Efficacy of durvalumab plus chemotherapy in small-cell lung cancer with Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare disease but is often associated with small-cell lung cancer (SCLC). We discuss the case of a 65-year-old man diagnosed with SCLC-LEMS and treated with carboplatin, etoposide, and durvalumab. Lower extremity weakness and high anti-P/Q voltage-gated calcium channel (VGCC) antibody levels were diagnostic and helpful. The patient showed a reduction in neurological symptoms with treatment for SCLC, including an immune checkpoint inhibitor (ICI), without standard treatment for LEMS. This treatment may be a treatment option, although the recurrence of LEMS as an immune-related adverse events (irAEs) should be noted.

Plus moist HS-W®: a new nasal packing material for the middle meatus in endoscopic sinus surgery.

PURPOSE: Removal of the current calcium alginate packing materials to the middle meatus in endoscopic sinus surgery (ESS) is usually accompanied by discomfort or pain owing to the hard and brittle nature of these materials. Plus moist HS-W® is a new calcium alginate packing material released in 2022 developed to overcome this issue by changing the uronic acid component. We aimed to compare the discomfort/pain during the removal of Plus moist HS-W® with Kaltostat®, as well as their suitability as packing materials in ESS. METHODS: Kaltostat® and Plus moist HS-W® were used as packing materials in 22 and 21 patients who underwent ESS in 2021 and 2022, respectively. Patients were asked to rate the pain during the packing removal 10 days after ESS using the Numerical Rating Scale (NRS). The ratio of residual packing materials, number of suctions (insertions/extractions of the suction cannula), and time required to remove packing materials were measured. Postoperative complications such as hemorrhage, local infection, lateralization of the middle turbinate, and synechia of the middle meatus were also evaluated. RESULTS: The Plus moist HS-W® group exhibited significantly lower NRS pain scores, a lower ratio of residual packing materials, a reduced number of suctions, and a shorter time required to remove the packing. No obvious postoperative complications occurred in both groups except for one suspicious case of a slight infection in the Kaltostat® group. CONCLUSION: Compared with Kaltostat®, Plus moist HS-W®, characterized by better gelatinization than Kaltostat®, benefits patients by minimizing discomfort/pain during removal. LEVEL OF EVIDENCE: Level 3.

First case report of erlotinib plus ramucirumab treatment for lung carcinosarcoma with EGFR L858R mutation.

Lung carcinosarcoma is acknowledged as a rare form of lung cancer. Due to its rarity, the inability to conduct large-scale clinical trials and interventions is currently carried out based on empirical evidence. In this study, we report the case of a 73-year-old female patient diagnosed with postoperative recurrence of lung carcinosarcoma. The resected tumor was diagnosed as lung carcinosarcoma, and genetic testing revealed the presence of the epidermal growth factor receptor (EGFR) exon21 L858R. Approximately 2 years postoperatively, the tumor recurred and the patient was treated with erlotinib plus ramucirumab, which were effective in controlling metastatic disease. Erlotinib plus ramucirumab is therefore a treatment option for EGFR mutation-positive lung carcinosarcoma.

The GR-SGK1-NDRG1 Pathway as a Predictor of Recurrence and Prognosis in Lung Adenocarcinoma After Radical Surgery.

BACKGROUND/AIM: The glucocorticoids (GCs)-glucocorticoid receptor (GR)-SGK1-NDRG1 pathway plays an important role in the response of tumor cells to various stresses including chemotherapy. In many solid tumors, the GCs-GR pathway acts as a tumor suppressor; however, its function varies depending on the type of cancer. This study investigated the relationship between the GR-SGK1-NDRG1 pathway and lung adenocarcinoma recurrence and overall survival. MATERIALS AND METHODS: Lung adenocarcinoma cases (n=121, Stage I-III) were included. Immunohistochemistry for GR, N-myc downstream regulated gene 1 (NDRG-1), serum and glucocorticoid-induced protein kinase 1 (SGK-1), Ki-67, and programmed cell death ligand 1 (PD-L1) was performed to examine their relationship with clinicopathological features, recurrence, and prognosis. RESULTS: SGK-1 and NDRG-1 were significant prognostic factors. Recurren ce was more likely in the SGK-1, NDRG-1, and Ki-67 high/positive groups. CONCLUSION: The GR-SGK1-NDRG1 pathway may be involved in the recurrence and prognosis of lung adenocarcinoma.

