FGFR2/3 genomic alterations (GA) in cell-free (cf)DNA from patients (pts) with advanced urothelial carcinoma (aUC).

565 Background: Erdafitinib is approved in pts with aUC with relevant FGFR2/3 GA. BLC2001 trials in pts with activating FGFR2/3 mutations reported 40% ORR to erdafitinib (49% for those with single nucleotide variants [SNVs] and 16% with fusions), 39% stable disease rate, and potentially reduced response to anti-PD-L1. Genomic profiling with plasma cfDNA next-generation sequencing (NGS) is increasingly used to identify targetable GA in pts with advanced solid tumors and presents a minimally invasive option for identification of FGFR2/3 GA. Methods: Genomic data from the Guardant360 database were queried from clinical results released from 10/19/15 - 8/28/19 for clinical samples submitted with diagnoses of aUC or related diagnoses (e.g. bladder cancer, renal pelvis carcinoma). All assays included FGFR2/3 fusions and complete sequencing of all critical exons harboring sensitizing FGFR2/3 SNVs. Results: 1349 results from 1096 unique pts were identified. Somatic GA were identified in 1192 tests (88%) from 997 pts. Fusions and/or nonsynonymous SNVs in FGFR2/3 were identified in 201 pts (20%); 141 pts (14%) had at least one characterized activating FGFR2/3 GA. Of 34 pts (3.4%) with FGFR3 fusions, partners included TACC3 (32), JAKMIP1 (1), and TNIP2 (1). Overall, most SNVs identified in FGFR3 were predicted to be activating (103/125, 82%) whereas in FGFR2 most were variants of uncertain significance (VUS; 62/72, 86%). Of 89 unique variants (59 in FGFR2, 30 in FGFR3), 19 (21%) were activating mutations (7 in FGFR2, 12 in FGFR3). The most common activating SNVs in FGFR3 were S249C (58 pts), Y373C (20) and R248C (10), and in FGFR2 was N549K (4). VUS in both genes were individually uncommon (no VUS recurring in >3 pts). Median copy number-adjusted clonality of SNVs in FGFR3 was higher than those in FGFR2 (0.80 vs 0.20); this remained true when limiting to only characterized activating mutations (0.84 vs 0.17). Conclusions: cfDNA NGS analysis identifies fusions and a broad spectrum of SNVs in FGFR2/3, including heterogeneous subclonal mutations, at a rate similar to reported tissue testing. cfDNA is a minimally invasive option for pts with aUC to assess candidacy for erdafitinib and clinical trials.

Download Full-text

Comparison of diagnostic methodologies to detect chromosomal abnormalities.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14617 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14617-e14617

Author(s):

Cynthie Wong ◽

Maya Thangavelu ◽

Michele Hibbard ◽

Forrest Blocker ◽

Lawrence M. Weiss ◽

...

Keyword(s):

