The influence of MRI-based pelvimetric measurements in mother's choice of delivery in fetal breech position.

INTRODUCTION: At term, about 3-4% of all singleton pregnancies present as breech. MRI-based pelvimetry is a valuable tool to support selection of adequate candidates for a trial-of-labor in women expecting term breech babies. Shared decision-making is playing an increasingly important role in obstetrics. Since the divergent existing knowledge of breech term delivery needs to be discussed with the pregnant woman, we examined the influence of MRI results on the shared decision-making process in women with term breech presentation. METHODS: Between 08/2021 and 12/2022, anamnestic and clinical parameters were collected from singleton pregnancies expecting term breech babies resulting in birth at the Hanover Medical School. After information, written consent and inclusion, clinical parameters, the course of birth and the maternal and fetal outcome were collected retrospectively. 32 women participated in a postpartum questionnaire study on inquiry. The subsequent acquisition of information and the arguments in the decision-making process were determined. In addition, the sense of security and self-determination was asked both before and during birth. RESULTS: 50% of the respondents had not decided for a mode of delivery before having MRI pelvimetry. After imaging and information, about the own pelvic dimensions and predictors for a successful vaginal birth, 80% of this subgroup decided to give birth vaginally. Over 40% of the collective descripted that they made a decision based on the result of MRI pelvimetry. None of the women felt to be insecure after having talked about the MRI results. The elective cesarean section group and the group of those who delivered vaginally were approximately equally highly satisfied with their feeling of self-determination of the birth mode. Overall, the study population had a very positive birth experience. The group of women who had delivered by elective cesarean showed a wider range in their assessment and appeared to perceive the experience more negative than the group of women who had a vaginal birth or emergency cesarean. Fetal and maternal outcomes did not differ between the groups. DISCUSSION: MRT pelvimetry measurements can be used as a predictor for a successful vaginal breech delivery. The additional information obtained from the MRI measurements can be used in the shared decision-making process to decide more easily on the mode of delivery while improving women's awareness and safety. A balanced education on rare and frequently adverse events of vaginal delivery and cesarean section and patient expectations about labor processes must be taken into account.

Comparing forces on the fetal neck in breech delivery in lithotomy versus all-fours position: a simulation model.

PURPOSE: To measure forces applied to the fetal neck, in a simulation model for breech delivery, in both lithotomy versus all-fours position. METHODS: We used a Laerdal SimMom simulator and a Birthing Baby together with PROMPT Flex Software. The descent of the fetus was accomplished using the Automatic Delivery Module 2. The baby was always in breech position; the SimMom in either all-fours or lithotomy positions. Sensors were located inside the fetal neck region to simulate forces applied to the plexus. RESULTS: The lowest force on the fetal neck region was recorded for the delivery in all-fours position without further maneuvers (mean force 58.70 Newton, standard deviation 2.54 N). As weight was added to the baby, the force increased (i.e. + 500 g, mean force 71.8 N, SD 3.08 N, p < 0.001). Delivery in lithotomy position resulted in a mean force of 81.56 N (SD 19.55 N). The force significantly increased in case of delivery of the head without assistance from contractions (mean force 127.93 N, SD 23.10 N). In all-fours position, the delivery of the fetal head from pelvic floor level without contractions (Frank's Nudge maneuver) resulted in a mean force of 118.45 N (SD 15.48 N, p = 0.02). Maneuvers for shoulder dystocia (the inverted type that can occur during breech delivery) led to significantly higher mean forces independent from birthing positions. CONCLUSION: Breech delivery in all-fours position was associated with the lowest force acting on the fetal neck in our simulation model.

Association of preoperative cone biopsy with recurrences after radical hysterectomy.

