The Total Synthesis of Hyperfirin via a Cyclooctadiene Strategy.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) combine compelling structural complexity with effective biological activity. The total synthesis of Hyperfirin is reported as one linear sequence. Key to this novel modular strategy is to access the bicyclo[3.3.1]nonane-2,4,9-trione framework via transannular acylation of a decorated eight-membered ring, followed by late stage bridgehead substitution. The described route adds flexibility to PPAP construction and broadens the scope of eight-membered ring chemistry.

Clinical Impact of Pelvic Sentinel Lymph Node Biopsy for Vulvar Squamous Cell Carcinoma.

BACKGROUND/AIM: This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC). PATIENTS AND METHODS: Sixty-two groins of 33 patients with SCVC who underwent sentinel lymph node (SLN) resection between 2010 and 2021 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. The frequency of additionally resectable PSLNs, histological findings, and count rates were analyzed and compared to the findings for inguinal sentinel lymph nodes (ISLNs). RESULTS: In all patients and in 61 (98%) of the 62 radiolabeled groins, at least one SLN could be resected. Five (8%) of the 62 groins had histologically confirmed lymph node metastases (4/33 patients, 12%). Twenty (33%) of the 62 groins underwent additional PSLN resection. Resection of these PSLNs was feasible without causing an additional burden for the patients. None of the PSLNs showed signs of tumor infiltration. Information on the extent of radioactivity for ISLNs and simultaneously for PSLNs, expressed as count rate of intraoperative measurement with the gamma probe, was available for 20 (32%) groins. In three (15%) of these cases, the highest count rate in a SLN was found in a PSLN and not in an ISLN. CONCLUSION: Resection of PSLNs is feasible and can be performed without short-term complications. In patients with early SCVC, resection of PSLNs is not necessary, even in those with early infiltration of inguinal lymph nodes. The intraoperative count rate of SLN is not relevant for the decision to perform resection.

Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer.

PURPOSE: More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer. METHODS: Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data. RESULTS: The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (p < 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (p < 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (p < 0.05). CONCLUSIONS: Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.

The Disorazole Z Family of Highly Potent Anticancer Natural Products from Sorangium cellulosum: Structure, Bioactivity, Biosynthesis, and Heterologous Expression.

Myxobacteria serve as a treasure trove of secondary metabolites. During our ongoing search for bioactive natural products, a novel subclass of disorazoles termed disorazole Z was discovered. Ten disorazole Z family members were purified from a large-scale fermentation of the myxobacterium Sorangium cellulosum So ce1875 and characterized by electrospray ionization-high-resolution mass spectrometry (ESI-HRMS), X-ray, nuclear magnetic resonance (NMR), and Mosher ester analysis. Disorazole Z compounds are characterized by the lack of one polyketide extension cycle, resulting in a shortened monomer in comparison to disorazole A, which finally forms a dimer in the bis-lactone core structure. In addition, an unprecedented modification of a geminal dimethyl group takes place to form a carboxylic acid methyl ester. The main component disorazole Z1 shows comparable activity in effectively killing cancer cells to disorazole A1 via binding to tubulin, which we show induces microtubule depolymerization, endoplasmic reticulum delocalization, and eventually apoptosis. The disorazole Z biosynthetic gene cluster (BGC) was identified and characterized from the alternative producer S. cellulosum So ce427 and compared to the known disorazole A BGC, followed by heterologous expression in the host Myxococcus xanthus DK1622. Pathway engineering by promoter substitution and gene deletion paves the way for detailed biosynthesis studies and efficient heterologous production of disorazole Z congeners. IMPORTANCE Microbial secondary metabolites are a prolific reservoir for the discovery of bioactive compounds, which prove to be privileged scaffolds for the development of new drugs such as antibacterial and small-molecule anticancer drugs. Consequently, the continuous discovery of novel bioactive natural products is of great importance for pharmaceutical research. Myxobacteria, especially Sorangium spp., which are known for their large genomes with yet-underexploited biosynthetic potential, are proficient producers of such secondary metabolites. From the fermentation broth of Sorangium cellulosum strain So ce1875, we isolated and characterized a family of natural products named disorazole Z, which showed potent anticancer activity. Further, we report on the biosynthesis and heterologous production of disorazole Z. These results can be stepping stones toward pharmaceutical development of the disorazole family of anticancer natural products for (pre)clinical studies.

Anion and ether group influence in protic guanidinium ionic liquids.

