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Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (HE)-stained frozen sections is the gold standard, but reliable pathology requires time-consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid-IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3-6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple HE staining. With HE staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors.

The diagnosis of mesothelioma in situ (MIS) is challenging with conventional diagnostic approaches. Although recent advances in genomic-based assays have made it possible to diagnose MIS, the prognosis, treatment indications, and prognostic factors remain unclear. Previous reports have shown that MIS progresses to invasive mesothelioma; however, to the best of our knowledge, progression to sarcomatoid mesothelioma has not yet been reported. A 73-year-old man was diagnosed with MIS associated with methylthioadenosine phosphorylase (MTAP) loss and a CDKN2A homozygous deletion. Strikingly, pathological examination revealed that the MIS lesion had progressed to sarcomatoid mesothelioma. In analyses of previously reported cases and our case, MIS with a CDKN2A homozygous deletion or MTAP loss progressed to invasive mesothelioma earlier than that without them, indicating that a CDKN2A homozygous deletion and MTAP loss could be poor prognostic factors. Genomic analyses might be useful for predicting the prognosis of MIS and contributing to an optimal treatment.

Background Smoking is a known risk factor for postoperative mortality and morbidity. However, the significance of cumulative smoking dose in preoperative risk assessment has not been established. We examined the influence of preoperative cumulative smoking dose on surgical outcomes after lobectomy for primary lung cancer. Methods A total of 80,989 patients with primary lung cancer undergoing lobectomy from 2014 to 2016 were enrolled. Preoperative cumulative smoking dose was categorized by pack-years (PY): nonsmokers, PY = 0; light smokers, 0 < PY < 10; moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. The risk of short-term outcomes was assessed according to PY by multivariable analysis adjusted for other covariates. Results Postoperative 30-day mortality, as well as pulmonary, cardiovascular, and infectious complications, increased with preoperative PY. Multivariable analysis revealed that the odds ratios (ORs) for postoperative mortality compared with nonsmokers were 1.76 for light smokers (P = .044), 1.60 for moderate smokers (P = .026), and 1.73 for heavy smokers (P = .003). The ORs for pulmonary complications compared with nonsmokers were 1.20 for light smokers (P = .022), 1.40 for moderate smokers (P < .001), and 1.72 for heavy smokers (P < .001). Heavy smokers had a significantly increased risk of postoperative cardiovascular (OR, 1.26; P = .002) and infectious (OR, 1.39; P = .007) complications compared with nonsmokers. Conclusions The risk of mortality and morbidity after lung resection could be predicted according to preoperative cumulative smoking dose. These findings contribute to the development of strategies in perioperative management of lung resection patients.

Adhesiolysis is often necessary in intrathoracic adhesion during ipsilateral repeat lung resection. This procedure has a risk of surgical complications, including unintentional intraoperative damage of the pulmonary vessels or lung parenchyma. We used an oxidized regenerated cellulose (ORC) sheet to prevent intrathoracic adhesion after lung resection in 55 patients. The sheet was placed on the surface of the resected region and on the lung surface under the wound. No major postoperative complications were observed. Three cases underwent ipsilateral thoracic surgery for the treatment of lung malignancies, and there were no intrathoracic adhesions around the ORC sheet-covered area.

Purpose Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur–uracil (UFT) as postoperative adjuvant chemotherapy. Methods The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. Results The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. Conclusions The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. Clinical trial registration This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

Managing thoracic empyema with massive air leakage can be challenging. We present a case with thoracic empyema with multiple bronchopleural fistulae and extensive lung parenchymal necrosis due to drain injury. Emergency surgery was performed for respiratory distress due to massive air leakage. As direct sutures could not be achieved due to extensive parenchymal necrosis, polyglycolic acid and oxidized regenerated cellulose sheets were packed into the lesion. Although open-window thoracostomy was required for bronchopleural fistulae, the stoma closure was achieved via vacuum-assisted closure therapy. The dual sheet coverings contributed to the successful recovery by resolving multiple bronchopleural fistulae.

