[Surgical Treatment for Congenital Bronchial Atresia and Intralobar Sequestration in the Same Lobe].

A 21-year-old man who had a history of pneumonia twice presented with chest discomfort. Computed tomography( CT) revealed dilatation of the atretic bronchus that was not continuous with the proximal one, and surrounding hyper-lucent lung fields in the outer and mediastinal sides of the right basal segment, and the absence of B10b+c. CT also demonstrated the presence of A10b+c in the former field and the aberrant artery from the inferior phrenic artery in the latter. Right basal segmentectomy was performed under the diagnosis of congenital bronchial atresia and intralobar sequestration. Pathological diagnosis accorded with preoperative one.

[Early VATS(Video-Assisted Thoracoscopic Surgery)Was Effective for a Case of Chylothorax after Lung Cancer Excision].

A 66-year-old man underwent a right upper lobectomy and lymph node dissection for lung cancer. We confirmed a milky white pleural effusion after diet initiation on the first postoperative day, and a chylothorax was diagnosed. The patient began a f at-restricted diet; however, the pleural effusion did not decrease. Therefore, we performed VATS(video-assisted thoracoscopic surgery)1 week after surgery with good results. Early VATS for a postoperative chylothorax was useful.

Successful treatment of refractory chylothorax by pedicled omentoplasty.

A 52-year-old female with a history of past surgery for arteriovenous malformation of the thoracic spinal cord presented with left chylothorax. Lymphangiography identified diffuse lymphatic vessel (LV) growth with ectasia at the left supradiaphragmatic level. On the right side, the LVs were absent due to previous surgery. Given the ineffectiveness of conservative management, the patient required surgery. Thoracotomy showed extensive pleural fibrosis, lung atelectasis, and diffuse chyle defluxion on the parietal pleura. The diffuse chyle defluxion was not resolved by ligation. Therefore, we performed pedicled omentoplasty to fill the pleural space and to utilize its drainage and angiogenic capacity. Two years after the procedure, there was no sign of relapse. There are very few reports of refractory chylothorax successfully treated by pedicled omentoplasty. The procedure would be useful for the treatment of chylothorax when non-surgical or typical surgical management fails.

A new technique of bronchial microsampling and proteomic analysis of epithelial lining fluid in a rat model of acute lung injury.

The standard technique to evaluate the proteins present in epithelial lining fluid (ELF) is bronchoalveolar lavage (BAL). Bronchoscopic microsampling (BMS) method has been developed for humans as a less invasive alternative. We establish the usefulness of a rat bronchial microsampling (rBMS) to evaluate various proteins in ELF in lipopolysaccharide (LPS)-induced lung injury models in rats. In the first experiment of this study, we validate that whether the rBMS can obtain information from ELF in place of BAL. Tumor necrosis factor (TNF)-α concentrations were increased in the rBMS samples similar to BAL 1 and 3h after LPS instillation. In the second part of this study, a proteomic analysis of the rBMS, using the Protein Chip(R) system, revealed the presence of proteins whose molecular weights corresponded to TNF-related proteins in the LPS-treated rats. In rats treated with a TNF-α converting enzyme inhibitor, the concentrations of these proteins in rBMS decreased or disappeared. In the third experiment, rBMS was performed without tracheostomy at 6 and 24h after instillation of LPS, and a rat multiple cytokines assay system detected heterogeneous variations in the concentrations of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, TNF-αand interferon (IFN)-γ in ELF. The cytokine profile was significantly modified by pre-treatment with dexamethasone. This new rBMS technique could be used to measure TNF-α in LPS-induced acute lung injury (ALI) as well as for proteomic analysis, without sacrificing the rats. Furthermore, this procedure enables the serial collection of ELF, which would allow the examination of time-dependent cytokine variations in rat ALI model.

Low papillary structure in lepidic growth component of lung adenocarcinoma: a unique histologic hallmark of aggressive behavior.

