Clinical and Diagnostic Utility of Genomic Profiling for Digestive Cancers: Real-World Evidence from Japan.

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is rapidly expanding in cancer treatment. ICIs have a unique safety profile, characterised by immune-related adverse events (irAEs). The safety profile of ICIs lacks patient experience and perspectives. This study primarily aims to obtain a database for descriptive research on the status of irAEs using the Patient-Reported Outcomes version of the Common Terminology Criteria (PRO-CTCAE) in patients with gastrointestinal cancer, lung cancer and malignant pleural mesothelioma treated with regimens containing ICIs. METHODS AND ANALYSIS: This is an ongoing, multicentre, observational study in Japan. Eligible patients must be at least 20 years old and have been diagnosed with lung cancer, malignant pleural mesothelioma or gastrointestinal cancer and plan to use ICIs. Participants will install the electronic PRO (ePRO) application and report adverse events via ePRO using PRO-CTCAE once weekly for up to 48 weeks. A registry will be established using background information obtained from medical records. The sample size is determined by 1 year projection without using statistical methods. Statistical analyses will include point estimates and 95% CIs for the incidence of each adverse event by cancer type and regimen at each time point. ETHICS AND DISSEMINATION: This research will be conducted per the Declaration of Helsinki, the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects issued by the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labor and Welfare, and the revised Personal Information Protection Law. The study protocol was approved by the Ethics Committee (approval ID T2021-0180) of Tokyo Medical University Hospital on 15 October 2021. REGISTRATION DETAILS: The study began enrolling patients in December 2021. The target enrolment is 260; as of October 2022, 141 have been enrolled, and the enrolment is scheduled to end on 30 June 2023. TRIAL REGISTRATION NUMBER: UMIN000046418.

Glasgow prognostic score for prediction of chemotherapy-triggered acute exacerbation interstitial lung disease in patients with small cell lung cancer.

BACKGROUND: Predicting the incidence of chemotherapy-triggered acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer is important because AE-ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation-based index composed of serum levels of C-reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE-ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. METHODS: Medical records of patients who received platinum-based first-line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE-ILD and overall survival (OS) between GPS 0, 1, and 2. RESULTS: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy-triggered AE-ILD. The AE-ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE-ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). CONCLUSIONS: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy-triggered AE-ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy-tolerant patients from those at high risk of AE-ILD.

Glasgow Prognostic Score predicts chemotherapy-triggered acute exacerbation-interstitial lung disease in patients with non-small cell lung cancer.

BACKGROUND: Interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD. METHODS: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS. RESULTS: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05). CONCLUSIONS: GPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC. WHAT THIS STUDY ADDS: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.

Impact of Glucose Uptake of Noncancerous Lung Area in Respiratory Events for Lung Cancer Patients.

BACKGROUND: Postoperative severe respiratory adverse events (SRAEs) are the major cause of perioperative morbidity in patients after thoracic surgery. In particular, SRAEs often occur in lung cancer patients concomitant with chronic inflammatory lung diseases (CILDs) such as interstitial lung disease, emphysema, infectious disease, and asthma. We aimed to clarify whether the measurement of the maximum of standardized uptake value in the noncancerous lung area (NCA-SUVmax) and CILDs on high-resolution computed tomography were useful for predicting the risk of SRAEs. METHODS: A total of 984 patients with lung cancer undergoing preoperative computed tomography, F-18 fluorodeoxyglucose-positron emission tomography/computed tomography followed by surgery between July 2012 and March 2019 were assessed. NCA-SUVmax was measured using a 3-dimensional workstation. We extracted the records of patients with CILDs and their disease history. Predictive factors associated with SRAEs were identified. RESULTS: SRAEs were observed in 75 patients (7.6%), and 7 patients (9.3%) died of SRAEs within 90 days after surgery. NCA-SUVmax in patients with CILDs (n = 325; emphysema = 161, interstitial lung disease = 134, infectious disease = 17, asthma = 13) were higher than that in patients without CILDs (n = 659; 1.3 ± 0.7 vs 1.1 ± 0.4, respectively; P < .001). On multivariate analysis, CILDs, percent vital capacity, and NCA-SUVmax were independently associated with SRAEs (P < .001). Rate of SRAEs in patients with CILDs, NCA-SUVmax ≥1.3, and percent vital capacity ≤ 110 was 31.8%. CONCLUSIONS: NCA-SUVmax was independently associated with the incidence of SRAEs in patients with resected lung cancer and was significantly increased in patients with CILDs.

Association between F-18 fluorodeoxyglucose uptake of noncancerous lung area and acute exacerbation of interstitial pneumonia in patients with lung cancer after resection.

