Indocyanine green as a new trend in sentinel lymphatic node detection in oncogynecology.

In oncological surgery the importance of the sentinel node concept is increasing, as we are capable of reducing the surgical burden of patients and its associated morbidity and preserving adequate oncological safety at the same time. Recently, there has been development of lymph node mapping techniques, where the most promising method appears to be the immunofluorescent one using indocyanine green dye. This technique provides high sensitivity in sentinel node detection in comparison with other existing methods using a dye in combination with a radionuclide. The indocyanine green technique has several advantages, and at the same time, we can use this method in non-oncological indications in gynecological surgery.

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.

Shadow cell differentiation in endometrioid carcinomas of the uterus. Its frequent occurrence and beta-catenin expression.

Shadow cell differentiation (SCD) is typical for pilomatrixoma and related follicular tumors of the skin. However, it has been described rarely in some extra-cutaneous lesions such as gonadal teratoma, craniopharyngioma, odontogenic cyst, and in rare visceral carcinomas (lung, bladder, gallbladder, uterus, ovary, and colon). In our practice, we have noticed that the occurrence of shadow cells is not very rare in endometrioid carcinoma (EC) of the uterus. For exact determination of SCD in these tumors, we reviewed 59 consecutive cases of uterine EC. The series included curettage and hysteroscopic specimens. We have found SCD in 9 (15.3 %) of the tumors. In these cases, the age of the patients and FIGO grade did not differ significantly from other ECs. Immunohistochemically, all ECs with SCD showed nuclear expression of beta-catenin in areas of SCD, indicating a possible role of the Wnt signaling pathway in tumorigenesis as well as a role of nuclear accumulation of beta-catenin by trans-differentiation from glandular toward squamous and shadow cell phenotypes. We have found that the relatively frequent presence of SCD in ECs can assists in the diagnosis of these tumors.

Laparoscopic surgery in women with endometrial cancer: the learning curve.

OBJECTIVE: The aim of this study was to assess the effect of increasing surgeons's experience in the laparoscopic surgery of women with endometrial cancer (EC) on the surgical outcome of these patients. STUDY DESIGN: Data were obtained from a prospectively collected database of 108 patients two oncolaparoscopic centers in Czech Republic who underwent laparoscopically assisted surgical staging (LASS) from April 1996 to March 2001. Patients were arranged in chronological order and divided into three groups, based on the date of their surgery. The three groups were compared in patient characteristics and surgical outcome using one-way analysis of variance (ANOVA) and Wilcoxon rank sum test. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital Kladno, Czech Republic. RESULTS: The three groups were similar in patient characteristics. Operative times for laparoscopic staging with pelvic lymphadenectomy (LN) decreased significantly from mean of 156.3 min for group 1 to 142.8 min for group 3 (P < 0.05). In cases LASS with pelvic lymphadenectomy was significant increase in the number lymph nodes harvested (12.4 for group 1, 13.9 for group 2, and 15.4 for group 3, P < 0.05). In cases LASS without lymphadenectomy was not significant difference in operating time, estimated blood loss, rate of conversion to laparotomy, operative complications, and length of hospital stay among the compared groups. The number of patients who underwent para-aortic lymphadanectomy was too small (n = 22), and their distribution was asymmetrical for comparison. CONCLUSION: A learning curve is demonstrated in the LASS of women with endometrial cancer. With increasing surgeon's team experience, there is significant decrease in operative time for staging with pelvic lymph node dissection and increase in the number of pelvic lymph nodes removed. The para-aortic lymphadenectomy (PALN) was found to be more challenging than pelvic lymphadenectomy.

Laparoscopic pelvic lymphadenectomy in the surgical treatment of endometrial cancer: results of a multicenter study.

OBJECTIVE: To analyze the results and determine the contribution of laparoscopic pelvic lymphadenectomy in the surgical treatment of women with endometrial cancer and compare with the open technique. METHODS: A prospective multicenter study was carried out on 120 women who underwent laparoscopic surgery (96 women) and open procedures (24 women) for endometrial cancer between April 1996 and March 2000. RESULTS: Four patients whose laparoscopic surgery was completed by laparotomy were excluded from the study. The other 92 laparoscopic procedures were successfully completed. Laparoscopically assisted surgical staging (LASS) was performed based on the grade of the tumor and the depth of myometrial invasion. Sixty-seven of the patients underwent hysterectomy, bilateral salpingooophorectomy (BSO), and pelvic lymphadenectomy, and 25 women also had para-aortic lymph node sampling dissection. Eleven of these patients had positive pelvic or para-aortic nodes. The mean operating time for the laparoscopic procedure was significantly longer (173.8 min, P < 0.0001) than the time for the open procedure (135.0 min). The rate of complications was similar in both groups. The recovery time was significantly reduced (P < 0.0001). CONCLUSION: The laparoscopic approach to hysterectomy and lymphadenectomy for early stage endometrial carcinoma is an attractive alternative to the abdominal surgical approach. The advantages of laparoscopically assisted surgical staging are patient related. Because the abdominal incision is avoided, the recovery time is reduced. Laparoscopic pelvic lymph node dissection is a procedure that is appropriate, when applicable.