Background Large mediastinal tumors are sometimes difficult to completely resect because they are surrounded by vital organs. We present the case of mediastinal liposarcoma successfully resected by the clamshell approach with a posterior pericardial wall incision. Case presentation An 81-year-old man visited the hospital because of a prolonged cough. Imaging studies revealed a large tumor of the left posterior mediastinum. The tumor surrounded the left inferior pulmonary vein and was suspected of invading the left lower lobe and esophagus. Complete resection of a large mediastinal tumor invading the left inferior pulmonary vein and esophagus was achieved by adding a posterior pericardial wall incision to the clamshell approach under cardiopulmonary bypass. Histopathological diagnosis was well-differentiated liposarcoma. Postoperative course was good, and the patient is alive without any sign of recurrence for 53 months. Conclusions This approach could represent a novel method to safely and effectively remove large mediastinal tumors invading the lung and esophagus.

Background: It had been difficult to distinguish between reactive and malignant conditions due to overlapping morphological characteristics. The development of methods based on detecting genomic abnormalities using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have contributed greatly to solving this problem. In order to lead it to efficient IHC and/or FISH and final diagnosis of mesothelioma, it is important to pick up bland mesothelioma cells on cytological screening because the first clinical manifestation of pleural mesothelioma (PM) is pleural effusion, which is first sample available for pathological diagnosis.Case presentation: This report describes a case of a 72-year-old man with a history of asbestos exposure presented with pleural effusion as first symptoms and was eventually diagnosed as mesothelioma. He was suspected for mesothelioma on cytology due to prominent cell-in-cell engulfment in mesothelial cells, and the diagnosis of mesothelioma in situ was confirmed by histology. Unexpectedly, the lesion progressed to sarcomatoid mesothelioma with 9 months interval. Both the initial mesothelioma in situ and invasive lesion showed immunohistochemical loss of methylthioadenosine phosphorylase (MTAP) and homozygous deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) on fluorescence in situ hybridization. The patient received medication therapy after the diagnosis of sarcomatoid mesothelioma, but the disease progressed and died 12 months after the diagnosis of sarcomatoid mesothelioma.Conclusion: Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early progression to invasive lesions and/or sarcomatoid changes. Although interest in and knowledge regarding mesothelioma in situ has been increasing, some diagnostic problems can be challenging even for experts. In our opinion, it is important to consider genetic abnormalities when deciding on individual patient management. At least, we believe that cases of mesothelioma, even if in situ lesion, with MTAP loss and/or CDKN2A deletion should be performed carefully followed up or early treatment intervention.

Background Fibrous bands (FBs) are one of the histological features in tumors which can be confirmed by hematoxylin and eosin (H&E)‐stained slides. FBs have been reported to correlate with malignancy in various tumors. This study aimed to investigate whether the presence of FBs is associated with malignancy in thymoma. Methods A total of 123 consecutive patients with thymoma who underwent microscopically complete resections from January 2000 to December 2018 were enrolled into this study. H&E‐stained slides of all thymoma patients were re‐examined. Study patients were classified into two groups: with FBs (n = 36) and without FBs (n = 87). Clinicopathological characteristics, overall survival (OS), and recurrence‐free survival (RFS) were compared between the two groups. Furthermore, multivariate analyses were performed to identify whether the presence of FBs was associated with higher Masaoka stage and poor prognosis in patients with thymoma. Results The Masaoka stage was found to be higher and recurrence more likely in thymoma patients with FBs than in those without. RFS was significantly poorer in thymoma patients with FBs than in those without, although no significant difference was observed in OS between them. The presence of FBs was significantly associated with higher Masaoka stage in the multivariate analysis using logistic regression. Additionally, the presence of FBs was an independent prognostic factor for poor RFS in multivariate analysis using Cox's proportional hazards model. Conclusions The presence of FBs in patients with thymoma was associated with higher Masaoka stage, higher recurrence rate, and poorer RFS. Key points Significant findings of the study Fibrous bands (FBs) are bands of fibrosis dividing tumors into different‐sized irregular islands. The presence of FBs is associated with higher Masaoka stage and poor recurrence‐free survival in patients with thymoma. What this study adds The presence of fibrous bands might be associated with the malignant behavior of thymoma. Confirming the presence or absence of FBs may result in personalized medication for patients with thymoma., • Fibrous bands (FBs) are bands of fibrosis dividing tumors into different‐sized irregular islands. • The presence of FBs is associated with the malignant behavior of thymomas. • Confirmation of FBs might lead to individualized medications in patients with thymoma.

