Risk factors and related miRNA phenotypes of chronic pain after thoracoscopic surgery in lung adenocarcinoma patients.

Chronic postsurgical pain may have a substantial impact on patient's quality of life, and has highly heterogenous presentation amongst sufferers. We aimed to explore the risk factors relating to chronic pain and the related miRNA phenotypes in patients with lung adenocarcinoma after video-assisted thoracoscopic lobectomy to identify potential biomarkers. Our prospective study involved a total of 289 patients with early invasive adenocarcinoma undergoing thoracoscopic lobotomy and a follow-up period of 3 months after surgery. Blood was collected the day before surgery for miRNA detection and patient information including operation duration, duration of continuous drainage of the chest, leukocyte count before and after operation, and postoperative pain scores were recorded. Using clinical and biochemical information for each patient, the risk factors for chronic postsurgical pain and related miRNA phenotypes were screened. We found that chronic postsurgical pain was associated with higher body mass index; greater preoperative history of chronic pain; longer postoperative drainage tube retention duration; higher numerical rating scale scores one, two, and three days after surgery; and changes in miRNA expression, namely lower expression of miRNA 146a-3p and higher expression of miRNA 550a-3p and miRNA 3613-3p in peripheral blood (p < 0.05). Of these factors, patient body mass index, preoperative history of chronic pain, average numerical rating scale score after operation, and preoperative peripheral blood miRNA 550a-3P expression were independent risk factors for the development of chronic postsurgical pain. Identification of individual risk markers may aid the development and selection of appropriate preventive and control measures.

[Effect of Preserving the Pulmonary Branch of Vagus Nerve on Postoperative Cough 
in Patients with Stage I Peripheral Lung Adenocarcinoma].

BACKGROUND: Cough is one of the main complications after pulmonary surgery, which seriously affects the postoperative quality of life. Preserving the pulmonary branch of vagus nerve may reduce the incidence of postoperative cough. Therefore, the aim of this study was to investigate whether preserving the pulmonary branch of the vagus nerve could reduce the incidence of postoperative chronic cough in patients with stage I peripheral lung adenocarcinoma. METHODS: A total of 125 patients who underwent single-port thoracoscopic radical resection for lung cancer in the Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China from June 2022 to June 2023 were retrospectively selected, and divided into two groups according to whether the vagopulmonary branch was preserved during the operation, namely, the vagopulmonary branch group (n=61) and the traditional group (n=64). The general clinical data, perioperative conditions, lymph node dissection, Mandarin Chinese version of The Leicester Cough Questionnaire (LCQ-MC) scores before and 8 weeks after operation were recorded in the two groups. Both the two groups were divided into tamponade group and non-tamponade group according to whether autologous fat or gelatin sponge was tamponade after lymph node dissection. LCQ-MC scores and postoperative chronic cough of both groups were calculated. RESULTS: The LCQ-MC score of the traditional group was significantly lower than that of the vagopulmonary branch group in physiological, psychological, social and total scores at 8 weeks after surgery, and the difference was statistically significant (P<0.05). There were more cough patients in the traditional group than the vagopulmonary branch group at 8 weeks after surgery, with significant difference (P=0.006). Subgroup analysis was conducted separately for the vagopulmonary branch group and the traditional group. Among the patients in the vagopulmonary branch group and the traditional group, the LCQ-MC scores of the non-tamponade group 8 weeks after surgery were lower than those of the tamponade group (P<0.05). There were more patients with cough in the group 8 weeks after surgery than in the tamponade group (P=0.001, P=0.024). CONCLUSIONS: For patients with stage I peripheral lung adenocarcinoma, the preservation of the pulmonary branch of vagus nerve is safe and effective, which can reduce the incidence of postoperative chronic cough and improve the postoperative quality of life of the patients.

[A case of Stiff-person syndrome with muscle tonicity of the extremities and neck after use of Dulvalumab for lung adenocarcinoma].

