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Owing to their unique physicochemical properties and diverse biological effects, ultrafine bubbles (UFBs) have recently been expected to be utilized for industrial and biological purposes. Thus, this study investigated the biological safety of UFBs in water for living beings in drinking the water with a view to future use in health sciences. In this study, we used H2-filled UFBs (NanoGAS®) that can hold hydrogen in the aqueous phase for a long time. Mice were randomly assigned to one of three groups: those receiving NanoGAS® water, reverse osmosis water, or natural mineral water, and they ingested it ad libitum for one month or three months. As a result, subchronic drinking of NanoGAS® water does not affect either the common blood biochemical parameters or the health of the organs and mucosal membranes. Our results, for the first time, scientifically demonstrated the biological safety of H2-filled UFBs water for subchronic oral consumption.
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Ingestión de Líquidos , Hidrógeno , Agua , Animales , Ratones , Agua/química , Hidrógeno/administración & dosificación , GasesAsunto(s)
Neoplasias de los Genitales Masculinos , Neoplasias Hepáticas , Enfermedad de Paget Extramamaria , Neoplasias del Colon Sigmoide , Humanos , Masculino , Antígeno Carcinoembrionario , Neoplasias de los Genitales Masculinos/patología , Genitales/patología , Queratina-19 , Neoplasias Hepáticas/diagnóstico , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/patología , AncianoRESUMEN
BACKGROUND: Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies. METHODS: We examined 44 cases of SPC of the breast to define the cytologic features. We also made a systemic review of reported cases of SPC and neuroendocrine tumor (NET) of the breast. RESULTS: Both of our and the reviewed cases with SPC were very similar in the cytologic finding. It included hypercellularity, highly discohesive clusters, numerous isolated cells, small nuclei, finely granular chromatin of salt-and-pepper appearance, inconspicuous nucleoli, low nuclear-cytoplasmic ratio, and a plasmacytoid appearance. Moreover, SPC and NET had frequently all of these features in common. Capillary vessels structures and mucinous substance were not frequently seen in our and the reviewed cases with SPC. Rosette and pseudorosette were very rare in the cytologic specimen. The immunocytochemistry with our 9 cases with SPC indicated diffuse positivity for chromogranin A and/or synaptophysin. CONCLUSION: Many cytologic features are frequently shared by SPC and NET of the breast. However, the vascular structure may not be a precise criterion for SPC. Rosette and pseudorosette are rarely helpful for the cytologic diagnosis.
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Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Neuroendocrino , Carcinoma Papilar , Tumores Neuroendocrinos , Femenino , Humanos , Mama/patología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Neuroendocrino/patología , Carcinoma Papilar/patología , Tumores Neuroendocrinos/patologíaRESUMEN
Solid papillary carcinoma of the breast (SPC) is a rare tumor of the breast with the unique histology and frequent neuroendocrine differentiation. However, a real nature and diagnostic importance of the neuroendocrine differentiation have not been properly handled. And relationship between SPC and the other types of invasive breast carcinoma, especially neuroendocrine tumor of the breast (NETb), has not been fully explained. We conducted a clinicopathological study of SPC to tackle these problems.In the study, we included 127 cases of SPC with long-term follow-ups of up to 30 years. The incidence in the breast carcinoma was 2.0%. The patients with SPC had a significantly better prognosis and no patients died of the tumor. The 35 cases had only SPC in situ (SPC-IS), while the 92 cases had both SPC-IS and SPC with invasion (SPC-INV). Immunohistochemically, 123 of the 127 cases exhibited diffuse expression of one or more neuroendocrine markers. Fifty of the 92 cases had exclusively invasive SPC (iSPC) as the invasive component. Twenty-two cases of iSPC were combined with NETb and the 18 cases with MUC. Six of 8 cases with metastatic SPC-INV disclosed iSPC in the axillary lymph node.This study suggests that SPC is immunohistochemically compatible with NET of the systemic organs (NETs). And the unique morphology of SPC may represent a traditional histology of NETs. The study also indicates that SPC has close relationship between NETb and type B MUC. And SPC and NETb may represent a spectrum of the same disease.