The rotational spectra of 1-butanol (1-BuOH), 1-butanethiol (1-BuSH), 2-methyl-1-propanol (iso-BuOH), and 2-methyl-1-propanethiol (iso-BuSH) were measured by Fourier transform microwave spectroscopy in the frequency region from 3.7 up to 25 GHz. The observed spectral lines were assigned by observation of the deuterium substitution effect and by ab initio or density functional theory calculations at the levels of MP2/6-311++G(d,p) or B3LYP and cam-B3LYP, respectively. For 1-BuOH and 1-BuSH, seven of the 14 conformations, anticipated to exist as stable, were detected, whereas four and three among the five possible conformations were identified for iso-BuOH and iso-BuSH, respectively. We further found that, of the seven conformers of 1-BuOH, five were trans and two gauche, with respect to the internal rotation axis: the C2-C3 bond, while three of iso-BuOH existed in gauche and one in trans. The most stable conformer of the two BuOH molecules was trans with respect to the C-O bond, while all the sulfur analogues were gauche to the C-S axis. The rare isotopomers examined included 13C and OD of 1-BuOH and OD of iso-BuOH, 34S, 13C, and SD of the two sulfur molecules, and the rotational constants obtained on these isotopomers were employed in the molecular structure derivation. The potential barrier to CH3 internal rotation and the deuterium quadrupole coupling constant, where available, were also derived from the spectral analysis, and the molecular parameters thus obtained were compared with those derived using quantum-chemical calculations; the values derived using cam-B3LYP/6-311++G(d,p) were in better agreement with the observed than those derived using MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p). The TTg form of 1-BuOH and of 1-BuSH and the Tg form of iso-BuSH exhibited additional spectral splittings, which were interpreted as caused by the OH or SH group tunneling between the symmetric and antisymmetric states. Some of the J = 8 rotational levels of 1-BuSH happened to be near-degenerate with others, and the splittings in them caused by mutual repulsion could be precisely determined by the observation of the transitions involving those split levels. Such splittings were determined for 1-BuSH, 1-BuSD, and iso-BuSH to be 1694.1731 (22), 56.3174 (16), and 6.4678 (14) MHz, respectively. A natural bond orbital analysis was performed to show that the most stable conformation of the primary and secondary alcohols is Gt because of the charge transfer from the lone-pair electron of the oxygen atom to the antibonding orbital of the C-H bond in 1-BuOH, whereas in iso-BuOH, the charge transfer to the antibonding orbital of the C1-C2 bond.

Purpose Caspase recruitment domain-containing protein 9 (CARD9) is expressed at high levels in bone marrow cells and has a crucial role in innate immunity. Current studies indicate that CARD9 also plays a key role in tumor progression, but there are few reports on the role of CARD9 in lung cancer. The aim of this study was to clarify the role of CARD9 in lung adenocarcinoma. Patients and methods Lung adenocarcinoma tumor samples from 74 patients who underwent complete resection at Kobe University Hospital from January 2014 to December 2014 were analyzed by immunohistochemistry. The role of CARD9 in cancer cells was analyzed using lung cancer cell lines treated with CARD9 siRNA. Results High expression of CARD9 was observed in 32.4% of tumors, and compared to low expression of CARD9, high expression was associated with poorer overall survival (P = 0.0365). Univariate and multivariate analyses showed that high expression of CARD9 was an independent prognostic factor. Knockdown of CARD9 in lung adenocarcinoma cells inhibited proliferation but did not increase apoptosis. In addition, CARD9 activated the NF-κB pathway in a lung adenocarcinoma cell line. Conclusion CARD9 was shown to be an independent prognostic factor of poor outcome for lung cancer and may represent a molecular target for treatment.

