Leiomyosarcoma of the chest wall mimicking schwannoma resected by a video-assisted thoracoscopic approach: a case report.

Chest wall sarcomas account for <20% of all soft tissue sarcomas of which leiomyosarcomas represent only 1-4%. We report a case of thoracic leiomyosarcoma that resembled schwannoma in preoperative image studies. A 79-year-old man presented to our hospital with a chest wall tumor that increased in size over 3 months. Computed tomography of the chest revealed a 3-cm mass arising from the chest wall. Thoracic magnetic resonance imaging showed a solid tumor that was hypo-intense on T1-weighted imaging and iso-intense on T2-weighted imaging. Chest wall resection was performed using a video-assisted thoracoscopic approach after a frozen section examination revealed sarcoma. The histological diagnosis was leiomyosarcoma. Liver and multiple lung metastases were detected 5 years after surgery. Malignant tumors should be considered in any patient with chest wall tumors. The thoracoscopic approach could be an optimal treatment for chest wall tumor.

[Dumbbell-shaped Intercostal Neurilemmoma of the Anterior Chest Wall;Report of a Case].

A 18-year-old man was referred to our hospital complaining of chest abnormal shadow of the left upper lung field in mass screening chest X-ray. Although his left anterior chest wall swelled, he did not recognize that. Computed tomography and magnetic resonance imaging demonstrated a dumbbell shaped tumor of the left 1st intercostal space which had grown both inside and outside the thoracic cavity. As a possibility of solitary fibrous tumor or myxoma was not excluded, the patient underwent tumor resection. A solid tumor connected to the 1st intercostal nerve was easily dissected from surrounding tissue. Pathological examination revealed the tumor was consisted of spindle shaped cells without atypia, and diagnosed as neurilemmoma without malignancy. Based on anatomical pathway of intercostal nerves, we speculate that the tumor originated from anterior cutaneous nerve.

[Anaphylaxis Induced by Fibrin Glue During Surgery for Pneumothorax].

We report here our experience with a case of anaphylactic shock caused by fibrin glue. A 51-year-old male underwent a thoracoscopic surgery for refractory pneumothorax under local anesthesia. Bullae were revealed, and subsequently covered with fibrin glue and a polyglycolic acid sheet. Twenty-minutes after application of the fibrin glue, sudden drop of blood pressure less than 80 mmHg and a skin rash appeared. Since the patient was not administered any other drugs prior to the reduction in blood pressure, anaphylactic shock was considered to be caused by fibrin glue. The patient recovered after the treatment by dopamine and steroid.

Tumor-related gene expression levels in pulmonary pleomorphic carcinoma.

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small-cell lung cancer that belongs to the family of sarcomatoid carcinomas and is associated with poor prognosis. We investigated the expressions of tumor-related genes in resected PPC specimens. METHODS: Specimens resected from patients with PPC from July 2006 through April 2012 were investigated. Tumor segments were collected from the specimens by micro-dissection to extract mRNA, then RT-PCR was performed according to Dannenberg's tumor profile method for semi-quantitation of tumor-related gene mRNA. To compare with other types of lung cancer, data from stage-matched adenocarcinoma (AC) and squamous cell carcinoma (SCC) cases in our database were also examined. RESULTS: The gene expression levels of thymidylate synthase were significantly higher in PPC and SCC as compared to the AC specimens (p < 0.001). The levels of dihydropyrimidine dehydrogenase and thymidine phosphorylase mRNA in PPC showed a similar tendency to those in SCC, in contrast to AC. Furthermore, the expression level of excision repair cross-complementation group 1 mRNA in PPC specimens was similar to that reported in NSCLC, while the level of vascular endothelial growth factor (VEGF) expression was higher as compared to that reported for colorectal cancer. CONCLUSIONS: Although gene expression of tumor cannot be directly correlated to its sensitivity for anti-cancer drugs, it is likely that PPC tumors are not sensitive to anti-metabolic drugs. Anti-VEGF therapy may be a candidate for PPC, while cisplatin also remains a viable option.

[Pulmonary Clear Cell Type Squamous Cell Carcinoma that Required Differential Diagnosis from Metastatic Ureter Cancer;Report of a Case].

