Rüdiger Klapdor

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.

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.

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

PurposeSurvival 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.MethodsUsing 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.ResultsHistory 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.ConclusionsHistories 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.

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

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.

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

PurposeEvaluating the application of the sentinel lymph node dissection (SLND) in gynecological cancers among German hospitals.MethodsBetween 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.ResultsIn 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.ConclusionEspecially 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.

Rare ATAD5 missense variants in breast and ovarian cancer patients

ATAD5/ELG1 is a protein crucially involved in replication and maintenance of genome stability. ATAD5 has recently been identified as a genomic risk locus for both breast and ovarian cancer through genome-wide association studies. We aimed to investigate the spectrum of coding ATAD5 germ-line mutations in hospital-based series of patients with triple-negative breast cancer or serous ovarian cancer compared with healthy controls. The ATAD5 coding and adjacent splice site regions were analyzed by targeted next-generation sequencing of DNA samples from 273 cancer patients, including 114 patients with triple-negative breast cancer and 159 patients with serous epithelial ovarian cancer, and from 276 healthy females. Among 42 different variants identified, twenty-two were rare missense substitutions, of which 14 were classified as pathogenic by at least one in silico prediction tool. Three of four novel missense substitutions (p.S354I, p.H974R and p.K1466N) were predicted to be pathogenic and were all identified in ovarian cancer patients. Overall, rare missense variants with predicted pathogenicity tended to be enriched in ovarian cancer patients (14/159) versus controls (11/276) (p = 0.05, 2df). While truncating germ-line variants in ATAD5 were not detected, it remains possible that several rare missense variants contribute to genetic susceptibility toward epithelial ovarian carcinomas.

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 (99mTc) 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 99mTc-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 99mTc-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 99mTc-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 99mTc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no 99mTc 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 99mTc-nanocolloid and worth to be evaluated in further studies.

Radiofrequency endometrial ablation for the treatment of heavy menstrual bleeding among women at high surgical risk

To evaluate quality of life (QoL) after radiofrequency endometrial ablation (RFEA) for heavy menstrual bleeding among women at high surgical risk.

Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium-99m-nanocolloid: SENTINEL LYMPHADENECTOMY IN CERVICAL CANCER USING ICG

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.

Postoperative anatomic and quality‐of‐life outcomes after vaginal sacrocolporectopexy for vaginal vault prolapse

To assess anatomic outcome and quality of life (QOL) after vaginal sacrocolporectopexy among patients with pelvic organ prolapse.