A 74-year-old woman taking dulvalumab for lung adenocarcinoma developed muscle tonicity in the extremities and trunk. Painful paroxysmal muscle spasms with profuse sweating were frequently observed, and surface electromyography showed simultaneous contraction of the active and antagonist muscles. Blood tests were strongly positive for anti-amphiphysin antibodies, and stiff-person syndrome (SPS) was diagnosed. Intravenous immunoglobulin therapy and clonazepam were initiated, and the paroxysmal painful muscle spasms disappeared. As the primary tumor was under control, and the onset occurred approximately six weeks after the resumption of immune checkpoint inhibitors, we considered SPS to be an immune-related adverse event. Although extremely rare, it should be considered a neuromuscular disease that can occur in association with immune checkpoint inhibitors.

Combining immune-checkpoint inhibitors with tocilizumab to treat a lung adenocarcinoma patient with pre-existing polymyalgia rheumatica: A case report.

Immune-checkpoint inhibitors (ICIs) have changed the management of advanced cancers. However, patients with pre-existing autoimmune diseases (ADs) have usually been excluded from clinical trials of ICIs due to concerns about exacerbation of AD. Here, we combined ICIs with selective immunosuppressant treatment in a metastatic lung adenocarcinoma patient with active pre-existing polymyalgia rheumatica (PMR). Remarkably, the strategy led to durable response and no exacerbation of PMR. Thus, we provide the first clinical evidence of treating metastatic cancer with ICIs and concomitant use of tocilizumab and hydroxychloroquine for active pre-existing PMR.

Guillain-Barré Syndrome as a paraneoplastic neurological disease of pulmonary adenocarcinoma and squamous cell carcinoma: A case report.

We present the case of a 69-year-old male who presented with profound weakness in the extremities. Remarkably, he lacked any identifiable precipitating factors preceding the onset of his illness. However, a diagnosis of Guillain-Barré syndrome (GBS) was established based on typical clinical symptoms, cerebrospinal fluid analysis, and neurological examination. During his hospitalization, an incidental discovery of lung cancer was made. Subsequent pathology confirmed adenocarcinoma and squamous cell carcinoma in the lungs. This case report serves to underscore the exceptional rarity of the simultaneous occurrence of lung cancer and GBS, renewing interest in investigating GBS as a potential paraneoplastic neurological syndrome. Keywords: Guillain-Barré syndrome, paraneoplastic neurological disease, pulmonary adenocarcinoma, squamous cell carcinoma.

Afatinib-Induced Tumor Lysis Syndrome in Pulmonary Adenocarcinoma: A Case Report and Literature Review.

Tumor lysis syndrome (TLS) is a potentially fatal oncological emergency that typically develops during the treatment of rapidly proliferating malignancies. It is infrequently reported in solid tumors, such as pulmonary adenocarcinoma. A 59-year-old male patient with shortness of breath presented with a 3.3 cm × 3.0 cm mass in the right upper lobe, along with massive right-sided pleural effusion. A percutaneous needle biopsy was performed, and a diagnosis of pulmonary adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation was made. The patient was treated with afatinib because of the malignant pleural effusion and multiple metastases to the intrathoracic lymph nodes, left scapula, and brain. After 4 days of afatinib treatment, he developed oliguric acute kidney injury and progressively worsening dyspnea. Based on the clinical and laboratory findings, the patient was diagnosed with afatinib-induced TLS. To the best of our knowledge, this is the first reported case of afatinib-induced TLS in pulmonary adenocarcinoma.

Lung adenocarcinoma presenting with intrapulmonary metastases through air spaces concomitant with silicosis: a case report and literature review.

Herein, we reported a rare case of bilateral intrapulmonary metastases spread through air spaces (STAS) and silicosis to advance understanding and knowledge of this disease. A middle-aged man was diagnosed with a left upper lung nodule with bilateral silicosis by preoperative imaging. Local pleural indentation and extensive metastases spread in the visceral pleura were observed during the operation. Pathological examination showed multiple metastases of lung adenocarcinoma, and STAS positive. Genetic testing indicated EGFR mutation, and ektinib was administered. STAS can promote lung cancer, leading to multiple pulmonary metastases, and silicosis can contribute to the carcinogenesis of lung cancer. This case provided valuable clinical lessons. More studies are warranted to elucidate the role and underlying mechanism of silicosis and STAS in the development of lung cancer. More accurate imaging methods and radiographic criteria should be formulated for different diffuse nodules and STAS grades, and the exploration of optimal therapeutic regimens to treat these concomitant patients is urgently needed to improve diagnostic rates and formulate more optimal therapies.