OBJECTIVE: To evaluate association of preoperative cone biopsy with the probability of recurrent disease after radical hysterectomy for cervical cancer. METHODS: This is a retrospective single-center study. Patients with cervical cancer stage IA1 with LVSI to IIA2 and squamous, adenosquamous and adenocarcinoma subtype were included. Patients were analyzed for general characteristics and recurrence-free survival (RFS). RESULTS: In total, of 480 patients with cervical cancer, 183 patients met the inclusion criteria (117 with laparoscopic and 66 with open surgery). The median tumor diameter was 25.0 mm (range 4.6-70.0 mm) with 66 (36.2%) patients having tumors smaller than 2 cm. During median follow-up of 54.0 months (range 0-166.0 months), the RFS for the laparoscopic cohort was 93.2% and 87.5% at 3 and 4.5 years, and 79.3% for the open cohort after 3 and 4.5 years, respectively. In total, 17 (9.3%) patients developed recurrent disease, 9 (7.3%) after laparoscopic, and 8 (12.1%) after open surgery. No preoperative cone biopsy (OR 9.60, 95% CI 2.14-43.09) as well as tumor diameter > 2 cm (OR 5.39, 95% CI 1.20-24.25) were significantly associated with increased risk for recurrence. In multivariate analysis, only missing preoperative cone biopsy was significantly associated with increased risk for recurrence (OR 5.90, 95% CI 1.11-31.29) CONCLUSION: There appears to be a subgroup of patients (preoperative cone biopsy, tumor diameter < 2 cm) with excellent survival and low risk for recurrence after radical hysterectomy which might benefit from the advantages of laparoscopic surgery.

Association between obesity and vulvar cancer recurrence: an analysis of the AGO-CaRE-1 study.

OBJECTIVE: Obesity is associated with worse survival and an increased risk of relapse in several malignancies. The influence of obesity on vulvar cancer recurrence has not been previously described. The primary objective of this study was to evaluate the association between obesity and tumor recurrence in patients with vulvar cancer. METHODS: This is an analysis of the AGO-CaRE-1 study. Patients diagnosed with squamous cell vulvar cancer (stage IB and higher), treated in 29 cancer centers between January 1998 and December 2008, were registered in a centralized database. The cohort was divided into two gropus depending on the body mass index (BMI) (<30 vs ≥30 kg/m²). Descriptive statistics, survival analyses, and multivariate Cox regression analyses were performed in order to evaluate the association between obesity and progression-free and overall survival. RESULTS: In 849 (52.4%) of 1618 patients in the database, the BMI was documented. Patients were grouped according to their BMI (<30 vs ≥30 kg/m²). There were 621 patients with a BMI <30 kg/m² and 228 patients with a BMI ≥30 kg/m². Besides age, there was no difference in baseline variables (tumor diameter, depth of infiltration, tumor stage, nodal metastasis, tumor grade). Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ between groups. However, patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1% vs 51.8%, p=0.04). During follow-up there was a higher recurrence rate in the group with BMI ≥30 kg/m² (43.4% vs 28.3%, p<0.01) due to an increased rate of local recurrences (33.3% vs 18.5%, p<0.01). There was a significantly shorter time to recurrence in obese patients on univariate analysis (BMI ≥30 kg/m² vs <30 kg/m²: 43.8 months (95% CI 23.3 to 64.3) vs 102.3 months (95% CI 72.6 to 131.9), p=0.001) and on multivariate Cox regression analysis (HR 1.94 (95% CI 1.4 to 2.8), p<0.001). CONCLUSIONS: In this study a BMI ≥30 kg/m² was associated with a shorter time to recurrence in patients with vulvar cancer and this was mainly attributed to a higher risk of local recurrence.

Radical hysterectomy for early cervical cancer: what shall we do after the LACC trial?

Surgical treatment of cervical cancer has led to one of the greatest controversies in gynecological oncology in recent years. After laparoscopic radical hysterectomy became increasingly widespread worldwide, it lost its importance dramatically when the data from the LACC study were published. In contrast to previous assumptions, there was a significantly reduced survival after laparoscopic hysterectomy compared to the open abdominal procedure. Multiple studies were subsequently published. Some confirm these results some do not. Some consider further studies to be unethical, others point to their own non-randomized results and call for a new LACC study. This article gives an overview of the current data situation and the possible criticisms of the individual studies. And, finally, calls for new RCT's under defined criteria.

Sentinel lymph node biopsy in vulvar cancer: status, level of knowledge, and counseling in outpatient setting.