Chromosomal Abnormalities ◽

Copy Number Variations ◽

Clinical Samples ◽

Single Nucleotide Variants ◽

Hematologic Disease ◽

Structural Abnormalities ◽

Abnormal Cells ◽

Numerical Aberrations ◽

Next Generation Sequencing Ngs ◽

Gains And Losses

e14617 Background: Traditional technologies such as cytogenetics, FISH, and microarray (CGH) are utilized in most clinical laboratories. Next-Generation Sequencing (NGS) is a relatively new tool to evaluate the cancer genome. Applications of this method include assessing single nucleotide variants (SNVs), indel mutations, and copy number variations (CNVs), including some large chromosomal deletions or gains. Methods: We used a custom Discovery+LOH NGS panel (Agilent, Santa Clara) to determine the utility of NGS in detecting CNV and loss of heterozygosity (LOH) events. Thirty six patients with known DNA structural abnormalities and hematologic disease were tested using cytogenetics, the NGS panel, and CytoScan HD microarray. Results: As shown in the table, NGS detected all abnormalities reported by CGH. NGS failed to detect 14 abnormalities reported by cytogenetics, but detected additional gains and losses from small chromosomal regions as well as LOH events. Notably, NGS found a 16p loss, but cytogenetics detected a full chr16 loss and a 7q loss. NGS detected an 11p loss which was missed by cytogenetics. Table: Comparison of Detection by Methodologies. Conclusions: This study highlights the benefits and limitations of each method using clinical samples with hematologic disease. Cytogenetics provided a gross view of a karyotype, but lacked resolution to detect small aberrations and LOH events. NGS provided high resolution of numerical aberrations and detected LOH events, but was unable to detect some gain and loss events. In examining those missed events, < 30% abnormal cells were found in those specimens, possibly explaining the reduced sensitivity. Importantly, we found two significant discrepant chromosomal aberrations between cytogenetics and NGS. This may result from cytogenetic culture where preferential growth of cells influence the detection of a chromosome gain or loss. These findings suggest advantages in assessing chromosomal abnormalities using NGS in coordination with more traditional methods to improve diagnostic and prognostic determination to assist in treatment selection.[Table: see text]

Download Full-text

Clinical results of minimally invasive anterolateral THA using a short femoral stem

10.26226/morressier.579b42c4d462b80290b4cbc4 ◽

2016 ◽

Author(s):

Toshie Sasaki

Keyword(s):

Minimally Invasive ◽

Femoral Stem ◽

Clinical Results ◽

Short Femoral Stem

Download Full-text

Microendoscopy-assisted extraforaminal lumbar interbody fusion for treating single-level spondylodesis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02313-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Motohide Shibayama ◽

Guang Hua Li ◽

Li Guo Zhu ◽

Zenya Ito ◽

Fujio Ito

Keyword(s):

Minimally Invasive ◽

Spinal Canal ◽

Interbody Fusion ◽

Facet Joint ◽

Clinical Results ◽

Invasive Technique ◽

Clinical Effects ◽

Lumbar Interbody Fusion ◽

Disc Space ◽

Single Level

Abstract Background Lumbar interbody fusion is a standard technique for treating degenerative lumbar disorders involving instability. Due to its invasiveness, a minimally invasive technique, extraforaminal lumbar interbody fusion (ELIF), was introduced. On surgically approaching posterolaterally, the posterior muscles and spinal canal are barely invaded. Despite its theoretical advantage, ELIF is technically demanding and has not been popularised. Therefore, we developed a microendoscopy-assisted ELIF (mELIF) technique which was designed to be safe and less invasive. Here, we aimed to report on the surgical technique and clinical results. Methods Using a posterolateral approach similar to that of lateral disc herniation surgery, a tubular retractor, 16 or 18 mm in diameter, was placed at the lateral aspect of the facet joint. The facet joint was partially excised, and the disc space was cleaned. A cage and local bone graft were inserted into the disc space. All disc-related procedures were performed under microendoscopy. The spinal canal was not invaded. Bilateral percutaneous screw-rod constructs were inserted and fixed. Results Fifty-five patients underwent the procedure. The Oswestry Disability Index and visual analogue scale scores greatly improved. Over 90% of the patients obtained excellent or good results based on Macnab’s criteria. There were neither major adverse clinical effects nor the need for additional surgery. Conclusions mELIF is minimally invasive because the spinal canal and posterior muscles are barely invaded. It produces good clinical results with fewer complications. This technique can be applied in most single-level spondylodesis cases, including those involving L5/S1 disorders.

Download Full-text

Genotype-Phenotype Correlations in Neurofibromatosis Type 1: A Single-Center Cohort Study

Cancers ◽

10.3390/cancers13081879 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1879

Author(s):

Marcello Scala ◽

Irene Schiavetti ◽

Francesca Madia ◽

Cristina Chelleri ◽

Gianluca Piccolo ◽

...

