The lesion site in malignant psoas syndrome influences the cancer pain intensity.

BACKGROUND: Malignant psoas syndrome (MPS) is characterized by pain and hip flexion fixation due to tumor infiltration of the iliopsoas muscle. However, the dose of opioid required to control pain varies markedly among MPS patients. As the ability to predict whether an MPS patient will need a higher opioid dose in the early period of pain control is clinically meaningful, we retrospectively evaluated the relationship between lesion site in MPS and the opioid dose required for pain control. METHODS: Fourteen patients received opioid control of cancer pain due to MPS between January 2014 and December 2018. Two patients with paraplegia who died during pain control were excluded from this study. The remaining 12 patients were divided into group of muscle attachment (group MA) (n=6), with the lesion in the iliopsoas MA to the spine, and group of muscle belly (group MB) (n=6), with the lesion in the iliopsoas MB. We compared opioid doses for pain control between groups. RESULTS: No significant differences in background characteristics were seen between groups. Opioid dose (in oral morphine equivalents) was significantly higher in group MB (1,374.3±504.5 mg/day) than in group MA (92±67.9 mg/day; P=0.0007). CONCLUSIONS: MPS patients with the lesion in the MB appear to need a higher opioid dose for pain control than patients with the lesion in the MA.

The International Association for the Study of Lung Cancer Early Lung Imaging Confederation Open-Source Deep Learning and Quantitative Measurement Initiative.

INTRODUCTION: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research. METHODS: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans. RESULTS: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans. CONCLUSIONS: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets.

TIM-3 expression induces resistance to PD-1 inhibitor in G-CSF-producing lung spindle cell carcinoma: A case report.

Lung spindle cell carcinoma is an aggressive subtype of pleomorphic lung cancer resistant to cytotoxic chemotherapy. Programmed cell death-1 (PD-1) inhibitors have been reported to have clinical effects in patients with spindle cell carcinoma; however, the resistance mechanism to PD-1 inhibitors is yet to be fully elucidated. Herein, we report the case of an 88-year-old man with G-CSF-producing spindle cell carcinoma who acquired resistance to PD-1/PD-ligand 1 (L1) inhibitor in an early setting after a remarkable response. A histopathological review of the resistant specimen revealed a low count of CD8+ T cells and a predominant presence of M2 and TIM-3+ macrophages, indicating the presence of an immunosuppressive microenvironment. Our findings suggest a novel resistance mechanism to PD-1/PD-L1 inhibitors in G-CSF-producing spindle cell carcinoma.

Differentiation Between Heterogeneous GGN and Part-Solid Nodule Using 2 D Grayscale Histogram Analysis of Thin-Section CT Image.

INTRODUCTION/BACKGROUND: To evaluate cases of surgically resected pulmonary adenocarcinoma (Ad) with heterogenous ground-glass nodules (HGGNs) or part-solid nodules (PSNs) and to clarify the differences between them, and between invasive adenocarcinoma (IVA) and minimally invasive adenocarcinoma (MIA) + adenocarcinoma in situ (AIS) using grayscale histogram analysis of thin-section computed tomography (TSCT). MATERIALS AND METHODS: 241 patients with pulmonary Ad were retrospectively classified into HGGNs and PSNs on TSCT by three thoracic radiologists. Sixty HGGNs were classified into 17 IVAs, 26 MIAs, and 17 AISs. 181 PSNs were classified into 114 IVAs, 55 MIAs, and 12 AISs. RESULTS: We found significant differences in area (P = 0.0024), relative size of solid component (P <0.0001), circumference (P <0.0001), mean CT value (P <0.0001), standard deviation of the CT value (P <0.0001), maximum CT value (P <0.0001), skewness (P <0.0001), kurtosis (P <0.0001), and entropy (P <0.0001) between HGGNs and PSNs. In HGGNs, we found significant differences in relative size of solid component (P <0.0001), mean CT value (P = 0.0005), standard deviation of CT value (P = 0.0071), maximum CT value (P = 0.0237), and skewness (P = 0.0027) between IVAs and MIA+AIS lesions. In PSNs, we found significant differences in area (P = 0.0029), relative size of solid component (P = 0.0003), circumference (P = 0.0004), mean CT value (P = 0.0011), skewness (P = 0.0009), and entropy (P = 0.0002) between IVAs and the MIA+AIS lesions. CONCLUSION: Quantitative evaluations using grayscale histogram analysis can clearly distinguish between HGGNs and PSNs, and may be useful for estimating the pathology of such lesions.

