Regular pulse checks for patients with non-cardioembolic stroke in rehabilitation hospitals to improve recognition and detection of atrial fibrillation (the ESCORT study): protocol for a prospective multicenter observational study.

Background: Cryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF. Objective: This study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics. Methods: This multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF. Results: The study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal. Conclusion: The findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists.

Effectiveness of rehabilitation for postoperative pain after surgery for spontaneous pneumothorax in young adults.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been established as a standard therapeutic approach for pneumothorax; however, patients may experience pronounced pain during the postoperative period, and the optimization of analgesic approaches during the postoperative period is necessary. The aim of this study was to determine for the first time the effect of a physical therapist-guided exercise program on pain perception and analgesic use in the postoperative period after VATS for spontaneous pneumothorax. METHODS: This retrospective study included 73 patients aged ≤40 years (mean age is 21, range is 15 to 40) with spontaneous pneumothorax treated with VATS that were divided in exercise-based rehabilitation (n=23) and no rehabilitation (n=50) groups. Postoperative pain perception and the use of analgesics were investigated in patients who did or did not undergo an aerobic exercise postoperatively. RESULTS: In patients who underwent an exercise-based postoperative rehabilitation program, the pain control was more effective, the numeric rating scale (NRS) (25.46/42.31, P=0.02), and the dose of analgetic medication was lower than the patients who undergo rehabilitation (P=0.008). CONCLUSIONS: Overall, our findings suggest for the first time that exercise-based postoperative rehabilitation may be a viable option for pain reduction after VATS for spontaneous pneumothorax in young adults.

NSAIDs may prevent EGFR-TKI-related skin rash in non-small cell lung cancer patients
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OBJECTIVES: Skin rash is a common adverse event induced by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Here, we aimed to predict factors that reduce EGFR-TKI-related skin rash. MATERIALS AND METHODS: We conducted a single-center, retrospective study to predict factors that reduce skin rash in patients undergoing treatment for non-small cell lung cancer (NSCLC) with EGFR-TKIs using Cox proportional hazards model. RESULTS: Cox proportional hazard analysis revealed that coadministration of non-steroidal anti-inflammatory drug (NSAID) had protective effects against rash. Steroid coadministration showed a trend to being effective in reducing rash. CONCLUSION: NSAIDs may be useful in preventing EGFR-TKI-related skin rash.
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Factors Influencing the Diagnostic Accuracy of Identifying the Histologic Type of Non--Small-Lung Cancer With Small Samples.

BACKGROUND: The pathologic diagnosis has become a greater consideration in decision-making regarding the treatment options for lung cancer. Therefore, the accurate diagnosis of the tumor histologic type is essential, even when only small biopsy or cytology samples are available. However, the risk of a misdiagnosis with smaller biopsy samples is greater. The factors underlying the increased risk of a misdiagnosis in small samples are unknown. The aim of the present study was to identify the clinical and pathologic factors (other than immunohistochemical staining) that influence the pathologic diagnostic accuracy in small biopsy and cytological lung samples obtained by bronchoscopy. PATIENTS AND METHODS: We performed transbronchial lung biopsy or brushing and lavage to determine the preoperative diagnosis of 126 of 299 surgically resected lung cancer specimens. We assessed the diagnostic accuracy of the preoperative transbronchoscopic examination findings against that of the surgically resected lung specimens. RESULTS: On univariate analysis, the mean pathologic tumor size in the noncorresponding cases was larger than that in corresponding cases. Vascular invasion was also more prevalent in the noncorresponding cases. The tumor differentiation grade in the noncorresponding cases was poorer than in the corresponding cases. The noncorresponding cases were at a more progressed stage. On multivariate analysis, the pathologic tumor size and tumor differentiation grade were associated with the noncorresponding cases. CONCLUSION: We found a larger tumor size and poor differentiation grade were indicative of lung cancer tissue with a greater content of heterogeneous cells. Therefore, a possibility exists of a false diagnosis using only these factors. Thus, treatment decisions should be made considering the pathologic diagnosis and other relevant factors.

Clinical usefulness of gefitinib for non-small-cell lung cancer with a double epidermal growth factor receptor mutation.

