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Since the publication of the updated German guideline in 2015, the recommendations for performing pelvic lymphadenectomy (LAE) in patients with vulvar cancer (VSCC) have changed considerably. The guideline recommends surgical lymph node staging in all patients with a higher risk of pelvic lymph node involvement. However, the current data do not allow the population at risk to be clearly defined, therefore, the indication for pelvic lymphadenectomy is still not clear. There are currently two published German patient populations who had pelvic LAE which can be used to investigate both the prognostic effect of histologically verified pelvic lymph node metastasis and the relation between inguinal and pelvic lymph node involvement. A total of 1618 patients with primary FIGO stage ≥ IB VSCC were included in the multicenter AGO CaRE-1 study (1998 – 2008), 70 of whom underwent pelvic LAE. During a retrospective single-center evaluation carried out at the University Medical Center Hamburg-Eppendorf (UKE), a total of 514 patients with primary VSCC treated between 1996 – 2018 were evaluated, 21 of whom underwent pelvic LAE. In both cohorts, around 80% of the patients who underwent pelvic LAE were inguinally node-positive, with a median number of three affected groin lymph nodes. There were no cases of pelvic lymph node metastasis without inguinal lymph node metastasis in either of the two cohorts. Between 33 – 35% of the inguinal node-positive patients also had pelvic lymph node metastasis; the median number of affected groin lymph nodes in these patients was high (> 4), and the maximum median diameter of the largest inguinal metastasis was > 40 mm in both cohorts. Pelvic lymph node staging and pelvic radiotherapy is therefore probably not necessary for the majority of node-positive patients with VSCC, as the relevant risk of pelvic lymph node involvement was primarily found in node-positive patients with high-grade disease. More, ideally prospective data collections are necessary to validate the relation between inguinal and pelvic lymph node involvement.

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.

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.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).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.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 tumors4 cm.

Hintergund/Zielsetzung: Abhangig vom Lymphknotenstatus entwickeln 15 – 40% der Patientinnen mit Vulvakarzinom ein Lokalrezidiv. Ein isoliertes Rezidiv im Bereich der Vulva gilt dabei als wenig relevant fur die weitere Prognose. Methoden: Die AGO-CaRE-1 Studie ist eine retrospektive Datensammlung zu Behandlungsstrategien und Prognosefaktoren des Vulvakarzinoms. Insgesamt wurden 1618 Patientinnen mit vulvarem Plattenepithelkarzinom FIGO Stadium ≥1B, behandelt an 29 deutschen Zentren 1998 – 2008, erfasst. Diese Subgruppenanalyse untersucht Patientinnen, die im Krankheitsverlauf ein isoliertes Lokalrezidiv entwickelten. Ergebnisse: 1249/1618 (77,2%) Patientinnen erhielten ein operatives Staging der Leiste und hatten einen bekannten Nodalstatus. Die meisten zeigten lokal begrenzte Primartumore [1124/1249 (90,0%) pT1b/pT2], die R0 reseziert wurden [1022/1249 (81,8%)]. 447/1249 (35,8%) Patientinnen waren nodalpositiv. Bei 324 (25,9%) wurde eine adjuvante Therapie durchgefuhrt. Das mediane Follow-up betrug 39,4 Monate. 360 Patientinnen (28,8%) entwickelten ein Rezidiv; davon 193 (53,6%) isoliert im Bereich der Vulva nach medianen 17,1 Monaten. Initial erhielten 38 (19,7%) dieser Patientinnen eine Radiotherapie der Vulva. Die Therapie des Lokalrezidives umfasste die alleinige Operation in 104 (53,9%), eine Operation und Radiotherapie in 40 (20,7%) und eine Radio(chemo)therapie in 14 (7,3%) Fallen [19 (9,8%) erhielten keine Rezidivtherapie und bei 16 (8,3%) war die Therapie unbekannt]. 58 (30,1%) entwickelten ein zweites Rezidiv in den folgenden Lokalisationen: 40 (20,7%) Vulva, 15 (7,8%) Leiste, 7 (3,6%) Becken, 12 (6,2%) Fernmetastasen, 2 (1,0%) unbekannt (multiple Nennung moglich). Die 1-Jahres-Rezidivfreie-Uberlebensrate nach Lokalrezidiv lag bei 58,5%. Das 3- und 5-Jahres-Gesamtuberleben betrug 76,7% bzw. 66,9% verglichen mit 85,9% und 80,6% bei Patientinnen ohne Lokalrezidiv. Zusammenfassung: Entgegen der allgemeinen Annahme zeigen AGO-CaRE-1 Patientinnen mit Lokalrezidiv eine beeintrachtigte Prognose. Ein wesentlicher Anteil der Betroffenen entwickelt ein Zweitrezidiv nach initial isoliertem Lokalrezidiv.

Aim of the study: A tumour-free pathological resection margin of >= 8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer.Methods: AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer >= FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289).Results: Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin = 8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p=0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267).Conclusions: The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database. (C) 2016 Elsevier Ltd. All rights reserved.

Aus alt mach neu: Calixpyrrole sind bekannte Anionenbinder und konnen nur schwer in Ubergangsmetallkomplexe uberfuhrt werden. Die vollstandige Hydrierung eines Calixpyrrols ergab nun einen Liganden, der leicht klassische Kupfer-, Nickel- und Palladiumkomplexe bilden kann. Die Metallkomplexe enthalten ein Netzwerk von vier ausgerichteten Wasserstoffbrucken, die spezifisch Gegenionen binden (siehe Bild; blau N, weis H, grun Cl, rot Cu, Ni oder Pd).

New tricks for an old dog: Calixpyrroles bind anions efficiently and can be transformed into transition-metal complexes only under forcing conditions. Reducing the macrocycle creates a ligand that easily forms classical Werner complexes with copper, nickel, and palladium ions. The metal complexes present an array of four directed hydrogen bonds, which specifically bind the counterions (see picture; blue N, white H, green Cl, red Cu, Ni, or Pd).

Calix[4]pyrrol ein leicht zuganglicher Makrocyclus, der seit uber 120 Jahren dank der Arbeiten von Adolf von Baeyer bekannt ist, andert seine Eigenschaften vollstandig bei einer Reduktion. Der reduzierte Makrocyclus wird in der Zuschrift von H. Stoeckli-Evans, R. Neier et al. auf S. 1716 ff. zum ersten Mal beschrieben. Metallkomplexe konnen leicht synthetisiert werden, wobei eine fixierte Anordnung von vier gerichteten Wasserstoffbruckendonoren gebildet wird.