Lung Cancer Screening in Asia: An Expert Consensus Report.

INTRODUCTION: The incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. METHOD: A group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. RESULTS: Significant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. CONCLUSIONS: Asian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.

Respiratory support with nasal high flow without supplemental oxygen in patients undergoing endoscopic retrograde cholangiopancreatography under moderate sedation: a prospective, randomized, single-center clinical trial.

BACKGROUND: Nasal high flow (NHF) may reduce hypoxia and hypercapnia during an endoscopic retrograde cholangiopancreatography (ERCP) procedure under sedation. The authors tested a hypothesis that NHF with room air during ERCP may prevent intraoperative hypercapnia and hypoxemia. METHODS: In the prospective, open-label, single-center, clinical trial, 75 patients undergoing ERCP performed with moderate sedation were randomized to receive NHF with room air (40 to 60 L/min, n = 37) or low-flow O2 via a nasal cannula (1 to 2 L/min, n = 38) during the procedure. Transcutaneous CO2, peripheral arterial O2 saturation, a dose of administered sedative and analgesics were measured. RESULTS: The primary outcome was the incidence of marked hypercapnia during an ERCP procedure under sedation observed in 1 patient (2.7%) in the NHF group and in 7 patients (18.4%) in the LFO group; statistical significance was found in the risk difference (-15.7%, 95% CI -29.1 - -2.4, p = 0.021) but not in the risk ratio (0.15, 95% CI 0.02 - 1.13, p = 0.066). In secondary outcome analysis, the mean time-weighted total PtcCO2 was 47.2 mmHg in the NHF group and 48.2 mmHg in the LFO group, with no significant difference (-0.97, 95% CI -3.35 - 1.41, p = 0.421). The duration of hypercapnia did not differ markedly between the two groups either [median (range) in the NHF group: 7 (0 - 99); median (range) in the LFO group: 14.5 (0 - 206); p = 0.313] and the occurrence of hypoxemia during an ERCP procedure under sedation was observed in 3 patients (8.1%) in the NHF group and 2 patients (5.3%) in the LFO group, with no significant difference (p = 0.674). CONCLUSIONS: Respiratory support by NHF with room air did not reduce marked hypercapnia during ERCP under sedation relative to LFO. There was no significant difference in the occurrence of hypoxemia between the groups that may indicate an improvement of gas exchanges by NHF. TRIAL REGISTRATION: jRCTs072190021 . The full date of first registration on jRCT: August 26, 2019.

Genetic profile of thymic epithelial tumors in the Japanese population: an exploratory study examining potential therapeutic targets.

