Publications by authors named "Domenico Ferraioli"

17 Publications

  • Page 1 of 1

Molecular Characterization of Ovarian Yolk Sac Tumor (OYST).

Cancers (Basel) 2021 Jan 9;13(2). Epub 2021 Jan 9.

Centre Léon Berard (CLB), 69008 Lyon, France.

Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient's tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in , , . Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
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http://dx.doi.org/10.3390/cancers13020220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826864PMC
January 2021

Affected Ovary Relative Volume: A Novel Sonographic Predictor of Ovarian Reserve in Patients with Unilateral Endometrioma-A Pilot Study.

J Clin Med 2020 Dec 17;9(12). Epub 2020 Dec 17.

Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Turin, 10126 Turin, Italy.

Background: The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian endometriosis. This study aimed to identify a sonographic parameter of ovarian reserve that could implement current available markers in patients with unilateral endometrioma.

Methods: Patients with unilateral endometrioma admitted to our Endometriosis Center between March 2018 and April 2019 were enrolled. Transvaginal ultrasonography for the evaluation of eight sonographic indicators and AMH level determination were performed. The relationship between AMH level and each indicator was assessed.

Results: Thirty-four women were included. There was a positive significant correlation between AMH level and the healthy ovary AFC (HO-AFC) ( = 0.36 = 0.034). A stronger, negative correlation between AMH level and the ratio between the volume of the affected and the healthy ovary (affected ovary relative volume, AORV) ( = -0.47; = 0.005) was evidenced. AORV had a satisfactory accuracy (AUC 0.73; CI 0.61-0.90; = 0.0008), and the cut-off value of 5.96 had the best balance of sensitivity/specificity in distinguishing between patients with a good ovarian reserve (AMH ≥ 2 ng/mL) and those at risk of ovarian reserve depletion after excisional surgery.

Conclusion: AORV may be a useful tool to assess ovarian reserve in patients with unilateral endometrioma without previous surgery and to guide physicians in clinical management.
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http://dx.doi.org/10.3390/jcm9124076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767191PMC
December 2020

A Fascial Reinterpretation of the Classical Female Pelvic Surgical Anatomy: Seeing Things from a Different Angle.

J Minim Invasive Gynecol 2021 May 26;28(5):940-941. Epub 2020 Nov 26.

Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Turin, Turin (Drs. Cosma, Carosso, and Benedetto).

Study Objective: The classical surgical anatomy of the female pelvis was born with radical hysterectomy [1] and focused on the pivotal role of the lateral parametrium, a conceptually complex structure, an artifact of surgical anatomy [2] without which the whole classical model would collapse. Here, using natural planes, we tried to simplify the puzzle of the virtual spaces surrounding this structure [3,4]. With the aim of better conceptualizing the classical model of the female pelvic surgical anatomy, we broadened its perspective, which had been narrowly focused on the historic gynecologic setting, by developing a comprehensive model of pelvic retroperitoneal compartmentalization. This dissection was based on the invariable anatomic (fasciae) rather than the surgical-anatomic (parametrium) structures and aimed at providing a holistic, more user-friendly approach intended for surgical and educational purposes [5]. Because each compartment has its own surgical function (hence the name), the excavation of a single compartment may be used as a rational guide to tailor surgery to the site of the pathologic condition to be treated or the type of procedure required, whereas the compartments' sequential development may be useful in planning surgical strategies. Redefining the classical model according to the anatomic fascial planes of dissection potentially allows for an intrinsic surgical reproducibility, minimizing dissective bias. A reinterpretation of the known anatomy is required to enhance education. The breaking down of such a complex system (the pelvis) into smaller parts (compartments) will hopefully provide a useful guide for conceptualization and navigation; surgical navigation requires a holistic mental map and a few invariable anatomic reference points or landmarks.

Design: A step-by-step laparoscopic demonstration of the fascial model, developed on a fresh frozen female pelvis, and its correlation with the classical female retroperitoneal surgical anatomy.

Setting: Cadaver Laboratory, Department of Legal Medicine, University of Turin.

