New technique to prevent prolonged air leak: use of 'Tachosuture' technique.

Prolonged air leak (defined as air leak >7 days), caused by pulmonary resection or alveolar-pleural fistula, increases postoperative morbidity, prolongs hospital stay and increases healthcare costs. We describe a new technique ('Tachosuture' technique) to prevent prolonged air leak. The key point of this new technique is that air leak is classified into three types and an absorbable suture is added to a TachoSil® patch in each type to prevent detachment from the lung parenchyma. Between August 2013 and March 2016, 40 patients underwent thoracoscopic surgery using 'Tachosuture' technique. Postoperative air leak always stopped within 3 days (95% confidence interval for the absence of prolonged air leak: 92.5-100%). It is considered that this simple technique is useful to prevent prolonged air leak.

Solitary lung metastasis from gestational choriocarcinoma resected six years after hydatidiform mole: A case report.

INTRODUCTION: Recently, the opportunity to encounter lung metastasis from choriocarcinoma has become very rare for thoracic surgeons, since chemotherapy works very well and the operative indications for lung metastasis are limited. PRESENTATION OF CASE: A 45-year-old woman with a past history of hydatidiform mole six years previously was found to have a nodulous chest shadow in the right middle lung field on a chest radiography. She was also suspected of having an ovarian tumor and underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. No malignancy was detected in the ovaries or uterus. A thoracoscopic partial pulmonary resection was then performed for the right lower lung nodule. The pathological diagnosis was choriocarcinoma. Her preoperative serum beta-human chorionic gonadotropin value was high (482.8mIU/mL). Thus, she was diagnosed as having a pulmonary metastasis from gestational choriocarcinoma arising six years after a complete hydatidiform mole. DISCUSSION: The possibility of choriocarcinoma arising as a solitary lung tumor should be considered regardless of the interval from the preceding molar pregnancy. The patient's medical history and high concentration of ß-hCG in preoperative residual serum were helpful in arriving at a diagnosis of metastatic gestational CCA. CONCLUSION: We presented pulmonary metastasectomy for very unique and rare metastatic choriocarcinoma arising six years after hydatidiform mole.

Long-term progress of six cases of malignant peripheral nerve sheath tumors of the mediastinum that underwent surgical treatment: Case report series.

INTRODUCTION: Malignant Peripheral Nerve Sheath Tumor is a rare type of soft tissue malignant tumor that occurs in only 5% of cases. It tends to occur in the arms and legs and trunk of the body, with mediastinal occurrence in only a few cases. Among mediastinal tumors, only 18.8% occur primarily in the nerves, and of these, only 10.3% are malignant, with very few reports indicating the long-term progress of patients with MPNST of the mediastinum. CASE PRESENTATION: We studied six cases of mediastinal primary malignant peripheral nerve sheath tumors in which surgery was carried out at this Center between 1977 and 2000. Four of the cases were men and two were women. The period of observation was between 14 and 277 months and the median follow-up time was 119.5 months. The tumors were contained in a membrane and completely excisable in three cases, with the patient demonstrating long-term survival with no recurrence in each case. The remaining three cases were not completely excisable due to invasion into the aorta. In two cases, the patients were treated post-surgically with chemotherapy; however, in all three cases the patient died as a result of the original condition. DISCUSSION AND CONCLUSIONS: Nerve sheath tumors localized within the membrane offer good long-term prognosis even if malignant. Furthermore, long-term survival is possible even if the tumor has invaded neighboring organs, provided it can be completely excised. In cases where complete excision is difficult, a multidisciplinary approach including radiotherapy and anti-cancer drug treatment may contribute to improved prognosis but this is a subject that requires further study.

Dual outline of navigating utensil in thoracoscopic segmentectomy: a new method.