Study of the clinicopathological features of soluble PD-L1 in lung cancer patients.

Objective: In recent years, an association between serum soluble immune checkpoint molecules (sICMs) and malignant tumors has been reported, which may become important biomarkers in the future. Although several reports have suggested a correlation between sICMs and prognosis, their origin is unclear. In this study, changes in serum soluble PD-L1 (sPD-L1) during the perioperative period and its origin were analyzed in patients with lung cancer. Patients and Methods: Patients with lung tumors (n=39) were included. Samples for sPD-L1 measurements were collected at five time points before and after surgery, and their changes over time were analyzed. ELISA was used to measure sPD-L1 levels. Results: Thirty-nine patients with lung tumors (31, males; 8, females; age, 74 (years) ± 7.7 (range: 51-89) years; malignancy/benign, 33/6) were enrolled. Eight cases of driver gene mutation-positive tumors were included. Twenty-eight (72%) patients were smokers, and their performance status was 0-1 in all 39 patients. PD-L1 TPS was ≥50%/1-49%/<1% in 8/10/14 patients. Stage I/II/III/IV/postoperative recurrence of lung cancer was observed in 21/0/6/5/1 patients, respectively. There were no significant correlations between sPD-L1 levels and clinicopathological features and no correlation with PD-L1 TPS. Comparing localized lesions (stages I-III) with advanced lesions (stage IV and postoperative recurrence), the distribution of sPD-L1 was slightly higher in advanced lesions, although the difference was not significant. No obvious changes in sPD-L1 expression were observed before and after surgery. Conclusion: sPD-L1 levels tended to be high in stage III and above lung cancer. There was no change in sPD-L1 levels before and after surgery. sPD-L1 levels did not correlate with the PD-L1 TPS.

Prediction of Postoperative Respiratory Complications after Lobectomy in Lung Cancer Patients with COPD by Quantitative Image Analysis: A Historical Cohort Study.

PURPOSE: We examined whether preoperative assessment of percentage of low attenuation area (LAA%) on the non-resected side can predict postoperative respiratory complications (PRC) after lobectomy. MATERIALS AND METHODS: We conducted a historical cohort study of 217 smokers (175 males and 42 females) who underwent lobectomy for primary lung cancer at our hospital between January 2014 and March 2021. First, the relationship between LAA% and respiratory function parameters (RFPs) calculated for both the bilateral and non-resected sides was used to estimate the most effective patient group. Next, multivariate analyses of the relationship between LAA% of the non-resected side and PRC were performed using logistic regression analysis after adjusting for basic patient attributes and respiratory function. RESULTS: A correlation was found between LAA% and RFP in smoking males. Multivariate analysis showed a strong relationship between model 3, adjusted for basic patient attributes and lung function factors, and PRC (odds ratio, 2.43; 95% confidence interval, 1.05-5.63). CONCLUSION: LAA% of the non-resected side suggested that it may be able to predict the occurrence of PRC after lung cancer lobectomy.

Effect of Dupilumab on Depression in Asthma with Eosinophilic Chronic Rhinosinusitis in the Japanese Population.

INTRODUCTION: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. RESULTS: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. DISCUSSION/CONCLUSION: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.

For which lung cancer patients is re-administration of immune checkpoint inhibitors effective?

