[Surgical Strategy for Multiple Synchronous Primary Lung Cancer Showing Ground Glass Opacities:Percutaneous Preoperative Computed Tomography-guided Lipiodol Marking Followed by Video-assisted Thoracic Surgery].

From May 2006 to March 2018, a total of 30 patients with multiple ground glass opacities( GGO) lessor equal to 2.0 cm underwent percutaneous preoperative computed tomography (CT)-guided Lipiodolmarking and subsequent video-assisted thoracic surgery( VATS). There were 22 patients with 2 GGOs,6 patients with 3 GGOs, 1 patient with 4 GGOs, and 1 patient with 5 GGOs. Of the 71 CT-guided Lipiodolmarking procedures were successfully completed. All 71 Lipiodol spots were detected with C-armshapedfluoroscopy and completely resected. Pneumothorax was the most common complication andoccurred in 22 (73.3%) of 30 cases. There were severe complications in two (6.7%) cases of pneumothoraxrequiring chest tube placement and three( 10.0%) cases of bloody sputum. Of 30 cases multipleGGOs revealed 24 synchronous lung cancer (19 patients with double lung cancer, 3 patients with triplelung cancer, 1 patient with quadruple lung cancer, and 1 patient with quintuple lung cancer). PreoperativeCT-guided lipiodol marking and VATS resection is a safe and reliable method for synchronous multiplelung cancer showing GGO.

Safety and reliability of computed tomography-guided lipiodol marking for undetectable pulmonary lesions.

OBJECTIVES: This study aimed to evaluate the safety and reliability of percutaneous computed tomography (CT)-guided lipiodol marking for undetectable pulmonary lesions before video-assisted thoracic surgery (VATS). METHODS: We retrospectively analysed the cases of CT-guided lipiodol marking followed by VATS in 9 institutes from May 2006 to March 2018. Lipiodol (0.2-0.5 ml) was percutaneously injected closely adjacent to undetectable pulmonary lesions with computed-tomography guidance. Lipiodol spots were identified using C-arm-shaped fluoroscopy during VATS. We grasped the lipiodol spots, including the target lesions, with ring-shaped forceps and resected them. RESULTS: Of 1182 lesions, 1181 (99.9%) were successfully marked. In 1 case, the injected lipiodol diffused, and no spot was created. Of the 1181 lesions, 1179 (99.8%) were successfully resected with intraoperative fluoroscopy. Two lipiodol spots were not detected because of the lipiodol distribution during the division of pleural adhesions. The mean lesion size was 9.1 mm (range 1-48 mm). The mean distance from the pleural surface was 10.2 mm (range 0-43 mm). Lipiodol marking-induced pneumothorax occurred in 495 (57.1%) of 867 cases. Of these, chest drainage was required in 59 patients (6.8%). The other complications were 19 (2.2%) cases of bloody sputum, 3 (0.35%) cases of intravascular air, 1 (0.12%) case of pneumonia and 1 (0.12%) case of cerebral infarction. There were no lipiodol marking-induced deaths or sequelae. CONCLUSIONS: Preoperative CT-guided lipiodol marking followed by VATS resection was shown to be a safe and reliable procedure with a high success rate and acceptably low severe complication rate.

Improvements in thoracic surgery outcomes: a multi-institutional collaboration study.

BACKGROUND: Treatment protocols (including those for thoracic surgery) tend to be customized for individual hospitals. Procedural standardization is required to improve surgical tasks and patient outcomes. This study aimed to evaluate the effects of an initiative to standardize surgical tasks for efficient and safe performance. METHODS: Hospitals associated with the Division of Chest Surgery of the Kyoto Prefectural University of Medicine held joint meetings involving their thoracic surgeons and operating room nurses between February 2011 and November 2012 to standardize surgical tasks. Operation times and blood loss were compared before and after standardization. RESULTS: The implementation rate of standardized surgical tasks was 97%. The pre-operative (from entry to the operating room until commencement of surgery) and post-operative (from conclusion of surgery until departure from the operating room) times were significantly decreased after the standardization. When compared according to operative group (all thoracic surgery, lung lobectomy, and partial lung resection), operation times were shorter for all three groups; in addition, the amount of blood loss was lower in all three groups after standardization. A post-standardization survey showed improved morale among the meeting participants. CONCLUSIONS: Interdisciplinary standardization of surgical tasks across institutions improved thoracic surgery tasks and surgical outcomes.

