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Introduction: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS) is a national cohort that was established in 2015 with the aim of improving quality of care of affected adults with eosinophilic esophagitis (EoE). Between 2020 and 2022, paper questionnaires were gradually replaced by fully electronic data capture using Research Electronic Data Capture (REDCap®) software. We aim to provide an update of the SEECS 8 years after its launch. Methods: The SEECS prospectively includes adults (≥18 years of age) with EoE as well as patients with gastroesophageal reflux disease (GERD) and healthy control subjects (HC). Upon inclusion and follow-up (typically once every 12-18 months), patients and physicians complete REDCap® questionnaires, which are available in German, French, and English. Patient-reported outcomes (PROs) and biologic findings are assessed on the same day using validated instruments (EEsAI PRO for symptoms; EoE-QoL-A for QoL; EREFS for endoscopic activity; modified EoE-HSS for histologic activity). The SEECS biobank includes biosamples from patients with EoE, GERD, and HC. Results: As of July 2023, the SEECS included 778 patients (716 [92%] with EoE, 29 [3.8%] with GERD, and 33 [4.2%] HC; 559/778 [71.9%] were male). Mean age ± SD (years) at enrollment according to diagnosis was as follows: EoE 41.9 ± 12.9, GERD 53.6 ± 16.4, HC 51.7 ± 17.2. Concomitant GERD was found in 200 patients (27.9%) of the EoE cohort. Concomitant allergic disorders (asthma, rhinoconjunctivitis, eczema) were present in 500 EoE patients (74.4%). At inclusion, 686 (95.8%) of EoE patients were on ongoing treatment (orodispersible budesonide tablet [Jorveza®] in 281 patients [41%]; budesonide or fluticasone syrup or swallowed powder in 290 patients [42.3%]; proton-pump inhibitors in 162 patients [23.6%]; elimination diets in 103 patients [15%]; and esophageal dilation at last visit in 166 patients [24.2%]). A total of 8,698 biosamples were collected, of which 1,395 (16%) were used in the framework of translational research projects. Conclusion: SEECS continuously grows and is operational using fully electronic data capture. SEECS offers up-to-date epidemiologic and real-world clinical efficacy data on EoE and promotes clinical and translational research.
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INTRODUCTION: Pulmonary pleomorphic carcinoma (PPC) is an aggressive and highly heterogeneous NSCLC whose underlying biology is still poorly understood. METHODS: A total of 42 tumor areas from 20 patients with PPC were microdissected, including 39 primary tumors and three metastases, and the histologically distinct components were subjected to whole exome sequencing separately. We further performed in silico analysis of microdissected bulk RNA sequencing and methylation data of 28 samples from 14 patients with PPC. We validated our findings using immunohistochemistry. RESULTS: The epithelial and the sarcomatoid components of PPCs shared a large number of genomic alterations. Most mutations in cancer driver genes were clonal and truncal between the two components of PPCs suggesting a common ancestor. The high number of alterations in the RTK-RAS pathway suggests that it plays an important role in the evolution of PPC. The metastases morphologically and genetically resembled the epithelial or the sarcomatoid components of the tumor. The transcriptomic and epigenetic profiles of the sarcomatoid components of PPCs with matched squamous-like or adenocarcinoma-like components differed from each other, and they shared more similarities to their matched epithelial components. NCAM1/CD56 was preferentially expressed in the sarcomatoid component of squamous-like PPCs, whereas CDH1/E-Cadherin expression was down-regulated in the sarcomatoid component of most PPCs. CONCLUSION: Lung adenocarcinoma-like PPCs are mainly driven by RTK-RAS signaling, whereas epithelial-mesenchymal transition programs as highlighted by increased NCAM1 and decreased CDH1 expression govern the epithelial-sarcomatoid transition between the clonally related tumor components. Several alterations in PPCs pinpoint therapeutic opportunities.
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DNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame.
