Quality of life, psychological states, and personality traits in patients with pectus excavatum.

Objective: The quality of life (QOL) and psychological states of patients with pectus excavatum (PE) have yet to be well understood. This study aimed to evaluate the health-related QOL (HRQOL), psychological states, and personality traits of patients with PE, alongside the associations of these factors with the severity of PE. Methods: A cross-sectional evaluation was prospectively performed in patients scheduled to undergo PE repair surgery between July 2019 and April 2021. The primary outcome was the patients' HRQOL, and the secondary outcomes were depression, social anxiety, self-efficacy, and personality traits. Results: In total, 129 patients were subjected to analyses. Patients' HRQOL had a lower role component summary score (mean ± standard deviation: 41.8 ± 12.8, P < .001) than the general population controls. Patients' HRQOL had a significantly better physical component summary (54.0 ± 10.4, P < .001) and mental component summary (53.3 ± 8.8, P < .001) than that of the general population. Fourteen patients' (10.9%) and 56 patients' (43.4%) scores indicated the presence of depression and social anxiety disorder, respectively. Patients' self-efficacy (46.1 ± 11.4, P, .001) and level of extraversion (46.5 ± 11.8, P < .001) were lower than those of the general population. No significant correlation was found between the severity of PE and these scores. Conclusions: Our study revealed that patients with PE had decreased social-role QOL, depressive tendencies, increased social anxiety, lower self-efficacy, and introversion. No correlation between the severity of PE and the patients' psychological outcomes leads us to conclude that surgical implications of PE should not be decided solely by a physical index.

Clinicopathological Features and Survival Outcomes of Resected Lung Adenosquamous Carcinoma: Results From a Nationwide Japanese Registry Data.

OBJECTIVES: The objective of this study was to clarify the clinicopathological features and prognostic factors of resected lung adenosquamous carcinoma (ASC) using a nationwide multi-institutional database. METHODS: We retrospectively reviewed the records of 15,542 patients who underwent complete R0 resection for ASC (n = 326), adenocarcinoma (AC, n = 11,820), or squamous cell carcinoma (SC, n = 3396) from a Japanese lung cancer registry in 2010. To reduce the selection bias, an inverse probability of treatment weighting (IPTW) method using a propensity score was implemented. RESULTS: The ASC group showed worse recurrence-free and overall survival (RFS and OS) than both the AC and SC groups (5-year OS: 57.5% in ASC, 83.9% in AC [< 0.001], and 62.3% in SC [P = .086]). In multivariate analyses, prognostic factors that affected OS for ASC included male, p-stage II-III, and postoperative complications within 30 days (grade ≥ 3 in the Clavien-Dindo classification). The sensitizing EGFR mutation was detected in 28 (21.5%) of 130 screened patients with ASC, but it did not affect either RFS, OS, or postrecurrence survival. Although more patients in the ASC group received adjuvant chemotherapy compared to the AC and SC groups, both multivariate and IPTW-adjusted analyses did not show positive impact of adjuvant chemotherapy on RFS and OS in ASC. CONCLUSIONS: In this nationwide registry study, lung ASC was more aggressive than both AC and SC. No apparent survival impact of conventional adjuvant chemotherapy prompted us to investigate novel adjuvant strategies to optimize survival outcomes.

Establishment of artificial intelligence model for precise histological subtyping of lung adenocarcinoma and its application to quantitative and spatial analysis.

