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Introduction: Stereotactic body radiation therapy (SBRT) is a well-established treatment option for patients with early-stage non-small cell lung cancer (NSCLC). We retrospectively identified 82 patients with early-stage NSCLC treated with SBRT at our institution between November 2009 and September 2019. Among these patients, two developed local recurrence or new primary lung cancer and lung metastasis or new primary lung cancer, respectively, and were treated with repeat SBRT. We herein report a case series of two patients with radiation pneumonitis after repeat SBRT. Case Series: Case A was an 80-year-old woman diagnosed with stage I (T1aN0M0) squamous cell carcinoma. She received initial SBRT at an irradiation dose of 48 Gy in 4 fractions at the isocenter. Two years and three months after initial SBRT, the patient was clinically diagnosed with post-SBRT local recurrence or primary lung cancer and, thus, was treated with repeat SBRT at an irradiation dose of 60 Gy in 10 fractions. Six months later, the patient developed grade 5 radiation pneumonitis. Case B was an 89-year-old man diagnosed with stage I (T1cN0M0) adenocarcinoma. He received initial SBRT at an irradiation dose of 48 Gy in 4 fractions at the isocenter. Three years and six months after initial SBRT, the patient was clinically diagnosed with post-SBRT lung metastasis or primary lung cancer and, thus, was treated with repeat SBRT at an irradiation dose of 50 Gy in 4 fractions. Six months later, the patient developed grade 3 radiation pneumonitis. Conclusion: Caution is needed when performing repeat SBRT.

Poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme responsible for catabolism of poly (ADP-ribose) (PAR), synthesized by PARP. PARG dysfunction sensitizes certain cancer cells to alkylating agents and cisplatin by perturbing the DNA damage response. The gene mutations that sensitize cancer cells to PARG dysfunction-induced death remain to be identified. Here, we performed a comprehensive analysis of synthetic lethal genes using inducible PARG knockdown cells and identified dual specificity phosphatase 22 (DUSP22) as a novel synthetic lethal gene related to PARG dysfunction. DUSP22 is considered a tumor suppressor and its mutation has been frequently reported in lung, colon, and other tumors. In the absence of DNA damage, dual depletion of PARG and DUSP22 in HeLa and lung cancer A549 cells reduced survival compared with single-knockdown counterparts. Dual depletion of PARG and DUSP22 increased the apoptotic sub-G1 fraction and upregulated PUMA in lung cancer A549, PC14, and SBC5 cells, and inhibited the PI3K/AKT/mTOR pathway in A549 cells, suggesting that dual depletion of PARG and DUSP22 induced apoptosis by upregulating PUMA and suppressing the PI3K/AKT/mTOR pathway. Consistently, the growth of tumors derived from double knockdown A549 cells was slower compared with those derived from control siRNA-transfected cells. Taken together, these results indicate that DUSP22 deficiency exerts a synthetic lethal effect when combined with PARG dysfunction, suggesting that DUSP22 dysfunction could be a useful biomarker for cancer therapy using PARG inhibitors.Significance:This study identified DUSP22 as a novel synthetic lethal gene under the condition of PARG dysfunction and elucidated the mechanism of synthetic lethality in lung cancer cells.

Figure S2 shows that cell growth inhibition by knockdown of both DUSP22 and PARG was recovered by the treatment with p38 MAPK inhibitor.

The accuracy of transbronchial lung cryobiopsy (TBLC) in each disease for pathological and multidisciplinary discussion (MDD) diagnosis is not yet established. Method: We investigated 431 patients who were classified by MDD diagnosis and were grouped into the disease categories. For each category or disease, we used TBLC samples to calculate the sensitivities of the pathological diagnosis compared with MDD diagnoses. Further, we compared these sensitivities to pathological diagnoses with all clinical/radiological information. Result: The sensitivity for diagnosing idiopathic interstitial pneumonia (IIPs) with TBLC was higher than connective tissue disease associated ILD (CTD-ILD). Idiopathic nonspecific interstitial pneumonia (iNSIP), fibrotic hypersensitivity pneumonitis, and some CTD-ILDs were diagnosed with lower sensitivities compared to IPF. The sensitivity of pathological diagnosis with all clinical/radiological information in IPF was higher than in iNSIP, but not significantly different from other diseases. The overall sensitivity of the pathological diagnosis with clinical/radiological information was 69.0%, significantly higher than without clinical/radiological information. Conclusion: The sensitivity of pathological diagnosis with TBLC was low for some diseases except IPF. The addition of all clinical/radiological information increased the sensitivity of pathology diagnosis by TBLC, which was no less sensitive than IPF for all diseases except iNSIP.