Interventions: The first part of the video shows the progressive development of the 3 hemicompartments in the right hemipelvis and of the fourth median compartment after the identification of 3 invariable anatomic reference points: the obliterated umbilical artery, the ureter, and the sacrouterine ligament as superficial landmarks of 3 deeper fascial-ligamentous structures: the umbilicovesical fascia, the urogenital-hypogastric fascia, and the sacropubic ligament, respectively (Figure 1). The areas delimited by the aforementioned deep fascial ligamentous structures have been designated as compartments: • the right parietal hemicompartment, so called because it is bordered by the sidewall of the pelvis, lateral to the umbilicovesical fascia • the right vascular hemicompartment, so called because of the presence of the internal iliac vessel's visceral branches between the umbilicovesical fascia and the urogenital-hypogastric fascia • the visceral compartment, so called because it contains the pelvic organs between the sacropubic ligaments • the right neural hemicompartment, so called because of the presence of the organ-specific vegetative bundles, medial to the urogenital-hypogastric fascia. The second part of the video describes the retrorectal, presacral, and retropubic connection areas between the neural, vascular, and parietal hemicompartments of each hemipelvis, justifying their overall crescent shape. Finally, the spaces of classical surgical anatomy included in each hemicompartment are listed not only according to their anatomic criterion, but also according to their functional criterion. In fact, the parietal compartment should be developed for the evaluation of the pelvic lymph node status or during exenterative and urogynecologic procedures. The vascular compartment must be prepared when sectioning of the vascular visceral pedicles at their origin is required. Development of the neural compartment is required whenever visceral neural components are to be spared. The visceral compartment has to be developed for complete organ mobilization and exposure.

Conclusion: Taken as a whole, our 4-compartment model of pelvic anatomic surgery is intended for use in planning and optimizing surgical strategies. Moreover, it is potentially able to simplify surgical teaching and training, allowing the fitting together of puzzle-like pieces of disjointed organ-specific retroperitoneal spaces according to their function (Figure 2). The correlation of this approach to clinical outcomes is still being determined.
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http://dx.doi.org/10.1016/j.jmig.2020.11.016DOI Listing
May 2021

Impact of multidisciplinary tumour board in the management of ovarian carcinoma in the first-line setting. Exhaustive analysis from the Rhone-Alpes region.

Eur J Cancer Care (Engl) 2020 Nov 7;29(6):e13313. Epub 2020 Sep 7.

Oncology Department, Leon Berard Cancer Center, Lyon, France.

Objective: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment.

Methods: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes.

Results: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001).

Conclusion: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion.
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http://dx.doi.org/10.1111/ecc.13313DOI Listing
November 2020

EVAN-G score in patients undergoing minimally invasive gynecology oncologic surgery in an Enhanced Recovery After Surgery (ERAS) program.

Int J Gynecol Cancer 2020 12 16;30(12):1966-1974. Epub 2020 Jun 16.

Surgery, Paoli-Calmettes Institute, Marseille, Provence-Alpes-Côte d'Azur, France.

Introduction: Enhanced Recovery After Surgery (ERAS) has been proven to decrease the length of hospital stay without increasing re-admission rates or complications. There are limited data on the satisfaction of patients undergoing minimally invasive surgery for gynecologic malignancy within ERAS programs. The aim of this study was to evaluate patient satisfaction after minimally invasive surgery for gynecologic malignancy within the ERAS program using the 'Evaluation du Vécu de l'Anésthésie Génerale (EVAN-G)' questionnaire.

Methods: This observational retrospective study was conducted at the Paoli-Calmettes Institute between June 2016 and December 2018. All the included patients underwent minimally invasive surgery for a gynecologic malignancy. EVAN-G, a validated questionnaire, was used to measure peri-operative patient satisfaction. This questionnaire consists of 26 items assessing six elements: attention, privacy, information, pain, discomfort, and waiting time. Each element is assessed via a 5-step numerical scale and then transformed to a 0-100 scale according to the degree of satisfaction. The EVAN-G questionnaire was given to patients before surgery and collected during the post-operative consultation (2-3 weeks after surgery).

Results: A total of 175 patients underwent minimally invasive surgery for gynecologic malignancy within the ERAS program. Of these, 92 patients were included in the study and 83 patients were excluded. The overall patient compliance rate with our ERAS program was 90%. The analysis of the EVAN-G score of all participants showed an overall high level of satisfaction with a mean score of 81.9 (range 41.6-100). Patients with peri-operative complications or having prolonged hospitalization also showed high levels of satisfaction with a mean score of 80.5 (41.6-100) and 83.2(55-100), respectively.

