Determining the exact type of epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation in lung cancer has become important. We found that not all ex20ins mutations reported by ...cobas EGFR test v2 could be validated by Sanger sequencing even using surgical specimens with high tumor contents. This study aimed to validate the ex20ins results reported by the cobas test and to determine whether there were clinicopathological factors associated with aberrant cobas ex20ins report. In total, 123 cobas-reported cases with ex20ins were retrospectively collected and validated by Sanger sequencing and Idylla assay. Clinicopathological features between ex20ins cobas+/Sanger+ group (n = 71) and cobas+/Sanger- group (n = 52) were compared. The Idylla assay detected ex20ins in 82.6% of cobas+/Sanger+ cases but only in 4.9% of cobas+/Sanger- cases. The cobas+/Sanger- group was significantly associated with higher tumor contents, poorly differentiated patterns, tumor necrosis, and a lower internal control cycle threshold value reported by the Idylla which suggesting the presence of increased EGFR gene copy numbers. EGFR fluorescence in situ hybridization (FISH) revealed the majority of cobas+/Sanger- group had EGFR high copy number gain (16%) or amplification (76%) according to the Colorado criteria. Among cases reported to have concomitant classic EGFR and ex20ins mutations by the cobas, the classic EGFR mutations were all detected by Sanger sequencing and Idylla, while the ex20ins mutations were undetected by Sanger sequencing (0%) or rarely reported by Idylla assay (3%). FISH revealed high EGFR copy number gain (17.9%) and amplification (79.5%) in cases reported having concomitant classic EGFR and ex20ins mutations by the cobas. This study demonstrated an unusually high frequency of EGFR amplification in cases with aberrant cobas ex20ins report which could not be validated by Sanger sequencing or Idylla assay. Ex20ins reported by the cobas test should be validated using other methods especially those reported having concomitant ex20ins and classic EGFR mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Hirschsprung's disease (HSCR) is a congenital disorder with the absence of myenteric and submucosal ganglion cells within distal gut. Due to multigenic inheritance and interactions, we ...employed next‐generation sequencing (NGS) to investigate genetic backgrounds of long‐segment HSCR (L‐HSCR) in Taiwan.
Methods
Genomic DNA extracted from peripheral blood of L‐HSCR patients was subjected to capture‐based NGS, based on a 31‐gene panel. The variants with allele frequency <0.05 and predicted by computational methods as deleterious were further validated by Sanger sequencing in patients and their family as well to tell de novo from inherited variants.
Results
Between 2015/04 and 2018/05, this study enrolled 23 L‐HSCR patients, including 15 (65.2%) sporadic cases and 8 (34.8%) familial patients in 4 different families. Six sporadic and seven familial cases showed possible harmful variants across eight different genes, accounting for an overall detection rate of 56.5%. These variants mainly resided in SEMA3C, followed by RET, NRG1, and NTRK1. Three sporadic and 2 familial cases exhibited strong pathogenic variants as a deletional frameshift or stop codon in RET, L1CAM or NRG1. In a HSCR family, the father passed on a pathogenic RET frameshift to two daughters; however, only one developed HSCR.
Conclusion
Using NGS, we disclosed deleterious mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L‐HSCR or even total colonic aganglionosis appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.
Using NGS in this study, we disclosed some definite harmful mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L‐HSCR or even TCA appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.
Introduction
Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on ...the clinical characteristics and outcomes of GTS in children with MGCTs are limited.
Methods
We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS.
Results
The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety‐five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event‐free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5‐year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001).
Conclusion
For patients with high‐risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.
Background
The transforming growth factor‐β (TGF‐β) pathway plays a pivotal role in inducing epithelial‐mesenchymal transition (EMT), which is a key step in cancer invasion and metastasis. However, ...the regulatory mechanism of TGF‐β in inducing EMT in colorectal cancer (CRC) has not been fully elucidated. In previous studies, it was found that S100A8 may regulate EMT. This study aimed to clarify the role of S100A8 in TGF‐β‐induced EMT and explore the underlying mechanism in CRC.
Methods
S100A8 and upstream transcription factor 2 (USF2) expression was detected by immunohistochemistry in 412 CRC tissues. Kaplan‐Meier survival analysis was performed. In vitro, Western blot, and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF‐β‐induced EMT. Mouse metastasis models were used to determine in vivo metastasis ability. Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription.
Results
During TGF‐β‐induced EMT in CRC cells, S100A8 and the transcription factor USF2 were upregulated. S100A8 promoted cell migration and invasion and EMT. USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region. Furthermore, TGF‐β enhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells. S100A8 expression in tumor cells was associated with poor overall survival in CRC. USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8‐positive stromal cells.
Conclusions
TGF‐β was found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis. USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.
In colorectal cancer, S100A8 in tumor cells predicts poor prognosis but that in stroma cells indicates good prognosis. We first proved that TGF‐β promotes metastasis through upregulated intracellular USF2/S100A8 axis, and USF2 maybe is the switcher on the opposite function of intracellular and extracellular S100A8.
In this work, a solution combustion followed by dissolution in hydrogen peroxide is adopted to achieve a precursor for decorating anatase TiO2 nanosheets along single-crystalline rutile TiO2 ...nanorods, which achieves balsam-pear-like core/shell nanorod arrays with enhanced photoelectrochemical water splitting. The enhanced photoelectrochemical performance is attributed to the novel nanoarchitecture, which can simultaneously offer a high surface area, enhanced light-harvesting, a rutile/anatase junction for charge carrier separation and a conductive pathway for charge carrier collection. The photoanode design can also give hints to other functional materials.
Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). The incidence in children and adolescents has risen since the 21st century globally, including Taiwan. The ...study aimed to disclose the characteristics and outcome of pediatric IBD (pIBD) patients in a tertiary center for the past two decades.
We retrospectively reviewed the charts of pIBD children from 2000 to 2018 in a tertiary center in Northern Taiwan. Demographics, presentations, diagnostic modalities, treatment, and outcomes were analyzed.
A total of 38 cases were enrolled, including 27 CD and 11 UC patients. An almost 3-folds increase in incidence after 2010 was observed. Twelve cases (32%) were early-onset, and six of them (16%) were very-early-onset; four of them were detected with single-gene mutations XIAP, TTC7A (2 siblings), and ZAP70. Eleven CD patients (40.7%) received bowel resection at the onset, and another two (7.4%) had bowel resection years after the diagnosis. Initial bowel resection was associated with fibrostenotic/penetrating behavior, early-onset disease, and growth failure.
This study demonstrated an increased incidence of pIBD in the past two decades in Taiwan, a low-prevalence region. The initial high bowel resection rate in CD was related to the fibrostenotic and/or penetrating behavior, younger age at diagnosis, and growth failure.
Identifying ischemic ovary as a complication of ovary torsion (OT) is a significant challenge in children. This study identified risk factors for ischemic OT among pediatric OT patients to prevent ...delayed treatment. This retrospective study included pediatric inpatients who underwent operation for OT over 20 years. We employed multivariable logistic regression to find the risk factors associated with ischemic OT. Among the 118 patients included in this study, 78 (66.1%) had ischemic OT. Patients with ischemic OT tended to be younger; had more frequent vomiting; and had elevated White blood cell (WBC), C-Reactive protein (CRP), and segments in comparison with non-ischemic OT patients. Multivariable regression showed increased odds of ischemic ovary torsion, associated with higher WBC (12.3 × 10
/mm
vs. 8.7 × 10
/mm
,
< 0.001), CRP (50.4 mg/L vs. 8.4 mg/L,
< 0.001), and vomiting (55.1% vs. 25%,
= 0.002) than in non-ischemic patients. A receiver-operating characteristic (ROC) analysis indicated that patients with vomiting, leukocytosis, or CRP ≧ 40 mg/L were more likely to have ischemic OT (sensitivity, 92%; specificity, 54%; PPV, 79.6; NPV, 78.9%). Ischemic OT is common among pediatric OT patients. The presence of potential risk factors of vomiting, leukocytosis, and CRP more significant than 40 mg/L may assist clinicians in ensuring an expedited surgical treatment.
Abstract Background There are no well-established indications for the surgical management of acute necrotizing pneumonitis in children. This study presents our experience regarding this challenging ...topic. Methods Between 2002 and 2009, 56 necrotizing pneumonitis patients with empyema were treated surgically. The outcomes were analyzed retrospectively. Computed tomography findings of massive lung necrosis or large cavities involving more than 50% of the involved lobe were deemed to be complicated necrotizing pneumonitis. Patients without the above indications were considered uncomplicated. Results Thirty-one cases were uncomplicated and 25 were complicated. Operative procedures included 38 decortications (31 uncomplicated and 7 complicated), 14 wedge resections and 4 lobectomies (complicated only). Preoperatively, complicated patients had higher incidence of pneumothorax (32% vs.14.3%; p = 0.001), endotracheal intubation (44% vs.9.7%; p = 0.008) and hemolytic uremic syndrome (20% vs.3.2%; p = 0.01). Complicated patients also had higher incidences of intraoperative transfusion (68% vs.9.7%; p = 0.03), major post-operative complications (16% vs.0; p = 0.02), re-operations (16% vs.0; p = 0.02) and longer post-operative stay (19.8 ± 24.2 vs.11.2 ± 5.8 days; p = 0.03). Four complicated patients, who initially had decortications and limited-resections, underwent reoperations. Compared with uncomplicated patients, those who underwent decortications and wedge resection required longer postoperative stays (23.6 ± 9.9 days, p < 0.01and 21.1 ± 30.7 days, p = 0.04), while the lobectomy patients had similar duration of recovery (9.0 ± 2.1days, p = 0.23). All patients improved significantly at follow up. Conclusions Children with complicated necrotizing pneumonitis have more pre-operative morbidities, more major post-operative complications, and require longer post-operative stays. Aggressive surgical treatment results in significant clinical improvement. Lobectomy in patients with complicated necrotizing pneumonitis may shorten the post-operative course and avoid subsequent surgery.
Background Our objective was to analyze demographics and characteristics of Meckel's diverticulum with different manifestations in pediatric patients. Methods This is a retrospective study in ...children with symptomatic Meckel's diverticulum who underwent resection between September 1998 and October 2010. The diagnosis was confirmed by surgery and pathology. Demographic characteristics, manifestations, Meckel's scan results, surgical and histological findings were analyzed. Results One hundred symptomatic Meckel's diverticula were identified in 74 boys and 26 girls aged from one day to 18 years old over 13 years. Depending on whether or not obstruction occurred, the patients were classified into two categories. Each category was further subdivided into two diagnostic groups: 17 intussusception and 24 non-intussusception bowel obstruction in the obstructive category and 44 gastrointestinal bleeding and 15 diverticulitis and/or perforation in the non-obstructive category. The sex discrepancy was higher in the non-obstructive category than in the obstructive category (male-to-female, 4.36 vs. 1.73, p < 0.05). Forty-one of 44 patients with gastrointestinal bleeding underwent a Meckel's scan with a high positive rate (92.7%). The ectopic tissues were identified in 73 patients and included 61 gastric type, two pancreatic type and 10 mixed type. Ectopic tissues were more prevalent in non-obstructive category ( p < 0.05) with ectopic gastric tissue even more pronounced ( p < 0.01). Ectopic pancreatic tissue was significantly more prevalent in intussusception ( p < 0.01). Laparoscopic surgery was performed more frequently in Meckel's diverticulum with non-obstructive symptoms ( p < 0.001). Conclusion Diverse presentations in pediatric Meckel's diverticulum are affected by different ectopic tissue types and male sex. Laparoscopic surgery is widely used for children with non-obstructive symptoms.
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