Identifying patients resistant to cisplatin treatment is expected to improve cisplatin-based chemotherapy for various types of cancers. Excision repair cross-complementing group 1 (ERCC1) is involved in several repair processes of cisplatin-induced DNA crosslinks. ERCC1 overexpression is reported as a candidate prognostic factor and considered to cause cisplatin resistance in major solid cancers. However, anti-ERCC1 antibodies capable of evaluating expression levels of ERCC1 in clinical specimens were not fully optimized. A mouse monoclonal antibody against human ERCC1 was generated in this study. The developed antibody 9D11 specifically detected isoforms of 201, 202, 203 but not 204, which lacks the exon 3 coding region. To evaluate the diagnostic usefulness of this antibody, we have focused on gastric cancer because it is one of the major cancers in Japan. When ERCC1 expression was analyzed in seventeen kinds of human gastric cancer cell lines, all the cell lines were found to express either 201, 202, and/or 203 as major isoforms of ERCC1, but not 204 by Western blotting analysis. Immunohistochemical staining showed that ERCC1 protein was exclusively detected in nuclei of the cells and a moderate level of constant positivity was observed in nuclei of vascular endothelial cells. It showed a clear staining pattern in clinical specimens of gastric cancers. Antibody 9D11 may thus be useful for estimating expression levels of ERCC1 in clinical specimens.

The trachea is a sporadic origin of paraganglioma. The purpose of the present study was to identify the features of tracheal paraganglioma and reveal the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) by reviewing both previous and current cases. In cases of tracheal tumors, we need to consider the bleeding risk associated with a biopsy, as the tumor may be paraganglioma, which is hypervascular. If a biopsy is not available, then CT and MRI can aid in making a pre-operative diagnosis. MRI in particular is useful for long-term observations.

About 4 and a half years have passed since"Cancer Genome Medicine"was first mentioned in the Third Phase of the Basic Plan to Promote Cancer Control Programs that started in October 2017. Currently, cancer genomic medicine is being carried out by the cancer gene panel test, which is covered by public insurance, mainly at the 12 Cancer Genome Medicine Core Center Hospital designated nationwide by the Ministry of Health, Labor, and Welfare in Japan. Cancer genomic medicine has come to be positioned as a standard medical treatment. However, there are various challenges in operating an expert panel that professionally examines the results of the gene panel tests and reports treatment recommendations and secondary findings that suggest hereditary tumors. In addition, there is an urgent need to disseminate and educate healthcare professionals and patients about cancer genomic medicine. In this panel discussion on January 14, 2022, 10 panelists discussed how to solve these issues and the prospects for the future.

Nagasaki University Hospital, which was designated as a"Designated Core Hospital for Cancer Genomic Medicine"by the Ministry of Health, Labor and Welfare in 2019, started an initiative for cancer genomic medicine in collaboration with 2 "Cooperative Hospital for Cancer Genomic Medicine"in Nagasaki prefecture. However, there are various issues such as 1 . eligibility criteria and strategies for inspections, 2 . training of specialized medical personnel, 3 . information dissemination and dissemination and enlightenment, etc. in the"equalization"of cancer genomic medicine in the prefecture, and we believe that measures against these issues are urgently needed.

At our hospital, anti-cancer drug administration is managed using a regimen-ordering system, and orders for the outpatient department and hospital wards have to be placed by 15:00 and 14:00 the day before they are required. On the day of treatment, the doctor examines the patient, confirms the test results, and places the final order for treatment on the patient's electronic medical record. In response, the pharmacist adjusts the anti-cancer drug preparation, and treatment is provided in the outpatient setting or in a ward. Although drug costs have increased due to the widespread use of immunotherapy, there have been cases where a drug was wasted after the required amount was adjusted on the day of treatment or drugs were discarded altogether, which pose serious problems. From April 2016 to March 2021, the total number of cases of drug wastage following placement of the final treatment order and drug disposal were 146 and 84, respectively, and the total associated economic loss was 5.81 million yen. The main causes were pre-confirmation mistakes and patients' physical condition on the day of treatment; some cancellations caused by patient-related factors were unavoidable. The current status of drug disposal is reported to the hospital director every 6 months, and the doctor-in-charge is interviewed regarding the reason for the wastage. In cases involving the disposal of large quantities of drugs(≥100,000 yen), the department manager and medical office manager are contacted, and an incident report is submitted. In 2021, drugs worth 2.03 million yen were discarded between April and September, which is worth serious consideration. It is essential to understand the reasons for drug wastage, pay attention to expensive regimens, and take appropriate measures at each facility.