Thoracoscopic segmentectomy requires an adequate surgical margin; however, only a few reports have described the procedure of how to maintain a constant distance from the tumour. We here suggest a novel simple method to secure an adequate surgical margin: the dual outline of navigating utensil in thoracoscopic segmentectomy (DONUTS) method. We used a DONUTS indicator sheet produced from a 1.5-mm thick absorbed sheet with a proper diameter to secure an adequate surgical margin. The indicator sheet, which was affixed to the pleura, indicated a new resection line. With this new line, an additional excision was performed in addition to conventional segmentectomy. The clinical records of 9 patients who underwent treatment with the DONUTS method between August 2011 and December 2013 were retrospectively reviewed. No postoperative complications of loco-regional recurrence were observed over a mean period of 20.3 months.

Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma.

The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA(-)/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA(-)/SOX2(+) classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

Down-regulation of SIX3 is associated with clinical outcome in lung adenocarcinoma.

BACKGROUND: Lung cancer is a common cancer and the leading cause of cancer-related death worldwide. SIX3 is a human homologue of the highly conserved sine oculis gene family essential during embryonic development in vertebrates, and encodes a homeo-domain containing transcription factor. Little is known about the role of SIX3 in human tumorigenesis. This study is to assess the expression/function of SIX3 and the significance of SIX3 as a prognostic biomarker in lung adenocarcinoma. METHODS: Quantitative real-time RT-PCR was used to analyze SIX3 mRNA expression and quantitative methylation specific PCR (MSP) was used to examine promoter methylation. MTS and colony formation assays were performed to examine cell proliferation. Wound healing assays were used to assess cell migration, and microarrays were utilized to examine genes regulated by SIX3 in lung cancer cells. Association of SIX3 expression levels with clinical outcomes of patients with lung adenocarcinoma was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. RESULTS: SIX3 was down-regulated in lung adenocarcinoma tissues compared to their matched adjacent normal tissues, and this down-regulation was associated with methylation of the SIX3 promoter. SIX3 was also methylation-silenced in lung cancer cell lines. Restoration of SIX3 in lung cancer cells lacking endogenous SIX3 suppressed cell proliferation and migration, and downregulated a number of genes involved in proliferation and metastasis such as S100P, TGFB3, GINS3 and BAG1. Moreover, SIX3 mRNA expression was associated with significantly improved overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients and patients with bronchioloalveolar carcinoma (BAC) features. CONCLUSIONS: SIX3 may play an important role as a novel suppressor in human lung cancer. SIX3 has potential as a novel prognostic biomarker for patients with lung adenocarcinomas.

Descending necrotizing mediastinitis associated with Lactobacillus plantarum.

BACKGROUND: Descending necrotizing mediastinitis (DNM), a severe infection with a high fatality rate, develops in mediastinal spaces due mainly to deep cervical abscesses. The majority of causative microbes of DNM are Streptococci and oral anaerobes. DNM associated with Lactobacillus-infection is rather rare. CASE PRESENTATION: A 69-year-old male with an unremarkable past medical history was referred to our hospital for surgical resection of advanced laryngeal cancer. Full examination revealed a neck abscess and DNM with a background of untreated diabetes mellitus. Initially, he was treated with meropenem. However, Lactobacillus plantarum was isolated from surgical drainage of a mediastinal abscess. Despite using antibiotics capable of eradicating all isolates with susceptibilities not differing significantly from those of the neck and mediastinal abscesses, we attributed DNM to the L. plantarum detected only in the mediastinal abscess. After DNM treatment, he underwent total pharyngolaryngectomy with bilateral neck dissection followed by reconstruction using free jejunum. He was discharged fully recovered. CONCLUSION: We concluded that L. plantarum as the sole cause of the mediastinal abscess in the present case cannot be ruled out. As the number of immunocompromised patients increases, we should be cautious regarding this "familiar" microbe.

Thoracoscopic surgery for non-small-cell lung cancer: elderly vs. octogenarians.

