J Korean Med Sci. doi: 10.3201/eid170310060. The most common lung cancer types were adenocarcinoma (six patients) followed by … Crit. The airways can lose their ability to clear mucus and the mucus that accumulates within the airways can serve as a nutrient source and home for NTM, helping it to evade the immune system. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. At the 23rd cycle of atezolizumab therapy, he developed wet cough and excessive sputum production. Two consecutive sputum cultures were positive for Mycobacterium intracellulare at the 17th cycle of nivolumab therapy. MAC infection is not contagious. [Nontuberculous Mycobacterial Pulmonary Disease - The New ATS/ERS/ESCMID/IDSA Guideline]. Previous cytotoxic chemotherapy before induction of ICIs might favor the clinical outcome moderately. There were 10 patients with lung cancer and MACLD and 15 without MACLD; significant differences in patient characteristics were not found between the two groups, and none of the 15 patients without MACLD subsequently developed MACLD. -, Prevots D.R., Shaw P.A., Strickland D., Jackson L.A., Raebel M.A., Blosky M.A., Montes de Oca R., Shea Y.R., Seitz A.E., Holland S.M., Olivier K.N. It is a disease about which little is known, with more questions than answers. MarinMarcus. A 66-year-old woman underwent surgical resection of right lower-lobe lung adenocarcinoma. Moreover, they received thoracic radiotherapy before the pathogenesis of MAC-LD. Unlike the others, NTM lung disease is not known to be contagious. We experienced 3 cases of acute development of Mycobacterium avium complex lung disease (MAC-LD) in patients with lung cancer on immune checkpoint inhibitors. A 66-year-old man was diagnosed with stage 4a advanced squamous cell carcinoma of the right upper lung lobe. also discovered similar profiles for CD4 T-cell-, CD8 T-cell-, and T-cell-mediated cytokine dynamics [11]. Please enable it to take advantage of the complete set of features! Results: Although lung cancer was diagnosed, CT images only showed bilateral emphysema but no bronchiectasis or nodules. In this article, we would look into the causes, symptoms and treatment of MAC pulmonary disease. 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The most common type of NTM bacteria in the U.S. is Mycobacterium avium complex (MAC). He received 1 cycle of combined carboplatin and nanoparticle albumin–bound paclitaxel (nabPTX) therapy, followed by radiotherapy (66 Gy). Ann. The following alternate interpretation is also important. Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. MAC culture-positive bronchial washing is positively associated with lung cancer. 2018 Oct;24(10):822-827. doi: 10.1016/j.jiac.2018.06.014. We performed a systematic review of the published literature on five-year all-cause mortality in patients with MAC lung disease… Follow-up data for patients with lung cancer but without MACLD were reviewed for subsequent development of MACLD. Potential conflicts of interest. These data suggested that Th1 function with anti-PD-1/PD-L1 antibodies might cause the development of tuberculosis. In patients receiving ICIs, Barber et al. MAC and LUNG CANCER. 2017 Dec;133:36-41. doi: 10.1016/j.rmed.2017.11.005. Immunotherapy with immune checkpoint inhibitors (ICIs), while ameliorating lung cancer, can cause infectious diseases, including tuberculosis, in addition to immune-related noninfectious complications. This suggests that patients with MAC lung disease should be better monitored to avoid irreversible lung … Clin Case Rep. 2018 Sep 27;6(11):2156-2159. doi: 10.1002/ccr3.1813. 2011;17(3):343–349. 2020 May;39(5):799-826. doi: 10.1007/s10096-019-03771-0. Dis. Because of adverse events, her chemotherapy regimen was revised to gemcitabine. 2014;11(1):1–8. 2016 May;31(5):649-59. doi: 10.3346/jkms.2016.31.5.649. Therefore, physicians in places with a high burden of NTM should pay more attention to the development of MAC-LD during immunotherapy regimens with ICIs. Emerg. In critical COVID-19 -- about 5% of total cases -- the infection can damage the walls … Thank you for submitting a comment on this article. Soc. Published by Oxford University Press on behalf of Infectious Diseases Society of America. In contrast, Barber et al. Concomitantly, he experienced right main bronchus stenosis because of tumor progression, and palliative radiotherapy (37.5 Gy) was administered. We report 3 cases of acute Mycobacterium avium complex lung disease during immunotherapy with ICIs. Please check for further notifications by email. In actual clinical settings, treatment with anti-PD-1/PD-L1 antibodies is expected to show similar responses. Am. MAC bacteria do not make most people sick. Of them, records for 1258 that had undergone bronchoscopy together with sampling for mycobacterial culture were reviewed. Of the 1258 patients with lung cancer, 25 (2.0%) had MAC-positive/other NTM-negative bronchial washings. The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. Clipboard, Search History, and several other advanced features are temporarily unavailable. Comparison of DNA Methylation Profiles of Hemostatic Genes between Liver Tissue and Peripheral Blood within Individuals. Second-line therapy with nivolumab was initiated. She received nivolumab as the third-line therapy. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. Therefore, the effects of ICIs with regard to mycobacterial diseases in clinical setting remain controversial. However, her disease progressed. The threat of mycobacterial infection has been particularly alarming because of multiple reported cases [ 4–7 ]. Gastroesophageal Reflux Disease and Need for Antireflux Surgery in Children with Cystic Fibrosis: A Systematic Review on Incidence, Surgical Complications, and Postoperative Outcomes. HHS However, disease progression was confirmed after 6 cycles of nivolumab therapy. The threat of mycobacterial infection has been particularly alarming because of multiple reported cases [4–7]. Urabe N, Sakamoto S, Sano G, Ito A, Homma S. J Infect Chemother. He attained 3 years of progression-free survival. Get the latest public health information from CDC: https://www.coronavirus.gov. Two consecutive sputum cultures at the 24th cycle of atezolizumab were positive for M. avium and M. intracellulare. 2019 Jun;152:74-80. doi: 10.1016/j.rmed.2019.05.001. The most common lung cancer types were adenocarcinoma (six patients) followed by squamous cell carcinoma … In people with … The great majority of NTM lung disease in the U.S. is caused by MAC… As the third-line therapy, he received 7 cycles of docetaxel and, subsequently, fourth-line therapy with atezolizumab after docetaxel failure. However, because of severe debilitation, treatment for MAC-LD was not initiated and atezolizumab immunotherapy was discontinued. She received 60-Gy stereotactic radiotherapy. Patient characteristics were compared between those with MAC-positive/other nontuberculous mycobacteria (NTM)-negative bronchial washings and those with MAC-negative/other NTM-negative bronchial washings. The website is designed to be informative and encourage you to be part of the solution of MAC lung disease. COVID-19 is an emerging, rapidly evolving situation. Sequential chemoradiotherapy was initiated. Care Med. The mean age at diagnosis of MAC-LD and lung cancer was 63.6 and 74.4 years, respectively. Results We identified 13 patients with MAC pulmonary disease and prior lung cancer, including 4 men and 9 women. MAC infection is a serious condition that can cause damage to the lungs. Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection. He underwent gamma knife therapy for brain metastasis and was initiated on second-line systemic immunotherapy with atezolizumab.  |  Is tomosynthesis an ingenious scheme for bronchoscopic diagnosis of lung nodules? I found only 1 thread on mycobacterium accidently under the catagory “Lungs”. The proportion of women (52% vs 30%; P = 0.0274) and patient age (72 years vs 69 years; P = 0.0380) were significantly higher in the MAC-positive/other NTM-negative lung cancer group (n = 25) than in the MAC-negative/other NTM-negative lung cancer group (n = 1223). Chest Med. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Among the several types of irAEs, cases of infectious diseases have been increasing steadily [3]. He received initial therapy with 6 cycles of combined carboplatin and nabPTX. Keywords: We have obtained written consent forms from all patients described in this study. Epub 2016 Mar 22. Posts: 1 Joined: Apr 2006 Apr 26, 2006 - 10:37 am ... Do not use this information to diagnose or treat a health problem or disease without consulting with a qualified … We believe in a … Characteristics of the Patients who Developed Mycobacterium avium Complex Lung Disease. Your comment will be reviewed and published at the journal's discretion. The median time to MAC-LD diagnosis from induction of initial ICI (range) was 17 (17–19) months. Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease. However, tumor progression was confirmed after 3 months.  |  Clin. Although lung cancer was diagnosed, CT images showed bilateral emphysemas but no bronchiectasis or nodules. Our present cases might partly reflect this paradoxical reaction, that is, overresponse to mycobacteria. On disease progression, she received 1 cycle of combined carboplatin and pemetrexed as initial therapy. Pulmonary MAC infection is associated with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), chronic bronchitis, bronchiectasis, cystic fibrosis, and lung cancer… Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Correspondence: Kohei Fujita, MD, PhD, Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Kyoto, Japan, 1-1, Fukakusa-Mukaihata, Fushimi-Ku, Kyoto, Japan (. Two consecutive sputum cultures at the fourth cycle of atezolizumab therapy were positive for M. intracellulare, and a diagnosis of MAC-LD was established. Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems. MAC Lung Disease is acquired from the environment (soil, air, natural waters, tap water, etc.) He was diagnosed with MAC-LD; specific treatment was initiated for MAC alongside the atezolizumab therapy. Four (30.8%) had no apparent immunosuppression or other risk factor(s) for MAC pulmonary disease. UpToDate: “Treatment of Mycobacterium avium complex lung infection in adultsTreatment of Myobacterium avium lung infection in adults,” “Myobacterium avium complex (MAC… Furuuchi K, Morimoto K, Yoshiyama T, Tanaka Y, Fujiwara K, Okumura M, Izumi K, Shiraishi Y, Mitarai S, Ogata H, Kurashima A, Yoshimori K, Ohta K, Goto H, Sasaki Y. Respir Med. Recent advances in immunotherapy with immune checkpoint inhibitors have improved the outcomes of patients with lung cancer [1, 2]. Some authors have suggested the development of tuberculosis to be similar to immune reconstitution inflammatory syndrome [4, 7]. Epub 2017 Nov 6. Although the precise mechanisms underlying MAC-LD are unknown, anti-PD-1/PD-L1 antibodies are known to have possible antimicrobial effects that are mediated by upregulation of T-cell-mediated immunity [8]. In their concluding remarks, the authors stated that additional cases of panhypopituitarism with pulmonary MAC … mycobacterium avium complex pulmonary disease (mac/mai) and/or bronchiectasis. The incidence of nontuberculous mycobacterial (NTM) pulmonary disease caused by Mycobacterium avium complex (MAC) in apparently immune-competent people is increasing worldwide. -, Sakatani M. The non-tuberculous mycobacteriosis. Chin KL, Sarmiento ME, Alvarez-Cabrera N, Norazmi MN, Acosta A. Eur J Clin Microbiol Infect Dis. Morimoto K., Iwai K., Uchimura K., Okumura M., Yoshiyama T., Yoshimori K., Ogata H., Kurashima A., Gemma A., Kudoh S. A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan. Abbreviations: ICI, immune checkpoint inhibitor; MAC, Mycobacterium avium complex; nabPTX, nanoparticle albumin-bound paclitaxel; NE, not evaluated; PD-L1, programmed cell death–ligand 1. aTime from initiation of immune checkpoint inhibitor therapy to diagnosis of Mycobacterium avium complex lung disease. In this study, CT images were retrospectively reviewed to assess possible changes of MAC-LD predating ICI immunotherapy. eCollection 2018 Nov. Taira N, Kawasaki H, Takahara S, Chibana K, Atsumi E, Kawabata T. Am J Case Rep. 2018 Jun 26;19:748-751. doi: 10.12659/AJCR.908090. There are two main clinical