Background: Combination chemotherapy including platinum agents is used to treat advanced thymic carcinoma; however, the therapeutic effects of such treatment are insufficient. A phase II study was conducted to investigate the efficacy and safety of concurrent chemoradiotherapy for locally advanced thymic carcinoma. Methods: Patients fulfilling the following eligibility criteria were enrolled: unresectable locally advanced thymic carcinoma, no prior treatment, a good performance status (PS; PS=0-1), being aged 20-75, and adequate organ function. The patients received 80 mg/m2/day S-1 orally on days 1-14 and 60 mg/m2/day cisplatin intravenously on day 1. Two cycles of chemotherapy were repeated every 4 weeks. Thoracic radiotherapy (2 Gy, once daily, commencing on day 1; total dose: 60 Gy) was also administered. The primary endpoint of this study was to estimate the objective response rate with a target sample size of 30.Results: Three patients were enrolled. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients’ characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55-72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both non-evaluable cases, the second course of chemotherapy was judged to be post-protocol treatment because it was delayed by ≥14 days, but a complete response (CR) and partial response were achieved after the end of the study, respectively. Grade 4 leukopenia/neutropenia and grade 3 febrile neutropenia occurred in one patient each (33%). There were no treatment-related deaths. The median time to tumor progression was 17.6 months, and the 1-, 2-, 3-, and 4-year survival rates were 67%, 33%, 33%, and 33%, respectively. The median overall survival time was not reached, and the 1-, 2-, 3-, and 4-year survival rates were 100%, 67%, 67%, and 67%, respectively. Conclusions: Although it was difficult to recruit patients, there was a long-term survivor, who survived for >4 years and seemed to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.

Purpose This study aimed to evaluate the clinical courses of patients with surgically resected stage IA pulmonary adenocarcinoma (Ad) who exhibited heterogeneous ground-glass nodules (GGNs) or part-solid nodules on thin-section computed tomography (TSCT) and to clarify the prognostic differences between them. Materials and methods The cases of 242 patients with proven pulmonary Ad with heterogeneous GGN or part-solid nodule who underwent surgical resection were retrospectively reviewed. After surgery, they were examined pathologically. Disease-free survival (DFS) and overall survival (OS) were also investigated. Results There were no cases of recurrent pulmonary Ad or death from the primary disease in the heterogeneous GGN group. In the part-solid nodule group, recurrent pulmonary Ad and death from the primary disease were observed in 12 and 6 of 181 patients, respectively. Heterogeneous GGNs were associated with significantly longer DFS than part-solid nodules (p = 0.042). While, there was no significant difference in OS between the two groups (p = 0.134). Pathological diagnoses were available for all 242 patients. 181 part-solid nodules were classified into 116 invasive Ads, 54 minimally invasive Ads (MIAs), and 11 Ad in situ (AIS) lesions, and 61 heterogeneous GGNs were classified into 18 invasive Ads, 25 MIAs, and 18 AIS lesions. Conclusion Heterogeneous GGNs were significantly associated with longer DFS than part-solid nodules. Pathologically, there were significant differences between the heterogeneous GGNs and part-solid nodules.

Chest, 157(5), pp.e165-e171; 2020

Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S‐1 treatment is effective against thymic carcinoma. S‐1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non‐small cell lung cancer (NSCLC). In addition, its safety has been confirmed, and it has been reported to have a marked effect against thymic carcinoma. Therefore, we conducted a phase II study of S‐1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced thymic carcinoma, in which the overall response rate was employed as the primary endpoint. The secondary endpoints were overall survival, progression‐free survival, and safety.

Poly (ADP-ribose) glycohydrolase (PARG) is the main enzyme responsible for catabolism of poly (ADP-ribose) (PAR), synthesized by PARP. PARG dysfunction sensitizes certain cancer cells to alkylating agents and cisplatin by perturbing the DNA damage response. The gene mutations that sensitize cancer cells to PARG dysfunction-induced death remain to be identified. Here, we performed a comprehensive analysis of synthetic lethal genes using inducible PARG knockdown cells and identified dual specificity phosphatase 22 (DUSP22) as a novel synthetic lethal gene related to PARG dysfunction. DUSP22 is considered a tumor suppressor and its mutation has been frequently reported in lung, colon, and other tumors. In the absence of DNA damage, dual depletion of PARG and DUSP22 in HeLa and lung cancer A549 cells reduced survival compared with single-knockdown counterparts. Dual depletion of PARG and DUSP22 increased the apoptotic sub-G1 fraction and upregulated PUMA in lung cancer A549, PC14, and SBC5 cells, and inhibited the PI3K/AKT/mTOR pathway in A549 cells, suggesting that dual depletion of PARG and DUSP22 induced apoptosis by upregulating PUMA and suppressing the PI3K/AKT/mTOR pathway. Consistently, the growth of tumors derived from double knockdown A549 cells was slower compared with those derived from control siRNA-transfected cells. Taken together, these results indicate that DUSP22 deficiency exerts a synthetic lethal effect when combined with PARG dysfunction, suggesting that DUSP22 dysfunction could be a useful biomarker for cancer therapy using PARG inhibitors. Significance: This study identified DUSP22 as a novel synthetic lethal gene under the condition of PARG dysfunction and elucidated the mechanism of synthetic lethality in lung cancer cells.

