A Preparatory Virtual Reality Experience Reduces Anxiety before Surgery in Gynecologic Oncology Patients: A Randomized Controlled Trial.

Perioperative anxiety is common among patients undergoing surgery, potentially leading to negative outcomes. Immersive virtual reality (VR) has shown promise in reducing anxiety in various clinical settings. This study aimed to evaluate the effectiveness of VR in reducing perioperative anxiety in patients undergoing gynecological oncology surgery and was conducted as a single-center, double-arm, single-blinded randomized controlled trial at the Gold Coast University Hospital, Queensland, Australia. Participants were randomized into the VR intervention + care as usual (CAU) group (n = 39) and the CAU group (n = 41). Anxiety scores were assessed using a six-tier visual facial anxiety scale at baseline, after the intervention/CAU on the same day, and, several days up to weeks later, immediately before surgery. There was no significant difference in baseline anxiety scores, type of operation, or suspected cancer between the two groups. The VR intervention significantly reduced anxiety scores from baseline to preoperative assessment (p < 0.001). The median anxiety score in the VR intervention group decreased from 3 (interquartile range 2 to 5) at baseline to 2 (2 to 3) prior to surgery, while the control group's scores were 4 (2 to 5) and 4 (3 to 5), respectively. Multivariate analysis showed that group assignment was the sole outcome predictor, not age, type of procedure, or the time elapsed until surgery. Thus, VR exposure was effective in reducing perioperative anxiety in patients undergoing gynecological oncology surgery. The use of VR as a preparation tool may improve patient experience and contribute to better surgical outcomes, warranting further research into exploring the potential benefits of VR in other surgical specialties and its long-term impact on patient recovery.

Virtual Reality for Anxiety Reduction in Women Undergoing Colposcopy: A Randomized Controlled Trial.

OBJECTIVE: To test whether headset-delivered virtual reality (VR) content affects satisfaction and/or anxiety in women with cervical squamous intraepithelial lesions undergoing colposcopy and colposcopically guided cervical biopsy. METHODS: In this single-center, randomized trial, the authors measured overall satisfaction (100-mm visual analog scale) and situation-specific anxiety (STAI-S) in 247 women with suspected cervical squamous intraepithelial lesions wearing either no VR headset (arm 1, control) or a VR headset before (arm 2) or before and during colposcopy (arm 3). Secondary endpoints were pain, discomfort, and anxiety during colposcopy, heart rate, and 72-hour follow-up parameters: overall satisfaction, bleeding severity, bleeding duration, pain, and use of analgesics. Analysis was by intention to treat. RESULTS: Median values for overall satisfaction were 100 (interquartile range, 90-100) in controls (n = 83), 100 (95-100) in arm 2 (n = 82), and 100 (95-100) in arm 3 (n = 82), respectively ( p = .92). The median Δ of situational anxiety (baseline vs after colposcopy) was -8 (-13 to -3), -8 (-16.5 to -4), and -10 (-20.5 to -4.5), respectively ( p = .09). The secondary endpoints pain during colposcopy (20 [10-50] vs 20 [10-40] vs 30 [10-50]; p = .65), discomfort during colposcopy (30 [10-50] vs 30 [10-50] vs 20 [10-50]; p = .46), and anxiety during colposcopy (20 [0-50] vs 10 [0-40] vs 10 [0-30]; p = .44), were not different between arms. Follow-up data showed no improvement in the 2 VR arms compared with controls (overall satisfaction, p = .37; bleeding severity, p = .09; pain level, p = .89; duration of pain; p = .23; and use of analgesics; p = .39). Per-protocol analysis did not change the results. CONCLUSIONS: A VR headset showing a 360-degree surround vision film has no effect on satisfaction or anxiety in women undergoing colposcopy.

Innovative Diagnostic and Therapeutic Interventions in Cervical Dysplasia: A Systematic Review of Controlled Trials.