The aim of this study was to investigate whether the pattern of epidermal growth factor receptor (EGFR) gene mutations affects sensitivity to gefitinib treatment. We investigated 44 surgically resected non-small-cell lung cancer (NSCLC) specimens obtained between 2001 and 2012 at the Tokyo Medical University Hospital. The specimens were obtained from patients treated with gefitinib as 1st-, 2nd-, or 3rd-line therapy for postoperative recurrent NSCLC. We detected EGFR mutations using the cycleave PCR technique. In addition, the specimens from non-responders were stained with antibodies against hepatocyte growth factor receptor (HGFR; MET) and hepatocyte growth factor (HGF). We assessed the progression of non-responders over a period of 2 months. Intermediate responders were considered to be patients who responded (exhibiting at least stable disease) to gefitinib therapy for 3-11 months, while long-term responders were defined as those who responded to gefitinib therapy for >12 months. The NSCLCs were histologically classified as 43 adenocarcinomas and one large-cell neuroendocrine carcinoma. One patient had an exon 18 point mutation, 23 an exon 19 deletion, 2 an exon 20 point mutation, 16 an exon 21 point mutation and 2 patients had both exon 20 and 21 point mutations. There were 4 non-responders, including the 2 patients with exon 20 mutation, 25 intermediate responders (including 10 patients under ongoing treatment) and 15 long-term responders (2 of whom are under ongoing treatment), including the 2 patients with both exon 20 and 21 mutations. Of the specimens obtained from non-responders, 3 stained with the anti- MET antibody and 1 stained with the anti-HGF antibody. Therefore, NSCLC with exon 20 mutation may respond to gefitinib treatment in the presence of an additional EGFR mutation.

[Metastatic lung tumors].

The lung metastasis remains the major cause of cancer related mortality in patients with solid malignant tumor. In general, the treatment of the lung metastasis is the systemic chemotherapy or the targeted therapy suitable for the primary lesion. However, the surgical resection of the lung metastases could enhance the survival for the chemotherapy-resistant lung metastasis only if, certain criteria are met. Recent advance of the thoracoscopic technology led to increase the number of the lung metastasectomy. Low-invasive video assisted thoracoscopic resection is beneficial for the lung metastasis as long as the primary lesion confined to the lung before systemic disease. This treatment has low complication rates and has a beneficial influence on the course of the disease. We reviewed our experience in evaluating the surgical outcomes in cancer patients who have undergone a lung metastasectomy by thoracoscopic resection.

The role of airway stent placement in the management of tracheobronchial stenosis caused by inoperable advanced lung cancer.

PURPOSE: To our knowledge there is no in-depth report on the benefits of airway stenting, which focuses specifically on patients with inoperable advanced lung cancer causing severe central airway obstruction. We evaluated the role of airway stenting as one aspect of the multidisciplinary management of advanced lung cancer. METHODS: We performed airway stenting in 40 lung cancer patients, placing a total of 58 stents. Stenting was done as a final modality in 22 patients with terminal-stage lung cancer (group A). The other 18 patients received additional therapy after stenting (group B), 12 (66.7%) of whom were treatment-naïve on admission. RESULTS: The performance status (PS) and Hugh-Jones classification (H-J) scores improved in both groups after stenting: from 3.56 to 2.48 (P = 0.001) and 4.29 to 3.20 (P = 0.004) in group A, and from 3.15 to 1.25 (P < 0.001) and 4.10 to 2.10 (P < 0.001) in group B, respectively. The median survival time and 1-year survival rate after stenting were 1.6 months and 5.1%, respectively, in group A, and 5.6 months and 25.0%, respectively, in group B. CONCLUSIONS: Airway stenting followed by adjuvant therapy may improve the survival of treatment-naïve patients with severe symptomatic airway obstruction caused by advanced lung cancer.

[A case of psuedocyst of the pancreas suspected to lung abscess].

A 83-year-old man visited a physician because of appetite loss. The chest X-ray film showed a cavity with air-fluids sign in the left lower lung field. He was admitted to our hospital for diagnosis of the cavity lesion on a suspicion of pulmonary abscess and pulmonary tuberculosis. Amylase in fluid aspirated from the cavity was elevated to 17930 IU/l. Pseudocyst of the pancreas was diagnosed. Pseudocyst of the pancreas was considered as one of the differential diagnosis of cavities on chest X-ray film.

Locally recurrent central-type early stage lung cancer < 1.0 cm in diameter after complete remission by photodynamic therapy.

