A Novel Urine Test Biosensor Platform for Early Lung Cancer Detection.

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection is essential to achieving a better outcome and prognosis. Volatile organic compounds (VOCs) reflect alterations in the pathophysiology and body metabolism processes, as shown in various types of cancers. The biosensor platform (BSP) urine test uses animals' unique, proficient, and accurate ability to scent lung cancer VOCs. The BSP is a testing platform for the binary (negative/positive) recognition of the signature VOCs of lung cancer by trained and qualified Long-Evans rats as biosensors (BSs). The results of the current double-blind study show high accuracy in lung cancer VOC recognition, with 93% sensitivity and 91% specificity. The BSP test is safe, rapid, objective and can be performed repetitively, enabling periodic cancer monitoring as well as an aid to existing diagnostic methods. The future implementation of such urine tests as routine screening and monitoring tools has the potential to significantly increase detection rate as well as curability rates with lower healthcare expenditure. This paper offers a first instructive clinical platform utilizing VOC's in urine for detection of lung cancer using the innovative BSP to deal with the pressing need for an early lung cancer detection test tool.

Comparison of early postoperative cytokine changes in patients undergoing intubated and non-intubated thoracic surgery: a randomized controlled trial.

OBJECTIVES: The inflammatory response after surgery is associated with patient prognosis. Patients who undergo thoracic surgery exhibit a profound systemic inflammatory response due to the surgical procedures used and application of one-lung ventilation. The aim of this study was to compare perioperative inflammatory changes in patients after intubated and non-intubated thoracic surgery for primary lung cancer resection. METHODS: This prospective randomized controlled study included forty patients who underwent surgical resection for stage I non-small-cell lung cancer. Blood samples for cytokine analysis were collected just before induction, at 1 and 24 h after surgery. Levels of the pro-inflammatory cytokine and anti-inflammatory cytokines were measured using quantitative sandwich enzyme immunoassay kits. RESULTS: The basal values of cytokines were comparable between 2 groups. Within each group, the postoperative levels of interleukin (IL)-1, IL-6 and tumour necrosis factor-α increased, while those of IL-4 and IL-10 did not change significantly. The levels of IL-6 and tumour necrosis factor-α were significantly lower in group NI at 1 and 24 h postoperatively. Other cytokines did not differ in both groups during postoperative period. The IL-6/IL-10 ratio at 1 h after surgery was lower in non-intubated patients than in intubated patients, but there was no difference at 24 h after surgery. CONCLUSIONS: Non-intubated thoracic surgery may attenuate the early inflammatory cytokine changes following major resection for primary lung cancer compared with intubated conventional surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT04007354.

KIF5B-RET Fusion gene may coincide oncogenic mutations of EGFR or KRAS gene in lung adenocarcinomas.

BACKGROUND: The KIF5B-RET rearrangement is detected with the frequency of 1 ~ 2% in 'triple marker'-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type. These mutational changes are known to be mutually exclusive, but the co-existence of ALK rearrangement with activating mutations of EGFR is rarely found. METHODS: We examined the KIF5B-RET fusion gene in frozen tissues from 154 surgically resected lung tumors using RT-PCR with direct sequencing and the mutation status of EGFR and KRAS genes using PNA clamping. We tested KIF5B-RET translocation in Formalin Fixed Paraffin Embedded using fluorescence in situ hybridization. We also measured RET mRNA and protein expression by RT-PCR and immunohistochemistry, respectively. RESULTS: The existence of KIF5B-RET fusion gene was identified in 9 patients. The mean age was 67.2 and M: F ratio 4:5. Of 9 patients, 3 patients harbored wild type of EGFR and KRAS gene. However, KIF5B-RET fusion gene coincided with EGFR or KRAS mutation in 6 patients. These six pts were also positive for both RET break-apart probes (23.9%) and KIF5B-RET fusion (44.4%). However, there were no correlations between RET mRNA and protein expression in the KIF5B-RET-positive patients. The median disease free survival and overall survival were 23.9 months and 29.5 months, respectively. CONCLUSIONS: Taken together, our data suggest one-step screening platform for KIF5B-RET as well as EGFR, K-RAS, ALK oncogenic mutations be necessary for lung adenocarcinoma patients because EGFR or KRAS mutation are not infrequently found in KIF5B-RET-positive patients.

How early can we repair pectus excavatum: the earlier the better?

