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Ciliated muconodular papillary tumor/bronchiolar adenoma (CMPT/BA) is a benign tumor with a high frequency of BRAF or EGFR mutations. It remains unclear whether CMPT/BA is associated with a specific type of lung cancer. Thus, we studied the clinicopathological and genetic characteristics of cases with coexisting CMPT/BA and primary lung cancer to explore this relationship. Among 1945 patients with resected stage 0-III primary lung cancer between 2015–2018, we identified eight patients with concurrent CMPT/BA (lung cancer associated with CMPT/BA; LCCM). We compared the gene mutation status of each lesion according to the target sequence using macro-dissected formalin-fixed paraffin-embedded specimens. Whole-exon sequencing (WES) was performed for six lung cancer cases. The LCCM cohort was male-dominant (male:female = 6:2); the median age was 72 years (range 66–81); and most were smokers (six smokers). The most common histological type corresponding to LCCM was adenocarcinoma; however, two squamous cell carcinomas and one small cell carcinoma were also detected. CMPT/BA lesions in LCCM showed a median size of 0.5 cm (range 0.3–1.1). The mutational test revealed no shared mutations between CMPT/BA and lung cancer, except for one invasive mucinous adenocarcinoma (IMA) harboring an HRAS mutation (I46N, c.137T > A). HRAS (I46N) is a rare variant, and all tumors showed an approximately 50% variant allele frequency, suggesting a single nucleotide polymorphism. Other driver gene alterations in lung cancer included EGFR (InDel, n = 2), BRAF (V600E) (n = 1), KRAS (n = 2), GNAS (n = 1), and TP53 (n = 2) mutations. BRAF (V600E) was the most frequent mutation in CMPT/BA. In contrast, lung cancer showed no specific trend in driver gene mutations. In conclusion, our study revealed differences in the gene mutation profiles of CMPT/BA and lung cancer in coexisting cases, suggesting a mostly independent tumorigenesis of CMPT/BA from lung cancer, except for one IMA with a rare HRAS SNV.

Background Salvage surgery is performed for selected patients with relapses of locally advanced lung cancer after definitive chemoradiation therapy (CRT), and seems to be effective. To date, the feasibility of such salvage surgery, particularly anatomical pulmonary resection, has not been fully evaluated. To assess the feasibility of salvage surgery after definitive CRT, we compared clinical outcomes of surgery after definitive CRT to those of surgery after induction CRT. Methods Medical records of patients who underwent surgery from January 2000 to January 2018 were reviewed. We compared patients with salvage anatomical pulmonary resection after definitive CRT to patients with surgery after induction CRT in terms of perioperative and long-term outcomes. Results Twenty-three patients underwent salvage surgery after definitive CRT for locally advanced lung cancer (salvage group) and 36 underwent surgery after induction CRT for cN2-stage III non-small cell lung cancer (induction CRT group). The surgical procedures in the salvage group were 2 segmentectomies, 13 lobectomies, 1 bi-lobectomy and 7 pneumonectomies, and those in the induction CRT group were 34 lobectomies and 2 bi-lobectomies. There was no 30-day or 90-day mortality in either group. The 5-year overall survival was 44.7% for the salvage group and 58.6% for the induction CRT group. The 5-year progression-free interval was 42.2% for the salvage group and 47.7% for the induction CRT group. Conclusions Salvage anatomical pulmonary resection after definitive CRT for locally advanced lung cancer is feasible with acceptable morbidity and prognosis in highly selected patients.

We aimed to visualize complicated patterns of lymph node metastases in surgically resected non-small cell lung cancer by applying a data mining technique.In this retrospective study, 783 patients underwent lobectomy or pneumonectomy with systematic mediastinal lymph node dissection for non-small cell lung cancer between January 2010 and December 2018. Surgically resected lymph nodes were classified according to the International Association for the Study of Lung Cancer lymph node map. Network analysis generated patterns of lymph node metastases from stations 1 to 14, and the degree of connection between 2 lymph node stations was assessed.The median number of lymph nodes examined per patient was 20, and the pathological N category was pN0 in 428 cases, pN1 in 132, pN2 in 221, and pN3 in 2. N1 lymph node stations had strong associations with superior mediastinal lymph node stations for patients with primary tumors in the upper lobes and with station 7 for the lower lobes. There was also a connection from the N1 lymph node stations to superior mediastinal lymph node stations in the lower lobes. In the right middle lobe, an even distribution from station 12m toward stations 2R, 4R, and 7 was noted. We released an interactive web application to visualize these data: http://www.canexapp.com.Lymph node metastasis patterns differed according to the lobe bearing the tumor. Our results support the need for clinical trials to further investigate selective mediastinal lymph node dissection.