Background Chest radiography (CR) is employed as the evaluation of pneumoconiosis; however, we sometimes encounter cases in which computed tomography (CT) is more effective in detecting subtle pathological changes or cases in which CR yields false-positive results. Purpose To compare CR to CT in the diagnosis of early-stage pneumoconiosis. Material and Methods CR and CT were performed for 132 workers with an occupational history of mining. We excluded 23 cases of arc-welder’s lung. Five readers who were experienced chest radiologists or pulmonologists independently graded the pulmonary small opacities on CR of the remaining 109 cases. We then excluded 37 cases in which the CT data were not sufficient for grading. CT images of the remaining 72 cases were graded by the five readers. We also assessed the degree of pulmonary emphysema in those cases. Results The grade of profusion on CR (CR score) of all five readers was identical in only 5 of 109 cases (4.6%). The CR score coincided with that on CT in 40 of 72 cases (56%). The CT score was higher than that on CR in 13 cases (18%). On the other hand, the CT score was lower than that on CR in 19 cases (26%). The incidence of pulmonary emphysema was significantly higher in patients whose CR score was higher than their CT score. Conclusion CT is more sensitive than CR in the evaluation of early-stage pneumoconiosis. In cases with emphysema, the CR score tends to be higher in comparison to that on CT.

Rheumatoid arthritis frequently complicates airway diseases and is associated with high rates of pneumonia and mortality. The relationship between microorganisms colonizing the lower respiratory tract and the subsequent incidence of pneumonia in patients with rheumatoid arthritis is unclear. In this study, we aimed to identify microorganisms colonizing the lower respiratory tract in patients with rheumatoid arthritis related to the risk of developing subsequent pneumonia in these patients.A retrospective cohort study was designed to include a total of 121 patients with rheumatoid arthritis (median age, 67 years; women, 78.5%) who underwent bronchoscopy at three hospitals from January 2008 to December 2017. The following information was extracted from their electronic medical records: patient characteristics, microorganisms detected by bronchoscopy, and subsequent incidences of pneumonia. The patients were divided into groups based on the microorganisms isolated from the lower respiratory tract and compared with control subjects. The cumulative incidence of pneumonia was assessed using the Kaplan–Meier method and log-rank test. Risk factors for pneumonia were analyzed using the Cox proportional-hazards analysis.The most frequently isolated microbes from the lower respiratory tract in descending order were Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae. The annual incidence rates of pneumonia per 1000 patients were 100, 62, 132, and 38, in the P. aeruginosa, S. aureus, H. influenzae, and control group, respectively. Patients colonized with P. aeruginosa had a higher frequency of macrolide use and a higher degree of bronchiectasis than patients in the control group. The rate of the subsequent incidence of pneumonia was higher in the P. aeruginosa group (P = 0.038), and P. aeruginosa was an independent risk factor for pneumonia (hazard ratio, 3.504; 95% confidence interval, 1.153–10.330).The colonization of the lower respiratory tract by P. aeruginosa in patients with rheumatoid arthritis was associated with the subsequent incidence of pneumonia.

We conducted a survey of the outpatient pharmacotherapy we administered from April 2016 to March 2019 to understand trends in chemotherapy for respiratory thoracic malignancies, such as lung cancer. Over the 3-year period, 19,408 were treated in the outpatient chemotherapy department. Of these, 1,270(6.5%)had respiratory thoracic malignancies. The total number of patients and the number of patients with thoracic malignancies(%) were 5,815 and 320(5.5%); 6,344 and 434(6.8%); and 7,247 and 516(7.1%)in FY2016, FY2017 and FY2018, respectively. This shows that both increased during the study period. Each patient was treated in the chemotherapy department multiple times, and treatment for thoracic malignancies was initiated in 161 patients. The female:male ratio was 27%:73%, and the patients' median age(range)was 68 years(range: 36-84 years). Lung cancer was the most common disease(91%), followed by malignant pleural mesothelioma(5%), thymoma(2%), thymic carcinoma(1%), and synovial sarcoma(1%). The most common histological type of lung cancer was adenocarcinoma(67%), followed by squamous cell carcinoma(17%), small cell carcinoma( 7%), and others(9%). Outpatient chemotherapy was introduced as a first-line, second-line, and third-line or later treatment in 46%, 28%, and 22% of cases, respectively. While the number of patients increased, the number of new patients with thoracic malignancies decreased from 58 in FY2016 to 52 in FY2017 and 51 in FY2018. Conversely, the number of visits to the chemotherapy department by each new patient almost doubled from 5.5 in FY2016 to 8.5 in FY2017 and 10.1 in FY2018. The proportion of patients for which immunotherapy was included in the induction treatment regimen increased from 28% and 24% in FY2016 and FY2017, respectively, to 39% in FY2018. The increase in the use of outpatient chemotherapy for respiratory thoracic malignancies was due to the increase in the proportion of patients undergoing immunotherapy and the number of visits to the chemotherapy department per patient. It is important to implement measures to help prolong and increase the use of outpatient pharmacotherapy for respiratory thoracic malignancies by cooperating with surrounding medical institutions and increasing the number of beds available.