OBJECTIVES: The optimal age for the repair of pectus excavatum using minimally invasive technique has yet to be determined. We hypothesized that the early repair of pectus excavatum may contribute in preserving chest wall integrity and also in enhancing patients' growth. The purpose of our present study was to verify a potential advantage of the early repair of pectus excavatum by using a minimally invasive technique. METHODS: For our study on minimally invasive pectus excavatum repair, 1571 patients from the period 1999 to 2011 were enrolled. Our strategy was to carry out routine repairs in patients older than 3 years of age. To examine the age factor on the results of the repairs the patients were divided into different age groups: Group 1 (≤ 5 years, 618 (39.3%)), Group 2 (6-11 years, 322 (20.5%)), Group 3 (12-20 years, 401 (25.5%)) and Group 4 (>20 years, 230 (14.6%)). A comparative analysis was performed for factors such as complication rates; growth-percentile scores of height, weight and body mass index (BMI); incidence of asymmetry and costal flare score to determine the potential to resume the normal chest wall conformation by earlier repair. RESULTS: The mean age of the patients was 10.2 years (16 months to 51 years). The incidence of asymmetry was found to be lowest in Group 1 (24.3, 45.5, 58.7, 48.4%, respectively, P < 0.001). The complication rate after repair was also lowest in Group 1 (7.6, 11.5, 16.3, 19.1%, respectively, P < 0.001). The growth of body weight was significant in Groups 1 and 2 (0.53 ± 1.02, P < 0.001). The costal flare score was found to have decreased in Groups 1 and 2 (Group 1: from 1.6 to 0.12, P < 0.001; Group 2: from 1.44 to 0.14, P < 0.001). In Groups 3 and 4, there was no improvement in costal flare after repair. CONCLUSIONS: Our results suggest that routine early repair of pectus excavatum in patients older than 3 years of age is safe and effective. We would recommend early repair to avoid asymmetry transformation of the deformity and to enhance the patients' growth potential.

Endoscopic cryotherapy of lung and bronchial tumors: a systematic review.

BACKGROUND/AIMS: We made a systematic review and evaluation of endoscopic cryotherapy of endobronchial tumors, investigating safety and efficacy. METHODS: Qualified studies regarding endoscopic cryotherapy of lung tumors were systemically evaluated using available databases according to predefined criteria. RESULTS: In total, 16 publications were included in the final assessment. A narrative synthesis was performed because a formal meta-analysis was not viable due to the lack of controlled studies and study heterogeneity. Overall success rates for significant recanalization of the obstruction were approximately 80%, although they varied, depending on disease status in the patient population. Complications from the procedure developed in 0-11.1% of cases, most of which were minor and controlled by conservative management. Although limited data were available on comprehensive functional assessment, some studies showed that respiratory symptoms, pulmonary function tests, and performance status were significantly improved. CONCLUSIONS: Endoscopic cryotherapy was found to be a safe and useful procedure in the management of endobronchial tumors although its efficacy and appropriate indications have yet to be determined in well-designed controlled studies.

Diffuse Alveolar Hemorrhage in a 39-year-old Woman: Unusual Initial Presentation of Microscopic Polyangiitis.

Microscopic polyangiitis (MPA) is a necrotizing vasculitis involving the small vessels without granulomatous inflammation. Most MPA initially presents with renal involvement without pulmonary involvement. Isolated and initially presenting alveolar hemorrhage is very rare. The patient was a 39-year-old female with a progressive cough, dyspnea, and blood-tinged sputum for the previous 5 days. We determined that her condition was MPA though VATS lung biopsy and renal biopsy. After 2 months of steroid therapy, the chest lesions had improved. We report here a rare case of MPA with isolated and initial involvement of the lung with a review of the literature.

Outcome of limited resection for lung cancer.

BACKGROUND: Up to now, lobectomy, bilobectomy and pneumonectomy combined with extensive lymph node dissection have been regarded as the standard procedures for non-small cell lung cancer (NSCLC). In high-risk patients, however, limited resection (LR) has been attempted as a salvage procedure, and, recently, indication for LR has been extended to selected cases with early-stage NSCLC. MATERIAL AND METHODS: Among the 773 patients who underwent surgical procedures for NSCLC in Seoul National University Bundang Hospital from May 2003 to December 2008, 43 patients received LR. Medical records of these patients were retrospectively reviewed. RESULTS: Mean age at operation was 66.0±12.4 years, and there were 30 males. Twenty-five patients underwent conservative limited resection (CLR) and 18 underwent intentional limited resection (ILR). Indications for CLR were multiple primary lung cancer in 9 (9/25, 36%) and severe concomitant diseases in 5 (5/25, 20%). Of these, 6 patients underwent segmentectomy and 19 received wedge resection. During the follow-up period of 28.0±17.8 months, 15 patient developed recurrent lung cancer. ILR was selectively performed in lesions almost purely composed of ground glass opacity (≥95%), or in small solid lesions (≤2 cm). Of these, 11 patients underwent segmentectomy and 7 underwent wedge resection. During the follow-up period of 31.7±11.6 months, no patient developed recurrence. CONCLUSION: Intermediate-term outcome of LR for early-stage lung cancer is comparable to that of standard operation. For the delineation of the indications and appropriate surgical techniques for LR, prospective randomized multi-institutional study may be expedient.

CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification.

INTRODUCTION: Metastasis-associated protein CD24 has been identified as a new prognostic factor and stem cell marker in the human neoplasm. However, the importance of the CD24 in non-small cell lung carcinomas (NSCLCs) has not been elucidated well. METHODS: We evaluated CD24 expression in 267 consecutive cases of NSCLC by immunohistochemistry using a tissue microarray technique and correlated with clinicopathologic parameters including forthcoming (seventh) new tumor node metastasis classification. RESULTS: CD24-high expression was demonstrated in 87 of 267 (33%) and was associated with adenocarcinoma (ADC) histology than in squamous cell carcinoma histology (64 of 165 [39%] vs. 20 of 88 [23%]; p = 0.023). Patients with CD24-high tumors tended to have a higher risk of disease progression (p < 0.001) and cancer-related death (p = 0.002). Multivariate analysis proved CD24-high expression as independent prognostic factors of disease progression and cancer-related death (p = 0.002, hazard ratio = 1.78, 95% confidence interval = 1.23-2.58 and p = 0.017, hazard ratio = 1.93, 95% confidence interval =1.13-3.31). CD24-high expression had a tendency to correlate with new pathologic stage (p-stage) (p = 0.089) rather than old p-stage (p = 0.253). Performance status and new p-stage, regardless of the tumor histology, were identified as consistent independent prognostic factors of disease progression and cancer-related death. However, age was related to a significantly shorter cancer-specific survival in ADC only. CONCLUSIONS: CD24 expression in NSCLC is associated with ADC histology and disease progression and cancer-related death, indicative of aggressive tumor behavior. Performance status and new p-stage, to a lesser extent, age correlated with progression-free survival and cancer-specific survival, regardless of tumor histology.

Clinical impact of computerised tomographic angiography performed for preoperative evaluation before coronary artery bypass grafting.

OBJECTIVE: In our institution, computerised tomographic (CT) angiography has been performed as a near-routine test before coronary artery bypass grafting (CABG) to evaluate the aorta and its branches. We aimed to determine its impact on operative procedure and perioperative management. METHODS: From January 2006 through December 2008, neck-to-leg systemic arteries were evaluated by 64-slice multidetector CT scan in 284 patients before CABG. For them, medical records and cardiac surgery database were retrospectively reviewed to investigate the incidence of pathologic lesions of the aorta and its major branches, other incidental lesions and procedure- or management-related decision affected by CT angiography. RESULTS: In 36 patients (12.7%), cannulation and clamping of the ascending aorta were thought too dangerous because of severe atherosclerotic change. The use of cardiopulmonary bypass was inevitable in 10 of them, and postoperative mortality rate was significantly higher (3/10, 30%) than in the remaining patients (2/274, 0.7%). Conduit selection or grafting strategy was changed due to severe left subclavian artery stenosis or leg vein varicosity in 18 patients (6.3%). For the following problems, surgical interventions were performed in 34 patients (12.0%) concomitantly or during the same admission with CABG; > or = 90% stenosis in carotid (5.6%), iliofemoral (11.6%) or renal (4.6%) arteries, aortic aneurysm (14.4%, six of them met surgical indication) and incidental malignant neoplasm (2.8%). Counting all of the above, preoperative CT angiography affected risk assessment, CABG procedure itself, perioperative management or follow-up plan in 142 patients (50%). CONCLUSIONS: Because preoperative CT angiography considerably affected management in one half of patients, we recommend its use as a routine test before CABG, unless contraindicated.

High MET gene copy number leads to shorter survival in patients with non-small cell lung cancer.

