Cancers

2022

Jump to: 2021

15 pages, 307 KiB

Open AccessArticle

Anastomotic Leakage after Colorectal Surgery in Ovarian Cancer: Drainage, Stoma Utility and Risk Factors

by Liliana Mereu, Francesca Dalprà, Valeria Berlanda, Riccardo Pertile, Daniela Coser, Basilio Pecorino, Maria Gabriella D’Agate, Francesco Ciarleglio, Alberto Brolese and Saverio Tateo

Cancers 2022, 14(24), 6243; https://doi.org/10.3390/cancers14246243 - 18 Dec 2022

Cited by 4 | Viewed by 1913

Abstract

Objective: to evaluate the incidence of anastomotic leakage (AL), risk factors and utility of drainage and stoma in patients undergoing intestinal surgery for ovarian cancer in a single institution and in a review of the literature. Methods: retrospective study that includes consecutive patients [...] Read more.

Objective: to evaluate the incidence of anastomotic leakage (AL), risk factors and utility of drainage and stoma in patients undergoing intestinal surgery for ovarian cancer in a single institution and in a review of the literature. Methods: retrospective study that includes consecutive patients undergoing debulking surgery with en bloc pelvic resection with rectosigmoid colectomy for ovarian cancer between 1 November 2011 and 31 December 2021. Data regarding patient and tumour characteristics, surgical procedure, hospitalisation, complications and follow-up were recorded and analysed. The PubMed database was explored for recent publications on this topic. Results: Seventy-five patients were enrolled in the study. All anastomoses were performed at a distance of >6 cm from the anal margin, with negative leak tests and tension-free anastomosis. Diverting stoma were performed in just three patients (4%). At least one perianastomotic pelvic drain was positioned in 71 patients (94.7%) and was removed on average on postoperative day 7. Four patients (5.3%) experienced AL. In all cases, the drain content was not the only sign of complication, as the clinical signs were also highly suggestive. Just one patient received conservative treatment. Average postoperative hospitalisation was 14.6 days (SD: ±9.7). There were no deaths at 30 and 60 days after surgery. Between the AL and non-AL groups, statistically significant differences were observed for age, Charlson Comorbidity Index, length of the intestinal resection and fitness for chemotherapy at 30 days. In ovarian cancer, rectosigmoid resection is a standardised procedure with comparable results for AL, and risk factors for AL are discretely homogeneous. What is neither homogeneous nor standardised according to the literature is the use of stomas and/or drains. Conclusion: use in the future of protective stoma and/or intra-abdominal drains is to be explored in selected and standardised situations to verify their preventive role. Full article

22 pages, 3137 KiB

Open AccessArticle

Metabolomic Analysis Points to Bioactive Lipid Species and Acireductone Dioxygenase 1 (ADI1) as Potential Therapeutic Targets in Poor Prognosis Endometrial Cancer

by Sònia Gatius, Mariona Jove, Cristina Megino-Luque, Manel Albertí-Valls, Andree Yeramian, Nuria Bonifaci, Miquel Piñol, Maria Santacana, Irene Pradas, David Llobet-Navas, Reinald Pamplona, Xavier Matías-Guiu and Núria Eritja

Cancers 2022, 14(12), 2842; https://doi.org/10.3390/cancers14122842 - 8 Jun 2022

Cited by 8 | Viewed by 2296

Abstract

Metabolomic profiling analysis has the potential to highlight new molecules and cellular pathways that may serve as potential therapeutic targets for disease treatment. In this study, we used an LC-MS/MS platform to define, for the first time, the specific metabolomic signature of uterine [...] Read more.