A 71-year-old woman was referred to our department for a nodular lesion in the left lung. She had been followed by urology department in our hospital for 6 years since right nephrectomy for ureter cancer. Chest X-ray and computed tomography (CT) scan demonstrated a small nodular shadow in the left lower lobe. The lung tumor was removed by wedge resection, and pathologically diagnosed during the operation as a metastasis from the ureter cancer. The lung tumor consisted of clear cells similar to the ureter cancer. However, the final pathological diagnosis changed to a primary lung cancer based on the findings of stratified differentiation and cancer cell nests in the tumor. Immunohistochemical staining for ureter epithelium-related antigens confirmed the diagnosis. Although we recommended left lower completion lobectomy, the patient refused additional surgery. She is suspected to have local recurrence in the left lower lobe 18 months after the surgery.

¹8F-fluorodeoxyglucose positron emission tomography for evaluation of thymic epithelial tumors: utility for World Health Organization classification and predicting recurrence-free survival.

OBJECTIVES: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of (18)F-FDG-PET for predicting the histological classification, stage and survival of thymic epithelial tumors. METHODS: We retrospectively analyzed 37 patients with thymic epithelial tumors who underwent PET before surgical resection and investigated the relationship between the maximum of standardized uptake value (SUVmax) of each tumor and the WHO classification, recurrence-free survival, and tumor-related gene expressions. RESULTS: The study included 15 males and 22 females, ranging in age from 22 to 81 years (mean 64 years). The tumor histology of 31 tumors was thymoma and that of the remaining tumors was thymic carcinoma. The Masaoka tumor stage was as follows: stage I in 18, II in 9, III in 5 and IV in 5 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymoma (types A, AB and B1, n = 21), high-risk thymoma (types B2 and B3, n = 10) and thymic carcinoma (n = 6). The SUVmax of low-risk group (SUVmax ≤4.27) was significantly lower than that of high-risk group (p = 0.0114) and that of thymic carcinomas (SUVmax >4.27) was also significantly higher than that of thymomas (p < 0.0001). The group of high SUVmax (SUVmax >4.27) had significantly inferior recurrence-free survival to that of less value (SUVmax ≤4.27) (p = 0.0009). The SUVmax were not correlated with tumor-related gene expressions. CONCLUSION: The SUVmax of (18)F-FDG-PET reflects WHO classification of thymic epithelial tumors. High SUVmax predicts lower recurrence-free survival of the tumors.

One-step nucleic acid amplification for detection of lymph node metastasis in lung cancer.

OBJECTIVE: Intraoperative diagnosis of lymph node (LN) metastasis is critical in lung cancer patients. The one-step nucleic acid amplification (OSNA) assay is a novel technique using a loop-mediated isothermal amplification method of gene amplification. The objective of this study was to investigate whether the OSNA assay provides sufficient diagnosis of LN metastasis in lung cancer patients. METHODS: A total of 40 LN stations were dissected from the 20 patients, who had curative lobectomy for lung cancer. The cut halves of LNs were used for pathological diagnosis, and other halves were for the OSNA assay. The OSNA assay used cytokeratin (CK) 19 mRNA as a marker. The CK19 mRNA copy number was detected using RD-100i (Sysmex Corp., Hyogo, Japan). One formalin-fixed section with the largest cutting surface of the other halves of LNs was used for pathological examination. When discordance was observed between OSNA assay and usual pathological examination, an additional examination using 1-mm interval sections was performed. RESULTS: In the forty LN stations, three stations were diagnosed as LN metastasis positive pathologically. In these three, the OSNA assays showed extremely high numbers of CK19 mRNA copies. When the cutoff value was set to 250 copies/µl, 4 stations with relatively low copy numbers were found to be discordant. Of the 4 discordant cases, one was shown to be micro-metastasis positive in the additional pathological assessment. The sensitivity of the OSNA assay was 100.0%, and its specificity was 91.7%. CONCLUSIONS: This method could be applied to intraoperative assessment LNs metastasis.

Lung cancer complicated with IgG4-related disease of the lung.

