Malgorzata Lanowska

Fertility outcome after radical vaginal trachelectomy: a prospective study of 212 patients.

Objective For treatment in patients with early-stage cervical cancer, radical vaginal trachelectomy (RVT) as a fertility-preserving surgery can be put on a par with radical hysterectomy as to oncologic safety. Our aim was to investigate the fertility concerns and outcome. Methods Prospective collection of fertility data of patients treated with RVT. The data were collected on personal communication, by telephone, or e-mail correspondence. Descriptive statistical analysis was performed. Results Between March 2005 and April 2010, 212 patients were followed up after RVT. Only 76 patients (35.9%) were seeking parenthood currently. Sixty pregnancies occurred in 50 women. Five patients (8.3%) had first-trimester miscarriage, 3 had second-trimester miscarriage (5.0%), 2 patients decided for pregnancy termination (3.3%), and 1 patient (1.7%) had an ectopic pregnancy. Three women (5.0%) delivered prematurely before 28th weeks of gestation, 15 (25.0%) delivered between 28 and 36 weeks, and 27 women (45.0%) reached full term. Four pregnancies are ongoing. Conclusions Preservation of childbearing function is a great advantage for patients with early-stage cervical cancer. Many patients do not seek parenthood immediately. We see no impairment of fertility and have solid data on pregnancy outcome. Premature labor is the main problem in pregnancy after RVT.

Radical vaginal trachelectomy (RVT) combined with laparoscopic lymphadenectomy: Prospective study of 225 patients with early-stage cervical cancer

Objective: The aim of the study was to prove the surgical and oncological safety of radical vaginal trachelectomy (RVT) and laparoscopic lymphadenectomy for patients with early-stage cervical cancer who are seeking parenthood. Methods: A database of 225 patients with early-stage cervical cancer and intention to treat by RVT after laparoscopic lymphadenectomy was prospectively maintained. A total of 212 patients were treated according to the protocol. The procedure was preformed in a standardized manner, and life table analysis was applied. Results: In the cohort of patients treated according to protocol, 8 recurrences occurred and 4 patients died from recurrence. The median follow-up time was 37 months (range, 0-171 months). The 5-year recurrence-free and overall survival was 94.4% and 97.4%, respectively. Perioperative and short-term postoperative complications were rare (2.8% and 7.5%, respectively). No severe long-term complications occurred. Conclusions: Radical vaginal trachelectomy combined with laparoscopic lymphadenectomy is a safe method for treatment of patients with early-stage cervical cancer who are seeking parenthood.

Radical vaginal trachelectomy after laparoscopic staging and neoadjuvant chemotherapy in women with early-stage cervical cancer over 2 cm: oncologic, fertility, and neonatal outcome in a series of 20 patients.

Objectives The aim of the study was to assess oncologic and fertility outcome of treatment in patients with cervical cancer of more than 2 cm seeking parenthood. Methods The regimen consisted of laparoscopic lymphadenectomy as a staging procedure to confirm no lymph node metastases before neoadjuvant chemotherapy (NACT) consisting of 2 or 3 cycles of paclitaxel/ifosfamide/cisplatin followed by radical vaginal trachelectomy (RVT). Oncologic and fertility outcome was evaluated prospectively. Results Twenty women were enrolled up to now. The mean age was 32 years (range, 26–41 years), and mean tumor size was 3 cm (range, 2.1–5.0 cm). Lymphadenectomy was performed before NACT without complications. During NACT, hematologic toxicity grade 3 was observed in 2 of 20 patients, and renal toxicity grade 3 in 1 of 20 patients. Radical vaginal trachelectomy was performed in 18 women until now with 2 intraoperative complications (ureter injury and injury of internal iliac vein). There were no severe postoperative or long-term complications. Complete pathologic remission was found in 9 of 18 patients. In 2 of 18 patients, chemoradiation was recommended because of insufficient pathologic response in the RVT specimen. After a mean follow-up of 23 months (range, 1–88 months), 1 relapse was observed. After RVT, 7 women tried to conceive until now. Seven pregnancies occurred in 5 women. Four children were born, 2 of whom were premature (31 weeks 2 days and 33 weeks 4 days of gestation); 1 pregnancy is ongoing. Conclusions Laparoscopic lymphadenectomy followed by NACT and RVT in pN0 patients with cervical cancer of more than 2 cm seems to be an oncologically safe procedure with promising fertility outcomes.

