledge, this is the first study reporting the feasibility and short-term results and complications of laparoscopic robotic-assisted treatment of DIE with colorectal involvement. We demonstrate that this approach is feasible and safe, without conversion to laparotomy.

Ultrasound evaluation of intra-abdominal sites of disease to predict likelihood of suboptimal cytoreduction in advanced ovarian cancer: a prospective study.

OBJECTIVES: To analyze in advanced ovarian cancer patients the ability of ultrasound to evaluate the extent of intra-abdominal disease and to predict the likelihood of suboptimal cytoreduction. METHODS: Into this prospective study, 147 patients with advanced ovarian cancer were enrolled consecutively between January 2005 and October 2008. All patients underwent standard laparotomy and maximal surgical effort was attempted. To create a new scoring system to predict suboptimal cytoreduction we considered the following sonographic parameters: peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement, ascites and liver and/or spleen metastases. Those parameters achieving a negative predictive value ≥ 50% and a positive predictive value ≥ 50% in predicting suboptimal cytoreduction were included in the ultrasound scoring system, which was then calculated for each patient. RESULTS: Ultrasound allowed a virtually conclusive diagnosis of massive pelvic involvement (sensitivity, 94%; specificity, 97%), parenchymal liver metastases of any size (sensitivity, 93%; specificity, 98%) and ascites (sensitivity, 98%; specificity, 97%) and a very reliable diagnosis of peritoneal carcinomatosis (sensitivity, 91%; specificity, 88%) and omental involvement (sensitivity, 94%; specificity, 90%), whereas it was not very good at excluding parenchymal spleen metastases or splenic hilum involvement (sensitivity, 75%; specificity, 98%) and bowel mesentery involvement (sensitivity, 67%; specificity, 88%). Ultrasound-assessed peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement and ascites were included in our ultrasound score (which had a range of 0-6 points). With a cut-off value of > 5, the sensitivity and specificity of the ultrasound score with regard to prediction of suboptimal cytoreduction were 31% (20/64) and 92% (46/50), respectively. CONCLUSIONS: Ultrasound examination is able to assess intra-abdominal disease in advanced ovarian cancer patients, with satisfactory concordance with laparotomic findings. Our ultrasound score can predict suboptimal cytoreduction and might be clinically useful.

Douglas peritonectomy compared to recto-sigmoid resection in optimally cytoreduced advanced ovarian cancer patients: analysis of morbidity and oncological outcome.

BACKGROUND: Rectosigmoidectomy (RR) with primary anastomosis or pelvic peritonectomy (PP) are often part of an optimal en bloc tumor resection in advanced ovarian cancer (AOC) patients with contiguous extension to or encasement of the reproductive organs, peritoneum of the cul-de-sac and sigmoid colon. We report our experience with two different surgical approaches in optimally cytoreduced AOC patients evaluating oncologic outcome and surgically associated morbidities METHODS: Data from all consecutive AOC patients undergoing PP or RR as part of the surgical procedure during primary cytoreduction from 2004 through 2009 were extrapolated and analyzed using the chi-squared test, Cox proportional hazard model and Kaplan-Meier method including log-rank test. RESULTS: During the study period, we identified 187 AOC patients, fitting the inclusion criteria: 71 (38%) were submitted to RR and 116 (62%) were managed with PP. The estimated mean disease-free survival (DFS) was 30.7 months (95% CI 24.6-36.8) in the RR arm vs. 25.9 months in the PP arm (95% CI 21.9-29.9) (p 0.299); similarly, the estimated mean overall survival (OS) was 38.8 months (95% CI 33.4-44.2) in the RR arm and 48.2 months in the PP arm (95% CI 43.1-53.3) (p = 0.122). No statistically significant differences were found in terms of DFS and OS according to the mesocolic lymphnode status (p = 0.65 and p = 0.81, respectively). CONCLUSIONS: In conclusion, the current study clearly supports evidence that survival rates are similar for patients who achieved optimal residual tumor (RT), independent to whether they had RR or PP.

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery.

OBJECTIVE: Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS: Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS: Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION: Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

Endometrioid adenocarcinoma with squamous differentiation arising from ureteral endometriosis in a patient with no history of gonadal endometriosis.