Background: Thymic epithelial tumors (TETs) are prone to developing in East Asian populations. However, little is known about the genomic profile of TETs in East Asian populations, and the genomic aberrations in TETs have not yet been fully clarified. Thus, molecular targeted therapies for patients with TETs have not been established. This prospective study was conducted to explore the genetic abnormalities of surgically resected TETs in a Japanese cohort and to identify clues for carcinogenesis and potential therapeutic targets in TETs. Methods: Genetic profiles of TETs were investigated using fresh-frozen specimens resected from operable cases with TETs. DNA sequencing was performed using a next-generation sequencing (NGS) gene panel test with Ion Reporter™ and CLC Genomics Workbench 11.0. The mutation sites were further confirmed by Sanger sequencing, digital droplet polymerase chain reaction (ddPCR), and TA cloning for validation. Results: Among 43 patients diagnosed with anterior mediastinal tumors between January 2013 and March 2019, NGS and validation analyses were performed in 31 patients [29 thymomas and two thymic cancers (TCs)] who met the study criteria. Of these, 12 cases of thymoma types A, AB, B1, and B2 harbored the general transcription factor 2-I (GTF2I) mutation (L424H). Conversely, the mutation was not detected in type B3 thymoma or TC, suggesting that the GTF2I mutation existed in indolent types of TETs. Rat sarcoma viral oncogene (RAS) mutations were detected in three cases [Harvey RAS (HRAS) in two cases of type AB thymoma and neuroblastoma RAS (NRAS)] in one case of type B1 thymoma), and additional sex combs like 1 (ASXL1) mutation was present in one case of TC. All RAS mutations were observed in GTF2I-mutated cases. Conclusions: The GTF2I mutation (L424H) is the most frequently occurring mutation in the limited histology of thymoma, consistent with those in the non-Asian population. HRAS and NRAS mutations co-occurred in cases harboring the GTF2I mutation. These findings suggest that the existence of the GTF2I mutation might be related to indolent types of TETs, and RAS mutations could be candidates as therapeutic targets in TETs.

Clinical Outcomes of Stereotactic Body Radiation Therapy for Early-stage Non-small Cell Lung Cancer.

BACKGROUND/AIM: To investigate the clinical outcomes of stereotactic body radiotherapy (SBRT) in patients with early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Among consecutive patients with early-stage NSCLC who received SBRT between November 2009 and September 2019, those with cT1-2N0M0 staged by the UICC TNM classification and staging system for lung cancer were retrospectively analyzed. RESULTS: Fifty-three patients with early-stage NSCLC received SBRT. The median follow-up period was 29 months (range=2-105 months). Twenty-one lung tumors were clinically diagnosed as early-stage primary lung cancers without histological confirmation. Histological examinations revealed adenocarcinoma in 24 patients and squamous cell carcinoma in 8. Two- and 5-year local control, cancer-specific survival, progression-free survival (PFS), and overall survival (OS) rates were 94.4 and 94.4%; 94.6 and 90.8%; 69.0 and 43.3%; and 80.0 and 59.3%, respectively. In a univariate analysis, the T stage, histology, and type of pulmonary nodule correlated with PFS and OS. CONCLUSION: Good clinical outcomes were achieved by patients with early-stage NSCLC who received SBRT.

Clinical Outcomes of Definitive Chemoradiotherapy for Cervical Esophageal Cancer.

BACKGROUND/AIM: To investigate the clinical outcomes of concurrent chemoradiotherapy (CCRT) in patients with cervical esophageal carcinoma and analyze the prognostic factors. PATIENTS AND METHODS: Thirty-nine patients with cervical esophageal carcinoma were retrospectively identified among consecutive patients who received CCRT between November 2009 and September 2019 at our institution. The patients were treated by intensity-modulated radiation therapy (N=13) or three-dimensional conformal radiotherapy (N=26). RESULTS: The median follow-up period was 35 months (range=2-158 months). There were 32 men and 7 women with a median age of 66 years (range=50-83 years). Clinical stages were I in 6 patients, II in 4, III in 19, and IV in 10. Hypopharyngeal invasion was noted in 8 patients. The initial treatment responses were evaluated 3-6 weeks after the final session of CCRT: a complete response (CR) in 24 patients, a partial response (PR) in 13, and stable disease (SD) in 2. Two- and 5-year overall survival (OS) rates were 73.8 and 59.4%, respectively. Two- and 5-year progression-free survival (PFS) rates were 57.8 and 48.0%, respectively. A univariate analysis identified the initial treatment response (CR or non-CR) as a significant factor for OS (p=0.0002) and PFS (p=0.0026). The CR rate was 81.0% in patients with T1-3 and 33.3% in those with T4 (p=0.0038). CONCLUSION: Patients with cervical esophageal carcinoma in Nagasaki University Hospital in Japan achieved superior outcomes compared with previous studies. CR rate was higher in patients with T1-3 and correlated with better OS.