Background Cisplatin (CDDP) and vinorelbine as an adjuvant chemotherapy improve the overall survival of patients with completely resected non‐small cell lung cancer (NSCLC). However, the treatment completion rate is low due to severe adverse events (AEs). Pemetrexed (PEM) has been used in advanced NSCLC due to its high safety and efficacy. Additionally, the safety of a short hydration method for CDDP administration has been previously reported. Here, we investigated the feasibility of CDDP plus PEM with a short hydration method as adjuvant chemotherapy. Methods A total of 21 completely resected nonsquamous NSCLC patients with pathological stage IIA to IIIA disease were enrolled into the study. Adjuvant chemotherapy consisted of four cycles of CDDP (75 mg/m2) plus PEM (500 mg/m2) every three weeks with a short hydration method. The primary endpoint was the treatment completion rate, and the secondary endpoints included toxicity, the two‐year relapse‐free survival (RFS) rate, and the outpatient treatment rate. Results A total of 21 patients (median age: 66 years; 12 males) were enrolled in two centers. All cases were adenocarcinoma with PS0 (71.4%) or PS1 (28.6%). A total of 81.0% of the patients received four cycles of therapy as scheduled and the primary endpoint was met. The rate of outpatient chemotherapy completion after the second cycle was 90.5%. The grade 3 or higher toxicities were anorexia (n = 2) and pulmonary thromboembolism (n = 1). No grade 3/4 hematological toxicities or creatinine level elevations were observed. The two‐year RFS rate was 57.3%. Conclusions CDDP and PEM with a short hydration is well tolerated in the outpatient setting with limited toxicity. Key points Significant findings of the study CDDP plus PEM adjuvant therapy with a short hydration method is well tolerated in the outpatient setting with limited toxicity. What this study adds CDDP plus PEM with a short hydration method has the potential to be one of the options of adjuvant therapy in the future., CDDP plus PEM adjuvant therapy with a short hydration method is well tolerated in the outpatient setting with limited toxicity.

OBJECTIVES Thoracotomy is a reliable approach for descending necrotizing mediastinitis (DNM), and the use of video-assisted thoracic surgery (VATS), a minimally invasive procedure, has been increasing. However, which approach is more effective for DNM treatment is controversial. METHODS We analysed patients who underwent mediastinal drainage via VATS or thoracotomy, using a database with DNM from 2012 to 2016 in Japan, which was constructed by the Japanese Association for Chest Surgery and the Japan Broncho-esophagological Society. The primary outcome was 90-day mortality, and the adjusted risk difference between the VATS and thoracotomy groups using a regression model, which incorporated the propensity score, was estimated. RESULTS VATS was performed on 83 patients and thoracotomy on 58 patients. Patients with a poor performance status commonly underwent VATS. Meanwhile, patients with infection extending to both the anterior and posterior lower mediastinum frequently underwent thoracotomy. Although the postoperative 90-day mortality was different between the VATS and thoracotomy groups (4.8% vs 8.6%), the adjusted risk difference was almost the same, −0.0077 with 95% confidence interval of −0.0959 to 0.0805 (P = 0.8649). Moreover, we could not find any clinical and statistical differences between the 2 groups in terms of postoperative 30-day and 1-year mortality. Although patients who underwent VATS had higher postoperative complication (53.0% vs 24.1%) and reoperation (37.9% vs 15.5%) rates than those who underwent thoracotomy, the complications were not serious and most could be treated with reoperation and intensive care. CONCLUSIONS The outcome of DNM treatment does not depend on thoracotomy or VATS.

Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma.ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction.High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines.ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

BackgroundAlthough COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported.MethodsWe investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination.ResultsAnti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups.ConclusionAlthough there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.Mini abstractTiters of anti-S1 antibody after the second dose of BNT162b2 were significantly lower in patients with solid tumors undergoing active anticancer treatment than in the healthy volunteers.

Purpose Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors >4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC. Patients and methods Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit. Results Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4-83.7). Two-year RFS was 56.8% (95% CI, 29.7-76.9). Conclusion The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.

Background Partner of Sld five 3 (Psf3) is a member of the heterotetrameric complex that consists of SLD5, Psf1, Psf2, and Psf3. We have shown in previous studies that high Psf3 expression was a poor prognostic marker for pulmonary adenocarcinoma. Here, we statistically evaluated the relationship between clinicopathologic factors and Psf3 expression in stage I pulmonary adenocarcinoma. Methods A total of 583 patients who had undergone complete resection of stage I pulmonary adenocarcinoma from January 2002 to December 2009 were included in the study. Tissue microarrays were performed, and the resected tumors were divided into groups according to Psf3 expression. Results Of 583 patients, high expression of Psf3 was observed in 211 (36.2%) and low expression of Psf3 observed in 372 (63.8%) patients. Among stage I patients, the five-year survival rate was 76.7% in the Psf3 high expression group and 90.9% in the Psf3 low expression group (P < 0.0001). On multivariate analysis, Psf3 was found to be the independent prognostic factor. Among stage I patients in the Psf3 high expression group, a significantly greater five-year survival rate was observed in patients who received postoperative chemotherapy with tegafur-uracil than in those who underwent surgery alone (P < 0.0001). In contrast, among stage I patients in the Psf3 low expression group, no difference was found in the five-year survival, regardless of the presence or absence of tegafur-uracil (P = 0.873). Conclusion The Psf3 expression was an independent prognostic factor and could be a biomarker of adjuvant tegafur-uracil for stage I pulmonary adenocarcinoma. Key points Significant findings of the study: The Psf3 expression could be a biomarker of adjuvant tegafur-uracil administration for stage I pulmonary adenocarcinoma. What this study adds: Appropriate patients of adjuvant chemotherapy for stage I pulmonary adenocarcinoma using Psf3 expression could be selected.

Malignant pleural mesothelioma (MPM), associated with unfavorable outcomes, is closely associated with asbestos exposure. Early detection and treatment are critical to prolong survival of patients with MPM because of the rapid progression and resistance to treatment. The recently defined malignant mesothelioma in situ (MIS) has been gaining increasing attention with advances in genome-based methods including fluorescence in situ hybridization (FISH) as well as immunohistochemistry. We herein report the case of a MIS in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity. Video-assisted thoracoscopic surgery with pleural biopsy of the right side revealed a single layer of atypical mesothelial cells without invasive lesions by hematoxylin and eosin staining. However, these mesothelial cells exhibited a loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry and homozygous deletion of CDKN2A (p16) by FISH, leading to the diagnosis of MIS.

Background: The efficacy of diaphragmatic plication (DP) has been proven in many studies. However, there are few reports on DP for patients with severe respiratory conditions requiring mechanical ventilation. The study aim was to demonstrate the efficacy of DP for patients with severe respiratory insufficiency after cardiothoracic surgeries. Methods: We retrospectively reviewed 10 patients who underwent DP for severe respiratory insufficiency due to postoperative diaphragmatic paralysis; eight of them required mechanical ventilation, and two needed high-flow oxygen therapy prior to DP. The symptoms, lung function, and elevation of the diaphragm were assessed before and after DP. Results: All patients were successfully withdrawn from mechanical ventilation after DP and discharged without the need for oxygen therapy. The mean perioperative Medical Research Council (MRC) dyspnea scale (ATS/ERS 2004) score improved in 30 days (from 4 to 1.8) and in 90 days (from 4 to 0.6) after DP. Lung dynamic compliance was also ameliorated (mean improvement: 41.9 to 60.7 mL/cmH 2 O). Radiography revealed improved elevation of the diaphragm (mean improvement of 1.8 intercostal spaces, range, 1–2). Mean hospital stay after DP was 65.5 days (range, 25–187 days). One patient who underwent DP with endostapler-only suturing required re-operation because of staple line ruptures. Conclusions: DP was found to be an effective form of treatment for patients with severe respiratory insufficiency after cardiothoracic surgery.

