Search

Background: Despite the autoimmune nature of psoriasis, the potential association between psoriasis and interstitial lung disease (ILD) remains underexplored. This study aimed to investigate the frequency and clinical features of ILD in patients with psoriasis and propose a new conceptual framework of "ILD associated with psoriasis"., Methods: A retrospective analysis of 117 patients with psoriasis was conducted, excluding those without chest imaging prior to methotrexate or biologic use and those with other comorbidities leading to ILD., Results: ILD was identified in 12 (10%) patients with psoriasis; 6/50 with psoriasis vulgaris and 6/65 with psoriatic arthritis. Three of 12 patients had no history of smoking. Serum Krebs von den Lungen-6 (KL-6) levels were elevated in patients with ILD compared to those in patients without ILD. The indeterminate for usual interstitial pneumonia (UIP) pattern was the most prevalent CT finding. A lung biopsy specimen from a representative case revealed equivalent indeterminate for UIP. Over a median 8.9-year observation period, ILD progressed in only 5 patients, with no cases of respiratory failure or death due to ILD progression, suggesting generally favourable prognoses., Conclusions: ILD associated with psoriasis would be present, and its frequency is 10% of patients with psoriasis. We propose that chest radiography and a serum KL-6 test at the initial diagnosis of psoriasis would be useful in screening for the detection of ILD. We also recommend that a physician diagnosing ILD should carefully examine the skin findings, considering if psoriasis could be associated with ILD., Trial Registration: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Kagawa University (no. 2022 − 177). All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards. We obtained appropriate informed consent for the use of patient information through an opt-out form because of the retrospective nature of the study. Clinical trial number: not applicable. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Arthritis is one of the most common symptoms of Behcet's Disease (BD) observed in 57% of Japanese patients with BD. The relationship between arthritis and other clinical symptoms of BD and the impact of arthritis on the quality of life (QOL) of patients with BD are still unclear. Therefore, the current study aimed to clarify the differences in clinical symptoms depending on the presence or absence of arthritis and evaluate the impact of arthritis on QOL in these patients. Fifty-three Japanese patients diagnosed with BD and being treated for more than 6 months were included in this study. Patients were divided based on the presence of arthritis symptoms into an arthritis and a non-arthritis group. Clinical symptoms, disease activity, and QOL of both groups were compared using the Patient's global assessment (PGA), Evaluator's global assessment (EGA), and Behcet's disease current activity form (BDCAF) as indices of disease activity. To evaluate disease activity related to lesions other than arthritis, BDCAF excluding arthritis items was also calculated. The Behcet's disease quality of life (BDQOL) scale was used to assess patients' QOL. Oral ulcers and skin lesions were significantly more frequent in the arthritis group than in the non-arthritis group (p = 0.009 and 0.048, respectively). Among skin domains, papulopustular lesions tended to be more frequent in the arthritis group. EGA and BDCAF (both including and excluding arthritis-related items) scores were significantly higher in the arthritis group (p = 0.019, < 0.0001, and 0.0004 respectively). Although PGA and BDQOL tended to be higher in the arthritis group, the difference between the two groups was not statistically significant. The disease course in Japanese BD patients with arthritis was more frequently complicated by oral ulcers and skin lesions than in those without arthritis. In addition, BD patients with arthritis tended to have generally higher disease activity and low QOL than their non-arthritis counterparts. Further research is required to confirm these results., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Faculty of Medicine, Kagawa University (2023-057) and conducted in accordance with the Declaration of Helsinki. The Ethics Committee of the Faculty of Medicine at Kagawa University waived the need for written informed consent due to the retrospective nature of the study., (© 2024. The Author(s).)

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed "tumor pseudoprogression." The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20 + large atypical lymphocytes forming residual nodules, encircled by CD4 + and CD8 + lymphocytes, with a predominance of CD8 + T cells over CD4 + T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management., (© 2024. Japanese Society of Hematology.)