BACKGROUND: It is well known that central-type early stage lung cancer < 1.0 cm in diameter shows almost 100% complete response (CR) to photodynamic therapy (PDT). However, we have encountered cases of local recurrence after CR of tumors with a surface diameter < 1.0 cm. PATIENTS AND METHODS: Ninety-three patients with 114 lesions were followed up, and cases of recurrence after CR has been obtained with initial tumors that had a diameter < 1.0 cm were examined. We compared the cytologic findings of local recurrence after CR to the cytologic findings before PDT. The relationship between the cell features and the depth of bronchial tumor invasion before PDT and on recurrence was evaluated. RESULTS: The CR and 5-year survival rates of patients with lesions < 1.0 cm were 92.8% (77 of 83 patients) and 57.9%, respectively; meanwhile, in the group of patients with lesions > or = 1.0 cm, CR and 5-year survival rates were 58.1% (18 of 31 patients) and 59.3%. There was a significant difference in efficacy between the two groups (p < 0.001). Recurrences after CR were recognized in 9 of 77 lesions (11.7%) < 1.0 cm. When the recurrent tumor cells showed type I-II (low-to-moderate atypia) at the same site initially treated, CR could be obtained by a second PDT. Type III cells (high-grade atypia) showed the characteristics of tumor cells from deeper layers of the bronchial wall. Local recurrence at the same site may be caused by residual tumor cells from deep layers because of inadequate laser irradiation and penetration. CONCLUSIONS: To reduce the recurrence rate, it is essential to accurately grasp the tumor extent and the depth of the bronchogenic carcinoma before performing PDT. Analysis of cell features of recurrent lesions after CR appears to be a useful source of information as to the depth of cancer invasion in the bronchial wall.

The characteristics of early bronchogenic carcinoma evaluated by cytomorphological features.

The relationship between the cell features of central type early lung cancer and the degree of invasion to the bronchial wall was investigated. Bronchial brushing specimens were obtained from 19 cases of central type early lung cancer preoperatively and the resected specimens were pathologically examined. The cell features were classified into three types: Type I: low grade atypia without increased nuclear chromatin, Type II: moderate grade atypia with increased chromatin and Type III: high grade atypia with irregular shaped nucleus and increased chromatin. The expression of Type I cells was significant in cases of carcinoma in situ or microinvasion and Type II and III cells were observed more frequently in cases with extramuscular bronchial wall invasion. The cell features as well as endoscopic findings can provide a basis for the more precise staging of early stage lung cancer and the determination of therapeutic strategy.

Immunologic parameters as significant prognostic factors in lung cancer.

Immunologic prognostic factors in lung cancer have not been fully clarified. We report the results of a prospective study undertaken to clarify the correlation between various cellular immunologic parameters and the survival of lung cancer patients. A total of 287 lung cancer patients were enrolled in this study. Representative in vitro cellular immune activities including lymphoblastogenesis and natural killer cell activities, in addition to the percentage of main lymphocyte subsets (CD3, CD4, CD8, HLA-DR, and Fc gamma R III on T cells) in the peripheral blood were evaluated before the initiation of therapy. The immune factors that influence the prognosis were analyzed by the log rank test and a multivariate analysis using the Cox proportional hazards model. Univariate analysis of the survival curves revealed a significant difference with regard to disease stage (P<0.0001), age (P=0.007), gender (P=0.0037), and HLA-DR (%) (P=0.048), when all the non-small cell lung cancer (NSCLC) patients (n=257) were analyzed together. This analysis, based on the histologic type, revealed that HLA-DR (%) was a significant predictor of survival in squamous cell carcinoma (P=0.0013) and small cell carcinoma (P=0.0025). A decreased CD4/CD8 ratio in small cell carcinoma (P=0.0062) and male gender in adenocarcinoma (P=0.0086) were factors associated with a worse prognosis. Multivariate analysis identified a significant correlation between survival and disease stage (P<0.0001) and gender (P=0.0243) in adenocarcinoma, disease stage (P<0.0001), age (P=0.0436) and HLA-DR (%) (P=0.0142) in squamous cell carcinoma, and HLA-DR (%) (P=0.0212) and CD4/CD8 (P=0.0112) in small cell carcinoma, suggesting independent prognostic significance. A variety of immunologic indices have prognostic significance for the different types of lung cancer. Among these, the HLA-DR (%) in the peripheral blood is the most reliable factor for squamous cell carcinoma and small cell carcinoma.

