HE4 as a serum biomarker for the diagnosis of pelvic masses: a prospective, multicenter study in 965 patients.

BACKGROUND: To evaluate the diagnostic value of adding human epididymis protein 4 (HE4), cancer antigen 125 (CA125) and risk of malignancy algorithm (ROMA) to ultrasound for detecting ovarian cancer in patients with a pelvic mass. METHODS: This was a prospective, observational, multicenter study. Patients aged > 18 years who were scheduled to undergo surgery for a suspicious pelvic mass had CA125 and HE4 levels measured prior to surgery, in addition to a routine transvaginal ultrasound scan. The diagnostic performance of CA125, HE4 and ROMA for distinguishing between benign and malignant adnexal masses was assessed using receiver operating characteristic (ROC) analysis and the corresponding area under the curve (AUC). RESULTS: Of 965 evaluable patients, 804 were diagnosed with benign tumors and 161 were diagnosed with ovarian cancer. In late-stage ovarian cancer, CA125, HE4 and ROMA all had an excellent diagnostic performance (AUC > 0.92), whereas in stage I and II, diagnostic performance of all three biomarkers was less adequate (AUC < 0.77). In the differential diagnosis of ovarian cancer and endometriosis, ROMA and HE4 performed better than CA125 with 99 and 98.1% versus 75.0% sensitivity, respectively, at 75.4% specificity. CONCLUSIONS: ROMA and HE4 could be valuable biomarkers to help with the diagnosis of ovarian cancer in premenopausal patients in order to differentiate from endometriosis, whereas CA125 may be more adequate for postmenopausal patients.

[Is There a Negative Night or Weekend Effect on the Child's Postnatal State Among Migrant Women?] / Gibt es einen negativen Nacht- oder Wochenendeffekt auf den kindlichen postnatalen Zustand bei Frauen mit Migrationshintergrund?

RESEARCH QUESTION: Is neonatal morbidity of women with a migration background (= a proxy variable for an increased risk of cultural/linguistic communication problems) increased in the sense of a "weekend effect"? METHODS: Data was collected at 3 Berlin maternity hospitals directly in the delivery room based on standardized interviews (questions on sociodemographics, care aspects, migration) and supplemented by maternal and clinical perinatal data. Surrogate markers for the child's morbidity were the Apgar score and umbilical cord pH value or transfer to a children's hospital. Descriptive and logistic regression analyses were carried out. RESULTS: The data sets of 2,014 1st-generation migrants, 771 2nd-generation migrants, and 2,564 women without a migrant background were included, including 39.7% so-called day-births (Monday - Friday, 7 a.m.-6 p.m.). In 2 models, the influence of birth time and various other parameters was examined for the 2 proxy parameters of childhood morbidity. The chances of unfavorable Apgar or umbilical pH levels were increased in births in the evening, at night, on weekends and public holidays (OR 1.84, 95% CI 1.23-2.76, p=0.003), in operative vaginal births (OR 3.36, 95% CI 2.07-5.46, p<0.001) or a secondary cesarean section (OR 1.94; 95% CI 1.28-2.96, p=0.002). The migration status of the woman giving birth was irrelevant. SUMMARY: Despite possible intercultural and linguistic communication problems, women with a migration background are treated as well as pregnant women without a migration background irrespective of the time of day or day of the week.

Closure of the cervical os in patients after fertility preserving treatment for early cervical cancer - results of a prospective observational study.

INTRODUCTION: Up to 50% of the infants delivered after radical vaginal trachelectomy (RVT) are born prematurely. An effective strategy to reduce this number could be the closure of the cervical os (CCO). PATIENTS AND METHODS: Fifteen pregnant patients who had a RVT due to early cervical cancer were included in this prospective case control study. All patients were scheduled for CCO early in the second trimester. CCO was performed in 12 patients. Their data were compared to data from 125 pregnancies after a RVT without CCO. RESULTS: The patients who had CCO were compared to patients without CCO. One patient had an early rupture of the amniotic membranes prior to CCO. Two patients chose not to undergo CCO. In 12 patients CCO was performed without complications. There was no early preterm delivery in the CCO group as compared to a rate of 5% in 125 pregnancies in the non-CCO group. DISCUSSION: We developed a protocol to reduce the risk of preterm deliveries after a RVT. Digital examinations should be avoided. Vaginal checks for pH can discover ascending infections - the main cause of preterm deliveries after a RVT. Infections should be treated adequately. CCO can further reduce the risk of preterm deliveries after a RVT.

Follow-up after radical vaginal trachelectomy (RVT): patients' problems and physicians' difficulties.

PURPOSE: Patients after radical vaginal trachelectomy (RVT) need specific follow-up treatment because their problems differ from those of other gyneco-oncologic patients. Anatomic changes after surgery complicate examinations. Recognition and treatment of these issues require physician's expertise. PATIENTS AND METHODS: We evaluated the follow-up data of 70 patients who underwent RVT for early cervical cancer between 03/2010 and 12/2013. The follow-up interval in the first 2 years was 3 and 6 months in the following 2 years. We used a tailored protocol to describe the special problems after RVT. RESULTS: Cervical stenosis was one of the central problems independent of time interval to RVT. Physicians' most significant problem was to locate the exact position of the neo-cervix and thus to receive valid pap smears. CONCLUSIONS: Follow-up of patients after RVT needs special expertise because the symptoms differ from those after hysterectomy and examinations ensuring oncologic safety require special attention.

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.

Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: rationale, description of the technique, and outcome.

OBJECTIVE: Individualized treatment of pregnant patients with cervical cancer is mandatory; hence, information on nodal status is pivotal to allow a waiting strategy in early-stage disease.We aimed to verify the oncological safety and surgical reproducibility of a standardized laparoscopic pelvic lymphadenectomy in pregnant patients with cervical cancer. METHODS: We standardized laparoscopic pelvic lymphadenectomy during the first and second term of gestation in 32 patients with cervical cancer since 1999. According to gestational week (GW) of less than 16 GWs or more than 16 GWs, 2 different techniques were used. RESULTS: The International Federation of Gynecology and Obstetrics stages were IA in 10 patients, IB1 in 17 patients, IB2 in 4 patients, and IIA in 1 patient. Mean (SD) GW was 17.5 (5.1) weeks. Mean (SD) operative time was 105.4 (29) minutes. Mean (SD) blood loss was 5.3 (10.2) mL. There were no conversion to laparotomy and no intraoperative complications. A median number of 14 pelvic lymph nodes (range, 8-57) were harvested. Median hospital stay was 6 days. Median follow-up is 42.5 months (range, 17-164). Four patients had lymph node metastases. Five patients interrupted their pregnancy. Fourteen patients were given neoadjuvant platin-based systemic therapy. All patients are alive and disease free. All children born through cesarean delivery at a mean (SD) 34 (1.9) GWs are well and show normal clinical neurological development. CONCLUSIONS: To the best of our knowledge, this is the largest series so far reported on laparoscopic pelvic lymphadenectomy during pregnancy. This procedure is safe and associated with good oncological and obstetrical outcomes.

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.

Vaginal-assisted laparoscopic radical hysterectomy (VALRH) versus laparoscopic-assisted radical vaginal hysterectomy (LARVH) in the treatment of cervical cancer: surgical results and oncologic outcome.

PURPOSE: The aim of this study was to compare the morbidity and survival rates of patients with early-stage cervical cancer treated by vaginal-assisted laparoscopic radical hysterectomy (VALRH) with pair-matched laparoscopic-assisted vaginal radical hysterectomy (LARVH) controls. METHODS: One hundred nine patients who underwent VALRH for cervical cancer stage FIGO Ia1, L1 to IIb between 2007 and 2009 and 200 patients who underwent LARVH between 1994 and 2002 were analysed in their entirety and in a group of matched pairs. RESULTS: In both groups, there was no conversion to laparotomy due to an intraoperative complication. Prevalence of blood transfusions was significantly lower in the VALRH group (2 vs. 39 patients; P < 0.001). Bladder function resumed sooner (P < 0.001), and patients were discharged earlier after VALRH (P < 0.001). There were no intraoperative injuries in the VALRH group. In the LARVH group, the most common intraoperative injury occurred to the bladder (7.0 %). Postoperatively, the most common complication in the VALRH group was ureterovaginal fistula (2.7 %) and fever (2.7 %) and in the LARVH ureterostenosis (3.5 %), uretero/bladder fistula (1 %), and fever (7 %). For patients with tumour stage Ib1 the 5-year recurrence-free survival was 92.8 % and 5-year overall survival 95.2 % following VALRH and 88.2 and 90.5 %, respectively, following LARVH. No significant difference in the survival rate was found (log rank, P = 0.740). CONCLUSION: VALRH is a feasible and oncologically safe surgical option for patients with early-stage cervical cancer. We believe the complication rate is lowered in VALRH by the combination of the laparoscopic and vaginal approach.

Neonatal outcome in infants of patients with radical vaginal trachelectomy.

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.

Volatile organic compounds (VOCs) in exhaled breath of patients with breast cancer in a clinical setting.

