We evaluated the value of UHRF1, a regulator of methylation, as a biomarker for lung cancer. UHRF1 is expressed at higher levels in both lung adenocarcinoma (AD) and squamous cell carcinoma (SQ); ...however, a meta-analysis showed that UHRF1 expression is correlated with worse survival in patients with AD but not in those with SQ. UHRF1 knockdown suppressed the growth of lung cancer cell lines through G1 cell cycle arrest in some cell lines. These results suggest that UHRF1 may server as a diagnostic marker for AD and SQ and as a prognostic marker for AD in lung cancer.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This study aimed to examine the feasibility and potential benefits of an optical see-through head-mounted display (OST-HMD) during real-time ultrasound-guided thoracentesis simulations.
Six ...physicians performed a thoracentesis simulation using an OST-HMD and a wireless image transmission system. The time required, puncture needle visibility, pleural fluid collection success rate, and head movement during the procedure using a smart glass equipped with an inertial measurement unit were all recorded and compared with and without the HMD.
Study participants successfully extracted effusions in all procedures. The use of OST-HMD did not significantly affect the time of the procedure, but notably decreased the horizontal and vertical head movements during the procedure.
The study demonstrated the feasibility of using an OST-HMD in a simulated real-time ultrasound-guided thoracentesis procedure and showed the potential of HMD in thoracentesis to improve ergonomics and accuracy. Further research is necessary to confirm these findings.
Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), ...cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518–1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.
Pulmonary infection is a relatively rare but serious complication of flexible bronchoscopy. The aim of this study was to identify the risk factors for pulmonary infectious complications after ...diagnostic bronchoscopy in patients with lung cancer. We retrospectively analyzed the medical records of 636 patients who underwent bronchoscopic biopsy for lung cancer diagnosis between April 2011 and March 2016. We compared patients' characteristics, chest computed tomography and bronchoscopic findings, undertaken procedures, and final diagnoses between patients who developed the complication and those who did not. Pulmonary infection after the diagnostic bronchoscopy occurred in 19 patients (3.0%) and included pneumonia in 16 patients and lung abscess in 3. Patients with larger lesions, presence of endobronchial lesions, histology of small cell lung cancer, and advanced disease stage tended to develop pulmonary infectious complications more often. Our multivariate analysis revealed that a larger lesion size and the presence of endobronchial lesions were independently associated with post-bronchoscopy pulmonary infection. Although we found no mortality associated with the infections, two patients were left with significant performance status deterioration after the pulmonary infection and received no anticancer treatment. In conclusion, endobronchial lesions and a larger lesion size are independent risk factors for the incidence of infections following bronchoscopic biopsy in patients with lung cancer.
Abstract. The programmed cell death 1 (PD-1) / programmed cell death 1 ligand 1 (PD-L1) axis is vital for immune resistance during tumor development, while PD-L1 inhibitors can also inhibit the ...PD-L1/B7-1 (CD80) interaction, indicating one of the molecular differences between PD-1 and PD-L1 inhibitors. However, the clinical benefits of PD-L1 inhibitors in patients previously treated with PD-1 inhibitors remain unknown. In this study, we retrospectively analyzed the clinical data of eight patients with non-small cell lung cancer who received the PD-L1 inhibitor atezolizumab and previously treated with the PD-1 inhibitor nivolumab. The median progression-free survival was 2.1 months (1.8-18.7 months), and 4 of 8 patients achieved at least stable disease. In two of these patients, atezolizumab treatment resulted in longer progression-free survival (PFS) compared with that of nivolumab. Conversely, one patient exhibited grade 4 diabetic ketoacidosis (DKA) within 2 weeks after the initial administration of atezolizumab. Another patient had developed type 1 diabetes mellitus (T1DM) during the prior nivolumab treatment and then developed DKA due to an infection after the initiation of atezolizumab. Both of them had high-risk human leukocyte antigen-DR/DQ types relevant to T1DM. These results demonstrate the potential efficacy of PD-L1 inhibitors to some tumors that have acquired resistance to PD-1 inhibitors and suggest that appropriate managements are required for not only a newly onset of T1DM but also blood glucose control after the development of T1DM during a reiteration of the PD-1/PD-L1 blockade.
Purpose
This study aimed to evaluate the clinicopathological significance of cancer stem-like cell (CSLC) markers in high-grade neuroendocrine carcinoma (HGNEC) of the lung, including small cell lung ...carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC).