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Epigenómica , Neoplasias , Humanos , Aprendizaje Automático no Supervisado , Nube Computacional , Neoplasias/diagnóstico , Neoplasias/genética , Metilación de ADNRESUMEN
Tumor cell fraction (TCF) estimation is a common clinical task with well-established large interobserver variability. It thus provides an ideal test bed to evaluate potential impacts of employing a tumor cell fraction computer-aided diagnostic (TCFCAD) tool to support pathologists' evaluation. During a National Slide Seminar event, pathologists (n = 69) were asked to visually estimate TCF in 10 regions of interest (ROIs) from hematoxylin and eosin colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities. Next, they re-evaluated the same ROIs while being provided a TCFCAD-created overlay highlighting predicted tumor vs nontumor cells, together with the corresponding TCF percentage. Participants also reported confidence levels in their assessments using a 5-tier scale, indicating no confidence to high confidence, respectively. The TCF ground truth (GT) was defined by manual cell-counting by experts. When assisted, interobserver variability significantly decreased, showing estimates converging to the GT. This improvement remained even when TCFCAD predictions deviated slightly from the GT. The standard deviation (SD) of the estimated TCF to the GT across ROIs was 9.9% vs 5.8% with TCFCAD (P < .0001). The intraclass correlation coefficient increased from 0.8 to 0.93 (95% CI, 0.65-0.93 vs 0.86-0.98), and pathologists stated feeling more confident when aided (3.67 ± 0.81 vs 4.17 ± 0.82 with the computer-aided diagnostic [CAD] tool). TCFCAD estimation support demonstrated improved scoring accuracy, interpathologist agreement, and scoring confidence. Interestingly, pathologists also expressed more willingness to use such a CAD tool at the end of the survey, highlighting the importance of training/education to increase adoption of CAD systems.
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Computadores , Patólogos , Humanos , SuizaRESUMEN
Background: Tumors of the vertebral column consist of primary spinal tumors and malignancies metastasizing to the spine. Although primary spine tumors are rare, metastases to the spine have gradually increased over past decades because of aging populations and improved survival for various cancer subtypes achieved by advances in cancer therapy. Metastases to the vertebral column occur in up to 70% of cancer patients, with 10% of patients demonstrating epidural spinal cord compression. Therefore, many cancer patients may face spinal surgical intervention during their chronic illness; such interventions range from simple cement augmentation over decompression of neural elements to extended instrumentation or spinal reconstruction. However, precise surgical treatment guidelines do not exist, likely due to the lack of robust, long-term clinical outcomes data and the overall heterogeneous nature of spinal tumors. Objectives of launching the Swiss Spinal Tumor Registry (Swiss-STR) are to collect and analyze high-quality, prospective, observational data on treatment patterns, clinical outcomes, and health-related quality of life (HRQoL) in adult patients undergoing spinal tumor surgery. This narrative review discusses our rationale and process of establishing this spinal cancer registry. Methods: A REDCap-based registry was created for the standardized collection of clinical, radiographic, surgical, histological, radio-oncologial and oncological variables, as well as patient-reported outcome measures (PROMs). Discussion: We propose that the Swiss-STR will inform on the effectiveness of current practices in spinal oncology and their impact on patient outcomes. Furthermore, the registry will enable better categorization of the various clinical presentations of spinal tumors, thereby facilitating treatment recommendations, defining the socio-economic burden on the healthcare system, and improving the quality of care. In cases of rare tumors, the multi-center data pooling will fill significant data gaps to yield better understanding of these entities. Finally, our two-step approach first implements a high-quality registry with efficient electronic data capture strategies across hospital sites in Switzerland, and second follows with potential to expand internationally, thus fostering future international scientific collaboration to further push the envelope in cancer research.