Surgically resected lung adenocarcinoma: do heterogeneous GGNs and part-solid nodules on thin-section CT show different prognosis?

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.

Sensitivity of transbronchial lung cryobiopsy in the diagnosis of different interstitial lung diseases.

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.

[Issues of Equalization of Cancer Genomic Medicine-Focusing on the Current Status in Nagasaki Prefecture].

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.

[Panel Discussion - Problems in the Cancer Genomic Medicine].

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.

[Wasted Anti-Cancer Agents Due to Cancellations after Dispensing].

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.

Phase II study of S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Results of the LOGIK1605/JART-1501 study.

BACKGROUND: Combination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient. METHODS: Previously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2 /day S-1 orally on days 1-14 plus 60 mg/m2 /day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy). RESULTS: Three patients were enrolled into the study. 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 nonevaluable cases, the second course of chemotherapy was judged to be post-protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). 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 >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.

The diagnosis of early pneumoconiosis in dust-exposed workers: comparison of chest radiography and computed tomography.

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.

A retrospective study on radiological findings of diffuse pleural thickening with benign asbestos pleural effusion in Japanese cases.

The requirement for compensation for diffuse pleural thickening in benign asbestos pleural effusion include five computed tomography findings of organized pleural effusion: [1] heterogeneity in the pleural effusion, [2] declined chest capacity, [3] "crow's feet" sign at the pleura, [4] immobilization of effusion volume, and [5] air in the effusion. Pleural effusion is diagnosed as organized, immobilized, and in the state of diffuse pleural thickening if at least three of these items are fulfilled, ([1] and [3] compulsory + one of the remaining items). This retrospective study investigated whether the requirement to confirm no organized pleural effusion changes after a follow-up of >3 months were available for cases fulfilling three of the five items; i.e., the confirmation of only [2] with [1] and [3]. Of 302 cases recognized by the Japanese laws, 105 cases with diffuse pleural thickening with organized effusion were enrolled. The number of subjects who fulfilled the diagnostic requirement for organized pleural effusion was confirmed. Eight subjects had a full score of 5 points, 82 subjects scored 4 points, and only 15 subjects scored 3 points. Furthermore, no changes were observed in the organized pleural effusion volume after a follow-up of >3 months.

Determining Response to Treatment for Drug-Induced Bronchocentric Granulomatosis by the Forced Oscillation Technique.

Anti-tumor necrosis factor alpha (TNFα) therapy is widely used to treat various inflammatory conditions. Paradoxically, there are several case reports describing the development of bronchocentric granulomatosis treated with TNFα inhibitors, and it is difficult to determine the effect of treatment using conventional spirometry because the lesions are located in small airways. However, it has been reported that the forced oscillation technique (FOT) is useful in the evaluation of small airway disease in bronchial asthma or chronic obstructive pulmonary disease. We performed the FOT to determine the effect of treatment on bronchocentric granulomatosis and found it to be useful. We report the case of a 55-year-old female with ulcerative colitis who was treated with golimumab and who developed bronchocentric granulomatosis as a sarcoid-like reaction to golimumab. She was successfully treated with prednisone, and the treatment efficacy was confirmed by the FOT. The FOT may be useful in the evaluation of small airway disease in bronchocentric granulomatosis. This case may help inform clinicians of the usefulness of the FOT to assess small airway disease in various diseases.

Real-World Incidence of Febrile Neutropenia among Patients Treated with Single-Agent Amrubicin: Necessity of the Primary Prophylactic Administration of Granulocyte Colony-Stimulating Factor.

BACKGROUND: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC); however, it can cause severe myelosuppression. PURPOSE: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. PATIENTS AND METHODS: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. RESULTS: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32-86); male/female: 126/30; performance status (0/1/2): 9/108/39; SCLC/NSCLC/others: 111/30/15; and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). CONCLUSIONS: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.

A newly established monoclonal antibody against ERCC1 detects major isoforms of ERCC1 in gastric cancer.

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.