BACKGROUND: Octogenarians are rarely referred for surgical treatment of lung cancer owing to the morbidity and mortality of pulmonary resection, their frailty, and limited lifespan. We reviewed the results of thoracoscopic surgery, performed completely under the monitor, for treatment of primary non-small-cell lung cancer in octogenarians, and compared them with those in elderly patients. PATIENTS AND METHODS: Between September 25, 2002 and August 25, 2011, a retrospective database of 24 octogenarians and 70 elderly patients (age range, 75-79 years) who underwent thoracoscopic surgery for treatment of primary non-small-cell lung cancer were reviewed. Demographic, histopathologic, preoperative, perioperative, postoperative, outcome variables, and survival were assessed. RESULTS: In the octogenarian group, 29% had postoperative respiratory complications, 4% had postoperative cardiac complications, operative mortality was 4%, the recurrence rate was 8%, and the postsurgical 5-year survival rate was 74%. In the elderly group, 25% had postoperative respiratory complications, 6% had postoperative cardiac complications, operative mortality was 3%, the recurrence rate was 6%, and the postsurgical 5-year survival rate was 80%. CONCLUSIONS: Thoracoscopic surgery for treatment of primary non-small-cell lung cancer can be performed with similar postoperative complication rates, operative mortality, and survival in octogenarians when compared to elderly patients.

A non-HIV case with disseminated Mycobacterium kansasii disease associated with strong neutralizing autoantibody to interferon-γ.

Disseminated non-tuberculous mycobacterium (dNTM) infection is rare in humans without human immunodeficiency virus (HIV) infection. Previous reports have shown autoantibodies to human interferon-gamma (IFN-γ), which play important roles in mycobacterium infection, in the sera of patients with non-HIV dNTM disease. Herein, we describe a 53-year-old male who was strongly suspected to have multicentric Castleman disease (MCD) based on bone marrow study and chest radiological findings. However, Mycobacterium kansasii was detected in respiratory samples including pleural effusion. We initiated anti-mycobacterial therapy under intensive care; he died on the 48(th) hospital day. We detected no hematological disorders, ruling out MCD postmortem. However, we detected M. kansasii in pulmonary, liver, spleen and bone marrow tissues. Moreover, anti-IFN-γ autoantibody was detected with strong neutralizing capacity for IFN-γ. We consider our present report to contribute to understanding of the relationship between anti-IFN-γ autoantibody and disease development.

Complete video-assisted thoracoscopic surgery for lung cancer in 400 patients.

BACKGROUND: We report the results of complete video-assisted thoracoscopic surgery for treatment of primary non-small cell lung cancer, which was performed completely through the monitor in 400 consecutive patients. PATIENTS AND METHODS: Between September 25, 2002 and August 25, 2011, a retrospective database of 400 consecutive patients who underwent complete video-assisted thoracoscopic surgery for treatment of primary non-small cell lung cancer was reviewed. Demographic, histopathologic, preoperative, perioperative, postoperative, and outcome variables were assessed using standard descriptive statistics and Kaplan-Meier survival analyses. RESULTS: Operating time was 258.13 ± 62.53 min, volume of blood loss was 253.21 ± 206.66 mL, duration of drainage was 3.6 ± 3.2 days, volume of drainage was 708.1 ± 522.8 mL, the postoperative respiratory complication rate was 14.8%, the reoperation rate was 1.3%, and operative mortality was 1.0%. The 5-year postsurgical survival rates for pathologic stages I, II, and III were 93.9%, 62.0%, and 61.6%, respectively; the 3-year postsurgical survival rate for pathologic stage IV was 40.0% CONCLUSIONS: Complete video-assisted thoracoscopic surgery for treatment of primary non-small cell lung cancer is associated with safety and acceptable postoperative complication rates, operative mortality rates, and survival rates.

Staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery for primary spontaneous pneumothorax in young patients.