Keyword(s):

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Copy Number Variations ◽

Single Nucleotide Variants ◽

Multivariate Statistical ◽

Gene Deletions ◽

Pathogenic Variants ◽

Lisch Nodules ◽

Next Generation Sequencing Ngs

Neurofibromatosis type 1 (NF1) is a proteiform genetic condition caused by pathogenic variants in NF1 and characterized by a heterogeneous phenotypic presentation. Relevant genotype–phenotype correlations have recently emerged, but only few pertinent studies are available. We retrospectively reviewed clinical, instrumental, and genetic data from a cohort of 583 individuals meeting at least 1 diagnostic National Institutes of Health (NIH) criterion for NF1. Of these, 365 subjects fulfilled ≥2 NIH criteria, including 235 pediatric patients. Genetic testing was performed through cDNA-based sequencing, Next Generation Sequencing (NGS), and Multiplex Ligation-dependent Probe Amplification (MLPA). Uni- and multivariate statistical analysis was used to investigate genotype–phenotype correlations. Among patients fulfilling ≥ 2 NIH criteria, causative single nucleotide variants (SNVs) and copy number variations (CNVs) were detected in 267/365 (73.2%) and 20/365 (5.5%) cases. Missense variants negatively correlated with neurofibromas (p = 0.005). Skeletal abnormalities were associated with whole gene deletions (p = 0.05) and frameshift variants (p = 0.006). The c.3721C>T; p.(R1241*) variant positively correlated with structural brain alterations (p = 0.031), whereas Lisch nodules (p = 0.05) and endocrinological disorders (p = 0.043) were associated with the c.6855C>A; p.(Y2285*) variant. We identified novel NF1 genotype–phenotype correlations and provided an overview of known associations, supporting their potential relevance in the implementation of patient management.

Download Full-text

Mid-term clinical results of minimally invasive decompression and posterolateral fusion with percutaneous pedicle screws versus conventional approach for degenerative spondylolisthesis with spinal stenosis

European Spine Journal ◽

10.1007/s00586-011-2114-x ◽

2011 ◽

Vol 21 (6) ◽

pp. 1171-1177 ◽

Cited By ~ 42

Author(s):

Yoshihisa Kotani ◽

Kuniyoshi Abumi ◽

Manabu Ito ◽

Hideki Sudo ◽

Yuichiro Abe ◽

...

Keyword(s):

Minimally Invasive ◽

Spinal Stenosis ◽

Degenerative Spondylolisthesis ◽

Pedicle Screws ◽

Clinical Results ◽

Conventional Approach ◽

Posterolateral Fusion ◽

Minimally Invasive Decompression

Download Full-text

Comparison of Short-Term Clinical Results and Radiologic Changes Between Two Different Minimally Invasive Decompressive Surgical Methods for Lumbar Canal Stenosis

Spine ◽

10.1097/brs.0000000000004052 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Sunao Tanaka ◽

Kanichiro Wada ◽

Gentaro Kumagai ◽

Toru Asari ◽

Shuichi Aburakawa ◽

...

Keyword(s):

Minimally Invasive ◽

Clinical Results ◽

Short Term ◽

Lumbar Canal Stenosis ◽

Canal Stenosis ◽

Surgical Methods

Download Full-text

Minimally Invasive Anterolateral Surgical Approach for Total Hip Arthroplasty: Early Clinical Results

Hip International ◽

10.1177/112070000601604s09 ◽

2006 ◽

Vol 16 (4_suppl) ◽

pp. 42-47 ◽

Cited By ~ 5

Author(s):

H. Röttinger

Keyword(s):

Total Hip Arthroplasty ◽

Minimally Invasive ◽

Hip Arthroplasty ◽

Surgical Approach ◽

Clinical Results ◽

Total Hip

Download Full-text

Tiled-ClickSeq for targeted sequencing of complete coronavirus genomes with simultaneous capture of RNA recombination and minority variants

eLife ◽

10.7554/elife.68479 ◽

2021 ◽

Vol 10 ◽

Author(s):

Elizabeth Jaworski ◽

Rose M Langsjoen ◽

Brooke Mitchell ◽

Barbara Judy ◽

Patrick Newman ◽

...