Ionic liquids are attractive liquid materials for many advanced applications. For targeted design, in-depth knowledge about their structure-property-relations is urgently needed. We prepared a set of novel protic ionic liquids (PILs) with a guanidinium cation with either an ether or alkyl side chain and different anions. While being a promising cation class, the available data is insufficient to guide design. We measured thermal and transport properties, nuclear magnetic resonance (NMR) spectra as well as liquid and crystalline structures supported by ab initio computations and were able to obtain a detailed insight into the influence of the anion and the ether substitution on the physical and spectroscopic properties. For the PILs, hydrogen bonding is the main interaction between cation and anion and the H-bond strength is inversely related to the proton affinity of the constituting acid and correlated to the increase of 1H and 15N chemical shifts. Using anions from acids with lower proton affinity leads to proton localization on the cation as evident from NMR spectra and self-diffusion coefficients. In contrast, proton exchange was evident in ionic liquids with triflate and trifluoroacetate anions. Using imide-type anions and ether side groups decreases glass transitions as well as fragility, and accelerated dynamics significantly. In case of the ether guanidinium ionic liquids, the conformation of the side chain adopts a curled structure as the result of dispersion interactions, while the alkyl chains prefer a linear arrangement.

Evidence of AlII Radical Addition to Benzene.

Electrophilic AlIII species have long dominated the aluminum reactivity towards arenes. Recently, nucleophilic low-valent AlI aluminyl anions have showcased oxidative additions towards arenes C-C and/or C-H bonds. Herein, we communicate compelling evidence of an AlII radical addition reaction to the benzene ring. The electron reduction of a ligand stabilized precursor with KC8 in benzene furnishes a double addition to the benzene ring instead of a C-H bond activation, producing the corresponding cyclohexa-1,3(orl,4)-dienes as Birch-type reduction product. X-ray crystallographic analysis, EPR spectroscopy, and DFT results suggest this reactivity proceeds through a stable AlII radical intermediate, whose stability is a consequence of a rigid scaffold in combination with strong steric protection.

Platinum(IV) Complexes of the 1,3,5-Triamino Analogue of the Biomolecule Cis-Inositol Designed as Innovative Antineoplastic Drug Candidates.

Metal complexes occupy a special place in the field of treatment and diagnostics. Their main advantages stem from the possibility of fine-tuning their thermodynamic properties and kinetic behavior in the biological milieu by applying different approaches such as properly constructed inner coordination sphere, appropriate choice of ligands, metal oxidation state, redox potential, etc., which are specific to these compounds. Here we discuss the design and synthesis of two octahedral cationic Pt(IV) complexes of the tridentate ligand all-cis-2,4,6-triaminocyclohexane-1,3,5-triol (taci) with composition, fac-[Pt(taci)I3]+, 1 and bis-[Pt(taci)2]4+, 2 as well as the potential for their application as antineoplastic agents. The complexes have been isolated in a solid state as: fac-[Pt(taci)I3]I·3H2O (1A), fac-[Pt(taci)I3]I (1B), fac-[Pt(taci)I3]I·2DMF (1C), bis-[Pt(taci)2](CO3)2·6H2O (2A) by changing the acidity of the reaction systems, the molar ratios of the reagents and the counterions, and by re-crystallization. The ligand taci is coordinated through the NH2-groups, each molecule occupying three coordination places in the inner coordination sphere of Pt(IV). Monitoring of the hydrolysis processes of 1A and 2A at different acidity showed that while 2A remained stable over the study period, the I--ions in 1A were successively substituted, with the main product under physiologically mimetic conditions being fac,cis-[Pt(taci)I(OH)2]+ (h2). The antiproliferative tests involved eight cancer cell models, among which chemosensitive (derived from leukemias and solid tumors) and chemoresistant human Acute myeloid leukemia lines (HL-60/Dox, HL-60/CDDP), as well as the non-malignant kidney' cells HEK-293T showed that the complexes 1A and 2A are characterized by a fundamentally different profile of chemosensitivity and spectrum of cytotoxic activity compared to cisplatin. The new Pt(IV) complexes were shown to be more effective in selectively inhibiting the proliferation of human malignant cells compared to cisplatin. Remarkable activity was recorded for 1A, which showed an effect (IC50 = 8.9 ± 2.4) at more than 16-fold lower concentration than cisplatin (IC50 = 144.4 ± 9.8) against the resistant cell line HL-60/CDDP. In parallel, 1A exhibited virtually the same cytotoxic effect against the parental HL-60 cells (IC50 = 9.0 ± 1.2), where cisplatin displays comparable chemosensitivity (IC50 = 8.3 ± 0.8). The determined resistance indices (RI~1) show unequivocally that the resistant lines are sensitive to both compounds tested; therefore, they are capable of overcoming the mechanisms of cisplatin resistance. The structural features of these compounds and their promising pharmacological properties justify their inclusion in the group of "non-classical metal-based antitumor compounds" and are a prerequisite for the admission of alternative mechanisms of action.