Small-sized lung adenocarcinomas often contain a lepidic growth component in part. The term lepidic growth has recently been used to represent a growth pattern of neoplastic cells along preexisting alveolar structures. We reviewed 91 small-sized (≤3 cm) invasive lung adenocarcinomas with a lepidic component to study the histopathologic and clinicopathologic characteristics. In the lepidic component of invasive adenocarcinoma, we have identified a morphologically unique structure characterized by proliferation of low papillae, consisting of neoplastic cells piling up toward the alveolar space, and we defined this architecture as "low papillary structure." There were 18 cases with the low papillary structure in the lepidic components, whereas 73 cases did not have the structure. In the lepidic component, the cases with the low papillary structure had higher Ki-67 labeling index (15.7%) and more frequent p53 overexpression (50.0%) than did those without the structure (9.4% and 16.4%, respectively). Based on clinicopathologic findings, the presence of low papillary structure was significantly associated with lymphatic invasion (P = .023) and lymph node metastasis (P = .001). Furthermore, the patients with the low papillary structure in the lepidic components demonstrated significantly shorter disease-free and overall survival than did those without the structure (P = .001 and P = .010, respectively). We conclude that the low papillary structure is a significant histologic feature in a lepidic component and is associated with aggressive cancer behavior in lung adenocarcinoma.

Vascular-type Ehlers-Danlos syndrome caused by a hitherto unknown genetic mutation: a case report.

INTRODUCTION: Vascular-type Ehlers-Danlos syndrome is an autosomal dominant disease that causes arterial spurting, intestinal perforation, uterine rupture and hemopneumothorax due to decreased production of type III collagen. The average age at death is 48 years old, and it is considered to be the most severe form of Ehlers-Danlos syndrome. We report the case of a 64-year-old Japanese woman and her 38-year-old daughter who were diagnosed with this disease. CASE PRESENTATION: A 64-year-old Japanese woman was referred to our hospital because of right anterior chest pain following cough and pharyngeal discomfort. Pleurisy was suspected due to the presence of right pleural effusion, so the next day she was referred to our department, where a detailed examination led to the diagnosis of hemothorax. The bleeding that caused the right hemothorax was difficult to control, so our patient was transferred to the Department of Thoracic Surgery for hemostasis control. Our patient's personal history of uterine hemorrhage and skin ulcers, as well as the finding of skin fragility during surgery, were indicative of a weak connective tissue disease; therefore, after improvement of the hemothorax, a genetic analysis was performed. This revealed a heterozygous missense mutation in COL3A1, c.2411 G>T p.Gly804Val (exon 36). A detailed investigation conducted at a later date revealed that her daughter also had the same genetic mutation. This led to the diagnosis of vascular-type Ehlers-Danlos syndrome characterized by a new gene mutation. CONCLUSION: We report a new genetic mutation associated with vascular-type Ehlers-Danlos syndrome. We present the clinical and imaging findings, and the disease and treatment course in this patient. We believe this information will be important in treating future cases of vascular-type Ehlers-Danlos syndrome in patients with this mutation.

[Vascular-type Ehlers-Danlos syndrome incidentally diagnosed at surgical treatment for hemothorax; report of a case].

Vascular-type Ehlers-Danlos syndrome(vEDS) is a rare autosomal dominant inherited disorder of the connective tissue, which often causes arterial ruptures and surgical complications. We report the case of a vEDS patient who was incidentally diagnosed at surgical treatment for hemothorax. A 64-year-old woman with a past history of hysterectomy due to excessive bleeding during childbirth visited our hospital complaining of chest pain. Chest computed tomography revealed right pleural effusion suspected of hemothorax and a high density area behind the right anterior chest wall. Emergency thoracoscopy revealed bloody spots throughout the mediastinal pleura, suggestive of bleeding from the right internal thoracic artery. During thoracoscopy, easy bruising of the tissue by surgical manipulation was noted which led us to suspect connective tissue disease. A biochemical analysis by cultured dermal fibroblasts and molecular biological examination established the diagnosis of vEDS.

