Thyroid metastasis of pulmonary adenocarcinoma with EGFR G719A mutation: Genetic confirmation with liquid-based cytology specimens

Presented is a case of advanced pulmonary adenocarcinoma and a thyroid tumour with calcification. EGFR gene mutation testing of the thyroid aspirate specimen revealed a G719A point mutation in exon 18 that was identical to that in the patient's known lung cancer. This case demonstrates the usefulness of liquid-based cytology samples, which enable genetic testing leading to a conclusive diagnosis while preserving the cytological specimens

MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression

There have been few advances in the treatment of small-cell lung cancer (SCLC) because of the lack of targets. MCL1, a member of the anti-apoptotic BCL-2 family, may be a treatment target in several cancers, including SCLC. However, whether the expression profile of the anti-apoptotic BCL-2 family affects MCL1 inhibition strategy is unknown. A tissue microarray (TMA) was created from consecutive patients who were diagnosed with SCLC and had previously undergone surgery at Kyoto University Hospital (Kyoto, Japan) between 2001 and 2017. We used S63845, a MCL1 inhibitor, to assess the cytotoxic capacity in SCLC cell lines including a patient-derived cell line in vitro and in vivo. The combination of S63845 with navitoclax, a double BCL-XL/BCL-2 inhibitor, was also employed to examine the comprehensive inhibition of the anti-apoptotic BCL-2 family. Immunohistochemistry of a TMA from patients with surgically resected SCLC demonstrated high MCL1 expression with low BCL-XL and BCL-2 to be the most common expression profile. S63845 was effective in high MCL1- and low BCL-XL-expressing SCLC cell lines. S63845 induced BAK-dependent apoptosis in vitro, and the anti-tumor efficacy was confirmed in an in vivo model. Although knockdown of BCL-XL and BCL-2 improved the cytotoxic activity of S63845 and its combination with navitoclax increased the anti-tumor cytotoxicity, the therapeutic range of S63845 with navitoclax was narrow in in vivo studies. Our study suggests MCL1 inhibition therapy be applied for high MCL1- and low BCL-XL-expressing SCLC patients

Evacuation after the Fukushima Daiichi Nuclear Power Plant Accident Is a Cause of Diabetes: Results from the Fukushima Health Management Survey

The Great East Japan Earthquake and Fukushima Daiichi nuclear disaster in 2011 forced the evacuation of a large number of residents and created changes in the lifestyle of the evacuees. These changes may have affected the evacuees\u27 glucose metabolism, thereby leading to an increase in the incidence of diabetes. This study included Japanese men and women who were living near the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture before the disaster. Subjects subsequently underwent annual health checkups with a focus on metabolic syndromes, which were conducted under the Health Care Insurers. Using the Comprehensive Health Check survey, we analyzed changes in the glucose metabolism before and after the disaster. A total of 27,486 subjects underwent follow-up examinations after the disaster, with a mean follow-up period of 1.6 years. After the disaster, the prevalence of diabetes increased significantly, and we observed that the incidence of diabetes was significantly greater among evacuees than among nonevacuees. Furthermore, multivariate logistic regression analysis revealed that evacuation was significantly associated with the incidence of diabetes. In conclusion, this is the first study to demonstrate that evacuation is associated with the incidence of diabetes. This information may be used to guide follow-up recommendations for evacuees

カイガン シンショク ト コウロ マイボツ ニ カンスル ケンキュウ

京都大学0048新制・論文博士工学博士乙第5247号論工博第1679号新制||工||598(附属図書館)UT51-59-D286(主査)教授 岩垣 雄一, 教授 土屋 義人, 教授 長尾 義三学位規則第5条第2項該当Kyoto UniversityDFA

Paratracheal Middle Mediastinal Thymic Carcinomas

We describe case studies of two patients who underwent resection of paratracheal middle mediastinal thymic carcinomas. In both patients, complete resection of these masses via right thoracotomy was performed using three-dimensional computed tomography. Final pathologic diagnoses were thymic squamous cell carcinoma and thymic atypical carcinoid tumor. Challenges and debates in preoperative, intraoperative, and postoperative management are discussed in this article

Disease Flare after Discontinuation of Crizotinib in Anaplastic Lymphoma Kinase-Positive Lung Cancer

We report the case of a 50-year-old male former smoker. He was diagnosed as having lung adenocarcinoma and treated with induction chemoradiation therapy followed by surgery and adjuvant chemotherapy. Molecular testing revealed that his tumor had an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangement. Therefore, he was treated with crizotinib when his disease recurred. He achieved a partial response, which persisted for 10 months until progressive disease was confirmed. Crizotinib was continued for 1 month and the tumor size increased slightly. At that time, crizotinib was discontinued and he participated in a clinical trial of erlotinib ± Met inhibitor; however, his disease progressed rapidly after discontinuation of crizotinib, and the diagnosis of disease flare was made. Readministration of crizotinib was started immediately; however, his disease progressed rapidly, and he died 2 days after starting crizotinib retreatment. Currently, the incidence of disease flare is unknown and it is impossible to predict who will experience it. Therefore, continuing crizotinib after disease progression may be a reasonable option to avoid disease flare

Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab

Nivolumab improves the prognosis of non-small cell lung cancer (NSCLC) but can cause immune-related adverse events (irAEs). Reports have indicated longer progression-free survivals (PFSs) in patients with irAEs than in those without irAEs. We reported associations between programmed death ligand-1 (PD-L1) single nucleotide polymorphisms (SNPs) and PFS after nivolumab treatment. We hypothesized that adverse events might be associated with the SNPs of PD-L1. We analyzed data from 111 patients with NSCLC treated with nivolumab. The response rate was 14%, and the median PFS was 68 days. We found patients with the adverse event of low free tetraiodothyronine (fT4) had significantly longer PFSs than those without low fT4 (not reached vs 67 days; hazard ratio [HR], 0.297; P = 0.010). Moreover, median overall survival was longer in patients with low fT4 than those without low fT4 (not reached vs 556 days, HR, 0.139; P = 0.020). Patients with the T allele of rs1411262 (P = 0.0073) and with the A allele of rs822339 (P = 0.0204) developed low fT4. Patients with the T/T genotype had longer PFSs than with those with the C/T and C/C genotypes of rs1411262 (165 vs. 67 days, HR, 1.65; P = 0.040), and those with the A/A genotype had longer PFSs than those with the A/G and G/G genotypes of rs822339 (182 vs. 67 days, HR, 1.76; P = 0.025). In the patients with advanced NSCLC, low fT4 after nivolumab treatment was associated with significantly longer PFSs. The SNPs of PD-L1 may be associated with the adverse events of nivolumab