Perianal Paget's disease complicated with lung adenocarcinoma and anal canal carcinoma: A case report and literature review. / 肛周Pagetç— åˆå¹¶è‚ºè ºç™Œå’Œè‚›ç®¡ç™Œ1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Perianal Paget's disease (PPD) is a rare malignant cutaneous tumor. This paper reported a case of PPD complicated by lung adenocarcinoma and anal canal cancer. The patient, a 76-year-old female, had been experiencing recurrent lower abdominal pain and perianal pruritus for the past 5 years. Upon physical examination, a cauliflower-like neoplasm in size of 5 cm×6 cm was observed on the right perianal skin, with local skin ulceration and a small amount of fluid discharge. The left perianal skin was also involved. In thoracoknee position, a hard mass was palpable in the rectal submucosa at 5-6 points 2 cm from the anal verge. Chest CT revealed multiple lesions in both lungs, indication of metastatic tumors. Further evaluation with fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) indicated multiple hypermetabolic nodules in the lungs, hypermetabolic lymph nodes throughout the body, early FDG uptake in a small patch of skin on the left hip, and increased FDG uptake in the anorectal region. Histopathological examination confirmed the diagnosis of lung adenocarcinoma. This resulted in the patient being diagnosed with PPD, lung adenocarcinoma, anal canal cancer, and systemic multiple lymph node metastasis. The combination of PPD with gastrointestinal tumors and other metachronous malignant tumors is highly prevalent. Colonoscopy, FDG-PET/CT, histopathology, and immunohistochemistry play crucial roles in early identification of local lymph node and distant involvement, facilitating the evaluation of potential malignant tumors and differential diagnosis. Treating methods for PPD are currently diverse, including postoperative combined or single chemotherapy, radiotherapy, targeted therapy, and photodynamic therapy. As trerapeutical options continue to develop, the extent and efficacy of surgery need to be reassessed.

Case Report: Life-threatening pancytopenia with tislelizumab followed by cerebral infarction in a patient with lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs.

Marantic Endocarditis in Metastatic Lung Adenocarcinoma.

Marantic endocarditis is a rare condition associated with autoimmune disease, malignancy, and hypercoagulable states. It is characterized by sterile friable vegetations composed of fibrin and platelets that confer a high risk of systemic embolism. Here we showcase imaging that led to the diagnosis of an interesting case of marantic endocarditis secondary to metastatic malignancy.

Chylothorax in the Setting of Lung Malignancy.

Chylothorax refers to chyle within the pleural space, which frequently arises from an interruption in the thoracic duct or because of reduced lymphatic drainage. Pleural fluid that is white/milky in appearance, with a triglyceride concentration of greater than 110 mg/dL, strongly supports the diagnosis of chylothorax. Chylothorax is nearly always exudative. Transudative chylothorax is extremely rare and typically presents due to a secondary cause, such as liver cirrhosis, nephrotic syndrome, or congestive heart failure. We present a case of chylothorax that occurs in the setting of lung adenocarcinoma. A 65-year-old African American man with a past medical history of metastatic right lung adenocarcinoma presented with dyspnea and palpitations. He denied fever, orthopnea, and paroxysmal nocturnal dyspnea. Therapeutic drainage of the left pleural effusion resulted in 650 mL of milky-white fluid. Pleural fluid analysis demonstrated a triglyceride concentration of 520 mg/dL, a pleural/serum protein ratio of 0.41, a pleural/serum lactate dehydrogenase (LDH) ratio of 0.26, a total pleural LDH of 127 IU/L, and a cholesterol level of 58 mg/dL. This effusion can be classified as transudative as per Light's criteria and exudative as per Heffner's and pleural cholesterol criteria. A subsequent pleural fluid cytology found malignant cells consistent with lung adenocarcinoma. Malignancy is the most common cause of nontraumatic, exudative chylothorax. Light's criteria misinterpret about 25% of transudative effusions as exudative. Therefore, to minimize this error, a combination of the 3-criterial consideration is ideal.

