Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Can a Relationship of Trust Be Built Between Student Doctors and Patients Through Remote Interviews During COVID-19?

INTRODUCTION: Clinical clerkships could not be conducted as usual in 2021, due to the COVID-19 pandemic. We conducted a questionnaire survey of medical students and patients to determine whether remote medical interviews conducted in such a scenario could build a trusting relationship between the two. MATERIALS AND METHODS: Fifth-year students at Tokai University School of Medicine conducted tablet-based medical interviews (remote medical interviews) with patients as part of their clinical clerkship of breast endocrine surgery. Later, both the patients and students had to rate the trustworthiness of their relationship and their preference for remote/face-to-face medical interviews in a questionnaire survey. Forty-three students and 42 patients took part in the survey. RESULTS AND DISCUSSION: All the patients and students agreed that a trusting relationship had been established. The results showed that most of the students preferred remote medical interviews, but patients were very divided in their preferences between face-to-face and remote medical interviews. Overall, we may conclude that remote medical interviews could be a safe tool for clinical practice in the future.

Trans-arterial Embolization in a Patient with Unilateral Absence of Pulmonary Artery: Treatment Success and the Four-year Prognosis.

Unilateral absence of the pulmonary artery (UAPA) with or without other anomalies in the heart is a rare congenital malformation. A 55-year-old Filipino woman without a remarkable medical history was admitted to our hospital for hemoptysis. Contrast-enhanced chest computed tomography revealed the absence of the left pulmonary artery. Echocardiography and right heart catheterization showed no cardiac malformations or pulmonary hypertension. We diagnosed her with isolated left-sided UAPA and performed transarterial embolization of the left inferior phrenic artery. This resolved the hemoptysis, and there was no recurrence during the four-year follow-up period.

Multicentre comparison of self-management in patients with COPD.

In patients with COPD, self-management plays an important role in disease management. Recently, self-management programmes have expanded patient education practices to include a variety of disease management techniques. We hypothesised that COPD patients have insufficient and/or different self-management needs according to institution. We compared information needs of patients between specialised clinics in Canada (SCC) and Japan and a hospital outpatient clinic in Japan (HCJ), all employing different self-management interventions. This cross-sectional study evaluated patients' information needs for disease management using the Lung Information Needs Questionnaire (LINQ). Furthermore, we assessed pulmonary function tests, modified Medical Research Council (mMRC) dyspnoea scale and frequencies of hospitalisations and emergency visits. The total number of patients was 183. Those attending SCC were younger (p=0.047), with lower forced expiratory volume in 1 s % predicted (p<0.0001), and scored higher on the mMRC dyspnoea scale. Total LINQ scores showed differences between institutions (p<0.0001). There was no difference for the smoking domain; however, SCC recorded significantly lower information needs for all other domains (p<0.02). No significant difference in emergency visits was seen between institutions, but HCJ recorded the highest rate of emergency visits, while SCC had significantly higher rates of hospitalisation (p=0.004). Differences were seen for frequency and duration of education between institutions. These results highlight the differences in information needs by institution and the importance of assessing individual needs. We believe, despite representing only one aspect of self-management, our findings reflect real-world circumstances, adding to the argument that self-management education should be structured, but flexible, to meet the changing needs of COPD patients.

Introducing a Remote Pre-graduate Medical Education Curriculum Planning Workshop During the COVID-19 Pandemic.

PURPOSE: To conduct a thorough online workshop on infection control under COVID-19 and to conduct a questionnaire survey on the online workshop. OBJECTIVE: The Tokai University School of Medicine has held 39 workshops to acquire the curriculum planning ability required as a faculty member of the School of Medicine. Due to the COVID-19 pandemic, this year (2020) we were unable to hold a workshop. Therefore, we attempted an online workshop using Zoom. METHODS: To shorten the amount of time required for the workshop, we excluded some content that was used the previous year. The day passed without any major problems, and both the participants and the individuals in charge of the workshop filled out a questionnaire at the end of the day. RESULTS: Conclusion: Online workshops appear to be a very useful tool in terms of infection control under the COVID-19 pandemic.

Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung.

BACKGROUND: The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis. METHODS: Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue. RESULTS: The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group. CONCLUSION: These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.

[A case of choriocarcinoma of suspected lung origin manifesting pulmonary embolism].

