Introduction: Histoplasmosis is a rare opportunistic, inhalation-acquired systemic mycosis caused by Histoplasma capsulatum, endemic to Southeast Asia, including Malaysia. Although classically seen in immunocompromised hosts, it is increasingly reported in immunocompetent individuals. Infection is associated with environmental exposures such as bat or bird droppings and soil disruption. Histoplasmosis is a progressive granulomatous disease that can closely mimic tuberculosis and malignancy, making diagnosis challenging. Case: An 87-year-old Malay male with a history of treated pulmonary tuberculosis presented with a 6-month history of intermittent fever, anorexia, weight loss, and hypotension. Initial computed tomography imaging demonstrated bilateral heterogeneous adrenal masses (right: 2.2 × 3.7 × 5.0 cm; left: 2.0 × 3.7 × 5.2 cm) with indeterminate washout characteristics. Biochemical adrenal evaluation, including a short Synacthen test, confirmed primary adrenal insufficiency. Extensive microbiological and malignancy workup, including bronchoscopy, cultures, and tumor markers, was non-diagnostic. In view of clinical deterioration and epidemiological risk, empirical antituberculous therapy was initiated; however, no clinical improvement was observed after 2 months. PET-FDG revealed intensely hypermetabolic bilateral adrenal masses (SUVmax right 16.7, left 13.2) with no other abnormal foci. Non-invasive fungal investigations were negative. Definitive diagnosis was established via computed tomography-guided adrenal biopsy, which demonstrated necrotizing granulomatous inflammation with intracellular yeasts, subsequently identified as H. capsulatum. The patient was treated with oral itraconazole and corticosteroid replacement, resulting in significant clinical improvement and planned interval radiological reassessment. Conclusion Disseminated histoplasmosis is a diagnostic challenge, particularly in frail elderly patients, where invasive procedures may be delayed. It can mimic tuberculosis and malignancy and may lack an identifiable exposure history. Non-invasive tests may be inconclusive, making tissue biopsy essential. Adrenal involvement may result in primary adrenal insufficiency, further complicating the clinical picture. Early consideration and timely confirmation are crucial for appropriate management.
Adrenal incidentaloma ; Lung Neoplasms

Introduction: Hashimoto's thyroiditis is a common autoimmune thyroid disease; however, pulmonary involvement is a rare manifestation. Lymphocytic interstitial pneumonitis is commonly associated with autoimmune diseases, but its association with Hashimoto's thyroiditis remains poorly understood. Case: A 63-year-old male with prior diagnosis of Hashimoto's thyroiditis presented with recurrent massive pleural effusion and progressive dyspnea. He also experienced fatigue, cold intolerance, and constipation. Physical examination revealed facial puffiness, diffuse goiter, and dry skin. Thyroid function tests performed 6 months before admission confirmed overt hypothyroidism (thyroidstimulating hormone [TSH] 80.30 µIU/mL, free thyroxine 4 [FT4] 0.46 ng/dL). One month prior to admission, laboratory findings showed subclinical hypothyroidism (TSH 9.09 µIU/mL, FT4 1.42 ng/dL). Despite levothyroxine treatment TSH levels remained elevated at 21.8 µIU/mL during admission. Anti-thyroid peroxidase antibodies were positive (13.95 IU/mL). Repeated thoracentesis revealed exudative pleural effusion with lymphocytic predominance and no evidence of malignancy in cytological examination. Infectious etiologies and malignancy were ruled out. Thyroid ultrasonography demonstrated diffuse hypoechoic enlargement of the thyroid gland. Chest radiography showed massive unilateral pleural effusion, while thoracic computed tomography revealed ground-glass opacities with a reticulogranular pattern and interlobular septal thickening, accompanied by multiple thin-walled cysts, highly suggestive of lymphocytic interstitial pneumonitis. Thyroid immunohistochemical analysis was performed (CD 20, CD 3, CD 10, CD 138, Ki 67, BCL 2, BCL 6, Thyroglobulin, MUM 1, Cyclin D1), consistent with lymphocytic thyroiditis. Significant clinical and laboratory improvement was achieved after combined treatment with levothyroxine and corticosteroid. Conclusion This case underscores the importance of considering autoimmune-related lymphocytic interstitial pneumonitis in patients with Hashimoto's thyroiditis who present with unexplained recurrent pleural effusion after exclusion of more common etiologies, such as infection and malignancy. Early recognition may lead to favorable improvement.
Lung Diseases, Interstitial ; Pleural Effusion ; Thyroiditis