Effects of high-risk human papillomavirus infection on P53, pRb, and survivin in lung adenocarcinoma-a retrospective study.

Objective: To observe the effects of high-risk human papillomavirus (HR-HPV) infection on P53, pRb, and survivin in lung adenocarcinoma (LUAD). Methods: The cancerous and cancer-adjacent tissues of 102 patients with LUAD from January 2020 to April 2022 were selected for the study. HR-HPV infection was detected by flow fluorescence method, and P53, pRb, and survivin protein expression was detected by immunohistochemical staining method. Statistical analysis was performed to determine the differences in the HR-HPV infection and the expression of P53, pRb, and survivin proteins between LUAD tissues and cancer-adjacent tissues; the correlation between HR-HPV infection and P53, pRb, and survivin protein expression in cancer tissues; and the correlation between HR-HPV infection and clinicopathological features of LUAD. Results: The infection rate of HR-HPV was higher in the LUAD tissues (28.43%) than in cancer-adjacent tissues (7.84%), and the difference was statistically significant (P < 0.05). The positive rates of P53 and survivin protein were higher in the LUAD group (33.33% and 67.16%, respectively) than in the cancer-adjacent group (3.92% and 11.73%, respectively), and the difference was statistically significant (P < 0.05). The positive rate of pRb protein was lower in the LUAD group (58.82%) than in the cancer-adjacent group (92.14%), and the difference was statistically significant (P < 0.05). The positive rates of P53 and survivin proteins were significantly higher in the HR-HPV LUAD group (58.62% and 86.21%, respectively) than in the non-HR-HPV LUAD group (41.38% and 67.12%, respectively), and the difference was statistically significant (P < 0.05). The expression rate of pRb protein was significantly lower in the HR-HPV LUAD group (37.93%) than in the non-HR-HPV LUAD group (67.12%), and the difference was statistically significant (P < 0.05). The expression of p53 and survivin protein was positively correlated with HR-HPV infection (r = 0.338 and 0.444, P < 0.05), whereas the expression of pRb protein was negatively correlated with HR-HPV infection (r =  - 0.268, P < 0.05). HR-HPV infection was not associated with gender, age, and smoking in patients with LUAD (P > 0.05). HR-HPV infection was associated with lymph node metastasis and clinical stage of LUAD (P < 0.05). Conclusions: HR-HPV infection was associated with lymph node metastasis and clinical stage of LUAD, which may be achieved by up-regulating p53 and survivin protein expression and down-regulating pRb protein expression.

Myasthenia-like paraneoplastic syndrome with multiple cranial nerve tumor infiltration: A case report and literature review.

RATIONALE: Approximately 0.001% of patients with cancer have paraneoplastic nerve system syndrome, which can affect the central nervous system, neuromuscular junction, or peripheral nervous system. Although myasthenia gravis (MG) may exist as a thymic paraneoplastic syndrome (PNPS), its association with primary lung cancer remains unknown. PATIENT CONCERNS: A 55-year-old female presented with slurred speech, weakness in chewing, sporadic difficulty in swallowing, and weakness in both lower limbs for half a year. DIAGNOSES: Based on cerebrospinal fluid and electromyography findings, we present the case of a female patient diagnosed with overlapping multicranial nerve tumor infiltration and MG-like neurological PNPS secondary to lung adenocarcinoma. INTERVENTIONS: The patient received intrathecal injections of pemetrexed and neurotrophic (vitamin B) therapy before ceasing chemoradiotherapy and chose cabozantinib on her own. OUTCOMES: Weakness of the proximal limbs, choking cough, and chewing problems did not improve significantly. LESSONS: Although it is unclear why MG coexists with lung cancer, it is probable that MG is a paraneoplastic condition. Cerebrospinal fluid testing should be carried out along with electrophysiological, serological, and pharmacological procedures pertinent to the diagnosis of MG to thoroughly examine if people simultaneously experience MG-like PNPS and tumor growth. Starting immunotherapy and anticancer medication at the same time that tumor development and MG-like syndrome are discovered is crucial.

Variations in pleural microbiota and metabolic phenotype associated with malignant pleural effusion in human lung adenocarcinoma.