Few have reported a concomitant malignant neoplasm with immunoglobulin G4 (IgG4)-related diseases. We describe a case of lung cancer and gastric cancer accompanied with IgG4-related disease. A 78-year-old man had an area of ground-glass opacity with central collapse in right upper lobe and a gastric cancer. The patient underwent a right upper lobectomy following a gastrectomy for the gastric cancer. Histological examination of the resected lung specimen revealed a lepidic pattern of an adenocarcinoma and a large amount of plasmacyte infiltration around the tumor. In immunohistochemical findings, the plasmacytes were stained for IgG4. Therefore, the lung tumor was considered to have associated with IgG4-related interstitial lesions.

Unexpected rapid growth of estrogen receptor positive lung cancer during pregnancy.

We report a case with lung cancer during pregnancy, which has a very poor prognosis.A 34-year old female at 30 weeks of pregnancy came to us with a cough and right lower chest pain. Chest computed tomography revealed a mass in the right lower lung lobe and the diagnosis of adenocarcinoma cT2aN1M0 was made. We performed a right sleeve pneumonectomy, as the tumor had progressed to the right main bronchus near carina. Histological sections of the specimens revealed a poorly differentiated adenocarcinoma that infiltrated surrounding structures. The pathological stage of lung cancer was T4N2M0 stage IIIB. Immunohistochemistry findings for estrogen receptor ß were positive in the nuclei of the adenocarcinoma. She had a rapid recurrence in spite of chemotherapy, and she died 7.5 months after operation. The positive estrogen receptor and hormonal condition during pregnancy might promote cancer and result in her poor prognosis.

[Pulmonary mucosa-associated lymphoid tissue(MALT) lymphoma after occupational exposure to organic solvent].

A 68-year-old woman was referred to our hospital due to a left chest abnormal shadow on chest film. She had a history of occupational exposure to organic solvent for about 30 years until 10 years ago. Computed tomography (CT) scan demonstrated a nodular shadow 12 mm in diameter in the left lower lobe. As a lung cancer was suspected, partial resection of the lobe including the small lesion was performed. Since mucosa-associated lymphoid tissue(MALT) lymphoma was diagnosed by intraoperative pathological examination, we finished the operation without any more lung resection. The diagnosis was finally confirmed by histological finding of small lymphoid cell proliferation and positive staining for CD20. Chronic inflammation, such as Helicobacter pylori infection, is considered to be a cause of MALT lymphoma. We speculate that the long term exposure to organic solvent may develop the disease by continuous chemical stimulation to bronchus.

[Outcome of pulmonary resection for metastases from hepatocellular carcinoma].

Because pulmonary metastasis is considered to be systemic spread of hepatocellular carcinoma (HCC), indication of pulmonary resection as a treatment for it is not well-described. We retrospectively reviewed clinical records of the patients who underwent pulmonary resection for metastases from HCC in our hospital. Seven patients, 6 men, 1 woman, and the mean-age 65.4 year-old, underwent pulmonary resection from April in 2001 to March in 2010. During the same period, we carried out pulmonary resection for 122 patients with metastases from other malignant diseases. Therefore, pulmonary resection for HCC metastases accounted for 5.4% of the total pulmonary metastasectomy. One of the 7 patients, a 70 year-old man, survives for 69 months after right middle lobectomy for solitary HCC metastasis. Other 6 patients with multiple pulmonary metastases or with increased level of alpha-fetoprotein (AFP) before pulmonary resection died of systemic recurrence. The mean survival time of 7 patients was 20 months and was 11.8 months except the long-time survivor. From our results, patients with multiple pulmonary metastases from HCC or with increased serum level of AFP before surgery should be carefully selected as candidates for pulmonary metastasectomy.

Benefits of rib head resection via costotransverse ligament release method for T3 lung cancer in the paravertebral space.

