Uniportal Video-Assisted Thoracoscopic Segmentectomy for Early-Stage Non-Small Cell Lung Cancer: Overview, Indications, and Techniques.

Twenty years have passed since uniportal video-assisted thoracoscopic surgery (VATS) was first reported. Several reports have already proven the minimal invasiveness of uniportal VATS. In addition, two large clinical trials recently demonstrated the benefits of segmentectomy for small peripheral early-stage non-small cell lung cancer. Uniportal VATS segmentectomy is considered the most beneficial minimally invasive surgery for patients with early-stage lung cancer. However, a high level of skill and experience are required to achieve this goal. Only a few reports have discussed specific techniques, particularly for complex segmentectomies. In this Special Issue, we reviewed previous reports on uniportal VATS segmentectomy regarding the indications, instrument selection, marking of the tumor location, methods of intersegmental plane identification, and lymph node dissection, including our own techniques with video content.

A descriptive epidemiology in syphilis in Tokyo, 2019-2022.

The number of syphilis cases in Tokyo has been found to increase in recent years. We conducted a descriptive epidemiology to elucidate the actual status of syphilis. Data on age, sex, disease stage, and presumed sexual partner of syphilis cases reported in Tokyo were tabulated and analyzed. A total of 9,419 syphilis cases have been reported between 2019 and 2022. There was a particularly sharp rise in the number of reported cases from 2021 to 2022. Comparing 2020 to 2022, the number of syphilis cases among women in their 20s, rapidly increased, more than triple. Furthermore, the number of pregnant women among syphilis cases increased in 2022. Despite the rapid increase in the number of young women with syphilis, there has been no increase in cases of congenital syphilis. One of the reasons may be that syphilis was detected early in pregnancy due to the high antenatal checkup rate in Tokyo. However, the continued incidence of syphilis among young women may increase congenital syphilis in the future. Public health strategy should include educational activities targeting high-risk populations or adolescents, early and appropriate testing, and treatment for preventing progression of syphilis.

Airway stent intervention in a high-volume center: safe procedures and educational perspectives.

Background: Airway intervention, including stenting, can rapidly improve a patient's respiratory condition, but the procedure requires highly specialized techniques and expertise. Therefore, educating young endoscopists and passing on the techniques are major issues. However, the best way to educate new doctors on these techniques remains unclear. This study analyzed our educational system for airway intervention and its outcomes. Methods: Patients who underwent airway intervention regarding airway stents under general anesthesia in our department between January 2010 and September 2023 were included. The outcomes of interventions related to airway stents in our hospital were evaluated retrospectively, including from an educational perspective. Results: A total of 96 patients (76 undergoing stenting for airway stenosis, 8 stenting for airway-esophageal fistula, and 12 stent removal) were analyzed. The median experience level of the main physician was 5 (range, 1-17) years, and that of the supervising physician was 18 (range, 5-23) years. The median number of physicians who participated in the interventions was four. A rigid bronchoscope was used in 86.5% of cases. The procedure success rate was 95.8%. Intraoperative complications occurred in 8.3% and postoperative complications in 10.5% of cases, and there was 1 procedure-related death (1.3%). In the analysis of factors related to the development of complications, the years of experience of the main physician had no influence. Conclusions: These findings indicate that our method of airway intervention is safe. Young endoscopists were able to master the technique by gaining experience under the supervision of experts.

Nursing students' self-assessed level of nursing skills at the time of graduation in a Japanese University: A retrospective observational study.

Objective: This study aimed to clarify nursing students' self-assessed levels of nursing skills at a nursing university at graduation and discuss how education and clinical experiences for students and post-licensure nurses should be improved, especially focusing on oncology nursing. Methods: The study population comprised fourth-year students from 2017 to 2019 at the Faculty of Health Science and Nursing, Juntendo University, who had completed all stipulated clinical placements. The Japanese government determined 141 nursing skills and their target levels. Students subjectively evaluated their achieved levels for the 141 nursing skills after the final clinical placement. Results: Of the 141 nursing skills, 81 (57%) were rated as "skills with easy-to-achieve targets" and five were rated as "skills with difficult-to-achieve targets." All nursing skills in the two subcategories of environmental adjustment skills and comfort management skills were rated as "skills with easy-to-achieve targets." Nursing skills with low target achievement rates were for patients with oral intake difficulties, unstable respiratory status, and those requiring glycemic control. These skills are also important in oncology nursing. Conclusions: It cannot be concluded that the nursing university students fully achieved the target levels of nursing skills, as determined by the Japanese government. These findings may facilitate discussions on teaching nursing skills and their target levels at the time of graduation from nursing universities or post-employment.