INTRODUCTION: Activation of MET, either by increased gene copy number (GCN) or mutation, has been detected in various cancers. We investigate the clinicopathologic features of MET gene copy in nonsmall cell lung cancer (NSCLC). METHODS: Tumor tissues were obtained from 180 resected NSCLCs, including 97 squamous cell carcinomas (SCCs) and 72 adenocarcinomas. No patient received epidermal growth factor receptor (EGFR)-targeted therapy. EGFR and MET GCNs were studied using fluorescence in situ hybridization (FISH) and were estimated according to the University of Colorado Cancer Center (UCCC) criteria. For MET, we also assessed GCNs using the Cappuzzo system. RESULTS: FISH-positive MET was observed in 16.7% using the UCCC criteria; specifically, amplification was seen in 3.9% and high polysomy in 12.8%. FISH-positive MET status was significantly correlated with FISH-positive EGFR (p = 0.003). In the Cappuzzo system, high MET GCN (mean, >/=5 copies/cell) was found in 6.7% and also associated with FISH-positive EGFR (p = 0.031). MET gene copy status was not associated with gender, smoking history, histology, or stage. However, true MET amplification was more frequent in patients with SCC than in those with adenocarcinoma. FISH-positive MET status predicted worse survival in patients with NSCLC at advanced stages (p = 0.034) and in patients with SCC (p = 0.028). In multivariate analyses, increased MET GCN was significantly associated with shorter survival in patients with SCC, as analyzed using both the UCCC and Cappuzzo criteria (p = 0.019 and 0.008). CONCLUSIONS: Our results suggest that increased MET GCN would be an independent poor prognostic factor in SCC of the lung.

Protein overexpression and gene amplification of epidermal growth factor receptor in nonsmall cell lung carcinomas: Comparison of four commercially available antibodies by immunohistochemistry and fluorescence in situ hybridization study.

Epidermal growth factor receptor (EGFR) overexpression in nonsmall cell lung carcinomas (NSCLC) is variable ranging from 19% to 89% and its prognostic value remains controversial. We tried to investigate (1) EGFR protein expression using four different antibodies, (2) the correlation between protein overexpression and EGFR gene amplification, and (3) the correlation between EGFR genetic status and clinicopathologic features in NSCLC. We examined EGFR protein expression using four different antibodies including Zymed EGFR kit (Clone 31G7), Dako EGFR pharmDx kit (Clone 2-18C9), Dako (Clone H11) and Novocastra (Clone EGFR 113) by immunohistochemical analysis. The protein overexpression was compared to gene amplification status by fluorescence in situ hybridization (FISH). EGFR protein overexpression was observed in 56% of tumors with Zymed EGFR kit, in 51% with Dako EGFR pharmDx kit, in 5% with Dako and in 18% with Novocastra (p=0.010). Both Zymed and Dako pharmDx kit were more sensitive than the Dako test (clone H11) and Novocastra clone EGFR 113. EGFR overexpression was more prominent in squamous cell carcinomas (SCC) than adenocarcinomas (ADC) (71% vs. 48%, p=0.001 with Zymed, 61% vs. 45%, p=0.011 with Dako pharmDx kit; respectively). EGFR FISH-positivity as represented by high polysomy and gene amplification was observed in 45% of the NSCLC patients. Protein expression levels significantly correlated with the gene copy number per tumor cell (p<0.001). Our data showed a higher percentage of positive cells detected by Zymed and Dako pharmDx tests. The EGFR protein overexpression rate varied from 4% to 72% according to different antibody clones and histologic types. EGFR protein expression detected by Zymed and Dako pharmDx was significantly associated with a high EGFR gene copy number.

The prognostic significance of ERCC1, BRCA1, XRCC1, and betaIII-tubulin expression in patients with non-small cell lung cancer treated by platinum- and taxane-based neoadjuvant chemotherapy and surgical resection.

