Surgical strategy of IgG4-related inflammatory abdominal aortic aneurysm with preoperative steroid therapy: A case report.

Immunoglobulin G4 (IgG4)-related disease, characterized by high serum IgG4 concentrations and IgG4-positive plasma cell infiltration, often presents as an inflammatory aneurysm. We herein report the case of a 78 year-old man, presenting with elevated inflammatory markers and IgG4 concentrations, who was diagnosed with IgG4-related inflammatory abdominal aortic aneurysm with dense perianeurysmal fibrosis. Before the surgical intervention, steroid therapy was administered to resolve his perianeurysmal inflammatory fibrosis. Half a year after the initiation of steroid therapy, there was an improvement in serum inflammatory markers and IgG4 concentrations, and the perianeurysmal fibrosis had regressed. Thus, we performed a surgical intervention including resection of the aneurysm and interposition with a prosthetic graft. Histopathological examination demonstrated few IgG4-positive plasma cells were distributed in the adventitia, which was suspected to be associated with the preoperative steroid therapy. This case study suggests preoperative steroid therapy is a useful therapeutic strategy for IgG4-related abdominal aortic aneurysm because it allows the use of open surgical procedures with reduced surgical risk.

Surgical Management of Incidental Profunda Femoris Artery Aneurysm: A Case Report.

Profunda femoris artery aneurysm is a rare vascular disorder, which is often diagnosed incidentally on identification of synchronous aneurysms. Herein, we report the case of a 63-year-old man, presenting with a hepatic cyst, who had left profunda femoris artery and left internal iliac artery aneurysms. We performed surgical intervention, including resection of the aneurysm and reconstruction of the profunda femoris artery using a prosthetic graft. The postoperative course was uneventful, and computed tomography revealed good graft patency. We believe surgical reconstruction of the profunda femoris artery should be completed except in complicated cases, such as rupture or aneurysm in the distal segment of the profunda femoris artery.

Undifferentiated intimal sarcoma mimicking a mycotic aneurysm.

Intimal sarcoma of arteries is a rare malignant tumor, which often mimics other vascular disorders; therefore, preoperative diagnosis is often challenging. We herein report a 71-year-old man who presented with fever and elevated inflammatory markers who had a mass in the left internal iliac artery with rapid growth. Based on clinical findings, a diagnosis of mycotic aneurysm was made. We performed surgical intervention, including resection of the affected vessels with omentopexy, although intraoperative findings were not typical of a mycotic aneurysm. Microscopic and immunohistochemical examination demonstrated undifferentiated intimal sarcoma. The patient died of multiorgan failure two months after the surgery. The vascular surgeon should consider the possibility of a diagnosis of intimal sarcoma for patients with atypical findings and the importance of histological and immunohistochemical examination for precise diagnosis in surgical vascular cases.

Effective Surveillance to Identify the Surgical Patients Carrying Methicillin-resistant Staphylococcus aureus on Admission in a Pediatric Ward.

Background To effectively detect surgical patients carrying methicillin-resistant Staphylococcus aureus (MRSA) in a pediatric ward, we investigated who should be tested through bacteriological surveillance on admission. Methods In 1124 patients, bacteriological examination of throat swabs and stool samples was performed within 48 hours after admission. The relations between carrier rate (CR) of MRSA and a history of hospitalization, neurological disorder (ND), and age group were retrospectively investigated. Results The CR of all patients was 7.8%. The CRs of the patients with no history of hospitalization, a history of hospitalization before the previous year, and a history of hospitalization within the past year (HWPY) were 2.3%, 3.4%, and 14.5%, respectively; the CR of those with HWPY was significantly higher than the CRs of the other 2 groups (p<0.0001). The CR of the patients with an ND (19.2%) was significantly higher than that of the patients without an ND (6.1%) (p<0.0001). The CRs of the patients <3 (11.7%) and 15 (11.9%) years old were higher than that of other patients (3.8%) (p< 0.05). With multivariate logistic regression analysis, HWPY, an ND and age groups <3 and k15 were independent risk factors. Conclusions - HWPY, an ND, and being <3 or k 15 years old were found to be risk fqctors for carrying MRSA on admission. Active bacteriological surveillance on admission should be performed for patients with these risk factors.