Multisource surveillance conducted by the Tokyo Metropolitan Government during the Tokyo 2020 Olympic and Paralympic Games.

The Tokyo 2020 Olympic and Paralympic Games (the Games) were held from 23 July to 5 September 2021 in Tokyo, Japan, after a 1-year delay due to the coronavirus disease (COVID-19) pandemic. The Tokyo Metropolitan Government was responsible for monitoring and responding to infectious disease outbreaks other than COVID-19 during the Games. A multisource surveillance system was used from 1 July to 12 September 2021 for the early detection and rapid response to infectious diseases. This included routine notifiable disease surveillance, sentinel surveillance, syndromic surveillance, cluster surveillance, ambulance transfer surveillance and the Tokyo Infectious Alert system. Daily reports were disseminated summarizing the data collected from the multisource surveillance system. No case of infectious disease under the Tokyo Metropolitan Government system required a response during the Games. The multisource surveillance was useful for providing intelligence during the Games and, if required, could contribute to the early detection and rapid response to outbreaks during other mass gatherings. The system could be improved to overcome the challenges implied by the findings of this multisource surveillance.

Soluble epoxide hydrolase maintains steady-state lipid turnover linked with autocrine signaling in peritoneal macrophages.

Soluble epoxide hydrolase is a widely distributed bifunctional enzyme that contains N-terminal phosphatase (N-phos) and C-terminal epoxide hydrolase (C-EH) domains. C-EH hydrolyzes anti-inflammatory epoxy-fatty acids to corresponding diols and contributes to various inflammatory conditions. However, N-phos has been poorly examined. In peritoneal macrophages, the N-phos inhibitor amino-hydroxybenzoic acid (AHBA) seemed to primarily interrupt the dephosphorylation of lysophosphatidates and broadly attenuated inflammation-related functions. AHBA activated intrinsic lysophosphatidate and thromboxane A2 receptors by altering lipid-metabolite distribution; downstream the signaling, phospholipase C was facilitated to dampen intracellular Ca2+ stores and AKT kinase (protein kinase B) was activated to presumably inhibit inflammatory gene expression. Our data suggest that N-phos maintains steady-state phospholipid turnover connecting autocrine signaling and is a prospective target for controlling inflammatory responses in macrophages.

Impact of ground glass opacity in a three-dimensional analysis for pathological findings and prognosis in stage IA pure solid lung cancer.

Background: We investigated whether a three-dimensional (3D) analysis could correct the discrepancy between conventional computed tomography findings and pathological findings and contribute to prognostic stratification in early pure solid lung cancer. Methods: A total of 370 patients with two-dimensional (2D) pure solid, clinical stage IA non-small cell lung cancer (NSCLC) who underwent complete resection at our hospital between January 2010 and March 2021 were included in the present study. We classified the patients into the 3D solid group and the 3D ground glass opacity (GGO) group according to the consolidation volume/tumor volume ratio (C/T volume ratio) measured using a Synapse Vincent 3D analysis workstation, and compared the pathological findings and prognosis between the two groups. Results: There were 142 (38.4%) patients in the 3D GGO group. Lepidic lesions were significantly more frequent in the 3D GGO group (27.6% vs. 59.2%, P<0.001). Lymphatic invasion, vascular invasion and lymph node metastasis were significantly more frequent in the 3D solid group (52.2% vs. 27.5%, P<0.001; 67.5% vs. 43.0%, P<0.001; 22.3% vs. 11.2%, P=0.04). A Cox proportional hazards multivariate analysis for overall survival (OS) and recurrence-free survival (RFS) showed that 3D solid was an independent poor prognostic factor [hazard ratio (HR): 1.981, P=0.02; HR: 1.815, P=0.02]. Kaplan-Meier curves for 5-year OS (74.1% vs. 87.8%, P<0.001) and 5-year RFS (65.6% vs. 84.9%, P<0.001) showed significant differences between the two groups. Conclusions: The C/T volume ratio determined by a 3D analysis detects GGO and reflects the pathological findings, and further prognostic stratification is possible in early 2D pure solid lung cancer.

