Effectiveness of Intraoperative Endoscopy for Localization of Early Gastric Cancer during Laparoscopic Distal Gastrectomy.

INTRODUCTION: Intraoperative localization of tumors has been considered crucial in determining adequate resection margins during laparoscopic gastrectomy for early gastric cancer (EGC). This study has evaluated the effectiveness of intraoperative endoscopy for localization of EGC during the totally laparoscopic distal gastrectomy. METHODS: Patients with EGC who received totally laparoscopic distal gastrectomy from January 2018 to March 2020 were included in this study. Except the tumors located in the antrum, the patients were categorized into two groups: no localization procedure (n = 144) and intraoperative endoscopy (n = 65). To evaluate the effectiveness of the localization procedure, proximal resection margin (PRM) involvement by the tumor and approximation of optimal PRM were compared, including their postoperative outcomes. RESULTS: There were 3 patients (2.1%) with tumor involvement of the PRM at the initial gastric resection in the no localization group. Distance from the tumor to the PRM was determined to be not significantly different between the no localization group and intraoperative endoscopy group. The PRM distribution pattern and reconstruction method were also not significantly different between the two groups. DISCUSSION/CONCLUSION: Intraoperative endoscopy for localization of EGC is an effective method to avoid tumor involvement at the resection margin during the laparoscopic gastrectomy with intracorporeal gastric resection and reconstruction.

Is Splenic Hilar Lymph Node Dissection Without Splenectomy Essential for Proximal Advanced Gastric Cancer?

BACKGROUND: The standard surgery for proximal advanced gastric cancer (PAGC) is total gastrectomy with D2 lymph node dissection (LND). Although prophylactic splenectomy for splenic hilar LND (No. 10) is not recommended due to any survival advantage, prophylactic LND (No. 10) without splenectomy remains controversial. Thus, we aimed to evaluate whether No. 10 LND is essential for patients' survival benefit in PAGC. METHODS: We conducted a retrospective study of 1038 patients with PAGC who underwent total gastrectomy without splenectomy. After adjusting for confounders and propensity score matching (PSM), patients were grouped into Group 1 (D2 LND without splenic hilar LN; n = 288) or Group 2 (D2 LND with splenic hilar LN; n = 288). Variables between the two groups (5-year overall survival [OS] and disease-free survival [DFS]) were compared, as well as in patients with tumors located in the greater curvature and those with Borrmann type IV disease. RESULTS: The 5-year OS and DFS rates after PSM were not significantly different between Groups 1 and 2 (57.3% vs. 62.1%, p = 0.300; 52.8% vs. 59.7%, p = 0.100, respectively). Furthermore, the 5-year OS and DFS rates in patients with greater curvature involvement (54.4% vs. 61.9%, p = 0.500; 50.0% vs. 57.6%, p = 0.400, respectively) and Borrmann type IV disease (23.8% vs. 38.6%, p = 0.400; 16.7% vs. 33.9%, p = 0.200, respectively) after PSM were also not significantly different between the two groups. CONCLUSIONS: Prophylactic splenic hilar LND without splenectomy does not improve long-term survival in PAGC. Therefore, this procedure might not be essential for patients with PAGC as well greater curvature involvement and Borrmann type IV disease.

Risk factors for lymph node metastasis in early gastric cancer without lymphatic invasion after endoscopic submucosal dissection.