OBJECTIVE: Lung cancer located in the paravertebral region occasionally invades the rib head (T3) and not the spine (T4). In such cases, a costotransverse ligament release (CTLR) method may be useful for complete resection without performing a vertebrectomy. METHODS: Eighteen patients with lung cancer underwent chest wall resection between 2001 and 2009 at our institutions. Of those, 7 who underwent chest wall removal with rib head resection via a CTLR method (group A) and 11 without rib head resection(conventional distal rib resection, group B) were retrospectively analyzed. RESULTS: Three patients in group A underwent induction chemoradiotherapy. All rib head resections were performed via a CTLR approach without postoperative complications. There were no deaths within 30 day in group A and 1 in group B. The mean number of resected rib heads was 2.1 in group A, while 2.0 ribs were removed in group B. There was no significant difference for operation time between groups A and B(332±112 vs. 287±114 mins, p = 0.449). Local recurrence was seen in 0 patients in group A and 3 in group B(p = 0.13). The median survival time was 1489 and 727 day, respectively, while 5-year survival rates were 0.48 and 0.41, respectively. CONCLUSION: A rib head resection via a CTLR method is an effective procedure for T3 lung cancer infiltrating the rib head.

Incidence of acute exacerbation of interstitial pneumonia in operated lung cancer: institutional report and review.

PURPOSE: Several small studies have reported that acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection for patients with non-small cell lung cancer, though the incidence rate is unclear. METHODS: We examined our institutional data and performed a search of the MEDLINE database for publications regarding AE of IIP following surgery for lung cancer. Studies reporting the incidence rates of IIP and AE were included. RESULTS: Eleven studies including our institutional data were determined to be eligible. Seven studies designated the incidence of IIP. Of 4749 patients (from 7 studies) who underwent lung resection for NSCLC, 277 had IIP, for an incidence rate of 5.8% (range 1.1%-11.7%). Eleven studies designated the incidence of AE from IIP patient, 67 (15.8%) of 424 IIP patients (from 11 studies) developed AE after surgery, of whom 38 (56.7%) died during the postoperative course. CONCLUSION: Coexistent IIP in patients with lung cancer increases the risk of lung cancer surgery. Furthermore, AE of IIP may be a major cause of operation-related death.

Src tyrosine kinase inhibition prevents pulmonary ischemia-reperfusion-induced acute lung injury.

PURPOSE: Pulmonary ischemia-reperfusion is a pathological process seen in several clinical conditions, including lung transplantation, cardiopulmonary bypass, resuscitation for circulatory arrest, atherosclerosis, and pulmonary embolism. A better understanding of its molecular mechanisms is very important. METHODS: Rat left lung underwent in situ ischemia for 60 min, followed by 2 h of reperfusion. The gene expression profiles and Src protein tyrosine kinase (PTK) phosphorylation were studied over time, and PP2, an Src PTK inhibitor, was intravenously administered 10 min before lung ischemia to determine the role of Src PTK in lung injury. RESULTS: Reperfusion following ischemia significantly changed the expression of 169 genes, with Mmp8, Mmp9, S100a9, and S100a8 being the most upregulated genes. Ischemia alone only affected expression of 9 genes in the lung. However, Src PTK phosphorylation (activation) was increased in the ischemic lung, mainly on the alveolar wall. Src PTK inhibitor pretreatment decreased phosphorylation of Src PTKs, total protein tyrosine phosphorylation, and STAT3 phosphorylation. It increased phosphorylation of the p85α subunit of PI3 kinase, a signal pathway that can inhibit coagulation and inflammation. PP2 reduced leukocyte infiltration in the lung, apoptotic cell death, fibrin deposition, and severity of acute lung injury after reperfusion. Src inhibition also significantly reduced CXCL1 (GRO/KI) and CCL2 (MCP-1) chemokine levels in the serum. CONCLUSION: During pulmonary ischemia, Src PTK activation, rather than alteration in gene expression, may play a critical role in reperfusion-induced lung injury. Src PTK inhibition presents a new prophylactic treatment for pulmonary ischemia-reperfusion-induced acute lung injury.

A case of Mullerian cyst arising in posterior mediastinum.

A mediastinal Mullerian cyst was initially reported as a new category of congenital cyst by Hattori, et al. in 2005. We treated a 53-year-old female referred to us with a posterior mediastinal tumor found at the Th5 prevertebral level by chest-computed tomography during a medical check-up. She had a history of mediastinal teratoma, which was removed at the age of 35. Chest magnetic resonance imaging revealed homogenous, high-intensity signals in T2-weighted images. The lesion was resected using a thoracoscopic procedure, and histologic and immunohistochemical staining revealed a ciliated cyst of Mullerian origin. The newly established mediastinal Mullerian cyst should be included in the differential diagnosis of posterior mediastinal cysts.