A 28-year-old woman visited a local hospital with a complaint of progressive dyspnea after a normal delivery. She was given a diagnosis of COP based on TBLB specimen and CT findings and received steroid pulse therapy at the hospital. Three months after her first visit she was referred to our hospital because her symptoms had not resolved despite receiving steroid therapy. The CT findings at our hospital suggested pulmonary thromboembolism. Although anticoagulation therapy was initiated, the CT findings and symptoms worsened. Thus thrombi were removed by open chest surgery and a diagnosis of choriocarcinoma was established. No primary lesion was found on gynecological examinations. Complete remission was achieved after systemic chemotherapy and there have been no event in the two years since diagnosis. Choriocarcinoma is a rare malignant tumor developing after pregnancy, with frequent metastases to the lung. However, when the tumors embolize into the pulmonary arteries, they resemble pulmonary thromboembolisms making correct diagnosis difficult. Since, owing to recent advances of cancer chemotherapy, choriocarcinoma is now curable tumor, physicians must suspect this disease in cases of pulmonary embolisms in women.

Proportion and clinical characteristics of non-asthmatic non-smokers among adults with airflow obstruction.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) mainly develops after long-term exposure to cigarette or biomass fuel smoke, but also occurs in non-smokers with or without a history of asthma. We investigated the proportion and clinical characteristics of non-smokers among middle-aged to elderly subjects with airflow obstruction. METHODS: We retrospectively analyzed 1,892 subjects aged 40-89 years who underwent routine preoperative spirometry at a tertiary university hospital in Japan. Airflow obstruction was defined as a forced expiratory volume in 1 second (FEV1)/forced vital capacity < 0.7 or as the lower limit of the normal. RESULTS: Among 323 patients presenting with FEV1/forced vital capacity < 0.7, 43 had asthma and 280 did not. Among the non-asthmatic patients with airflow obstruction, 94 (34%) were non-smokers. A larger number of women than men with airflow obstruction had asthma (26% vs. 7.6%, p < 0.001), or were non-smokers among non-asthmatics (72% vs. 20%, p < 0.001). Non-asthmatic non-smokers, rather than non-asthmatic smokers, asthmatic non-smokers, and asthmatic smokers, exhibited better pulmonary function (median FEV1: 79% of predicted FEV1 vs. 73%, 69%, and 66%, respectively, p = 0.005) and less dyspnea on exertion (1% vs. 12%, 12%, and 28%, respectively, p = 0.001). Pulmonary emphysema on thoracic computed tomography was less common in non-smokers (p < 0.001). Using the lower limit of the normal to define airflow obstruction yielded similar results. CONCLUSIONS: There are a substantial number of non-smokers with airflow obstruction compatible with COPD in Japan. In this study, airflow obstruction in non-smokers was more common in women and likelier to result in mild functional and pathological abnormalities than in smokers. Further studies are warranted to investigate the long-term prognosis and appropriate management of this population in developed countries, especially in women.

Post-bronchoscopy pneumonia in patients suffering from lung cancer: Development and validation of a risk prediction score.

BACKGROUND: The incidence, risk factors, and consequences of pneumonia after flexible bronchoscopy in patients with lung cancer have not been studied in detail. METHODS: We retrospectively analyzed the data from 237 patients with lung cancer who underwent diagnostic bronchoscopy between April 2012 and July 2013 (derivation sample) and 241 patients diagnosed between August 2013 and July 2014 (validation sample) in a tertiary referral hospital in Japan. A score predictive of post-bronchoscopy pneumonia was developed in the derivation sample and tested in the validation sample. RESULTS: Pneumonia developed after bronchoscopy in 6.3% and 4.1% of patients in the derivation and validation samples, respectively. Patients who developed post-bronchoscopy pneumonia needed to change or cancel their planned cancer therapy more frequently than those without pneumonia (56% vs. 6%, p<0.001). Age ≥70 years, current smoking, and central location of the tumor were independent predictors of pneumonia, which we added to develop our predictive score. The incidence of pneumonia associated with scores=0, 1, and ≥2 was 0, 3.7, and 13.4% respectively in the derivation sample (p=0.003), and 0, 2.9, and 9.7% respectively in the validation sample (p=0.016). CONCLUSIONS: The incidence of post-bronchoscopy pneumonia in patients with lung cancer was not rare and associated with adverse effects on the clinical course. A simple 3-point predictive score identified patients with lung cancer at high risk of post-bronchoscopy pneumonia prior to the procedure.