Resistance to immune-checkpoint blockade remains challenging in patients with non-small cell lung cancer (NSCLC). Tumor-infiltrating leukocyte (TIL) quantity, composition, and activation status profoundly influence responsiveness to cancer immunotherapy. This study examined the immune landscape in the NSCLC tumor microenvironment by analyzing TIL profiles of 281 fresh resected NSCLC tissues. Unsupervised clustering based on numbers and percentages of 30 TIL types classified adenocarcinoma (LUAD) and squamous cell carcinoma (LUSQ) into the cold-, myeloid cell-, and CD8+ T cell-dominant subtypes. These were significantly correlated with patient prognosis; the myeloid cell subtype had worse outcomes than the others. Integrated genomic and transcriptomic analyses, including RNA sequencing, whole-exome sequencing, T cell receptor repertoire, and metabolomics of tumor tissue, revealed that immune reaction-related signaling pathways were inactivated, while the glycolysis and K-ras signaling pathways activated in LUAD and LUSQ myeloid cell-subtypes. Cases with ALK and ROS1 fusion genes were enriched in the LUAD myeloid subtype, and the frequency of TERT copy number variations was higher in LUSQ myeloid subtype than in the others. These classifications of NSCLC based on TIL status may be useful for developing personalized immune therapies for NSCLC.

OBJECTIVES We evaluated the potential of preoperative fluorine-18-fluorodeoxyglucose positron emission tomography to predict invasive thymic epithelial tumours in patients with computed tomography-defined clinical stage I thymic epithelial tumours ≤5 cm in size who are generally considered to be candidates for minimally invasive approaches. METHODS From January 2012 to July 2022, we retrospectively analysed patients who exhibited tumour-node-metastasis (TNM) clinical stage I thymic epithelial tumours with lesion sizes ≤5 cm as determined by computed tomography. All patients underwent fluorine-18-fluorodeoxyglucose positron emission tomography preoperatively. We analysed the association of maximum standardized uptake values with both the World Health Organization histological classification and the TNM staging classification. RESULTS A total of 107 patients with thymic epithelial tumours (thymomas, 91; thymic carcinomas, 14; carcinoids, 2) were evaluated. Nine patients (8.4%) were pathologically upstaged: TNM pathological stage II in 3 (2.8%), III in 4 (3.7%) and IV in 2 (1.9%). Among these 9 upstaged patients, 5 had thymic carcinoma with stage III/IV, 3 had type B2/B3 thymoma with stage II/III and 1 had type B1 thymoma with stage II. Maximum standardized uptake values were a predictive factor that distinguished pathological stage >I thymic epithelial tumours from pathological stage I [best cut-off value, 4.2; area under the curve = 0.820] and thymic carcinomas from other thymic tumours (best cut-off value, 4.5; area under the curve = 0.882). CONCLUSIONS Thoracic surgeons should carefully determine the surgical approach for high fluorodeoxyglucose-uptake thymic epithelial tumours and keep in mind the issues associated with thymic carcinoma and potential combined resections of neighbouring structures.

We synthesized a molecule-based proton-electron mixed conductor (PEMC), a Pt(III) dithiolate complex with 1,4-naphthoquinone skeletons. The π-planar Pt complex involves a π-stacking column, which is connected by one-dimensional hydrogen bonding chains composed of water molecules. The room-temperature (RT) proton conductivity is 8.0 × 10

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy according to real-world data. Therefore, robust predictive biomarkers for selecting adjuvant chemotherapy (ADJ) or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by fluorescence in situ hybridization (FISH). Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were performed. Formalin-fixed, paraffin-embedded (FFPE) samples from 1,136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients ≥ 65 years, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (HR: 0.084, 95% CI: 0.009, 0.806; P = 0.032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages, HR: 1.214, 95% CI: 0.848, 1.738; P = 0.289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative adjuvant chemotherapy for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side effects of adjuvant chemotherapy, and saving medical costs.