Efficacy and Safety Evaluation of Tolvaptan on Management of Fluid Balance after Cardiovascular Surgery Using Cardiopulmonary Bypass.

Background: Tolvaptan is an orally administered selective vasopressin 2 receptor antagonist that promotes aquaresis. This study aimed to evaluate the efficacy and safety of tolvaptan on management of systemic fluid balance after cardiovascular surgery using cardiopulmonary bypass. . Methods: Sixty-four patients who underwent cardiovascular surgery using cardiopulmonary bypass in our hospital were enrolled for this prospective, randomized study. These patients were divided into three groups: tolvaptan 15 mg+furosemide 20 mg (TH group), tolvaptan 7.5 mg+furosemide 20 mg (TI group), and furosemide 40 mg+spironolactone 50 mg (C group). The endpoint was safety management of systemic fluid balance using tolvaptan without renal dysfunction and electrolyte imbalance. Results: The mean daily urine output in the TH and TL groups (2656±767 and 2505 ±684 mL) was significantly higher than that in the C group (1956±494 mL, TH vs C: p<0.01 and TL vs C: p=0.03). The lowest serum sodium level during medication in the TH group (139.3 ±2.3 mEq/L) was significantly higher than that in the C group (137.1±2.9 mEq/L, p=0.03) The lowest serum osmolality during medication in the TH group was significantly higher than that in the C group (284.8 ±4.3 vs 279.5± 6.3 mOsm/kg, p<0.01). None had critical hypernatremia, hyperosm6lality, or renal dysfunction in any. of the groups. Conclusions: Tolvaptan exerts, a strong diuretic effect compared with conventional diuretics (furosemide and spironolactone) during the postoperative period after an operation using cardiopulmonary bypass without adverse effects on electrolyte balance and renal function.

Hepatic resection for hepatocellular carcinoma in super-elderly patients aged 80 years and older in the first decade of the 21st century.

PURPOSE: We evaluated the preoperative and postoperative characteristics and prognosis of super-elderly patients with hepatocellular carcinoma (HCC). METHODS: Four hundred and thirty-one patients who underwent hepatic resection for HCC were classified into three groups according to their age at the time of surgery: super-elderly (≥80 years; n = 20), elderly (70-80 years; n = 172) and younger (<70 years; n = 239). We compared the clinical characteristics, preoperative and postoperative factors and prognosis among the groups to evaluate whether liver resection is appropriate for super-elderly patients. RESULTS: The liver function was not significantly different among the groups. The proportion of patients with preoperative cardiovascular and respiratory disease and hypertension was higher in the super-elderly group compared to the other groups. The super-elderly group had shorter operations and reduced hemorrhage rates compared to the other groups. Postoperative cardiovascular complications and delirium were more frequently observed in the super-elderly group. The overall and tumor-free survival rates were not significantly different among the groups. Super-elderly patients had a lower rate of liver or HCC-related death and a higher rate of death due to other causes than the other groups. CONCLUSIONS: Super-elderly HCC patients who are appropriately evaluated and selected might have a favorable prognosis after undergoing hepatic resection.

C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage after Esophageal Reconstruction.

BACKGROUND: Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period. METHODS: In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6. RESULTS: Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL. CONCLUSIONS: The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.

[Risk Factors in Surgical Intervention for Prosthetic Valve Endocarditis].