BACKGROUND: The histological subtype of lung adenocarcinoma is a major prognostic factor. We developed a new artificial intelligence model to classify lung adenocarcinoma images into seven histological subtypes and adopted the model for whole-slide images to investigate the relationship between the distribution of histological subtypes and clinicopathological factors. METHODS: Using histological subtype images, which are typical for pathologists, we trained and validated an artificial intelligence model. Then, the model was applied to whole-slide images of resected lung adenocarcinoma specimens from 147 cases. RESULT: The model achieved an accuracy of 99.7% in training sets and 90.4% in validation sets consisting of typical tiles of histological subtyping for pathologists. When the model was applied to whole-slide images, the predominant subtype according to the artificial intelligence model classification matched that determined by pathologists in 75.5% of cases. The predominant subtype and tumor grade (using the WHO fourth and fifth classifications) determined by the artificial intelligence model resulted in similar recurrence-free survival curves to those determined by pathologists. Furthermore, we stratified the recurrence-free survival curves for patients with different proportions of high-grade components (solid, micropapillary and cribriform) according to the physical distribution of the high-grade component. The results suggested that tumors with centrally located high-grade components had a higher malignant potential (P < 0.001 for 5-20% high-grade component). CONCLUSION: The new artificial intelligence model for histological subtyping of lung adenocarcinoma achieved high accuracy, and subtype quantification and subtype distribution analyses could be achieved. Artificial intelligence model therefore has potential for clinical application for both quantification and spatial analysis.

Prognostic significance of ground-glass areas within tumours in non-small-cell lung cancer.

OBJECTIVES: To validate or refute the hypothesis that non-small-cell lung cancers (NSCLC) with ground-glass areas (GGA+) within the tumour on high-resolution computed tomography are associated with a more favourable prognosis than those without GGA (GGA-). METHODS: We analysed data from a multicentre observational cohort study in Japan including 5005 patients with completely resected pathological stage I NSCLC, who were excluded from the Japan Clinical Oncology Group (JCOG) 0707 trial on oral adjuvant treatment during the enrolment period. The patients' medical and pathological records were assessed retrospectively by physicians and re-staged according to the 8th tumour, node, metastasis edition. RESULTS: Of the 5005 patients, 2388 (48%) were ineligible for the JCOG0707 trial and 2617 (52%) were eligible but were not enrolled. A total of 958 patients (19.1%) died. Patients with GGA+ NSCLC and pathological invasion ≤3 cm showed significantly better overall survival than others. In patients with tumours with an invasive portion ≤4 cm, GGA+ was associated with better survival. The prognoses of patients with GGA+ T2a and GGA- T1c tumours were similar (5-year overall survival: 84.6% vs 83.1%, respectively). The survival with T2b or more tumours appeared unaffected by GGA, and GGA was not prognostic in these larger tumours. CONCLUSIONS: Patients with GGA+ NSCLC on high-resolution computed tomography and ≤4 cm invasion size may have a better prognosis than patients with solid GGA- tumours of the same T-stage. However, the presence or absence of radiological GGA has little impact on the prognosis of patients with NSCLC with greater (>4 cm) pathological invasion.

Clinicopathological predictors of postoperative long-term myasthenic status in resected thymoma with myasthenia gravis.

PURPOSE: Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. METHODS: We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. RESULTS: All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1-B3 and 35% had type A-AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6 months after surgery. This controlled status was observed more frequently in type A-AB than in B1-B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A-AB or B1-B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1-B3, hazard ratio: 3.23, 95% confidence interval: 1.12-9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. CONCLUSION: The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.

Nuss procedure for the treatment of pectus excavatum with dyspnea following oropharyngeal cancer surgery: a case report.

Pectus excavatum (PE) causes cardiopulmonary dysfunction depending on the degree and form of the depression. The patient was a 74-year-old woman with a history of PE. Fourteen years ago, a total glossolaryngectomy was performed for oropharyngeal cancer. Two years later, the patient gradually experienced difficulty in breathing. Computed tomography (CT) revealed severe PE and right main bronchial stenosis. We performed a Nuss procedure for PE repair to surgically release the stenosis of the right main bronchus. Postoperative chest CT showed improvement in the sternal depression and right main bronchial stenosis. Furthermore, shortness of breath was relieved postoperatively. Oropharyngeal cancer surgery may cause tracheal support disruption, leading to leftward shift and severe stenosis of the right main bronchus due to sternum depression. This is an important report regarding respiratory distress caused by a combination of PE and post-oropharyngeal cancer surgery.

Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair.