Minute pulmonary meningothelial-like nodules coexisting with pulmonary cryptococcosis mimicking lung cancer.

A 68-year-old woman was found to have an abnormal shadow on chest X-ray. Computed tomography showed some small ground-glass opacities in the bilateral lung field and also a 22-mm tumor in the left lower lobe, which showed high accumulation on (18)F fluorodeoxyglucose positron emission tomography. Each of them was difficult to distinguish from lung cancer clinically. Preoperative localization of a small ground-glass opacity nodule with computed tomography-guided lipiodol marking and resection of each using a fluoroscopic unit was performed. Pathological findings from the small nodule showed minute pulmonary meningothelial-like nodule, and those from the tumor and fungal culture showed pulmonary cryptococcosis. To the best of our knowledge, this is the first reported case of coexisting minute pulmonary meningothelial-like nodules and pulmonary cryptococcosis mimicking lung cancer. Thoracoscopy assisted by computed tomography-guided lipiodol marking enabled us to diagnose them.

Impact of the integrin signaling adaptor protein NEDD9 on prognosis and metastatic behavior of human lung cancer.

PURPOSE: In a substantial population of non-small cell lung cancer (NSCLC), expression and activation of EGF receptor (EGFR) have been reported and is regarded as a novel molecular target. A growing body of evidence has shown the signaling crosstalk between EGFR and integrins in cellular migration and invasion. NEDD9 is an integrin signaling adaptor protein composed of multiple domains serving as substrate for a variety of tyrosine kinases. In the present study, we aimed at elucidating a role of NEDD9 in the signaling crosstalk between EGFR and integrins. EXPERIMENTAL DESIGN: Using NSCLC cell lines, we conducted immunoblotting and cellular migration/invasion assay in vitro. Next, we analyzed metastasis assays in vivo by the use of xenograft transplantation model. Finally, we retrospectively evaluated clinical samples and records of patients with NSCLCs. RESULTS: We showed that tyrosine phosphorylation of NEDD9 was reduced by the inhibition of EGFR in NSCLC cell lines. Overexpression of constitutively active EGFR caused tyrosine phosphorylation of NEDD9 in the absence of integrin stimulation. By gene transfer and gene knockdown, we showed that NEDD9 plays a pivotal role in cell migration and invasion of those cells in vitro. Furthermore, overexpression of NEDD9 promoted lung metastasis of an NSCLC cell line in NOD/Shi-scid, IL-2Rγ(null) mice (NOG) mice. Finally, univariate and multivariate Cox model analysis of NSCLC clinical specimens revealed a strong correlation between NEDD9 expression and recurrence-free survival as well as overall survival. CONCLUSION: Our data thus suggest that NEDD9 is a promising biomarker for the prognosis of NSCLCs and its expression can promote NSCLC metastasis.

[Mediastinal lymph node carcinoma of unknown primary site; report of a case].

A 71-year-old woman was admitted to our hospital because of a mediastinal mass. Chest computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) showed only 1 swollen mediastinal lymph node. Serum levels of carcinoembryonic antigen (CEA) were found to be elevated. Preoperative examination did not detect the primary lesion. A mediastinal lymphadenectomy was performed, and histologically, the tumor demonstrated poorly differentiated adenocarcinoma. Immunohistochemical staining for cytokine( CK) 7 and thyroid transcription factor( TTF) -1 were positive but were negative for CK20, suggesting a pulmonary origin. During 2-years postoperative follow-up, no signs of primary site growth can be detected. Surgical resection of mediastinal lymph node carcinoma of unknown primary site has the possibility of a good prognosis.

High serum immunoglobulin G4-related retrosternal fibrosclerosis.

