ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer.

BACKGROUND: ASC amino-acid transporter 2 (ASCT2) is a major glutamine transporter that has an essential role in tumour growth and progression. Although ASCT2 is highly expressed in various cancer cells, the clinicopathological significance of its expression in non-small cell lung cancer (NSCLC) remains unclear. METHODS: One hundred and four patients with surgically resected NSCLC were evaluated as one institutional cohort. Tumour sections were stained by immunohistochemistry (IHC) for ASCT2, Ki-67, phospho-mTOR (mammalian target of rapamycin), and CD34 to assess the microvessel density. Two hundred and four patients with NSCLC were also validated by IHC from an independent cohort. RESULTS: ASC amino-acid transporter 2 was expressed in 66% of patients, and was closely correlated with disease stage, lymphatic permeation, vascular invasion, CD98, cell proliferation, angiogenesis, and mTOR phosphorylation, particularly in patients with adenocarcinoma (AC). Moreover, two independent cohorts confirmed that ASCT2 was an independent marker for poor outcome in AC patients. CONCLUSIONS: ASC amino-acid transporter 2 expression has a crucial role in the metastasis of pulmonary AC, and is a potential molecular marker for predicting poor prognosis after surgery.

Clinicopathological and prognostic significance of interleukin-8 expression and its relationship to KRAS mutation in lung adenocarcinoma.

BACKGROUND: On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas. METHODS: IL-8 expression was examined by quantitative RT-PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed. RESULTS: IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8. DFS and OS were significantly shorter in the patients with mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis. CONCLUSIONS: Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma.

Effect of landiolol hydrochloride, an ultra-short-acting beta 1-selective blocker, on supraventricular tachycardia, atrial fibrillation and flutter after pulmonary resection.

WHAT IS KNOWN AND OBJECTIVE: Supraventricular tachycardia is a common complication after pulmonary resection. The objective of this study was to investigate the efficacy of landiolol hydrochloride, an ultra-short-acting ß1-blocker, in patients with post-operative supraventricular tachycardia after pulmonary resection. METHODS: The response to continuous intravenous infusion of landiolol was evaluated in 25 patients who developed post-operative atrial fibrillation or atrial flutter after major pulmonary resection. Four patients had preoperative rate-controlled chronic atrial fibrillation. The heart rate and blood pressure were compared before and after infusion of landiolol. Side effects and recurrence of supraventricular tachycardia after termination of landiolol infusion were also monitored. RESULTS AND DISCUSSION: The heart rate was reduced from 135±24 bpm before landiolol infusion to a plateau rate of 85±19 bpm during infusion (P<0·0001). Heart rate reduction occurred in all but two patients. Conversion to normal sinus rhythm from supraventricular tachycardia occurred in 14 patients (56%). Recurrence of supraventricular tachycardia after stopping landiolol infusion was observed in 17 patients (68%), but all patients without preoperative AF were cured of post-operative AF. There were no detectable side effects, including no adverse influence on the circulatory and respiratory systems. WHAT IS NEW AND CONCLUSION: Continuous intravenous infusion of landiolol was found to be effective and safe for supraventricular tachycardia after pulmonary resection.

[Surgical treatment for secondary pneumothorax in elderly patients].

Surgical treatment for secondary pneumothorax in elderly patients is very difficult because of having a high perioperative risk related to the presence of underlying chronic lung disease. In this study, we performed a retrospective review of elderly (> or = 70 years old) 35 patients with secondary pneumothorax who underwent surgical treatment between 2000 and 2009. Of the 35 patients, 31 were men and 4 were women with an average age 77.9 years old. Seventeen patients of them had already received oxygen therapy. They were not only in chronic respiratory failure but also malnutrition. Hospital mortality rate was 14.3%. Three patients died within 30 postoperative days and 2 patients were with hospital death after operation. The 5-year survival rate in patients with secondary pneumothorax was 41.7%. Although secondary pneumothorax is one of benign pulmonary diseases, its prognosis in elderly patients is poor. In conclusion, prompt diagnosis and treatment of secondary pneumothorax in elderly patients are mandatory. They could improve the outcome of this disease.

[Collision cancer of squamous cell carcinoma and small cell carcinoma of the lung; report of a case].

We report a rare case of a primary collision cancer in the lung consisting of squamous cell carcinoma and small cell carcinoma. A 65-year-old man with an abnormal shadow in the right S6 was diagnosed as squamous cell carcinoma by transbronchial lung biopsy. A right lower lobectomy with mediastinal lymph node dissection was performed. The pathological stage of squamous cell carcinoma was IIIA (T2N2M0). The other element diagnosed by pathological examination was small cell carcinoma of which pathological stage was IA (T1N0M0). Each element was clearly distinguished and touched each other. Following the operation, the patient received systemic chemotherapy against small cell carcinoma with cisplatin and irinotecan hydrochloride for 1 course, and cisplatin and etoposide for 3 courses. Since the prognosis of collision cancer is generally reported to be influenced by more advanced element of cancer, the prognosis of the present case is suspected to be dependent on the squamous cell carcinoma.

[Pleomorphic lung cancer; a clinicopathologic study].

Pulmonary pleomorphic carcinoma is a comparatively rare histologic type of lung carcinoma, and the incidence among all lung carcinomas has been reported to be 0.4%. We reported our experience with 8 patients who had been diagnosed as pulmonary pleomorphic carcinoma, and discussed clinicopathologically the preoperative diagnosis and treatment. In 2 of 8 patients, preoperative transbronchial lung biopsy revealed spindle cell component, highly suggesting pulmonary pleomorphic carcinoma. All patients underwent surgical treatment and 2 of then had incomplete resections because of intrathoracic disseminations or carcinomatous pericarditis. Pathological findings showed invasions into the surrounding thoracic organs such as the chest wall, pericardium, adjacent pulmonary lobe or mediastinal pleura in 5 cases, intrapulmonary metastasis of the same lobe in 3 and lymph node involvement in 3. Recurrence occurred in 6 patients immediately after the operation. Although the preoperative diagnosis of biphasic tumor such as pulmonary pleomorphic carcinoma is difficult, it is possible to suspect the diagnosis when sarcomatous components were detected by preoperative biopsy. The efficacy of chemotherapy and radiotherapy have not been established yet, and thus we would like to emphasize that surgery might be the treatment of choice.

[Thoracoscopic clipping of the thooracic duct for chylothorax following esophagectomy: report of a case].

Thoracoscopic clipping of the thoracic duct was successfully performed for the treatment of postoperative chylothorax. Chylothorax occurred in a 67-year-old man following an esophagectomy for esophageal cancer. Following unsuccessful conservative therapy for 3 weeks, we performed thoracoscopic surgery to examine the thoracic duct and found a leaking point of chylous fluid. The thoracic duct was successfully clipped resulting in complete elimination of the effusion immediately after surgery. Generally, chylothorax complicated by an esophagectomy has been managed by medical treatment first, followed by surgical intervention in case of uncontrollable pleural effusion. We think you should try this method at first in case chylothorax was able to be treated with not thoracotomy but thoracoscopic surgery: minimal invasiveness.

[Surgical resection of T3 and T4 lung cancer].

Lung cancer invading neighboring anatomical structures such as the chest wall, pericardium, diaphragm, and left atrium are categorized as T3 or T4, which is regarded as locally advanced lung cancer. The purpose of this study was to evaluate results of surgical treatment of T3-4N0-2M0 non-small cell lung cancer according to involved organs. From 1981 to April 2005, 148 patients with lung cancer invading neighboring organs were surgically treated in our hospital. The 5-year survival was 41.4% in all cases. According to 5-year survival of clinical characteristics, the chest wall (parietal pleura) group (45.5%) had a significantly better prognosis compared with the left atrium (0%, p = 0.03) and diaphragm (0%, p = 0.04) groups. T3N0 (50.3%), IIB (55.4%), IIIA (44.6%), and complete resection groups (49.0%) showed a significantly better prognosis compared with T3N2 (27.9%, p = 0.01), III B (0%, p < 0.0001), and incomplete resection groups (13.9%, p < 0.0001), respectively. These results indicate that the prognosis of patients with N2 disease or incomplete resection remains poor in regardless with the type of involved organs.

[Perioperative management for lung cancer with interstitial pneumonia].

The purpose of this study was to review perioperative managements from the clinical features and the postoperative course of lung cancer patients with interstitial pneumonia (IP). Twenty-two patients with IP were divided into 2 groups: the acute exacerbation (AE) group (6 patients) and the non-acute exacerbation (NAE) group (16 patients). There was no significant difference in the patient background between the 2 groups. In hematological examination, KL-6 levels were significantly higher in the AE group than in the NAE group. There was no significant difference in the respiratory function tests in the both groups, and the heart rate after 2 flights test was significantly higher in the AE group than in the NAE group. There was no significant difference in operation-related factors, tumor-related factors and the postoperative course in the both groups. No postoperative death occurred in our 22 patients probably due to adequate treatments of IP which was managed by our detailed manual. Long-term follow-up for lung cancer patients with IP undergoing surgical intervention is needed to prevent AE.

[Secondary abnormal development of the bronchial artery: report of a case].