PURPOSE: We investigated surgical results of staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery for treating primary spontaneous pneumothorax in young patients. METHODS: Forty-seven patients younger than 40 years underwent 48 thoracoscopic surgical procedures for spontaneous pneumothorax at the Division of Thoracic Surgery, Department of Surgery, Nippon Medical School, from May 2007 through August 2010. All patients underwent thoracoscopic bullectomy with stapling devices and pleural abrasion performed with a gauze sponge held by forceps until the pleura became petechial. Finally, the staple line was covered with a polyglycolic acid sheet (10 × 10 cm). No fibrin glue was used. We investigated both short-time results after surgery and the postoperative recurrence of pneumothorax. RESULTS: There was no operative mortality or morbidity, such as air leakage from staple lines or hemorrhage due to pleural abrasion. Pneumothorax recurred after surgery in 3 cases. In 2 cases, neither re-operation nor tube thoracostomy was necessary because intrapleural adhesions allowed only partial collapse of the lung. One patient underwent re-operation for an overlooked bulla facing the diaphragm in left lower lobe of the lung 2 days after the first operation. The rate of freedom from pneumothorax 4 years after surgery was 94%. CONCLUSIONS: Staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery is a useful method for preventing morbidity and the postoperative recurrence of pneumothorax.

Clinicopathological characteristics and prognosis of non-small cell lung cancer patients associated with a family history of lung cancer.

INTRODUCTION: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established. METHODS: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were performed using unpaired two-tailed t tests or the chi-square test. The Cox proportional hazards model was used to evaluate the hazard ratio of death. RESULTS: Of the 1013 NSCLC patients, 124 (12.2%) had a FHLC of whom 119 (96%) were the first-degree relatives. The frequency of early stages of lung cancer was high in both groups of FHLC and non-FHLC patients. Patients with FHLC had a significantly higher frequency of early pathological stages and a prepomderance of adenocarcinoma, and a hazard ratio of death of 0.870 (95% confidence interval: 0.599-1.263, p value: 0.465) compared with the non-FHLC patients. CONCLUSIONS: NSCLC patients with FHLC could be characterized by early pathological stages and preponderance of adenocarcinoma, however they were not at a decreased hazard ratio of death. These findings emphasize the importance of early detection of lung cancer and employment of less invasive therapeutic interventions.

Unification of T2a and T2b tumors to T2 tumors in non-small cell lung cancer staging.

INTRODUCTION: We investigated the validation of the seventh edition of the TNM staging (2009) system for lung cancer, retrospectively. METHODS: From January 1990 to March 2004, 1629 patients who underwent lung resection with systemic lymph node dissection for non-small cell lung cancer at Nippon Medical School and Saitama Cancer Center were included. The overall survivals after surgery by each pathological stage according to the 1997 and 2009 systems were statistically analyzed using Kaplan-Meier estimated survival curves, and the significance of the difference was analyzed by the log-rank test. RESULTS: The 2009 system had significant prognostic distinction between each T descriptor except for T2a and T2b, and between each M descriptor. The 2009 system had better prognostic distinction between each pathological stage except for stages IB and IIA, and stages IIIB and IV. In the simulation, we unified T2a and T2b tumors into T2 tumors, and T2bN0M0 and T2bN1M0 were moved to stages IB and IIA, respectively. This proposed system had significant prognostic distinction between the proposed IB, IIA, and IIB stages. CONCLUSIONS: The 2009 system provides better patient selection for surgery and prognostic distinction between each stage except for stages IB and IIA, and stages IIIB and IV, compared with the 1997 system. Unification of T2a and T2b tumors to T2 tumors can improve prognostic distinction between stages IB and IIA.

Downregulation of EMX2 is associated with clinical outcomes in lung adenocarcinoma patients.

