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A 76-year-old woman presented with dyspnea. Computed tomography showed massive pericardial effusion, so percutaneous catheter drainage was performed. The usual causes of exudate were ruled out, and no diagnosis was reached. Thoracoscopic pericardial fenestration was performed for the purpose of pericardial biopsy and to create a passage allowing longer-term drainage. We observed the pericardial cavity after removing effusion, and incidentally revealed a tumor measuring 2 cm in diameter located between the left atrial appendage and left pulmonary artery. Surgical resection of the tumor attached to the left atrial appendage was performed. The pathological diagnosis was hemangioma.

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non–small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I–IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.

Atopic dermatitis (AD, also called atopic eczema) is a long-term skin disease that causes intensely itchy, red skin. Healthcare providers can prescribe medicated creams and ointments to reduce the signs and symptoms of AD. However, these treatments are not always enough to provide relief. A new medicine called abrocitinib, which is taken every day as a tablet, reduces part of the body’s immune response that happens in AD. The clinical study described in this plain language summary, called JADE COMPARE, investigated how well and how safely 16 weeks of treatment with abrocitinib worked in adults with AD compared to placebo (‘dummy treatment’) and a medicine that is already approved for AD, called dupilumab. The study showed that abrocitinib was better than placebo in improving the signs and symptoms of AD after 16 weeks. In addition, patients who were taking abrocitinib 200 mg for 2 weeks experienced greater relief from itch than patients who were taking abrocitinib 100 mg, placebo, or dupilumab. More people who took abrocitinib 200 mg reported side effects than those taking abrocitinib 100 mg, placebo, or dupilumab, but most of these side effects were mild or moderate. ClinicalTrials.gov NCT number: NCT03720470 .

Thyroid transcription factor-1 (TTF-1) has been widely used as a marker of primary lung cancer. However, there have been few reports on TTF-1 expression in thymomas. We here report the case of an asymptomatic 63-year-old man who presented with a right upper lung nodule and cystic mid-mediastinal tumor. The right upper lobe of the lung and the mediastinal tumor were resected. Histological examination of the operative specimen revealed TTF-1-positive type B2 thymoma and invasive pulmonary adenocarcinoma. Although rare, thymoma should be included in the different diagnosis of TTF-1-positive tumors.

The predictive importance of galectin-3 in non-small cell lung cancer (NSCLC) has not been elucidated. We examined whether galectin-3 could serve as a predictor for tumor recurrence in NSCLC. In 42 consecutive patients with NSCLC who underwent radical resection, galectin-3 expression in tumor cells was examined by immunohistochemistry. Galectin-3 levels in serum were assessed before surgery and 1 month after surgery by enzyme-linked immunosorbent assays. Higher expression of galectin-3 in tumor cells was associated significantly with lymphatic invasion (p = 0.049) and tumor recurrence (p = 0.001). The Kaplan–Meier curves for relapse-free survival after radical resection showed that patients with high expression of galectin-3 had significantly shorter relapse-free survival than those with low expression of galectin-3 (p

Moderate to severe atopic dermatitis (AD) has a high disease burden and a significant effect on quality of life. Observational studies are necessary to determine the patient disease burden and long‐term disease control in the Japanese population. ADDRESS‐J is a non‐interventional, observational registry of adult Japanese patients with moderate to severe AD. Herein, we report baseline data from the ADDRESS‐J study describing disease characteristics and current treatment practices. At baseline, 300 adult AD patients with Investigator's Global Assessment (IGA) scores (range, 0–4) of 3 (moderate) or 4 (severe) whose treatments for AD were intensified, were assessed for clinical and patient‐reported outcomes and current AD treatments. The registry patients’ median age was 34.0 years; 60.7% were male and 71.7% had had AD for more than 20 years. At baseline, 220 study patients had an IGA score of 3 and 80 had an IGA score of 4. The median Eczema Area and Severity Index score was 21.7 (range, 0–72), the median body surface area involvement was 46.25%, and the median pruritus numerical rating scale score was 7.0 (range, 0–10); for each of these measures, higher scores represent greater severity. Most registry patients (86.7%) had recently used topical corticosteroids or topical calcineurin inhibitors as treatment for AD. This registry cohort represents a population of Japanese patients with moderate to severe AD and provides an important resource for characterizing the disease burden and evaluating the safety and effectiveness of various AD treatments.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16.A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively.In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. Methods: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients’ sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between “baseline levels of 18 biomarkers” and “% change from baseline of EASI at 16 weeks of dupilumab treatment.” Discussion: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