Uterus-preserving management of pyomyoma: Case report of a rare complication after uterine artery embolization.

Background: Pyomyoma of the uterus is a rare but severe complication of uterine artery embolization (UAE). This report describes the uterus-preserving management of a case of fast-developing pyomyoma. Screening methods to minimize the risk of this condition are discussed. Case: A 46-year-old woman presented with fever, abdominal pain and blood stream infection on the third day after UAE, which had been performed to treat symptomatic uterine myomatosus. Broad-spectrum antibiotics proved inadequate. Magnetic resonance imaging (MRI) showed a possible superinfection of the necrotic myoma. Vaginal smear showed the same organism, a resistant Escherichia coli, as in the blood culture. Because the patient declined hysterectomy, multiple hysteroscopies with removal of necrotic pyomyoma were performed. In addition, an intrauterine gentamicin chain was placed. To our knowledge, this is the first case of pyomyoma immediately after UAE and the first report of successful hysteroscopic treatment in a septic patient. Conclusion: In order to reduce the risk of pyomyoma, pre- and postinterventional algorithms should be used.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

Transition Metal Complexes of Heavier Vinylidenes: Allylic Coordination vs Vinylidene-Alkyne Rearrangement at Nickel.

Transition metal π-allyl complexes are key reagents/intermediates of various catalytic and stoichiometric allylation reactions. We now report the first transition metal complex of a heavier allylic π-system. The η3-Si2Ge allyl nickel complex is formally obtained by the oxidative addition of the Si-Cl bond of the heavier vinylidene [R2(Cl)Si-(R)Si═(NHC)Ge:] to [Ni(COD)2] (R = 2,4,6-triisopropylphenyl; NHC = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene; COD = 1,5-cyclooctadiene). Due to geometric constraints, the coordination to the Ni(II) center occurs through the formal Si═Ge double bond instead of the residual lone pair of electrons at germanium. In contrast, the Si-N bond of the analogous vinylidene [R2(Me2N)Si-(R)Si═(NHC)Ge:] (obtained by nucleophilic substitution of Cl by NMe2) does not oxidatively add to Ni(0), and a hydridosilagermene-η2-nickel complex is obtained instead. The formation of this complex necessarily implies the isomerization of the heavier vinylidene to the corresponding heteroalkyne with the Si≡Ge triple bond in the coordination sphere of nickel followed by the activation of a C-H bond of one of the isopropyl groups of an N-heterocyclic carbene (NHC) ligand.

First description of hematogenously metastasized sclerosing epithelioid fibrosarcoma arising in the uterine cervix.

•First Case of hematogenously metastasized sclerosing epithelioid fibrosarcoma arising primarily in the cervix uteri.•Tumor cells were strongly and diffusely positive for MUC4.•Tumor showed a rare EWSR1-CREB3L2 gene fusion.

Morbidity and quality of life in patients with vulvar cancer after inguinal sentinel lymphadenectomy compared to radical inguinofemoral lymphadenectomy.

AIM: Probability of survival of patients with vulvar cancer directly depends on the lymph node status. Surgery of lymph nodes can be performed as radical inguinofemoral lymphadenectomy or in cases with certain conditions as sentinel lymph node surgery. The aim of this study is to obtain an overview of the intervention-related morbidity and quality of life in patients with vulvar carcinoma after lymphadenectomy. METHODS: Quality of life and morbidity was compared between patients who underwent radical inguinofemoral lymphadenectomy with those who underwent sentinel lymph node surgery. RESULTS: All recorded postoperative complications occur more frequently in the non-sentinel group, Significant difference was shown for the occurrence of lymphedema (p-value = 0.024) and sensitivity loss (p-value = 0.024). Recurrence of disease was more frequent in the non-sentinel group (38 % vs. 20 %, p = 0.621, n.s.) and satisfaction with groin surgery is slightly higher in the sentinel group (94 % vs. 89 %, p = 1.000, n.s.). CONCLUSION: We could demonstrate a significantly lower morbidity of sentinel lymphadenectomy compared to conventional inguinofemoral lymphadenectomy while maintaining the same oncological safety. The low morbidity of sentinel- lymphadenectomy does not seem to influence the postoperative quality of life significantly. However, recording of the individual burden of lymphadenectomy by questionnaires should be optimized.

Patient with ovarian insufficiency: baby born after anticancer therapy and re-transplantation of cryopreserved ovarian tissue.

BACKGROUND: The second major cause of death is cancer. In fact, the effectiveness of anticancer treatments and positive long-term prognosis for young women has increased. However, the problem of post-cancer infertility plays a significant role, because chemotherapy can be gonadotoxic and lead to the functional death of ovaries. There is potential key solution to this problem: cryopreservation of ovarian tissue before cancer therapy with re-implantation after convalescence. Data regarding cryopreservation and re-transplantation of ovarian tissue from patients with ovarian insufficiency is limited. The aim of this treatment was the re-transplantation of cryopreserved ovarian tissue after anticancer therapy of patient with ovarian insufficiency (56 IU/l FSH, 8 ng/l ß-estradiol, < 1.1 ng/ml anti-Mullerian hormone, 1 primary follicle per 10mm3). CASE PRESENTATION: After the operation, four tissue fragments (10-16 × 8-13 × 1.0-1.2 mm) were cooled to 5 °C in the freezing medium (culture medium+ 6% ethylene glycol+ 6% dimethyl sulfoxide+ 0.15 M sucrose) for 24 h, frozen and thawed. Freezing was performed in four standard 5 ml cryo-vials with ice formation at - 9 °C, cooling from - 9 to - 34 °C at a rate of - 0.3 °C/min and plunging at - 34 °C into liquid nitrogen. After thawing in a 100 °C (boiling) water bath, the removal of cryoprotectants was performed in 0.5 M sucrose with 20 min. exposure in sucrose and 30 min. stepping rehydration. After thawing of one cryo-vial, part (5 mm3) of experimental ovarian tissue after 7 day in vitro culture was histological evaluated and two ovarian fragments (8 × 7 × 1.0 mm and 7 × 6 × 1.0 mm) were re-transplanted. The quantity of follicles after cryopreservation and in vitro culture was not increased (P > 0.1): it was found 1 primordial follicle in 5 mm3 of tissue. Thirty seven days after the re-transplantation of ovarian tissue, the restoration of the menstrual cycle of Patient W. was noted. Three months after the transplantation, the patient became spontaneously pregnant and delivered a healthy baby girl at term. CONCLUSIONS: Described protocol of conventional cryopreservation of ovarian tissue can be used for treatment of patients with ovarian insufficiency.

3D Versus 4K Display System - Influence of "State-of-the-art"-Display Technique on Surgical Performance (IDOSP-study) in Minimally Invasive Surgery: A Randomized Cross-over Trial.

OBJECTIVE: To evaluate if "state-of-the-art" 3D- versus 4K-display techniques could influence surgical performance. BACKGROUND: High quality minimally invasive surgery is challenging. Therefore excellent vision is crucial. 3D display technique (3D) and 2D-4K technique (4K) are designed to facilitate surgical performance, either due to spatial resolution (3D) or due to very high resolution (4K). METHODS: In randomized cross-over trial the surgical performance of medical students (MS), non-board certified surgeons (NBC), and board certified surgeons (BC) was compared using 3D versus 4K display technique at a minimally invasive training Parkour. RESULTS: One hundred twenty-eight participants were included (February 2018 through October 2019, 49 MS, 39 NBC, 40 BC). The overall Parkour time (s) 3D versus 4K was 712.5 s ± 17.5 s versus 999.5 s ±â€Š25.1 s (P < 0.001) for all levels of experience. It was (3D vs 4K) for MS (30 tasks) 555.4 s ±â€Š28.9 s versus 858.7 s ±â€Š41.6 s, (P < 0.0001), for NBC (42 tasks) 935.9 s ±â€Š31.5 s versus 1274.1 s ±â€Š45.1 s (P =< 0.001) and for BC (42 task) 646.3 s ±â€Š30.9 s versus 865.7 s ±â€Š43.7 s (P < 0.001). The overall number of mistakes was (3D vs 4K) 10.0 ±â€Š0.5 versus 13.3 ±â€Š0.7 (P < 0.001), for MS 8.9 ±â€Š0.9 versus 13.1 ±â€Š1.1 (P < 0.001), for NBC 12.45 ±â€Š1.0 versus 16.7 ±â€Š1.2 (P < 0.001) and for BC 8.8 ±â€Š1.0 versus 10.0 ±â€Š1.2 (P = 0.18). MS, BC, and NBC showed shorter performance time in 100% of the task with 3D (significantly in 6/7 tasks). For number of mistakes the effect was less pronounced for more experienced surgeons. The National Aeronautics and Space Administration-task load index was lower with 3D. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 4K technique. Surgeons benefit from the improved visualization regardless of their individual surgical expertise.

Preoperative biopsies as predictor for the necessity of inguinal lymph node surgery in squamous cell carcinoma of the vulva-a retrospective tertiary center analysis.

PURPOSE: Squamous cell carcinoma of the vulva (SQCV) is the fifth common cancer in women. Necessity of inguinal lymph node surgery depends on the depth of stromal invasion, inducing lymph node surgery, if depth of invasion is more than 1 mm. In this study we tested the prediction of stromal infiltration depth by measurements in preoperative biopsies. METHODS: We analyzed whether a different operative strategy in respect to lymph node surgery would have been chosen based on the pre- or postoperative depth of stromal invasion for each patient. Examination of infiltration depth in preoperative biopsies and surgical specimen were compared. RESULTS: In total 77 patients were included in this study. Of those 89.6% showed different depths of stromal invasion comparing the pre- and postoperative specimen. Within seventeen patients (22.1%) preoperative depth was 1 mm or less and a postoperative depth was > 1 mm. CONCLUSION: We pointed, that only in 77.9% of the patients who should have undergo lymph node surgery based on the postoperative depth of infiltration underwent this procedure. Consequentially in 22.1% of the cases a second operation could not be prevented with a preoperative taken biopsy as indicator for the necessity of lymph node surgery.

Long-term (24h) cooling of ovarian fragments in the presence of permeable cryoprotectants prior to freezing: Two unsuccesful IVF-cycles and spontaneous pregnancy with baby born after re-transplantation.

Cancer is the second major cause of death in the world. The problem of post-cancer infertility plays a significant role, because chemotherapy can be gonadotoxic. Cryopreservation of ovarian tissue before cancer therapy with re-implantation after convalescence is the potential key solution to this problem. The aim of this study was to test the viability of cryopreserved human ovarian cortex after long-term cooling in culture medium composed of permeable cryoprotectants. Ovarian fragments from sixteen patients were randomly divided into two groups. After the operation, tissue pieces assigned to both groups were cooled to 5 °C for 22-24 h, frozen and thawed. Group 1 pieces (n = 32) were cooled before cryopreservation in the standard culture medium, and Group 2 pieces (n = 32) were cooled in the freezing medium (culture medium+6% ethylene glycol+6% dimethyl sulfoxide+0.15 M sucrose). Freezing was performed in standard 5 ml cryo-vials with ice formation at -9 °C, cooling from -9 to -34 °C at a rate of -0.3 °C/min and plunging at -34 °C into liquid nitrogen. After thawing in a 100 °C (boiling) water bath, the removal of cryoprotectants was performed in 0.5 M sucrose with 20 min exposure in sucrose and 30 min stepping rehydration. The effectiveness of the pre-freezing cooling of tissue was evaluated by the development of follicles (histology). Six months after the autotransplantation, oocytes from the twenty-seven-year old, hormonally stimulated patient were retrieved and fertilized with her partner sperm through the intracytoplasmic spermatozoa injection (ICSI). For groups 1 and 2, 93.5 ± 1.9% and 96.4 ± 2.0% of the preantral follicles, respectively, were morphologically normal (P > 0.1) (with a tendency toward increasing in quality in Group 2). Six months after the auto-transplantation, two ICSI cycles resulted in the gathering and transplantation of high quality embryos, but no pregnancy had been established. Thirteen months after the auto-transplantation, the patient became spontaneously pregnant and delivered a healthy baby girl at term. Long-term (24 h) cooling of ovarian tissue to 5 °C before cryopreservation in the presence of permeable cryoprotectants simplifies the protocol of cryopreservation and has a tendency of increasing of the cells viability after thawing.

Crystal structure and Hirshfeld surface analysis of tris-(2,2'-bi-pyridine)-nickel(II) bis-(1,1,3,3-tetra-cyano-2-eth-oxy-propenide) dihydrate.

The title compound, [Ni(C10H8N2)3](C9H5N4O)2·2H2O, crystallizes as a racemic mixture in the monoclinic space group C2/c. In the crystal, the 1,1,3,3-tetracyano-2-ethoxypropenide anions and the water molecules are linked by O-H⋯N hydrogen bonds, forming chains running along the [010] direction. The bpy ligands of the cation are linked to the chain via C-H⋯π(cation) inter-actions involving the CH3 group. The inter-molecular inter-actions were investigated by Hirshfeld surface analysis and two-dimensional fingerprint plots.

The Role of Previous Therapies and Sites of Metastasis as Influencing Factors on Discordance of ER, PR and HER2 Status Between Primary and Metastasized Breast Cancer.

BACKGROUND/AIM: The aim of the present study was to analyze metastasized breast cancer (BC) patients with regard to the discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). We especially aimed to analyze the association between the change of tumor biology and previous treatment or metastatic sites. PATIENTS AND METHODS: Patients with metastasized BC who were treated at the Department of Gynecology/Breast Center of the University Hospital of Cologne were analyzed. RESULTS: Loss of HER2 occurred more frequently in lymph node metastases that were not in the axillary region (p=0.026). Letrozole showed a significant correlation with loss of ER and/or PR (p=0.041). Improved overall survival and post-metastasis survival were noticed with a gain of HER2 (p=0.044 and p=0.009, respectively) and concordant positive ER and PR status (p=0.002 and p=0.001, respectively). CONCLUSION: The discordance of receptors and the dependence of BC on therapies as well as metastatic sites stresses the necessity of early sample taking to offer patients suitable therapy options.

Comparison of Minimally Invasive Surgery and Abdominal Surgery Among Patients With Cervical Cancer.

BACKGROUND/AIM: The aim of this study was to evaluate the difference in clinical outcomes in patients with histologically confirmed cervical cancer of the uterus treated with either laparoscopy or laparotomy with curative intent between 2011 and 2017 at the Department of Gynecology and Obstetrics of University Hospital Cologne. MATERIALS AND METHODS: This retrospective analysis included all patients who received surgical treatment with curative intent between January 2011 and December 2017 for stages IA1 to IIB cervical carcinoma. Patients receiving primary or secondary surgery after neoadjuvant chemotherapy were also included. RESULTS: In total, 75 patients were included, of whom 34 patients underwent minimally invasive surgery and 41 underwent open surgery. Neoadjuvant chemotherapy was performed in 10 patients in the minimally-invasive group and in 14 patients in the laparotomy group. Statistically, no significant difference in overall survival (OS) was observed in both groups. Disease-free survival showed a significant difference in favor of the minimally invasive group. CONCLUSION: Minimally invasive surgical therapy for cervical cancer improves disease-free-survival. Prospective trials are needed to further confirm these results.

Clinical impact of PD-L1 and PD-1 expression in squamous cell cancer of the vulva.

PURPOSE: Squamous cell carcinoma of the vulva (SQCV) is the fifth most common cancer in women and accounts for about 5% of all genital cancers in women. The PD-L1 signaling pathway is activated in many malignant neoplasms and its blockade enhances anti-cancer immunity. The aim of our study was to examine the protein expression of PD-L1 and PD-1 in squamous cell cancer of the vulva, its correlations with clinicopathologic features and prognostic value. METHODS: Patients with SQCV treated in one institution were used for the analyses. PD-L1 immunohistochemistry was performed on 4 µm-thick section of the respective FFPE tissue blocks using the 28-8 antibody. PD-L1 scoring was performed separately for tumour cells (TC) and tumour associated immune cells. DNA was extracted to determine HPV status. Kaplan-Meier estimates for disease-free-survival and overall-survival were calculated and compared by log-rank test. RESULTS: PD-L1 expression in tumour cells could be observed in 32.9% of the patients. The expression of PD-L1 in peritumoural immune cells was confirmed in 91.4% of the patients. A significant correlation between PD-L1 expression in tumour cells and tumour stage was detected (p = 0.007). PD-L1 expression was independent from HPV status. Using the log-rank test we could not prove any significant differences in disease-free survival (p = 0.434) and overall survival (p = 0.858). Regression analysis showed that nodal status is a predictive factor of survival (p < 0.001). CONCLUSION: The present study showed that a relevant amount of patients with squamous cell cancer of the vulva express PD-L1 in both, tumour cells and tumour-associated immune cells. Furthermore, the significant correlation of PD-L1 expression in TCs with tumour stage indicated the clinical impact of PD-L1 expression during tumour development. These data indicate that SQCV might be amenable to immune checkpoint-inhibition and constitute a rational for the future clinical trials.