BACKGROUND: Idiopathic pulmonary fibrosis is defined as a specific form of progressive fibrosing interstitial pneumonia. Postoperative acute exacerbation is considered a lethal comorbidity for patients with lung cancer, particularly when it is accompanied with idiopathic pulmonary fibrosis. Thus, pretherapeutic risk stratification for acute exacerbation has been anticipated. In this study, we aimed to investigate whether the maximum standardized uptake value of F-18 fluorodeoxyglucose is useful for assessing the postoperative risk of acute exacerbation and severe respiratory adverse events in patients with lung cancer after surgical resection. METHODS: A total of 822 patients with lung cancer who underwent preoperative high-resolution computed tomography, fluorodeoxyglucose-positron emission tomography/computed tomography, and pulmonary resection between July 2012 and July 2018 were assessed. Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were measured using a 3-dimensional workstation. Multivariable analyses for acute exacerbation and severe respiratory adverse events were performed using the logistic regression model. RESULTS: Among all patients, 120 (14.6%) had idiopathic pulmonary fibrosis findings on high-resolution computed tomography whereas severe respiratory adverse events were observed in 35 (4.2%) patients, including those with acute exacerbation (n = 15, 1.8%). Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with both acute exacerbation and severe respiratory adverse events on multivariable analysis, both in all patients and in the 120 patients with idiopathic pulmonary fibrosis. Risk stratification analysis showed that 19.0% and 30.2% of patients who were positive for idiopathic pulmonary fibrosis on high-resolution computed tomography and with a maximum standardized uptake value of the main tumor and that of the noncancerous lung area 1.69 or greater (the optimal cutoff value relevant to acute exacerbation) experienced acute exacerbation and severe respiratory adverse events, respectively. CONCLUSIONS: Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with the incidence of postoperative acute exacerbation and severe respiratory adverse events in patients with lung cancer.

Treatment status and safety of crizotinib in 2028 Japanese patients with ALK-positive NSCLC in clinical settings.

OBJECTIVE: Post-marketing surveillance (PMS) was performed in Japan to obtain information on the safety and efficacy of crizotinib. METHODS: Target patients included almost all patients with anaplastic lymphoma kinase-positive non-small cell lung cancer who were administered crizotinib. The observation period was 52 weeks. In the present study, we focused on the treatment status and safety of crizotinib therapy and analyzed the real-world data obtained by this PMS (ClinicalTrials.gov: NCT01597258). RESULTS: The safety analysis set included 2028 Japanese patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of adverse drug reactions (ADRs) was 91.6%, and common ADRs (incidence ≥15%) were nausea (32.2%), diarrhea (24.3%), photopsia (18.9%), vomiting (17.5%) and dysgeusia (16.8%). Many patients (623 patients) discontinued treatment of crizotinib because of adverse events within 12 weeks after therapy initiation, which tended to frequently occur in the following cases: (1) elderly, (2) body weight <40 kg, (3) body surface area <1.2 m2 (4) ECOG PS 2-4, (5) higher Brinkman index and (6) history of occupational/environmental exposure such as asbestos/pneumoconiosis. The proportions of patients remaining on crizotinib therapy were 68.2% for 3 months, 55.2% for 6 months and 36.1% for 12 months, with a median duration of 7.9 months. Multivariate analysis with a Cox proportional hazard model identified 10 statistically significant patient background factors influencing the duration of crizotinib therapy. CONCLUSIONS: No new safety concerns were observed in this PMS study. Our results provide useful information regarding the status of crizotinib therapy in the clinical setting.

Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib.

INTRODUCTION: The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib, in a real-world clinical setting. METHODS: Post-marketing surveillance was performed in Japan to obtain information on the safety and efficacy of crizotinib. Target patients included all patients with anaplastic lymphoma kinase-positive NSCLC who received crizotinib during the enrollment period between May 2012 and December 2014. The observation period was 52 weeks. Expert analysis of the ILD incidence was performed by an ILD independent review committee composed of five medical specialists. RESULTS: The safety analysis set included 2028 patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of ILD associated with crizotinib therapy was 5.77%; and 3.45% patients showed grade 3 or greater. Pulmonary edema-like shadows with or without diffuse alveolar damage pattern were observed in crizotinib-associated ILD (incidence: 0.39%), but a causal relationship with the prognosis could not be identified. ILD developed within 4 weeks from initiation of crizotinib administration in 41.9% and within 8 weeks in 69.2% of the patients. Age 55 years or older, Eastern Cooperative Oncology Group performance status 2-4, smoking history, previous or concomitant ILD, and comorbid pleural effusion were statistically determined as significant risk factors for crizotinib-induced ILD. CONCLUSIONS: Crizotinib therapy should be applied to the NSCLC patients with any of above risk factors under a cautious monitoring for ILD occurrence, and clinicians should pay attention to the risks of severe ILD.