BACKGROUND: Carcinogenic products in the exhaled breath of cancer patients are of growing medical interest as they can serve as noninvasive disease markers. Breath analysis can be used as an alternative or complementary diagnostic tool in breast cancer patients who have a different pattern of chemical composition in their breath. This study aims to verify the existence of specific volatile organic compounds (VOCs) in the breath of breast cancer patients. METHODS: This prospective study included ten patients suffering from breast cancer and ten healthy pair-matched women. Breath samples of each member of the two respective groups were taken and scanned by gas chromatography/mass spectometry for the presence of volatile organic compounds such as alkanes, ketones, halogenated hydrocarbon, aldehydes, and esters. RESULTS: The spectrum of VOCs differed significantly within the two groups. Five specific VOCs could be identified as typical discriminatory markers in the breath samples. Four VOCs were elevated in the healthy controls, one specific VOC was found to be elevated in women affected by breast cancer CONCLUSIONS: This pilot study revealed a specific VOC pattern using gas chromatography in the breath of breast cancer patients. Five specific breast cancer-VOCs were identified. At relatively low cost the identification of VOCs may be used to detect breast cancer.

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.

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.

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.

Addressing concerns about cisplatin application during pregnancy.

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.

Vaginal-assisted laparoscopic radical hysterectomy: rationale, technique, results.

OBJECTIVE: Total laparoscopic radical hysterectomy (TLRH) makes it difficult to resect adequate vaginal cuff according to tumor size and to avoid tumor spread after opening the vagina. Laparoscopic-assisted radical vaginal hysterectomy (LARVH) is associated with higher risk for urologic complications. METHODS: The vaginal-assisted laparoscopic radical hysterectomy (VALRH) technique comprises 3 steps: (1) comprehensive laparoscopic staging, (2) creation of a tumoradapted vaginal cuff, and (3) laparoscopic transsection of parametria. We retrospectively analyzed data of 122 patients who underwent VALRH for early stage cervical cancer (n=110) or stage II endometrial cancer (n=12) between January 2007 and December 2009 at Charité University Berlin. RESULTS: All patients underwent VALRH without conversion. Mean operating time was 300 minutes, and mean blood loss was 123cc. On average, 36 lymph nodes were harvested. Intra- and postoperative complication rates were 0% and 13.1%, respectively. Resection was in sound margins in all patients. After median follow-up of 19 months, disease-free survival and overall survival for all 110 cervical cancer patients was 94% and 98%, and for the subgroup of patients (n=90) with tumors ≤pT1b1 N0 V0 L0/1 R0, 97% and 98%, respectively. CONCLUSION: VALRH is a valid alternative to abdominal radical hysterectomy and LARVH in patients with earlystage cervical cancer and endometrial cancer stage II with minimal intraoperative complications and identical oncologic outcomes.

Implication of the examining pathologist to meet the oncologic standard of lymph node count after laparoscopic lymphadenectomy.

OBJECTIVE: The lymph node number as benchmark in oncologic operations depends on the patient's anatomy, surgeon's skill and pathologist's accuracy. The influence of the pathologist is barely evaluated. METHODS: A retrospective analysis of lymph node numbers after 700 laparoscopic lymphadenectomies in correlation to the examining pathologists was done. Three surgeons from the same department performed all operations at 2 campi, where 2 separate pathology institutions exist. Lymph node specimens were assigned randomly to any of the 62 involved pathologists. RESULTS: The mean number of lymph nodes was equal for all surgeons. Lymph node specimens were analyzed in the pathology institute of campus I and II in 416 and 284 cases, respectively. The mean number of lymph nodes following pelvic and para-aortic lymphadenectomy was 36 at campus II and 30 at campus I (p < 0.0001). There was also a significant difference for pelvic (19.9 vs. 17.7; p < 0.0001) and para-aortic lymph node counts (16.2 vs. 14.1; p < 0.01) between both pathology institutes. At campus II, 22.6% of lymph node counts did not meet the oncologic standard for pelvic and 16.7% did not meet the standard for para-aortic lymph nodes. Moreover, at campus I, 35.5 and 20.8% of pathologists described less than the oncologic limit of pelvic and para-aortic lymph nodes, respectively. CONCLUSION: The number of removed lymph nodes is not an absolute parameter for surgical radicality. Interdisciplinary cooperation with pathologists is mandatory to meet oncologic standards.

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.

Histopathology-based combined surgical approach to rectovaginal endometriosis.

OBJECTIVE: To describe a new surgical approach to rectovaginal endometriosis. Rectovaginal endometriosis can be infiltrative or superficial involving the bowel. Only infiltrative disease should be treated by intestinal resection. However, infiltration of endometriosis cannot be confirmed by preoperative imaging techniques. METHODS: A total of 48 women with infiltrative rectovaginal endometriosis were included in this prospective study. Surgery was performed using a newly developed technique. All bowel resections were indicated according to operative findings and not on the basis of preoperative imaging technique results. RESULTS: The decision for rectosigmoidal resection was based on the results of the intraoperative dissection of the rectovaginal septum. Histologically, infiltration of the ventral bowel wall was confirmed in all cases. CONCLUSION: This new surgical technique for the treatment of rectovaginal endometriosis allows precise diagnosis and treatment with low morbidity. A resection of the mesorectum is not necessary because the endometriotic nodules are always located on the antimesenteric surface of the bowel.

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.