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Adenocarcinoma Papilar , Neoplasias de la Mama , Carcinoma Papilar , Tumores Neuroendocrinos , Humanos , Femenino , Estudios de Seguimiento , Carcinoma Papilar/patología , Mama/patología , Neoplasias de la Mama/patología , Tumores Neuroendocrinos/patología , Proteínas Tirosina Quinasas Receptoras , Biomarcadores de TumorRESUMEN
Objectives: The Glasgow-Blatchford score (GBS) is a widely used risk assessment tool for patients with upper gastrointestinal bleeding. However, it only identifies a relatively low proportion of patients at low risk for adverse events and poor outcomes. We developed a simple diagnostic algorithm combining the GBS and nasogastric aspirate and evaluated its diagnostic performance. Methods: A total of 115 consecutive patients with suspected nonvariceal upper gastrointestinal bleeding who underwent nasogastric tube placement and upper endoscopy at our emergency department were prospectively evaluated. We compared the diagnostic accuracy of the GBS and our algorithm for predicting high-risk endoscopic lesions (HRELs) using receiver operating characteristic curve analysis. Results: Thirty-five patients had HRELs. Compared with the GBS, our algorithm showed superior performance with respect to the prediction of HRELs (area under the curve, 0.639 and 0.854, respectively; p < 0.001). With set optimal threshold values, the algorithm identified a significantly higher proportion of patients who did not have HRELs than the GBS (23.5% vs. 2.6%, p < 0.001). Conclusions: The novel algorithm has improved the diagnostic performance of the GBS and predicted more patients who did not have HRELs than the GBS alone. After further validation, it may be a useful tool for making clinical management decisions for patients with nonvariceal upper gastrointestinal bleeding.
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Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, â¼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)-based production system for an induced pluripotent stem cell-derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB.
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Antígenos de Plaqueta Humana , Trasplante de Células Madre Hematopoyéticas , Células Madre Pluripotentes Inducidas , Trombocitopenia , Animales , Humanos , Conejos , Transfusión de Plaquetas/efectos adversos , Células Madre Pluripotentes Inducidas/metabolismo , Plaquetas/metabolismo , Trombocitopenia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
We report the case of a 63-year-old man who underwent annual surveillance esophagogastroduodenoscopy, during which a small squamous cell carcinoma and a tiny yellowish granular lesion were found in the middle esophagus, slightly apart from each other. Magnifying endoscopy with narrow-band imaging of the yellowish granular lesion showed yellowish spots and blots scattered within an approximately 2-mm area. The larger spots appeared nodular and were overlaid with tortuous microvessels. Subsequently, both the lesions were excised en masse via endoscopic submucosal dissection, and the yellowish lesion was determined to be xanthoma. Histologically, an aggregated nest of foam cells surrounded by intrapapillary capillary vessels filled the intraepithelial papillae; the foam cells also extended inferiorly, below the rete ridges, and were sparsely distributed through the lamina propria mucosae. To our knowledge, the latter finding is the first to be described in literature, which leads us to postulate that the number of foam cells in the lamina propria mucosae may affect how thick and yellow a xanthoma appears on endoscopy. We believe that this case that presents a highly detailed comparison between endoscopic and histologic findings improves our understanding of the endoscopic appearance of esophageal xanthomas and may facilitate a precise diagnosis of this rare disease.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Xantomatosis , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Endoscopía Gastrointestinal , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/cirugía , Esofagoscopía/métodos , Humanos , Masculino , Persona de Mediana Edad , Imagen de Banda Estrecha , Xantomatosis/complicaciones , Xantomatosis/diagnóstico por imagen , Xantomatosis/cirugíaRESUMEN
There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.
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Microbioma Gastrointestinal , Neoplasias/epidemiología , Neoplasias/microbiología , Estado Nutricional , Disbiosis/microbiología , Trasplante de Microbiota Fecal , Humanos , Factores de RiesgoRESUMEN
Citrus mosaic virus (CiMV) is one of the causal viruses of citrus mosaic disease in satsuma mandarins (Citrus unshiu). Prompt detection of trees infected with citrus mosaic disease is important for preventing the spread of this disease. Although rabbit monoclonal antibodies (mAbs) exhibit high specificity and affinity, their applicability is limited by technical difficulties associated with the hybridoma-based technology used for raising these mAbs. Here, we demonstrate a feasible CiMV detection system using a specific rabbit mAb against CiMV coat protein. A conserved peptide fragment of the small subunit of CiMV coat protein was designed and used to immunize rabbits. Antigen-specific antibody-producing cells were identified by the immunospot array assay on a chip method. After cloning of variable regions in heavy or light chain by RT-PCR from these cells, a gene set of 33 mAbs was constructed and these mAbs were produced using Expi293F cells. Screening with the AlphaScreen system revealed eight mAbs exhibiting strong interaction with the antigen peptide. From subsequent sequence analysis, they were grouped into three mAbs denoted as No. 4, 9, and 20. Surface plasmon resonance analysis demonstrated that the affinity of these mAbs for the antigen peptide ranged from 8.7 × 10-10 to 5.5 × 10-11 M. In addition to CiMV, mAb No. 9 and 20 could detect CiMV-related viruses in leaf extracts by ELISA. Further, mAb No. 20 showed a high sensitivity to CiMV and CiMV-related viruses, simply by dot blot analysis. The anti-CiMV rabbit mAbs obtained in this study are envisioned to be extremely useful for practical applications of CiMV detection, such as in a virus detection kit.
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Anticuerpos Monoclonales/biosíntesis , Citrus/virología , Virus del Mosaico/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/química , Especificidad de Anticuerpos/inmunología , Proteínas de la Cápside/inmunología , Cinética , Hojas de la Planta/virología , ConejosRESUMEN
BACKGROUND: Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in several advanced cancers. We report results from JAVELIN Solid Tumor JPN, a phase 1 trial of avelumab in Japanese patients with advanced solid tumors with expansion in patients with advanced gastric cancer/gastroesophageal junction cancer. METHODS: In the dose-escalation part, eligible patients had various previously treated metastatic or advanced solid tumors. In the dose-expansion part, patients had stage IV gastric cancer/gastroesophageal junction adenocarcinoma and disease progression after prior therapy that included a platinum and fluoropyrimidine agent. Patients received avelumab every 2 weeks intravenously at 3, 10, or 20 mg/kg during dose escalation and 10 mg/kg during dose expansion. RESULTS: Among 17 patients who received avelumab in the dose-escalation part, no dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. 40 patients were enrolled in the dose-expansion part, of whom 21 (52.5%) had received ≥ 3 prior lines of therapy for advanced disease. In these patients, the objective response rate was 10.0% (95% CI, 2.8-23.7%) and median overall survival was 9.1 months (95% CI, 7.2-11.2 months). Three of 40 patients (7.5%) had a grade 3 treatment-related adverse event (alanine aminotransferase increase, anemia, and hyponatremia), and no grade ≥ 4 treatment-related adverse events occurred. Five patients (12.5%) had an immune-related adverse event (all grade 1/2). CONCLUSIONS: Avelumab showed acceptable safety in Japanese patients with advanced solid tumors and clinical activity in patients with advanced gastric cancer/gastroesophageal junction cancer and disease progression after chemotherapy.
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Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Neoplasias Esofágicas/patología , Unión Esofagogástrica/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/patología , Tasa de Supervivencia , Distribución TisularRESUMEN
Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Sarcoma de Ewing/diagnóstico , Anciano , Resultado Fatal , Humanos , MasculinoRESUMEN
Aim: Outside of Japan, recombinant-human chorionic gonadotropin (r-hCG) is widely used for the induction of final follicular maturation and early luteinization in women undergoing ovulation induction; whereas in Japan, urine-derived hCG (u-hCG) is predominantly used. The primary objective of this study was to demonstrate the non-inferiority of r-hCG to u-hCG for ovulation induction, as assessed by the ovulation rate. Methods: This was an open-label, parallel-group, randomized, multicenter, phase III trial in Japanese women with anovulation or oligo-ovulation secondary to hypothalamic-pituitary dysfunction or polycystic ovary syndrome, undergoing ovulation induction with recombinant-human follicle-stimulating hormone. The women were randomized (2:1) to receive either a single 250 µg s.c. dose of r-hCG or a single 5000 IU i.m. dose of u-hCG for ovulation triggering. Results: Eighty-one women were randomized to either r-hCG (n=54) or u-hCG (n=27). Ovulation occurred in 100% of the participants and treatment with r-hCG was observed to be non-inferior to u-hCG for ovulation induction. Overall, the type and severity of adverse events were as expected for women receiving fertility treatment. Conclusion: This study demonstrated that r-hCG was non-inferior to u-hCG for inducing ovulation. Furthermore, r-hCG demonstrated an expected safety profile, with no new safety concerns identified.
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Aim: This study evaluated the efficacy and safety of vaginal progesterone gel that was administered daily for luteal phase support as part of in vitro fertilization/embryo transfer (IVF/ET) cycles in Japanese women. Methods: This was a phase III, multicenter, open-label, single-arm trial in Japanese women undergoing IVF/ET, using the Japanese Society of Obstetrics and Gynecology 2009 registry as a historical control. The primary objective was to demonstrate the non-inferiority, with regard to the clinical pregnancy rate per ET, of vaginal progesterone gel that was administered once daily, compared with the historical standard value in IVF/ET cycles in Japan. The biochemical pregnancy (positive serum ß-hCG pregnancy test but no clinical pregnancy) rate per ET also was investigated, as were the safety and tolerability of the vaginal progesterone gel. Results: Of the 178 women who were enrolled, 123 underwent IVF/ET. The clinical pregnancy rate per ET was non-inferior in the prospective arm, compared with the historical population. The biochemical pregnancy rate per ET was 7.3%. The safety profile of the vaginal progesterone gel was as expected, with no new safety issue identified. Conclusion: The vaginal progesterone gel was efficacious, with a safety profile as expected, in this study in Japanese women undergoing IVF/ET cycles.