The aim of this retrospective study was to detect the risk factors for in-hospital mortality after surgery for active prosthetic valve endocarditis ( PVE). We reviewed 35 operations for active PVE, including 6 cases of early PVE. Seven patients were New York Heart Association (NYHA) functional class IV. Preoperative mechanical ventilation was necessary in 3 patients, 1 patient required intra-aortic balloon pumping, and another needed percutaneous cardiopulmonary support. Preoperatively, cerebrovascular events were observed in 13 patients, annular abscess in 12, and perivalvular leakage in 14. Valve replacement was performed in 24 patients and aortic root replacement in 11. Annular reconstruction was required in 18 patients. There were 6 hospital deaths (17.1%). The results of risk factor analysis showed that early PVE, NYHA functional class IV, and preoperative mechanical ventilation were independent risk factors for in-hospital death after surgery. In conclusion, surgical treatment of PVE should be performed before hemodynamic deterioration.

[Surgical treatment for pseudoaneurysm of the sinus of valsalva ruptured into the right atrium after mycotic right coronary artery aneurysm repair;report of a case].

A 67-year-old man was admitted to our hospital by ambulance after syncope due to complete A-V block. He had received surgical treatment for mycotic aneurysm of the right coronary artery 3 months before, with patch plasty of the right sinus of Valsalva and bypass grafting to the right coronary artery (RCA) as well as the left anterior descending branch. Computed tomography revealed pseudoaneurysm of the right Valsalva sinus of about 8 cm in diameter and a shunt flow to the right atrium. The previous bypass graft to RCA had been occluded due to compression by the aneurysm. As he was in a shock state, emergency operation was performed. Cardiopulmonary bypass was first established, and after the rectal temperature reached to 26 degrees centigrade, the chest was opened. The pseudoaneurysm burst out when the sternum was re-opened. Under circulatory arrest, the ascending aorta was clamped, and then the circulation was resumed. The previous bovine pericardium patch repairing the Valsalva sinus was detached due to infection, and mural thrombus and pus were observed in the aneurysm. At the bottom of the aneurysm, a fistula connected to the right atrium was found. Debridement around the aneurysm was performed as much as possible. The defect of the Valsalva sinus was repaired with a Dacron patch immersed in gentian violet. The postoperative course was uneventful without any recurrence of infection.

Clinical value of exogenous factor XIII for prolonged air leak following pulmonary lobectomy: a case control study.

BACKGROUND: We examined the effect of exogenous factor XIII (FXIII) concentrate in patients with prolonged air leak (PAL) after pulmonary lobectomy for non-small cell lung cancer. METHODS: We performed a retrospective analysis of 297 patients who underwent pulmonary lobectomy between July 2007 and March 2014: 90 had an air leak on the first postoperative day, which resolved spontaneously within 5 days in 53 cases (SR group). FXIII concentrate was administered to the remaining 37 patients (PAL group) for 5 days. This group was subdivided into those in whom the air leak resolved during FXIII treatment (EF group) and those who needed additional intervention (inEF group). The clinical and perioperative characteristics of the groups were compared. RESULTS: Although plasma FXIII activity did not differ significantly between the SR and PAL groups before surgery or on the fifth postoperative day, the proportional perioperative fall in FXIII activity was significantly greater in the SR group (33%) than the PAL group (22%, p = 0.044) and inEF group (14%, p = 0.048). On the fifth postoperative day, FXIII activity was significantly lower in the EF group than in the inEF group (74% versus 91%, p = 0.030). The optimal cut-off point for postoperative plasma FXIII activity to distinguish between the EF and inEF groups was 86%. CONCLUSIONS: Insufficient plasma FXIII consumption and lower postoperative FXIII activity may play a role in the resolution of PAL, and exogenous FXIII concentrate may be an effective, safe and non-invasive treatment.

Sialyl Lewis X as a predictor of skip N2 metastasis in clinical stage IA non-small cell lung cancer.