OBJECTIVES: The DNA repair pathway and isotype composition of beta-tubulin are known to be associated with resistance to platinum- and taxane-based chemotherapy, respectively. The aim of this study was to identify the clinical significance of excision repair cross-complementation 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), X-ray repair cross-complementation 1 (XRCC1) and betaIII-tubulin on the chemotherapy response and overall survival in patients with non-small cell lung cancer (NSCLC) who received neoadjuvant chemotherapy. METHODS: Protein expression profiles were evaluated by immunohistochemistry on surgical specimens of 82 NSCLC patients who underwent platinum- and taxane-based neoadjuvant chemotherapy. The expression levels of proteins were measured semi-quantitatively and the correlation with tumor responses, pathologic cell death rate and survival were evaluated. RESULTS: There were 73 (89.0%) clinical stage III patients. Lobectomy, bilobectomy, and pneumonectomy were performed in 54 (65.0%), 11 (13.4%), and 17 (20.7%) patients, respectively. There was no correlation between clinical response and protein expression. The expression levels of ERCC1, BRCA1, and XRCC1 increased proportionally to the cell death rate (p<0.05); however, betaIII-tubulin expression did not correlate with cell viability. Multivariate analysis demonstrated that early pathologic stage, adjuvant chemotherapy, high ERCC1 and low betaIII-tubulin expression were good prognostic factors for overall survival (p<0.05). CONCLUSIONS: The inverse correlation between DNA repair proteins and cell viability suggests that these protein expression levels can be markers for chemotherapy responsiveness. However, only ERCC1 and betaIII-tubulin were prognostic factors after platinum- and taxane-based neoadjuvant chemotherapy following surgical resection.

Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread.

INTRODUCTION: No standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread. METHODS: Twenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18-21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients. RESULTS: High frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change. CONCLUSIONS: This study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO.

Differences in the expression profiles of excision repair crosscomplementation group 1, x-ray repair crosscomplementation group 1, and betaIII-tubulin between primary non-small cell lung cancer and metastatic lymph nodes and the significance in mid-term survival.

INTRODUCTION: This study aimed to compare the expression profiles of excision repair crosscomplementation group 1 (ERCC1), x-ray repair crosscomplementation group 1 (XRCC1), and betaIII-tubulin between patients with primary non-small cell lung cancer (NSCLC) and those with metastatic lymph nodes and to identify the prognostic significance of each chemotherapy resistance protein. MATERIALS: Those who met the inclusion criteria were patients (1) with NSCLC, (2) with metastatic lymph nodes (N1 or N2), and (3) who underwent surgical resection followed by platinum-based adjuvant chemotherapy. A total of 82 patients were included in the study. The expression profile of each protein was evaluated by immunohistochemistry and compared according to tumor location. RESULTS: The mean age of the patients was 57.5 +/- 8.4 years. There were 30 N1 and 52 N2 patients. ERCC1 expression was upregulated in 55% and downregulated in 8% of metastatic lymph nodes, when compared with primary tumors (p < 0.05). XRCC1 was also upregulated in 56% and downregulated in 6% (p < 0.05). However, betaIII-tubulin was upregulated in 12% and downregulated in 45% of patients (p < 0.05). betaIII-tubulin expression in metastatic lymph nodes was greater in patients with adenocarcinoma than other cell types. Upregulation of ERCC1 in metastatic lymph nodes was a poor prognostic factor in N1 patients but not in N2 patients. CONCLUSIONS: Significant changes in the expression profile of each protein were observed in metastatic lymph nodes. The resistance protein-guided treatment should be performed after integrative interpretation of expression profiles of each protein in both primary and metastatic sites.

Additional mechanical pleurodesis after thoracoscopic wedge resection and covering procedure for primary spontaneous pneumothorax.

BACKGROUND: Additional mechanical pleurodesis for the treatment of primary spontaneous pneumothorax (PSP) is believed to reduce the recurrence of PSP, and a covering procedure with absorbable mesh also shows comparable results. This study was conducted to determine whether additional mechanical pleurodesis would be effective in reducing recurrence after thoracoscopic wedge resection and covering procedure. MATERIALS AND METHODS: Between May 2003 and August 2005, 99 patients underwent thoracoscopic bullectomy with staple line covering with absorbable cellulose mesh and fibrin glue followed by an additional mechanical pleurodesis. These patients were compared with 98 patients who underwent thoracoscopic bullectomy with staple line coverage alone. RESULTS: The additional mechanical pleurodesis group had findings comparable to those of the coverage group for duration of postoperative chest drainage, length of hospital stay, and complication rate. After median follow-up of 29.2 months, postoperative recurrence occurred in four patients (4.0%). CONCLUSIONS: Additional mechanical pleurodesis after covering procedure is also effective in decreasing postoperative recurrence of PSP.

Risk of recurrence in surgically resected stage I adenocarcinoma of the lung: histopathologic and immunohistochemical analysis.

STUDY OBJECTIVES: Stage I adenocarcinoma of the lung is the most common type of lung cancer. A better understanding of the histopathology and molecular biology of lung cancer might improve the capability to predict the outcome for any individual patient. The purpose of this study was to evaluate several histopathologic and molecular markers in order to assess their prognostic value in stage I adenocarcinoma. METHODS: Fifty-five patients at the Seoul National University Bundang Hospital were enrolled in the study. Histopathologic factors and molecular markers were selected. RESULTS: Multivariate analysis demonstrated that necrosis, lymphatic vessel invasion, E-cadherin, p53, and Ki-67 emerged as independent prognostic factors of recurrence. When patients were grouped according to low or high risk according to the number of factors involved, the difference in disease-free survival between these groups was statistically significant. CONCLUSIONS: In resected stage I adenocarcinoma, necrosis, lymphatic vessel invasion, E-cadherin, and p53 have been identified as independent predictors of disease-free survival.

The impact of multiple metastatic nodal stations on survival in patients with resectable N1 and N2 nonsmall-cell lung cancer.

BACKGROUND: The aim of the study was to identify common prognostic factors in nonsmall-cell lung cancer (NSCLC) with N1 and N2 nodal involvement. METHODS: A retrospective review of NSCLC patients who underwent primary surgical resection without neoadjuvant chemotherapy was performed. In all, 280 patients were included in this study, and there were 132 patients with N1 disease (N1 group) and 148 patients with N2 disease (N2 group). The median follow-up period was 26 months, and complete follow-up was possible in 269 patients (96%). RESULTS: Lobectomy was performed in 194 patients (69%), bilobectomy was performed in 43 (15%), and pneumonectomy was performed in 43 (15%). Complete resection was possible in 273 patients (98%), and operative death occurred in 5 patients (2%). The overall and disease-free 5-year survival rates were 63% and 55%, respectively, in the N1 group, and 44% and 32%, respectively, in the N2 group (p < 0.05). The prognostic factors for overall survival in both the N1 and N2 groups were age and the number of metastatic nodal stations; however, N2 metastasis was not a significant prognostic factor in the multivariate analysis. The poor prognosis of the patients in the N2 group was due to the greater incidence of multiple node involvement in comparison with the N1 group (73% versus 15%; p < 0.05). CONCLUSIONS: Multiple metastatic nodal stations was the common prognostic factor in resectable NSCLC patients with nodal metastasis, and mediastinal nodal involvement was associated with a higher chance of multiple-station metastasis in this study.

Difficulties in diagnosis and management of ectopic Cushing syndrome.

A 18-year-old man presented to a local hospital with muscle weakness, facial edema, and a 6 kg weight gain over 2 months. After a complete work-up, he was diagnosed with pituitary Cushing syndrome and treated with a bilateral adrenalectomy for Cushing syndrome and pituitary radiotherapy for Nelson syndrome. Twenty-five years later, his ectopic source of adrenocorticotropic hormone was revealed as a pulmonary neuroendocrine tumor, and a pulmonary resection was performed. Subsequently, a biochemical and clinical remission including hyperpigmentation was achieved.

Surgical treatment of malignant mediastinal nonseminomatous germ cell tumor.

BACKGROUND: The aim of this study was to evaluate the role of surgical treatment for mediastinal nonseminomatous germ cell tumors (MNSGCT) and identify the factors of long-term survival. METHODS: A retrospective review of the medical records of patients with primary MNSGCT who registered at our institute between 1988 and 2005 was performed. Of 29 patients who presented with primary MNSGCT, 21 patients (72.4%) underwent curative resection and were included in this study. RESULTS: All patients were male and symptomatic at presentation. Mean patient age was 24.4 years (range, 9 to 53 years). Three different regimens were used for preoperative chemotherapy, and 14 patients (66.7%) achieved partial response, 4 (19.0%) had stable disease, and 2 (9.5%) had progressive disease. Complete en bloc excision was possible in 16 patients (76.2%). The most common cause of incomplete resection was great vessel invasion (n = 3). Concomitantly resected organs were lung in 13 patients (61.9%) and superior vena cava in 5 (23.8%). Viable germ cell tumor was identified in pathology specimens in 12 (57.1%), total necrosis in 7 (33.3%), and remnant teratoma in 2 (9.5%). Five-year overall and disease-free survivals were 63.6% and 61.1%. Risk factors for poor overall survival by multivariate analysis were beta-human chorionic gonadotrophin (beta-HCG) elevation at initial diagnosis (p = 0.02) and incomplete resection (p = 0.002). CONCLUSIONS: Surgical resection of MNSGCT after chemotherapy showed favorable long-term survival. Complete resection should be performed to achieve long-term survival. An elevated beta-HCG level at initial diagnosis was associated with a poor prognosis despite multimodality therapy.