presentations for NTM infection, which means that the symptoms and signs associated with this disorder are expressed in two specific ways. Japan has one of the highest burdens of NTM globally [13, 14]. Previous reports indicate that development of tuberculosis during ICI immunotherapy has become an emerging concern [4–7]. Introduction: Although immune checkpoint inhibitors manifest drastic effects, unique adverse events, including skin rash, hepatotoxicity, and endocrine disturbances, are known to occur during treatment. Mycobacterium avium complex (MAC) refers to infections caused by two types of bacteria: Mycobacterium avium and Mycobacterium intracellulare. ICI immunotherapy was continued in 2 patients after they were diagnosed with MAC-LD. reported that PD-1/PD-L1 knockout mice displayed increased susceptibility to tuberculosis through enhanced CD4 T-cell-mediated tissue destruction [10]. Moreover, ICI immunotherapy is becoming popular in Japan. Patients with MAC-positive lung cancer were cross-sectionally divided into MACLD and non-MACLD groups, and their features were assessed. Alternatively, ICI immunotherapy might initiate a state of autoimmunity that mimics diseases like rheumatoid arthritis, which are known to be strongly associated with NTM-LD. Epub 2019 May 8. The newer macrolides are the cornerstones of the treatment strategy against Mycobacterium avium complex (MAC) pulmonary disease (1–3).However, macrolide resistance, which is induced by …  |  Well-designed population-based studies are required to investigate such causal associations. However, the cancer recurred in the form of a single brain metastasis and multiple lower left nodules. RESULTS: We identified 13 patients with MAC pulmonary disease and prior lung cancer, including 4 men and 9 women. Thorac. Flow diagram of patients with lung cancer receiving bronchoscopy between 2003 and 2011. The Lung Cancer Stream provides multidisciplinary care including diagnosis and treatment for cancers of the lung, thymus and mesothelioma. Pulmonary non-tuberculous mycobacterial infections: current state and future management. Multiple cases of tuberculosis were suspected reactivation of latent infection. Infect. 2010;182(7):970–976. These may emerge as thought-provoking cases. -. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (. These events are termed immune-related adverse events (irAEs). Clinical characteristics and treatment outcomes of pleural effusions in patients with nontuberculous mycobacterial disease. A diagnosis of MAC-LD was established, and specific treatment for MAC was initiated along with continued nivolumab therapy. Her adenocarcinoma recurred after 12 years. Epub 2019 Dec 18. Interrelational changes in the epidemiology and clinical features of nontuberculous mycobacterial pulmonary disease and tuberculosis in a referral hospital in Japan. Introduction: The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. CT images showed infiltration in the upper left lung lobe and lingula. Of the 29 patients with NTM and lung cancer, 62% had Mycobacterium avium complex as the pathogenic organism. Of course, the odds are not in favor of anyone with "other" chronic conditions including heart disease, diabetes, those fighting cancer, and those with chronic lung … The prevalence of Mycobacterium avium complex (MAC) pulmonary disease (PD) is increasing significantly in Japan. Conclusion: See this image and copyright information in PMC. J. Respir. Clinics are held three times a week, and are staffed by respiratory physicians, thoracic surgeons, radiation oncologists and medical oncologists, all of whom are recognised for their particular expertise in lung … 2005;80(1):25–30. The mean age at diagnosis of MAC-LD and lung cancer was 63.6 and 74.4 years, respectively. We experienced 3 acute cases of MAC-LD during ICI immunotherapy. Three Antibiotic Therapies for Pulmonary Mycobacterium Avium Complex Disease Rochester, MN The purpose of this study is to determine whether 2-drug therapy is non-inferior to 3-drug therapy against pulmonary mycobacterium avium complex (MAC) disease… 2015;36(1):13–34. Each of us, every one of