Ryo Miyata

Successful resection of recurrent mediastinal liposarcoma using preoperative evaluation of organ invasion by four-dimensional computed tomography

We report the case of a 64-year-old woman with recurrent mediastinal dedifferentiated liposarcoma. She had undergone surgical resection twice. Subsequently, on regular follow-up visits, chest computed tomography demonstrated a third local recurrence of the tumor with invasion into adjacent intrathoracic organs. Adhesion of the heart to the anterior chest wall through a pericardial defect that had been inadvertently created at the second operation was suspected. We decided to use a thoracoabdominal approach with four-dimensional computed tomography (4DCT) for preoperative guidance. The patient had also undergone MRI; however, the result was equivocal regarding adhesion of intrathoracic organs. The use of 4DCT enabled successful en bloc resection of the tumor. Results of the pathology examination showed complete resection of a dedifferentiated liposarcoma. The patient’s postoperative course was uneventful, and she was discharged on postoperative day 19.

Efficacy of Ramelteon for delirium after lung cancer surgery

OBJECTIVES The aim of the study was to evaluate the feasibility of Ramelteon for the prevention of delirium after lung cancer surgery in elderly patients. METHODS Medical records of patients over 70 years old, who underwent anatomical pulmonary resection for lung cancer at our institution from January 2013 to December 2015, were reviewed. Patients treated in 2013 and 2014 were used as a control group. Ramelteon was administered daily for 7 days after surgery. The incidence of delirium was determined based on the Intensive Care Delirium Screening Checklist (ICDSC). Scores of ≥4 and 1-3 points were used for the diagnoses of delirium and a pre-delirious state, respectively. RESULTS There were 24 patients in the Ramelteon group and 58 patients in the control group. ICDSC scores of ≥4 points were found for no patients in the Ramelteon group and 5 (9%) in the control group, whereas 21 (88%) and 49 (85%) patients, in the respective groups, had ICDSC scores of 0 points. The average incidence of events, associated with delirium, showed a trend of being lower in the Ramelteon group (0.25 ± 0.74 vs 1.58 ± 4.93, P = 0.061), and all events in the Ramelteon group occurred on the day of surgery. Thus, only one day was required for complete recovery from delirium in the Ramelteon group, whereas 8 days were needed in the control group. The peak delirious state occurred after 5 days in the control group. CONCLUSIONS Ramelteon is likely to reduce the incidence and intensity of delirium after surgery for lung cancer in elderly patients.

PO-238 Clinicopathological significance of EMT markers in thymic epithelial tumours

Introduction Thymic epithelial tumours (TETs) are the relatively rare tumours originated from thymus. TETs are histologically categorised according to the WHO classification based on the morphology of epithelial tumour cells and proportion of lymphocytic involvement. Epithelio-mesenchymal transition (EMT) has reported to play pivotal roles in tumour progression including invasion/metastasis, drug resistance, and cancer stemness. However, the precise clinicopathological associations with EMT characteristics in TETs remain to be elusive. Herein, we have examined EMT markers in TETs integrated with their clinicopathological information. Material and methods A total of 109 patients with TETs were surgically resected between 2002 and 2017 in our institution. Tissue samples were collected from the paraffine-embedded tumour blocks of these patients. The 2 mm cores in diameter of the most representative areas of the tumours were selected by the pathologist and assembled to make tissue microarrays. Immunohistochemical (IHC) stainings for E-cadherin (E) and vimentin (V) were performed. P63 and pan-cytokeratin were additionally stained to detect epithelial tumour cells. The expressions of these molecules were scored and quantified to categorise the activation level of EMT into three groups based on the combination of E and V levels: Full; E-V+, Partial; E+V+ or E-V-. Null; E+V-. For statistical analyses, chi-square tests and Cox hazard models were applied. P-value less than 0.05 was considered significant. Results and discussions The median follow-up time was 54.3 months (range, 0.3–178.7). Predominant WHO histological subtypes were as follows: A;8, AB;18, B1;30, B2;30, B3;6. C;15, others;2. Pathologic stage distributions by TNM classfication were as follows: 1;80, 2;2, 3;13, 4a;7, 4b;4. The positive rates of E-cadherin or vimentin expression in epithelial tumour cells were 54.2% and 57.9%, respectively. EMT activation was significantly exhibited in indolent predominant WHO subtype, and in the early stage of pT factor and the Masaoka classification (p=0.0005, 0.0493, and 0.0366, respectively). Multivariate analyses of overall survival time including pT, pN, pM, age, and EMT levels showed that pT factor was significantly prognostic (p=0.0218), but not for EMT. Conclusion EMT activation mechanisms in TETs were inversely correlated with their histological subtype and the primary tumour progression. Further studies are necessary to elucidate tumour progression mechanisms in TETs.