BACKGROUND: The 5-year survival rate for stage I non-small-cell lung cancer (NSCLC) of 50% to 70% indicates that our current staging methods do not adequately predict outcome. Empty spiracles homeobox 2 (EMX2) is a homeo-domain-containing transcription factor that regulates a key developmental pathway known to promote lung tumorigenesis. This study assessed the significance of EMX2 as a prognostic biomarker in lung adenocarcinoma including bronchioloalveolar carcinoma (BAC). PATIENTS AND METHODS: 144 patients with lung adenocarcinoma undergoing surgical resection were studied. Quantitative real-time reverse transcriptase polymerase chain reaction and Immunohistochemistry were used to analyze EMX2 mRNA and protein expression, respectively. Association of EMX2 mRNA expression levels with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. RESULTS: EMX2 mRNA expression was significantly downregulated in lung adenocarcinoma compared with matched adjacent normal tissue (P < .001). EMX2 protein expression was similarly found to be downregulated in lung adenocarcinoma. The EMX2-high mRNA expressing group had statistically significant better overall survival (OS) than the EMX2-low mRNA expressing group (P = .005). Subgroup analysis also demonstrated improved survival in stage I patients (P = .01) and patients with BAC (P = .03). Lastly, the EMX2-high mRNA expressing group had statistically significant better recurrence-free survival (RFS) than the EMX2-low mRNA expression group in patients with adenocarcinoma (P < .001). CONCLUSION: EMX2 expression is downregulated in lung adenocarcinoma. Low EMX2 mRNA expression is significantly associated with decreased OS and RFS in patients with lung adenocarcinoma, particularly with stage I disease and BAC.

Surgical results of completion pneumonectomy.

PURPOSE: We report our experience with completion pneumonectomy (CP). METHODS: We report on operative procedure and morbidity, mortality, and survival rates. RESULTS: CP was performed for malignancy in 12 patients and postoperative complications after the first operation in 4 patients. Intrapericardial dissection of vessels was performed in 14 patients (87.5%). Partial vertebrectomy from the second to the fifth vertebrae was performed in 1 patient. Carinal resection was performed in 2 patients. Morbidity including bronchopleural fistula, pulmonary insufficiency, pyothorax, and pulmonary infarction developed in 6 of the 16 patients (37.5%). Mortality rate was 18.8%. The actuarial 1-, 3-, and 5-year overall survival after CP for all malignancy was 80.8%, 49.0%, and 49.0% respectively. CONCLUSIONS: The morbidity and mortality rates are high in CP. Combined resection, especially carinal resection, appears to be contraindicated in CP. CP is one of the treatments of choice, even for malignancy, if complete resection is possible because of the good long-term survival.

Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest.

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway plays pivotal roles in fundamental cellular functions including cell proliferation and cell survival. Its deregulation has been implicated in many types of human malignancies. We investigated the role of PI3K/AKT signaling pathway in human malignant pleural mesothelioma (MM). Here, we report that aberrant activation of the PI3K/AKT signaling pathway is associated with cell cycle progression in MM cells. Inhibition of the PI3K activity by its small molecule inhibitor LY294002 led to significant G1 cell cycle arrest and suppression of cell proliferation in all MM cell lines that we examined. In addition, we found that the protein level of p27Kip1 was up-regulated and the protein level of cyclin D1 was down-regulated following LY294002 treatment in those MM cell lines. However, no noticeable apoptosis induction was observed following 24 h of LY294002 treatment in those MM cell lines. These results confirm that the PI3K/AKT signaling pathway is aberrantly active and plays a critical role for the cell cycle progression in human MM cells.

Surgical treatment of metachronous nonsmall cell lung cancer.