Chondromyxoid fibroma with secondary aneurysmal bone cyst of the rib.

Chondromyxoid fibroma (CMF) is a rare, benign cartilaginous tumor, comprising less than 1% of primary bone tumors, and usually occurs in the metaphysis of a long tubular bone around the knee. We report a rare case of CMF of the rib. The patient was a 25-year-old man who visited the hospital for left upper back pain. Roentgenography revealed an 8-cm mass in the left upper lung field; computed tomography revealed a large multicystic tumor with aneurysmal bone cyst (ABC)-like features in the posterior mediastinum. ABCs are also a rare benign tumor representing 2.5% of primary bone tumors, and most of ABCs are located in the metaphysis of long bones and vertebrae. To the best of my knowledge, there is no report of CMF with secondary ABC of the rib. We performed total resection of the tumor. Complete tumor resection may be the best treatment option for a cure.

Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines.

In order to clarify the mechanisms of resistance to paclitaxel in lung cancer, three human lung cancer cell lines which exhibit different sensitivity to paclitaxel were investigated from the following viewpoints: overexpression of ATP-binding cassette, sub-family B, member 1 (ABCB1), mutations on paclitaxel binding site of ß-tubulin genes, quantity of polymerized tubulin and the intracellular localization of paclitaxel. ABCB1 expression was evaluated by real-time RT-PCR. No correlations were noted between the ABCB1 expression in the sensitive and resistant cell lines at the mRNA level. No mutations on the paclitaxel binding site of the ß-tubulin genes were detected in either the resistant or sensitive cells. Live cell images obtained by confocal laser microscopy revealed that the resistant cell line, RERF-LC-KJ, had more accumulation of Oregon Green® 488 conjugated paclitaxel in the lysosomal and extra-lysosomal compartments of cytoplasm than other cell lines. The results obtained in this study indicated that the changes in the subcellular localization could contribute to the production of paclitaxel resistance in lung cancer cell lines. Further studies should be conducted to elucidate the molecular mechanisms that differentiate the intracellular localization of paclitaxel.

Analysis of surgeon's line of sight using an optical tracking system with a multifaceted marker device.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is a widely used technique where operating surgeons alternate between direct vision through minithoracotomy and monitor-aided vision as required. We analyzed surgeons' line of sight to assess their proficiency at using an optical tracking system with a multifaceted marker device. METHODS: An infrared optical tracking system was developed that is capable of integrating information from a multifaceted marker device and analyzing three-dimensional (3D) dynamic movements including flexion and rotation. Using this system, we analyzed multiple aspects of surgeons' head poses, thereby indirectly identifying their visual line of sight. A multifaceted device comprising 4 surfaces and 4 markers was constructed and attached to surgeons' heads. The surgeons' head motions were tracked using this multifaceted device and videotaped their face while they performed wedge resection. Both data sets were compared. RESULTS: The system could document 98.5% of surgeons' head motions, with a high correlation ( = 0.935) between data acquired using the multifaceted device and video analysis. An inverse correlation was observed between tumor size and the monitor-viewing time ratio by surgeons in pulmonary wedge resection (R(2) = 0.728). CONCLUSION: An optical tracking system with a multifaceted device was able to measure 3D dynamic movements of thoracic surgeons. The associated problems of reflection angle and marker shielding were solved. The utility of this device for analyzing surgeons' visual line of sight during VATS was established.

A novel p53-dependent apoptosis function of TARSH in tumor development.

A target of NESH-SH3/Abi3bp (TARSH) was originally identified as an SH3 domain-binding molecule of the NESH-SH3/Abi3 protein that is involved in Rac-dependent actin polymerization. In recent studies, TARSH gene expression was dramatically induced in mouse embryonic fibroblasts (MEFs) replicative senescence and suppressed in human lung carcinoma specimens and thyroid carcinomas. However, the molecular mechanism underlying the regulation of TARSH in tumorigenesis remains unclear. Here, we address a p53-dependent apoptosis function of the mouse TARSH gene using RNAi-mediated suppression of endogenous TARSH expression. Our results will be useful in the discovery of a novel therapeutic target in lung carcinoma.

Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression.

A novel target of NESH-SH3 (TARSH) was identified as a cellular senescence related gene in mouse embryonic fibroblasts (MEFs) replicative senescence, the expression of which has been suppressed in primary clinical lung cancer specimens. However, the molecular mechanism underlying the regulation of TARSH involved in pulmonary tumorigenesis remains unclear. Here we demonstrate that the reduction of TARSH gene expression by short hairpin RNA (shRNA) system robustly inhibited the MEFs proliferation with increase in senescence-associated beta-galactosidase (SA-beta-gal) activity. Using p53-/- MEFs, we further suggest that this growth arrest by loss of TARSH is evoked by p53-dependent p21(Cip1) accumulation. Moreover, we also reveal that TARSH reduction induces multicentrosome in MEFs, which is linked in chromosome instability and tumor development. These results suggest that TARSH plays an important role in proliferation of replicative senescence and may serve as a trigger of tumor development.

Generation and characterization of novel monoclonal antibodies against murine and human TARSH proteins.

TARSH/Abi3bp was originally isolated as a novel target of NESH-SH3 by a two-hybrid yeast system. We have already identified murine TARSH (mTARSH) as a cellular senescence-related gene because of its robust induction in the early phase of mouse embryonic fibroblast cellular senescence. We have also revealed that the expression of this gene was dramatically reduced in human lung cancer cell lines and primary lung tumor, while it was predominantly expressed in normal conditions. This evidence suggests that TARSH is involved in both stress-induced senescence and prevention of cancer development; however, little is known about its molecular mechanisms. To reveal the further physiological function of this molecule, we established rat anti-TARSH monoclonal antibodies (MAb). Recombinant His-tagged partial mouse TARSH protein was expressed in Escherichia coli, affinity purified and used as an antigen to immunize rats. Hybridomas were screened by enzyme-linked immunosorbent assay, and we generated six stable hybridoma cell lines that produced antibody against murine TARSH protein, including three clones that represented cross-reactivity with human TARSH. We determined their isotypes and further examined capabilities or limitations in immunoblotting, immunoprecipitation, and immunofluorescence microscopy, realizing the most suitable antibody for each application. These MAbs should therefore be very useful tools for the study of TARSH expression and for following biological function in cellular senescence and tumor suppression.

Autocrine growth by granulocyte colony-stimulating factor in malignant mesothelioma.

We report the first case of a malignant mesothelioma expressing not only granulocyte-colony stimulating factor (G-CSF), but also its receptor. A 59-year-old male carpenter underwent a panpleuropneumonectomy, but the tumor relapsed and spread rapidly, accompanied by leukocytosis. The white blood cell count reached 147,000/mm3 (96.2% neutrophils), and the concentration of serum G-CSF was 77 pg/mL. An autopsy demonstrated that some of the tumor cells produced G-CSF, but more tumor cells and endothelial cells in the tumor expressed G-CSF receptor. It was hypothesized that an autocrine loop involving G-CSF and the G-CSF receptor greatly accelerated the tumor growth.

Cancer-associated loss of TARSH gene expression in human primary lung cancer.

PURPOSE: We have previously identified mouse Tarsh as one of the cellular senescence-related genes and showed the loss of expression of TARSH mRNA in four human lung cancer cell lines. TARSH is a presumptive signal transduction molecule interacting with NESH, which is implicated to have some roles in lung cancer metastasis. METHODS: The amplification of complete ORF-encoding TARSH cDNA was done with reverse transcription-PCR. Northern blotting was carried out using TARSH cDNA probes. To clarify the relationship between TARSH and lung cancer, we quantified TARSH mRNA expression in 15 human lung cancer cell lines and 32 primary non-small cell lung cancers. RESULTS: We first determined the complete ORF-encoding cDNA sequence which is expressed in the human lung. On the Northern hybridization analysis, TARSH was strongly expressed in the human lung. The expression of TARSH mRNA is remarkably downregulated in all the lung cancer cell lines examined. Furthermore, TARSH expression was significantly low in all of the tumor specimens when compared to the expression in corresponding non-neoplastic lung tissue specimens. CONCLUSION: The cancer-associated transcriptional inactivation of TARSH suggests that TARSH could be used as a biomarker for lung cancer development as well as a molecular adjunct for lung carcinogenesis in human.