In elderly patients with lung cancer, the presumed fear of postoperative complications has resulted in the delivery of limited resection. Surgical decision-making for such patients would become easier if clinicians could predict who is at high risk of postoperative complications. The purpose of this study is to propose a scoring system to predict the risk of postoperative complications for elderly patients with lung cancer. We reviewed patients aged 75 years or older who underwent lobectomy for lung cancer at a single hospital (n = 199). A multivariable logistic regression model was utilized to determine risk factors for postoperative complications. Six risk factors for postoperative complications were identified, and we derived a risk score by assigning weights to these factors based on their odds ratios, as follows: Risk score = 7 × (performance status of 2) + 6 × (coronary artery disease) + 3 × (a history of cerebrovascular accident) + 2 × (restrictive ventilatory impairment) + 1 × (male sex) + 1 × (interstitial pneumonia). The postoperative complication rates in patients with risk scores of 0, 1–2, 3–5, 6–8, and 9–14 were 19, 29, 56, 68, and 90%, respectively. The proposed risk score was able to predict the incidence of postoperative complications. The risk score can be used to identify high-risk patients and to select proper treatment strategies.

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p

BACKGROUND\ud Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits\ud signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important\ud drivers of atopic or allergic diseases such as atopic dermatitis.\ud METHODS\ud In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1\ud and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose\ud disease was inadequately controlled by topical treatment. Patients were randomly\ud assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg)\ud or placebo weekly or the same dose of dupilumab every other week alternating\ud with placebo. The primary outcome was the proportion of patients who had both\ud a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment\ud and a reduction of 2 points or more in that score from baseline at week 16.\ud RESULTS\ud We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary\ud outcome occurred in 85 patients (38%) who received dupilumab every other week and\ud in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received\ud placebo (P

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution of the eczema; and (iii) chronic and chronically relapsing course. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice.

What is known and objective Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). Methods We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. Results and discussion The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. What is new and conclusion There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.

Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized.\ud \ud Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL.\ud \ud Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness.\ud \ud Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p

Background: Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Objectives: To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. Methods: A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Results: Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–

Surgery remains the best treatment for obtaining cure in patients with resectable lung cancer, regardless of age. In elderly patients, however, the presumed fear of decreased performance status (PS) after lobectomy has resulted in the delivery of sub-optimal cancer surgery. Surgical decision making for such patients would become easier if post-lobectomy survival benefits and changes in PS were well defined.We reviewed patients aged 75 years or older who received lobectomy for non-small cell lung cancer (NSCLC) at our hospital between January 2004 and December 2014. Eastern Cooperative Oncology Group PS was preoperatively and postoperatively assessed in 137 patients. Patients were classified into 2 groups based on the change in PS: in Group 1, postoperative and preoperative PS were the same; in group 2, postoperative PS was less than preoperative PS. We compared the characteristics of patients in groups 1 and 2.Overall 5-year survival was 47.4% in group 1 and 0% in group 2 (P0.001). History of cardiac ischemia (P=0.001) and squamous cell carcinoma (P=0.015) were identified as significant predictors of reduced postoperative PS.Our results show that maintenance of PS after lobectomy is expected to be associated with a good prognosis. However, reduction of PS after lobectomy indicates an extremely poor prognosis in elderly patients with lung cancer. History of cardiac ischemia and squamous cell carcinoma are possible risk factors for decreasing PS. Thus, careful patient evaluation and selection are needed when deciding whether to use lobectomy in clinical practice.

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

症例は乳癌・胃癌・腎癌の既往のある75歳女性．胸部CTで右肺下葉に異常陰影を認めるとのことで当科に紹介となった．胸部CTで右S8に8mm大の小結節影を認めた．retrospectiveにみると3年前の胸部CTで同部に3mm大の結節影を，2年前の胸部CTで4mm大の結節影を認めていた．増大傾向を認めており転移性肺腫瘍を疑われたため手術を行った．術中迅速組織診で腎癌肺転移と診断された．術後永久標本において豊富な淡明細胞質を有する細胞が薄壁性の類洞様血管を伴ってシート状に配列しており，免疫染色ではPAS・MelanA陽性，CD10・HMB45陰性であり淡明細胞腫と診断された．肺原発淡明細胞腫は比較的稀な腫瘍である．腎細胞癌肺転移との鑑別を要するが実際に腎細胞癌の既往を有する症例の報告は我々が検索した限り認められなかった．本症例の経過を若干の文献的考察を加えて報告する．