BACKGROUND: Malignant transformation may occur in up to 1% of women with endometriosis and only 20% of these cases occur at extragonadal pelvic sites. Similarly, urinary tract endometriosis is rare and occurs in only 1% of all endometriotic lesions. CASE: An endometrioid carcinoma with squamous differentiation arising from periureteral endometriosis presented as a pelvic mass encasing the right ureter. The patient had a history of total hysterectomy and bilateral salpingo-oopherectomy 8 years earlier because of bilateral serous benign cysts with right hemorrhagic corpus luteum and uterine fibroids, and has since been under unopposed estrogen replacement therapy for 5 years. CONCLUSION: This is the second case of a malignancy arising in endometriosis presenting as an obstructive ureteral mass and the first case of a patient with this condition whose endometriosis is not consistent with a gonadal origin. An analysis of the case and related literature is presented together with the discussion of possible pathogenetic mechanisms.

Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer.

This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 microg/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 x 10(5) IU/m(2)/day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO- and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P = 0.034 and P = 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA(+) T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P = 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P = 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results.

The aim of this study was to assess the long-term impact of high-dose chemotherapy (HDC) as consolidation in a large series (n = 55) of advanced chemosensitive ovarian cancer patients who were optimally cytoreduced at time of first surgery or at interval debulking surgery (IDS). HDC consisted of carboplatin (600 mg/m(2) days 1 and 2), etoposide (450 mg/m(2) days 1 and 2) and melphalan (50 mg/m(2), days 3 and 4). The primary endpoint of the study was the assessment of time to progression (TTP) and overall survival (OS). In September 2000 the overall population had a median follow-up of 55 months (range 17--137) and a TTP of 35 months with a 5-year TTP rate of 35% (CI 95%: 21--49) whereas OS averaged 75 months with a 5-year OS of 59% (CI 95%: 45--73). In patients achieving optimal primary cytoreduction the median TTP was 44 months with a 5-year rate of 43% (CI 95%: 26--60). In the same series the 5-year OS rate was 62% (CI 95%: 45--79) (median OS = 75 months). In patients who were optimally cytoreduced at the time of IDS the median TTP was 25 months and the 5-year TTP rate was 22% (CI 95%: 3--41) and median OS was 46 months with a 5-year OS rate of 50% (CI 95%: 27--73). HDC with hematopoietic support could represent an effective approach for the treatment of advanced optimally cytoreduced ovarian cancer patients with chemosensitive disease. Patients who underwent IDS because of unresectable tumors at the time of first surgery had the greater survival benefit from HDC.

Docetaxel and epirubicin plus G-CSF as mobilizing treatment to support high-dose chemotherapy in breast cancer.

BACKGROUND: In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC). PATIENTS AND METHODS: Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis. RESULTS: The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed. CONCLUSIONS: Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

Peripheral blood progenitor cell collection after epirubicin, paclitaxel, and cisplatin combination chemotherapy using EPO-based cytokine regimens: a randomized comparison of G-CSF and sequential GM-/G-CSF.

BACKGROUND: The peripheral blood progenitor cell (PBPC) mobilization capacity of EPO in association with either G-CSF or sequential GM-CSF/G-CSF was compared in a randomized fashion after epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy. STUDY DESIGN AND METHODS: Forty patients with stage IIIB, IIIC, or IV ovarian carcinoma were enrolled in this randomized comparison of mobilizing capacity and myelopoietic effects of G-CSF + EPO and GM-/G-CSF + EPO following the first ETP chemotherapy treatment. After ETP chemotherapy (Day 1), 20 patients received G-CSF 5 microg per kg per day from Day 2 to Day 13 and 20 patients received GM-CSF 5 microg per kg per day from Day 2 to Day 6 followed by G-CSF 5 microg per kg per day from Day 7 to Day 13. EPO (150 IU per kg) was given every other day from Day 2 to Day 13 to all patients in both arms of the study. Apheresis (two blood volumes) was performed during hematologic recovery. RESULTS: The magnitude of CD34+ cell mobilization and the abrogation of patients' myelosuppression were comparable in both study arms; however, GM-/G-CSF + EPO patients had significantly higher CD34+ yields because of a higher CD34+ cell collection efficiency (57.5% for GM-/G-CSF + EPO and 46.3% for G-CSF + EPO patients; p = 0.0009). Identical doses of PBPCs mobilized by GM-/G-CSF + EPO and G-CSF + EPO drove comparable hematopoietic recovery after reinfusion in patients treated with identical high-dose chemotherapy. CONCLUSION: The sequential administration of GM-CSF and G-CSF in combination with EPO is feasible and improves the PBPC collection efficiency after platinum-based intensive polychemotherapy, associating high PBPC mobilization to high collection efficiency during apheresis.

