Statement of the AGO Kommission Ovar, AGO Study Group, NOGGO, AGO Austria, Swiss AGO, BGOG, CEEGOG, GEICO, and SFOG regarding the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in epithelial ovarian cancer.

An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.

Lower-Limb Lymphedema after Sentinel Lymph Node Biopsy in Cervical Cancer Patients.

BACKGROUND: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. METHODS: A prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. RESULTS: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. CONCLUSIONS: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Central Pathology Review in SENTIX, A Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2).

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

Successful ablation of acardiac twin with Histoacryl.

OBJECTIVE: Acardiac twin occurs in 1:35,000 pregnancies. Several techniques have been described to treat this condition. Some techniques have been suggested as golden standard; however, new are still being tried. CASE REPORT: This is a case of a 32-year-old patient who had successful ablation of the acardiac twin with Histoacryl. The diagnosis of the acardiac twin was made in the 11 weeks + 3 weeks of pregnancy. Due to the development of myocardial hypertrophy and pericardial transudate of the pumping fetus, we had performed ablation of the acardiac twin with Histoacryl in the 21 weeks' +5 weeks' gestation. The procedure was uneventful, and the healthy fetus had no signs of distress. In the 33 weeks' +5 weeks' gestation, she had Cesarean section due to distress of the healthy fetus. The female baby was healthy, weighing 2380 g, Apgar score 9/10. The mummified mass of acardiac fetus weighted 300 g. Nine months later, the child is doing well. CONCLUSION: Histoacryl is suitable for the ablation of an acardiac twin. Further studies are needed to prove the efficacy of this technique.

Pregnancy after uterine artery embolization for the treatment of myomas: a case series.

PURPOSE: Uterine artery embolization (UAE) has become an alternative therapy for the treatment of symptomatic myomas. The questions of fertility and pregnancy outcome after uterine artery embolization are still not answered. The study presents the results of pregnancies after UAE. The main goal was to evaluate the course of these pregnancies and concentrate on possible complications. METHODS: This was a prospective study from June 2009 till October 2011. Patients with symptomatic uterine myomas were included. The evaluation of the symptoms was done by quality of life questionnaire and bleeding charts. UAE was performed by superselective microcatheterization technique. Women still planning pregnancy were included in the study after signing detailed informed consent. Pregnant women after UAE were followed as high-risk pregnancies. RESULTS: A total of 98 patients underwent uterine artery embolization for symptomatic myomas; 21 expressed their wish to become pregnant, out of which 6 had successful spontaneous conception (23.08 %) and 1 patient was pregnant twice, and altogether there were seven pregnancies. During gestation and delivery, there was no serious complication. There was one missed abortion and one placental retention. Myomas did not show growth pattern during pregnancy. CONCLUSIONS: Data from further prospective, randomized trials comparing fertility and pregnancies after UAE with other treatment modalities are needed. UAE, with the new techniques of superselective microcatheterization, could be, in the future, a possible approach even in women with future maternity plans.

Myoma expulsion after uterine artery embolization.

Uterine artery embolization (UAE) has become a standard therapy in the treatment of symptomatic uterine myomas. The procedure is associated with a few complications. One of them is myoma expulsion. A 32-year-old woman was sent to our hospital with diagnosed intramural myoma with dysmenorrhea and pressure symptoms. UAE was performed since the patient preferred conservative treatment. The procedure was without any complications. Three weeks after embolization, she was readmitted because of vaginal discharge and minor bleeding. We diagnosed expulsion of necrotic myoma and performed transvaginal resection. Four months later, the patient is symptom free. Expulsion of intramural myoma can be thus considered as definite treatment and not a complication of embolization therapy.

An alternative management for growth retarded fetus with absent end-diastolic velocity in umbilical artery and normal cardiotocography.

OBJECTIVES: Intrauterine growth retardation (IUGR) is associated with fetal adverse conditions. The most important cause of growth restriction and poor perinatal outcome is chronic fetal hypoxemia (CFH). Adaptation to CFH can be studied by Doppler velocity waveform on umbilical and fetal arteries and cardiotocography (CTG). METHODS: Preterm delivery, as an elimination of CFH, has to be confronted with the risks of prematurity. A special situation may occur when CTG is normal at the absence of end-diastolic velocity (AEDV). AEDV in the umbilical artery precedes the onset of abnormal CTG, whose duration differs considerably among the fetuses. The time after the onset of AEDV in pregnancy may be utilized for performing exact diagnosis by fetal blood analysis. CASE: Primigravida at 30 gestational weeks was referred because of IUGR. IUGR, AEDV, oligohydramnion, and normal fetal anatomy were revealed. CTG was normal. Indication for cordocentesis was to perform cord blood gases analysis and to obtain fetal caryotype. Cordocentesis revealed normal caryotype, values of pH, and fetal blood gases were considered satisfactory. Continuation of pregnancy was decided in spite of persistent AEDV. At 33 gestational weeks pathological CTG was an indication for induction of labor. Labor, delivery, umbilical blood gases, postpartal and neonatal outcome were normal. CONCLUSION: In the case of fetal monitoring controversy assessment of umbilical blood analysis may be crucial. This examination is significant and independent of the interval between cordocentesis and the onset of CTG pathology. This interval may be utilized for intrauterine treatment and for optimizing obstetric management.