Case: 72-yr-old manChief complaint: Breathing difficulty with wheezingwhen cutting Falcata.Personal medical history: Eczema since infancy.Tubercular pleurisy at the age of 28.Family medical history: Nothing of special note.Occupational history: Worker in wood furnitureproduction. Had been working with wood sincegraduation from junior high school.Working inpresent position since the age of 18.Smoking status: Nonsmoker, both present and past.Alcohol consumption: One bottle of beer and twoglasses of brandy every day.Pets: None.History of present illness: The patient had bronchialasthma at the age of 17. The main symptom was coughingwith slight breathing difficulty. At 30 yr of age, he wasstruck by a severe asthma attack, and was unconsciousovernight. From that time, his asthma attacks appearedonly at the turn of the season. Control by drug therapywas excellent for about ten years from when he was 60yr old, and there were no asthma attacks. The patientbecame conscious of breathing difficulty with wheezingafter entering the factory at the age of 70 yr. He began toregularly visit a local doctor’s office once a week. Hedid not have the complaint of itchy eyes. Theophyllinetablets were prescribed three times a day after each meal.Becromesazon inhalation medicine and Predonizorontablets were prescribed for use during an attack. Recently,he noticed that the symptoms appeared when cuttingFalcata with a circular saw. He could not enter the factorywhen Falcata was being cut. His symptoms appearedeven if he entered the factory without knowing thatFalcata had been cut. The severity of his symptomsgradually decreased when he left the factory and did notappear with wood other than Falcata. His symptomsdisappeared after the processing of Falcata wasdiscontinued.Two other employees also complained of sneezing,runny nose and voice change after cutting Falcata.However, they did not suffer from breathing difficultywith wheezing. Employees at other factories have alsocomplained of sneezing and runny nose after handlingFalcata.To confirm the diagnosis of occupational asthma (OA)induced by Falcata, the patient was hospitalized at theOsaka Prefectural Medical Center for Respiratory andAllergic Diseases on September 12, 2005. Signedinformed consent was obtained from the patient for thisstudy and the bronchial provocation test. This study andthe bronchial provocation test were approved by theHospital Ethics Committee. Findings on admission: Height 160.8 cm, weight 60Kg, temperature 36.5 °C, pulse 76 beats per minute, bloodpressure 140/75 mmHg, SpO

An abnormal shadow was detected in a 75-year-old man on a chest roentgenogram, and the patient was referred to our institution. A transbronchial biopsy was carried out and the specimen resulted in a diagnosis of organizing pneumonia. During the follow-up period, the left lung lesion became enlarged. Partial resection of the left lung was performed. Postoperatively, pathological examination of the tumor showed an organizing pneumonia. Approximately 3 years later, a new calcified heterogeneous mass shadow was detected in the left lung and left pleura, which had gradually enlarged. Computed tomography (CT)-guided fine-needle biopsy of the nodule of the left pleura was performed. Microscopically, the specimen led to the diagnosis of low-grade osteosarcoma. Re-evaluation of the primary and secondary lesions were confirmed as the same histopathological findings. A further systemic examination was performed. Finally, the lesion was confirmed as low-grade osteosarcoma of the lung. The patient refused further treatment and died due to respiratory failure.