Pectus excavatum (PE) is often associated with scoliosis and can elicit cardiovascular disturbances under rare conditions. Here we report a patient who was treated with a combined Ravitch and Nuss procedure for PE with dyspnea following scoliosis repair to improve her symptoms. The patient was a 49-year-old woman with a history of PE and scoliosis. Right inferior pulmonary vein stenosis was caused by posterior spinal fusion for scoliosis prior to the PE repair. We could safely correct the chest wall deformity and treat dyspnea by performing a modified Ravitch repair in combination with the Nuss procedure.

Combined Ravitch and Nuss procedure for patients with severe pectus excavatum: technique and initial results.

The Nuss procedure for pectus excavatum (PE) is both less invasive and very simple compared to the Ravitch procedure. However, it may be difficult to perform the Nuss procedure in cases of severe PE. Therefore, we developed a Combined Ravitch and Nuss (CRN) procedure and examined its effectiveness in patients with severe PE. Nine patients with severe PE underwent the CRN procedure. Data on patient characteristics and perioperative results were collected retrospectively. The median Haller index (HI) was 15.4 (range, 6.3-29.3). No significant intraoperative adverse events were noted. Postoperatively, marked improvements in HI were seen in all cases (3.29, range, 2.72-4.96). Two surgical site infections on the shallow layer and one wound seroma occurred. No recurrences were observed during the observation period. Our novel CRN procedure is useful for achieving adequate and sustainable sternal elevation with less invasiveness for patients with severe PE.

Prognostic factors affecting survival in patients with non-small cell lung cancer treated with salvage surgery after drug therapy: a multi-institutional retrospective study.

BACKGROUND: The prevalence of salvage surgeries after drug therapy for non-small cell lung cancer (NSCLC) has risen, mainly due to recent progress in molecular-targeted drugs and immune checkpoint inhibitors for NSCLC. While the safety and effectiveness of salvage surgery after drug therapy for NSCLC have been studied, its indications remain unclear. We aimed to identify the prognostic factors affecting survival in patients with advanced-stage (stages III-IV) NSCLC treated with salvage surgery after drug therapy. METHODS: A retrospective investigation was conducted on patients who received salvage surgery after drug therapy at four hospitals between 2007 and 2020. Salvage surgery was defined as surgery after drug therapy for local progression, tumor conversion to resectable status, and discontinuation of prior drug therapy owing to serious complications. RESULTS: Thirty-two patients received cytotoxic agents alone (n = 12 [38%]), tyrosine kinase inhibitors (TKIs; n = 16 [50%]), or immune checkpoint inhibitors (n = 4 [13%]) as prior drug therapy. In 11 (34%) and 21 (66%) patients, the clinical stage before treatment was III or IV, respectively. The median initial and preoperative serum carcinoembryonic antigen (CEA) levels were 10.2 (range, 0.5-1024) ng/mL and 4.2 (range, 0.6-92.5) ng/mL, respectively. Among the patients, 28 (88%) underwent lobectomy, 2 (6%) underwent segmentectomy, and 2 (6%) underwent wedge resection. Complete resection of the primary lesion was accomplished in 28 (88%) patients. Postoperative complications were documented in six (19%) patients. Mortality rates were 0% at 30 days and 3% at 90 days post-operation. The 5-year overall survival rate stood at 66%, while the 5-year progression-free survival rate was 21%. Multivariate analyses showed that prior TKI therapy and preoperative serum CEA level < 5 ng/mL were prognostic factors influencing overall survival (hazard ratio [95% confidence interval]: 0.06 [0.006-0.68] and 0.03 [0.002-0.41], respectively). The 5-year overall survival in the 11 patients with both favorable prognosticators was 100%. CONCLUSIONS: In this study, prior TKI therapy and preoperative serum CEA level < 5 ng/mL were favorable prognostic factors for overall survival in patients with NSCLC treated with salvage surgery. Patients with these prognostic factors are considered good candidates for salvage surgery after drug therapy.