BACKGROUND: Radical segmentectomy has been performed for small-sized non-small cell lung cancer (NSCLC). However, underestimation of mediastinal lymph node metastasis in the absence of hilar or interlobar metastasis (skip N2) affects surgical strategy. Our aim was to investigate preoperative and intraoperative predictors of skip N2 in clinical stage (c-stage) IA NSCLC. METHODS: From 1998 to 2011, 279 patients (155 men and 124 women) with c-stage IA NSCLC (230 pN0, 17 pN1, 12 skip N2, 20 non-skip N2) underwent systematic lobectomy (R0 resection) at our institute. We compared preoperative serum concentrations of carcinoembryonic antigen, cytokeratin 19 fragment, sialyl Lewis X (SLX), and pre- and intraoperative clinicopathological features of pN0 and skip N2 patients. Receiver operator characteristic (ROC) curve analysis was performed to distinguish between the two patient groups. RESULTS: The 5-year survival rate of skip N2 patients was 78.6%, higher than that of non-skip N2 patients (44.9%), and not significantly different than that of pN0 (86.7%) or pN1 patients (82.4%). The mean serum SLX concentration in skip N2 patients (28.0 U/ml) was elevated compared to that in pN0 patients (22.9 U/ml). In ROC analysis of SLX, the area under the curve was 0.710, and the optimal cut-off value was 21.4 U/ml (sensitivity, 91.7%; specificity, 51.7%). In multivariate analysis, SLX was an independent predictor of skip N2 in patients with c-stage IA NSCLC (odds ratio, 9.43; p = 0.006). CONCLUSIONS: Skip N2 metastasis is common in patients with c-stage IA NSCLC with high serum SLX, and lobectomy with complete dissection of hilar and mediastinal lymph nodes should remain the standard surgical procedure for these cases.

Clinicopathological significance of combined analysis of cytokeratin19 expression and preoperative serum CYFRA21-1 levels in human lung squamous cell carcinoma.

BACKGROUND: To identify a useful biomarker for human lung squamous cell carcinoma (SCC), the expression of cytokeratin19 (CK19) in human SCC tissue was investigated. In addition, we examined the significance of CK19 expression levels by immunostaining and CYFRA21-1 levels in preoperative serum, and their correlation with the clinicopathologic features of human lung SCC. METHODS: To identify proteins in cancerous and non-cancerous tissues for the diagnosis and prognosis of SCC, QSTAR Elite LC-MS/MS was used. Immunostaining for CK19 was classified as either "CK19-strong" or "CK19-weak". Correlations between prognosis and both CK19 expression in tumor tissues and serum concentrations of CYFRA 21-1 were analyzed in 107 cases of lung SCC. RESULTS: The upregulation of CK19 in human squamous cell carcinoma tissues was observed by LCMS/MS. The weak expression of CK19, as determined by immunostaining intensity, was a significant predictor of poorer disease-specific survival (p = 0.032). The prognosis was significantly poorer for patients with weak CK19 immunostaining in tumor tissues and a high serum concentration of CYFRA21-1 compared with the other groups (p = 0.003). CONCLUSIONS: The combination of weak CK19 expression and high serum CYFRA21-1 levels is a predictor of poorer prognosis for patients with human lung SCC.

Diagnostic accuracy of transthoracic and transesophageal echocardiography for the diagnosis of bicuspid aortic valve: comparison with operative findings.

BACKGROUND: Bicuspid aortic valve (BAV) is associated with an increased risk of aortic valve (AV) dysfunction, aortic dissection, and infective endocarditis. Therefore, its accurate diagnosis is critical. The morphological features of AVs are generally evaluated by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE), however, the difference in the diagnostic capability of these imaging modalities for detecting BAV remains unclear. Here, we compared these 2 methods to determine their accuracy, and to clarify each role in the diagnosis of BAV. METHODS: This blind study evaluated 126 patients (age, 70.3 +/- 7.8 years) who subsequently underwent AV replacement. The number of AV cusps of each patient was estimated by TTE and TEE and compared to the number of AV written in the operative record. Patients with poor echocardiographic images were not excluded. RESULTS: Surgical findings showed 97 tricuspid AVs and 29 BAVs. The sensitivity, specificity, and accuracy for the diagnosis of BAV were 61%, 81%, and 77%, respectively, for TTE and 86%, 90%, and 89%, respectively, for TEE. The accuracy of TEE was significantly higher than that of TTE (p = 0.016). In non-calcified AVs, the accuracy of TTE was similar to that of TEE (96%, each) whereas in calcified AVs, TTE had a lower accuracy than TEE (72% vs 87%, p = 0.011). The feasibility was significantly higher for TEE than for TTE (98% vs 90%, p = 0.003). CONCLUSIONS: TEE provides higher accuracy and feasibility than TTE in the diagnosis of BAV, and it should therefore be indicated when morphological features of AVs cannot be evaluated by TTE.