Metabolomic profiling analysis has the potential to highlight new molecules and cellular pathways that may serve as potential therapeutic targets for disease treatment. In this study, we used an LC-MS/MS platform to define, for the first time, the specific metabolomic signature of uterine serous carcinoma (SC), a relatively rare and aggressive variant of endometrial cancer (EC) responsible for 40% of all endometrial cancer-related deaths. A metabolomic analysis of 31 ECs (20 endometrial endometrioid carcinomas (EECs) and 11 SCs) was performed. Following multivariate statistical analysis, we identified 232 statistically different metabolites among the SC and EEC patient samples. Notably, most of the metabolites identified (89.2%) were lipid species and showed lower levels in SCs when compared to EECs. In addition to lipids, we also documented metabolites belonging to amino acids and purine nucleotides (such as 2-Oxo-4-methylthiobutanoic acid, synthesised by acireductone dioxygenase 1 (ADI1) enzyme), which showed higher levels in SCs. To further investigate the role of ADI1 in SC, we analysed the expression protein levels of ADI1 in 96 ECs (67 EECs and 29 SCs), proving that the levels of ADI1 were higher in SCs compared to EECs. We also found that ADI1 mRNA levels were higher in p53 abnormal ECs compared to p53 wild type tumours. Furthermore, elevated ADI1 mRNA levels showed a statistically significant negative correlation with overall survival and progression-free survival among EEC patients. Finally, we tested the ability of ADI1 to induce migration and invasion capabilities in EC cell lines. Altogether, these results suggest that ADI1 could be a potential therapeutic target in poor-prognosis SCs and other Ecs with abnormal p53 expression. Full article

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24 pages, 9159 KiB

Open AccessArticle

Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

by Diana Gomes, Shivani Yaduvanshi, Samuel Silvestre, Ana Paula Duarte, Adriana O. Santos, Christiane P. Soares, Veerendra Kumar, Luís Passarinha and Ângela Sousa

Cancers 2022, 14(12), 2834; https://doi.org/10.3390/cancers14122834 - 8 Jun 2022

Cited by 9 | Viewed by 3641

Abstract

Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all [...] Read more.

Cervical cancer is the fourth leading cause of death in women worldwide, with 99% of cases associated with a human papillomavirus (HPV) infection. Given that HPV prophylactic vaccines do not exert a therapeutic effect in individuals previously infected, have low coverage of all HPV types, and have poor accessibility in developing countries, it is unlikely that HPV-associated cancers will be eradicated in the coming years. Therefore, there is an emerging need for the development of anti-HPV drugs. Considering HPV E6’s oncogenic role, this protein has been proposed as a relevant target for cancer treatment. In the present work, we employed in silico tools to discover potential E6 inhibitors, as well as biochemical and cellular assays to understand the action of selected compounds in HPV-positive cells (Caski and HeLa) vs. HPV-negative (C33A) and non-carcinogenic (NHEK) cell lines. In fact, by molecular docking and molecular dynamics simulations, we found three phenolic compounds able to dock in the E6AP binding pocket of the E6 protein. In particular, lucidin and taxifolin were able to inhibit E6-mediated p53 degradation, selectively reduce the viability, and induce apoptosis in HPV-positive cells. Altogether, our data can be relevant for discovering promising leads for the development of specific anti-HPV drugs. Full article

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23 pages, 925 KiB

Open AccessSystematic Review

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

by Julia M. Hecken, Günther A. Rezniczek and Clemens B. Tempfer

Cancers 2022, 14(11), 2670; https://doi.org/10.3390/cancers14112670 - 27 May 2022

Cited by 8 | Viewed by 3490

Abstract

Cervical dysplasia is a common precancerous lesion affecting 1% to 2% of women worldwide. Significant progress in the diagnosis and treatment of cervical dysplasia have been made in the last decade. We performed a systematic literature search of the databases PubMed and Cochrane [...] Read more.

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

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22 pages, 2408 KiB

Open AccessArticle

Biomarker-Based Models for Preoperative Assessment of Adnexal Mass: A Multicenter Validation Study

by Rafał Watrowski, Eva Obermayr, Christine Wallisch, Stefanie Aust, Nicole Concin, Elena Ioana Braicu, Toon Van Gorp, Annette Hasenburg, Jalid Sehouli, Ignace Vergote and Robert Zeillinger

Cancers 2022, 14(7), 1780; https://doi.org/10.3390/cancers14071780 - 31 Mar 2022

Cited by 6 | Viewed by 2538

Abstract

Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and [...] Read more.