[Clinicopathological Features and Imaging Characteristics of Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma].

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease. We report seven cases of pulmonary MALT lymphoma. CASES: Chest computed tomography (CT) revealed various morphological features, including a solitary mass, a solid nodule, and ground-glass opacity. Multiple nodules were observed in one patient. However, the tumor margins were ill-defined in all seven cases, and air bronchograms were identified in five cases. The solitary mass was found to extend along the pulmonary lymphatic vessels. Six patients underwent R0 resection, while one underwent an open lung biopsy. Histopathological findings in all seven cases showed lymphoepithelial lesions. Regarding their immunohistological findings, all patients were diagnosed with pulmonary MALT lymphoma. Two patients received postoperative chemotherapy with rituximab. The progression-free survival time was 52 (range, 22-122) months. Postoperative course was uneventful in all patients. CONCLUSION: MALT lymphoma is characterized by an ill-defined margin, air bronchogram, and tumor extension along the pulmonary lymphatic vessels, all of which aid in diagnosis. MALT lymphoma is a low-grade lymphoma, and the prognosis is favorable. Therefore, follow-up examination without treatment can be one of the therapeutic options if patients are diagnosed with pulmonary MALT lymphoma.

Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma.

Human lung cancer is a constellation of tumors with various histological and molecular properties. To build a preclinical platform that covers this broad disease spectrum, we obtained lung cancer specimens from multiple sources, including sputum and circulating tumor cells, and generated a living biobank consisting of 43 lines of patient-derived lung cancer organoids. The organoids recapitulated the histological and molecular hallmarks of the original tumors. Phenotypic screening of niche factor dependency revealed that EGFR mutations in lung adenocarcinoma are associated with the independence from Wnt ligands. Gene engineering of alveolar organoids reveals that constitutive activation of EGFR-RAS signaling provides Wnt independence. Loss of the alveolar identity gene NKX2-1 confers Wnt dependency, regardless of EGFR signal mutation. Sensitivity to Wnt-targeting therapy can be stratified by the expression status of NKX2-1. Our results highlight the potential of phenotype-driven organoid screening and engineering for the fabrication of therapeutic strategies to combat cancer.

Feasibility and safety of percutaneous cryoablation under local anesthesia for the treatment of malignant lung tumors: a retrospective cohort study.

Background: In our institution, computed tomography (CT)-guided percutaneous cryoablation has been performed in patients with malignant lung tumors under local anesthesia. This study aimed to examine the feasibility and safety of percutaneous cryoablation for the treatment of malignant lung tumors. Methods: From July 2002 to December 2016, 227 patients (56 with primary lung cancer and 171 with metastatic lung tumor) underwent percutaneous cryoablation for the treatment of malignant lung tumors using a cryosurgical unit at our institution. Demographic factors, duration of post-treatment hospitalization, and adverse event and mortality rates were retrospectively investigated in 366 treatment sessions targeting 609 lesions. Results: The median diameter of the targeted tumor was 1.3 cm. All the cryoablation procedures were completed under local anesthesia, and the median duration of post-treatment hospitalization was two days. Adverse events (grade 2 or higher) were observed in 79 sessions (21.6%), with pneumothorax being the most common. In five sessions (1.4%), patients had grade 3 adverse events. There was no 30-day mortality; however, there were two 60-day mortality (0.5%) due to acute exacerbation of interstitial pneumonia. In multivariate analysis, independent predictors of adverse events were comorbid interstitial pneumonia [odds ratio (OR) =2.20; 95% confidence interval (CI): 1.04-4.64] and no history of pulmonary resection on the treated side (OR =3.04; 95% CI: 1.65-5.62). Conclusions: Cryoablation is a feasible and safe treatment for malignant lung tumors with acceptable adverse event rates. However, the mortality risk in patients with comorbid interstitial pneumonia should be fully recognized.

Double stapling method for closure of intraoperative alveolar air leakage adjacent to the staple line: a randomized experimental study on ex vivo porcine lungs.