[Axillo-axillary bypass for coronary-subclavian steal syndrome].

We describe a case of coronary-subclavian steal syndrome in a 77-year-old man who presented with progressive coronary ischemia 8 years after coronary artery bypass grafting with an in-situ left internal thoracic artery graft. Coronary and left subclavian artery angiogram revealed completely patent internal thoracic artery graft and 90% stenosis in the proximal left subclavian artery. We performed axilloaxillary artery bypass using expanded polytetrafluoroethylene (ePTFE)[8 mm] graft. No coronary ischemia was noted postoperatively. Axillo-axillary artery bypass grafting was effective for coronary subclavian steal syndrome.

Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization.

BACKGROUND: Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown. METHOD: We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively. RESULTS: Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other. CONCLUSION: This is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.

Preoperative serum value of sialyl Lewis X predicts pathological nodal extension and survival in patients with surgically treated small cell lung cancer.

BACKGROUND AND OBJECTIVES: We investigated various tumor markers in patients with surgically treated small cell lung cancer (SCLC) to identify the markers closely correlated to pathological staging and to predict survival by retrospective analyses. METHODS: Reviewing database records between 1990 and 2007 revealed 36 patients with SCLC, that were grouped according to clinical and pathological stages. Receiver operating characteristic (ROC) curves were calculated for serum levels of various tumor makers to predict the pathological stage. The cut-off value was calculated from the ROC curve of the significant marker. Survival in patient groups divided by the new cut-off value was calculated. RESULTS: Serum levels of various tumor makers were not significantly different between the pathological stage groups, except for serum sialyl Lewis X (SLX). ROC curve of SLX was significantly correlated to pathological stages (P = 0.0136). The calculated SLX cut-off value was 25.1 U/ml, with 80% sensitivity and 70% specificity. Five-year survival of patients selected by this new cut-off was 82.5%, whereas that with the standard cut-off (38.0 U/ml) was 55.9%. CONCLUSIONS: Serum SLX values were associated with pathological stage and survival after surgery in SCLC patients.

Preoperative serum oxidative stress marker as a strong indicator of nodal involvement in clinical stage I lung adenocarcinoma.

BACKGROUND: Reactive oxygen species stimulate lymphatic metastasis by accelerating epithelial-to-mesenchymal transition and lymphangiogenesis in the tumor microenvironment. Hence, systemic oxidative stress level may correlate with nodal involvement in patients with a malignant tumor. METHODS: We examined 46 patients with clinical stage I lung adenocarcinoma who had undergone pulmonary resection with mediastinal lymph node dissection. Serum reactive oxygen metabolite (ROM) level was measured as an indicator of systemic oxidative stress. We investigated the association between nodal involvement and clinicopathological factors. RESULTS: Preoperative serum carcinoembryonic antigen (CEA; P = 0.045), cytokeratin 19 fragment (CYFRA21-1; P = 0.038), and ROM (P = 0.007) levels were significantly higher in patients with nodal involvement than in those without nodal involvement. A receiver operating characteristic curve was constructed to determine whether patients with and without nodal involvement could be differentiated on the basis of their serum ROM levels. The area under curve was 0.763 and the prognostic cut-off value was set at 318 Carratelli units. In univariate analysis, clinical stage IB (odds ratio [OR] = 4.55; P = 0.033), CEA-positive (OR = 5.56, P = 0.018), and ROM-positive (OR = 10.46, P = 0.006) were significant predictive factors for nodal involvement. In multivariate analysis, ROM-positive was an independent predictive factor for nodal involvement (OR = 6.22, P = 0.045). CONCLUSION: Preoperative serum ROM level was an independent significant predictive factor for nodal involvement in patients with clinical stage I lung adenocarcinoma. Hence, serum ROM level may be a useful biomarker for staging of lung adenocarcinoma.