Clinical contributions of exhaled volatile organic compounds in the diagnosis of lung cancer.

BACKGROUND: Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer. METHODS: Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography. RESULTS: The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (p = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both p < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively). CONCLUSION: Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.

Scholastic Achievements: Graduate-entry vs. School-leaver-entry Medical Students.

OBJECTIVE: The objective of the present study is to conduct a retrospective analysis comparing graduate-entry program (GEP) and school-leaver-entry program (SEP) students from the perspective of scholastic achievements from admission through the national examination for medical practitioners. METHODS: The number of students who repeated one or more years, because of their poor results on examinations, the scores of graduation examinations, and the pass rates for the national examination for medical practitioners were compared, retrospectively, over the last 8 academic years between GEP and SEP students at Tokai University School of Medicine. RESULTS: The ratio of students who graduated in the prescribed course length was significantly higher (p = 0.002) in GEP students than that in SEP students. There were no differences between the average scores on the graduation examinations for GEP and SEP students, except in two academic years. The pass rate of GEP students (97%) of the national examination for medical practitioners was significantly higher (p < 0.001) than that of SEP students (89%). CONCLUSIONS: These results suggest that GEP students are more favorable candidates in terms of becoming physicians in the usualprescribed number of years than SEP students.

High-flow nasal cannula oxygen therapy for acute exacerbation of interstitial pneumonia: A case series.

We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non-rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40 L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP.

Progressive Multifocal Micronodular Pneumocyte Hyperplasia in the Lungs of a Patient with Tuberous Sclerosis Complex: A Case Report.

We report a case of multifocal micronodular pneumocyte hyperplasia (MMPH) in a patient with tuberous sclerosis complex, in whom the lung nodules increased in the number and size over the course of 8 years. We diagnosed MMPH following a lung biopsy performed during video-assisted thoracic surgery. In most of the previously reported cases, the number and size of lung nodules is unchanged during the clinical course. Our case is the first report of progressive disease in pathologically proven MMPH.

Relationship between IL-1beta gene polymorphism and gastric mucosal IL-1beta levels in patients with Helicobacter pylori infection.

BACKGROUND: Interkeukin-1 (IL-1) gene cluster polymorphisms that are thought to enhance the production of IL-1beta are associated with an increased risk of gastric cancer. To determine the role of host genetic factors in Helicobacter pylori infection, we examined the relationship between gastric mucosal IL-1beta levels and IL-1B polymorphisms in patients with H. pylori infection. METHODS: Biopsy tissues obtained from 99 patients were homogenized and gastric mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay (ELISA). Single-base polymorphisms at positions -511 and -31 in IL-1B were analyzed. RESULTS: The IL-1beta level in the antrum was significantly higher in genotype IL-1B-511C/C than in H. pylori-negative patients (P < 0.05). The IL-1B polymorphism did not influence the degree of gastric neutrophil and mononuclear cell infiltration, or gastric atrophy. IL-1beta levels in the corpus, but not those in the antrum, correlated to the severity of gastric atrophy. CONCLUSIONS: These findings indicate that IL-1B polymorphisms enhance IL-1beta production in the antrum; however, other factors might regulate the production of IL-1beta in the corpus of the stomach, regardless of IL-1B polymorphisms, and high IL-1beta production may be associated with the grade of gastric atrophy in the corpus mucosa in patients with H. pylori infection.

The threshold of the intermittent hypoxic exposure period to elicit polycythemia in rats.

It is not yet clear whether there is an intermittent hypoxia (IHx) threshold to elicit polycythemia and blood pressure elevation, and whether blood hemoglobin concentration ([Hb]) increases with an increase in the hypoxic exposure period. We have previously shown that repetitive exposure to 10% O2 for 60 min/day for up to 5 weeks does not produce polycythemia. In the present study, we evaluated the effect of IHx of 10% O2, 120 min/day for 1, 2, 3 and 4 weeks on [Hb], arterial blood pressure, heart rate and arterial blood gases in the rat. IHx of 10% O2, 120 min/day induced polycythemia at 1 week and produced a time-dependent increase in [Hb] from 0 week to 4 weeks. Arterial blood pressure significantly increased during IHx exposure for 4 weeks probably due to a combination of an increased sympathetic activity as well as increased blood viscosity. The IHx threshold for polycythemia might exist between 60 min/day and 120 min/day in this level of hypoxia.