OBJECTIVE: To observe the clinical efficacy of Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction on acute pharyngitis with lung-stomach heat accumulation. METHODS: A total of 88 patients with acute pharyngitis of lung-stomach heat accumulation were randomly divided into an observation group (44 cases, 4 cases dropped out) and a control group (44 cases, 4 cases dropped out). The control group was treated with oral Qingyan Lige decoction, 150 mL each time, twice a day for 6 continuous days. On the basis of the treatment in the control group, Xujiang Xie's bloodletting therapy was applied at bilateral Shaoshang (LU11), Shangyang (LI1), and Erjian (EX-HN6) in the observation group, 0.1-0.5 mL of bloodletting per site, once every other day for 3 times in total. The TCM symptom and sign score, complete blood count (white blood cell [WBC] count, neutrophilic granulocyte percentage [NE%]), inflammation indexes (serum levels of C-reactive protein[CRP], interleukin[IL]-1β, IL-6, tumor necrosis factor [TNF]-α) and immune indexes (？？, ？？, ？？) of the two groups were observed before treatment and after 6 days of treatment, and the clinical efficacy was evaluated. RESULTS: After 6 days of treatment, the sore throat scores, redness and swelling scores of pharyngeal mucosa and uvula, pharyngeal dry and burning scores, hyperemia scores of posterior pharyngeal lymphoid follicles, chill and fever scores, total scores of TCM symptom and sign, WBC count, NE%, CRP, IL-1β, IL-6, TNF-α and ？？ in both groups were decreased compared with those before treatment (P<0.05), the above indexes in the observation group were lower than those in the control group (P<0.01, P<0.05, P<0.001). After 6 days of treatment, the levels of ？？ and ？？ in both groups were increased compared with those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.001). The total effective rate of the observation group was 95.0% (38/40), which was higher than 90.0% (36/40) in the control group (P<0.001). CONCLUSION Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction could improve the symptoms in patients with acute pharyngitis of lung-stomach heat accumulation, inhibit inflammatory response and improve immune function.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Pharyngitis/drug therapy* ; Adult ; Middle Aged ; Bloodletting ; Young Adult ; Lung/drug effects* ; Combined Modality Therapy ; Interleukin-6 ; Adolescent ; Tumor Necrosis Factor-alpha ; Acute Disease/therapy* ; Treatment Outcome

OBJECTIVE: To observe the effect of governor vessel moxibustion on improving cardiopulmonary fitness in patients with stable chronic obstructive pulmonary disease (COPD) of qi deficiency of lung and kidney. METHODS: A total of 40 patients with stable COPD of qi deficiency of lung and kidney were randomized into an observation group (20 cases) and a control group (20 cases). The routine basic treatment and nursing were adopted in the control group. In the observation group, on the basis of the treatment in the control group, governor vessel moxibustion was applied at the area from Dazhui (GV14) to Yaoshu (GV2) of the governor vessel, 1 hour a time, once a week. Both groups were treated for 8 weeks consecutively. The maximal oxygen uptake (VO₂max), 6-minute walking test (6MWT) and Borg score, pulmonary function indexes (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC] and ratio of FEV₁ and FVC [FEV₁/FVC]), chronic obstructive pulmonary disease assessment test (CAT) score, and TCM syndrome score were observed in the two groups before and after treatment respectively. RESULTS: After treatment, the VO₂max, 6MWT, FEV₁, FVC and FEV₁/FVC were increased compared with those before treatment in the two groups (P<0.001, P<0.05), the above indexes in the observation group were higher than those in the control group (P<0.05, P<0.01). After treatment, the Borg, CAT and TCM syndrome scores were decreased compared with those before treatment in the two groups (P<0.05, P<0.001), the above indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION Governor vessel moxibustion can effectively improve the cardiopulmonary fitness, clinical symptoms and the quality of life in patients with stable COPD of qi deficiency of lung and kidney.
Humans ; Moxibustion ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Aged ; Qi ; Lung/physiopathology* ; Kidney/physiopathology* ; Acupuncture Points