Human-rabbit Hybrid Translation System to Explore the Function of Modified Ribosomes.

In vitro translation systems are a useful biochemical tool to research translational regulation. Although the preparation of translation-competent cell extracts from mammals has often been a challenge, the commercially available rabbit reticulocyte lysate (RRL) is an exception. However, its valid use, investigating the mechanism of translation machinery such as ribosomes in RRL, presents an analytic hurdle. To overcome this issue, the hybrid translation system, which is based on the supplementation of purified human ribosomes into ribosome-depleted RRL, has been developed. Here, we describe the step-by-step protocol of this system to study translation driven by ribosomes lacking post-translational modifications of the ribosomal protein. Moreover, we combined this approach with a previously developed reporter mRNA to assess the processivity of translation elongation. This protocol could be used to study the potency of heterologous ribosomes.

Multiple solitary fibrous tumors of the pleura with multicentric and unilateral involvement: a case report.

BACKGROUND: Solitary fibrous tumor of the pleura (SFTP) is a mesenchymal tumor. Patients with SFTP generally have only one lesion. We herein report an extremely rare case of multiple SFTPs that were multicentric and unilateral. CASE PRESENTATION: The patient was a 21-year-old asymptomatic young man who was referred to our hospital due to abnormal shadows on a chest X-ray. Computed tomography showed 6 tumors of heterogeneous sizes in the left thoracic cavity. The tumors were suspected to be multiple benign or low-grade malignant thoracic tumors, and tumor resection was performed. The tumors had almost the same appearance, with uniform fibroblastic spindle cell proliferation, and arose from the pleura in microscopy. Immunohistochemical staining revealed that the tumor cells were positive for CD34, CD99, Bcl-2, and STAT6. Based on these findings, the tumors were diagnosed as multiple SFTPs with multicentricity. At 1 year and 6 months after the first surgery, 2 new lesions were found above the diaphragm, and these were resected. These tumors were arose from the pleura with a fibrous capsule structure. Their pathological findings were identical to the initial tumor without evidence of malignant transformation. CONCLUSION: We experienced an extremely rare case of multiple SFTPs with multicentric and unilateral lesions.

Preoperative detection of pleural adhesions using dynamic chest radiography: prospective analysis.

Background: To plan a surgical approach and predict the operative time or bleeding volume, it is important to determine the presence of pleural adhesions before surgery. Dynamic chest radiography (DCR) is a new modality that can dynamically capture X-rays, and we assessed the utility of DCR for detecting pleural adhesions preoperatively. Methods: The subjects of this study were those who underwent DCR before surgery from January 2020 to May 2022. The preoperative evaluation was performed by three imaging analysis modes, and pleural adhesion was defined as the that spreading to more than 20% of the thoracic cavity and/or taking more than 5 minutes to dissect. Results: Of the 120 total patients, DCR was performed properly for 119 (99.2%). Accurate preoperative evaluations of pleural adhesions were confirmed in 101 patients (84.9%), with a sensitivity of 64.5%, specificity of 91.0%, positive predictive value of 74.1%, and negative predictive value of 88.0%. Conclusions: DCR was very easy to perform in all preoperative patients with all manner of thoracic disease. We demonstrated the utility of DCR, showing its high specificity and negative predictive value. DCR has the potential to become a common preoperative examination for detecting pleural adhesions with further improvements in software programs.

RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function.

Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

Identification of aminobenzoic acids as selective inhibitors of the N-terminal phosphatase of soluble epoxide hydrolase.

Soluble epoxide hydrolase (EC 3.3.2.10) is a key enzyme in the regulation of inflammation and metabolism, whereas, the role of its N-terminal phosphatase activity (N-phos) has been poorly understood because of a lack of selective inhibitors. Here we report 4-aminobenzoic (Ki 15.3 µm) and 3-amino-4-hydroxy benzoic acid (Ki 11.7 µm) as selective competitive inhibitors of N-phos.

Bronchiolar adenoma/ciliated muconodular papillary tumor mixed with adenocarcinoma in situ in the same tumor.