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Gene rearrangement is a widely-shared phenomenon in spore forming bacteria, in which prophage(-like) elements interrupting sporulation-specific genes are excised from the host genome to reconstitute the intact gene. Here, we report a novel class of gene-intervening elements, named gin, inserted in the 225 bp gerE-coding region of the B. cereus ATCC10987 genome, which generates a sporulation-specific rearrangement. gin has no phage-related genes and possesses three site-specific recombinase genes; girA, girB, and girC. We demonstrated that the gerE rearrangement occurs at the middle stage of sporulation, in which site-specific DNA recombination took place within the 9 bp consensus sequence flanking the disrupted gerE segments. Deletion analysis of gin uncovered that GirC and an additional factor, GirX, are responsible for gerE reconstitution. Involvement of GirC and GirX in DNA recombination was confirmed by an in vitro recombination assay. These results broaden the definition of the sporulation-specific gene rearrangement phenomenon: gene-intervening elements are not limited to phage DNA but may include non-viral genetic elements that carry a developmentally-regulated site-specific recombination system.
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Bacillus cereus/fisiología , Proteínas Bacterianas/genética , Esporas Bacterianas , Secuencia de Aminoácidos , Bacillus cereus/virología , Proteínas Bacterianas/química , Secuencia de Bases , Orden Génico , Reordenamiento Génico , Genes Bacterianos , Sitios GenéticosRESUMEN
Synovial sarcoma (SS) is a mesenchymal spindle cell tumor which displays variable epithelial differentiation. It commonly arises around the major joints or tendon sheaths in young adults, but is not commonly seen in the stomach. We experienced a case of primary gastric SS. The patient is a 22-year-old male, who presented with epigastric pain. Upper endoscopy showed an ulcer of 25 mm in diameter with marginal elevation on the posterior mid-gastric body. Biopsy of the ulcer base showed monotonous proliferation of small spindle-shaped cells on HE-stain. On immunohistochemical staining, these cells were positively stained with vimentin, cytokeratin, epithelial membrane antigen, and CD99, but were negative for KIT, CD34, desmin, and S-100 protein. These findings were compatible with SS of monophasic type. Diagnosis of primary gastric SS was made because there were no other primary lesions, nor metastatic lesions. The wedge resection was performed. Reverse transcriptase polymerase chain reaction (RT-PCR), using the RNA from frozen neoplastic tissue of the resected specimen, detected a fusion gene called SYT-SSX1, specific for SS. Though SS arising in the stomach is rare, it should be considered in the differential diagnosis of KIT-negative gastric spindle cell tumor.
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Sarcoma Sinovial , Neoplasias Gástricas , Dolor Abdominal/etiología , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Diagnóstico Diferencial , Endosonografía , Gastrectomía , Gastroscopía , Humanos , Inmunohistoquímica , Masculino , Proteínas de Fusión Oncogénica/genética , Valor Predictivo de las Pruebas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sarcoma Sinovial/química , Sarcoma Sinovial/complicaciones , Sarcoma Sinovial/genética , Sarcoma Sinovial/patología , Sarcoma Sinovial/cirugía , Neoplasias Gástricas/química , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
OBJECTIVE: Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations. METHODS: We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult. RESULTS: COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations. INTERPRETATION: Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions.
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Encefalopatías/genética , Colágeno Tipo IV/genética , Hemiplejía/genética , Malformaciones del Desarrollo Cortical/genética , Mutación/genética , Fenotipo , Anemia Hemolítica/genética , Anemia Hemolítica/patología , Encefalopatías/patología , Niño , Preescolar , Colágeno Tipo IV/deficiencia , Hemiplejía/patología , Humanos , Lactante , Malformaciones del Desarrollo Cortical/patología , PorencefaliaAsunto(s)
Coristoma , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Timo , Niño , Coristoma/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Timo/fisiopatologíaRESUMEN
A 67-year-old man with submaxillary lymphadenopathy diagnosed as reactive follicular hyperplasia of the lymph node was referred to us for pulmonary evaluation. Pathological findings of the lung and hilar lymph node biopsies showed the histological feature of Castleman's disease (CD). Interestingly, infiltrated plasma cells had strong immunoreactivity for IgG4. In addition, this patient had coexisting lung cancer. We believe this is the first described case of IgG4-related lung disease associated with multicentric CD (MCD) and lung cancer. To establish a therapeutic strategy for IgG4-related lung disease, the association between IgG4-related disease and MCD needs to be clarified.