MET FISH-positive status predicts short progression-free survival and overall survival after gefitinib treatment in lung adenocarcinoma with EGFR mutation.

BACKGROUND: Lung adenocarcinoma patients with EGFR gene mutations have shown a dramatic response to gefitinib. However, drug resistance eventually emerges which limits the mean duration of response. With that in view, we examined the correlations between MET gene status as assessed by fluorescence in situ hybridization (FISH) with overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients with EGFR gene mutations who had received gefitinib therapy. METHODS: We evaluated 35 lung cancer samples with EGFR mutation from adenocarcinoma patients who had received gefitinib. Gene copy numbers (GCNs) and amplification of MET gene before gefitinib therapy was examined by FISH. MET protein expression was also evaluated by immunohistochemistry (IHC). RESULTS: FISH assessment showed that of the 35 adenocarcinoma samples, 10 patients (29%) exhibited high polysomy (5 copies≦mean MET per cell) and 1 patient (3%) exhibited amplification (2≦MET gene (red)/CEP7q (green) per cell). IHC evaluation of MET protein expression could not confirm MET high polysomy status. The Eleven patients with MET FISH positivity had significantly shorter progression-free survival (PFS) and overall survival (OS) than the 24 patients who were MET FISH-negative (PFS: p = 0.001 and OS: p = 0.03). Median PFS and OS with MET FISH-positivity were 7.6 months and 16.8 months, respectively, whereas PFS and OS with MET FISH-negativity were 15.9 months and 33.0 months, respectively. Univariate analysis revealed that MET FISH-positivity was the most significant independent factor associated with a high risk of progression and death (hazard ratio, 3.83 (p = 0.0008) and 2.25 (p = 0.03), respectively). CONCLUSIONS: Using FISH analysis to detect high polysomy and amplification of MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples.

Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4-ALK-rearranged non-small-cell lung cancer harbored coexisting EGFR mutation.

BACKGROUND: The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs). The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS. CASE PRESENTATION: We report that a case of EML4-ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor. CONCLUSIONS: We described the first clinical report of a patient with EML4-ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4-ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4-ALK-positive NSCLC.

Alternating chemotherapy with amrubicin plus cisplatin and weekly administration of irinotecan plus cisplatin for extensive-stage small cell lung cancer.

BACKGROUND: A phase II study was conducted in order to determine the tumor efficacy and tolerance of alternating chemotherapy for extensive-stage small cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Twenty patients with previously-untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of amrubicin and cisplatin with weekly administration of irinotecan and cisplatin at 3- or 4-week intervals. RESULTS: The overall response rate was 85.0% (17/20). The median duration of overall survival and progression-free survival were 359 days and 227 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 20 (100%), 4 (20%) and 6 (30%) patients, respectively. With regard to non-hematological adverse events, grade 3 or 4 anorexia, diarrhea, febrile neutropenia and infection were observed in 5 (25%), 2 (10%), 2 (10%) and 2 (10%) patients, respectively. No treatment-related death occurred during either regimen. CONCLUSION: The novel alternating non-cross-resistant chemotherapy was probably active against ED-SCLC and had acceptable toxicities. Further evaluation of this treatment for ED-SCLC in randomized phase III trials is warranted.

Pitfalls in training simulated patients to respond appropriately to questions from medical students in family history-taking activities: the current situation surrounding the training of simulated patients for learning activities at Nippon Medical School.

Our goal was to train simulated patients (SPs) to respond appropriately to questions about family history from medical students in simulated medical interviews. To this end, we carried out a survey of 91 SPs and 76 4th-year medical students to investigate their notions of what constitutes a family. All of the SPs and students surveyed deemed parents and children living together to be members of a family. In a situation where one spouse's parents live together with the basic family unit, 93% of the SPs considered them to be members of the family, whereas only 79% of the students did. Married children living apart from their parents were considered members of the family by 18% of the SPs and 39% of the students. These results indicate clear differences between the SPs and students in their notions of the family. To verify the level of understanding of the definitions of family and blood relatives in particular scenarios used in simulated medical interviews, we administered a written test to 14 SPs who were training to assist in the nationwide common achievement test in medicine, the Objective Structured Clinical Examination (OSCE). The overall score of the SPs was 93.5%; the incorrect answers were "a sibling is not a blood relative" and "a spouse is a blood relative." We analyzed the performance of these 14 SPs in medical interviews carried out after training for the OSCE, in which they were asked questions that required them to reveal their understanding of blood relatives, cohabiting relatives, and the family. All of the SPs responded appropriately to the students' questions about family history. After the OSCE, we asked the SPs to assess themselves on how well they had given their family histories and to evaluate the usefulness of the SP training they had received. Their mean self-assessment score on providing a family history was 3.6 (scale: 1-4); on the usefulness of training, it was 3.4 (scale: 1-4). In conclusion, training SPs to respond appropriately to questions about family history in medical interviews is very important. Medical students have to learn how to take family histories accurately, so SP trainers should pay attention to training SPs in giving appropriate responses to students' questions, bearing in mind the differences between family history taking and everyday conversations about the family.