Conclusion: In this study we showed a high patient satisfaction with the ERAS program. When comparing length of stay and complications, neither extended length of stay nor development of complications after minimally invasive surgery impacted patient satisfaction.
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http://dx.doi.org/10.1136/ijgc-2019-001173DOI Listing
December 2020

A simplified fascial model of pelvic anatomical surgery: going beyond parametrium-centered surgical anatomy.

Anat Sci Int 2021 Jan 11;96(1):20-29. Epub 2020 Jun 11.

Gynecology and Obstetrics 1, Department of Surgical Sciences, City of Health and Science, University of Torino, Via Ventimiglia 3, 10126, Turin, Italy.

The classical surgical anatomy of the female pelvis is limited by its gynecological oncological focus on the parametrium and burdened by its modeling based on personal techniques of different surgeons. However, surgical treatment of pelvic diseases, spreading beyond the anatomical area of origin, requires extra-regional procedures and a thorough pelvic anatomical knowledge. This study evaluated the feasibility of a comprehensive and simplified model of pelvic retroperitoneal compartmentalization, based on anatomical rather than surgical anatomical structures. Such a model aims at providing an easier, holistic approach useful for clinical, surgical and educational purposes. Six fresh-frozen female pelves were macroscopically and systematically dissected. Three superficial structures, i.e., the obliterated umbilical artery, the ureter and the sacrouterine ligament, were identified as the landmarks of 3 deeper fascial-ligamentous structures, i.e., the umbilicovesical fascia, the urogenital-hypogastric fascia and the sacropubic ligament. The retroperitoneal areolar tissue was then gently teased away, exposing the compartments delimited by these deep fascial structures. Four compartments were identified as a result of the intrapelvic development of the umbilicovesical fascia along the obliterated umbilical artery, the urogenital-hypogastric fascia along the mesoureter and the sacropubic ligaments. The retroperitoneal compartments were named: parietal, laterally to the umbilicovesical fascia; vascular, between the two fasciae; neural, medially to the urogenital-hypogastric fascia and visceral between the sacropubic ligaments. The study provides the scientific rational for a model of pelvic retroperitoneal anatomy based on identifiable anatomical structures and suitable for surgical planning and training.
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http://dx.doi.org/10.1007/s12565-020-00553-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806572PMC
January 2021

Correction to: Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer.

Breast Cancer Res Treat 2019 10;177(3):773

Department of Internal Medicine (DiMI), University of Genoa and Ospedale Policlinico San Martino, Viale Benedetto XV, 6, 16132, Genoa, Italy.

In the original publication of the article, the funding information was incorrectly published. The corrected funding statement is given in this correction article.
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http://dx.doi.org/10.1007/s10549-019-05348-zDOI Listing
October 2019

Schlafen-11 expression is associated with immune signatures and basal-like phenotype in breast cancer.

Breast Cancer Res Treat 2019 Sep 20;177(2):335-343. Epub 2019 Jun 20.

Department of Internal Medicine (DiMI), University of Genoa and Ospedale Policlinico San Martino, Viale Benedetto XV, 6, 16132, Genoa, Italy.

Purpose: Breast cancer (BC) is a heterogeneous disorder, with variable response to systemic chemotherapy. Likewise, BC shows highly complex immune activation patterns, only in part reflecting classical histopathological subtyping. Schlafen-11 (SLFN11) is a nuclear protein we independently described as causal factor of sensitivity to DNA damaging agents (DDA) in cancer cell line models. SLFN11 has been reported as a predictive biomarker for DDA and PARP inhibitors in human neoplasms. SLFN11 has been implicated in several immune processes such as thymocyte maturation and antiviral response through the activation of interferon signaling pathway, suggesting its potential relevance as a link between immunity and cancer. In the present work, we investigated the transcriptional landscape of SLFN11, its potential prognostic value, and the clinico-pathological associations with its variability in BC.

Methods: We assessed SLFN11 determinants in a gene expression meta-set of 5061 breast cancer patients annotated with clinical data and multigene signatures.