BACKGROUND: Lymphatic invasion (LI) is a potent risk factor for lymph node metastasis (LNM) in early gastric cancer (EGC) after endoscopic submucosal dissection (ESD). However, there are also other risk factors for LNM. Hence, to identify the need for additional surgery in some case of EGC without LI, the present study aimed to identify the risk factors for LNM in patients with EGC without LI. METHODS: Data from 2284 patients diagnosed with EGC who underwent curative surgery at National Cancer Center in Korea from January 2012 to May 2019 were collected. The clinicopathological characteristics of patients with EGC without LI were compared on the basis of LNM status. RESULTS: There were 339 (17.1%) and 1648 (82.9%) patients with and without LI respectively. Among these patients with and without LI, 118 (34.8%) and 91 (5.5%) patients presented with LNM, respectively. In patients with EGC without LI, tumor size larger than 3 cm (OR = 2.12, 95% CI = 1.22-3.68; p = 0.007), submucosal invasion (OR = 4.14, 95% CI = 2.57-6.65; p < 0.001), and undifferentiated histologic type (OR = 2.33, 95% CI = 1.45-3.76; p < 0.001) were significant risk factors for LNM. Rates of LNM in patients meeting absolute, expanded, and beyond expanded criteria without LI were 0%, 1.5% (OR = 3.27, 95% CI = 0.18-59.41; p = 0.423), and 7.3% respectively. When the expanded criteria were divided into four subtypes patients with EGC, without LI within each subtype did not show significant risk of incidence of LNM compared to the absolute criteria. CONCLUSIONS: The current expanded criteria for endoscopic resection (ER) are tolerable in cases without LI, even though minimal risk LNM exists. Therefore, additional surgery may not be needed for patients meeting expanded criteria for ER.

A comparative study of the short-term operative outcome between intracorporeal and extracorporeal anastomoses during laparoscopic total gastrectomy.

BACKGROUND: Several studies have reported that intracorporeal anastomosis reduces the requirement for the additional incision for anastomosis, resulting in early recovery compared to extracorporeal anastomosis during laparoscopic distal gastrectomy. However, few studies have investigated postoperative outcome after laparoscopic total gastrectomy (LTG). We compared short-term postoperative outcomes between totally laparoscopic total gastrectomy (TLTG) with intracorporeal anastomosis and conventional laparoscopy-assisted total gastrectomy (LATG) with extracorporeal anastomosis for gastric cancer. METHODS: This retrospective case-control study included 202 patients who underwent LTG from January 2012 to June 2019. LATG was performed in the period before July 2015; TLTG was performed in the period after July 2015. Postoperative short-term outcomes and white blood cell (WBC) count, and C-reactive protein (CRP) levels at 1, 3, and 5 days postoperatively were compared between the groups. RESULTS: One hundred ten patients underwent LATG; 92 underwent TLTG. The pathologic stage was significantly higher in the TLTG group (p = 0.010). Intraoperative estimated blood loss was significantly lower in the TLTG group than in the LATG group (median [range]: 100 [50-150] mL versus [vs.] 50 [30-100], p < 0.001). Postoperative hospital stay duration was significantly longer in the TLTG group than in the LATG group (median [range]: 7 [7-9] days vs. 8 [7-11], p < 0.001). WBC count (6.3 109/L ± 1.9 vs. 8.2 ± 2.5, p = 0.004) and CRP levels (8.3 mg/L ± 6.1 vs. 13.3 ± 9.4, p < 0.001) were lower in the LATG group than in the TLTG group. The overall complication rate was higher in the TLTG group than in the LATG group (16.3% vs. 32.6%, p = 0.007). A higher American Society of Anesthesiologist score was the only significant risk factor for postoperative complications. CONCLUSION: Both procedures are feasible, although TLTG has more risk for postoperative complications than LATG. TLTG should be improved to reduce postoperative complications and provide better postoperative outcomes.

Prognostic impact of infectious complications after curative gastric cancer surgery.

INTRODUCTION: There have been few studies about the effect of infectious complications on recurrence or long-term survival outcome after curative gastric cancer surgery in large populations. This study was conducted to investigate the impact of infectious complications on long-term survival after curative gastrectomy in high volume center. METHOD: From January 2002 to December 2012, patients who underwent curative gastrectomy were enrolled. Infectious complications were defined as wound infection, intra-abdominal infection or postoperative pneumonia. Five-year overall survival was compared between two groups and followed by multivariable analysis using a Cox proportional hazards model. RESULT: Of 6585 patients who underwent curative gastrectomy, 413 (6.2%) had infectious complications after curative gastrectomy. The five-year overall survival rate was 86.0% in non-complication patients and 74.1% in infectious complications patients (P < 0.001). In univariate analysis, Age over 70 years, male sex, higher ASA score, total or proximal gastrectomy, advanced stage and infectious complication had statistically worse survival. A Cox proportional hazards model indicated that the infectious complication was independent prognostic factor (HR = 1.478, CI 95% 1.242-1.757 p < 0.001) as well as age over 70 years (HR = 2.434, CI 95% 2.168-2.734 p < 0.001), male sex (HR = 1.153, CI 95% 1.022-1.302 p = 0.014), higher ASA score (p < 0.001) and advanced Stage (p < 0.001). Local recurrence (P = 0.044), LN recurrence (P = 0.038) and hematologic recurrence (P = 0.033) were significantly associated with infectious complications. CONCLUSION: Postoperative infectious complication was an independent prognostic factor for five-year overall survival after curative gastrectomy as well as known factors. A significant association between infectious complications and recurrence were also noted. The surgeon should try to prevent the infectious complications in gastric cancer surgery to improve the long term survival.