A 65-year-old man with a history of exposure to asbestos complained of left leg edema. Computed tomography showed a flat, symmetrical, and longitudinal retrosternal thickening in addition to a presacral tumor. Retroperitoneal fibrosis was suspected. Serum immunoglobulin G4 (IgG4) levels were elevated (213 mg/dL). Thoracoscopic biopsy was performed. Histopathologic findings showed fibrotic tissue accompanied by proliferation of IgG4-positive plasma cells (proportion of IgG4/IgG-positive plasma cells ≥70%) indicative of multifocal fibrosclerosis.

KL-6 and CEA levels in epithelial lining fluid microsamples predict response to gefitinib in patients with advanced non-small cell lung cancer.

BACKGROUND AND OBJECTIVE: Both Krebs von den Lungen-6 (KL-6) and carcinoembryonic antigen (CEA) are known to be tumour markers in non-small cell lung cancer (NSCLC). The aim of the present study was to assess whether or not intrabronchial epithelial lining fluid (ELF) levels of these markers predicted tumour response better than serum levels in patients with advanced NSCLC treated with gefitinib. METHODS: ELF samples were obtained both from near the tumour and from the contralateral lung using a bronchoscopic microsampling technique, before and 2 weeks after the start of gefitinib treatment. Serum samples were taken concurrently. Among the 22 patients enrolled in the study, 14 (64%) showed partial responses or stabilization of disease with gefitinib treatment (treatment responders), while 8 (36%) showed progression of disease (treatment non-responders), 4 weeks after the start of treatment. RESULTS: ELF KL-6 levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.011), whereas there was a marginal increase in the treatment non-responders group (P = 0.049). ELF CEA levels near the tumour decreased significantly after 2 weeks in the treatment responders group (P = 0.004), whereas there was no significant change in the treatment non-responders group. For both markers, neither the serum levels nor the levels in contralateral ELF showed any significant changes in either group of patients. CONCLUSIONS: Both KL-6 and CEA levels in ELF near the tumour predicted tumour response in NSCLC patients treated with gefitinib, whereas serum levels did not.

[Diaphragmatic hernia complicated with perforated stomach during pregnancy].

Diaphragmatic hernia complicating pregnancy is rare and results in a high mortality rate, if early surgical intervention is not undertaken. We report a case of a woman at 32 week's gestation who was admitted to our hospital due to severe epigastralgia. Diaphragmatic relaxation had been pointed out since her birth. The patient was initially diagnosed with acute gastritis, but she developed acute respiratory insufficiency on day 3 of hospitalization. Chest X-ray and computed tomography showed niveau in the left pleural cavity. She was treated with chest tube drainage and an emergency caesarean was performed. The next day, gastric fiberscope demonstrated perforation of gastric ulcer in the left hemithorax. She was diagnosed as having diaphragmatic hernia complicated by a perforated stomach. Emergency thoracotomy was carried out and primary repair of both stomach and diaphragma was performed.

Efficacy of goshajinkigan for peripheral neurotoxicity of oxaliplatin in patients with advanced or recurrent colorectal cancer.

Peripheral neurotoxicity is the major limiting factor for oxaliplatin therapy. Goshajinkigan (GJG), a traditional Japanese herbal medicine, was recently shown to be effective in protecting against the neurotoxicity of taxanes in Japan. We retrospectively investigated the effect of GJG on peripheral neurotoxicity associated with oxaliplatin therapy. Ninety patients with metastatic colorectal cancer that received FOLFOX4 or modified FOLFOX6 therapy were assigned to receive one of the following adjuncts: oral GJG at 7.5 g day(-1) (Group A, n = 11), intravenous supplementation of calcium gluconate and magnesium sulfate (1 g each before and after FOLFOX) (Group B, n = 14), combined GJG and calcium gluconate and magnesium sulfate therapies (Group C, n = 21), or no concomitant therapy (Group D, n = 44). The incidence of peripheral neurotoxicity was investigated when the cumulative dose of oxaliplatin exceeded 500 mg m(-2). When the cumulative dose of oxaliplatin exceeded 500 mg m(-2), the incidence of neuropathy (all grades) in Groups A-D was 50.0%, 100%, 78.9%, and 91.7%, respectively. It was lowest in the group that received GJG alone. Concomitant administration of GJG reduced the neurotoxicity of oxaliplatin in patients that received chemotherapy for colorectal cancer.