Keyword(s):

Full Range ◽

Virus Genome ◽

Clinical Samples ◽

Rna Recombination ◽

Single Nucleotide ◽

Reverse Transcription Reaction ◽

Minority Variants ◽

Next Generation Sequencing Ngs ◽

Unique Molecular Identifier ◽

Generation Sequencing

High-throughput genomics of SARS-CoV-2 is essential to characterize virus evolution and to identify adaptations that affect pathogenicity or transmission. While single-nucleotide variations (SNVs) are commonly considered as driving virus adaption, RNA recombination events that delete or insert nucleic acid sequences are also critical. Whole genome targeting sequencing of SARS-CoV-2 is typically achieved using pairs of primers to generate cDNA amplicons suitable for next-generation sequencing (NGS). However, paired-primer approaches impose constraints on where primers can be designed, how many amplicons are synthesized and requires multiple PCR reactions with non-overlapping primer pools. This imparts sensitivity to underlying SNVs and fails to resolve RNA recombination junctions that are not flanked by primer pairs. To address these limitations, we have designed an approach called ‘Tiled-ClickSeq’, which uses hundreds of tiled-primers spaced evenly along the virus genome in a single reverse-transcription reaction. The other end of the cDNA amplicon is generated by azido-nucleotides that stochastically terminate cDNA synthesis, removing the need for a paired-primer. A sequencing adaptor containing a Unique Molecular Identifier (UMI) is appended to the cDNA fragment using click-chemistry and a PCR reaction generates a final NGS library. Tiled-ClickSeq provides complete genome coverage, including the 5’UTR, at high depth and specificity to the virus on both Illumina and Nanopore NGS platforms. Here, we analyze multiple SARS-CoV-2 isolates and clinical samples to simultaneously characterize minority variants, sub-genomic mRNAs (sgmRNAs), structural variants (SVs) and D-RNAs. Tiled-ClickSeq therefore provides a convenient and robust platform for SARS-CoV-2 genomics that captures the full range of RNA species in a single, simple assay.

Download Full-text

Results of a novel surgical technique for iridodialysis repair using segments

10.21203/rs.3.rs-339853/v1 ◽

2021 ◽

Author(s):

Ugur Unsal ◽

Huri Sabur ◽

Mehmet Soyler

Keyword(s):

Surgical Technique ◽

Minimally Invasive ◽

Clinical Results ◽

Study Data ◽

Invasive Technique ◽

Minimally Invasive Surgical ◽

Corrected Distance Visual Acuity ◽

History Of ◽

Surgical Manipulation

Abstract Purpose: To describe a novel surgical technique for iridodialysis repair using iris retractor segments and report its clinical results.Methods: 53 eyes of 53 patients who underwent surgery for iridodialysis repair were enrolled in this retrospective study. Data recorded from patient files consisted of age, sex, history of trauma, surgical indications and type of surgery, preoperative and postoperative corrected distance visual acuity (CDVA), intraocular pressure (IOP), complications, and follow-up time. The novel, minimally invasive surgical technique was explicitly described in detail.Results: Mean follow-up time was 34.4 (range 12-84) months. The subjects were 29 (54.7%) men and 26 (45.3%) women, and the mean age was 56.6±14.0 years. Iridodialysis repair performed using one segment in 37 (69.8%) eyes, two segments in 15 (28.3%) eyes, and three segments in 1 (1.9%) eye. Pupilloplasty was performed in 17 eyes due to wide pupil diameter. The iridodialysis repair was combined with lens removal in 48 eyes, and anterior vitrectomy was performed in 10 eyes. CDVA significantly improved after surgery (p<0.001). Post-traumatic IOP rise was the most common complication, and six patients needed medical therapy for glaucoma control.Conclusion: Iridodialysis repair using iris retractor segment is a minimally invasive technique and found to be safe and effective, providing less surgical manipulation and surgical time than other techniques.

Download Full-text