BACKGROUND: Lung cancer is the most common cancer-related death worldwide. In 2022, the number of daily deaths of lung cancer was estimated to reach around 350 in the United States. Lung adenocarcinoma is the main subtype of lung cancer and patients with malignant pleural effusion (MPE) suffer from poor prognosis. Microbiota and its metabolites are associated with cancer progression. However, the effect of pleural microbiota on pleural metabolic profile of MPE in lung adenocarcinoma patients remains largely unknown. METHODS: Pleural effusion samples collected from lung adenocarcinoma patients with MPE (n = 14) and tuberculosis pleurisy patients with benign pleural effusion (BPE group, n = 10) were subjected to microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography tandem mass spectrometry [LC-MS/MS]) analyses. The datasets were analyzed individually and integrated for combined analysis using various bioinformatic approaches. RESULTS: The metabolic profile of MPE in lung adenocarcinoma patients were clearly distinguished from BPE with 121 differential metabolites across six significantly enriched pathways identified. Glycerophospholipids, fatty and carboxylic acids, and derivatives were the most common differential metabolites. Sequencing of microbial data revealed nine significantly enriched genera (i.e., Staphylococcus, Streptococcus, Lactobacillus) and 26 enriched ASVs (i.e., species Lactobacillus_delbrueckii) in MPE. Integrated analysis correlated MPE-associated microbes with metabolites, such as phosphatidylcholine and metabolites involved in the citrate cycle pathway. CONCLUSION: Our results provide substantial evidence of a novel interplay between the pleural microbiota and metabolome, which was drastically perturbed in MPE in lung adenocarcinoma patients. Microbe-associated metabolites can be used for further therapeutic explorations.

Infection with human cytomegalovirus, Epstein-Barr virus, and high-risk types 16 and 18 of human papillomavirus in EGFR-mutated lung adenocarcinoma.

AIM: To assess the frequency of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and high-risk types of human papillomavirus (HPV16 and HPV18) infections in lung adenocarcinoma samples. METHODS: Lung adenocarcinoma cytological smears and their DNA isolates were obtained from patients hospitalized at the Department for Lung Diseases Jordanovac, Zagreb, in 2016 and 2017. Overall, 67 lung adenocarcinoma samples were examined: 34 with epidermal growth factor receptor gene (EGFR) mutations and 33 without EGFR mutations. The EGFR mutation status and virus presence were assessed with a polymerase chain reaction, and random samples were additionally tested for EBV with Sanger sequencing. HCMV, EBV, HPV16, and HPV18 infections were evaluated in relation to EGFR mutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed. RESULTS: More frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples with EGFR mutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutated EGFR. In the group with EGFR mutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients with EGFR mutations had a higher odds of HPV infection. CONCLUSION: HCMV, EBV, and high-risk HPV infections are more frequent in EGFR-mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype.

Anti-synthetase syndrome-associated interstitial lung disease possibly caused by atezolizumab in a patient with lung adenocarcinoma: a case report.

BACKGROUND: Anti-aminoacyl-tRNA synthetase (ARS) antibody-positive patients present with a variety of symptoms, including interstitial lung disease (ILD), which is termed anti-synthetase syndrome (ASS). But it is rare that ASS-ILD is considered an immune-related adverse event after the use of immune checkpoint inhibitors (ICIs). CASE PRESENTATION: A 47-year-old male with advanced lung adenocarcinoma was treated with platinum and ICI combination immunotherapy and was followed up as an outpatient. Nine months after the start of treatment, he developed a fever and cough, and imaging findings showed lung consolidations in the bilateral lower lung fields. The patient was positive for anti- ARS antibodies and was considered to have developed ASS-ILD due to ICIs remitted with steroid therapy. The patient was found to be positive for anti-ARS antibodies before ICI administration, and the antibody titer was elevated compared to that before ICI administration. CONCLUSIONS: The examination of anti-ARS antibodies pior to the administration of ICIs may be useful in predicting the development of ASS-ILD.

Fatal limbic encephalitis as paraneoplastic neurological syndrome in a patient with lung adenocarcinoma positive for antiamphiphysin antibody after durvalumab treatment.

A 69-year-old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody-positive PNS in our patient. Treatment with systemic high-dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment.