Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial.

BACKGROUND: Most patients with epithelial ovarian cancer (EOC) relapse despite primary debulking surgery and chemotherapy (CT). Autologous dendritic cell immunotherapy (DCVAC) can present tumor antigens to elicit a durable immune response. We hypothesized that adding parallel or sequential DCVAC to CT stimulates antitumor immunity and improves clinical outcomes in patients with EOC. Based on the interim results of sequential DCVAC/OvCa administration and to accommodate the increased interest in maintenance treatment in EOC, the trial was amended by adding Part 2. METHODS: Patients with International Federation of Gynecology and Obstetrics stage III EOC (serous, endometrioid, or mucinous), who underwent cytoreductive surgery up to 3 weeks prior to randomization and were scheduled for first-line platinum-based CT were eligible. Patients, stratified by tumor residuum (0 or <1 cm), were randomized (1:1:1) to DCVAC/OvCa parallel to CT (Group A), DCVAC/OvCa sequential to CT (Group B), or CT alone (Group C) in Part 1, and to Groups B and C in Part 2. Autologous dendritic cells for DCVAC were differentiated from patients' CD14+ monocytes, pulsed with two allogenic OvCa cell lines (SK-OV-3, OV-90), and matured in the presence of polyinosinic:polycytidylic acid. We report the safety outcomes (safety analysis set, Parts 1 and 2 combined) along with the primary (progression-free survival (PFS)) and secondary (overall survival (OS)) efficacy endpoints. Efficacy endpoints were assessed in the modified intention-to-treat (mITT) analysis set in Part 1. RESULTS: Between November 2013 and March 2016, 99 patients were randomized. The mITT (Part 1) comprised 31, 29, and 30 patients in Groups A, B, and C, respectively. Baseline characteristics and DCVAC/OvCa exposure were comparable across the treatment arms. DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5.9%) in Group A and 2 of 53 patients (3.8%) in Group B. Median PFS was 20.3, not reached, and 21.4 months in Groups A, B, and C, respectively. The HR (95% CI) for Group A versus Group C was 0.98 (0.48 to 2.00; p=0.9483) and the HR for Group B versus Group C was 0.39 (0.16 to 0.96; p=0.0336). This was accompanied by a non-significant trend of improved OS in Groups A and B. Median OS was not reached in any group after a median follow-up of 66 months (34% of events). CONCLUSIONS: DCVAC/OvCa and leukapheresis was not associated with significant safety concerns in this trial. DCVAC/OvCa sequential to CT was associated with a statistically significant improvement in PFS in patients undergoing first-line treatment of EOC. TRIAL REGISTRATION NUMBER: NCT02107937, EudraCT2010-021462-30.

Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.

OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

An Adsorptive and Antioxidant Vaginal Gel Clears High-Risk HPV- and p16/Ki-67-Associated Abnormal Cytological Cervical Findings: A post-hoc Subgroup Analysis of a Prospective Randomized Controlled Trial on CIN2 and p16 Positive CIN1.

Objective: To analyze the course of p16/Ki-67-positive abnormal cytological cervical findings and high risk (hr)-HPV- and p16/Ki-67-clearances in women treated with a vaginal gel. Methods: 172 women with a histological diagnosis of CIN2 or p16-positive CIN1 lesions were selected based on a positive cytological p16/Ki-67 test. For 3 months, 75 patients in the active arm (AA) daily administered 5 ml of a vaginal gel. Ninety seven patients in the control arm (CA) underwent no treatment ("watchful waiting"). Endpoints were cytological evolution, p16/Ki-67- and hr-HPV-clearances. Results: At 3 months, cytological regression was observed in 76% (57/75) of patients in the AA compared with 25% (24/97) in the CA. Progression occurred in 5% (4/75) of the AA compared with 15% (15/97) of the CA. The p16/Ki-67 status change was statistically significantly (p < 0.001) in favor of the AA: 77% (58/75) became negative compared to 21% (20/97) in the CA. hr-HPV prevalence decreased significantly (p < 0.001) in the AA from 87 to 44%, while increasing in the CA from 78 to 84%. Cytological regression and p16/Ki-67 changes persisted in the AA at 6 months. Conclusions: The vaginal gel significantly cleared hr-HPV and p16/Ki-67 and was associated with improved cytological findings, thereby potentially offering an effective option against oncogenic risk. Clinical Trial Registration: Identifier: [ISRCTN11009040].

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial.