Background: Lung cancer was often diagnosed by malignant pleural effusion (MPE). Excessive MPE is generally discarded. The establishment of cell lines and the generation of cancer mouse models have the potential to be directly linked to personalized medicine. This study aimed to establish cell lines and generate mouse models using MPE., Methods: Cells derived from 5 mL of MPE were cultured in several conditions, including 100% MPE supernatant and Roswell Park Memorial Institute-1640 supplemented with 10% fetal bovine serum (FBS) or 10% MPE supernatant. When steady cell growth was observed, fewer cells were spread and the colonies were selected to establish the cell line. Cells derived from 10 mL of MPE were inoculated subcutaneously into non-obese diabetic-severe combined immunodeficiency (NOD- scid ) and NOD.Cg- Prkdc scid Il2rg tmlWjl /SzJ (NSG) mice to assess tumorigenic potential., Results: MPEs were obtained from 28 lung cancer patients, 23 of whom had adenocarcinoma. Cell lines were established from 5 patients (18%). Tumorigenesis was observed in 6 of 28 cases (21%). However, in 7 cases, the mice (7 NSG and 1 NOD- scid mice) became progressively weaker, lost their hair, and died within 12 weeks without tumorigenesis. The appearance and pathological findings were consistent with graft-versus-host disease. Cell line establishment and tumorigenesis in mice were associated with a lower response to first-line therapy and poorer prognosis of patients., Conclusions: When MPEs were simply utilized, the cell line establishment rate was 18% and the engraftment rate in mice was 21%. The prognosis of patients who underwent cell line establishment and engraftment in mice was poor., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-143/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor is an extremely rare malignant neoplasm and a subtype of fibroblastic reticular cell tumor, classified within the dendritic cell tumor group. We describe a case of an epicardial CIRC tumor that was resected and subsequently recurred in the left pulmonary hilum. This recurrence was treated with immunotherapy followed by radiotherapy. A 71-year-old man with a history of colon cancer incidentally had a mass bordering the epicardium on a postoperative follow-up computed tomography scan. Pericardial tumor resection was performed due to suspected metastasis from colon cancer. Histopathologically, the patient was diagnosed as a CIRC tumor (programmed death ligand 1 expression rate > 95%). Seven months after pericardial surgery, the patient was treated with nivolumab because of local recurrence in the left pulmonary hilum, but the tumor size gradually increased. Three months after the initiation of nivolumab, the patient had a completely atelectatic left lung due to tumor invasion into the left main bronchus and was treated with external beam radiotherapy of 66 Gy in 33 fractions. One and a half months after the completion of radiotherapy, the atelectasis disappeared, and aeration was greatly improved. Three months after the completion of radiotherapy, atelectasis and pericardial effusion appeared owing to tumor regrowth, and the patient died of heart failure 2 months later. This report provides insights into the efficacy of immunotherapy and radiotherapy for CIRC tumor., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Tixagevimab and cilgavimab (EVA, Evusheld®), monoclonal antibody combination treatments, consisted of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). EVA showed prophylactic and therapeutic effects against coronavirus disease 2019. The Japanese Society of Hematology recommended EVA for such patients with active treatment, but each institution decided on comprehensive administration. We develop a systematic procedure for comprehensive EVA injection prophylactically in patients with hematological malignancies without any over/under-indication. We listed all patients with the required indications from November 2022 to March 2023. We included 178 cases, 84 females and 94 males, with a median age of 70 (range: 19-90) years. Underlying diseases are myeloid neoplasms in 36 (20%), lymphoid neoplasms in 75 (73%), and others. Indications were intensively hematological malignancy treatment, rituximab treatment within 12 months, burton kinase inhibitor treatment, after chimeric antigen receptor T cell immunotherapy, and after stem cell transplantation in 74 (41%), 73 (41%), 3 (2%), 5 (3%), and 23 (13%) cases, respectively. Of the 178 cases, 22 (12.4%) refused EVA injection. Further, 42 and 136 cases were administered outpatient and inpatient, respectively. Over 95% of the listed cases received EVA injection within 3 months. No severe toxicities were observed among them (N = 156), and 8 (5.2%) cases had breakthrough SARS-CoV-2 infection, which was significantly lower (P = 0.02) than those without EVA (4 [18.2%] of 22 cases). Both groups showed no moderate or severe infection cases. This single-center experience showed that comprehensive EVA injection management effectively generated safer completion with preferable clinical impact., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS)., Methods: CTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups., Results: Twenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups., Conclusions: This study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD., (© 2024. The Author(s).)

Background Aims: Tacrolimus (TAC) plus short-term methotrexate (stMTX) is used for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). TAC blood concentrations are frequently adjusted to enhance the graft-versus-leukemia/lymphoma effect or attenuate severe GVHD. Limited information is available on the clinical impact of these adjustments and the optimal time to perform them in order to achieve good clinical outcomes., Methods: We retrospectively analyzed 211 patients who underwent allo-HSCT at our institutes., Results: Higher TAC concentrations in week 3 correlated with a significantly higher cumulative incidence of relapse (CIR) (P = 0.03) and lower nonrelapse mortality (P = 0.04). The clinical impact of high TAC concentrations in week 3 on CIR was detected in the refined disease risk index: low/intermediate (P = 0.04) and high (P < 0.01), and conditioning regimens other than cyclophosphamide/total body irradiation and busulfan/cyclophosphamide (P = 0.07). Higher TAC concentrations in week 1 correlated with a lower grade 2-4 acute GVHD rate (P = 0.01). Higher TAC concentrations in weeks 2 and 3 correlated with slightly lower (P = 0.05) and significantly lower (P = 0.02) grade 3-4 acute GVHD rates, respectively. Higher TAC concentrations in weeks 1 and 3 were beneficial for severe acute GVHD in patients with a human leukocyte antigen-matched donor (P = 0.03 and P < 0.01, respectively), not treated with anti-thymocyte globulin (P = 0.02 and P = 0.02, respectively), and receiving three stMTX doses (P = 0.03 and P = 0.02, respectively)., Conclusions: The clinical impact of TAC concentrations varied according to patient characteristics, including disease malignancy, conditioning regimens, donor sources, and GVHD prophylaxis. These results suggest that TAC management needs to be based on patient profiles., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD)., Methods: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD., Results: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively., Conclusion: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD., (© 2024. The Author(s).)

Background: The ARROW study demonstrated that once-weekly carfilzomib and dexamethasone (wKd) therapy significantly prolonged progression-free survival compared with twice-weekly carfilzomib and dexamethasone therapy in relapsed or refractory multiple myeloma patients. Aim: To describe the treatment patterns, effectiveness and safety of wKd therapy in real-world settings in Japan. Methods: We investigated data from the medical records of 126 Japanese patients with relapsed or refractory multiple myeloma. Results: The overall response rate was 66.3%. The median progression-free survival was 9.5 months. The incidence of treatment-emergent adverse events of any grade and grade ≥3 were 45.8 and 20.8%, respectively. Conclusion: There were no new or unexpected safety signals in this study. This study demonstrated the effectiveness and safety profiles of wKd therapy in Japan.

A 38-year-old female was referred with a history of fever, polyarthralgia, and bone pain. She was diagnosed with chronic recurrent multifocal osteomyelitis based on imaging and biopsy findings. Non-steroidal anti-inflammatory drugs and bisphosphonate caused no improvement. Then, she developed recurrent diarrhoea and abdominal pain. Genetic testing revealed MEFV mutation. Based on the symptoms and genetic mutation results that emerged during the course of these events, she was diagnosed with familial Mediterranean fever. All symptoms, including bone pain, improved with daily colchicine administration. This case was considered familial Mediterranean fever complicated with a clinical diagnosis of chronic recurrent multifocal osteomyelitis, which is included in the spectrum of pyrine autoinflammatory diseases. Considering this case, patients with chronic recurrent multifocal osteomyelitis with MEFV gene variants may respond to colchicine., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Superior vena cava syndrome is rarely attributed to chronic obstructive pulmonary disease., Case Presentation: We present the case of an 82-year-old Japanese man who experienced gradually progressive dyspnea on exertion. His physical examination revealed small vascular dilatations on his chest and upper abdominal skin characterized by blood flow from head to leg, indicating superior vena cava syndrome. Radiographic findings included lung hyperinflation with a drop-like heart on chest X-ray, and emphysematous changes on computed tomography. The superior vena cava appeared extremely narrow and slit-like, with no adjacent mass or giant bulla. Pulmonary function testing indicated a forced expiratory volume in 1 second of 0.82L (44.4% of predicted value) and a forced expiratory volume in 1 second/forced vital capacity of 31.29%. A diagnosis of chronic obstructive pulmonary disease was made. We discuss how longitudinal forces can narrow the superior vena cava, particularly when it protrudes toward the lung field due to its anatomical location in the upper mediastinum. The absence of mediastinal adipose tissue may render the superior vena cava susceptible to compression, resulting in a loss of its typical columnar structure. The protrusion of the superior vena cava toward the lung field may be a contributing factor to superior vena cava narrowing in chronic obstructive pulmonary disease., Conclusion: This case represents the first reported instance of superior vena cava syndrome associated with chronic obstructive pulmonary disease, characterized by lung hyperinflation, in the absence of a giant bulla., (© 2023. The Author(s).)