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BACKGROUND: In clinical trials, therapy with immune checkpoint inhibitors has improved the survival of patients with metastatic non-small-cell lung cancer (NSCLC). These trials were important for drug approval and for defining new treatment standards but the effect of checkpoint inhibitors in patients treated outside of clinical trials is not well known. The goal of this study was to assess the effect of immunotherapy on the overall survival of patients with metastatic NSCLC in the region of central Switzerland. MATERIALS AND METHODS: The study included 274 patients with histologically confirmed metastatic (stage IV) NSCLC in central Switzerland in the years 2015 to 2018. Patients with NSCLC and actionable driver mutations were excluded. Patients with checkpoint inhibitor treatment (immuno-oncology [IO] group, n = 122) were compared with patients without checkpoint inhibitor treatment (no-IO group, n = 152). Baseline demographics, disease characteristics and therapies applied were collected retrospectively. The primary endpoint was median overall survival calculated either from diagnosis or from the start of checkpoint inhibitor therapy to death or data cut-off (21 July 2021). We used the Kaplan-Meier method and an adjusted Cox proportional-hazards regression model. The expression of programmed-death ligand 1 (PD-L1) on tumour cells was used for exploratory analysis. RESULTS: Patients had a median age of 68.4 years, most were male (61.7%) and more than half were current or former smokers (65%). A test for PD-L1 expression was available for 55.8% of the tumours. Patients in the IO group were younger than patients in the no-IO group. Among the 122 patients in the IO group, the median overall survival was 15 months (95% confidence interval [CI] 12-20). In the no-IO group, the median overall survival was 4 months (95% CI 3-7) with chemotherapy and 2 months (95% CI 1-2) with best supportive care. Patients with high (≥50%) PD-L1 expression and checkpoint inhibitor therapy had a slightly longer overall survival than patients with low PD-L1 and checkpoint inhibitor therapy. CONCLUSION: These results suggest that treatment with checkpoint inhibitors improves overall survival in patients with metastatic NSCLC and that PD-L1 expression could have a predictive value in patients treated outside of clinical trials. Further studies are needed to study the magnitude of the benefit of checkpoint inhibitors according to molecular NSCLC subtype.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Anciano , Femenino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antígeno B7-H1 , Neoplasias Pulmonares/tratamiento farmacológico , Estudios Retrospectivos , Suiza , Inmunoterapia/métodosRESUMEN
Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kinase-AKT signaling at the early stages of HCC development.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Estudios Longitudinales , MicroARNs/genética , Fosfatidilinositol 3-Quinasa/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genéticaRESUMEN
We previously published in the Journal of Thoracic Oncology the case of a patient with EGFR and MET-driven lung cancer and extracranial response to capmatinib and osimertinib. Here, we report on a second patient treated with the same combination, revealing complete and durable intracranial response. Adding capmatinib to osimertinib seems to be an effective salvage therapy for patients with EGFR-mutant lung cancer and acquired MET amplification.
