The exon 20 T790M mutation confers resistance to 1^st- and 2^nd-generation EGFR-TKIs while the C797S mutation confers resistance to the 3^rd-generation EGFR-TKI, osimertinib. The presence of C797S in trans with T790M restores sensitivity to 1^st/2^nd-generation EGFR-TKIs. In the current study, we analyzed whether the T790M mutation was present in cis or trans with activating mutations in tumors treated with osimertinib. We analyzed tissue specimens harboring both T790M and activating mutations in patients with non-small cell lung cancer obtained from May 2016 to June 2018. After the presence of EGFR mutation was confirmed using the PNA-LNA PCR clamp method, we determined whether activating mutations were located in cis or trans with the T790M mutation using RT-PCR. Results were validated using colony PCR followed by Sanger sequencing, which allowed us to calculate the allele frequency of each. Both EGFR mutations were detected in 11 out of 23 cases. All 11 cases had cis configuration. The low allele frequency of T790M might be related to the short duration of osimertinib treatment. The cis configuration of T790M and activating mutations in all specimens was confirmed, and this result was in contrast to the existence of trans configuration of C797S and T790M.

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Hepatocellular carcinoma (HCC) is frequently observed in patients infected with hepatitis B virus (HBV); however, early detection of HBV-related HCC is difficult due to the lack of an optimal biomarker allowing discrimination of early stage HCC patients from non-HCC HBV carriers. Here, we identify circulating microRNAs (miRNAs) allowing identification of early stage HCC patients among HBV carriers at low to high risk of hepatocarcinogenesis. We conducted a case-control study to estimate serum microRNA levels in hepatitis B surface-antigen (HBsAg)-positive patients with early-stage HCC for comparison with controls matched according to ethnicity, age, sex, presence or absence of hepatitis B e antigen, treatment with a nucleoside/nucleotide analogue, and presenting with clinical forms of HBV infection, including inactive carrier, chronic hepatitis, or cirrhosis. We recruited and obtained sera from 20 HBsAg-positive patients [HCC group and controls (n = 10 each)] and performed microarray analysis, which identified five candidate miRNAs (miR-548a, miR-1281, miR-4634, miR-4646-3p, and miR-4659a) exhibiting significantly different levels between the two groups. These results suggest these miRNAs as potential biomarkers for predicting early stage HCC development in patients with HBV infection.

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This study was conducted to clarify efficient initial training for total laparoscopic hysterectomy (TLH). Twenty patients with benign gynecological diseases who underwent TLH were included. The first author recognized the issues that needed to be improve from the first 10 video reviews and continued self-training to overcome them. Among the TLH process, we observed changes in the time required for “identification of ureter to cutting the uterine artery”, “colpotomy”, and “suturing of vaginal stump”. In addition, we compared surgery-related factors (total operative time, blood loss, postoperative hospitalization days, complications) retrospectively between the early and late groups. From the video review, we obtained 149 findings, of which about 40% (58/149) were associated with “colpotomy” and “suturing of vaginal stump”. The time required for each process became stable below the median after the 13th case. There were no differences in surgical factors between the early and late groups, and no serious complications were observed. These results indicate that visualizing the task by reviewing surgical videos can be effective for overcoming the initial learning phase of TLH.

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Endoscopic surgery is minimally invasive as compared to open surgery and is becoming more popular as a standard approach to malignant tumors. We introduced endoscopic surgery for endometrial cancer in Iwate Prefecture, and have performed 15 robot-assisted surgeries (R) and 14 laparoscopic surgeries (L) so far. The total operation time and postoperative hospitalization days for the R group were longer than those for the L group (333.0 min vs. 222.0 min; p ‹ 0.0001, 6.0 days vs. 5.0 days; p = 0.040). On the other hand, there were no differences between the two groups in blood loss, postoperative CRP elevation and surgical Apgar score. There were no serious perioperative complications such as transition to open surgery or blood transfusion in either group. Postoperative adjuvant therapy was given to 4 of 29 cases, but there have been no recurrence cases so far. In Iwate Prefecture, where access to medical resources is limited, endoscopic surgery for endometrial cancer has been successfully introduced. In order to spread the use of endoscopic surgery in this prefecture, it is necessary to improve the skill of the surgeon, and to train qualified technicians for laparoscopic surgery and robot-assisted endoscopic surgery.

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