Methods
We retrospectively studied patients who underwent surgical resection of SCLC (
n
= 60) and LCNEC (
n
= 45) to analyze their clinicopathological profiles and the immunohistochemical expression of putative CSLC markers (Caveolin, Notch, CD44, CD166, SOX2, ALDH1, and Musashi1). Staining scores for these markers in tumor cells were calculated by multiplying the percentage of positive tumor cells per lesion by the staining intensity level (0, 1, and 2); a score of ≥10 represented positive expression.
Results
There was a difference between SCLC and LCNEC with respect to both SOX2 (55 vs. 27 %,
p
= 0.003) and CD166 (27 vs. 47 %,
p
= 0.034) expression. ALDH1 expression was equally observed in SCLC and LCNEC (67 vs. 73 %,
p
= 0.46), and patients with ALDH1-positive HGNEC had significantly worse recurrence-free survival (RFS) and overall survival (OS) rates than those with ALDH1-negative HGNEC (5-year RFS: 39 vs. 67 %,
p
= 0.009; 5-year OS: 50 vs. 79 %,
p
= 0.021). A multivariate analysis revealed that positive ALDH1 expression was an independent unfavorable prognostic factor with respect to both RFS and OS.
Conclusions
The differences in the expression profiles of CSLC markers might reflect morphological differences between SCLC and LCNEC. Positive ALDH1 expression in lung HGNEC was associated with an unfavorable patient prognosis, which suggested that ALDH1-positive tumor cells might be future therapeutic targets for the treatment of lung HGNEC.
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EMUNI, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Background. Endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) was shown to be unsatisfactory for the diagnosis of pulmonary actinomycosis. The definitive diagnosis ...of pulmonary actinomycosis using EBUS-GS often necessitates penetration of the lesion to obtain samples. Case. A 52-year-old woman was referred to our hospital for the evaluation of an increase in nodules observed on chest computed tomography over 2 years prior to presentation. Results. A histopathological evaluation of specimens retrieved using EBUS-GS TBB revealed nonspecific findings, such as inflammatory cells. However, specimens retrieved via transbronchial needle aspiration through a guide sheath (GS-TBNA) using the PeriView FLEX device in addition to those obtained via EBUS-GS TBB showed necrotic tissue. Culture of tissue obtained using EBUS-GS TBB yielded Actinomyces odontolyticus. Based on these results, we diagnosed the lesion as pulmonary actinomycosis, and the patient was administered antibiotics, which led to the improvement of the lesion. Conclusion. GS-TBNA performed in addition to EBUS-GS TBB facilitated direct penetration of the lesion to obtain samples for an accurate diagnosis of pulmonary actinomycosis.
MET-deregulated non-small cell lung cancer represents an urgent clinical need because of the lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in ...patients harboring MET gene alterations, no conclusive data are currently available. Therefore, we designed the Co-MET study, a single-arm phase II study to assess the efficacy and safety of crizotinib in patients with advanced non-small cell lung cancers harboring MET gene alterations.
Co-MET is an open-label, multi-center, single-arm, phase II trial to assess the safety and efficacy of oral crizotinib in patients with advanced non-small cell lung cancer harboring MET exon 14 skipping mutation (cohort 1) or a high MET gene copy number of ≥ 7 (cohort 2). We will identify MET gene alterations using RT-PCR and/or next-generation sequencing. Oral crizotinib 250 mg BID will be administered until disease progression or unacceptable toxicity. A radiology committee will review tumor scans according to the RECIST criteria. The primary endpoint is the objective response rate. Assuming a null hypothesis of 20% objective response rate and an alternative hypothesis of 50% objective response rate for cohort 1, and a one-sided alpha error of 0.05 and 80% power based on the exact binomial distribution, the required number of evaluable patients is 19. We set the exploratory sample size for cohort 2 at 10 patients.
The results of this study are expected to provide evidence regarding the usefulness of oral crizotinib for advanced MET exon 14 skipping mutation-positive or MET high gene copy number-positive non-small cell lung cancer.
This study was registered with the University Hospital Medical Information Network Clinical Trials Registry as UMIN000031623 on 3 March 2018.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate. Most advanced NSCLC ...patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood. The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.
A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution. Finally, 85 evaluable patients were included in this study. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).
Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD. The COPD group were older and had fewer never-smokers than the non-COPD group. The objective response rate did not differ between groups (
=0.14). There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test
=0.57). In the multivariate Cox's proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496-19.359;
=0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223-0.948;
=0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158-31.497;
=0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330-1.325;
=0.24). Toxicity profile in COPD group was favorable, as in the non-COPD group.
Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients.
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