Ex-vivo 1.5T MR Imaging versus CT in Estimating the Size of the Pathologically Invasive Component of Lung Adenocarcinoma Spectrum Lesions.

PURPOSE: The purpose of this study was to investigate whether ex-vivo MRI enables accurate estimation of the invasive component of lung adenocarcinoma. METHODS: We retrospectively reviewed 32 patients with lung adenocarcinoma who underwent lung lobectomy. The specimens underwent MRI at 1.5T. The boundary between the lesion and the normal lung was evaluated on a 5-point scale in each three MRI sequences, and a one-way analysis of variance and post-hoc tests were performed. The invasive component size was measured histopathologically. The maximum diameter of each solid component measured on CT and MR T1-weighted (T1W) images and the maximum size obtained from histopathologic images were compared using the Wilcoxon signed-rank test. Inter-reader agreement was evaluated using intraclass correlation coefficients (ICC). RESULTS: T1W images were determined to be optimal for the delineation of the lesions (P < 0.001). The histopathologic invasive area corresponded to the area where the T1W ex-vivo MR image showed a high signal intensity that was almost equal to the intravascular blood signal. The maximum diameter of the solid component on CT was overestimated compared with the maximum invasive size on histopathology (mean, 153%; P < 0.05), while that on MRI was evaluated mostly accurately without overestimation (mean, 108%; P = 0.48). The interobserver reliability of the measurements using CT and MRI was good (ICC = 0.71 on CT, 0.74 on MRI). CONCLUSION: Ex-vivo MRI was more accurate than conventional CT in delineating the invasive component of lung adenocarcinoma.

Folliculin haploinsufficiency causes cellular dysfunction of pleural mesothelial cells.

Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant inheritance disease caused by folliculin (FLCN) mutations, is associated with lung cysts and spontaneous pneumothorax. The possibility of FLCN haploinsufficiency in pleural mesothelial cells (PMCs) contributing to development of pneumothorax has not yet been clarified. Electron microscopy revealed exposed intercellular boundaries between PMCs on visceral pleura and decreased electron density around the adherens junctions in BHDS. To characterize cellular function of PMCs in BHDS patients (BHDS-PMCs), during surgery for pneumothorax, we established the flow cytometry-based methods of isolating high-purity PMCs from pleural lavage fluid. BHDS-PMCs showed impaired cell attachment and a significant decrease in proliferation and migration, but a significant increase in apoptosis compared with PMCs from primary spontaneous pneumothorax (PSP) patients (PSP-PMCs). Microarray analysis using isolated PMCs revealed a significant alteration in the expression of genes belonging to Gene Ontology terms "cell-cell adhesion junction" and "cell adhesion molecule binding". Gene set enrichment analysis demonstrated that CDH1, encoding E-cadherin, was identified in the down-regulated leading edge of a plot in BHDS-PMCs. AMPK and LKB1 activation were significantly impaired in BHDS-PMCs compared with PSP-PMCs. Our findings indicate that FLCN haploinsufficiency may affect the E-cadherin-LKB1-AMPK axis and lead to abnormal cellular function in BHDS-PMCs.

[Extreme Obese Patients who Underwent Cardiac Surgery after Preoperative Weight Reduction;Report of Two Cases].

Obesity is a risk factor of postoperative complications. We experienced 2 extremely obese patients:a 32-year-old male with coronary artery disease and a 75-year-old female with aortic valve stenosis. Their initial body weights were 133 kg and 88.5 kg, respectively, and their initial body mass indexes (BMIs) were both 41. Their BMIs were reduced to 35.5 and 35, respectively, after preoperative weight reduction. Off-pump coronary artery bypass grafting and aortic valve replacement were performed, respectively. After surgery, the non-invasive positive pressure ventilation( NPPV) support was effective, and their postoperative courses were uneventful. Preoperative weight reduction and NPPV are useful for extremely obese patients who undergo cardiac surgery.

Pleural Covering Application for Recurrent Pneumothorax in a Patient with Birt-Hogg-Dubé Syndrome.

Birt-Hogg-Dubé syndrome (BHDS) is a rare hereditary disease that presents with multiple lung cysts and recurrent pneumothorax. These cysts occupy predominantly the lower-medial zone of the lung field adjacent to the interlobar fissure, and some of them abut peripheral pulmonary vessels. For the surgical management of pneumothorax with BHDS, the conventional approach of resecting all subpleural cysts and bullae is not feasible. Thus, after handling several bullae by using a stapler or performing ligation as a standardized treatment, we applied to a pleural covering technique to thicken the affected visceral pleura and then to prevent recurrence of pneumothorax. We herein report the successful application of a pleural covering technique via thoracoscopic surgery to treat the recurrent pneumothorax of a 30-year-old man with BHDS. This technique is promising for the management of intractable pneumothorax secondary to BHDS.

Anterior mediastinal abscess diagnosed in a young sumo wrestler after closed blunt chest trauma.

Most mediastinal abscesses result from infections after thoracotomy, esophageal perforation or pene- trating chest trauma. This disease is rarely caused by closed blunt chest trauma. All previously reported such cases after closed blunt chest trauma presented with hematoma and sternal osteomyelitis resulting from sternal fracture. Here we report a 15-year-old sumo wrestler who presented with an anterior mediastinal abscess without any mediastinal fracture. The mediastinal abscess resulted from the hematogenous spread of Staphylococcus aureus to a hematoma that might have been caused by a closed blunt chest trauma incurred during sumo wrestling exercises.

Thoracic endometriosis-related pneumothorax distinguished from primary spontaneous pneumothorax in females.

PURPOSE: Thoracic endometriosis-related pneumothorax (TERP) is a secondary condition specific for females, but in a clinical setting, TERP often is difficult to distinguish from primary spontaneous pneumothorax (PSP) based on a relationship between the dates of pneumothorax and menstruation. The purpose of this study was to clarify the clinical features of TERP compared with PSP. METHODS: We retrospectively reviewed the clinical and histopathological files of female patients with pneumothorax who underwent video-assisted thoracoscopic surgery in the Pneumothorax Research Center during the 6-year period from January 2005 to December 2010. We analyzed the clinical differences between TERP and PSP. RESULTS: The study included a total of 393 female patients with spontaneous pneumothorax, of whom 92 (23.4 %) were diagnosed as having TERP and 33.6 % (132/393) as having PSP. We identified four factors (right-sided pneumothorax, history of pelvic endometriosis, age ≥31 years, and no smoking history) that were statistically significant for predicting TERP and assigned 6, 5, 4, and 3 points, respectively, to establish a scoring system with a calculated score from 0 to 18. The cutoff values of a calculated score ≥12 yielded the highest positive predictive value (86 %; 95 % confidence interval (CI) 81.5-90.5 %) for TERP and negative predictive value (95.2 %; 95 % CI 92.3-98 %) for PSP. CONCLUSIONS: TERP has several distinct clinical features from PSP. Our scoring system consists of only four clinical variables that are easily obtainable and enables us to suspect TERP in female patients with pneumothorax.

Malignant pleural mesothelioma detected by spontaneous pneumothorax.

We report a middle-aged man, without occupational or environmental exposure to asbestos, who presented with spontaneous pneumothorax. Computed tomography showed a 13-mm right apical mass. He underwent tumorectomy and was diagnosed with malignant pleural mesothelioma. A local recurrence with multiple and diffuse pleural involvement later appeared. The patient eventually underwent panpleuropneumonectomy, recovered well, and has been doing well for 18 months.

A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.

PURPOSE: Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated Valpha24 NKT cell therapy. EXPERIMENTAL DESIGN: Patients with advanced or recurrent non-small cell lung cancer received i.v. injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5 x 10(7)/m2) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases. RESULTS: Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24 NKT cells was observed in two of three cases receiving a level 2 dose of activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in peripheral blood mononuclear cells increased after the administration of activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response. CONCLUSIONS: The clinical trial with activated Valpha24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.

Lymphangioleiomyomatosis with a giant bulla: report of a case.

We report a case of lymphangioleiomyomatosis (LAM) with a giant bulla. A 33-year-old woman was referred to our department for treatment of dyspnea. Chest computed tomography showed a giant bulla with many smaller bullae. To obtain a definitive diagnosis and relieve the dyspnea, we performed a lung biopsy and bullectomy, after which her symptoms and pulmonary function improved remarkably. She was commenced on progesterone, which improved her condition even further. This case report retrospectively follows the progression of her disease from the onset of symptoms 5 years before she was referred to us for treatment.

A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer.

PURPOSE: Human Valpha24 natural killer T (NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murine Valpha14 NKT cells, are activated by a specific ligand, alpha-galactosylceramide (alphaGalCer, KRN7000), in a CD1d-dependent manner. I.v. administration of alphaGalCer-pulsed dendritic cells (DC) induces significant activation and expansion of Valpha14 NKT cells in the lung and resulting potent antitumor activities in mouse tumor metastatic models. We did a phase I dose escalation study with alphaGalCer-pulsed DCs in lung cancer patients. EXPERIMENTAL DESIGN: Patients with advanced non-small cell lung cancer or recurrent lung cancer received i.v. injections of alphaGalCer-pulsed DCs (level 1: 5 x 10(7)/m(2); level 2: 2.5 x 10(8)/m(2); and level 3: 1 x 10(9)/m(2)) to test the safety, feasibility, and clinical response. Immunomonitoring was also done in all completed cases. RESULTS: Eleven patients were enrolled in this study. No severe adverse events were observed during this study in any patient. After the first and second injection of alphaGalCer-pulsed DCs, dramatic increase in peripheral blood Valpha24 NKT cells was observed in one case and significant responses were seen in two cases receiving the level 3 dose. No patient was found to meet the criteria for partial or complete responses, whereas two cases in the level 3 group remained unchanged for more than a year with good quality of life. CONCLUSIONS: In this clinical trial, alphaGalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.