Arc-welders' pneumoconiosis (AWP) is a less fibrogenic pneumoconiosis with radiographic shadows that can improve after isolation from dusty environments. Therefore, early diagnosis is important. However, the exact role of chest radiograph and computed tomography (CT) for diagnosing AWP is not fully understood. This study was performed to assess the CT appearance of AWP using semi-quantitative methods and to compare the findings with those of silicosis. The profusion of pulmonary abnormality on chest radiograph were also compared with the semi-quantitative CT score.Sixty-six patients with clinically diagnosed AWP were included and compared with 33 patients with silicosis. The CT images were interpreted according to the International Classification of HRCT for Occupational and Environmental Respiratory Diseases (ICOERD). Data on the profusion score by chest radiograph were also compared with CT score.Ill-defined centrilobular nodules, ground-glass opacity (GGO) and centrilobular branching opacity were more frequently observed (p = 0.0031) in AWP, whereas well-defined rounded opacity (p 0.0001), progressive massive fibrosis (p 0.0001), and mediastinal lymphadenopathy (p 0.0001) were more frequently observed in silicosis. Regarding lung nodules, there was a high correlation between the ICOERD and CXR profusion scores in silicosis, but CXR underestimated AWP.Ill-defined centrilobular nodules, GGO and centrilobular branching opacity were more frequently observed in AWP than silicosis. Because these findings are difficult to detect by chest radiograph, CT should be considered for the assessment of patients with suspected AWP.

Background The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. Methods The eligibility criteria were: lung cancer patients scheduled to undergo irinotecan therapy, aged ≥ 20 years, with a performance status of 0-2. Thirty-one patients were enrolled and their blood was collected and used to examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy. Results The patients' characteristics were as follows: male/female 25/6, median age 71 years (range 55-84), stage IIB/IIIA/IIIB/IV 2/6/11/12, and adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 14/10/3/4, respectively. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those observed in the wild-type patients. SN-38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with UGT1A1*27 or UGT1A1*28 polymorphisms. No severe myelotoxicity was seen in the patients with UGT1A1*7. Conclusion UGT1A1*27 can occur separately from UGT1A1*28 and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan-induced toxicities, and UGT1A1*29 seems to have little clinical impact.

Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups.A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD-1 group and 2460 patients in the PD-L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD-L1 (32% vs 25%; P = .6). There was no difference in response rate noted between PD-1 (19%) and PD-L1 (18.6%) inhibitors (P = .17). The incidence of overall adverse events (AEs) was comparable between the PD-1 and PD-L1 inhibitors (64% [95% confidence interval (95% CI), 63%-66%] vs 66% [95% CI, 65%-69%]; P = .8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P = .07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P = .01) compared with patients who received PD-L1 inhibitors.In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2018;124:271-7. © 2017 American Cancer Society.

Our hospital has an established outpatient chemotherapy room, and medical doctors have accessed veins for infusion so far. We trialed venous access by nurses for the purpose of managing safe and proper cancer chemotherapy, reducing the work of doctors, and reducing patient waiting time. A questionnaire was conducted in June 2013, and nurses secured routes at 19 facilities(58%)of the 33 national university hospitals. In November of the same year, the working group was established, and from September 2016 to March 2017, lectures, practical skills, a paper test, and a practical test were conducted; successful applicants were approved as in-hospital certified nurses. From April 2017, we started intravenous injection of anti-cancer drugs by nurses in outpatient chemotherapy rooms and always waiting for doctor in chemotherapy room. There have been many favorable reports of reduced pain and less route failure from patients, and issues, such as extravasation and dyspnea, have not occurred yet. The doctors who were interrupting their work by 29 minutes(20 minutes to and from the patient for a 9-minute procedure)could concentrate on their own tasks. However, patient waiting time increased from 14 minutes to 21 minutes because the amount of work for nurses increased. In the future, reducing the burden on nurses, for example, by increasing the number of nurses, is warranted.