Background: Alveolar air leakage from a pleural defect around the staple line is one of the complications after wedge resection of the lung. An intraoperative closure of the pleural defect by suturing can cause additional pleural rupture due to tension of the pleura adjacent to staple lines. Therefore, we have introduced a novel closure method for pleural defect adjacent to the staple line, named the double stapling method. This study compared the efficacy of two closure methods; the double stapling method and conventional suturing method with pledgets using ex vivo porcine lungs. Methods: The double stapling method involves closing the pleural defect by suturing the two parallel staple lines at both sides of the pleural defect. This method was developed to distribute the pleural tension around the needle holes of suturing. As a model of pleural defect adjacent to the staple line after wedge resection, wedge resection of the caudal lobe of left porcine lungs was performed, and a superficial square pleural defect (10 mm × 10 mm) adjacent to the staple line was made by scalpel. The defect was closed using the following two methods: (I) suturing with pledgets (n=10); and (II) double stapling method (n=10). The lobe was inflated in water at an airway pressure of 20, 25, and 30 cmH2O; closure success or failure was judged by the absence or presence of air leakage. Results: The closure success was confirmed in 2 (20%) out of 10 cases in the suturing with pledgets group and 9 (90%) out of 10 in the double stapling method group (P=0.007). In 4 out of 10 cases in the suturing with pledgets group, new pleural clefts longer than 3 mm were created around the needle holes of suturing. Conclusions: Ex vivo experiments have suggested the superiority of the double stapling method for the intraoperative closure of alveolar air leakage adjacent to the staple line after wedge resection, compared to conventional suturing with the pledget method.

Separate evaluation of unilateral lung function using upright/supine CT in a patient with diaphragmatic paralysis.

Background: Unilateral diaphragmatic paralysis is a condition in which the unilateral diaphragm is paralyzed and elevated. Orthopnea due to lung compression by an elevated diaphragm in the supine position is common in patients with unilateral diaphragmatic paralysis. Although its symptom is posture-dependent, the effect of posture on lung function in unilateral diaphragmatic paralysis has not been studied. Computed tomography (CT) can be used to assess lung volume. However, conventional CT cannot be performed in the upright position. A pulmonary function test can be performed in both upright and supine positions. However, it cannot evaluate the function of each lung separately. Case presentation: We report a case of a 79-year-old man with unilateral diaphragmatic paralysis. He presented with difficulty in inspiration, specifically in the supine position, and underwent both conventional supine CT and newly developed upright CT to assess the effect of posture on the function of each lung. The difference between expiratory and inspiratory lung volumes on CT in the supine position was less than that in the upright position by 46% and 4% on affected and healthy sides, respectively. We previously reported that the difference between expiratory and inspiratory lung volumes on CT correlated with inspiratory capacity on the pulmonary function test. A 46% decline in inspiratory capacity on the affected side in the supine position likely caused orthopnea in this patient. Conclusions: Supine/upright CT is helpful to assess the influence of posture on unilateral lung function in patients with unilateral diaphragmatic paralysis.

Efficacy of Adjuvant Chemotherapy With Tegafur-Uracil in Patients With Completely Resected, Node-Negative NSCLC-Real-World Data in the Era of Molecularly Targeted Agents and Immunotherapy.