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NUTM1 gene rearrangements were originally identified in NUT carcinoma. Recently, NUTM1 has been discovered to rearrange with a variety of gene partners in malignancies of diverse location and type. Only one NUTM1-rearranged tumor occurring in the colon has been reported. Herein we report five such tumors. The five tumors occurred in four females and one male, ranging from 38 to 67 years of age (median 51 years). The masses occurred in the colon (cecum, descending, sigmoid) and ileocecal valve region, measuring 2.5-20 cm in size (median 7 cm). Four patients had metastases at presentation (liver, n = 4; lymph nodes, n = 3). Histologically, the lesions arose in the submucosa, infiltrating into the mucosa and muscularis propria, and grew in fibrosarcoma-like fascicles and sheets of epithelioid or rhabdoid cells, with foci of hyalinized to vaguely osteoid-like matrix. The tumors were composed of relatively monomorphic, spindled to epithelioid cells with focal rhabdoid morphology, hyperchromatic nuclei, and small nucleoli. Mitotic activity was usually low (range 1-14/10 HPF; median 5/10 HPF); necrosis was present in two cases. Variable keratin expression and uniform nuclear NUT expression was present; KIT/DOG1 were negative and SMARCB1/SMARCA4 were retained. Next-generation sequencing identified MXD4-NUTM1 rearrangement in all cases (breakpoints: MXD4 exon 5, NUTM1 exons 2 or 3). Follow-up showed one of the four patients who presented with metastases to be dead of disease at 30 months; the other three patients were alive with metastatic disease. The final patient is disease-free, 5 months after diagnosis. NUTM1-rearranged colorectal sarcomas have characteristic morphologic, immunohistochemical, and molecular genetic features, suggesting that they represent a distinct entity within the family of NUTM1-rearranged neoplasia. A NUTM1-rearranged tumor should be considered for any difficult-to-classify submucosal spindle cell neoplasm of the gastrointestinal tract, in particular keratin-positive tumors showing an unusual combination of fibrosarcomatous, epithelioid to rhabdoid and hyalinized morphologies. Recognition of MXD4-NUTM1 rearranged sarcomas may be therapeutically important, even though best treatment is currently elusive/unknown.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas Represoras/genética , Sarcoma/genética , Sarcoma/patología , Adulto , Anciano , Biomarcadores de Tumor/genética , Femenino , Reordenamiento Génico/genética , Humanos , Masculino , Persona de Mediana Edad , Fusión de Oncogenes/genética , Proteínas de Fusión Oncogénica/genética , PronósticoRESUMEN
Pulmonary lymphoid malignancies comprise various entities, 80% of them are pulmonary marginal zone B-cell lymphomas (PMZL). So far, little is known about point mutations in primary pulmonary lymphomas. We characterized the genetic landscape of primary pulmonary lymphomas using a customized high-throughput sequencing gene panel covering 146 genes. Our cohort consisted of 28 PMZL, 14 primary diffuse large B-cell lymphomas (DLBCL) of the lung, 7 lymphomatoid granulomatoses (LyG), 5 mature small B-cell lymphomas and 16 cases of reactive lymphoid lesions. Mutations were detected in 22/28 evaluable PMZL (median 2 mutation/case); 14/14 DLBCL (median 3 mutations/case) and 4/7 LyG (1 mutation/case). PMZL showed higher prevalence for mutations in chromatin modifier-encoding genes (44% of mutant genes), while mutations in genes related to the NF-κB pathway were less common (24% of observed mutations). There was little overlap between mutations in PMZL and DLBCL. MALT1 rearrangements were more prevalent in PMZL than BCL10 aberrations, and both were absent in DLBCL. LyG were devoid of gene mutations associated with immune escape. The mutational landscape of PMZL differs from that of extranodal MZL of other locations and also from splenic MZL. Their landscape resembles more that of nodal MZL, which also show a predominance of mutations of chromatin modifiers. The different mutational composition of pulmonary DLBCL compared to PMZL suggests that the former probably do not present transformations. DLBCL bear more mutations/case and immune escape gene mutations compared to LyG, suggesting that EBV infection in LyG may substitute for mutations.
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Neoplasias Pulmonares/genética , Linfoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Laparoscopic Sleeve Gastrectomy (LSG) is nowadays an established bariatric procedure. Although preoperative gastroscopy is recommended to rule out severe pathologies, there is little evidence about the role of routine histopathologic examination of resected specimens. We sought to identify the prevalence of histopathological relevant findings in patients undergoing LSG and to evaluate their impact in clinical practice. METHODS: A retrospective analysis on a prospectively collected dataset on patients undergoing LSG between August 2009 and May 2018 in two bariatric centers was performed. Demographic and clinical data and histopathological results were analyzed. RESULTS: Sixhundred-thrirteen patients were identified, mean age was 43.1 years (14-75), average body mass index was 44.8 kg/m2 (34.4-73.9). Histopathology revealed abnormal findings in 47.97% of the patients, most common pathology was chronic non-active or minimally to moderate active gastritis (n = 202;32.95%). Among others, Helicobacter-associated gastritis (n = 33;5.38%), intestinal metaplasia (n = 13;2.12%), micronodular enterochromaffine-like cell hyperplasia (n = 2; 0.33%) and gastrointestinal stromal tumors (n = 6; 0.98%) were present. No malignancies were found. Histopathological results required a change in the postoperative management in 48 patients (7.83%). The costs of histopathological assessment ranged between 0.77% and 2.55% of per-case payment. CONCLUSION: A wide range of histopathological findings occur in specimens after LSG, requiring a relevant number of patients additional therapies or surveillance. Therefore, routine histopathological examination after LSG is recommendable.