PURPOSE: Evaluating the counseling of patients with vulvar cancer in outpatient setting regarding the application of sentinel lymph node dissection (SLND), the selection of hospitals for further treatment, and level of knowledge. METHODS: A questionnaire containing 29 questions about SLND in vulvar cancer was sent to gynecologists in Lower Saxony. The questionnaire contained multiple choice questions and open questions. The study was approved by the local ethics committee. RESULTS: The median age of the 86 respondents was 54 (26-66) years. Most participants (83.1%) reported to only treat one to five patients with vulvar cancer per year. Interestingly, 70.5% of the gynecologists send their patients to university hospitals and 64.1% to hospitals offering maximum care, respectively. Of all, 32.7% replied that SLND was performed rarely or never in their patients. The gynecologists answered that only 36.7% of the patients are well informed about advantages and possible disadvantages of SLND. Most (84%) felt responsible to counsel patients on treatment decisions independently from or additionally to the hospital. Of all, 72% replied that they are not completely sure about the exact recurrence rates after SLND. Of notice, 66% believe that SLND for vulvar cancer is safe if applied in specialized centers and 92% stated that focusing treatment on specialized centers is required for best results. CONCLUSION: SLND for vulvar cancer is widely accepted and regularly recommended among gynecologists. Outpatient doctors report to send most patients to specialized centers. However, it appears that patients remain uninformed after counseling in the clinics and that there is a lack of detailed knowledge about risks and complication rates of groin treatment in the outpatient setting.

Predictive factors for lymph node metastases in vulvar cancer. An analysis of the AGO-CaRE-1 multicenter study.

BACKGROUND: Lymph node (LN) metastasis is the most important prognostic factor in primary vulvar cancer. Assessing risk factors for the incidence and extent of LN metastases may help to select the optimal treatment strategy for each individual patient. METHODS: In a subgroup analysis of the large multicenter AGO-CaRE-1 study we included all patients treated with radical groin dissection. Univariate and multivariate regression analyses were performed in order to detect factors associated with the prevalence and extent of nodal involvement. RESULTS: In total, 1162 patients were analyzed. Univariate analyses detected age, ECOG as well as multiple tumor characteristics such as FIGO stage, grading, depth of invasion, tumor diameter, and (lymph)vascular space invasion to be related with the prevalence of LN metastases. Interestingly, only tumor stage, tumor diameter and depth of infiltration were found to be significantly associated with the number of LN metastases. In multivariate analysis, age (OR 1.03), lymphvascular space invasion (OR 4.97), tumor stage (OR 2.22) and depth of infiltration (OR 1.08) showed an association with the prevalence of LN metastases. Regarding the number of metastatic LNs, only tumor stage (OR 2.21) or, if excluded, tumor diameter (OR 1.02) were tested significant. CONCLUSION: This large analysis of the multicenter AGO-CaRE-1-study identified lymphvascular space invasion, tumor stage, and depth of infiltration as factors with the strongest association regarding the prevalence of LN metastasis. Interestingly, tumor stage or, if excluded, tumor diameter were the only factors associated with the prevalence as well as the extent of LN metastases.

Peritoneal contamination with ICG-stained cervical secretion as surrogate for potential cervical cancer tumor cell dissemination: A proof-of-principle study for laparoscopic hysterectomy.

INTRODUCTION: Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. MATERIAL AND METHODS: In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. RESULTS: By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. CONCLUSIONS: Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.

Characterization of a Novel Third-Generation Anti-CD24-CAR against Ovarian Cancer.

Novel therapeutic approaches against ovarian cancer (OC) are urgently needed because of its high rate of recurrence even after extensive surgery and multi-agent chemotherapy. We aimed to develop a novel anti-CD24 chimeric antigen receptor (CAR) as an immunotherapeutic approach against OC cells and cancer stem cells (CSC). CSC represents a subpopulation of the tumor characterized by enhanced chemoresistance as well as the increased capability of self-renewal and metastasis. We designed a codon-optimized third-generation CAR containing the highly active single chain variable fragment (scFv) "SWA11" against CD24. We equipped the human NK-cell line NK-92 with the anti-CD24 CAR and an anti-CD19 control CAR using lentiviral transduction. Engineered NK-92 cells showed high cytotoxic activity against CD24-positive OC cell lines (SKOV3, OVCAR3). This effect was restricted to CD24-expressing cells as shown after lentiviral transduction of CD24-negative cell lines (A2780, HEK-293T) with CD24 transmembrane proteins. Additionally, NK-92 cells equipped with our novel anti-CD24 CAR were highly effective against patient-derived primary ovarian cancer cells. The activation of NK cells was shown by specific IFNγ secretion upon antigen stimulation. To further reduce possible off-target effects in vivo, we applied a dual-CAR approach using an anti-CD24-CD28-41BB fusion protein linked via a 2A sequence to an anti-mesothelin-CD3ζ-CAR. The dual-CAR was simultaneously active against CD24 and mesothelin expressing cells. Our novel anti-CD24-CAR showed a highly cytotoxic effect against OC cell lines and primary OC cells and will be evaluated in future in vivo trials as a promising immunotherapeutic approach against OC.

Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium-99m-nanocolloid.

OBJECTIVE: Sentinel diagnostic in cervical cancer is performed using Technetium-99m-nanocolloid as a radioactive marker with or without patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule which emits a light signal in the near infrared band after excitation. Our study aims to evaluate indocyanine green compared to the gold standard Tc-99m-nanocolloid. MATERIALS AND METHODS: We included patients with early cervical cancer up to FIGO stage IIA with clinically node-negative pelvic sites and the indication for nodal staging in this prospective trial. Sentinel diagnostic was carried out using Tc-99m-nanocolloid, indocyanine green and patent blue. We examined each pelvic site for light signals from the near infrared band, for radioactivity and for blue staining. A sentinel lymph node was defined as a Tc-99m-nanocolloid positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested; then sent to histologic examination. RESULTS: Thirty-three patients were included in which we found 211 Tc-99m-nanocolloid-positive sentinel lymph nodes in 66 pelvic sites. Two hundred and seven of these lymph nodes were positive for indocyanine green, too, giving a sensitivity of 98.1% (95%CI 94.9-99.4%) compared to Tc-99m-nanocolloid. One hundred and sixty additional lymph nodes showed indocyanine green fluorescence but no Tc-99m-positivity, so that the sensitivity was 79.6% (95%CI 76.6-82.3%). In one patient, a pelvic site was only identified to be tumor infiltrated due to an ICG-positive, but Tc-99m-negative lymph node. CONCLUSION: Our results show that indocyanine green is a promising approach for pelvic sentinel identification in cervical cancer. ICG has a similar sensitivity as radioactive Tc-99m-nanocolloid and may enhance both patient safety and surgeons' comfort. Lasers Surg. Med. 50:994-1001, 2018. © 2018 Wiley Periodicals, Inc.

History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report.

BACKGROUND: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. METHODS: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. RESULTS: Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. CONCLUSIONS: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium.

PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. METHODS: Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma. We used Cox proportional hazards regression models adjusted for age and stage to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and within strata of histological subtypes. RESULTS: History of diabetes was associated with increased risk of mortality (n = 7,674; HR = 1.12; 95% CI = 1.01-1.25). No significant mortality associations were observed for hypertension (n = 6,482; HR = 0.95; 95% CI = 0.88-1.02) or heart disease (n = 4,252; HR = 1.05; 95% CI = 0.87-1.27). No association of these comorbidities was found with PFS in the overall study population. However, among patients with endometrioid tumors, hypertension was associated with lower risk of progression (n = 339, HR = 0.54; 95% CI = 0.35-0.84). Comorbidity was not associated with OS or PFS for any of the other histological subtypes. Ever use of beta blockers, oral antidiabetic medications, and insulin was associated with increased mortality, HR = 1.20; 95% CI = 1.03-1.40, HR = 1.28; 95% CI = 1.05-1.55, and HR = 1.63; 95% CI = 1.20-2.20, respectively. Ever use of diuretics was inversely associated with mortality, HR = 0.71; 95% CI = 0.53-0.94. CONCLUSIONS: Histories of hypertension, diabetes, and use of diuretics, beta blockers, insulin, and oral antidiabetic medications may influence the survival of ovarian cancer patients. Understanding mechanisms for these observations could provide insight regarding treatment.

Outcome After Sentinel Lymph Node Dissection in Vulvar Cancer: A Subgroup Analysis of the AGO-CaRE-1 Study.