Results: We found that 537 transcripts are highly correlated with SLFN11, identifying "immune response", "lymphocyte activation", and "T cell activation" as top Gene Ontology processes. We established a strong association of SLFN11 with stromal signatures of basal-like phenotype and response to chemotherapy in estrogen receptor negative (ER-) BC. We identified a distinct subgroup of patients, characterized by high SLFN11 levels, ER- status, basal-like phenotype, immune activation, and younger age. Finally, we observed an independent positive predictive role for SLFN11 in BC.

Conclusions: Our findings are suggestive of a relevant role for SLFN11 in BC and its immune and molecular variability.
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http://dx.doi.org/10.1007/s10549-019-05313-wDOI Listing
September 2019

Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas.

Expert Opin Pharmacother 2019 04 6;20(6):713-723. Epub 2019 Feb 6.

a Academic Unit of Obstetrics and Gynecology , IRCCS Ospedale Policlinico San Martino , Genoa , Italy.

Introduction: Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis.

Areas Covered: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials.

Expert Opinion: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.
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http://dx.doi.org/10.1080/14656566.2019.1571042DOI Listing
April 2019

Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer.

Expert Opin Investig Drugs 2019 02 21;28(2):131-142. Epub 2018 Dec 21.

a Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI) , University of Genova , Italy.

Introduction: Endometrial cancer (EC) is the most common neoplasm of the female genital tract in developed countries. Despite the progress in early detection and treatment, a significant number of cases of advanced ECs are still diagnosed. These patients have few treatment options and a poor prognosis. Our understanding of EC pathogenesis and progression has been enhanced by recent genomic studies. Among the relevant biological pathways, phosphatidylinositol 3-kinase/AKT (PIK3/AKT)-mammalian target of rapamycin (mTOR) signaling is frequently upregulated in this cancer.

Areas Covered: This review covers investigational EC therapeutics acting on the PI3K/AKT/mTOR pathway. The authors review the results of clinical studies and highlight ongoing trials.

Expert Opinion: Several new agents are under evaluation for treating patients with metastatic, recurrent, and persistent EC. Clinical trials investigating PI3K/AKT/mTOR inhibitors have yielded controversial results. In the near future, new studies with dual inhibitors or multi-pathways inhibitors as mono or combination therapies with conventional chemotherapy (CT) or other targeted drugs may provide more promising data. Moreover, the evaluation of new serum and histological biomarkers is an attractive strategy for patient selection.
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http://dx.doi.org/10.1080/13543784.2018.1558202DOI Listing
February 2019

Location of Mutation in Gene and Survival in Patients with Ovarian Cancer.

Clin Cancer Res 2018 01 30;24(2):326-333. Epub 2017 Oct 30.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of gene affects the clinical outcome of ovarian cancer patients. A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for and genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer ( = 316) was used as a validation cohort. In the study cohort, 78 patients were carriers of germline mutations of After adjustment for FIGO stage and macroscopic residual disease, carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; = 0.001] and prolonged PFI (29.7 vs. 15.5 months, = 0.011), compared with noncarriers. carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; = 0.094) or PFI (19 vs. 15.5 months, = 0.146). In the TCGA cohort, only carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; = 0.001). Among ovarian cancer patients, carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2136DOI Listing
January 2018

Report on the first SLFN11 monothematic workshop: from function to role as a biomarker in cancer.

J Transl Med 2017 10 2;15(1):199. Epub 2017 Oct 2.

Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Martino IST-Istituto Nazionale Tumori, Genoa, Italy.

SLFN11 is a recently discovered protein with a putative DNA/RNA helicase function. First identified in association with the maturation of thymocytes, SLFN11 was later causally associated, by two independent groups, with the resistance to DNA damaging agents such as topoisomerase I and II inhibitors, platinum compounds, and other alkylators, making it an attractive molecule for biomarker development. Later, SLFN11 was linked to antiviral response in human cells and interferon production, establishing a potential bond between immunity and chemotherapy. Recently, we demonstrated the potential role of SLN11 as a biomarker to predict sensitivity to the carboplatin/taxol combination in ovarian cancer. The present manuscript reports on the first international monothematic workshop on SLFN11. Several researchers from around the world, directly and actively involved in the discovery, functional characterization, and study of SLFN11 for its biomarker and medicinal properties gathered to share their views on the current knowledge advances concerning SLFN11. The aim of the manuscript is to summarize the authors' interventions and the main take-home messages resulting from the workshop.
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http://dx.doi.org/10.1186/s12967-017-1296-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625715PMC
October 2017

Her2 assessment using quantitative reverse transcriptase polymerase chain reaction reliably identifies Her2 overexpression without amplification in breast cancer cases.