Features and outcome after liver resection for non-B non-C hepatocellular carcinoma.

BACKGROUND/AIMS: We investigated the clinicopathological findings and outcome after surgery for hepatocellular carcinoma in patients without hepatitis B or C virus infection. METHODOLOGY: Among 562 patients who underwent curative resection for hepatocellular carcinoma, the sera from 97 patients (B group) were positive for hepatitis B surface antigen alone, sera from 355 patients (C group) were positive for anti-hepatitis C virus antibody alone and sera from 104 patients (NBNC group) were negative for both hepatitis B surface antigen and anti-hepatitis C virus antibody. We compared the clinicopathological findings and postoperative outcomes in the 3 groups. RESULTS: The prevalence of diabetes mellitus, hypertension, hyperlipidemia and alcohol abuse were higher in the NBNC group than in the other groups. The prevalence of obesity was higher in the NBNC group than in the B group. Non-alcoholic steatohepatitis was detected in 16 NBNC patients. The tumor- free survival rate was higher in the NBNC group than in the C group. CONCLUSIONS: Obesity, diabetes mellitus, hypertension, hyperlipidemia, alcohol abuse and non-alcoholic steatohepatitis were the possible risk factors for hepatocellular carcinoma in the NBNC group. The patients in the NBNC group are expected to show a better outcome as compared to patients in the C group.

Efficacy of landiolol hydrochloride for prevention of atrial fibrillation after heart valve surgery.

The goal of this prospective study was to examine the effects of landiolol hydrochloride on prevention of atrial fibrillation and on hemodynamics in the acute postoperative phase after heart valve surgery. The subjects were 60 patients who underwent valve surgery at our hospital from April 2008 to July 2010. The patients were randomly divided into two groups: the landiolol group (30 patients) and the control (no landiolol) group (30 patients). In the landiolol group, continuous intravenous landiolol was initiated immediately on admission to the intensive care unit at a dose of 10 µg/kg/ minute. Occurrence of atrial fibrillation was compared between the groups over an observation period of 72 hours after surgery. Atrial fibrillation occurred in 6 patients (20%) in the landiolol group and 16 (53.3%) in the control group during the observation period. Landiolol hydrochloride significantly reduced the occurrence of atrial fibrillation in the acute postoperative phase after heart valve surgery. Heart rate was significantly decreased by landiolol, but aggravation of hemodynamics was not observed. These results suggest that landiolol is a useful drug for prevention of atrial fibrillation after valve surgery.

AGR2 as a potential biomarker of human lung adenocarcinoma.

BACKGROUND: The present study aimed to identify useful candidate biomarkers of lung adenocarcinoma for clinical diagnosis and treatment using proteomics technology. METHODS: We assessed frequently highly overexpressed proteins in 12 cases of lung adenocarcinoma compared with adjacent normal tissue samples by liquid chromatography tandem mass spectrometry (LC-MS/MS) coupled with isobaric tags for relative and absolute quantitation (iTRAQ) technology, and validated the expression of target proteins by immunohistochemistry in 268 lung adenocarcinoma cases. Protein expression and clinicopathological variables were compared statistically for the evaluation of novel biomarkers. RESULTS: One hundred seventy-seven proteins displaying significant quantitative changes compared with adjacent normal-appearing lung tissue were identified in more than 9 out of 12 lung adenocarcinoma patients. Based on the results of liquid chromatography tandem mass spectrometry, Ingenuity Pathway, and immunohistochemical analyses, anterior gradient homolog 2 (AGR2) (upregulated 9.9-fold) was selected as a potential biomarker of human lung adenocarcinoma. AGR2 was positive in 94% of lung adenocarcinoma patients. Negative AGR2 expression was associated with poor survival (p = 0.007). CONCLUSIONS: AGR2 is likely to become a biomarker for clinical applications.