Exposure to hypoxia results in uneven pulmonary blood flow distribution prior to pulmonary edema.

The effects of hypoxia on pulmonary arterial pressure (PAP) and on development of pulmonary edema, ascertained by changes in lung water and pulmonary vascular permeability were studied in rats using bronchoalveolar lavage (BAL). Rats were exposed to hypobaric hypoxia (P(B) = 290 Torr) for 24 h followed by 4 h of normobaric hypoxia (F(IO)2 0.07) (Hx). Controls were rats maintained in a normoxia (Nx). Mean PAP was 28.3 +/- 0.8 mmHg in Hx, and 18.8 +/- 1.7 mmHg in Nx (mean +/- SD). The wet-to-dry lung weight ratio was significantly higher in Hx. The ratio of fluorescence activity between BAL fluid and plasma 4 h after i.v. injection of FITC-albumin was higher in Hx, suggesting an increased pulmonary microvascular permeability in Hx. In a separate study, pulmonary blood flow distribution, measured after 10 min of hypoxia (F(IO)2 0.07) using non-radioactive microspheres, was significantly more heterogeneous than Nx, suggesting a non-homogeneous hypoxic pulmonary vasoconstriction. The combined data of both studies suggest that hypoxia induces heterogeneous pulmonary blood flow distribution which is followed by increased vascular permeability and the development of pulmonary edema.

A pheochromocytoma causing limited coagulopathy with hemoptysis.

We treated a 59-year-old woman presenting with hemoptysis, a rare symptom of pheochromocytoma. Multiple factors including hypertension caused by sudden catecholamine release may result in pulmonary edema. It should be noted that the increased activation of coagulation cascade, which was demonstrated by increased thrombin-antithrombin III complex (TAT) and prothrombin fragment factor 1 and 2 (F1 + 2), as well as endothelial or platelet stimulation evidenced by the increased plasma von Willebrand factor, may have contributed to hemoptysis. These abnormalities were normalized after adrenalectomy. Our case indicates the important role of catecholamine in coagulopathy and possibly in vasculopathy.

Eosinophilic pleurisy induced by dantrolene.

A 70-year-old male developed eosinophilic pleurisy fifteen years after dantrolene sodium had been started for his spastic paraplegia due to spinocerebellar degeneration. Drug lymphocyte stimulation test (DLST) for dantrolene was positive. After discontinuance of dantrolene, pleural effusion gradually decreased and inflammatory reaction improved. During two-year observation, we have found no relapse of pleurisy without special medication. We present this case and compare this case with other 10 reported cases.

Relationship between gastric mucosal IL-8 levels and histological gastritis in patients with Helicobacter pylori infection.

To determine the role of host immune responses in H. pylori infection, we examined the relationship between gastric mucosal IL-8 levels and histological gastritis in patients with H. pylori infection. Biopsy tissue obtained from 99 patients were homogenizedand mucosal IL-8 levels measured by ELISA. The gastric mucosal IL-8 levels in both the antrum and corpus were higher in patients with H. pylori than in H. pyloi negativepatients. IL-8 levels in the corpus but not the antrum correlated with the severity of the atrophy. The IL-1B polymorphism had no influence on the degree of IL-8 production. These findings indicate that IL-8 production is independent of IL-1B polymorphisms and IL-8 may play an important role in the development of atrophic gastritis.

Pulmonary non-caseating granuloma in Waldenström macroglobulinemia.

Lung involvement is rare in Waldenström macroglobulinemia (WM). We encountered a male patient with WM who complained of breathlessness. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. Transbronchial biopsy showed infiltration of atypical plasmacytoid lymphocytes and non-caseating granuloma. We treated the patients with fludarabine phosphate, and both his symptom and X-ray findings were then improved. To our knowledge, this is the first case showing non-caseating granuloma with lung involvement of WM. We discuss a mechanism of non-caseating granuloma formation in this case.