Ovarian cancer (OC) is the most lethal genital malignancy in women. We aimed to develop and validate new proteomic-based models for non-invasive diagnosis of OC. We also compared them to the modified Risk of Ovarian Malignancy Algorithm (ROMA-50), the Copenhagen Index (CPH-I) and our earlier Proteomic Model 2017. Biomarkers were assessed using bead-based multiplex technology (Luminex^®) in 356 women (250 with malignant and 106 with benign ovarian tumors) from five European centers. The training cohort included 279 women from three centers, and the validation cohort 77 women from two other centers. Of six previously studied serum proteins (CA125, HE4, osteopontin [OPN], prolactin, leptin, and macrophage migration inhibitory factor [MIF]), four contributed significantly to the Proteomic Model 2021 (CA125, OPN, prolactin, MIF), while leptin and HE4 were omitted by the algorithm. The Proteomic Model 2021 revealed a c-index of 0.98 (95% CI 0.96, 0.99) in the training cohort; however, in the validation cohort it only achieved a c-index of 0.82 (95% CI 0.72, 0.91). Adding patient age to the Proteomic Model 2021 constituted the Combined Model 2021, with a c-index of 0.99 (95% CI 0.97, 1) in the training cohort and a c-index of 0.86 (95% CI 0.78, 0.95) in the validation cohort. The Full Combined Model 2021 (all six proteins with age) yielded a c-index of 0.98 (95% CI 0.97, 0.99) in the training cohort and a c-index of 0.89 (95% CI 0.81, 0.97) in the validation cohort. The validation of our previous Proteomic Model 2017, as well as the ROMA-50 and CPH-I revealed a c-index of 0.9 (95% CI 0.82, 0.97), 0.54 (95% CI 0.38, 0.69) and 0.92 (95% CI 0.85, 0.98), respectively. In postmenopausal women, the three newly developed models all achieved a specificity of 1.00, a positive predictive value (PPV) of 1.00, and a sensitivity of >0.9. Performance in women under 50 years of age (c-index below 0.6) or with normal CA125 (c-index close to 0.5) was poor. CA125 and OPN had the best discriminating power as single markers. In summary, the CPH-I, the two combined 2021 Models, and the Proteomic Model 2017 showed satisfactory diagnostic accuracies, with no clear superiority of either model. Notably, although combining values of only four proteins with age, the Combined Model 2021 performed comparably to the Full Combined Model 2021. The models confirmed their exceptional diagnostic performance in women aged ≥50. All models outperformed the ROMA-50. Full article

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10 pages, 706 KiB

Open AccessArticle

Pelvic Exenteration for the Treatment of Locally Advanced Vulvar Cancer in South West Wales

by Ganiy Opeyemi Abdulrahman, Nagindra Das, Thipparajapura V. Chandrasekaran, Umesh Khot, Peter J. Drew, Pradeep Bose, Jessica N. Vet, Nasima Tofazzal, Shaun Roberts and Kerryn Lutchman Singh

Cancers 2022, 14(7), 1767; https://doi.org/10.3390/cancers14071767 - 31 Mar 2022

Cited by 5 | Viewed by 1882

Abstract

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. [...] Read more.

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. Among the 19 women included during the study period, 14 women (73.7%) had primary LAVC while 5 women (26.3%) had recurrent disease. Surgical resection margins were microscopically clear (R0) in 94.7% of patients—14/14 undergoing primary treatment and 4/5 undergoing treatment for recurrent disease. Complete closure of the wound was achieved in 100% of women, with no wound left to heal by secondary intention. Tumour size was a predictor of requiring myocutaneous flap reconstruction, with all tumours less than 40 mm undergoing primary closure, while almost all tumours 40 mm diameter or greater (14/15 women) required flap reconstruction (p = 0.001). The 30-day major morbidity rate was 42% and there was no perioperative death. The mean overall survival was 144.8 months (2–206 months), with 1-, 2- and 5-year survival rates of 89.5%, 75.1% and 66.7%, respectively. In our centre, a primary surgical approach to the management of LAVC has resulted in good survival outcomes with acceptable morbidity rates. Full article

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19 pages, 971 KiB

Open AccessFeature PaperArticle

Therapeutic Challenges in Patients with Gynecologic Carcinosarcomas: Analysis of a Multicenter National Cohort Study from the French Prospective TMRG Network

by Clémence Romeo, Olivia Le Saux, Margaux Jacobs, Florence Joly, Gwenael Ferron, Laure Favier, Jean-David Fumet, Nicolas Isambert, Pierre-Emmanuel Colombo, Renaud Sabatier, Ludovic Bastide, Amandine Charreton, Mojgan Devouassoux-Shisheboran, Witold Gertych, Coraline Dubot, Diana Bello Roufai, Guillaume Bataillon, Dominique Berton, Elsa Kalbacher, Patricia Pautier, Christophe Pomel, Caroline Cornou, Isabelle Treilleux, Audrey Lardy-Cleaud and Isabelle Ray-Coquard Show full author list Hide full author list

Cancers 2022, 14(2), 354; https://doi.org/10.3390/cancers14020354 - 12 Jan 2022

Cited by 6 | Viewed by 2890

Abstract

Background: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment [...] Read more.