Introduction Because several articles have reported a prognostic association with the radiologic features of ground-glass opacity, we explored whether the histologic presence of a lepidic component had similar significance. Methods We retrospectively evaluated 380 consecutive surgically resected lung adenocarcinomas (ADCs) of pathologic (p)stage IA. The tumors were classified into lepidic-positive and lepidic-negative ADCs. Clinicopathologic characteristics, radiographic ground-glass opacity status, and disease-free survival were compared between lepidic-positive and lepidic-negative ADCs and between part-solid and solid nodules on computed tomography images. Results Of the 380 cases, 176 (46.3%) were lepidic-positive ADCs. Of the overall patients with pT1, lepidic-positive ADCs were found to have significantly better recurrence-free survival (5 y, 95.4% versus 87.0%, p = 0.005), but this significance was not reproduced in pT1 subcategories (pT1a, pT1b, and pT1c). Furthermore, the presence of the lepidic component was not an independent prognostic factor in the multivariate analysis (hazard ratio = 0.46 [95% confidence interval: 0.19–1.14], p = 0.09). We also analyzed the extent of the lepidic component with 10% incremental valuables. Although we found that a 10% or greater extent of lepidic component made the recurrence-free survival difference the largest, a clear prognostic impact was not obtained with this cutoff point. Conclusions Although lepidic-positive ADCs tended to have a favorable outcome, the lepidic component was not a clear independent prognostic factor in pstage I ADC.

Inflammatory factors in the peripheral blood, such as the C-reactive protein level and neutrophil-to-lymphocyte ratio (NLR), are prognostic markers in multiple types of cancer, including non-small cell lung cancer (NSCLC). However, the association between inflammatory factors and prognosis based on histological types has not been adequately reported. In addition, the relationship between these factorsand the immune condition of the tumor microenvironment (TME) is unclear. In this study, we first investigated the relationship between preoperative inflammatory markers and clinical outcomes in 176 patients with NSCLC who underwent surgery. Lung adenocarcinoma (LUAD) showed no significant prognostic marker, whereas for lung squamous cell carcinoma (LUSC), a multivariate analysis showed that a high NLR was significantly associated with postoperative recurrence. In LUSC patients, the median time of postoperative recurrence-free survival in patients with a low NLR was longer than that in patients with a high NLR. We then compared the tumor-infiltrating lymphocyte (TIL) profile with inflammatory markers in peripheral blood and found that the NLR was negatively correlated with the frequencies of T cells and B cells in LUSC tissues. Thus, the NLR is a useful predictive biomarker for postoperative recurrence and may reflect the immune condition of the TME in LUSC.

OBJECTIVESWith recent improvements in surgical techniques for segmentectomy, we hypothesized that segmentectomy is feasible and more effective than wedge resection for non-small-cell lung cancer (NSCLC). We compared perioperative and oncological outcomes for segmentectomy and wedge resection.METHODSWe performed a retrospective analysis of 720 patients who underwent sublobar resection (segmentectomy, 479; wedge resection, 241) for clinical stage 0 or I NSCLC from January 2017 to June 2020. An adequate surgical margin was defined as a surgical margin distance of ≥2 cm or ≥ the total tumour size. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method for clinical stage IA.RESULTSThere was no significant difference in the rate of major (grade ≥III) complications between segmentectomy (1.7%) and wedge resection (1.2%) (P = 0.76). The probability of obtaining adequate surgical margins was significantly higher with segmentectomy (71.4%) versus wedge resection (59.5%) (P = 0.002), and the difference was especially prominent for clinical stage IA2 (75.3% vs 56.9%; P = 0.012). Among patients with clinical stage IA, segmentectomy significantly improved the RFS compared with wedge resection (hazard ratio 2.7; 95% confidence interval 1.60–4.61; log-rank P < 0.001). Subgroup analysis based on the tumour status revealed that segmentectomy had a better RFS in clinical stage IA2 (P < 0.001) and in pure-solid tumours (P = 0.022) than wedge resection.CONCLUSIONSWe demonstrate that segmentectomy is a feasible procedure with comparable safety outcomes and better surgical margins and cancer control than wedge resection, particularly for clinical stage IA2 NSCLC.