Soluble Vascular Endothelial Growth Factor Receptor-1 (sFLT-1) Mediates Downregulation of FLT-1 and Prevents Activated Neutrophils From Women With Preeclampsia From Additional Migration by VEGF

Neutrophil activation and increased migration is associated with preeclampsia and is resolved after delivery. Preeclampsia is an inflammatory disorder where altered levels of vascular endothelial growth factor (VEGF) and the circulating soluble fms-like tyrosine kinase 1 (sFlt-1) have a pathogenic role. VEGF, by binding to FLT-1, induces leukocytic chemotaxis. We studied expression and function of FLT-1 in maternal neutrophils during preeclampsia and normal pregnancies. Analysis of maternal neutrophils showed the relationship between FLT-1 expression and week of gestation. Preeclamptic women express lower FLT-1 and sFLT-1 in neutrophils. In contrast, serum levels of sFLT-1 in patients with preeclampsia are increased and, therefore, inhibit upregulation of FLT-1 in neutrophils by neutralizing VEGF. VEGF-dependent FLT-1 expression is regulated by changing FLT-1-promoter activity. Promoter activity is decreased by sFLT-1. In vitro experiments demonstrated that migration of neutrophils is regulated by VEGF via FLT-1 and excess of sFLT-1. Thus, VEGF-dependent migration of neutrophils is decreased during preeclampsia as a consequence of excess circulating sFlt1. But, they still increase migration by fMLP and, therefore, migration of neutrophils from preeclamptic women is highly activated when compared with the normotensive group. In conclusion, besides being involved in inducing an antiangiogenic state in the serum, excess of sFLT-1 seems to prevent activated neutrophils from women with preeclampsia from additional migration by VEGF. We provide evidence that neutrophils may be involved in the pathophysiology of pregnancy-related hypertensive disorders.

Exenterations 60 years after first description: results of a survey among US and German Gynecologic Oncology Centers.

Objective: Sixty years after exenterative surgery was introduced into gynecologic oncology, the indications and contraindications, techniques, and adjuvant therapies after exenteration are controversially discussed between gynecologic oncologists. Methods: To evaluate the current patterns of care, a questionnaire with 48 items was sent to 40 Society of Gynecologic Oncologists member clinics with fellowship programs and all 38 German teaching hospitals for gynecologic oncology. Results: The mean number of exenterations performed during the last 5 years was comparable in both countries. Consistently, (central) recurrent cervical cancer or persistent tumor after chemoradiation is the main indication. Before exenteration, positron emission tomography-computed tomography is mostly performed in the United States, whereas magnetic resonance imaging is the preferred imaging tool in Germany. Staging is more often done surgically in the United States (61%) compared with Germany (32%). None of the US institutions recommend an exenteration for patients with International Federation of Gynecology and Obstetrics stage IVA in contrast to 43% in Germany. In the case of fistula to the bladder and/or rectum, exenteration was recommended only by 29% and 61% in US and German clinics, respectively. In Germany, interdisciplinarity with general surgeons, urologists, plastic surgeons, and radio-oncologists is more common. There is consensus to apply adjuvant therapy after exenteration in patients with positive margins and/or positive lymph nodes. However, adjuvant therapy is more frequently recommended in Germany (93%) than in the United States (74%). Conclusions: Our data reflect considerable differences about indications and contraindications, preoperative staging, and adjuvant therapy for pelvic exenteration between Germany and the United States.

Pattern of cancer recurrence in 320 patients after radical vaginal trachelectomy.