us, with or without an underlying chronic lung condition is susceptible to COVID-19. Eight patients had structural lung disease that can predispose to MAC pulmonary disease, including bronchiectasis (23.0%) and COPD (46.2%). Female sex and advanced age, but not lung cancer characteristics, were found to be associated with MAC infection in patients with lung cancer. Physicians should be cautious toward the development of MAC-LD in patients on immunotherapy with ICIs, especially in countries such as Japan, which has a high burden of NTM. bDuration included that of docetaxel treatment. Most people who get MAC infections are those living with HIV/AIDS, certain cancers, and lung diseases like chronic obstructive pulmonary disease, cystic fibrosis, or bronchitis. I’m hoping by starting a subject matter directly related to MYCOBACTERIUM AVIUM COMPLEX PULMONARY DISEASE (MAC… The aim of this study was to identify the clinical features of MAC … In the clinical setting, the efficacy of ICIs to treat mycobacterial infection remains controversial. A previous report suggested a favorable effect of nivolumab for the treatment of Mycobacterium abscessus lung disease [9]. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. MAC infection may not always progress into lung disease, but the likelihood of this infection turning into a lung disease is higher for those suffering from an underlying lung condition or AIDS. Kohei Fujita, Yuki Yamamoto, Osamu Kanai, Misato Okamura, Koichi Nakatani, Tadashi Mio, Development of Mycobacterium avium Complex Lung Disease in Patients With Lung Cancer on Immune Checkpoint Inhibitors, Open Forum Infectious Diseases, Volume 7, Issue 3, March 2020, ofaa067, https://doi.org/10.1093/ofid/ofaa067. The less severe form is known as nodular bronchiectasis, in which the airways of the lungs become damaged, and subsequently dilate and become scarred. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. The most common lung cancer histology was adenocarcinoma (62.1%). Among the patterns of MAC-PD, a solitary pulmonary nodule (SPN) is less common and often resembles lung cancer. USA.gov. All patients had advanced lung cancer and received cytotoxic chemotherapy before treatment with ICIs. Cumulative experience will reveal the complete picture. Scientists and physicians who have studied MAC believe people who develop MAC lung disease become infected because of a defect in the structure or function of their lungs (especially a disease … Search for other works by this author on: Department of Drug Discovery for Lung Diseases, Graduate School of Medicine, Kyoto University, Immune checkpoint blockade: a common denominator approach to cancer therapy, Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer, Emerging concerns of infectious diseases in lung cancer patients receiving immune checkpoint inhibitor therapy, Anti-PD1 antibody treatment and the development of acute pulmonary tuberculosis, Pericardial tamponade caused by a hypersensitivity response to tuberculosis reactivation after anti-PD-1 treatment in a patient with advanced pulmonary adenocarcinoma, Infectious complications associated with the use of immune checkpoint inhibitors in oncology: reactivation of tuberculosis after anti PD-1 treatment, Paradoxical response in a patient with non-small cell lung cancer who received nivolumab followed by anti-, Anti-PD-1/PD-L1 therapy for infectious diseases: learning from the cancer paradigm, CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition, Tuberculosis following PD-1 blockade for cancer immunotherapy, Analysis of the impact of lung cancer treatment on nontuberculous mycobacterial lung diseases, A steady increase in nontuberculous mycobacteriosis mortality and estimated prevalence in Japan, Epidemiology of pulmonary nontuberculous mycobacterial disease, Japan. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease. Therefore, it is unclear whether MAC-LD developed from reactivation of existing disease or was a de novo infection. Kamata H, Asakura T, Suzuki S, Namkoong H, Yagi K, Funatsu Y, Okamori S, Uno S, Uwamino Y, Fujiwara H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N. BMC Pulm Med. After 15 cycles of nivolumab, she developed wet cough with excessive sputum. The Presence of Coexisting Lung Cancer and Non-Tuberculous Mycobacterium in a Solitary Mass. CT images revealed multiple reticulonodular infiltrates in the lower left lung lobe. I… Computed tomography (CT) images acquired at that time showed no bronchiectasis or nodules in the bilateral lobes. Zhongguo Dang Dai Er Ke Za Zhi. doi: 10.1164/rccm.201002-0310OC. This case study was partly supported by a Grant-in-Aid for Young Scientists (B), KAKENHI, Japan Society for the Promotion of Science, Japan (Grant Number, 17K16067). All authors: no reported conflicts of interest. Eight patients had structural lung disease that can predispose to MAC pulmonary disease, including bronchiectasis (23.0%) and COPD (46.2%). © The Author(s) 2020. When occam's razor can fail- active mycobacteria infection and lung cancer: A case of neuroendocrine lung cancer diagnosed in the setting of refractory mycobacterium avium-intracellulare. Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. 2019 Mar;21(3):277-281. doi: 10.7499/j.issn.1008-8830.2019.03.017. All of our patients had advanced-stage lung cancer and had received relatively long-term treatment, including cytotoxic chemotherapy; therefore, the influence of both the cancer and the treatment in the development of MAC-LD cannot be ignored. Gupta K, Feinstein MB, Goldman DA, Patail HS, Stover DE. NLM In our 3 cases, no fibro-cavitary or reticulonodular shadow was noted that could indicate nontuberculous mycobacteria (NTM) infection at the initial diagnosis of lung cancer. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Materials and methods: Untreated patients with a nodular bronchiectatic form of Mycobacterium avium complex (MAC) suffer long deterioration in the long run despite their lack of symptoms, a new Korean study shows.. Am. Four (30.8%) had no apparent immunosuppression or other risk factor(s) for MAC … Get the latest research from NIH: https://www.nih.gov/coronavirus. -, Simons S., van Ingen J., Hsueh P.R., Van Hung N., Dekhuijzen P.N., Boeree M.J., van Soolingen D. Nontuberculous mycobacteria in respiratory tract infections, eastern Asia. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Table 1 shows the summary of all 3 cases. -, Prevots D.R., Marras T.K. To the Editor: We read with interest the report by Yamakita and Yasuda1 in the February 2005 issue of the Mayo Clinic Proceedings of 2 patients with Mycobacterium avium complex (MAC) lung disease associated with panhypopituitarism. Furthermore, cytotoxic chemotherapy can exacerbate NTM disease [12]. Research Assistant Professor of Epidemiology, Board Certified or Board Eligible AP/CP Full-Time or Part-Time Pathologist, Chief of ID, VA Ann Arbor Healthcare System, Copyright © 2020 Infectious Diseases Society of America. 2020 Mar;12(3):142-149. doi: 10.14740/jocmr4058. Kekkaku. Critical Cases. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex (MAC), which is … However, people with immune systems that do not work well (from HIV/AIDS or certain cancers for example) or people with lung disease (such as chronic obstructive pulmonary disease … Financial support. The medical records of 1382 untreated lung cancer patients between 2003 and 2011 were collected using our hospital database. Epub 2020 Mar 2. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. doi: 10.1016/j.ccm.2014.10.002. Granier C, De Guillebon E, Blanc C, et al.Â, Picchi H, Mateus C, Chouaid C, et al.Â, Ishii S, Tamiya A, Taniguchi Y, et al.Â, Barber DL, Mayer-Barber KD, Feng CG, et al.Â, Barber DL, Sakai S, Kudchadkar RR, Fling SP, et al.Â, Tsuji T, Tsuyuguchi K, Tachibana K, et al.Â, Morimoto K, Iwai K, Uchimura K, et al.Â, Namkoong H, Kurashima A, Morimoto K, et al.Â, Oxford University Press is a department of the University of Oxford. NIH CT images acquired during atezolizumab therapy revealed rapidly worsening right lower lobe infiltration. [Intermittent abdominal pain and abdominal distension with fatigue and massive ascites in a 13-year-old boy].

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