Cervical dysplasia is a common precancerous lesion affecting 1% to 2% of women worldwide. Significant progress in the diagnosis and treatment of cervical dysplasia have been made in the last decade. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled clinical trials reporting on the efficacy and safety of diagnostic and therapeutic interventions for cervical dysplasia. Data were analyzed according to PRISMA guidelines. In total, 33 studies reporting on 5935 women were identified. We recommend intravenous or intracervical lidocaine for pain reduction during colposcopically-directed cervical biopsies but not topical lidocaine, music, or video colposcopy. Monsel's solution might be used to control bleeding after cervical biopsies. The acetic acid test should be scored 1 min after the application of acetic acid and should be followed by Lugol's iodine test for an optimal yield of LSIL/HSIL. LEEP/LLETZ remains the standard and techniques such as SWETZ, C-LETZ, and TCBEE are not superior. LEEP/LLETZ should be performed under local anesthesia and with direct colposcopic vision. Cryotherapy and thermoablation might be used in women with LSIL, especially in women with HIV infection, but LEEP/LLETZ remains the standard for HSIL. Topical imiquimod remains an experimental procedure. In conclusion, significant progress has been made in the last decade regarding both diagnostic interventions as well as therapeutic interventions for women with cervical dysplasia. Based on >30 controlled clinical trials, we were able to formulate specific and evidence-based recommendations.

Development and technical validation of an ultrasound nebulizer to deliver intraperitoneal pressurized aerosols in a rat colon cancer peritoneal metastases model.

BACKGROUND/AIM: To develop and validate a nebulizer device for anti-cancer research on pressurized intraperitoneal aerosol supply in a preclinical peritoneal metastases (PM) rat model. MATERIAL AND METHODS: For aerosol generation, an ultrasonic nebulizer (USN) was modified. Aerosol analyses were performed ex-vivo by laser diffraction spectrometry (LDS). Intraperitoneal (IP) 99mtechnetium sodium pertechnetate (99mTc) aerosol distribution and deposition were quantified by in-vivo single photon emission computed tomography (SPECT/CT) and compared to liquid IP instillation of equivalent volume/doses of 99mTc with and without capnoperitoneum. PM was induced by IP injection of HCT116-Luc2 human colon cancer cells in immunosuppressed RNU rats. Tumor growth was monitored by bioluminescence imaging (BLI), 18F-FDG positron emission tomography (PET) and tissues examination at necropsy. RESULTS: The USN was able to establish a stable and reproducible capnoperitoneum at a pressure of 8 to 10 mmHg. LDS showed that the USN provides a polydisperse and monomodal aerosol with a volume-weighted diameter of 2.6 µm. At a CO2 flow rate of 2 L/min with an IP residence time of 3.9 s, the highest drug deposition efficiency was found to be 15 wt.-%. In comparison to liquid instillation, nebulization showed the most homogeneous IP spatial drug deposition. Compared to BLI, 18F-FDG-PET was more sensitive to detect smaller PM nodules measuring only 1-2 mm in diameter. BLI, 18F-FDG PET and necropsy analyses showed relevant PM in all animals. CONCLUSIONS: The USN together with the PM rat model are suitable for robust and species-specific preclinical pharmacological studies regarding intraperitoneal delivery of pressurized aerosolized drugs and cancer research.

Video colposcopy versus headlight for large loop excision of the transformation zone (LLETZ): a randomised trial.

PURPOSE: To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. METHODS: Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. RESULTS: LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98-2.37] vs. 1.67 [1.15-2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41-95.2] vs. 90 [47.2-130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5-9] vs. 9 [8-10]; P < 0.001) and general satisfaction (7.5 [5-9] vs. 10 [8-10]; P < 0.001). CONCLUSION: Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons' satisfaction. CLINICAL TRIAL REGISTRATION: NCT04326049 (ClinicalTrials.gov).

Sequential Application of Lugol's Iodine Test after Acetic Acid for Detecting Cervical Dysplasia: A Prospective Cohort Study.