PURPOSE: Analyzing the large patient cohort of the multicenter AGO-CaRE-1 study, we compared isolated sentinel lymph node dissection (SLND) with radical lymph node dissection (LND) of the groin in relation to recurrence rates and survival. METHODS: The AGO-CaRE-1 study retrospectively collected data on treatment patterns and follow-up of vulvar cancer patients [International Federation of Gynecology and Obstetrics (FIGO) stage ≥1B] treated at 29 gynecologic cancer centers between 1998 and 2008. This subgroup analysis evaluated the influence of SLND alone on progression-free survival (PFS) and overall survival (OS). RESULTS: In 487 (63.1%) of 772 included patients with tumors smaller than 4 cm, an LND was performed and no metastatic lymph nodes were detected (LN0). Another 69/772 (8.9%) women underwent SLND alone, showing a negative SLN (SLN0). Tumors in the LN0 group were larger and showed a deeper invasion (LN0 vs. SLN0 tumor diameter: 20.0 vs. 13.0 mm, p < 0.001; depth of invasion: 4.0 vs. 3.0 mm, p = 0.002). After a median follow-up of 33 months (0-156), no significant differences in relation to isolated groin recurrence rates (SLN0 3.0% vs. LN0 3.4%, p = 0.845) were detected. Similarly, univariate 3-year PFS analysis showed no significant differences between both groups (SLN0 82.7% vs. LN0 77.6%, p = 0.230). A multivariate Cox regression analysis, including tumor diameter, depth of invasion, age, grading, and lymphovascular space invasion was performed: PFS [hazard ratio (HR) 0.970, 95% confidence interval (CI) 0.517-1.821] and OS (HR 0.695, 95% CI 0.261-1.849) did not differ significantly between both cohorts. CONCLUSION: This subgroup analysis of the large AGO-CaRE-1 study showed similar results for groin LND and SLND alone with regard to recurrence rates and survival in node-negative patients with tumors <4 cm.

Groin Recurrences in Node Negative Vulvar Cancer Patients After Sole Sentinel Lymph Node Dissection.

OBJECTIVE: This study aimed to evaluate the recurrence rates after sole sentinel dissection in vulvar cancer and describe characteristics of groin recurrences. METHODS: All vulvar cancer cases between 2008 and 2014 were reviewed. Inclusion criteria were restricted to lymph node-negative patients, sole sentinel lymph node dissection (SLND), and tumor diameter less than 4 cm. In all patients, Tc-99m nanocolloid was used for preoperative SLN imaging. Regularly, planar lymphoscintigraphy and single-photon emission computed tomography with computed tomography were performed. Ultrastaging was routinely conducted on all negative lymph nodes. RESULTS: Of 140 vulvar cancer cases, 30 node-negative patients underwent sole SLND and met inclusion criteria. Keratinizing squamous cell carcinoma was determined in final histology in 20/30 (66.7%) patients and the mainly diagnosed tumor stage was pT1b (21/30, 70%). Three perioperative complications occurred. On average, 4.6 (1-9) SLNs were dissected per patient and 2.5 (1-6) per each groin, respectively. During a median follow-up of 43.5 (4-75) months, 5/30 (16.7%; 95% confidence interval, 7.3%-33.6%) local recurrences occurred. In addition, 2/30 (6.6%; 95% confidence interval, 1.9%-21.3%) groin recurrences were identified within a period of 12 months after the primary surgery. Both patients had large (>2 cm) midline tumors. Despite surgical as well as adjuvant treatment of the recurrent disease, both patients with groin recurrences died. CONCLUSIONS: Sentinel lymph node dissection is a safe and feasible alternative in early vulvar cancer. But false-negative sentinel carry a high risk of mostly fatal groin recurrences. Especially, midline tumors larger than 2 cm have to be treated with caution, because they are mostly found in cases with groin recurrences after sole SLND.

Sentinel Lymphadenectomy in Vulvar Cancer Using Near-Infrared Fluorescence From Indocyanine Green Compared With Technetium 99m Nanocolloid.

OBJECTIVE: Nowadays, sentinel diagnostic is performed using technetium 99m (Tc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard Tc-nanocolloid. METHODS: We included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using Tc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a Tc-nanocolloid-positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination. RESULTS: In all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%-100%) compared with Tc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no Tc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%-96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found. CONCLUSIONS: Our results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive Tc-nanocolloid and worth to be evaluated in further studies.

Photodynamic diagnosis with 5-aminolevulinic acid for intraoperative detection of peritoneal metastases of ovarian cancer: A feasibility and dose finding study.