Up-regulated gene expression of angiogenesis factors in post-chemotherapeutic lung cancer tissues determined by cDNA macroarray.

The differential expressions of hundreds of tightly transcriptionally controlled genes in freshly isolated human lung cancers and respective normal lung tissues were analyzed by the cDNA macroarray technique. Three lung cancer patients received pre-operative chemotherapy with cisplatin containing regimens. After chemotherapy, these patients underwent surgery, and poly (A)-RNA expressions of 588 genes in the samples prepared from the lung cancer and normal lung tissues were compared. These expressions of the 588 genes were demonstrated by spotting onto a filter. Histogram analysis of gene expression revealed the tumors to show commonly up-regulated expression of angiogenesis and invasion related genes and adhesion molecules such as fibroblast growth factor 3 (FGFR3), matrix metalloproteinase (MMP)15, 16 and 10, integrin beta 4, integrin alpha 9, endonexin, and several types of collagens. Thus, post-chemotherapeutic tissues from lung cancer parents are characterized by remarkable up-regulation of molecules related to angiogenesis, invasion and adhesion. Tree view showed close clustering of angiogenesis related genes. Furthermore, when the angiogenesis related genes were selected and clustered, they were categorized into three groups depending upon gene expression profiles. These results suggest that angiogenesis related molecules are suitable candidates for target-based therapeutics and angiogenesis inhibitors are expected to be effective in lung cancer patients pretreated with chemotherapy.

The incidence and the risk of pneumothorax and chest tube placement after percutaneous CT-guided lung biopsy: the angle of the needle trajectory is a novel predictor.

STUDY OBJECTIVE: Pneumothorax remains the most common complication of percutaneous CT-guided lung biopsy, despite improved techniques. The rate of pneumothorax reported in the literature ranges from 19 to 60%. The aims of this study were to estimate the risk of pneumothorax in patients undergoing CT-guided lung biopsy, and to determine which factors affect its occurrence. DESIGN: Retrospective study. PATIENTS AND METHODS: This study involved 289 consecutive patients who underwent biopsy in our hospital under consistent methods, using only one type of needle, the 19-gauge Tokyo Medical College (TMC) Needle (Takei; Tokyo, Japan), under CT guidance. RESULT: Seventy-seven patients (26.6%) had pneumothorax after percutaneous CT-guided lung biopsy. Forty-one of the 77 patients (53.2%) who had pneumothorax (14.2% of the entire series) required placement of a chest tube. Our present study, using multivariate logistic regression analysis, confirmed that greater lesion depth, wider trajectory angle, and increasing FVC percent predicted are independent risk factors of pneumothorax, and that two former factors are independent risk factors of chest tube placement following percutaneous CT-guided lung biopsy. CONCLUSIONS: The angle of needle route is a novel predictor of this complication. Our findings suggest that low pneumothorax rates are achieved by combining several techniques to reduce the risk of pneumothorax.

Telomerase activity during carcinogenesis in the bronchus.

Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomeric DNA onto chromosome ends, and is not detected in most normal cells. It has been clarified that some bronchial squamous cell carcinomas may arise through the metaplasia and dysplasia sequence accompanied by accumulation of genetic mutations in metaplastic cells. Recently a highly sensitive polymerase chain reaction (PCR)-based telomerase assay (TRAP assay) was developed for the detection of telomerase activity. Telomerase activity has been found in most malignant neoplasms, including lung cancer. The objective of this study was to determine whether telomerase RNA might increase in precancerous lesions of the bronchi. Bronchial-brushing extracts were analyzed for telomerase activity (F-TRAP) and in situ telomerase activity using a fluorescence-based TRAP assay (in situ TRAP) and compared to cytological features. The fluorescence-based semi-quantitative TRAP assay detected telomerase activity in 8 out of 12 lung cancer cases (66.7%). In squamous cell carcinoma, 6 out of 9 cases (66.7%) showed telomerase activity. On the other hand, in normal and precancerous lesions of the bronchi, telomerase activity was not detected using either the F-TRAP method or in situ TRAP method. We concluded that dysplastic cells might not contain immortalized cells, and that the increase of telomerase activity is a relatively late event during the bronchial carcinogenesis. It is difficult to distinguish between dysplasia and in situ carcinoma of the bronchus morphologically, but the measurement of telomerase activity is clinically valuable for the determination of treatment.