[Lung abscess which needed to be distinguished from lung cancer; report of a case].

BACKGROUND: Differential diagnosis of lung abscess from lung cancer is sometimes difficult. CASE: In February 2009, a 57-year-old man consulted our hospital complaining of bloody sputum. Chest computed tomography (CT) demonstrated a 2.5 cm nodule with pleural indentation, spicula and vascular involvement in the right S(3). Bronchofiberscope could not establish a definitive diagnosis. Blood test showed no abnormality. Three months later, progression of the nodule to the adjacent middle lobe was demonstrated by follow-up CT, and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed isotope accumulation in the nodule and hilar lymph node. A diagnosis of lung cancer was suspected and surgery was performed. The diagnosis of possible lung cancer was made by needle biopsy, and the patient underwent right upper lobectomy and partial resection of middle lobe with standard nodal dissection. The final pathological diagnosis was lung abscess. CONCLUSION: Lung abscess must be kept in mind as a possible differential diagnosis when abnormal shadow suspected of lung cancer is observed.

ADAM28 is a serological and histochemical marker for non-small-cell lung cancers.

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small-cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross-reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9-fold higher than that in the non-neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6-fold higher in the NSCLC patients (5.41 +/- 8.62 ng/ml; n = 102) than in the control subjects (1.17 +/- 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false-negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false-positive and false-negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of

Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma.

The micropapillary pattern is characterized by small papillary tufts with no fibrovascular core lying in spaces and has been reported as an aggressive variant of carcinoma in several organs. We investigated the histopathobiological properties of the micropapillary pattern with immunohistochemistry, serial sections, and electron microscopy in lung adenocarcinoma. We further analyzed its clinicopathological character and prognosis. The subjects included 383 adenocarcinoma cases, of which 184 (48%) were micropapillary pattern-positive and 199 (52%) were micropapillary pattern-negative. On histology, micropapillary tufts seemed to float in the alveolar space or spaces encased by connective tissues, whereas serial sections revealed that most tufts had continuity with other tufts and even with the main tumor. Positive staining for the adhesion molecules E-cadherin and beta-catenin suggested the preservation of tight adhesion, and electron microscopy showed the existence of intercellular junctions. Negative staining for laminin and loss of basement membrane as determined by electron microscopy suggest a loss of cell-matrix contact. Positive staining for Ki-67 indicates that cells constituting micropapillary tufts retained their proliferation potency. There were no CD34-positive cells in micropapillary tufts, and the loss of the vascular core was confirmed. In micropapillary pattern-positive cases, lymphatic invasion was identified significantly more frequently than in micropapillary pattern-negative cases (P<0.001), even at stageIA (without lymph node metastasis, N=197) (P<0.001). The 5-year and 10-year overall survival rates of the micropapillary pattern-positive stageIA group were 77.6 and 67.6%, respectively, which were significantly less than those of the micropapillary pattern-negative stageIA group (98.1 and 98.1%) (P=0.001). In conclusion, cells constituting the micropapillary pattern are likely to have acquired anchorage-independent growth and a potential for high malignancy.

Syndrome of inappropriate secretion of antidiuretic hormone after chemotherapy with vinorelbine.

PURPOSE: To describe a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after administration of vinorelbine (VNB) for recurrence of lung cancer. CASE: A 76-year-old man underwent bronchial arterial infusion (BAI) of VNB for postoperative recurrence of lung cancer. Seven days later, hyponatremia and natriuresis developed. Based on his clinical and laboratory findings, we diagnosed him with SIADH. He improved within a couple of days with fluid restriction only. CONCLUSIONS: Administration of VNB may potentially cause SIADH. This is the second report of the SIADH caused by VNB. It is important to monitor the serum sodium level and clinical findings after chemotherapy with VNB.