Introduction The purpose of this study was to evaluate the natural course of the progression of pulmonary subsolid nodules (SSNs). Materials and Methods Eight facilities participated in this study. A total of 795 patients with 1229 SSNs were assessed for the frequency of invasive adenocarcinomas. SSNs were classified into three categories: pure ground-glass nodules (PGGNs), heterogeneous GGNs (HGGNs) (solid component detected only in lung windows), and part-solid nodules. Results The mean prospective follow-up period was 4.3 ± 2.5 years. SSNs were classified at baseline as follows: 1046 PGGNs, 81 HGGNs, and 102 part-solid nodules. Among the 1046 PGGNs, 13 (1.2%) developed into HGGNs and 56 (5.4%) developed into part-solid nodules. Among the 81 HGGNs, 16 (19.8%) developed into part-solid nodules. Thus, the SSNs at the final follow-up were classified as follows: 977 PGGNs, 78 HGGNs, and 174 part-solid nodules. Of the 977 PGGNs, 35 were resected (nine minimally invasive adenocarcinomas [MIAs], 21 adenocarcinomas in situ [AIS], and five atypical adenomatous hyperplasias). Of the 78 HGGNs, seven were resected (five MIAs and two AIS). Of the 174 part-solid nodules, 49 were resected (12 invasive adenocarcinomas, 26 MIAs, 10 AIS, and one adenomatous hyperplasia). For the PGGNs, the mean period until their development into part-solid nodules was 3.8 ± 2.0 years, whereas the mean period for the HGGNs was 2.1 ± 2.3 years ( p = 0.0004). Conclusion This study revealed the frequencies and periods of development from PGGNs and HGGNs into part-solid nodules. Invasive adenocarcinomas were diagnosed only among the part-solid nodules, corresponding to 1% of all 1229 SSNs.

Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL., Internal Medicine, 55(21), pp.3147-3150; 2016

Although Takayasu arteritis (TA) is rare as a form of chronic inflammatory arteritis, it is important that it is diagnosed early because the 10-year survival rate is only 84% to 87%. Many reported patients have been young women in East Asia. We report a case of a young woman who originally presented with unexplained pulmonary consolidation. Five years later, contrast-enhanced computed tomography (CT) imaging showed thickening of the walls of the aorta and its branches and of the main and right pulmonary artery (PA), and occlusion of the left subclavian and left PAs. A diagnosis of TA was made based on these CT findings. Patients with TA often have PA involvement, and this can be the initial site of arteritis. Therefore, TA should be included in the differential diagnosis of young women with unexplained pulmonary consolidation.

Pneumoconiosis is an occupational respiratory illness that occur by inhaling dust to the lungs. 240,000 participants are screened for diagnosis of pneumoconiosis every year in Japan. Radiograph is used for staging of severity rate in pneumoconiosis worldwide. CT imaging is useful for the differentiation of requirements for industrial accident approval because it can detect small lesions in comparison with radiograph. In this paper, we extracted lung nodules from 3D pneumoconiosis CT images by two manual processes and automatic process, and created a database of pneumoconiosis CT images. We used the database to analyze, compare, and evaluate visual diagnostic results of radiographs and quantitative assessment (number, size and volume) of lung nodules. This method was applied to twenty pneumoconiosis patients. Initial results showed that the proposed method can assess severity rate in pneumoconiosis quantitatively. This study demonstrates effectiveness on diagnosis and prognosis of pneumoconiosis in CT screening.

The purpose was to identify distinguishing CT features of pathologically diagnosed asbestosis, and correlate diagnostic confidence with asbestos body burden. Thirty-three workers (mean age at CT: 73 years) with clinical diagnoses of asbestosis, who were autopsied (n = 30) or underwent lobectomy (n = 3), were collected. Two radiologists independently scored high-resolution CT images for various CT findings and the likelihood of asbestosis was scored. Two pathologists reviewed the pathology specimens and scored the confidence of their diagnoses. Asbestos body count was correlated with CT and pathology scores. Pathologically, 15 cases were diagnosed as asbestosis and 18 cases with various lung fibroses other than asbestosis. On CT, only the score of the subpleural curvilinear lines was significantly higher in asbestosis (p = 0.03). Accuracy of CT diagnosis of asbestosis with a high confidence ranged from 0.73 to 0.79. Asbestos body count positively correlated with CT likelihood of asbestosis (r = 0.503, p = 0.003), and with the confidence level of pathological diagnosis (r = 0.637, p