Objective: Currently, immune checkpoint inhibitors (ICIs) play a central role in the treatment of lung cancer. However, ICI re-administration is still uncommon, and its utility should be evaluated as early as possible. Patients and Methods: Twenty-five patients who received ICIs twice or more in any of the drug treatment lines for advanced/relapsed non-small cell lung cancer were included. OS, PFS, ORR, and DCR were examined, and factors such as age, sex, histopathological type, PD-L1 expression, whether radical surgery was performed, driver gene mutations, and immune-related adverse events (irAEs), were evaluated for their relevance and as prognostic factors. Results: Of the 25 patients, 17 were men and 8 were women, with an average age of 68 ± 8.4 (range, 48-85 years), and histology was non-squamous cell carcinoma/squamous cell carcinoma in 19/6 cases. One driver gene mutation positive case was included. PD-L1 TPS was ≥50%/1-49%/0-1%/ unknown in 7/8/5/5 cases. The first ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/13/7 cases. The median number of courses was 9 (range, 1-52) months, and the median PFS was 9 (95% CI, 6.0-12.0) months. Cytotoxic chemotherapy or radiation therapy was administered to 6 patients during the interval up to re-administration. The second ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/8/12 cases, and all patients received antibody drugs different from those given as the first ICI. The median number of courses was 5 (range, 1-24), and the median PFS was 3 months (95% CI, 1.0-5.0) months. In 5 of the 6 patients (24%) who achieved PFS of 6 months or longer after re-administration, the order of administration was anti-PD-1 antibody to anti-PD-L1 antibody. Conclusion: The effect of re-administration is limited, but it may be effective depending on the type of cases and the order of ICI administration. Further studies are required to verify its effectiveness.

Prediction of effectiveness of potassium-competitive acid blocker and serotonin noradrenaline reuptake inhibitor on abnormal sensation in the throat: use of patient-reported outcome measures (PROMs).

PURPOSE: To determine patients with abnormal sensation in the throat (AST) who would respond to potassium-competitive acid blocker (P-CAB) or serotonin noradrenaline reuptake inhibitor (SNRI) treatment. METHODS: AST patients were randomly divided into two groups. Thirty-one and 21 patients received P-CAB and SNRI treatment, respectively. GETS-J, the Japanese version of Glasgow Edinburgh Throat Scales (GETS), consisted of three subscales of throat symptoms (globus sensation, pain/swelling of the throat, and dysphagia) and somatic distress due to the disease, Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (FSSG), and Hospital Anxiety and Depression Scale (HADS) were used before and after treatments. Responders to treatments were defined as those who showed 50% or more decrease in symptom scores or somatic distress. RESULTS: Pre-treatment GETS-J pain/swelling scores and FSSG acid reflux scores were higher in P-CAB responders and decreased after treatment. Receiver operating characteristic curve for pain/swelling subscale had an area under the curve (AUC) of 0.792 to predict P-CAB responders and a score of 11 provided the best combination of sensitivity (62.5%) and specificity (80%). Somatic distress and HADS anxiety scores, but no other GETS-J symptom scores, decreased after SNRI treatment. Pre-treatment globus scores were lower in SNRI responders. AUC value for globus subscale to predict SNRI responders was 0.741 and a score of 6.5 provided the best combination of sensitivity (70%) and specificity (73%). CONCLUSIONS: Pain/swelling is a characteristic symptom in AST patients who respond to P-CAB treatment. SNRI treatment would be effective for somatic distress in cases with mild symptoms.

[Clinical Efficacy of Monotherapy with Immune Checkpoint Inhibitors for Advanced Non-Small Cell Lung Cancer].