Background: Gynecological carcinosarcomas are rare and aggressive diseases, with a poor prognosis. The rarity of these tumors explains the lack of robust and specific data available in the literature. The objective of this study was to investigate the impact of initial adjuvant treatment and recurrent therapeutic strategies. Patients and methods: A multicentric cohort study within the French national prospective Rare Malignant Gynecological Tumors (TMRG) network was conducted. Data from all included carcinosarcomas diagnosed between 2011 and 2018 were retrospectively collected. Results: 425 cases of uterine and ovarian carcinosarcomas (n = 313 and n = 112, respectively) were collected and analyzed from 12 participating centers. At diagnosis, 140 patients (48%) had a FIGO stage III–IV uterine carcinosarcoma (UCS) and 88 patients (83%) had an advanced ovarian carcinosarcoma (OCS) (FIGO stage ≥ III). Two hundred sixty-seven patients (63%) received adjuvant chemotherapy, most preferably carboplatin-paclitaxel regimen (n = 227, 86%). After a median follow-up of 47.4 months, the median progression-free survival (mPFS) was 15.1 months (95% CI 12.3–20.6) and 14.8 months (95% CI 13.1–17.1) for OCS and UCS, respectively. The median overall survival for OCS and UCS was 37.1 months (95% CI 22.2–49.2) and 30.6 months (95% CI 24.1–40.9), respectively. With adjuvant chemotherapy followed by radiotherapy, mPFS was 41.0 months (95% CI 17.0–NR) and 18.9 months (95% CI 14.0–45.6) for UCS stages I–II and stages III–IV, respectively. In the early stage UCS subgroup (i.e., stage IA, n = 86, 30%), mPFS for patients treated with adjuvant chemotherapy (n = 24) was not reached (95% CI 22.2–NR), while mPFS for untreated patients (n = 62) was 19.9 months (95% IC 13.9–72.9) (HR 0.44 (0.20–0.95) p = 0.03). At the first relapse, median PFS for all patients was 4.2 months (95% CI 3.5–5.3). In the first relapse, mPFS was 6.7 months (95% CI 5.1–8.5) and 2.2 months (95% CI 1.9–2.9) with a combination of chemotherapy or monotherapy, respectively (p < 0.001). Conclusions: Interestingly, this vast prospective cohort of gynecological carcinosarcoma patients from the French national Rare Malignant Gynecological Tumors network (i) highlights the positive impact of adjuvant CT on survival in all localized stages (including FIGO IA uterine carcinosarcomas), (ii) confirms the importance of platinum-based combination as an option for relapse setting, and (iii) reports median PFS for various therapeutic strategies in the relapse setting. Full article

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2021

Jump to: 2022

13 pages, 1259 KiB

Open AccessArticle

Cell-Free-DNA-Based Copy Number Index Score in Epithelial Ovarian Cancer—Impact for Diagnosis and Treatment Monitoring

by Elena Ioana Braicu, Andreas du Bois, Jalid Sehouli, Julia Beck, Sonia Prader, Hagen Kulbe, Bernd Eiben, Philipp Harter, Alexander Traut, Klaus Pietzner, Ralf Glaubitz, Beyhan Ataseven, Radoslav Chekerov, Christoph Keck, Thomas Winkler, Sebastian Heikaus, Peggy Gellendin, Ekkehard Schütz and Florian Heitz

Cancers 2022, 14(1), 168; https://doi.org/10.3390/cancers14010168 - 30 Dec 2021

Cited by 6 | Viewed by 3194

Abstract

Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results [...] Read more.

Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. Methods: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. Results: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. Conclusion: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor. Full article

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12 pages, 432 KiB

Open AccessArticle

Association of a Combined Cancer Exhaustion Score with Circulating Tumor Cells and Outcome in Ovarian Cancer—A Study of the OVCAD Consortium

by Eva Obermayr, Elena Ioana Braicu, Stephan Polterauer, Liselore Loverix, Nicole Concin, Linn Woelber, Sven Mahner, Jalid Sehouli, Toon Van Gorp, Ignace Vergote, Robert Zeillinger and Stefanie Aust

Cancers 2021, 13(23), 5865; https://doi.org/10.3390/cancers13235865 - 23 Nov 2021

Cited by 3 | Viewed by 1756

Abstract

We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, [...] Read more.

We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment. Full article

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17 pages, 2713 KiB

Open AccessArticle

Photodynamic Priming Improves the Anti-Migratory Activity of Prostaglandin E Receptor 4 Antagonist in Cancer Cells In Vitro

by Aaron J. Sorrin, Cindy Liu, Julia Cicalo, Jocelyn Reader, Daniel Najafali, Yuji Zhang, Dana M. Roque and Huang-Chiao Huang

Cancers 2021, 13(21), 5259; https://doi.org/10.3390/cancers13215259 - 20 Oct 2021

Cited by 6 | Viewed by 2935

Abstract

The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to [...] Read more.

The combination of photodynamic agents and biological inhibitors is rapidly gaining attention for its promise and approval in treating advanced cancer. The activity of photodynamic treatment is mainly governed by the formation of reactive oxygen species upon light activation of photosensitizers. Exposure to reactive oxygen species above a threshold dose can induce cellular damage and cancer cell death, while the surviving cancer cells are “photodynamically primed”, or sensitized, to respond better to other drugs and biological treatments. Here, we report a new combination regimen of photodynamic priming (PDP) and prostaglandin E₂ receptor 4 (EP4) inhibition that reduces the migration and invasion of two human ovarian cancer cell lines (OVCAR-5 and CAOV3) in vitro. PDP is achieved by red light activation of the FDA-approved photosensitizer, benzoporphyrin derivative (BPD), or a chemical conjugate composed of the BPD linked to cetuximab, an anti-epithelial growth factor receptor (EGFR) antibody. Immunoblotting data identify co-inhibition of EGFR, cAMP-response element binding protein (CREB), and extracellular signal-regulated kinase 1/2 (ERK1/2) as key in the signaling cascades modulated by the combination of EGFR-targeted PDP and EP4 inhibition. This study provides valuable insights into the development of a molecular-targeted photochemical strategy to improve the anti-metastatic effects of EP4 receptor antagonists. Full article

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12 pages, 613 KiB

Open AccessArticle

One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA)

by María Dolores Diestro, Alberto Berjón, Ignacio Zapardiel, Laura Yébenes, Irune Ruiz, Arantza Lekuona, Marta Rezola, Ibon Jaunarena, Jaime Siegrist, Margarita Sánchez-Pastor, María Cuadra, Amaia Sagasta, Isabel Guerra, Luis I. Lete, Fernando Roldán, Carlo B. Marta, María J. Boillos, María J. Cardiel, Carlos López-de la Manzanara, Fernanda Relea, Pluvio J. Coronado, Alejandro Pascual, María J. Román, Gloria Peiró, Luis J. Matute, Beatriz Montero, Juan C. Muruzábal, Rosa Guarch, Cristina Zorrero, Ana Calatrava, Laia Ribot, Irmgard Costa, Alicia Hernández and David Hardisson Show full author list Hide full author list

Cancers 2021, 13(17), 4465; https://doi.org/10.3390/cancers13174465 - 4 Sep 2021

Cited by 11 | Viewed by 3777

Abstract

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from [...] Read more.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 μm intervals and examined by hematoxylin–eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis. Full article

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16 pages, 9640 KiB

Open AccessArticle

Efficacy and Safety of Auricular Acupuncture for the Treatment of Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial

by Melanie D. Höxtermann, Katja Buner, Heidemarie Haller, Wiebke Kohl, Gustav Dobos, Mattea Reinisch, Sherko Kümmel, Holger Cramer and Petra Voiss

Cancers 2021, 13(16), 4082; https://doi.org/10.3390/cancers13164082 - 13 Aug 2021

Cited by 24 | Viewed by 12653

Abstract

Among women, breast cancer is the most commonly diagnosed cancer worldwide. Sleep problems impair 40–70% of breast cancer survivors. This randomized controlled trial evaluates the effect of auricular acupuncture on sleep quality in breast cancer survivors suffering from insomnia. Fifty-two female breast cancer [...] Read more.