Metal string complexes, linearly aligned transition metal arrays coordinated with the multidentate organic ligands, have gained much attention both in unique electronic/structural properties and in potential applications as conductive molecular nanowires. Here we report on a dimerized NiII trinuclear complex, [Ni6Cl2(dpa)8](I5)2·0.25I2 (dpa- = 2,2'-dipyridylamide anion). X-ray structural analysis revealed that two trinuclear moieties are bridged by a Cl anion to form a dimerized string structure. This is the first example of two Ni string complexes that are connected. In the electronic absorption and Raman spectra, characteristic absorption bands and a vibration mode based on the dimer string structure were observed. In the solid state, dimer complexes align in one dimension in an MMMXMMMX (M = metal, X = halogen) manner, leading to the intra- and interdimer antiferromagnetic interactions.

Background Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively. Methods A serum miRNA profile (miRNomes)–based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified. Results Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type–specific serum miRNomes. Conclusions This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.

Prolonged air leak (PAL) is one of the most common complications after pulmonary resection for lung cancer. This study aimed to identify the factors that predict PAL, and to evaluate the impact of PAL on the development of additional complications and cost of hospitalization.A total of 2278 patients who underwent pulmonary resection other than pneumonectomy for lung cancer from 2014 to 2018 were retrospectively enrolled in this study. PAL was defined as air leak that continued more than 5 days after the operation. Multivariate analyses were conducted to identify significant predictors of PAL, using clinical information. Development of complications other than PAL, and cost of hospitalization care were also analyzed.PAL was observed in 91 (4.0%) cases. Multivariate logistic regression analysis revealed that the presence of intrathoracic adhesion (odds ratio [OR] 4.476, p 0.001), smoking history 20 pack-year (OR 2.441, p = 0.005), male sex (OR 2.269, p = 0.013), and lobectomy or bilobectomy (OR 1.935, p = 0.025) were significant risk factors for PAL. The presence of PAL was related to the development of additional complications (p 0.001). The cost of hospitalization care in patients with PAL was about 1.3 times higher than that in patients without PAL (p 0.001).PAL is related to additional complications and higher cost of hospitalization care. Surgeons should pay careful attention to minimize the incidence of PAL in patients with risk factors including intrathoracic adhesion, history of heavy smoking, male sex, and lobectomy or bilobectomy.

Insulated molecular wires have gained significant attention owing to their potential contribution in the fields of nanoelectronics and low-dimensional chemistry/physics. Based on molecular charge transfer salts, we demonstrate, for the first time, the rational construction of molecular electron-conducting wires encapsulated in a proton-conducting matrix, which possibly paves the way to ionoelectronics. As expected from the molecular structure of the newly designed complex anion (i.e., propeller-shaped structure with hydrogen-bonding sites at four edges), a three-dimensional hydrogen-bonded framework was constructed within the crystal, which contains a one-dimensional array of an electron donor, tetrathiafulvalene (TTF). From the single-crystal crystallographic and spectroscopic studies, it was clarified that the nonstoichiometric deprotonation of anions and partial oxidation of TTFs occur, whereas the anion is electronically inert. Moderate conductivities of electron and proton were confirmed by dc and ac conductivity measurements. In addition, the electronic isolation of TTF wires was confirmed by the magnetic susceptibility data.

Reactions of (dppe)NiCl2 (dppe = 1,2-bis(diphenylphosphino)ethane) with chlorido-substituted phenyl thiolates (RClS−) produced the corresponding nickel thiolate complexes (dppe)Ni(SRCl)2 (RCl = 3,5-C6H3Cl2 (1), C6Cl5 (2)) in high isolated yields. Complexes 1 and 2 were characterized by spectroscopic techniques such as (UV–Vis, IR, 1H-, 31P{1H}-, 13C{1H}-NMR) as well as elemental analysis. The molecular structures of complexes 1 and 2, determined by X-ray diffraction measurements, have a cis square planar geometry.

Serological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect antibodies against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various antigen-specific antibody isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via polymerase chain reaction test. We developed IgG, IgM and IgA measurement assays for each antigen, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full length S protein, S trimer and nucleocapsid (N) domain, based on enzyme-linked immunosorbent assay. The assays of the S protein for all isotypes showed high specificity, while the assays for all isotypes against N protein showed lower specificity. The sensitivity of all antigen-specific antibody isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 days post-symptom onset. The best correlation with virus neutralizing activity was found for IgG against RBD (RBD-IgG), and levels of RBD-IgG in sera from four severe COVID-19 patients increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.