PURPOSE: The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. METHODS: 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. RESULTS: Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. CONCLUSION: SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. TRIAL REGISTRATION NUMBER: ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.

Live Birth Following Uterine Transplantation From a Nulliparous Deceased Donor.

BACKGROUND: Nulliparous uterine grafts have never been used in uterus transplantation (UTx), possibly due to presumed infertility. Our objective was to verify the feasibility of nulliparous uterine graft transplantation. METHODS: The Czech Uterus Transplant Trial (registered under ClinicalTrials.gov, identifier NCT03277430) is a 2-arm trial comparing the efficacy of deceased donor (DD) versus live-donor uterus transplant (10 patients in both arms). A 25-year-old patient suffering from inborn absolute uterine factor infertility underwent a DD uterus transplant. The donor was a 20-year-old nulliparous brain-dead donor. RESULTS: The transplant procedure was uneventful. The posttransplant period was complicated by (1) recurrent episodes of acute cellular rejection, (2) neutropenia necessitating the administration of granulocyte colony-stimulating factor, (3) vaginal anastomotic stenosis treated with the insertion of a self-expanding stent, (4) the concurrence of Clostridium difficile colitis and acute appendicitis, and (5) temporary renal function impairment of a combined cause. Two years after the UTx, after the fourth embryo transfer, the patient became pregnant. Apart from gestational diabetes mellitus, the pregnancy was uneventful. Due to preterm contractions, delivery was achieved via caesarean section at gestational age 34 + 6 years. The postoperative course was uneventful for both the mother and the newborn. CONCLUSIONS: Herein, we report the first live birth after a DD UTx in Europe. This report provides a proof of concept that nulliparous uteri may present a suitable source of uterine grafts for UTx. Stenting may serve as a feasible treatment method for vaginal anastomotic stenosis.

Intraoperative consultation in gynecologic pathology.

Intraoperative consultation represents an integral part of diagnostic protocols in gynecologic oncology. It may be indicated 1) to evaluate the biologic nature of a pathologic process (distinction between nonneoplastic lesions and tumors), 2) to classify the histologic type of tumor and assess its biologic behavior (typing), 3) to confirm or rule out the metastatic origin of a tumor, 4) to determine the degree of differentiation and extent of local spread of a malignant tumor (grading and staging), 5) to detect tumor deposits in lymph nodes, 6) to examine surgical resection margins, 7) to detect products of conception in uterine curettings when ectopic pregnancy is suspected and 8) to collect native tumor tissue for ancillary studies (molecular methods, flow cytometry). A frozen section of adnexal masses is commonly requested and focused primarily on the recognition of malignant tumors, the distinction between borderline tumors and carcinomas, and the identification of a metastatic process in the ovary. An intraoperative consultation may also be beneficial in the risk stratification of patients with endometrial carcinoma for the indication of lymphadenectomy, in the assessment of an endocervical surgical resection margin during fertility sparing and less radical surgery for the carcinoma of uterine cervix and in the detection of tumor spread into the lymph nodes (including sentinel lymph nodes). For the appropriate evaluation of a frozen section, awareness of the relevant clinical data and history of the patient, interpretation of the histologic findings in the context of macroscopic appearance of a specimen and an active interaction with the surgeon are required as essential conditions. Keywords: intraoperative consultation - frozen section - gynecologic pathology - tumors of ovary - metastases - sentinel lymph node.

Review of neoadjuvant chemotherapy and trachelectomy: which cervical cancer patients would be suitable for neoadjuvant chemotherapy followed by fertility-sparing surgery?

The number of patients given neoadjuvant chemotherapy (NAC) followed by fertility-sparing surgery in cervical cancer is still scarce. Only a few centres perform these procedures, and thus, such procedures remain largely in the experimental stage. Patients that do not fulfil the criteria for standard fertility-sparing procedure can be included in studies with NAC followed by fertility-sparing procedure. We must consider that both oncological and pregnancy outcomes are important. Patients with only microscopic disease after NAC are apparently the best candidates for fertility-sparing surgery. Current data are not sufficient to identify the optimal procedure after NAC [abdominal radical trachelectomy (ART) or vaginal radical trachelectomy (VRT) or simple trachelectomy]. Some evidence suggests that pregnancy outcome is better after simple trachelectomy as compared with VRT or ART. Long-term results regarding oncological outcome for this concept are still lacking. Adjuvant chemotherapy in patients with histopathological risk factors (lymphovascular space involvement (LVSI), macroscopic residual disease) would decrease a risk of recurrence.