To retrospectively review the clinical, radiological and pathological data in patients who underwent surgical resection for pulmonary pleomorphic carcinoma (PC), and to analyse the prognostic predictors of survival. The data were retrospectively examined for 33 consecutive patients (28 males and five females) who had undergone surgical resection for pulmonary PC. Cox’s proportional-hazards model was used to analyse the prognostic predictors of survival. The size of the tumours ranged from 1.1 to 12.0 cm (mean 5.4 cm). The majority (26) of the tumours were located at the lung periphery, five tumours had cavitation, two had calcification and 14 had peritumoral ground-glass opacity. Most of the tumours showed heterogeneous enhancement and contained a low-density area (LDA) within the tumour. The 5-year overall survival of surgically resected PC was 36 % (standard error = 0.093). A multivariate analysis revealed the LDA grade [hazard ratio (HR), 2.019], pathological stage (HR, 7.552) and pathological N factor (HR, 0.370) to be significant predictors of a poorer prognosis. A greater component of LDA within the tumour on contrast-enhanced CT is associated with a poorer prognosis in patients with PC. • PC has a poorer prognosis than other conventional NSCLC. • The five-year OS of surgically resected PC was 36 %. • A greater component of LDA on contrast-enhanced CT suggests a poorer prognosis.

Background Measuring the size of invasiveness on computed tomography (CT) for the T descriptor size was deemed important in the 8th edition of the TNM lung cancer classification. We aimed to correlate the maximal dimensions of the solid portions using both lung and mediastinal window settings on CT imaging with the pathologic invasiveness (> 0.5 cm) in lung adenocarcinoma patients. Materials and Methods The study population consisted of 378 patients with a histologic diagnosis of adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IVA)-lepidic, IVA-acinar and/or IVA-papillary, and IVA-micropapillary and/or solid adenocarcinoma. A panel of 15 radiologists was divided into 2 groups (group A, 9 radiologists; and group B, 6 radiologists). The 2 groups independently measured the maximal and perpendicular dimensions of the solid components and entire tumors on the lung and mediastinal window settings. The solid proportion of nodule was calculated by dividing the solid portion size (lung and mediastinal window settings) by the nodule size (lung window setting). The maximal dimensions of the invasive focus were measured on the corresponding pathologic specimens by 2 pathologists. Results The solid proportion was larger in the following descending order: IVA-micropapillary and/or solid, IVA-acinar and/or papillary, IVA-lepidic, MIA, and AIS. For both groups A and B, a solid portion > 0.8 cm in the lung window setting or > 0.6 cm in the mediastinal window setting on CT was a significant indicator of pathologic invasiveness > 0.5 cm (P Conclusion A solid portion > 0.8 cm on the lung window setting or solid portion > 0.6 cm on the mediastinal window setting on CT predicts for histopathologic invasiveness to differentiate IVA from MIA and AIS.

Objectives The primary aim was to reveal the prevalence of lung cancer (LC) and malignant pleural mesothelioma (MPM) in subjects with past asbestos exposure (AE). We also examined pulmonary or pleural changes correlated with the development of LC. Materials and methods This was a prospective, multicenter, cross-sectional study. There were 2132 subjects enrolled between 2010 and 2012. They included 96.2% men and 3.8% women, with a mean age of 76.1 years; 78.8% former or current smokers; and 21.2% never smokers. We screened subjects using low-dose computed tomography (CT). The CT images were taken with a CT dose Index of 2.7 mGy. The evaluated CT findings included subpleural curvilinear shadow/subpleural dots, ground glass opacity or interlobular reticular opacity, traction bronchiectasia, honeycombing change, parenchymal band, emphysema changes, pleural effusion, diffuse pleural thickening, rounded atelectasis, pleural plaques (PQs), and tumor formation. Results The PQs were detected in most of subjects (89.4%) and emphysema changes were seen in 46.0%. Fibrotic changes were detected in 565 cases (26.5%). A pathological diagnosis of LC was confirmed in 45 cases (2.1%) and MPM was confirmed in 7 cases (0.3%). The prevalence of LC was 2.5% in patients with a smoking history, which was significantly higher than that in never smokers (0.7%, p = 0.027). The prevalence of LC was 2.8% in subjects with emphysema changes, which was higher than that of subjects without those findings (1.6%); although, the difference was not statistically significant (p = 0.056). The prevalence of LC in subjects with both fibrotic plus emphysema changes was 4.0%, which was significantly higher than that of subjects with neither of those findings (1.8%, p = 0.011). Logistic regression analysis revealed smoking history, fibrotic plus emphysema changes, and pleural effusion as significant explanatory variables. Conclusions Smoking history, fibrotic plus emphysema changes, and pleural effusion were correlated with the prevalence of LC.