PURPOSE: We report surgical results of metachronous nonsmall cell lung cancer (NSCLC). METHODS: We report mortality and analyze prognostic factors for overall survival in patients with metachronous NSCLC at Nippon Medical School from July 1982 to July 2008. RESULTS: Thirty-three out of 1726 patients (1.9%) who underwent lung resection had metachronous NSCLC. Mortality rate was 10%. On univariate analyses, the different histologies at the first and second operations were the only significant poor prognostic factor. Twenty-two patients (73%) had the same histology at the first and second operations: adenocarcinoma in 18 (60%) and squamous cell carcinoma in 4 (13%). Their actuarial 5- and 10-year overall survivals were both 71%, compared to 47% and 16% for patients with different histology (p = 0.0174). Sex (p = 0.1742), locations of the first and second cancers (p = 0.3957), operative procedures in patients with p-stage I at the second operation (p = 0.2782), pathological stage at the first operation (p = 0.5958), and pathological stage at the second operation (p = 0.0609) were not prognostic factors. Different histology at the first and second operations was significant based on a multivariate analysis (Hazard ratio: 3.918; p value: 0.0269; 95% confidence interval: 1.169-13.131). The actuarial 5- and 10-year overall survivals for the first cancer was 86% and 64%, compared to 65% and 45% for the second (p = 0.0609). CONCLUSIONS: Our study shows that a surgical approach is beneficial for patients with metachronous NSCLC. Good prognosis in patients with the same histology may support the current criteria of metachronous NSCLC mainly based on the histology.

Surgical results of lung cancer associated with postobstructive pneumonia.

PURPOSE: We report surgical results of lung cancer associated with postobstructive pneumonia. MATERIALS AND METHODS: We report on morbidity and mortality, and we analyze the risk factors for them and the prognostic factors for overall survival of patients without mortality. RESULTS: Morbidity developed in 13 of the 38 patients (34.2%). Mortality rate was 10.5%. Hemoglobin concentration before surgery and predicted postoperative forced expiratory volume in one second were significantly low in patients with morbidity and mortality based on the univariate analyses. Predicted postoperative forced expiratory volume in one second was a significant risk factor for morbidity based on a multivariate analysis. Poor prognostic factors for overall survival were serum albumin concentration, hemoglobin concentration, and performance status before surgery, combined resection, and pathological stage. Serum albumin concentration was significant based on a multivariate analysis. CONCLUSIONS: Morbidity and mortality are high in patients with lung cancer associated with postobstructive pneumonia. Morbidity demonstrates significant association with low predicted postoperative forced expiratory volume in one second and hemoglobin concentration, indicating the need for preoperative transfusion in severe anemia or bronchoplasty if possible. Poor nutritional state before surgery possibly derived from cachexia may influence not only morbidity and mortality, but also prognosis.

First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy.

PURPOSE: This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS). PATIENTS AND METHODS: Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and >or= 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone. RESULTS: Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from >or= PS 3 at baseline to

Serum levels of nicotinamide N-methyltransferase in patients with lung cancer.

PURPOSE: The aim of this study was to determine if nicotinamide N-methyltransferase (NNMT) is useful as a biomarker of lung cancer (stages I-III). METHODS: We established an ELISA system for NNMT. We determined the levels of NNMT and carcinoembryonic antigen (CEA) in sera of 113 non-small cell lung cancer (NSCLC) patients undergoing surgery and sera of 50 non-neoplastic lung disease patients with chronic obstructive pulmonary disease (COPD) and of 24 healthy donors. RESULTS: The serum levels of NNMT were significantly higher in lung cancer patients than in COPD patients and healthy donors. The relationship between the specificity and sensitivity of NNMT and CEA measurements for the detection of lung cancer was analyzed by means of receiver-operating characteristic curves. The corresponding areas under the curves were 0.703 for NNMT and 0.621 for CEA, indicating slightly better sensitivity of NNMT. With 90% specificity, the sensitivities of NNMT and CEA as lung cancer markers were 25 and 24%, respectively. There was no significant correlation between NNMT and CEA. Therefore, the sensitivity of NSCLC detection at 90% specificity increased from 25 to 32% when NNMT was used in combination with CEA. CONCLUSION: The NNMT serum level may have significance in the early detection of NSCLC patients.