A prospective study in the evaluation of quality of life after vulvar cancer surgery.

OBJECTIVE: The aim of this study was to prospectively monitor the patients' quality of life (QoL) after vulvar cancer surgery. DESIGN: The design was prospective clinical study. SETTING: The study was set in the Department of Obstetrics and Gynecology, 2nd Medical Faculty of the Charles University and University Hospital Motol, Prague, Czech Republic. METHODS: A group of 36 patients underwent vulvar cancer surgery: 24 patients were subject to inguinofemoral lymphadenectomy (RAD) and 12 to sentinel lymph node biopsy. To evaluate QoL, the European Organisation for Research and Treatment of Cancer, QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 and 12 months after surgery. RESULTS: In patients with vulvar cancer after inguinofemoral lymphadenectomy, increased fatigue and impaired lymphedema were observed. In the group of patients after sentinel lymph node biopsy, none of the QoL variables worsened postoperatively. Comparing both groups 12 months after surgery, the RAD group had significantly worse outcomes in body image and cognitive functioning than the sentinel lymph node biopsy group.Patients in the RAD group, who received adjuvant radiotherapy (n = 13), had worse QoL in symptom experience (P < 0.05) at 6 and 12 months after the surgery than patients without radiotherapy (n = 11). CONCLUSIONS: Less radical surgery showed objectively better QoL results.

Oncological and pregnancy outcomes after high-dose density neoadjuvant chemotherapy and fertility-sparing surgery in cervical cancer.

OBJECTIVE: 28 women under 35years with early-stage cervical cancer and strong desire for fertility preservation that do not fulfil standard criteria for fertility-sparing surgery (tumour larger than 2cm or with deep of infiltration more than half of stroma) were included in prospective study. METHODS: Dose-dense neoadjuvant chemotherapy (NAC) was performed on all 28 patients in 10-day intervals: cisplatin plus ifosfamide in squamous cell cancer (15 women-53.6%) or cisplatin plus doxorubicin in adenocarcinoma (13 women-46.3%). Patients underwent laparoscopic lymphadenectomy and vaginal simple trachelectomy after NAC. Patients with positive lymph nodes or inadequate free surgical margins underwent radical hysterectomy. RESULTS: No residual disease was found in 6 women (21.4%), microscopic disease was observed in 11 women (39.3%) and macroscopic tumour in was observed in 11 women (39.3%). Ten women (35.7%) lost fertility. Four women (20%) after fertility-sparing surgery recurred, two died of the disease (10%). Fertility was spared in 20 (71.4%) women and 10 of them became pregnant (50%). Eight women delivered ten babies (6 term and four preterm deliveries). There were two miscarriages in second trimester (in one woman) and one in first trimester. One woman underwent four unsuccessful cycles of IVF, one failed to become pregnant and one recurred too early. Two women underwent chemoradiotherapy for recurrence and lost chance for pregnancy. CONCLUSIONS: Downstaging by NAC in IB1 and IB2 cervical cancer before fertility-sparing surgery is still an experimental procedure, but shows some promise. Long-term results in relation to oncological outcome for this concept are still needed.

The association of taxane resistance genes with the clinical course of ovarian carcinoma.

Taxane and platinum-based chemotherapy regimens are standard treatment for advanced ovarian carcinoma. Expression levels of putative markers of taxane resistance in carcinoma tissues and paired peritoneal samples (n=55) and in 16 samples of ovaries without signs of carcinoma were compared with clinical data and the patients' time to progression. KIF14, PRC1, CIT and ABCC1 genes were significantly overexpressed in carcinomas when compared with normal ovarian tissues, while ABCB1 and CASP9 expression was decreased. Associations of protein expression of the proliferation marker Ki-67 with KIF14, PRC1, ABCB1 and CASP2 were found. Lastly, it was discovered that ABCB1 and CASP2 levels associated with FIGO stage and that the CIT level associated with the time to progression of ovarian carcinoma patients (P<0.0001). In conclusion, ABCB1, CASP2, KIF14, PRC1 and CIT genes seem to associate with surrogate markers of ovarian carcinoma progression and CIT gene associates with therapy outcome.

Current status of sentinel lymph node mapping in the management of endometrial cancer.