Frequent hemizygous deletion at 1p36 and hypermethylation downregulate RUNX3 expression in human lung cancer cell lines.

Runt-related transcription factor 3 (RUNX3) has been recognized as a tumor suppressor gene in gastric cancer because its expression level was reduced or disappeared due to epigenetic changes. To evaluate the usefulness of the RUNX3 gene as a biomarker of lung cancer, we have analyzed the expression of the RUNX3 gene in 15 lung cancer cell lines by real-time reverse transcription-polymerase chain reaction (RT-PCR), and demonstrated that RUNX3 gene expression was reduced or disappeared in all cell lines examined (100%). In addition, we have attempted to classify all the cell lines into three groups according to the expression level; less than 10% (group I), 10-30% (group II) and approximately 50% (group III). We further investigated methylation status of the CpG sites in the exon 1 region of RUNX3 by methylation specific PCR (MSP), and studied the correlation between the expression level and hemizygous deletion as revealed by bicolor fluorescence in situ hybridization (FISH). The CpG sites were hypermethylated in 8 cell lines (53%) and the RUNX3 loci were hemizygously deleted in another 8 cell lines (53%). Furthermore group I, II, and III corresponded well to methylation-positive cell lines, cell lines showing hemizygous deletion, and the rest of cell lines without methylation or hemizygous deletion, respectively. These results suggest that a comprehensive study on RUNX3 using real-time RT-PCR, MSP, and FISH could be beneficial in understanding the pathogenetic mechanisms of human lung cancer at the molecular level.

Lung metastasis of thymoma manifesting as myasthenia gravis 12 years after thymomectomy: report of a case.

A 51-year-old woman, who had undergone thymomectomy for asymptomatic noninvasive thymoma 12 years before, was admitted to our hospital with blepharoptosis caused by myasthenia gravis. A chest computed tomogram (CT) showed an abnormal shadow in the right lower lung field and CT-guided needle biopsy revealed findings of a thymoma. We performed extended thymectomy and partial resection of the right lung using three different approaches, via a cervical incision and bilateral video-assisted thoracoscopic surgery. The resected specimen was a lung metastasis of thymoma, and the residual mediastinal tissue showed no sign of malignancy. Because thymoma and post-thymomectomy myasthenia gravis can both recur, we recommend performing extended thymectomy or thymothymectomy, even for patients who are asymptomatic.

Expression of TARSH gene in MEFs senescence and its potential implication in human lung cancer.

To reveal the molecular mechanism of cellular senescence, we have surveyed the genes that are specifically upregulated via MEFs senescence by suppression subtractive hybridization method. We show here that mTARSH was induced particularly in the relative early phase of MEFs cellular senescence. Further structural analysis of mTARSH disclosed five splicing variants shared a common reading frame whose diversity was derived from the SH3-binding motif cluster in the middle of the gene. We also show that mTARSH mRNA predominantly expressed in lung and that conspicuous expression of TARSH was drastically declined in all several lung cancer cell lines we tested. Thus, TARSH presumably represents a trigger gene for evoking cellular senescence, which has also been suggested to be involved in the prevention of tumorigenesis.

Extrapericardial pulmonary vein clamp technique for pulmonary arteriovenous fistula: report of a case.

The major concern when operating on a patient with a neurologically symptomatic pulmonary arteriovenous fistula (PAVF) is how to prevent a thromboembolic event during surgery. We describe a new technique whereby the extrapericardial pulmonary vein is clamped before transecting the afferent and efferent vessels of the fistula. The potentially pooled clots that can form while manipulating lung are stopped by the clamp. Before the extrapericardial pulmonary vein is declamped, one of the drainage veins is incised halfway and the pooled blood containing the potential clots is completely washed out. We successfully performed segmentectomy using this technique in a 66-year-old man with chronic left hemianopia and a large PAVF in the left anteromedial and lateral basal segments, and no thromboembolic events occurred.