J Transl Med 2017 05 1;15(1):91. Epub 2017 May 1.

Department of Internal Medicine (Di.M.I.), University of Genoa and IRCCS AOU San Martino-IST, Viale Benedetto XV, 6, 16132, Genoa, Italy.

Background: Immunohistochemistry (IHC) and fluorescent-in situ hybridization (FISH) are standard methods to assess human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients. Real-time quantitative polymerase-chain-reaction (qRT-PCR) is able to detect HER2 overexpression. Here we compared FISH, IHC, quantitative PCR (qPCR), and qRT-PCR to determine the concordance rates and evaluate their relative roles in HER2 determination.

Patients And Methods: We determined HER2 status in 153 BC patients, using IHC, FISH, Q-PCR and qRT-PCR. In discordant cases, we directly measured HER2 protein levels using Western blotting.

Results: The overall agreement (OA) between FISH and Q-PCR was 94.1, with a k value of 0.87. Assuming FISH as the standard reference, Q-PCR showed an 86.1% sensitivity and a 99.0% specificity with a global accuracy of 91.6%. OA between FISH and qRT-PCR was 90.8% with a k value of 0.81. Of interest, the disagreement between FISH and qRT-PCR was mostly restricted to equivocal cases. HER2 protein analysis suggested that qRT-PCR correlates better than FISH with HER2 protein levels, particularly where FISH fails to provide conclusive results.

Significance: qRT-PCR may outperform FISH in identifying patients overexpressing HER2 protein. Q-PCR cannot be used for HER2 status assessment, due to its suboptimal level of agreement with FISH. Both FISH and Q-PCR may be less accurate than qRT-PCR as surrogates of HER2 protein determination.
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http://dx.doi.org/10.1186/s12967-017-1195-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412048PMC
May 2017

Genital melanoma: prognosis factors and treatment modality.

Arch Gynecol Obstet 2016 11 30;294(5):1037-1045. Epub 2016 Jun 30.

Leon Berard Cancer Center, 28 Promenade Léa et Napoléon Bullukian, 69008, Lyon, France.

Purpose: Genital melanoma is a rare pathology. We present the experience of two comprehensive cancer centers in Lyon (France) in the management of genital melanoma in order to identify prognostic factors and optimal treatments.

Methods: Between April 1992 and Mars 2014, 16 patients with a primary genital melanoma were referred to our department. Nine patients presented a vaginal melanoma, six vulvar melanomas and only one cervical melanoma. The median dimension of the lesion was 33.7 mm (5-100 mm). The AJCC stage ranged from IB to IIIC. 12 cases were the classic dark-blue flat melanoma and the other 4 cases were an atypical amelanotic tumor. Wide local surgery was performed in nine patients. A radical surgery was performed in six patients. In the large cervical melanoma, radiotherapy was performed as first-line treatment. In all the patients regional lymph node staging was performed. Adjuvant treatment was realized in nine patients.

Results: Two patients are alive without recurrence. Only one patient was lost to the first follow-up. The other 13 patients experienced a rapid recurrence. The median disease-free survival and the median overall survival were 11.8 months (2-49 m) and of 30.4 m (11-144 m), respectively. The disease-free survival and overall survival could be linked to a clinical presentation (Breslow thickness and morphology of lesion) associated to the early diagnosis.

Conclusions: In our small series, the most important prognosis factor remains the tumor thickness. These rare lesions should be treated in experienced centers in order to improve their prognostic.
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http://dx.doi.org/10.1007/s00404-016-4144-4DOI Listing
November 2016

The incidence and clinical significance of the micrometastases in the sentinel lymph nodes during surgical staging for early endometrial cancer.