OBJECTIVE: To retrospectively assess data on immune checkpoint inhibitors(ICIs)in an actual clinical setting, examine the factors that contribute to response and survival using real-world data, and compare the effectiveness of the 3 types of ICIs for patients with non-small cell lung cancer(NSCLC). METHODS: A retrospective analysis of 127 patients with NSCLC treated with ICIs at our hospital was conducted. RESULTS: Nivolumab(56 patients)showed a 3-year survival rate of 21.6% and a disease control rate of 57.1%. These results are consistent with the clinical trials of Nivolumab. Pembrolizumab(36 patients) showed a 2-year survival rate of 60.3%, a response rate of 50.0%, and a disease control rate of 63.9%. Atezolizumab(35 patients)displayed a particularly low response rate with a 1-year survival rate of 58.4%, response rate of 8.6%, and disease control rate of 25.7%. The treatment results for recurrence after surgery for lung cancer were comparable to those for unresectable lung cancer. CONCLUSION: Anti-PD-1 antibody displayed better therapeutic results than anti-PD-L1 antibody. The efficacy of ICI administration for postoperative recurrent lung cancer was also shown in this study.

[Acute Megakaryoblastic Leukemia Developed after the Surgical Treatment of Mediastinal Malignant Germ Cell Tumor].

A 26-year-old man was admitted to our hospital for an examination of a mediastinal tumor. Chest computed tomography(CT) showed a giant anterior mediastinal tumor narrowing the trachea and right main bronchus. Although needle biopsy could not be done because of patient respiratory condition, non-seminomatous mediastinal germ cell malignant tumor was strongly suspected by high level of serum AFP without no abnormal finding in his testis. After 1 cycle of chemotherapy by cisplatin, etoposide and bleomycin, the mediastinal tumor decreased in size. Percutaneous biopsy was challenged, however, definite diagnosis could not be established and the surgical resection was performed. The tumor was pathologically diagnosed as mature teratoma with elements of a yolk-sac tumor and some sort of sarcoma. Sudden onset of back pain and thrombocytopenia were encountered 5 months after the operation. Hematologic examination confirmed acute megakaryoblastic leukemia, and remission-induction therapy and allogeneic hematopoietic stem cell transplantation were performed. Twelve months after the operation, the patient is well without recurrence of either disease.

[Pericardial Fenestration and Multidisciplinary Treatment to Improve the Prognosis of the Malignant Pericarditis Due to Lung Cancer].

We experienced 3 cases in whom multidisciplinary treatment with pericardial fenestration was effective for malignant pericardial effusion associated with lung cancer. Case 1:Right upper lobectomy for lung adenocarcinoma, EGFR (-) and ALK (-) had been performed. After 34 months, malignant pericarditis occurred and left pericardial fenestration was performed. After fenestration, anticancer drugs and immune checkpoint inhibitor( ICI) were administered. He died of lung cancer in 53 months after fenestration. Case 2:Thirty-three months after left upper lobectomy for lung adenocarcinoma [EGFR (+) and ALK (-)], malignant pleuritis and pericarditis occurred and right pericardial fenestration was performed. After fenestration, anticancer drugs, EGFR-TKI and ICI were administered. He died of lung cancer in 35 months after fenestration. Case 3:Pericardial fenestration was performed for malignant pericarditis due to lung adenocarcinoma with EGFR (-), ALK (-) and PD-L1 [tumor propotion score (TPS) 0%]. After fenestration, anticancer drugs and ICI were administered. The patient died of lung cancer in 15 months after fenestration. Pericardial fenestration for malignant pericarditis is possibly useful for the management of patients, which in turns is also useful in continuing the medical treatment to prolong the prognosis.

[Association Between Juvenile Spontaneous Pneumothorax and Smoking].

We assessed the relation between smoking and pneumothorax in patients aged <40. Of 526 patients who underwent surgery for pneumothorax in 2011~2015, 311 were under the age of 40 and they were included in this study. Of 311, 54 cases( 17.4%) were diagnosed with spontaneous pneumothorax associated with emphysematous change by pathological assessment. By the multivariate analysis, 2 parameters exhibited significance for the risk of these spontaneous pneumothorax:a Brinkmann index of ≥165 and a smoking period of ≥9.5 years. It was suggested that smoking is strongly related to the onset of spontaneous pneumothorax even in the younger population less than 40 years of age.

[Bronchial Artery Aneurysm with Hoarseness;Report of a Case].