INTRODUCTION: The high prevalence and mortality rates of breast cancer and lung cancer in Singapore necessitate robust screening programmes to enable early detection and intervention for improved patient outcomes, yet 2024 uptake and coverage remain suboptimal. This narrative review synthesises expert perspectives from a recent roundtable discussion and proposes strategies to advance breast cancer and lung cancer screening programmes. METHOD: A 2024 roundtable convened clinical practitioners, health policymakers, researchers and patient advocates discussed current challenges and opportunities for improving cancer screening in Singapore. Perspectives and insights were analysed to identify themes related to existing programme gaps, opportunities for innovation and implementation challenges. DISCUSSION: Singapore's national breast cancer screening programme has been in place for over 2 decades, yet screening uptake remains suboptimal. A national lung cancer screening programme, in contrast, is still in its early stages of implementation. Regardless, employment of risk stratification approaches that integrate genetic, demographic and lifestyle factors could enhance screening effectiveness by identifying high-risk indivi-duals, while also taking local epidemiological trends into consideration. Integration of digital health technologies, artificial intelligence and behavioural change models can enhance cancer screening uptake and accuracy to overcome barriers such as low awareness, cultural beliefs and socioeconomic factors that contribute to low participation rates. CONCLUSION Key recommendations include enhancing public awareness, refining screening guidelines, expanding access and applying innovative technologies. A coordinated effort among stakeholders is crucial to continually assess and enhance screening programmes to narrow the practice-policy gap and ultimately reduce breast cancer and lung cancer burden in Singapore.
Humans ; Singapore/epidemiology* ; Lung Neoplasms/epidemiology* ; Breast Neoplasms/epidemiology* ; Early Detection of Cancer/methods* ; Female ; Mass Screening/organization & administration*

BACKGROUND: Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. METHODS: Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen's kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. RESULTS: A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. CONCLUSION ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Circulating Tumor DNA/blood* ; High-Throughput Nucleotide Sequencing/methods* ; Female ; Male ; Lung Neoplasms/pathology* ; Middle Aged ; Mutation/genetics* ; Aged ; Adult ; Aged, 80 and over

Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods*

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

With the increasing utilization of cancer therapy, the incidence of lung injury associated with these treatments continues to rise. The recognition of pulmonary toxicity related to cancer therapy has become increasingly critical, for which interstitial lung disease (ILD) is a common cause of mortality. Cancer therapy-related ILD (CT-ILD) can result from a variety of treatments including chemotherapy, targeted therapy, immune checkpoint inhibitors, antibody-drug conjugates, and radiotherapy. CT-ILD may progress rapidly and even be life-threatening; therefore, prompt diagnosis and timely treatment are crucial for effective management. This review aims to provide valuable information on the risk factors associated with CT-ILD; elucidate its underlying mechanisms; discuss its clinical features, imaging, and histological manifestations; and emphasize the clinical-related views of its diagnosis. In addition, this review provides an overview of grading, typing, and staging treatment strategies used for the management of CT-ILD.
Humans ; Lung Diseases, Interstitial/diagnosis* ; Neoplasms/therapy* ; Risk Factors ; Immune Checkpoint Inhibitors/adverse effects* ; Antineoplastic Agents/therapeutic use*

Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell-cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
Humans ; Tumor Microenvironment/drug effects* ; Adenocarcinoma of Lung/drug therapy* ; Lung Neoplasms/pathology* ; Adenocarcinoma/metabolism* ; Animals ; Apoptosis/physiology*