Among women, breast cancer is the most commonly diagnosed cancer worldwide. Sleep problems impair 40–70% of breast cancer survivors. This randomized controlled trial evaluates the effect of auricular acupuncture on sleep quality in breast cancer survivors suffering from insomnia. Fifty-two female breast cancer survivors with insomnia (mean age 55.73 ± 8.10 years) were randomized either to 10 treatments of auricular acupuncture within five weeks (n = 26), or to a single session of psychoeducation plus an insomnia advice booklet (n = 26). The primary outcome was sleep quality (measured by the Pittsburgh Sleep Quality Index) at week 5. Secondary outcomes were inflammation parameter (interleukin-6), stress, anxiety, depression, quality of life, and fatigue at week 5, and sleep quality, stress, anxiety, depression, quality of life, and fatigue 17 and 29 weeks after randomization. Intention-to-treat analysis showed a significantly stronger increase in sleep quality in the auricular acupuncture group compared to the psychoeducation group (p = 0.031; η²_p = 0.094) at week 5. Furthermore, auricular acupuncture improved stress (p = 0.030; η²_p = 0.094), anxiety (p = 0.001; η²_p = 0.192), and fatigue (p = 0.006; η²_p = 0.148) at week 5 compared to psychoeducation. No significant group difference was found concerning the other outcomes at week 5, or in any outcome at week 17 or week 29. No serious adverse events occurred during the study period. In conclusion, a semi-standardized group auricular acupuncture might be an effective and safe intervention in treating insomnia in breast cancer survivors in the short term, and may reduce stress, anxiety, and fatigue as well. Long-term effects remain questionable. Full article

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22 pages, 17440 KiB

Open AccessArticle

Functional Analysis of Non-Genetic Resistance to Platinum in Epithelial Ovarian Cancer Reveals a Role for the MBD3-NuRD Complex in Resistance Development

by Tabea L. Bauer, Katrin Collmar, Till Kaltofen, Ann-Katrin Loeffler, Lorena Decker, Jan Mueller, Sabine Pinter, Stephan A. Eisler, Sven Mahner, Patricia Fraungruber, Stefan Kommoss, Annette Staebler, Lewis Francis, R. Steven Conlan, Johannes Zuber, Udo Jeschke, Fabian Trillsch and Philipp Rathert

Cancers 2021, 13(15), 3801; https://doi.org/10.3390/cancers13153801 - 28 Jul 2021

Cited by 6 | Viewed by 4515

Abstract

Epithelial ovarian cancer (EOC) is the most lethal disease of the female reproductive tract, and although most patients respond to the initial treatment with platinum (cPt)-based compounds, relapse is very common. We investigated the role of epigenetic changes in cPt-sensitive and -resistant EOC [...] Read more.

Epithelial ovarian cancer (EOC) is the most lethal disease of the female reproductive tract, and although most patients respond to the initial treatment with platinum (cPt)-based compounds, relapse is very common. We investigated the role of epigenetic changes in cPt-sensitive and -resistant EOC cell lines and found distinct differences in their enhancer landscape. Clinical data revealed that two genes (JAK1 and FGF10), which gained large enhancer clusters in resistant EOC cell lines, could provide novel biomarkers for early patient stratification with statistical independence for JAK1. To modulate the enhancer remodeling process and prevent the acquisition of cPt resistance in EOC cells, we performed a chromatin-focused RNAi screen in the presence of cPt. We identified subunits of the Nucleosome Remodeling and Deacetylase (NuRD) complex as critical factors sensitizing the EOC cell line A2780 to platinum treatment. Suppression of the Methyl-CpG Binding Domain Protein 3 (MBD3) sensitized cells and prevented the establishment of resistance under prolonged cPt exposure through alterations of H3K27ac at enhancer regions, which are differentially regulated in cPt-resistant cells, leading to a less aggressive phenotype. Our work establishes JAK1 as an independent prognostic marker and the NuRD complex as a potential target for combinational therapy. Full article

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Innovative Concepts in the Diagnosis and Treatment of Gynecologic Malignancies (Closed)

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2022

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2021

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