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Infecciones por Helicobacter , Laparoscopía , Obesidad Mórbida , Adulto , Gastrectomía , Humanos , Obesidad Mórbida/diagnóstico , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Femenino , Humanos , Incidencia , Sistema de Registros , SuizaAsunto(s)
Neoplasias Pulmonares , Acrilamidas , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Compuestos de Anilina , Benzamidas , Receptores ErbB/genética , Humanos , Imidazoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , TriazinasRESUMEN
With the approval of pembrolizumab for first- and second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC), PD-L1 testing by immunohistochemistry (IHC) has become a necessity. However, the DAKO autostainer ASL48 for the FDA approved DAKO 22C3 pharmDx assay is not broadly available in Switzerland and other parts of Europe. The primary goal of this study was to cross-validate the 22C3 anti-PD-L1 antibody on Benchmark Ultra (VBMU) and Leica Bond (LBO) immunostainers. IHC protocols were developed for 22C3 on both platforms with the 22C3phDx using ASL48 as reference. A tissue microarray (TMA) was constructed from 23 NSCLC specimens with a range of PD-L1 staining results. Empty TMA sections and the 22C3 antibody were distributed to 16 participants for staining on VBMU (8 centers) and/or LBO (12 centers) using the centrally developed protocols. Additionally the performance of the Ventana SP263 assay was tested in five centers. IHC scoring was performed centrally. Categorical PD-L1 staining (0-49% vs. 50-100%) did not significantly differ between centers using VBMU, whereas data from LBO were highly variable (p < 0.001). The SP263 assay was well concordant with 22C3 on VBMU and with 22C3 pharmDx. PD-L1 IHC using a standardized 22C3 protocol on VBMU provides satisfactory results in most centers. The SP263 assay is confirmed as a valid alternative to 22C3 pharmDx. 22C3 PD-L1 IHC on LBO shows major staining variability between centers, highlighting the need for local validation and adjustment of protocols.
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Anticuerpos/inmunología , Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/química , Inmunohistoquímica/métodos , Neoplasias Pulmonares/química , Automatización de Laboratorios , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Inmunohistoquímica/instrumentación , Inmunohistoquímica/normas , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Suiza , Análisis de Matrices TisularesRESUMEN
OBJECTIVE: This study was designed to investigate the presence of residual breast tissue (RBT) after skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) and to analyse patient- and therapy-related factors associated with RBT. Skin-sparing mastectomy and NSM are increasingly used surgical procedures. Prospective data on the completeness of breast tissue resection is lacking. However, such data are crucial for assessing oncologic safety of risk-reducing and curative mastectomies. METHODS: Between April 2016 and August 2017, 99 SSM and 61 NSM were performed according to the SKINI-trial protocol, under either curative (n = 109) or risk-reducing (n = 51) indication. After breast removal, biopsies from the skin envelope (10 biopsies per SSM, 14 biopsies per NSM) were taken in predefined radial localizations and assessed histologically for the presence of RBT and of residual disease. RESULTS: Residual breast tissue was detected in 82 (51.3%) mastectomies. The median RBT percentage per breast was 7.1%. Of all factors considered, only type of surgery (40.4% for SSM vs. 68.9% for NSM; P < 0.001) and surgeon (P < 0.001) were significantly associated with RBT. None of the remaining factors, e.g., skin flap necrosis, was associated significantly with RBT. Residual disease was detected in three biopsies. CONCLUSIONS: Residual breast tissue is commonly observed after SSM and NSM. In contrast, invasive or in situ carcinomas are rarely found in the skin envelope. Radicality of mastectomy in this trial is not associated with increased incidence of skin flap necrosis. ClinicalTrials.gov Identifier NCT03470909.