A 65-year-old man was admitted to our hospital because of massive hemoptysis. The patient had suffered from pneumonia since 1999, but he had refused to undertake further examinations. In 2002, the patient was transferred to our emergency room because of massive hemoptysis. Following endotracheal intubation, the patient underwent bronchial artery embolization. The X-ray and computed tomography (CT) films on admission revealed localized bronchiectasis in the left upper lung. Bronchoscopic findings revealed massive bleeding from the left upper bronchus. Bronchial arteriography of the left bronchial artery showed peripherally hypervascular finding in the left upper lobe. A segmentectomy of the left upper division was performed as a radical therapy for localized lesions with massive hemoptysis. The pathological diagnosis was secondary abnormal development of the bronchial artery. We speculated that massive hemoptysis had occurred probably due to infection in the focus.

[Congenital bronchial atresia treated with video-assisted thoracoscopic surgery; report of a case].

We report an adult case of congenital lobar emphysema due to bronchial atresia. A 24-year-old man was referred to our department because of cough and fever. A chest roentgenogram on admission showed multiple cystic shadows in the left lower lung field. Chest computed tomography (CT) demonstrated multiple cysts with neveau and scattered infiltration in the left lingual segment and lower lobe. Surgical treatment was scheduled because of no improvement of the chest lesions. The interlobar fissure was not found between the upper and the lower lobes, but between the upper and the lingual divisions. Additionally, the lingual bronchus was not bifurcated from the upper bronchus, but from the lower bronchus. As inflammatory changes were extended to the lingual division and the lower lobe, a left lingual segmentectomy and a lower lobectomy with video-assisted thoracoscopic surgery were performed. His postoperative course was uneventful and he was discharged at the seventh day after surgery.

[Duodenal metastasis from squamous cell carcinoma of the lung; report of a case].

Metastatic carcinoma from primary lung cancer is usually recognized in the brain, adrenal glands, and bone. It is uncommon in the digestive system, particularly in the duodenum. We report a 63-year-old man who had undergone a left lower lobectomy for lung cancer. Anemia (Hb 6.9 g/dl) had been observed 2 months after surgery for primary lung cancer. Gastroduodenoscopy showed duodenal metastasis, and further examination demonstrated adrenal metastasis. Palliative treatment was selected and the patient died 5 months after surgery.

[The clinicopathological features of peripheral small-sized (2 cm or less) squamous cell carcinoma of the lung].

Recently the diagnosis of peripheral small-sized lung cancers has increased with the development of computed tomography. The vast majority of them are adenocarcinoma, whereas squamous cell carcinoma is rare. From 1981 to 2002, 1,054 patients underwent pulmonary resection for primary lung cancer in National Nishigunma Hospital. Among of them, 17 patients with peripheral small-sized (2 cm or less) squamous cell carcinoma underwent lobectomy and systemic nodal dissection were retrospectively reviewed. These were 15 men and 2 women, with a mean age of 68 years (range, 56-75). Regarding the pathologic stage, 15 patients were classified in stage IA, 1 in IIA, and 1 in IIIA. Among of them, only 1 patient with n 2 disease died of cancer at 17 months after surgery. Overall 5-year and 10-year survival rates of this disease were 84.4% and 73.8%, respectively. Based on the present data, we conclude that mediastinal nodal dissection would be unnecessary in the patients with peripheral small-sized squamous cell carcinoma of the lung.

Clinical significance of the preoperative serum-soluble intercellular adhesion molecule-1 in non-small cell lung cancer.

BACKGROUND: The serum-soluble intercellular adhesion molecule-1 (sICAM-1) is reported to correlate with both the metastatic potential and a poor prognosis. We analyzed the sICAM-1 concentrations and investigated whether or not the serum levels of these adhesion molecules in the peripheral venous blood could help predict the clinical staging in patients with NSCLC. METHODS: From January to December 1999, 66 patients (79.5%) underwent either a lobectomy or a pneumonectomy with a mediastinal lymph node dissection at the National Sanatorium Nishi-Gunma Hospital. RESULTS: The sICAM-1 concentration in the NSCLC patients was a mean value of 212.0+/-106.6 ng/ml. In contrast, the concentration of sICAM-1 in 20 healthy controls was a mean value of 117.9+/-64.1 ng/ml. In patients with NSCLC, the sICAM-1 concentrations were significantly higher than in the normal control group (p=0.002). In addition, the difference in the serum concentrations was significant between the patients with T1 and T2 disease (p=0.042), and N0 and N2 patients (p=0.042). No significant differences were observed in aging, smoking history, histological type, or pathological staging. CONCLUSIONS: The sICAM-1 concentrations in lung cancer patients are thus suggested to play a role in staging, and may also serve as a useful indicator of advanced disease.