Introduction: In Japan, adjuvant tegafur-uracil (UFT) chemotherapy is recommended for patients with completely resected, stage I NSCLC. This treatment requires real-world re-evaluation because of recent advances in target-based and immuno-oncological treatments and refinement of lung cancer staging. Methods: The Japan Clinical Oncology Group (JCOG) 0707, a phase 3 trial comparing the benefits of UFT and S-1 (tegafur-gimeracil-oteracil) in patients with completely resected stage I NSCLC (T1 >2 cm and T2 in the TNM sixth edition), was conducted in Japan. A multicenter observational cohort study (Comprehensive Support Project for Oncology Research [CSPOR]-LC03) was also conducted for those patients excluded from JCOG 0707 during the study enrollment period. Physicians from institutions that participated in JCOG 0707 retrospectively assessed the medical records of each patient. The efficacy of UFT was evaluated in the CSPOR-LC03 cohort. Results: In the entire study population (n = 5005), patients treated with UFT (n = 1549) had significantly longer overall survival (OS) than those without any adjuvant chemotherapy (n = 3338). There was no significant difference in OS between the patients treated with UFT (n = 1061) and those without adjuvant chemotherapy (n = 1484) in the JCOG 0707-eligible population (logrank p = 0.755). For tumors without ground-glass attenuation and size greater than 3 cm, patients treated with UFT had significantly longer survival than those without adjuvant chemotherapy, on univariate but not on multivariate analysis. Conclusions: There was no significant difference in OS between the patients treated with UFT and those without adjuvant chemotherapy in the clinical trial-eligible population. Adjuvant UFT for patients with completely resected NSCLC may be recommended only in patients with a tumor without ground-glass attenuation and size greater than 3 cm. In patients with node-negative early NSCLC, further study is needed to select patients who will benefit from adjuvant chemotherapy.

Safety and efficacy of salvage surgery for non-small cell lung cancer: a retrospective study of 46 patients from four Keio-affiliated hospitals.

OBJECTIVES: Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer. METHODS: We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals. RESULTS: Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively. CONCLUSION: The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.

Debulking surgery for malignant tumors: the current status, evidence and future perspectives.

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.

Direct derivation of human alveolospheres for SARS-CoV-2 infection modeling and drug screening.

Although the main cellular target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is thought to be alveolar cells, the absence of their tractable culture system precludes the development of a clinically relevant SARS-CoV-2 infection model. Here, we establish an efficient human alveolosphere culture method and sphere-based drug testing platform for SARS-CoV-2. Alveolospheres exhibit indolent growth in a Wnt- and R-spondin-dependent manner. Gene expression, immunofluorescence, and electron microscopy analyses reveal the presence of alveolar cells in alveolospheres. Alveolospheres express ACE2 and allow SARS-CoV-2 to propagate nearly 100,000-fold in 3 days of infection. Whereas lopinavir and nelfinavir, protease inhibitors used for the treatment of human immunodeficiency virus (HIV) infection, have a modest anti-viral effect on SARS-CoV-2, remdesivir, a nucleotide prodrug, shows an anti-viral effect at the concentration comparable with the circulating drug level. These results demonstrate the validity of the alveolosphere culture system for the development of therapeutic agents to combat SARS-CoV-2.

Estimating copy number using next-generation sequencing to determine ERBB2 amplification status.

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as "equivocal", which means that some ERBB2 amplification cases diagnosed as "HER2 negative" might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

Invasive pulmonary aspergillosis after liver transplantation: lessons from successfully treated cases and review of the literature.

PURPOSE: Invasive pulmonary aspergillosis (IPA) after liver transplantation (LT) is most often fatal. We analyzed the outcomes of IPA in a single center. METHODS: We reviewed, retrospectively, the medical records of recipients of living donor LT (LDLT) or deceased donor LT (DDLT) performed between 1995 and 2019 at our institute. We analyzed the incidence of IPA and assessed the treatment courses of patients treated successfully and those not treatment successfully. RESULTS: Among 326 recipients, IPA was diagnosed in 6 (1.8%). The incidence of IPA was significantly higher in patients with acute liver failure (ALF, 9.8%) than in those without ALF (0.4%), after DDLT (8.8%) than after LDLT (1.0%), and in recipients who received preoperative steroid pulse therapy (16.0%) than in those who did not (0.7%). Complete cure of IPA was achieved in the most recent three patients, by administering voriconazole immediately after the diagnosis of IPA and performing lung resection, while the IPA lesion was single and localized. CONCLUSIONS: Patients with risk factors for IPA must be monitored closely. Our three successfully treated cases demonstrate that initiating immediate voriconazole treatment and making a calculated decision about lung resection can contribute to a favorable outcome.