Int J Gynecol Cancer 2015 May;25(4):673-80

Gynecology Department, Leon Berard Cancer Center; †Gynecology Department, Femme Mere Enfant Hospital, Lyon, France; and ‡Gynecology Department, University of Lausanne, Lausanne, Switzerland.

Introduction: The status of regional node remains one of the most important factors to guide adjuvant therapy in endometrial cancer (EC). Pelvic recurrence occurs in up to 15% of early EC patients with negative pelvic lymph nodes (LNs). The prognostic significance of detecting micrometastases (μM) in LN is debated. This retrospective case-control study performed in the Oncological Gynecology Department in Lyon between December 1998 and June 2012 reports the incidence and the clinical significance of μM detected during ultrastaging of negative sentinel lymph node (SLN) in EC.

Patients And Methods: Ninety-three patients affected by type I and II EC were submitted to surgery with SLN. Dual-labeling method was used to detect SLN. All the SLNs were subjected to ultrastaging researching μM. The patients with a locoregional or distant relapse represented the case-series (CS). The patients without locoregional or distant recurrences were the case-controls (CC).They were matched (1:2 ratio) according to age, International Federation of Gynecology and Obstetrics stage, and histopathologic features.

Results: Ten patients presenting a relapse represented CS. In the remaining 83 patients without recurrence, 20 CC were individualized. The detection rate of SLN per hemipelvis was of 17 (85%) of 20 hemipelvis and of 33 (82.5%) of 40 hemipelvis for CS and CC, respectively. Two SLN of CS arm were positives at frozen section. One of the 8 patients of CS arm with negative SLNs was positive for μM by immunohistochemistry analysis.

Conclusions: Lymph node status is one of the most important histopathologic features to determine the adjuvant treatment. The SLN technique could be proposed in selected patients affected by early EC. The μM in SLN could be researched and could help to modulate the following treatment. The multicenter study must be performed to clarify the optimal method of research of SLN in EC and the significance of μM in the LN.
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http://dx.doi.org/10.1097/IGC.0000000000000408DOI Listing
May 2015

Early invasive cervical cancer during pregnancy: different therapeutic options to preserve fertility.

Int J Gynecol Cancer 2012 Jun;22(5):842-9

Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Genoa, Italy.

Introduction: Cervical cancer is the second most common cancer diagnosed during pregnancy. Conservative management is possible, and different options should be discussed with patients. The main decision parameters are stage of disease, lymph node status, trimester of pregnancy and wishes of the patient. We reviewed our experience on cases of early-stage cervical cancer discovered during pregnancy and treated with different options of fertility-sparing management.

Materials And Methods: Between 1990 and 2010, 5 patients with early-stage cervical cancer diagnosed during pregnancy were referred to our department for fertility-sparing treatment. The mean age at diagnosis was 28.6 years (range, 26-30 years). The stages of the tumors according to the International Federation of Gynecology and Obstetrics were IA2 in 2 women and IB1 in 3 women. The histological type was squamous carcinoma in 3 cases and adenocarcinoma in 2 cases. All patients willing to preserve their fertility were treated with vaginal radical trachelectomy (VRT) and pelvic lymph nodes dissection (PLN-D).

Results: Three procedures were performed in the first trimester: 1 patient was treated with medical abortion and then VRT and PLN-D, 2 patients were submitted to VRT and PLN-D during the first trimester, and 1 patient's case was complicated by spontaneous abortion. One patient was observed during the second trimester (20 weeks of gestation) and treated with VRT and PLN-D during pregnancy. Because this patient had pelvic lymph nodes positive for cancer, a cesarean delivery (CD) with radical hysterectomy and para-aortic lymph nodes dissection was performed followed by chemoradiotherapy. The last patient was evaluated during the third trimester of her pregnancy. Treatment included CD followed by VRT and PLN-D, which was delayed, to allow fetal maturity.

Conclusions: Diagnosis of cervical cancer can occur during pregnancy. Different options of fertility-sparing treatment can be discussed on the basis of several factors: tumor stage, gestational age, and the patient's desire regarding fertility and pregnancy sparing.
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http://dx.doi.org/10.1097/IGC.0b013e31824ff142DOI Listing
June 2012
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