Ferroelectric spin crossover (SCO) behavior is demonstrated to occur in the cobalt(II) complex, [Co(FPh-terpy)2 ](BPh4 )2 ⋅3ac (1⋅3 ac; FPh-terpy=4'-((3-fluorophenyl)ethynyl)-2,2':6',2''-terpyridine) and is dependent on the degree of 180° flip-flop motion of the ligand's polar fluorophenyl ring. Single crystal X-ray structures at several temperatures confirmed the flip-flop motion of fluorobenzene ring and also gave evidence for the SCO behavior with the latter behavior also confirmed by magnetic susceptibility measurements. The molecular motion of the fluorobenzene ring was also revealed using solid-state 19 F NMR spectroscopy. Thus the SCO behavior is accompanied by the flip-flop motion of the fluorobenzene ring, leading to destabilization of the low spin cobalt(II) state; with the magnitude of rotation able to be controlled by an electric field. This first example of spin-state conversion being dependent on the molecular motion of a ligand-appended fluorobenzene ring in a SCO cobalt(II) compound provides new insight for the design of a new category of molecule-based magnetoelectric materials.

Objective Delineation of the intersegmental plane during pulmonary segmentectomy by systemic injection of indocyanine green (ICG) has been rapidly emerging. We evaluated the feasibility of the use of ICG in a large-scale cohort according to the type of segmentectomy and the presence of obstructive lung disorder and compared the demarcation status with air injection. Methods We collected the data of 209 patients who underwent segmentectomy using ICG at National Cancer Center Hospital, Tokyo, Japan. Data of the operation including the demarcation status of the intersegmental plane were analyzed retrospectively. Results The median operation duration and blood loss were 105 minutes (interquartile range, 94-118 minutes) and 12 mL (interquartile range, 5-24 mL), respectively. Good demarcation of the intersegmental plane by ICG was observed in 184 (88.0%) cases, with no correlation to the type of resected segments or the presence of obstructive lung disorder. Postoperative complications of Clavien–Dindo classification grade 3 or more were observed in 5 cases (2.4%), and no ICG-related adverse event was noted. High-frequency jet ventilation was also used in 160 cases (76.6%) to delineate the intersegmental inflation–deflation plane. The air injected by high-frequency jet ventilation tended to spread further beyond the intersegmental plane that was depicted by ICG. Conclusions The use of ICG might demarcate the intersegmental plane more restricted to the target segment compared with air injection. Delineation of the intersegmental plane by ICG is feasible regardless of the type of segmentectomy or the presence of obstructive lung disorder, and it can be commonly applicable in pulmonary segmentectomy., Graphical abstract

Proton-coupled electron transfer (PCET) of metal complexes has been widely studied, especially in biochemistry and catalytic chemistry. Although metal complexes bearing redox-active ligands play a part in these research areas, those with π-planar structure remain entirely unexplored, which are vital for future development of iono-electronics. Here, proton-electron coupling of a π-planar nickel complex bearing redox-active N, S-ligands, Ni(itsq)2, was investigated by combining experimental and theoretical approaches. Strong proton-electron coupling was manifested in a large potential shift, which is twice greater than that of a typical PCET-type π-planar metal complex with redox-inactive ligands, [Ni(dcpdt)₂]²⁻. Theoretical calculations affirmed that the stabilization of frontier orbitals by protonation is greater in Ni(itsq)2 than that in [Ni(dcpdt)₂]²⁻. These results indicate that π-planar metal complexes with redox-active ligands are promising for developing novel PCET-type materials.

A cardiac herniation is a rare but life-threatening complication after pneumonectomy. In most cases, it manifests suddenly as severe hypotension and cardiac arrest within 24 h of pneumonectomy. Here, we report a case of sudden-onset cardiac herniation after right pneumonectomy during which the pericardium was incised. The diagnosis was made immediately based on chest X-ray and electrocardiogram findings, and the heart was repositioned by repeat thoracotomy as an urgent life-saving measure. Surgeons should be aware of this potential surgical complication as well as its clinical manifestations, given that delayed diagnosis would directly lead to a fatal outcome.