Background: Large-cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are categorized as high-grade neuroendocrine carcinoma (HGNEC). We analyzed the efficacy of perioperative chemotherapy for HGNEC and the prognostic factors. Methods: We retrospectively reviewed the medical records of patients who underwent tumor resection and were diagnosed with HGNEC between January 2001 and December 2014. The overall survival (OS) was estimated by the Kaplan-Meier method. Propensity score matching was performed to compare the OS between the treatment groups. Multivariate analyses using a Cox proportional hazards model were performed to search for prognostic factors for HGNEC. Results: We analyzed 146 HGNEC patients (LCNEC n=92, SCLC n=54) without synchronous multiple cancers, who underwent complete resection. Seventy patients (LCNEC n=31, SCLC n=32) received perioperative chemotherapy and all of them received a platinum-based anticancer drug. Perioperative chemotherapy significantly improved the 5-year OS rates of HGNEC patients (all stages: 74.5% vs. 34.7%, P

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.

The genus Shewanella comprises over 70 species of heterotrophic bacteria with versatile respiratory capacities. Some of these bacteria are known to be pathogens of fishes and animals, while many are non-pathogens considered to play important roles in the global carbon cycle. A representative strain is Shewanella oneidensis MR-1 that has been intensively studied for its ability to respire diverse electron acceptors, such as oxygen, nitrate, sulfur compounds, metals, and organics. In addition, studies have been focused on its ability as an electrochemically active bacterium that is capable of discharging electrons to and receiving electrons from electrodes in bioelectrochemical systems (BESs) for balancing intracellular redox states. This ability is expected to be applied to electro-fermentation (EF) for producing value-added chemicals that conventional fermentation technologies are difficult to produce efficiently. Researchers are also attempting to utilize its electrochemical ability for controlling gene expression, for which electro-genetics (EG) has been coined. Here we review fundamental knowledge on this bacterium and discuss future directions of studies on its applications to electro-biotechnology (EB).

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of various diseases, including cancer. As such, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively and prospectively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were retrospectively performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.

A 63‐year‐old man suspected of having lung cancer underwent right upper lobectomy and was diagnosed with large cell neuroendocrine carcinoma (LCNEC). Eleven months after surgery, he developed an oligorecurrence in the adrenal gland and underwent left adrenalectomy. The specimen revealed LCNEC metastasis. Forty‐one months after surgery, enlargement of a lesion near the surgical site was seen. Biopsy showed LCNEC metastasis and he is currently undergoing radiotherapy for the recurrent lesion. We report a case of LCNEC with adrenal gland oligorecurrence treated by adrenalectomy, which led to long‐term survival., We report a case of large cell neuroendocrine carcinoma (LCNEC) with adrenal gland oligorecurrence treated by adrenalectomy, which led to long‐term survival.

Backgrounds and objectives Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of pulmonary neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with pulmonary high-grade neuroendocrine carcinomas (HGNEC) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients. Methods Seventy-five consecutive patients with HGNEC who underwent complete surgical resections from January 2000 to December 2018 were enrolled in this study. We classified these patients into two groups: the INSM1-positive group (n = 59) and INSM1-negative group (n = 16). We compared the clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) between the groups. In addition, we performed univariate and multivariate analyses to identify the prognostic factors associated with postoperative survival. Results Significant differences in tumor diameter and vascular invasion between the groups were found. OS and RFS were significantly poorer in the INSM1-positive group than in the INSM1-negative group. Univariate and multivariate analyses revealed that INSM1 expression was the strongest predictor of poor prognosis for OS and RFS. Conclusions INSM1 expression had the greatest influence on the prognosis in patients with HGNEC and may be a prognostic biomarker in these patients.