[Diaphragmatic metastasis from uterine corpus cancer].

We report a case of metastatic diaphragm tumor from uterine corpus cancer. A 72-year-old female had a tumor on right diaphragm 4-years after operation for uterine corpus cancer. After chemotherapy, tumor resection was performed by right lung basal segmentectomy, partial liver resection, and partial diaphragm resection. The pathological examination revealed adenocarcinoma, compatible with uterine corpus cancer, metastasizing in diaphragm and involving lung and liver. After the operation, a local recurrence occurred at parasternal lymph node, which is considered to be present on the efferent route of lymph flow from diaphragm.

[Radical resection following to concurrent chemoradiotherapy for eighty-five year-old patient with superior sulcus tumor].

An 85-year-old male with superior sulcus tumor was referred to our hospital complaining right brachial pain and omalgia. Chest computed tomography showed right apical lung tumor involving the 1st rib, and bronchoscopy established a diagnosis of squamous cell carcinoma, cT3NOM0. After concurrent chemoradiotherapy [cisplatin (CDDP) + 60 Gy], functional examination indicated him to be tolerable to lobectomy, and he underwent right upper lobectomy + chest wall resection (1st-3rd ribs) + lymph-node dissection. Pathological examination revealed that the effect of chemoradiotherapy was Ef. 3. The postoperative course was uneventful. He is free from recurrence for 7 years after the surgery.

The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy.

Many newly discovered therapeutic agents require a delivery platform in order to translate them into clinical applications. For this purpose, a nanoscale formulation strategy was developed for the Src tyrosine kinase inhibitor PP2. The formulation utilizes the combination of the self-assembling peptides (EAK16-II) and amino acids to minimize the use of the toxic organic solvent DMSO; hence, the biocompatibility of the PP2 nanoformulations was significantly improved. They were found to be non-hemolytic and safe for intravenous and intratracheal administration; the formulations did not alter PP2 activity in Src inhibition on cultured cells. The PP2 nanoformulation was further evaluated on a lipopolysaccharide (LPS)-induced acute lung injury mouse model. Results revealed that the pretreatment of PP2 nanoformulation could decrease the inflammatory cell infiltration and the pro-inflammatory cytokine TNF-α production in the bronchoalveolar lavage fluid after LPS stimulation. The promising therapeutic efficacy and the formulation strategy developed in this work may help further translate PP2 and other hydrophobic therapeutic agents into clinical applications.

XB130, a novel adaptor protein, promotes thyroid tumor growth.

Adaptor proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel adaptor protein, XB130, which binds the p85α subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G(1)-S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the top-ranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.

Anti-allergic agent tranilast decreases development of obliterative airway disease in rat model of heterotopic tracheal transplantation.

BACKGROUND: Tranilast is an anti-allergic agent known to inhibit the release of histamine, interleukin-1beta, transforming growth factor beta1, and platelet-derived growth factor from various cells and currently is used to treat allergic diseases, keloids, and hypertrophic scars. We evaluated the ability of tranilast to inhibit the development of obliterative airway disease (OAD) in a rat model of heterotopic tracheal transplantation. METHODS: We transplanted tracheal segments from donor rats (Brown Norway) into subcutaneous pouches in major histocompatibility complex-incompatible recipient rats (Lewis). At Days 21 and 28 after transplantation, we histologically assessed the harvested allografts scored the degree of OAD, on a scale from zero to 4 as previously described, caused by fibroproliferative tissue. RESULTS: Recipient animals treated orally with 400 mg/kg/day tranilast throughout the experiment showed significantly decreased OAD compared with control animals, with a histologic score of 1.1 +/- 0.4 vs 3.0 +/- 1.3, respectively (mean +/- SD, p=0.007), at Day 21 after transplantation and 2.0 +/- 1.4 vs 3.9 +/- 0.4, respectively (mean +/- SD, p=0.017), at Day 28 after transplantation. CONCLUSION: These results showed that treatment with tranilast significantly decreased fibroproliferative airway changes associated with allograft rejection in a rat model of tracheal transplantation, suggesting that tranilast may be useful in preventing bronchiolitis obliterans after lung transplantation.