The 8th edition of the TNM stage classification of lung cancer was developed based on an evaluation of the 5-year prognosis using an international database. Since recurrence after 5 years postoperatively is known to develop, the applicability of the stage classification beyond 5 years after treatment needs to be evaluated.Postoperative prognosis and prognostic indicators were analyzed using data for 648 patients of pathological stage IA adenocarcinoma, who underwent complete resection between 2007 and 2012.The median age was 66 years (interquartile range 60-73 years), and the median follow-up duration was 100 months (interquartile range 70-116 months). Overall survival probabilities for pathological stage IA1, IA2, and IA3 patients were 100%, 96.3%, and 91.5% at 5 postoperative years, and 94.2%, 89.8%, and 83.5% at 10 postoperative years, respectively (IA1 vs IA2: p = 0.05; IA2 vs IA3: p = 0.05). Multivariate analysis for overall survival of patients who survived without recurrence for 5 postoperative years revealed that age (hazard ratio 3.21, p = 0.02) was the only factor that was significantly associated with long-term survival. Stage classification (IA1, IA2, or IA3) was not an associated factor. The incidence of secondary primary lung cancer continued to increase, resulting in an estimated probability of 8.6% at 10 postoperative years.For patients who survived without recurrence for 5 postoperative years, age, not stage classification, was associated with survival thereafter. The long-term follow-up strategy does not need to be modified according to the stage classification, and screening for secondary primary lung cancer should be considered.

Objectives The aim of JCOG1610 (randomized controlled phase III trial) was to confirm the superiority of preoperative denosumab to curettage with adjuvant local therapy for patients with giant cell tumor of bone without possible post-operative large bone defect. Methods The primary endpoint was relapse-free survival and the total sample size was set at 106 patients. Patient accrual began in October 2017. However, the accrual was terminated in December 2020 due to a recommendation from the Data and Safety Monitoring Committee because of poor patient accrual. Now, we report the descriptive results obtained in this study. Results A total of 18 patients had been registered from 13 Japanese institutions at the time of termination on December 2020. Eleven patients were assigned to Arm A (curettage and adjuvant local therapy) and 7 to Arm B (preoperative denosumab, curettage and adjuvant local therapy). Median follow-up period was 1.6 (range: 0.5–2.8) years. Protocol treatment was completed in all but one patient in Arm A who had a pathological fracture before surgery. All patients in Arm B were treated with five courses of preoperative denosumab. Relapse-free survival proportions in Arm A and B were 90.0% (95% confidence interval: 47.3–98.5) and 100% (100–100) at 1 year, and 60.0% (19.0–85.5) and 62.5% (14.2–89.3) at 2 years, respectively [hazard ratio (95% confidence interval): 1.51 (0.24–9.41)]. Conclusion In terms of relapse-free survival, the superiority of preoperative denosumab was not observed in patients with giant cell tumor of bone without possible post-operative large bone defect.

OBJECTIVES The prognosis of patients with mediastinal lymph node (LN) metastasis (pN2 stage III disease) is still unsatisfactory. Both systemic and local recurrence should be prevented after curative surgery. The aim of this study was to explore the pattern of recurrence in patients with completely resected pN2 non-small-cell lung cancer (NSCLC) in the era of adjuvant chemotherapy. METHODS We investigated 337 patients with completely resected cN0-1 and pN2 NSCLC from 2005 to 2016 at National Cancer Center Hospital, Japan. The patterns of recurrence were compared between patients who were managed by observation alone and those with adjuvant chemotherapy. In patients with regional LN recurrence, the pattern and site of recurrence were also explored. RESULTS There were 195 (58.5%) men and 142 (41.5%) women with a mean age of 63.2 years. Fifty-five (16.3%) patients developed only regional LN recurrence, 116 (32.6%) patients developed only distant recurrence and 65 (19.3%) patients developed both regional LN recurrence and distant recurrence. The difference in the pattern of recurrence between patients with observation alone and those with adjuvant chemotherapy was not statistically significant (P = 0.145). As for the pattern of regional LN recurrence, 68 (20.2%) patients had LN recurrence inside the systematic nodal dissection area. CONCLUSIONS Regional LN recurrence was observed in >30% of patients with completely resected pN2 NSCLC. About 20% of patients had recurrence inside the systematic nodal dissection area. Postoperative radiotherapy might be considered as an additional treatment strategy for these patients.