Background The objective of this study was to evaluate the effects of gene polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan therapy. Methods The eligibility criteria were: lung cancer patients scheduled to undergo irinotecan therapy, aged ≥ 20 years, with a performance status of 0–2. Thirty‐one patients were enrolled and their blood was collected and used to examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the concentrations of irinotecan, SN‐38, and SN‐38G after irinotecan therapy. Results The patients’ characteristics were as follows: male/female 25/6, median age 71 years (range 55–84), stage IIB/IIIA/IIIB/IV 2/6/11/12, and adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 14/10/3/4, respectively. The −/−, *6/−, *7/−, *27/−, *28/−, and *29/− UGT1A1 gene polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0 (0%) cases, respectively. The UGT1A1*27 polymorphism occurred separately from the UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those observed in the wild‐type patients. SN‐38 tended to remain in the blood for a prolonged period after the infusion of irinotecan in patients with UGT1A1*27 or UGT1A1*28 polymorphisms. No severe myelotoxicity was seen in the patients with UGT1A1*7. Conclusion UGT1A1*27 can occur separately from UGT1A1*28 and is related to leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan‐induced toxicities, and UGT1A1*29 seems to have little clinical impact.

BackgroundIt is occasionally difficult to distinguish progressive massive fibrosis (PMF) from lung cancer on computed tomography (CT) in patients with pneumoconiosis.PurposeTo evaluate the magnetic resonance imaging (MRI) features of PMF and to assess its ability to differentiate PMF from lung cancer.Material and MethodsBetween 2000 and 2014, 40 pulmonary lesions suspected to be lung cancer on the basis of CT in 28 patients with known pneumoconiosis were evaluated. Twenty-four of the 40 lesions were pathologically or clinically diagnosed as PMF. The signal pattern on T2-weighted (T2W) images, post-contrast enhancement pattern on T1-weighted (T1W) images, and the pattern of the time intensity curve (TIC) on contrast-enhanced dynamic studies were evaluated. All images were analyzed independently by two chest radiologists.ResultsAll 24 PMF lesions showed low signal intensity (SI) on T2W images (sensitivity, 100%), while 15 of 16 lung cancer lesions showed intermediate or high SI on T2W images (specificity, 94%) when PMF was regarded as a positive result. Six of 17 PMF lesions showed a homogeneous enhancement pattern (sensitivity, 35%), and 4/9 lung cancer lesions showed an inhomogeneous or a ring-like enhancement pattern (specificity, 44%). Six of 16 PMF lesions showed a gradually increasing enhancement pattern (sensitivity, 38%), and 7/9 lung cancer lesions showed rapid enhancement pattern (specificity, 78%).ConclusionWhen differentiation between PMF and lung cancer in patients with pneumoconiosis is difficult on CT, an additional MRI study, particularly the T2W imaging sequence, may help differentiate between the two.

The purpose of this article is to investigate whether there is a difference in susceptibility to transcatheter arterial chemoembolization between hepatocellular carcinomas (HCCs) showing high uptake and those showing low uptake of gadoxetic acid in the hepatobiliary phase of MRI.One hundred HCCs that achieved optimal chemoembolization, as assessed by immediate CT in 60 patients, were classified as having high (n = 19) or low (n = 81) uptake of gadoxetic acid on MRI performed before chemoembolization. The local recurrence rates were estimated using the Kaplan-Meier method, and differences between the groups were compared using the log-rank test. The following factors were also correlated with the local recurrence rate using the Cox proportional hazards model for a univariate analysis: high uptake of gadoxetic acid, number of feeding arteries, extrahepatic arterial supply, Child-Pugh class, clinical tumor stage, size, location, and iodized oil accumulation in the noncancerous tissue surrounding the lesion. Parameters that were significant at p0.05 were entered into a multivariate model.The 1- and 3-year local recurrence-free rates were 95% in high-uptake HCCs and 66% and 54%, respectively, in low-uptake HCCs (log-rank test, p0.01). The low uptake of gadoxetic acid was the only significant predictor of early local recurrence (hazard ratio = 9.24; p = 0.03) by multivariate analysis.HCCs showing high uptake of gadoxetic acid appear to be susceptible to chemoembolization.

In 2008, Kawabata etal. described a lesion which they termed "airspace enlargement with fibrosis" that could be included on the spectrum of smoking-related interstitial lung diseases. This group also reported that patients with airspace enlargement with fibrosis but without coexisting interstitial pneumonia of another type had no acute exacerbations and favorable prognoses on clinical follow-up. Here we describe the first case, to our knowledge, of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of another type. An 82-year-old man was referred to our department for worsening dyspnea and new alveolar opacities on chest radiograph following left pulmonary segmentectomy (S6) for cancer. A diagnosis of acute exacerbation of airspace enlargement with fibrosis without coexisting interstitial pneumonia of other types was made, based on pathological evidence of airspace enlargement with fibrosis and organizing diffuse alveolar damage. Treatment with high-dose methylprednisolone followed by tapered oral prednisolone resulted in gradual improvement of the clinical condition and chest radiographic findings. Clinicians should be aware that patients with airspace enlargement with fibrosis may experience acute exacerbation., Respiratory Medicine Case Reports, 13, pp.19-23; 2014