[Clinical study of synchronous multiple primary lung cancers; problems in diagnosis and treatment].

We evaluated retrospectively 33 patients with synchronous multiple primary lung cancers. These were 20 men and 13 women, with a mean age of 67 years (range, 51-79 years). In 27 cases, the tumors were located in the ipsilateral lung, and in 6 cases, they were in the bilateral lung. In patients with synchronous multiple primary lung cancers, combinations of adenocarcinoma and adenocarcinoma (12 cases, 36.4%), adenocarcinoma and others (6 cases, 18.2%) were most commonly observed histologically. Lobectomy was performed in 18, bi-lobectomy in 3, pneumonectomy in 4, lobectomy with partial resection in 6, and lobectomy with laser therapy or irradiation in 2 patients. Overall 5-year survival rate of this disease was 78.3%. Eight patients died within 1 year after surgical resection, and 2 of them died of treatment-related accident. Although optimal treatment of choice for synchronous multiple primary lung cancers remains an unresolved problem, we think that careful planning of the treatment for this disease including selection of surgical methods is much important.

Percutaneous ulnar artery approach for coronary angiography: a preliminary report in nine patients.

The radial artery approach is becoming more popular for diagnostic cardiac catheterization and interventional procedures because of its lower incidence of access site complications and decreased patient discomfort after the procedure. However, Allen's test reveals inadequate blood supply through the ulnar artery to the hand, and therefore the approach does not seem to be suitable in 10%-30% of patients. Here we demonstrated a new percutaneous ulnar artery approach for coronary angiography in nine patients. We succeeded in obtaining an entry site into the left ulnar artery in seven patients. The average time for cannulation and that for catheterization procedure were comparable with those of the radial approach previously reported from other laboratories. Complications such as bleeding, loss of an ulnar pulse, ulnar nerve injury, and the formation of an aneurysm or fistula were not observed in any patient. The ulnar approach may be another technique that decreases patient discomfort and risk, while preserving the radial artery as a potential coronary bypass graft for surgical myocardial revascularization. Cathet Cardiovasc Intervent 2001;53:410-414.

Extralobar pulmonary sequestration in the posterior mediastinum.

Extralobar pulmonary sequestration was incidentally detected in a 65-year-old man. Preoperatively, the lesion presented as a posterior mediastinal mass. At operation the mass was found to be attached to the paravertebral region at the level of the seventh thoracic vertebra by a feeding artery originating from the descending aorta. Only two cases of extralobar pulmonary sequestration in the posterior mediastinum have been previously reported.

Mediastinal lymph node evaluation by computed tomographic scan in lung cancer.

BACKGROUND: Computed tomography (CT) has been widely used for preoperative mediastinal lymph node evaluation in lung cancer. But its accuracy has remained controversial. We studied the predictability of N-staging by CT scan. METHODS: From 1981 to 1996, 546 patients had preoperative CT scan and underwent a surgical resection with mediastinal lymph node dissection for primary pulmonary adenocarcinoma and squamous cell carcinoma. Nodes larger than 1.0 cm at short axis were considered abnormal. The discrepancy between clinical and pathologic findings in N factor was analyzed. RESULTS: Sensitivity (ST), specificity (SP) and accuracy (AC) were 33.0%, 90.4% and 78.9%, respectively. No statistically significant difference in the results is detected for individual years or types of scanning device. There were statistically significant differences as follows: ST and SP by histologic type, SP by gender, SP and AC by tumor size, SP by Brinkman index, ST by tumor location, and AC by serum CEA value. CONCLUSIONS: We should pay attention to false positive nodes in heavy smokers (or males), and positive nodes in adenocarcinoma, tumor larger than 3 cm or rising of serum CEA value, regardless of negative lymph node on CT scan.

Video-assisted thoracic surgery (VATS) in a patient with impaired pulmonary function.

A 72-year-old woman successfully underwent thoracoscopic wedge resection of the lung with the assistance of a minithoracotomy. Poor pulmonary function made her a high-risk operative candidate. Video-assisted thoracic surgery with the assistance of minithoracotomy may be the treatment of choice for high-risk patients with a peripheral pulmonary nodule.

A case of esophageal sarcomatoid carcinoma with molecular evidence of a monoclonal origin.

A case of polypoid tumor of the esophagus consisting of a sarcomatous tumor partly covered with superficial squamous cell carcinoma is described. The sarcomatous component consisted of anaplastic spindle and pleomorphic tumor cells that mimicked malignant fibrous histiocytoma (MFH). Both the sarcomatous and carcinomatous components were positive for p53 immunohistochemically. Further molecular analysis revealed that the two components had the same somatic mutation in the p53 gene. These results suggest a monoclonal origin of this biphasic tumor.