Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment (P < 0.01). We used the 10 most differentially‐methylated genes between responders and non–responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes (ROBO1, ULK4P3, MYOD1, LBX1, CACNA1A, IRX4, DPYSL3 and ELAVL2) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression‐free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.     

Fork injuries with the tines inserted bilaterally between the mandibular interdental spaces

In this paper, we report two rare cases of foreign body oral injuries caused by forks inserted tightly into both sides of the lingual interdental spaces between the mandibular deciduous canines and first deciduous molars (FDMs). These pediatric cases of foreign body insertion caused not only soft tissue injuries but also the potential luxation of affected deciduous teeth, i.e., the FDMs in the present cases, during the removal of the object by force.     

Venous Sac and Feeding Artery Embolization versus Feeding Artery Embolization Alone for Treating Pulmonary Arteriovenous Malformations: Draining Vein Size Outcomes

PurposeTo investigate and compare venous sac and feeding artery embolization (VFE) with feeding artery embolization (FAE) alone for treatment of pulmonary arteriovenous malformations (PAVMs), based on difference in outcomes in decrease of the size of the draining vein.Materials and MethodsTwenty-six patients (7 male and 19 female; median age [interquartile range], 58 years [46–65 years]) with 42 simple PAVMs treated with coil embolization between August 2005 and December 2018 were retrospectively evaluated. Twenty PAVMs were treated with FAE early in the study period and compared with 22 PAVMs treated with VFE later in the study period. Follow-up computed tomography images obtained 8–20 months after embolotherapy were used for outcome analysis. Data related to patient demographics; follow-up period; baseline diameters of the feeding artery, venous sac, and draining vein; draining vein diameter after treatment; and decrease in the size of the draining vein, including the number reaching a threshold of 70% decrease, were compared between the 2 groups.ResultsThe draining vein decreased in size by a median of 46.4% in the FAE group and 66.3% in the VFE group, and the difference between the 2 groups was statistically significant (P = .009). There were no significant differences in the other parameters.ConclusionsVFE leads to a greater decrease in the size of the draining vein than FAE, suggesting that VFE results in more complete occlusion than FAE for treatment of PAVMs.     

Feasibility and utility of transbronchial cryobiopsy in precision medicine for lung cancer: Prospective single‐arm study

Cryoprobe is a novel transbronchial biopsy (TBB) tool that yields larger tissue samples than forceps. Pathological diagnosis and biomarker analysis, such as genetic alterations and programmed death‐ligand 1 (PD‐L1) expression, are paramount for precision medicine against lung cancer. We evaluated the safety and usefulness of cryoprobe TBB for lung cancer diagnosis and biomarker analysis. In this single‐center, prospective single‐arm study, patients suspected of having or diagnosed with primary lung cancer underwent cryoprobe TBB using flexible bronchoscopy after conventional forceps TBB from the same lesion. Cryoprobe TBB was performed in 121 patients. The incidence rate of severe bleeding and serious adverse events (4% [90% confidence interval: 2%‐9%]) was significantly lower than the expected rate (20% with 30% threshold, P < 0.01). Combining both central and peripheral lesions, the diagnostic yield rate of cryoprobe samples was 76% and that of forceps samples was 84%. Compared with forceps TBB samples, cryoprobe TBB samples were larger (cryoprobe 15 mm² vs forceps 2 mm²) and resulted in a larger proportion of definite histomorphological diagnosis (cryoprobe 86% vs forceps 74%, P < 0.01), larger amounts of DNA extracted from samples (median: cryoprobe, 1.60 µg vs forceps, 0.58 µg, P = 0.02) and RNA (median: cryoprobe, 0.62 µg vs forceps, 0.17 µg, P < 0.01) extracted from samples, and tended to yield greater rates of PD‐L1 expression >1% (51% vs 42%). In conclusion, cryoprobe is a safe and useful tool for obtaining lung cancer tissue samples of adequate size and quality, which allow morphological diagnosis and biomarker analysis for precision medicine against lung cancer.     

Immune checkpoint inhibitor-induced diarrhea: Clinicopathological study of 11 patients

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICI-induced diarrhea aged 46–81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICI-induced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.