The prognosis of endometrial cancer (EC) is generally favorable, while lymph node status remains the most important prognostic factor. Sentinel lymph node mapping (SLNM) could help to find women in whom adjuvant therapy could be omitted. This review analyzes different techniques of injection and histopathologic elaboration of SLNM in EC. Results of studies on SLNM in ECs seem to be promising, but only a small series have been published so far. The studies are subdivided into three groups by the technique of injection (hysteroscopic, subserosal and cervical). Range of detection rate for SLNM varies from 45 to 100%. Hysteroscopic injection is not easy to learn; moreover, exact peritumoral injection in large tumors is often impossible. Subserosal administration of tracer is difficult during laparoscopic or robotic surgery. Cervical injection is quite a controversial technique because distribution of SLNs in ECs is different from cervical cancer; moreover, there is no large study using cervical injection with systematic pelvic and para-aortic lymphadenectomy.

High-dose density neoadjuvant chemotherapy in bulky IB cervical cancer.

OBJECTIVE: The endpoint of this prospective study is to evaluate response rate, survival and toxicity of high-dose density neoadjuvant chemotherapy (NAC) in bulky IB cervical cancer. MATERIAL AND METHODS: Between January 1998 and December 2009, 154 women were enrolled into study. Three patients were withdrawn. Of the 151 women, 119 had stage IB2 cervical cancer (78.8%) and 32 had stage IB1 cancer (21.2%) infiltrating the whole cervical stroma. Women received 3-4cycle cisplatin-75mg/m(2) and ifosfamide-2g/m(2) in cases of squamous-cell cancer or cisplatin-75mg/m(2) and doxorubicin-35mg/m(2) in adenocarcinoma every 10days and then underwent radical hysterectomy type III. Patients who had non-resectable disease underwent chemoradiotherapy. RESULTS: The overall response rate (reduction of tumor volume more than 50%) was 78.8%. Reduction of tumor volume less than 50% was seen in 15.2%. Tumor progression during chemotherapy occurred in nine patients (6.0%). There were positive lymph-nodes in 26 patients (18.3%) of the 142 that underwent surgery. 38 women underwent adjuvant radiotherapy (26.7%). There were 26 recurrences (17.2%). After surgery 20 women recurred from 142 (14.1%) and after primary radiotherapy 6 from 9 women recurred (66.7%). 25 of 151 women died from disease (16.5%). At the time of the study, surgery was performed in 118 women 5 or more years ago, 19 of them died of disease. Five-year specific survival is 83.6%. Grade 3-4 neutropenia was found in only 7.3% of the women, and grade 3-4 thrombocytopenia were found in 1.3%. CONCLUSION: High-dose density NAC appears to be feasible in the treatment IB bulky cervical cancer and toxicity is acceptable. Adjuvant radiotherapy was used only in 26.7%.

A prospective study in detection of lower-limb lymphedema and evaluation of quality of life after vulvar cancer surgery.

BACKGROUND: Lower-limb lymphedema is one of the most disabling adverse effects of vulvar cancer surgery. Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a modern noninvasive method to detect lymphedema. The first aim of this study was to prospectively determine the prevalence of secondary lower-limb lymphedema after surgical treatment for vulvar cancer using objective methods, circumference measurements and MFBIA technique. The second aim was to compare quality of life (QoL) before and 6 months after vulvar surgery. METHODS: Twenty-nine patients underwent vulvar cancer surgery in our study: 17 underwent inguinofemoral lymphadenectomy (RAD), and 12 underwent sentinel lymph node biopsy (CONS). Patients were examined before and 6 months after vulvar surgery by measuring the circumference of the lower limbs and with MFBIA. A control group of 27 healthy women was also measured. To evaluate QoL, the European Organisation for Research and Treatment of Cancer (EORTC) QoL questionnaires (QLQ-C30 and QLQ-CX24) were administered to patients before and 6 months after surgery. RESULTS: Using circumference measurement, 9 lymphedemas (31%) were diagnosed: 3 (25%) in the CONS and 6 (37.5%) in the RAD group (P = 0.69). After vulvar surgery, patients in the RAD group reported more fatigue and worsening of physical and role functioning. When comparing both groups, the RAD group had significantly worse parameters in social functioning, fatigue, and dyspnea. CONCLUSIONS: Lower radicality in inguinofemoral lymphadenectomy shows a trend toward lower morbidity and significantly improves QoL. Multifrequency Bioelectrical Impedance Analysis was tested in these patients as a noninvasive, objective method for lymphedema detection. Detection of lymphedema based on subjective evaluations proved to have an unsatisfactory sensitivity. Less radical surgery showed objectively better results in QoL.

The role of neoadjuvant chemotherapy and surgery in cervical cancer.