Topotecan and gemcitabine in platinum/paclitaxel-resistant ovarian cancer.

24 patients were enrolled into a phase I-II study conducted to determine the maximum tolerated doses of topotecan-gemcitabine in sequential combination and the response rate in platinum/paclitaxel resistant ovarian cancer patients. A total of 83 courses are evaluable, with a median number of three cycles administered per patients (range 2-7). Topotecan was administered on days 1-5 by 30 min i.v. infusion immediately after gemcitabine given by 30 min i.v. on days 1 and 3; cycles were repeated every 28 days. The starting doses were topotecan 0.7 mg/m(2) and gemcitabine 200 mg/m(2). Following dose levels were 08/400; 0.9/600; 0.9/800 for topotecan and gemcitabine, respectively. The maximum tolerated dose (MTD) was reached at dose level 3, the dose-limiting toxicity being represented by febrile neutropenia and thrombocytopenia. After the MTD was reached, granulocyte-colony-stimulating factor was administered in 27% of cycles. Mild and manageable was non hematological toxicity. All patients are so far evaluable for response. Among them 2 complete responses (8.3%; 95% CI: 2.6-19), 1 partial response (4.2%; 95% CI: 3.8-12), 9 no change (37.5%; 95% CI: 18-56.8) and 12 progressions (50%; 95% CI: 30-70) have been registered. Based on these data, there is no evidence that combining topotecan and gemcitabine is better than using either of the two drugs used separately.

p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer.

The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III-IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I-II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III-IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients.

Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer.

The aim of this study was to analyse the long-term survival and the relationships between prognostic factors at presentation, chemoresponsiveness and disease outcome in patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery (RS). Two consecutive studies of neoadjuvant chemotherapy containing cisplatin, bleomycin plus/minus methotrexate followed by radical hysterectomy and systematic aortic and pelvic lymphadenectomy were carried out between January 1986 and September 1990 on 130 patients with > or = 4 cm stage IB2-III cervical cancer. Survival analysis was performed using the Kaplan and Meier test and Cox's multivariate regression analysis. 128 (98%) of the patients enrolled were evaluable for clinical response and survival, 83% (106) of the patients responded to chemotherapy, with a 15% complete response rate. Logistic regression analysis demonstrated that International Federation of Gynecology and Obstetrics (FIGO) stage, cervical tumour size, parametrial involvement and histotype are highly predictive of response. Responding patients underwent laparotomy, but 8% were not amenable for radical surgery. The 10-year survival estimates were 91%, 80% and 34.5% for stage IB2-IIA bulky, IIB and III, respectively (P < 0.001). After Cox's regression analysis, the parameters significantly associated with survival were the same factors predicting response to neoadjuvant chemotherapy. No stage IB2-IIA bulky patient has so far relapsed, while 12% stage IIB and 56% stage III patients recurred. The 10-year disease-free survival estimates are 91% and 44% for stage IB2-IIB and III, respectively (P < 0.001). Metastatic nodes and persistent tumour in the parametria were the only two independent factors for disease-free survival after multiple regression analysis. After a long-term follow-up (median follow-up 98 months (20-129+)), our results give new evidence of the prognostic value of response to neoadjuvant chemotherapy and of a possible therapeutic benefit of the sequential treatment adopted which, however, must be verified in a randomised setting.

High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration.

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCT-related complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

Modified type IV-V radical hysterectomy with systematic pelvic and aortic lymphadenectomy in the treatment of patients with stage III cervical carcinoma. Feasibility, technique, and clinical results.