The synergistic role of ATP-dependent drug efflux pump and focal adhesion signaling pathways in vinorelbine resistance in lung cancer

The vinorelbine (VRB) plus cisplatin regimen is widely used to treat non–small cell lung cancer (NSCLC), but its cure rate is poor. Drug resistance is the primary driver of chemotherapeutic failure, and the causes of resistance remain unclear. By focusing on the focal adhesion (FA) pathway, we have highlighted a signaling pathway that promotes VRB resistance in lung cancer cells. First, we established VRB‐resistant (VR) lung cancer cells (NCI‐H1299 and A549) and examined its transcriptional changes, protein expressions, and activations. We treated VR cells by Src Family Kinase (SFK) inhibitors or gene silencing and examined cell viabilities. ATP‐binding Cassette Sub‐family B Member 1 (ABCB1) was highly expressed in VR cells. A pathway analysis and western blot analysis revealed the high expression of integrins β1 and β3 and the activation of FA pathway components, including Src family kinase (SFK) and AKT, in VR cells. SFK involvement in VRB resistance was confirmed by the recovery of VRB sensitivity in FYN knockdown A549 VR cells. Saracatinib, a dual inhibitor of SFK and ABCB1, had a synergistic effect with VRB in VR cells. In conclusion, ABCB1 is the primary cause of VRB resistance. Additionally, the FA pathway, particularly integrin, and SFK, are promising targets for VRB‐resistant lung cancer. Further studies are needed to identify clinically applicable target drugs and biomarkers that will improve disease prognoses and predict therapeutic efficacies.

A novel germline mutation in a patient with nevoid basal cell carcinoma syndrome showing cystic lesion in the lung

Nevoid basal cell carcinoma syndrome (NBCCS) manifests multiple defects involving the skin, endocrine and nervous systems, eyes and bones. Mutations in the patched homologue 1 (PTCH1) gene are the underlying causes of NBCCS, leading to aberrant cell proliferation through constitutive activation of the hedgehog signaling pathway. We identified a novel frameshift mutation (c.1207dupT) of PTCH1 in a NBCCS patient, which might explain multiple cystic lesions and neoplastic growth in the patient.

External fistulous wound with Pseudomonas aeruginosa infection and massive bleeding following rupture of pulmonary suppuration.

We present a 54-year old man with a pulmonary infectious cavity continuing to a cutaneous fistula. Before he was admitted to our hospital, he had undergone open-window surgery for a left thoracic empyema due to the rupture of pulmonary suppuration of the left upper lobe. He had then undergone thoracoplasty with the plombage of the cavity using left pectoralis major muscle. However, this procedure had failed and the external fistulous wound remained infected by Pseudomonas aeruginosa and occasional massive bleeding from the cavity occurred. He underwent en bloc left upper lobectomy for the external fistulous wound. The pedicled left latissimus dorsi muscle flap was transposed to fill the dead space and reinforce the bronchial stump. He remained in good health and did not experience intrathoracic infection or haemoptysis.