Three dimensional computed tomography lung modeling is useful in simulation and navigation of lung cancer surgery.

The number of minimally invasive operations, such as video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy, has enormously increased in recent years. These operations require extreme knowledge of the anatomy of pulmonary vessels and bronchi in each patient, and surgeons must carefully dissect the branches of pulmonary vessels during operation. Thus, foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The development of multi-detector computed tomography (MDCT) has promoted three dimensional (3D) images of lung structures. It is possible to see the vascular and bronchial structures from the view of the operator; therefore, it is employed for preoperative simulation as well as navigation during operation. Due to advances in software, even small vessels can be accurately imaged, which is useful in performing segmentectomy. Surgical simulation and navigation systems based on high quality 3D lung modeling, including vascular and bronchial structures, can be used routinely to enhance the safety operation, education of junior staff, as well as providing a greater sense of security to the operators.

Bevacizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer with malignant pleural effusion.

PURPOSE: The presence of malignant pleural effusion (MPE) indicates a poorer prognosis for patients with non-small-cell lung cancer (NSCLC) and impairs their quality of life. Because vascular endothelial growth factor (VEGF) is the key mediator MPE production, we evaluated the efficacy and safety of chemotherapy plus bevacizumab, an anti-VEGF antibody, in non-squamous NSCLC patients with MPE, especially regarding the control of pleural effusions. METHODS: From November 1, 2009 to September 30, 2011, medical charts of 13 consecutive patients with MPE who received bevacizumab plus chemotherapy as the initial or secondary treatment were retrospectively analyzed. RESULTS: Of the 13 patients, 6 did not undergo pleurodesis, 3 were unsuccessfully treated by pleurodesis, 2 had encapsulated pleural effusion, and 2 had no re-expansion of the lung. Twelve patients (92.3 %) achieved MPE control lasting >8 weeks following bevacizumab plus chemotherapy. Five of 10 patients with measurable lesions had confirmed partial responses. Of 3 patients without measurable lesions, one had confirmed CR. Median progression-free survival time without re-accumulation of MPE was 312 days. Grade 3 or 4 neutropenia, thrombocytopenia, hypertension, or proteinuria was observed in 2, 2, 1, or 1 patient, respectively. CONCLUSIONS: This is the first study to report that bevacizumab plus chemotherapy is highly effective for the management of MPE in non-squamous NSCLC patients. Prospective clinical trials are warranted to investigate the efficacy of bevacizumab for MPE.

Combination chemotherapy of alternating etoposide and carboplatin with weekly administration of irinotecan and cisplatin in extensive-stage small-cell lung cancer.

BACKGROUND: A phase II study was conducted to determine the tumor efficacy and tolerance of alternating chemotherapy in extensive-stage small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Thirty-six patients with previously untreated ED-SCLC were enrolled in the study. At least four courses of chemotherapy consisting of alternation of two drug combinations were given: alternating cycles of etoposide and carboplatin (EC) with weekly administration of irinotecan and cisplatin (IP) at 3- or 4-week intervals. RESULTS: The overall response rate was 81.8%. The median duration of survival and progression-free survival were 314 days and 144 days, respectively. Hematological toxicity was the main adverse event. Grade 3 or 4 neutropenia, thrombocytopenia and anemia were observed in 69.2, 25.6 and 23.1% of the patients, respectively. Severe diarrhea (10.8%) was remarkable during the IP regimen. CONCLUSION: This novel alternating chemotherapy for patients with ED-SCLC showed moderate tumor efficacy and an acceptable safety profile.

MiR-23a regulates TGF-ß-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells.

Transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases including lung cancer. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. MiR-23a/24/27a is a miRNA cluster located in chromosome 19p13.12, which can function as an oncogene in several human cancers. In this study, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer (NSCLC) cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and TGF-ß/Smad signaling was evaluated. We found that miR-23a could be regulated by TGF-ß1 in a Smad-dependent manner in A549 lung adenocarcinoma cells showing the EMT phenomenon. Knockdown of miR-23a partially restored E-cadherin expression under conditions of TGF-ß1 stimulation. In contrast, overexpression of miR-23a could suppress E-cadherin expression and stimulate EMT. Furthermore, A549 cells with overexpressed miR-23a were more resistant to gefitinib compared to the parental cells. These findings suggest that miR-23a regulates TGF-ß-induced EMT by targeting E-cadherin in lung cancer cells and may be useful as a new therapeutic target in NSCLC.

An effective training program for chest tube drainage for medical interns in a clinical simulation laboratory.

The Department of Respiratory Medicine of Nippon Medical School Hospital and the Working Committee of Clinical Simulation Laboratory have held training sessions for chest tube drainage since 2007. The training program consists of the preparation of a training manual, a small-group session, and a review of the process of chest tube drainage using a checklist of steps after the session. A total of 21 medical interns of Nippon Medical School Hospital participated in training sessions from April 2010 through February 2011. A questionnaire survey at the end of the session revealed that most participants rated highly both the explanations given by the instructors and the descriptions in the manual for comprehensibility. Only 3 interns felt that they had successfully acquired the clinical skill, and the other 18 interns felt that they had somewhat acquired the skill. Research after the interns had completed the program of the department showed that 80% of interns had performed chest tube drainage for patients during the rotation. The interns assessed the training program as useful, and some interns felt they could perform the skill with confidence or without anxiety. Other systematic programs of skill training for medical interns are recommended to ensure definite acquisition of basic skills.

Clinical clerkship course for medical students on lumbar puncture using simulators.

Lumbar puncture is a medical technique that physicians must learn and is, therefore, considered a basic medical procedure. The lumbar puncture simulators Lumbar-Kun (Lumbar Puncture Simulator) and Lumbar-Kun II (Lumbar Puncture Simulator II) (Kyoto Kagaku, Kyoto, Japan) are teaching aids designed for practicing spinal insertions. We describe and results of a lumbar puncture clerkship course, provided to 5th-year medical students during clinical clerkship activity. The aim of this study was to evaluate the effectiveness of the lumbar puncture clerkship course in the medical education program. Comprehension, technical achievement, and satisfaction were scored by students and instructors using a 6-point Likert scale. Scores for both comprehension and technical achievement were high, but technical achievement scores tended to be higher than comprehension scores. In addition, the scores students gave themselves were higher than the scores they were given by instructors. Student satisfaction was high. The lumbar puncture simulators, Lumbar-Kun and Lumbar-Kun II, achieved excellent overall impressions and represent useful tools for training in lumbar puncture procedures. In addition to the simulators, an appropriate preparatory text and a short lecture before training seemed to increase the educational effect of this lumbar puncture clerkship course for medical students.

The feasibility study of Carboplatin plus Etoposide for advanced small cell lung cancer with idiopathic interstitial pneumonias.

BACKGROUND: Idiopathic interstitial pneumonias (IIPs) are among the most common complications in patients with lung cancer. In such patients with cancer, the most serious expression of toxicity in Japan is acute exacerbation of IIPs caused by anticancer treatment. Nevertheless, there has been no consensus and no evidence presented, regarding optimal treatment for advanced lung cancer with IIP. PATIENTS AND METHODS: Chemotherapy-naive patients with advanced small cell lung cancer (SCLC) with IIP who were ineligible for curative radiotherapy were enrolled. Patients received carboplatin every 21 days at a dose of area under the curve 6.0 on day 1 and etoposide at a dose of 100 mg/m on days 1 to 3. RESULTS: Between July 2002 and October 2008, 17 patients with SCLC with IIP, including 14 men, eight of whom were diagnosed with idiopathic pulmonary fibrosis, were enrolled and treated for a mean of 3.5 cycles of carboplatin plus etoposide. One patient (5.9%; 95% confidence interval, 0-18.4%) with clinically confirmed idiopathic pulmonary fibrosis had acute exacerbation of IIPs associated with the treatment. The overall response rate was 88.2%. The median progression-free survival, median survival time, and 1-year survival rate were 5.5 months, 8.7 months, and 29.4%, respectively. CONCLUSION: This is the first report indicating that patients with advanced SCLC with IIPs may benefit from chemotherapy. Patients with advanced SCLC with IIP treated with etoposide and carboplatin combination chemotherapy gain benefits, with safety equivalent to that seen in patients without IIP. The results from this study would support, on ethical grounds, the conduct of a large-scale study to evaluate this regimen.