BACKGROUND: Due to the high prevalence of perioperative major morbidity and the difficulties in achieving surgical disease free margins, surgery has had no role in the treatment of patients with Stage III cervical carcinoma. METHODS: Forty-two women with International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical carcinoma responding to platinum-based neoadjuvant chemotherapy underwent the maximum surgical effort, comprised of a modified type IV-V radical hysterectomy (37 patients) or anterior pelvectomy (5 patients) with systematic pelvic and aortic lymphadenectomy. Feasibility, modifications of surgical technique, and pathologic and clinical data were analyzed. RESULTS: Surgery was feasible in all 42 patients intraoperatively selected. Disease free margins were achieved in all but one patient. The median operating time was 390 minutes, and the median estimated blood loss was 800 mL. In the last series of patients, these figures declined to 320 minutes and 600 mL, respectively. Major morbidity consisted of severe intraoperative hemorrhage in two patients, pulmonary embolism in four, ureteral fistula in three, and laparocele in three. The number of lymph nodes removed ranged from 30 to 117 with a median of 56. The mean lengths of vagina and lateral parametrium resected were 55 and 48 mm, respectively. Despite perioperative chemotherapy, lymph node metastasis was present in 36% of patients, parametrial disease in 38%, and vaginal disease in 45%. After a median follow-up of 53 months, the 5-year overall and disease-free survival rates of radically operated patients were 70% and 58%, respectively. CONCLUSIONS: Thanks to improved surgical technique and perioperative care, extended radical surgery appears to be feasible with acceptable morbidity in chemosensitive women with Stage III cervical carcinoma and may constitute a valid alternative to radiotherapy in these patients.

Locally advanced cervical adenocarcinoma: is there a place for chemo-surgical treatment?

The increased frequency and poor prognosis of cervical adenocarcinoma call for new therapeutic strategies, especially in locally advanced disease. Combined neoadjuvant chemotherapy (NACT)-radical surgery (RS) has been investigated to assess its feasibility and the possible impact on disease outcome. Data were pooled from three consecutive trials on a total of 42 patients with FIGO Stage IB-IIA >4 cm (9), IIB (19), and IIIB (14) cervical adenocarcinomas. NACT regimens consisted of cisplatin (P), bleomycin (B) and methotrexate, high-dose PB, and P and doxorubicin combinations for one to three cycles. Responding patients underwent RS while those still ineligible for RS underwent radiotherapy. Fisher and chi squared tests were used to detect significant factors affecting response to NACT. Cox multivariate regression analysis was used to evaluate parameters affecting response and survival. Medians and life tables were computed by the method of Kaplan and Meier. Median follow-up times were 56 (17-95) and 54 months (15-92) from enrollment and RS, respectively. NACT-induced toxicity was generally mild and did not compromise RS when indicated. The 33 (79%) responders underwent laparotomy, while the 9 nonresponders received radiotherapy. RS was feasible in 29 (69%) patients. Macroscopic intraperitoneal tumor (IPT) excluded abandoning RS in 4 cases. Mild to moderate RS-related complications were seen in 41% of cases with the same pattern as in the absence of any prior treatment. In patients undergoing RS, node metastasis and microscopic IPT were detected in 2 (7%) and 3 (10%) patients, respectively. The 5-year overall and disease-free survivals were 71% (100% IB-IIA and 84% IIB vs 36% IIIB; P = 0.001) and 88%, respectively. None of the nonresponders survived (median 10 months, 6-25), compared with an 84% 5-year survival of responders (P < 0.001). FIGO stage and parametrial involvement significantly predicted response to NACT which was the only independent variable affecting survival (P = 0.006). This retrospective study provided evidence of the chemosensitivity of locally advanced cervical adenocarcinoma and that chemoresponsiveness is the most potent predictor of cure, as demonstrated in squamous cell cervical cancer. Combined NACT and RS is a feasible treatment which seems to be able to improve the outcome of Stage IB-IIB cervical adenocarcinoma. Randomized trials comparing this new strategy with conventional treatments seem to be warranted.