In tumor tissues, tumor cells and tumor stromal cells interact with each other, generating the complex tumor microenvironment (TME). Whereas cancer-associated fibroblasts (CAFs) are dominant cells among tumor stromal cell types, the induction of CAFs in TME still remains unclear. Given that TME turns to be hypoxic while tumor is growing, we hypothesized that hypoxia in TME would contribute to induction of CAFs. In this study, we focused on a role of hypoxia-inducible factor-1 (HIF-1), a key transcription factor in hypoxic responses, and examined the implication of HIF-1 in the induction of CAFs in TME. The mouse lymphoma cell line, E.G7 cells, which had been transfected with HIF-1α shRNA (E.G7- HIF-1α shRNA) were cultured under hypoxia with an O2 concentration of 1.0%. As controls, E.G7 cells or those which had been transfected with control shRNA (E.G7-control shRNA) were also cultured under the same hypoxic condition as in case of E.G7- HIF-1α shRNA. Three days later, the culture medium was harvested for following experiments. To evaluate a role of HIF-1α in migration of CAFs progenitor cells into TME, mouse bone marrow cells as CAFs progenitor cells were put in the upper compartment, and hypoxic culture medium was added in the lower compartment of a transwell chamber. We observed that the number of α-smooth muscle actin (α-SMA)-positive cells that had migrated was decreased when hypoxic culture medium from E.G7- HIF-1α shRNA was added in the lower compartment. Transforming growth factor-beta (TGF-β) has been reported to be one of soluble factors which are responsible for induction of CAFs. Thus, we examined the level of TGF-β in hypoxic culture medium by ELISA, demonstrating that it was decreased in the medium from E.G7- HIF-1α shRNA as compared with E.G7-control shRNA or E.G7 cells. Next, we examined the association between HIF-1α inhibition and CAFs induction in a tumor-bearing mouse model. C57BL/6 mice were subcutaneously administered E.G7-HIF-1α shRNA, E.G7-control shRNA, or E.G7 cells at the flank. Three weeks later, tumor tissues were harvested from the mice, and α-SMA-positive cells in tumor tissues were examined by immunohistochemistry. The data showed that α-SMA-positive CAFs were decreased in E.G7-HIF-1α shRNA tumor tissues as compared with E.G7-control shRNA, or E.G7 tumor tissues. In addition, tumor growth was significantly suppressed in mice bearing E.G7-HIF-1α shRNA, while inhibition of HIF-1α did not exert a suppressive effect on the proliferation of E.G7 cells in vitro. These data indicated that HIF-1α would play a critical role in the induction of CAFs via TGF-β in hypoxic TME. Inhibition of HIF-1α could have contributed to reduction of CAFs in tumor tissues, leading to suppression of tumor growth. These results provide a novel rationale with TME-targeted strategy against cancer. Citation Format: Koji Teramoto, Yoko Kataoka, Tomoyuki Igarashi, Yasuhiko Ohshio, Jun Hanaoka, Yataro Daigo. HIF-1 is responsible for the induction of cancer-associated fibroblasts in hypoxic tumor microenvironment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5080. doi:10.1158/1538-7445.AM2015-5080

Itch (pruritus) is an unpleasant sensation that leads to the desire to scratch (1). Pruritus may compromise quality of life and sleep in affected individuals. Pruritus is simi -lar to pain, in being a subjective symptom; assessment of its intensity is a key issue in evaluating severity and therapeutic outcome of patients with pruritic disorders of diverse origins (cutaneous, systemic, neuropathic, psychogenic) (2). Various types of rating scales have been used and validated in the study of clinical itch, including the visual analogue scale (VAS), numerical rating scale, verbal rating scale, and behavioural rating scale (2–4). Among these measurement tools, the VAS seems to be one of the most commonly used methods of assessing pruritus severity, as it provides an easy and rapid estima -tion of itch (3, 4). The VAS is a 10-cm long line, oriented horizontally or vertically, on which patients indicate the intensity of pruritus by marking the line at the point that corresponds to the severity of their pruritus, where the beginning of the scale refers to no pruritus (0 point) and the end of the scale to the most severe pruritus (10 points) (3, 4). On behalf of the International Forum for the Study of Itch (IFSI), we discussed methodological problems of the VAS in clinical settings. During our discussion we identified that it is necessary to clarify the verbal expres-sion of the 10-point end, because it varies from study to study. It includes expressions such as “worst imaginable itch”, “the most severe pruritus they can imagine”, “most intense sensation imaginable”, “maximal itch”, “severe itching” and “unbearable pruritus” (3–8). In this report, we propose to consolidate the verbalization of extremes of VAS for “itch intensity” and “sleep disturbance (noc-turnal itch)”.CONSENSUS STATEMENTMembers of the Japanese Society for Dermatoallergo -logy and Contact Dermatitis (JSDACD) (MF, TE, AI, ST, YK, KT, TS, and HS) discussed possible core items for evaluating pruritus in clinical settings, including clinical trials, in Japan. Nine items were proposed and we evaluated the importance of each item by assigning a weight score (maximum points, 10) to each. The 2 highest-ranked items were “itch intensity” (score, 10