The ET•+ molecules in a charge-transfer salt (ET)Ag4(CN)5 form a three-dimensional diamond spin-lattice with S = 1/2 (ET: bis(ethylenedithio)tetrathiafulvalene), where a geometrical spin-frustratio...

Introduction This study explored the predictors of a histological aggressive component in ground glass opacity-containing lung adenocarcinoma. Methods Of the 2388 patients who underwent resection for lung cancer at our institute between 2017 and 2020, we collected data on the 501 patients with ground glass opacity-containing adenocarcinoma with a total diameter of ≤2 cm. Using a historical cohort, we identified histological aggressive components that were related to a poor prognosis in early-stage adenocarcinoma. A multivariable analysis was conducted to identify predictors for the presence of a histological aggressive component. Results Lymphovascular invasion and predominant micropapillary or solid patterns were identified as histological aggressive components by a prognostic analysis using a historical cohort. Of the 501 patients included, 36 (7.2%) had at least one histological aggressive component. A multivariate analysis showed that a consolidation/tumour ratio > 0.5 (P 20 pack-years (P = 0.01) were predictors of the presence of a histological aggressive component. A total of 98% of cases without any of the above factors did not have a histological aggressive component. Conclusions Approximately 7% of ground glass opacity-containing small adenocarcinomas contained histological aggressive component. A consolidation/tumour ratio > 0.5, maximum standardized uptake value ≥ 1.5 and smoking index >20 pack-years were predictors for such cases. These predictors may be useful for screening patients with a potentially high risk of a poor prognosis and for prioritizing resection without delay.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

Background Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. Methods Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. Results A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor p = 0.070). Conclusion The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. Trial registration UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer deaths worldwide. Surgery or surgery plus radiotherapy and/or chemotherapy for patients with metastatic CRC (mCRC) were accepted as the main therapeutic strategies until the early 2000s, when targeted drugs, like cetuximab and bevacizumab, were developed. The use of targeted drugs in clinical practice has significantly increased patients’ overall survival. To date, the emergence of several types of targeted drugs has opened new possibilities and revealed new prospects for mCRC treatment. Therapeutic strategies are continually being updated to select the most suitable targeted drugs based on the results of clinical trials that are currently underway. This review discusses the up-to date molecular evidence of targeted therapy for mCRC and summarizes the Food and Drug Administration-approved targeted drugs including the results of clinical trials. We also explain their mechanisms of action and how these affect the choice of a suitable targeted therapy.

We report the synthesis of molybdenum–ruthenium–carbon alloy nanoparticles with molybdenum-rich composition by an annealing treatment following a thermal decomposition. We first found its supercond...

A reversible transformation between 1D, 2D, and 3D is demonstrated for the first time in coordination polymers comprising Cu

The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the histologically predominant subtype and high-grade component. Because the predominant subtypes are associated with characteristic subsets, unique subsets can be identified by this grading system.We analyzed the clinicopathologic, genotypic, and prognostic features of a cohort of 781 consecutive patients with invasive nonmucinous adenocarcinoma of the lung.Grade 3 tumors were associated with younger age, male sex, a higher smoking dose, and aggressive features (tumor size, lymph node metastasis, stage, lymphovascular invasion, and pleural invasion). Recurrence-free survival and 3-year overall survival were well-stratified according to tumor grade, and the differences were confirmed with multivariate analysis using the Cox proportional hazard model. Radiologically, most grade 3 tumors exhibit a solid nodular pattern on computed tomography images and a high maximum standardized uptake value with positron emission tomography. Genotypically, 43% of the grade 3 adenocarcinomas lacked any driver mutations, although one of the driver mutations was detected in 79% of grade 1 or 2 tumors. Patient age, positive smoking history, solid nodule on computed tomography image, and higher maximum standardized uptake value were identified as significant preoperative predictive factors of grade 3 tumors, with a prediction rate greater than 90%.Besides stratifying the patient outcomes, the new grading system characterized unique clinicopathologic subsets and this study suggested that grade 3 tumors could be predicted using the preoperative variables.

Metal string complexes, linearly aligned transition metal arrays coordinated with the multidentate organic ligands, have gained much attention both in unique electronic/structural properties and in potential applications as conductive molecular nanowires. Here we report on a dimerized Ni

A molecule-based mixed conductor of proton and electron was synthesized by modifying a nickel(III) dithiolene complex with 1,4-naphthoquinone skeletons. The complex forms a π-stacking column flanke...