The role of neoadjuvant chemotherapy (NAC) in "bulky" and locally advanced cervical cancer has been of interest for the last 25 years, and in many countries, NAC has become the standard of care. In the present paper, we review our 10 years' experience with high-dose-density NAC in cervical cancer management in 141 women (CervNAC I protocol). High-dose-density neoadjuvant chemotherapy and radical surgery has resulted in high clinical response rates and seems to be feasible in the management of stage IB bulky cervical cancer. Neoadjuvant chemotherapy reduces tumor volume and positivity of lymph nodes and thus minimizes the need for postoperative radiotherapy or chemoradiotherapy. Tumor size reduction and node negativity allows less radical surgical procedures such as modified radical hysterectomy or nerve-sparing radical hysterectomy. Early and especially late toxicity of our high-dose density chemotherapy is acceptable. Neoadjuvant chemotherapy followed by surgery represents a valid alternative to primary chemoradiotherapy in young and sexually active patients. Five-year survival in patients who underwent surgery in our study was 80.6%. Currently, 3 papers with 3 approaches have been published on NAC before fertility-sparing surgery. One of the limitations of fertility-preserving surgery is deep stromal invasion and tumors larger than 2 cm. The idea underlying NAC is to reduce the size of the cervical tumor to preserve fertility. In the present paper, we also review our experience with high-dose-density NAC in fertility-sparing surgery in 15 women (LAP3-NAC protocol).

Advances in fertility-sparing surgery for cervical cancer.

This article reviews the literature on fertility-sparing surgery in early cervical cancer. The article evaluates selection criteria, preoperative management and the most frequent surgical procedures used for preservation of fertility in cervical cancer. The article also analyzes oncological, fertility and pregnancy results. Oncological outcomes are not statistically different among single groups (vaginal radical trachelectomy, abdominal radical trachelectomy, simple trachelectomy or cone with or without neoadjuvant chemotherapy). Oncological results after fertility-sparing procedures in women with tumors smaller than 2 cm are comparable with women with the same risk factors after radical hysterectomy. Pregnancy following fertility-sparing surgery is associated with a variety of adverse pregnancy outcomes, especially second-trimester loss and preterm delivery. Less radical procedures (simple trachelectomy or cone with or without neoadjuvant chemotherapy) show statistically significant better pregnancy results. The pregnancy rate after abdominal radical trachelectomy was dramatically lower than in women treated with other types of fertility-sparing surgery. In the future, it will be necessary to optimize the technique and management of fertility-sparing surgery in order to attain good oncological results. Pregnancy outcomes should be given high priority. Fertility-sparing surgery is valuable for women who want to preserve their reproductive capability.

A prospective study of postoperative lymphedema after surgery for cervical cancer.

OBJECTIVE: Lymphedema is a severe postoperative complication in oncological surgery. Multifrequency bioelectrical impedance analysis (MFBIA) is a new method for early lymphedema detection. The objective was to establish the methodology of MFBIA for lower-limb lymphedema and to detect a lymphedema in patients undergoing cervical cancer surgery. METHODS: From a population of 60 patients undergoing cervical cancer surgery, 39 underwent radical hysterectomy Wertheim III (RAD group), and 21 underwent conservative surgery (laparoscopic lymphadenectomy plus simple trachelectomy/simple hysterectomy--CONS group). A control group of 29 patients (CONTR group) was used to determine the SD of impedance at zero frequency (R0). Patients were examined before surgery and at 3 and 6 months after surgery by MFBIA and by measuring the circumference of the lower limbs. RESULTS: No differences were found between the CONS and RAD groups on age, height, weight, and histopathologic type of tumor. However, the number of dissected lymph nodes differed significantly between the groups (17.3 in the CONS group vs 25.8 in the RAD group, P = 0.0012). The SD of R0 in the CONTR group was 36.0 and 39.0 for the right and the left leg, respectively. No difference in prevalence of lymphedema based on circumference method was found (35.9% in the RAD and 47.6% in the CONS groups, not statistically significant). CONCLUSIONS: No difference in the prevalence of lymphedema was found between the CONS and RAD groups. A methodology for MFBIA for the detection of lower-limb lymphedema was described.

Less radical surgery than radical hysterectomy in early stage cervical cancer: a pilot study.

OBJECTIVE: The purpose of this pilot study was to evaluate the feasibility and safety of a less radical surgery; laparoscopic lymphadenectomy followed by a simple vaginal hysterectomy in sentinel lymph node (SLN) negative early cervical cancer patients. Treatment-associated morbidity and oncological outcome were evaluated. PATIENTS AND METHODS: From December 2000 to September 2007, 60 patients (50 squamous and 10 adenocarcinoma patients) in stages 3-IA1, 11-IA2 and 46-IB1 with median age of 44.6 years (range 33-64 years) were enrolled. Patients were selected based on favorable cervical tumors (IA1 with lymph-vascular space invasion [LVSI], IA2 and IB1 with tumor size less than 20 mm and less than half of stromal invasion). All patients underwent laparoscopic SLN identification using frozen section (FS). Negative SLN patients underwent complete pelvic laparoscopic lymphadenectomy and vaginal hysterectomy. FS positive patients underwent radical hysterectomy with low paraaortic lymphadenectomy. RESULTS: The average number of sentinel nodes per side was 1.4 with detection rate per side of 95%. The average number of removed nodes was 23.2. Five patients (8.3%) were SLN positive. There were two false negative FS results (both were micrometastases in SLN). Median follow-up was 47 months (range 12-92). There were no recurrences in 55 SLN negative patients and in 5 SLN positive patients. CONCLUSION: Lymphatic mapping and SLN identification improved safety in less radical surgery in early stage cervical cancer. This preliminary study showed that it is both feasible and safe to reduce the radicality of parametrial resection for small tumor volume in SLN negative patients. Results also indicated that treatment-associated morbidity is low.

A less radical treatment option to the fertility-sparing radical trachelectomy in patients with stage I cervical cancer.

The purpose of the two pilot studies was to determine the feasibility and safety of using less-radical fertility-preserving surgery: laparoscopic lymphadenectomy with sentinel lymph node identification (SLNI) followed by a large cone or simple trachelectomy (LAP-I protocol) and the LAP-III protocol, which includes neoadjuvant chemotherapy (NAC). LAP-I: Forty women underwent laparoscopic SLNI, frozen-section analysis, and a complete pelvic lymphadenectomy as the first step of treatment. Seven days after final histopathological processing of dissected nodes, a large cone or simple vaginal trachelectomy was performed in patients with negative nodes. Nine women had a tumor larger than 20 mm, prompting the administration of three cycles of NAC before surgery. LAP-I: Six frozen sections were positive (15%). In these cases, a type III Wertheim was immediately performed. There were no false-negative SLNs. There was one central recurrence, but after chemoradiation therapy, there was no evidence of the disease 62 months post-treatment. Twenty-four of 32 women whose reproductive ability had been maintained tried to conceive. Of these 24 women, 17 became pregnant (71% pregnancy rate). Eleven mothers gave birth to 12 children (1 at 24 weeks, 1 at 34 weeks, 1 at 36 weeks, and 9 between 37 and 39 weeks). LAP-III: Nine patients were included. In 7 of these 9 women, reproductive ability was maintained, with 3 women becoming pregnant (1 full term and 2 ongoing). SLNI improves safety in fertility-sparing surgery. Large cone or simple trachelectomy combined with laparoscopic pelvic lymphadenectomy can be a feasible method that yields a high, successful pregnancy rate. NAC followed by fertility-sparing surgery is an experimental alternative treatment for larger tumors.

A prospective study of sentinel lymph node status and parametrial involvement in patients with small tumour volume cervical cancer.

OBJECTIVE: The purpose of prospective study is to determine incidence and distribution of pelvic lymph node (LN) involvement, sentinel lymph node (SLN) involvement and pathologic parametrial involvement (PI) in stage Ia2 and small Ib1 cervical cancer. PI is defined as positive parametrial LN or discontinuous malignant cells in parametrium. METHODS: After radical abdominal hysterectomy, 158 women patients were stratified into two groups based on tumour size: In Group 1 (91 women) tumours were less than 20 mm and less than half of stromal invasion. In Group 2 (67 women) tumours were between 20 and 30 mm and infiltration was not more than 2/3 of cervical stroma. RESULTS: In Group 1 positive SLN was detected in 11(12.1%) patients; of these, 3 (27.3%) had positive PI. In 80 women with negative SLN PI was not detected. In Group 2 positive SLN was detected in 14 (20.9%) patients: PI was found in four (28.6%) of these 14 patients. No PI was detected in 53 women with negative SLN. CONCLUSION: No PI was observed in early cervical cancer if SLNs were negative. However, we found PI in 28.0% of women with positive SLN. Statistical analysis revealed that the results were highly significant. Based on our results, radical removal of parametrium in SLN negative patients is questionable.