Objective The oncological outcome regarding disease-free survival and overall survival after radical vaginal trachelectomy (RVT) is the same as the rates after radical hysterectomy. We aim to analyze predictive and risk factors and death in patients with cervical cancer undergoing fertility preservation by laparoscopic lymphadenectomy and RVT. Methods Three hundred twenty patients with cervical cancer underwent RVT between March 1995 and February 2013. In our study, we examined recurrence rates analyzed by risk factors. We classified the presence of lymphovascular space invasion, depth of tumor infiltration, tumor size, and tumor grading as risk factors. The mean follow-up time was 48 months. Results Ten of the 320 patients had cancer recurrence. Recurrence appeared at a mean time of 26.1 months (3–108 months) after RVT. Five patients died within 8.8 months (4–15 months) after recurrence was diagnosed. Two of these 5 patients had distant metastasis at the time of recurrence. Five patients were treated successfully by surgery, and 4 patients were treated successfully by chemotherapy. The mean follow-up after the recurrence of these 5 patients is 76 months (6–120 months). None of the 10 patients with recurrences in our series showed significant high-risk factors. Conclusion There seems to be no pattern in the recurrence of cancer after RVT. It is strictly mandatory to follow up the patients closely every 3 months after RVT to diagnose recurrence at an early stage so therapeutic options such as chemoradiation are still available. Once distant metastasis occurs, prognosis is not good.

Prevalence of lymph nodes in the parametrium of radical vaginal trachelectomy (RVT) specimen.

OBJECTIVE In order to evaluate radicality in fertility preserving surgery in women with early invasive cervical cancer we analyzed the parametrium of specimens of patients treated by radical vaginal trachelectomy for the presence of lymph nodes. We tried to identify morphologic factors associated with the presence of parametrial lymph nodes. METHODS We analyzed surgical specimens of 112 patients who underwent radical trachelectomy between June 2004 and April 2009 at the Department of Gynecologic Oncology at Charité Campus Benjamin Franklin and Campus Mitte. All parametrial tissue was step sectioned and a total of 1878H&E stained histological sections were analyzed. RESULTS In 8 patients (7.1%) a total of 13 lymph nodes were detected. Five lymph nodes in four patients had been primarily detected by routine histological examination. In one of these patients (0.9%) a 2mm lymph node metastasis was found. Serial sectioning revealed additional seven lymph nodes in four patients. The thickness of parametrium correlated significantly with the presence of lymph nodes in the parametrium. CONCLUSION The presence of small lymph nodes in the parametrium of specimens of radical trachelectomy is low. In patients with early-stage cervical cancer, the incidence of metastasis is less than 1%. Preoperative assessment of the volume of the parametrium may indicate which patients need parametrial resection.

Vaginal robot‐assisted radical hysterectomy (VRARH) after laparoscopic staging: feasibility and operative results

To describe a technique of vaginal robot‐assisted radical hysterectomy (VRARH) that utilizes the advantages of a robotic system and eliminates the manipulation of cancer tissue.

Neonatal outcome in infants of patients with radical vaginal trachelectomy

Abstract Objective: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40% and 80%. Outcome of infants is complicated by a preterm delivery rate of 30–50%. We investigated pregnancy and neonatal outcome after RVT. Methods: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants’ data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. Results: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43%) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52%) were born preterm, of with 17 (29%) were <32 gestational weeks (GW) and seven (12%) were <28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. Conclusion: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.

Addressing concerns about cisplatin application during pregnancy.

Abstract Introduction: Cervical cancer in second trimester of pregnancy is an oncologic challenge. Cisplatin is recommended to prevent cancer progression. This is a series correlating in vivo cisplatin concentration in the fetomaternal compartment and in breast milk with child development. Methods: Eight consecutive patients with cervical cancer diagnosed during the second trimester underwent conization/biopsy and/or pelvic laparoscopic lymphadenectomy (LAE). Delay of pregnancy in combination with neoadjuvant monochemotherapy was performed. After 2–4 cycles of cisplatin monochemotherapy cesarean section followed by radical hysterectomy was performed above 31 weeks of gestation. Synchronous samples from maternal blood, umbilical cord blood, and amniotic fluid were taken and analyzed. A probe of breast milk was taken from three patients. Pediatric aftercare was done every three months postpartum. Results: Laparoscopic LAE was uncomplicated in all patients. In seven out of eight patients lymph nodes were tumor free. Nine healthy babies were delivered. Pediatric follow-up showed normal development. Cisplatin concentrations in the umbilical cord and amniotic fluid were 31–65% and 13–42% of the amount in maternal blood, respectively. In breast milk, cisplatin was detectable in 1–10% of maternal blood concentration. Conclusion: Knowledge of significant lower cisplatin concentrations in fetal compartment and normal child growth provides additional security to apply cisplatin in pregnancy. Breastfeeding cannot be recommended.