The patient was a 72-year-old man with a history of bronchiectasis. He was admitted to our hospital for an examination of hoarseness. Chest computed tomography (CT) showed bronchiectasis in the bilateral lungs and bronchial artery aneurysm in the mediastinum. To prevent rupture of the aneurysm, we imaged the bronchial artery aneurysm by selective bronchial artery angiography and performed bronchial artery embolization (BAE) with 19 platinum coils. Three months after successful BAE, his hoarseness had improved, and the bronchial artery aneurysm was reduced in size after 12 months. To our knowledge, this is the 1st report of BAE improving hoarseness due to bronchial artery aneurysm.

Age-related Hearing Loss Is Strongly Associated With Cognitive Decline Regardless of the APOE4 Polymorphism.

OBJECTIVE: To examine the association between hearing impairment and cognitive decline and to identify possible risk factors for presbycusis. STUDY DESIGN: Cross-sectional survey in prospective cohort study. SETTING: University hospital. PATIENTS: A total of 322 participants aged >60 years, for whom all the below data were available, were enrolled in the study. There were 168 females and 154 males with a median age of 71 years (range: 60-89 yrs). INTERVENTIONS: PROST (Project in Sado for Total Health), a medical database in Sado island Japan, was analyzed. MAIN OUTCOME MEASURES: Data on pure-tone audiometry, mini-mental state examination (MMSE), polymorphism of apolipoprotein E4 (ApoE4), diabetes mellitus, hypertension, smoking, and alcohol consumption were extracted. Hearing impairment was defined as an average frequency between 0.25 and 8 kHz that exceeded 30 dB. Multivariate analysis was used to identify which of the above factors could predict the hearing impairment. Hearing threshold of each Hz was compared between the ApoE4 (+/+), (+/-), and (-/-) groups. RESULTS: Among various factors, only low MMSE scores (<24) showed significant association with hearing impairment. There were no differences in the hearing threshold of all frequencies between ApoE status groups. CONCLUSIONS: Hearing impairment was associated with low MMSE sores, regardless of the ApoE4 status. If ApoE4 status would be a common upstream predictor for both the hearing and cognitive impairment, hearing threshold would be related to ApoE4 status. However, these results may suggest that hearing impairment may be causally related to the cognitive dysfunction, perhaps via the cognitive load mechanisms.

Thymoma appearing 9 years after the resection of squamous cell carcinoma of the lip: A case report of triple primary tumors and literature review.

The occurrence of second primary tumor (SPT)following malignancy treatment is common. In patients with head and neck (H&N) cancer, SPTs principally occur in the H&N region, lungs or esophagus. Therefore, patient follow-up after cancer treatment is important in order to detect recurrence, metastasis and new primary tumors. However, no standard guidelines on lifelong follow-up imaging are available. Herein, we report a patient who presented with three metachronous primary tumors-squamous cell carcinoma (SCC) of the tongue, SCC of the lip and type A thymoma. The third tumor was incidentally detected during follow-up using contrast-enhanced computed tomography (CT) 9 years following resection of the second tumor. To the best of our knowledge, this specific combination of metachronous tumors has not yet been reported. Based on the literature review, we observed that thymoma occurs following H&N cancer treatment. Therefore, to ensure that the presence of subsequent thymomas is not overlooked, we suggest regular lifelong follow-up using contrast-enhanced CT in patients who had previously been diagnosed with H&N cancer. The literature review revealed that thymomas occur in patients with H&N cancer and should be detected at the earliest convenience.

[Idiopathic Bilateral Chylothorax which Presented Difficulty in Treatment].

A 57-year-old woman was referred to our hospital because of bilateral chylothorax. She was previously treated with dietary restriction and pleurodesis resulting in failure. She did not have diseases causing chylothorax, and was diagnosed as having idiopathic chylothorax. To control chylothorax, 2 surgical operations to ligate bilateral thoracic ducts, right pleurodesis, and 2 times of left pleurodeses was necessary.