Applying Lugol's iodine solution to the cervix followed by colposcopic assessment is an established standard test to identify low grade/high grade squamous intraepithelial lesions (LSIL/HSIL). Here, we assessed the performance of Lugol's iodine test during colposcopy using a standardized protocol with 5% acetic acid followed by 5% Lugol's iodine solution and recording the most severe acetowhite (MSAWL) and iodine-negative (MSINL) lesions in a prospective cohort of consecutive women referred to our specialized colposcopy unit. The primary study endpoint was the sensitivity/specificity of MSINL for the detection of LSIL/HSIL. Secondary endpoints were the time to first appearance of the MSINL, MSINL staining intensity, and fading of MSINL. Three hundred and twenty women were included. The sensitivity and specificity of MSINL for the detection of LSIL/HSIL was 81.4 (95%-confidence interval (CI) 77.3-85.0)% and 29.5 (24.2-35.5)%, respectively. Ninety-six MSINL were identified exclusively by Lugol's iodine test (no pathology, n = 46; LSIL, n = 29; HSIL, n = 21) (number needed to biopsy to identify one additional LSIL/HSIL = 1.9). In 17/320 (5.3%) patients, the clinical management was changed based on the result of Lugol's iodine test. Video analysis showed an instant appearance of the MSINL within 10 s in 100% of cases. Intensity of MSINL significantly correlated with the presence/absence of LSIL/HSIL (Spearman rank order correlation; p < 0.0001). Fading of iodine-induced staining intensity over time was not observed. Thus, Lugol's iodine showed moderate sensitivity and poor specificity, but changed clinical management in 5% of cases when used in addition to acetic acid.

Establishment of a Mouse Ovarian Cancer and Peritoneal Metastasis Model to Study Intraperitoneal Chemotherapy.

Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics were assessed using PET scan, bioluminescence imaging (BLI), and histological tumor analysis. Liquid IPC was achieved by intraperitoneal injection with/without capnoperitoneum (6-7 mmHg). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was mimicked using an intratracheal drug aerosol administration system (micro-nozzle), which, as demonstrated by ex vivo granulometric analysis using laser diffraction spectrometry, produced a polydisperse, bimodal aerosol with a volume-weighted median diameter of (26.49 ± 2.76) µm. Distribution of Tc-99m-labeled doxorubicin in mice was characterized using SPECT and was dependent on the delivery mode and most homogeneous when the micro-nozzle was used. A total of 2 mg doxorubicin per kg body weight was determined to be the optimally effective and tolerable dose to achieve at least 50% tumor reduction. Repeated PIPAC (four times at seven-day-intervals) with doxorubicin in SKOV3-luc tumor-bearing mice resulted in halted tumor proliferation and tumor load reduced after the second round of PIPAC versus controls and the number of tumor nodules was significantly reduced (27.7 ± 9.5 vs. 57.3 ± 9.5; p = 0.0003). Thus, we established the first mouse model of OC PM for the study of IPC using a human xenograft with SKOV3 cells and an experimental IPC setup with a miniaturized nozzle. Repeated IPC was feasible and demonstrated time-dependent anti-tumor activity.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for rare gynecologic indications: peritoneal metastases from breast and endometrial cancer.

BACKGROUND: Peritoneal metastasis (PM) in patients with breast (BC) and endometrial cancer (EC) is rare and treatment options are limited. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has demonstrated efficacy against PM from various cancers, but its efficacy in BC/EC patients is unknown. METHODS: Retrospective cohort study of patients with PM from BC/EC undergoing PIPAC with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were collected within an international prospective PIPAC registry. Study outcomes were microscopic tumor regression grade (TRG), survival, adverse events (CTCAE), and quality of life (QoL). RESULTS: 150 PIPAC procedures in 44 patients (BC/EC = 28/16; mean age 58.8 ± 10.1 and 63.2 ± 10.1 years, respectively) were analyzed. The mean number of PIPACs per patient was 3 (range 0-9) and 3.5 (range 0-10), respectively. Primary/secondary non-access occurred in 4/3 of 150 (5%) procedures. PIPAC induced objective tumor regression as demonstrated by repetitive PM biopsies in 73% (32/44) of patients. Peri- and postoperative CTCAE grade 3 and 4 complications were observed in 12/150 (8%) of procedures. No grade 5 event was observed. After a median follow up of 5.7 (IQR 2.7-13.0) months, overall median survival was 19.6 (95% CI: 7.8-31.5) months (from first PIPAC). QoL indicators (general health, nausea, fatigue, constipation, pain, dyspnea, social, cognitive, emotional, and physical functioning) all improved or were maintained throughout PIPAC treatments. CONCLUSIONS: Repetitive intraperitoneal chemotherapy with PIPAC is feasible and safe in patients with PM from BC and EC. PIPAC induces significant histological regression of PM while maintaining QoL.

Menopausal Hormone Therapy and Risk of Endometrial Cancer: A Systematic Review.

BACKGROUND: Menopausal hormone therapy (MHT) is an appropriate treatment for women with the climacteric syndrome. The estrogen component of MHT effectively alleviates climacteric symptoms but also stimulates the endometrium and thus may increase the risk of endometrial cancer (EC). MATERIALS AND METHODS: We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify controlled and uncontrolled clinical trials reporting on the prevalence and/or incidence of EC among women using MHT. RESULTS: 31 publications reporting on 21,306 women with EC diagnosed during or after MHT were identified. A significantly reduced risk of EC among continuous-combined (cc)MHT users with synthetic progestins (SPs) was demonstrated in 10/19 studies with odds ratios (ORs)/hazard ratios (HRs) between 0.24 and 0.71. Only one study documented an increased risk of EC among long-term users (≥10 years), not confirmed in three other sub-group analyses of women with ≥6, ≥5, and >10 years of ccMHT use. A significantly increased risk of EC among users of sequential-combined (sc)MHT with SPs was demonstrated in 6/12 studies with ORs/HRs between 1.38 and 4.35. Number of days of progestin per month was a significant modulator of EC risk. A decreased risk of EC was seen in obese women. Two studies documented an increased risk of EC among users of cc/scMHT with micronized progesterone. A significantly increased risk of EC among estrogen-only MHT users was demonstrated in 9/12 studies with ORs/HRs between 1.45 and 4.46. The adverse effect of estrogen-only MHT was greatest among obese women. CONCLUSION: ccMHT with SPs reduces the risk of EC, whereas estrogen-only MHT increases the risk. scMHT with SPs and cc/scMHT with micronized progesterone increase the risk of EC depending on type of progestin, progestin dosage, and duration of MHT use.

Syringe or mask? Loop electrosurgical excision procedure under local or general anesthesia: a randomized trial.

BACKGROUND: Loop electrosurgical excision procedure may be performed under local anesthesia or general anesthesia, and practice patterns differ worldwide. No randomized head-to-head comparison has been published to confirm or refute either practice. OBJECTIVE: This study aimed to compare loop electrosurgical excision procedure under local anesthesia vs general anesthesia regarding patient satisfaction and procedure-related outcomes such as rates of involved margins, complications, pain, and blood loss. STUDY DESIGN: Consecutive women referred to our colposcopy unit were recruited. Loop electrosurgical excision procedure was performed under local anesthesia with 4 intracervical injections of bupivacaine hydrochloride 0.5% or under general anesthesia with fentanyl, propofol, and a laryngeal mask with sevoflurane maintenance. The primary endpoint was patient satisfaction assessed on the day of surgery and 14 days thereafter using a Likert scale (score 0-100) and a questionnaire. Secondary endpoints included rates of involved margins, procedure-related complications, pain, blood loss, and surgeon preference. Results were compared using nonparametric and chi-square tests. RESULTS: Between July 2018 and February 2020, we randomized 208 women, 108 in the local anesthesia arm and 100 in the general anesthesia arm. In the intention-to-treat analysis, patient satisfaction did not differ between the study groups directly after surgery (Likert scale 100 [90-100] vs 100 [90-100]; P=.077) and 14 days thereafter (Likert scale 100 [80-100] vs 100 [90-100]; P=.079). In the per-protocol analysis, women in the local anesthesia arm had significantly smaller cone volumes (1.11 cm3 [0.70-1.83] vs 1.58 cm3 [1.08-2.69], respectively; P<.001), less intraoperative blood loss (Δhemoglobin, 0.2 g/dL [-0.1 to 0.4] vs 0.5 g/dL [0.2-0.9]; P<.001), and higher satisfaction after 14 days (100 [90-100] vs 100 [80-100]; P=.026), whereas surgeon preference favored general anesthesia (90 [79-100] vs 100 [90-100], respectively; P=.001). All other secondary outcomes did not differ between groups (resection margin status R1, 6.6% vs 2.1% [P=.26]; cone fragmentation, 12.1% vs 6.3% [P=.27]; procedure duration, 151.5 seconds [120-219.5] vs 180 seconds [117-241.5] [P=.34]; time to complete hemostasis, 60 seconds [34-97] vs 70 seconds [48.25-122.25] [P=.08]; complication rate, 3.3% vs 1.1% [P=.59]). In a multivariate analysis, parity (P=.03), type of transformation zone (P=.03), and cone volume (P=.02) and not study group assignment, age, body mass index, and degree of dysplasia independently influenced the primary endpoint. CONCLUSION: Loop electrosurgical excision procedure under local anesthesia is equally well tolerated and offers patient-reported and procedure-related benefits over general anesthesia, supporting the preferred practice in some institutions and refuting the preferred practice in others.

How long is too long? Application of acetic acid during colposcopy: a prospective study.

BACKGROUND: Application of acetic acid to the cervix followed by colposcopic assessment with or without colposcopically directed biopsy is the standard test used to detect dysplastic lesions of the cervix. However, there is no evidence-based common standard defining how exactly to perform this test. OBJECTIVE: To prospectively define the optimal timing for the colposcopic assessment of acetowhite lesions. MATERIALS AND METHODS: Consecutive women referred to our colposcopy unit were recruited. Using a standardized colposcopy protocol, we recorded the most severe colposcopic lesion 1, 3, and 5 minutes after application of acetic acid (primary study end point). The time to first appearance of the most severe colposcopic lesion, highest staining intensity, and fading of the most severe colposcopic lesion were video documented (secondary study end points, assessed independently by 3 raters). Results were compared using parametric and nonparametric tests. RESULTS: A total of 300 women were included. After 1 minute, 290 of 300 patients (96.7%) were diagnosed with the most severe colposcopic lesion. This proportion did not improve after 3 minutes (290/300 [96.7%]) or after 5 minutes (233/264 [88.3%]). The proportion of minor and major changes continuously declined over time from 142 in 300 (47.3%; 1 minute) to 107 in 264 (40.5%; 5 minutes) and from 110 in 300 (36.7%) to 91 in 264 (34.5%), respectively. The median time until the first appearance of the most severe colposcopic lesion was 13.5 (interquartile range, 3-27.25) seconds and was significantly lower in high-grade squamous intraepithelial lesion (7 [interquartile range, 1-20] seconds) compared to low-grade squamous intraepithelial lesion (19 [interquartile range, 9-39.5] seconds; P < .001). We observed fading of acetowhite lesions in 78% of cases, occurring at a median of 191 (interquartile range, 120-295) seconds after application of acetic acid. Fading started earlier in high-grade squamous intraepithelial lesion compared to low-grade squamous intraepithelial lesion (179.5 [interquartile range, 110- 253.25] versus 212.5 [interquartile range, 146.5-300]; P = .044). Overall, the net difference between colposcopic assessments at 3 minutes versus at 1 minute was 1 more high-grade squamous intraepithelial lesion and 1 less low-grade squamous intraepithelial lesion. CONCLUSION: It is reasonable to conclude that the best time to identify lesions is 1 minute after the application of acetic acid. Continued evaluation for up to 3 minutes may be considered reasonable for an optimal high-grade squamous intraepithelial lesion yield. However, fading of acetowhite lesions is common, especially in high-grade squamous intraepithelial lesions, and supports a recommendation of not prolonging colposcopy beyond 3 minutes.

Ionizing radiation increases the endothelial permeability and the transendothelial migration of tumor cells through ADAM10-activation and subsequent degradation of VE-cadherin.

BACKGROUND: We analyzed the changes in permeability of endothelial cell layers after photon irradiation, with a focus on the metalloproteases ADAM10 and ADAM17, and on VE-cadherin, components crucial for the integrity of endothelial intercellular junctions, and their roles in the transmigration of cancer cells through endothelial cell monolayers. METHODS: Primary HUVEC were irradiated with 2 or 4 Gy photons at a dose rate of 5 Gy/min. The permeability of an irradiated endothelial monolayer for macromolecules and tumor cells was analyzed in the presence or absence of the ADAM10/17 inhibitors GI254023X and GW280264X. Expression of ADAM10, ADAM17 and VE-Cadherin in endothelial cells was quantified by immunoblotting and qRT. VE-Cadherin was additionally analyzed by immunofluorescence microscopy and ELISA. RESULTS: Ionizing radiation increased the permeability of endothelial monolayers and the transendothelial migration of tumor cells. This was effectively blocked by a selective inhibition (GI254023X) of ADAM10. Irradiation increased both, the expression and activity of ADAM10, which led to increased degradation of VE-cadherin, but also led to higher rates of VE-cadherin internalization. Increased degradation of VE-cadherin was also observed when endothelial monolayers were exposed to tumor-cell conditioned medium, similar to when exposed to recombinant VEGF. CONCLUSIONS: Our results suggest a mechanism of irradiation-induced increased permeability and transendothelial migration of tumor cells based on the activation of ADAM10 and the subsequent change of endothelial permeability through the degradation and internalization of VE-cadherin.

Chronic ectopic pregnancy: case report and systematic review of the literature.

BACKGROUND: Chronic ectopic pregnancy (CEP) is a variant of ectopic pregnancy (EP) characterized by low or absent serum human chorionic gonadotropin (hCG) levels, resistance to methotrexate (MTX), and an adnexal mass with fibrosis, necrosis, and blood clots due to repeated and gradual fallopian tube wall disintegration. CEP may complicate the course of patients with EP and is difficult to diagnose. CASE PRESENTATION: The case of a 36-year-old woman with EP, low serum hCG levels, a small echogenic adnexal mass, and resistance to MTX is presented. Salpingectomy was performed and histology demonstrated CEP with fibrosis, necrosis, and a hematocele within degenerated chorionic villi. SYSTEMATIC LITERATURE REVIEW: In a database search, 19 case reports, 3 case-control studies, and 3 case series describing 399 patients with CEP were identified. Serum hCG was negative in 40/124 cases (32%) with reported levels of serum hCG. The most common presenting symptom was abdominal pain (284/399 [71%]), followed by irregular vaginal bleeding (219/399 [55%]), and fever (20/399 [5%]). 73/399 (18%) women were asymptomatic. An adnexal mass was seen in 144/298 (48%) cases with perioperative ultrasound examination and with a mean largest diameter of 6.8 cm. Data on treatment modalities and outcomes were available for 297 women. Of these, 89% underwent surgery as first-line therapy. Laparoscopy was performed in most cases. MTX was the first-line therapy in a minority of cases. Complete resolution was achieved by first-line therapy in 287/297 (97%) cases. Adverse events were reported in 218 patients with CEP. Among those, adverse events ≥ grade 3 were seen in 186/218 (85%) cases. There was no case of treatment-related mortality. CONCLUSION: CEP is a variant of EP with low or absent trophoblast activity. A prolonged clinical course is typical and surgery is the mainstay of treatment.

Acute colonic pseudoobstruction (Ogilvie's syndrome) in gynecologic and obstetric patients: case report and systematic review of the literature.

BACKGROUND: Acute colonic pseudo-obstruction or Ogilvie's syndrome (OS) is a rare form of postsurgical or posttraumatic complication. OS rarely occurs in the postoperative course of gynecologic and obstetric patients and is difficult to diagnose. CASE PRESENTATION: We present the case of an 83-years-old patient with carcinosarcoma of the uterus who developed OS with non-obstructive dilation of the right hemicolon and intraabdominal compression after total abdominal hysterectomy, omentectomy, and lymphadenectomy. Laparotomy with colonic decompression and abdominal dressing was performed. Subsequently, the patient developed pneumonia and peritonitis and died due to septic shock. SYSTEMATIC LITERATURE REVIEW: We identified 49 case reports and 10 case series describing 17 gynecologic (cervical cancer, n = 2; carcinosarcoma of the uterus, n = 1; benign gynecologic condition, n = 14) and 76 obstetric patients (cesarean section, n = 66; OS during pregnancy or after vaginal delivery, n = 10). Outcome data were available for 59 patients. First-line treatment was conservative in 22/59 (37%) cases, laparotomy with decompression or colon resection was performed in 20/59 (34%) cases, endoscopic decompression in 12/59 (20%) cases, and i.v. neostigmine in 4/59 (7%) cases. Resolution was achieved in 22/59 (37%) of patients. The most common second-line treatment was right hemicolectomy. Adverse events grade 3 and 4 were observed in 8/59 and 31/59 patients (together 66%), respectively, mortality was 3/59 (5%). CONCLUSION: OS is a rare postoperative complication of gynecologic and obstetric patients with a good prognosis, but a high morbidity. Pregnancy seems to be a predisposing factor for OS. Conservative treatment is a successful first-line approach.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review.

Cytoreductive surgery (CRS) is an appropriate treatment for selected patients with endometrial cancer (EC)-derived peritoneal metastases (PM). Hyperthermic intraperitoneal chemotherapy (HIPEC) may enhance the therapeutic efficacy of CRS in these patients. We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials and case reports reporting on the safety and efficacy of CRS and HIPEC in patients with EC-derived PM. Eight publications reporting on 68 patients were identified. The mean patient age was 57.1 years and the mean time from initial treatment of EC to CRS and HIPEC was 22.3 months. 41/64 patients had adenocarcinomas, type II cancers were present in 23/64 patients. The mean peritoneal carcinomatosis index (PCI) was 16.7. A complete surgical resection CC-0 was achieved in 44/63 (70%) patients. The chemotherapy regimens used for HIPEC were variable, but all included cisplatin, administered either alone (39/68 patients) or combined with doxorubicin or paclitaxel or mitomycin (29/68 patients). The duration of HIPEC was 60 min in 51/68 patients and 90 min in 17/68 patients. Mostly, the closed technique was used (55/68 patients). Adverse events grades 1/2, 3, and 4 were observed in 23/63, 12/63, and 6/63 patients, respectively. Treatment-associated mortality was 1% (1/63). After CRS and HIPEC, most patients received systemic chemotherapy (46/63 patients). Median disease-free and overall survival ranged from 7 to 18 and 12 to 33 months, respectively. In conclusion, CRS and HIPEC in EC with PM is safe and feasible. An additional therapeutic value of HIPEC is suggested, but prospective comparative trials are warranted.

Calprotectin in pregnancy and pregnancy-associated diseases: a systematic review and prospective cohort study.

PURPOSE: Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy. METHODS: We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy. RESULTS: We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1-3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none. CONCLUSION: Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1-3 and post-partum.

ROBO1 Expression in Metastasizing Breast and Ovarian Cancer: SLIT2-induced Chemotaxis Requires Heparan Sulfates (Heparin).

BACKGROUND: The members of the slit homolog (SLIT) and roundabout homolog (ROBO) families have emerged as important signaling molecules in tumor metastasis. This study analyzed their role in regulating breast cancer (BC) cell motility and chemotaxis and assessed expression of ROBO1 in brain metastases (BMs) of breast, lung, and colon cancer, and in peritoneal metastases (PMs) of ovarian cancer. MATERIALS AND METHODS: The BC cell line MDA-MB231 was subjected to scratch, motility, and chemotaxis assays using heparin and a purified recombinant N-terminal SLIT2 fragment. Protein expression was assessed in primary tumors and metastases by immunohistochemistry. RESULTS: Exposure to SLIT2 induced MDA-MB231 cell motility, but no significant chemotaxis without the presence of heparin. ROBO1 was expressed in 4/5 primary BC and in 18/21 BC-derived BM samples; 7/9 BM primary lung cancer samples also stained positive. In contrast, BMs from colorectal cancer were negative for ROBO1. Primary ovarian cancer and ovarian PM showed ROBO1 expression in 0/6 and in only 2/6 samples, respectively, whereas SLIT2 was observed in 1/6 primary cancer and in 6/6 PMs samples. CONCLUSION: SLIT2 can induce BC cell motility and chemotaxis, but the latter requires the presence of heparin. BM expression of ROBO1 is a common feature of some, but not all cancer types. SLIT2 expression appears to be a general feature of ovarian cancer-derived PMs.

Treatment of Cervical Dysplasia by Clinicians Who Perform Colposcopy in German-speaking Countries - a Questionnaire-based Study.

Introduction In connection with the reorganisation of cervical carcinoma screening, the importance of colposcopy as an integral part of the planned series of clarification testing will greatly increase. Quality standards for performing the colposcopic examination should therefore be defined in detail. A precondition for this is surveying the current standard in clinical practice. The objective of this study was to evaluate the current practice of colposcopy and conisation in Germany by means of a questionnaire aimed at gynaecologists who perform colposcopies in order to document the actual therapeutic standard of treatment of cervical dysplasia. Materials and Methods Gynaecologists were invited via e-mail or during events to participate in a web-based survey. The questionnaire contained 38 questions on management before, during and after the examination as well as questions on the technical implementation of colposcopy and conisation. Results From February 2018 to April 2018, 961 e-mails were sent. A response was received in 197 cases (response rate 20.5%). Responses were received for another 40 questionnaires during events (response rate approx. 80%). After taking the inclusion criteria into account, 160 questionnaires were evaluated. The majority of those surveyed take an average of 2 cervical biopsies (67.3%) and nearly all of those surveyed (94.5%) do not use any local anaesthetic. As a standard method for removing cervical precancerous cells, most of the physicians surveyed perform a loop excision with the electrosurgical loop (91.2%) under colposcopic visualisation (61.2%) under general anaesthesia (92.5%). Postoperative bleeding prophylaxis by means of tamponade is performed only in 27.6% of all cases. Conclusion A differential colposcopy with two colposcopically targeted biopsies and treatment with the electrosurgical loop are the methods most frequently used by clinicians who perform colposcopy in Germany. A uniform procedure should be defined in detail within the scope of directives or guidelines.

What defines a good website of a Department of Obstetrics and Gynecology? A user survey.

PURPOSE: The Internet has become a widely used source of healthcare information. Many Departments of Obstetrics and Gynecology use their websites for public relations purposes. It is, however, unclear, what relevant stakeholders such as patients, relatives of patients, physicians, and medical students expect of an Obstetrics and Gynecology Department's website. Therefore, we evaluated the opinions and expectations of the various stakeholders using a structured questionnaire. METHODS: We asked gynecologic patients, obstetric patients, relatives of patients, medical students, and physicians to fill in an anonymous questionnaire consisting of general facts about the informant, one open-ended question on expectations and wishes regarding the website, and 28 rating scale questions (7-step visual analog scale ranging from, not important' to, very important') covering the topics "website navigation" (4 questions), "first contact" (3 questions), "clinic processes" (7 questions), "facts and figures about the Department" (4 questions), "visual impressions" (5 questions), and "obstetrics-specific items" (5 questions). Questionnaires for physicians included four additional questions about the value of Department websites as an information tool for themselves and their patients. We used descriptive statistics to analyze the data. RESULTS: 1458 questionnaires were analyzed (gynecologic patients, n = 615 [42%]; obstetric patients, n = 479 [33%]; relatives of patients, n = 77 [5%]; medical students n = 238 [16%]; physicians, n = 41 [3%]). The number of circulated questionnaires was not recorded and thus, the response rate is unknown. 1304 (89%) respondents used the Internet as a regular source of health care information, 642 (44%) had previously searched an Obstetrics and Gynecology Department website. All respondents rated contact data and information about processes in the clinic highest; whereas, other issues such as medical facts, visual impressions, and website design issues were significantly less important. Pregnant women rated contact information and obstetric facts highest. 90% of physicians regularly used Department websites for patient referrals and rated contact information and medical team details most important. CONCLUSIONS: When designing a website of an Obstetrics and Gynecology Department, contact information and information about processes in the clinic should be displayed most prominently and be easily accessible. Subsections specifically targeted at obstetric patients and physicians should be provided.