Bronchiolar adenoma (BA)/ciliated muconodular papillary tumor (CMPT) is defined as a benign tumor composed of epithelial and basal cells. Recently, some cases with driver mutations or malignant transformation have been observed. Thus, whether BA/CMPT is benign or malignant remains controversial. We herein report an extremely rare case of a 68-year-old woman with a CMPT accompanied by adenocarcinoma in situ (AIS). BA/CMPT existed inside the AIS. The BA/CMPT component did not show any driver mutations; however, the AIS component had an EGFR driver mutation in exon 19. The accumulation of cases and further studies are needed to discuss the malignant potential of BA/CMPT.

Pathologically noninvasive cancer predictors and surgical procedure for peripheral lung cancer.

BACKGROUND: In this retrospective study, based on recent studies reporting the superiority of sublobar resection to lobectomy for peripheral small size non-small cell lung cancer (NSCLC), we investigated the optimal pathological factors for predicting noninvasive cancer and the selection of operative procedure. METHODS: Patients with peripheral NSCLC of ≤2 cm who underwent surgery at our hospital between January 2010 and June 2020 were included in this study. We evaluated the relationship between pathologically noninvasive cancer and predictive factors according to the area under the curve (AUC) and accuracy, and the cutoff value was set to investigate indications for sublobar resection. RESULTS: The comparison of the AUCs revealed that the maximum standardized uptake value and consolidation to tumor (C/T) volume ratio were better predictors than the C/T ratio. Among the three factors, the C/T volume ratio showed the best accuracy. The patients were divided into two groups (low and high) using the cutoff value of the C/T volume ratio and compared according to the surgical procedure (lobectomy vs. segmentectomy). In the low-group, there was no significant difference in the prognosis. In the high-group, the 5-year recurrence-free survival rate of the patients who received lobectomy was 87.8%, while that of patients who received segmentectomy was 75.8% (p = 0.08). CONCLUSIONS: The C/T volume ratio was the best preoperative pathologically noninvasive predictive factor. Sublobar resection should be performed with caution in cases with significant solid components on three-dimensional images.

Direct cell-cell interaction regulates division of stem cells from PC-3 human prostate cancer cell line.

Cancer stem cells (CSCs) are a subpopulation that can drive recurrence and metastasis. Therefore, therapies targeting CSCs are required. Although previous findings have suggested that non-CSCs regulate the proliferation and differentiation of CSCs in the tumor microenvironment, the precise molecular mechanism is largely unknown. In this study, we found that a direct interaction between CSCs and non-CSCs downregulated CSC division in the PC-3 human prostate cancer cell line. We found that the proliferation of PC-3-derived CSCs (PrSCs) was significantly decreased (∼47%) in the presence of non-CSC-rich parental PC-3 cells compared with that in a culture in which they were absent. We observed no differences in PrSC proliferation when we indirectly cocultured them with PC-3 cells across a Transwell insert, and PrSCs that were transiently bound to immobilized PC-3 cells proliferated more slowly than those bound to PrSCs. The frequency of cell division with prior PrSC-PrSC contact was 2.8 times higher in the PrSC monoculture compared with that in the coculture with PC-3 cells. We found that the PrSCs were approximately 1.3 times more closely associated in the monoculture compared with the coculture with PC-3 cells, as determined by a cell proximity assay. The frequency of asymmetric PrSC division was 6.5% in the monoculture compared with 1.0% in the coculture with PC-3 cells (P < 0.045). By analyzing our data, we determined the importance of PrSC-non-CSC contact in regulating the frequency and mode of PrSC division. This regulation might be a valuable target for treating cancer.

Amine-Regulated pri-SMTP Oxidation in SMTP Biosynthesis in Stachybotrys: Possible Implication in Nitrogen Acquisition.

SMTP (the name SMTP is derived from Stachybotrys microspora triprenyl phenol) is a family of triprenyl phenol secondary metabolites from a black mold, Stachybotrys microspora. Some SMTP congeners exhibit anti-inflammatory and profibrinolytic activities that, in combination, contribute to the treatment of ischemic stroke. The final step in the SMTP biosynthesis is a non-enzymatic amine conjugation with an o-phthalaldehyde moiety of the precursor pre-SMTP, which can form adducts with proteins and nucleic acids. Thus, pre-SMTP formation should be a precisely regulated, rate-limiting step in the SMTP biosynthesis. To address the mechanism backing this regulation, we purified a metabolite that rapidly disappeared following amine feeding, identifying a novel compound, pri-SMTP. Furthermore, an enzyme, designated as pri-SMTP oxidase, responsible for pri-SMTP conversion to pre-SMTP, was purified. The formation of pri-SMTP, which is regulated by nitrogen and carbon nutrients, occurred in particular septate mycelia. Although pri-SMTP oxidase was expressed constitutively, the consumption of pri-SMTP was accelerated only when a primary amine was fed. Thus, SMTP biosynthesis is regulated by at least three mechanisms: (i) pri-SMTP formation affected by nutrients, (ii) the compartmentalization of pri-SMTP formation/storage, and (iii) amine-regulated pri-SMTP oxidation. Amine-regulated SMTP formation (i.e., amine-capturing with pre-SMTP) may play a role in the nitrogen acquisition/assimilation strategy in S. microspora, since pri-SMTP synthesis occurs on non-preferred nitrogen.