OBJECTIVE: With a prospective feasibility study, we aimed to analyse the effect of different time points for application and dosage of preoperative oral 5-aminolevulinic acid administration for photodynamic diagnosis of peritoneal metastases in ovarian cancer patients. MATERIALS AND METHODS: In this prospective cohort study patients were randomly divided into three different groups. 5-Aminolevulinic acid was orally administered 3-14 hours before surgery using a dosage of 1 mg/kg, 4-9 hours using 10 mg/kg, and 9-16 hours using 10 mg/kg, respectively. Fluorescence was recorded intraoperatively using endoscopic equipment. The number and localization, of fluorescing nodules were documented. To analyze sensitivity and specificity samples from fluorescent and non-fluorescent tissues were evaluated histologically. Plasma protoporphyrin concentrations as well as any adverse events were assessed perioperatively. RESULTS: In total, 26 patients suspected for ovarian cancer underwent intraoperative photodynamic diagnosis with 5-aminolevulinic acid. Most of them suffered from advanced cancer, 72% from FIGO-Stage IIIc. No severe adverse events were observed. Orally applied 5-aminolevulinic acid with a dosage of 1 mg/kg revealed no detectable fluorescence. However, at a dosage of 10 mg/kg fluorescence of metastatic tissue was significantly stronger than of non-affected tissue. If administered 4-9 hours preoperatively best detection rates for peritoneal metastases were obtained resulting in a sensitivity of 75% and a specificity of 100%. CONCLUSIONS: Photodynamic diagnosis with 5-aminolevulinic acid leads to safe and specific fluorescence detection of peritoneal metastases. 5-Aminolevulinic acid should be used at a dosage of at least 10 mg/kg 4-9 hours preoperatively. Further phase I-II studies are recommended. Lasers Surg. Med. 49:169-176, 2017. © 2016 Wiley Periodicals, Inc.

Application of sentinel lymph node dissection in gynecological cancers: results of a survey among German hospitals.

PURPOSE: Evaluating the application of the sentinel lymph node dissection (SLND) in gynecological cancers among German hospitals. METHODS: Between March and June 2016 an online questionnaire on SLND in gynecologic cancers was sent by email to all German gynecologic cancer centers, all university hospitals and general hospitals for which an email address was available. The survey contained 61 questions regarding the SLND in vulvar, cervical, endometrial and ovarian cancer. RESULTS: In total, 63 clinics, including 13 (20.6%) university hospitals, 28 (44.4%) hospitals offering maximum care and 22 (34.9%) general hospitals, responded to the questionnaire. Most clinics (46/63, 73%) performed SLND in vulvar cancer with a median amount of 7.8 (range 1-43) SLND per year. 56.5% of the clinics included patients according to the German national guidelines and performed ultrastaging of negative SLN. Furthermore, 18/63 (28.5%) of the responding clinics applied SLND in cervical cancer including 7 (77.8%) centers which conducted isolated SLND without radical pelvic lymph node dissection (LND). Preoperative imaging with planar lymphoscintigraphy (LSG) was applied in 12/18 (66.7%) of the clinics. SLND in endometrial cancer was reported by 4/63 (6.4%) hospitals. Three of them (75%) regularly performed a subsequent radical pelvic LND. One clinic (1.5%) reported SLND in ovarian cancer in combination with radical LND. CONCLUSION: Especially in vulvar and cervical cancer, isolated SLND appears to be partially implemented in the routine surgical treatment. However, this survey illustrates a wide heterogeneity regarding inclusion criteria and application of the SLND approach.

Association between intraabdominal pressure during gynaecologic laparoscopy and postoperative pain.

PURPOSE: Laparoscopy is nowadays a well-established surgical method and plays a main role in an ever-increasing range of indications in gynaecology. High-quality studies of surgical techniques are necessary to improve the quality of patient care. The present study aims at evaluating postoperative pain after gynaecological laparoscopy depending on the intraoperative CO2 pressure. METHODS: In a prospective, monocentric, randomized single-blind study at the Department of Gynaecology and Obstetrics at the Hannover Medical School, we include patients scheduled for different laparoscopic procedures. Randomization of the intraoperative CO2 pressure was carried out in six groups. Pain was assessed the day after surgery by the blinded nurse using a visual analogue scale. RESULTS: 550 patients were included in the period from May 2013 to January 2016. The analysis of the per protocol population PPP (n = 360) showed no statistically significant difference between the six intervention groups with regard to mean postoperative pain perception. In direct comparison between two groups, an intraoperative CO2 pressure of 15 mmHg was associated with a significant higher pain score than a pressure of 12 mmHg. The difference was 7.46 mm on a 10 cm VAS. CONCLUSIONS: The results of our study indicate that a CO2 pressure of 12 versus 15 mmHg can be advantageous. However, the clinical relevance remains unclear due to the low difference in pain. The additional benefit of an even lower pressure of 10 or 8 mmHg cannot be reliably assessed; we found signs of poor visibility conditions in these low pressure groups.

Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer: evidence from the Ovarian Cancer Association Consortium.

BACKGROUND: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality. METHODS: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years. RESULTS: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18-1.52) and without (HR=1.22, 95% CI: 1.12-1.33) further adjustment for residual disease, respectively. CONCLUSION: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.