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Neoplasias de la Mama/cirugía , Mastectomía/métodos , Neoplasia Residual/patología , Pezones/cirugía , Tratamientos Conservadores del Órgano/métodos , Piel , Colgajos Quirúrgicos/patología , Adulto , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: The Swiss Federal Office of Public Health has recommended vaccination against human papillomavirus (HPV) to prevent cervical cancer since 2008. To establish monitoring of the future public health impact of vaccination, baseline population-based data are required. The objectives of this study were to examine the distribution of oncogenic HPV genotypes in biopsies with cervical intraepithelial neoplasia stage 3 or more severe lesions (CIN3+) at the beginning of HPV vaccination programmes and to compare sociodemographic and behavioural factors of women with CIN3+ with women in the Swiss general population. METHODS: We conducted a retrospective and prospective cross-sectional study with women diagnosed with CIN3+ in Switzerland. Ten pathology institutes from six cantons and three language regions participated. We conducted HPV typing on formaldehyde fixed-paraffin embedded specimens from 2014 and 2015. Women enrolled in 2015 were asked to complete a questionnaire. We described frequencies of HPV types. We also compared demographic characteristics and socioeconomic status in the CIN3 + plus group with the Swiss National Cohort in 2014 and compared risk factors for HPV infection with the Swiss Health Survey in 2012. RESULTS: We included 768 biopsies from 767 women. Four hundred and seventy-five (61.8%) biopsies were positive for HPV 16 and/or 18, 687 (89.5%) were positive for oncogenic HPV genotypes 16, 18, 31, 33, 45, 52, and/or 58 and five (0.7%) were HPV negative. Twenty-eight (10.3%) of the 273 women who completed the patient questionnaire reported having received at least one dose of an HPV vaccine. When compared with Swiss women in the six study cantons, fewer women in the CIN3+ plus study group were of Swiss nationality, more were born abroad and more were single. The study group also had a higher proportion of women with ≥2 partners in the last year, current smokers and was younger at age of first sexual intercourse. CONCLUSIONS: Introduction of the nonavalent vaccine could cover approximately 90% of CIN3+ lesions in Swiss women compared with around 60% with the quadrivalent vaccine. Surveillance of HPV genotype distribution in CIN3+, together with information about vaccination and CIN3+ incidence will allow monitoring of the public health impact of vaccination programmes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02323997 . Registered 24 December 2014.
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Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Vacunación/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Genotipo , Humanos , Incidencia , Persona de Mediana Edad , Estadificación de Neoplasias , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Vigilancia de la Población , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Suiza/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Adulto Joven , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patologíaRESUMEN
PURPOSE OF REVIEW: We describe recent developments in the rapidly evolving field of anaplastic lymphoma kinase-targeting agents. RECENT FINDINGS: Five targeted drugs are currently available in the clinic via regular approval or named patient programs, including crizotinib, ceritinib, alectinib, brigatinib and lorlatinib. Further drugs are tested in clinical trials. This review summarizes published data, together with drug-specific information on dosing and toxicity. Moreover, we discuss different clinical scenarios and potential treatment options in patients with tumor progression, based on current literature and our own experience. SUMMARY: Patients with metastatic, anaplastic lymphoma kinase-rearranged nonsmall cell lung cancer should be managed by interdisciplinary expert teams. New drugs with enhanced brain activity are available, and some patients may benefit from local therapies.