Association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan.

BACKGROUND: There is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial. We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan. METHODS: From the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests (Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study), 1205 patients managed with SPECT were stratified by 10 % myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year. RESULTS: Patients with ≥10 % myocardial ischemia (n = 173) were less likely to be women than patients with <10 % myocardial ischemia (n = 1032) and had a significantly higher 1-year cumulative incidence of MACEs (6.9 % vs. 1.8 %, p < 0.0001). After adjusting for confounders, the risk of ≥10 % myocardial ischemia relative to <10 % myocardial ischemia for MACEs remained significant [adjusted hazard ratio (95 % confidence interval), 2.40 (1.09-5.26), p = 0.029]. After adjusting including treatments, the risk of MACEs became insignificant between the ≥10 % myocardial ischemia group and the <10 % myocardial ischemia group [adjusted hazard ratio (95 % confidence interval), 1.04 (0.45-2.45), p = 0.92]. CONCLUSION: The presence of ≥10 % myocardial ischemia at diagnosis was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease.

Treatment of secondary pneumothorax with interstitial lung disease: the surgical indications at the start of treatment is important.

Background: Secondary pneumothorax with interstitial lung disease (ILD) is often difficult to treat in comparison to primary pneumothorax. The purpose of this study was to analyze the actual management and outcome, and to find the most effective treatment. Methods: Among 180 patients with pneumothorax caused by ILD, who were managed between January 2000 and April 2021, 129 patients were included. Fifty-one patients with observation only were excluded. In the present study, a patient was considered to be cured if their chest tube could be removed. Results: The managements included chest tube drainage alone (n=41), pleurodesis (n=67), bronchoscopic treatment (n=14), and surgery (include overlapping cases) (n=25). The mean number of pleurodesis treatments was 2.4 (range, 1-9), and the most frequently used agent was blood-patch. All patients who received bronchoscopic treatment underwent bronchial occlusion with silicon spigots. The surgical procedures included bullectomy (n=20), lung cyst ligation (n=3), pleural covering with oxidized cellulose sheet (n=1), and spraying of fibrin glue alone (n=1). One hundred patients (77.5%) were curatively treated, 27 patients (20.9%) died, and 2 patients were transferred without chest tube removal. Among 25 patients who received surgery [including 6 patients with performance status (PS) ≥2], 24 patients (96.0%) were cured, and 1 patient died due to an acute exacerbation of ILD after surgery. The univariate analysis revealed that PS ≥2 and >3 pleurodesis treatments were significant non-curative factors, while steroid treatment before the development of pneumothorax was not. Conclusions: The outcomes of surgery for pneumothorax in patients with ILD were good, and it is desirable to consider the surgical indications.

METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance.

Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a methylation substrate. However, a limited number of enzymes responsible for this modification have been reported. Moreover, the biological role of histidine methylation has remained poorly understood to date. Here, we report that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traversal on Tyr codons, allowing the proper folding of synthesized proteins. By performing an in vitro methylation assay with a methyl donor analog and quantitative mass spectrometry, we found that His245 of RPL3 is methylated at the τ-N position by METTL18. Structural comparison of the modified and unmodified ribosomes showed stoichiometric modification and suggested a role in translation reactions. Indeed, genome-wide ribosome profiling and an in vitro translation assay revealed that translation elongation at Tyr codons was suppressed by RPL3 methylation. Because the slower elongation provides enough time for nascent protein folding, RPL3 methylation protects cells from the cellular aggregation of Tyr-rich proteins. Our results reveal histidine methylation as an example of a ribosome modification that ensures proteome integrity in cells.