Prognostic Model to Predict Survival Outcome for Curatively Resected Liposarcoma: A Multi-Institutional Experience.

PURPOSE: We performed this study to analyze the clinical features and prognosis of Korean patients with liposarcoma. PATIENTS & METHODS: Between October 1986 and April 2013, 231 patients who were diagnosed with liposarcoma by histologic examination were enrolled in this study. RESULTS: The distribution of histologic subtypes was well-differentiated (n = 97, 42%), myxoid (n = 74, 32%), dedifferentiated (n = 32, 13.9%), pleomorphic (n = 15, 6.5%), and round-cell liposarcoma (n = 13, 5.6%). The majority of liposarcomas were located in the lower extremities (35.5%) and retroperitoneum (34.2%). Prognosis was worse for the trunk group compared with the extremity group (median disease-free survival [DFS] 3.3 vs. 9.9 years, respectively, P <0.001). Median DFS was significantly worse in patients with high grade histology compared to those with low grade histology (16.9% vs. 65.7%, P <0.001). The independent prognostic factors associated with survival were histology (hazard ratio [HR] 3.01; 95% confidence interval [CI], 1.82-4.97; P <0.001) and primary site (HR 1.80; 95% CI, 1.12-2.89; P = 0.015). Three risk groups with different survival outcomes were identified: group 1 (n = 98), no risk factors; group 2 (n = 92), one risk factor; and group 3 (n = 41), two risk factors. CONCLUSIONS: Histologic subtype and primary site were independent prognostic factors for curatively resected liposarcoma. A prognostic model for patients with liposarcoma clarified distinct groups of patients with good prognostic discrimination.

Population pharmacogenetic pharmacokinetic modeling for flip-flop phenomenon of enteric-coated mycophenolate sodium in kidney transplant recipients.

PURPOSE: Enteric-coated mycophenolate sodium (EC-MPS) is effective and safe in preventing rejection after transplantation and is mainly transported by ABCs and OATPs and metabolized by UGTs. The genetic polymorphisms affect the inter-individual variation in drug disposition and elimination. The aims of this study were to develop a population pharmacokinetic (PK) model and to evaluate the influence of genetic and clinical factors on the PK of mycophenolic acid (MPA) in Korean renal transplant recipients. METHODS: Population analysis of EC-MPS was performed using non-linear mixed effects modeling (NONMEM). After clinical and genetic factors were evaluated using a stepwise covariate method, we selected clinically relevant covariates considering covariate effects. The final model was validated by bootstrap and visual predictive check. At last, we performed the model-based simulations in order to explore an optimal dose to achieve target area under the curve (AUC) in hypothetical scenarios. RESULTS: From 166 plasma concentrations (n=34), a time-lagged two-compartment with a flip-flop model best describes the PK of MPA. The covariate analysis identified lower creatinine clearance (CLcr) and SLCO1B1 variant genotype were correlated with lower MPA clearance, on the contrary, UGT1A9 variant had decreased distribution of MPA, contributing to lower absorption. When considering to UGT1A9, SLCO1B1 genotypes, and renal function, the new recommended dose of 540 mg twice daily resulted in a higher success of achieving the target AUC0-12h in the 30-60 mg.h/L. CONCLUSIONS: CLcr, UGT1A9 and SLCO1B1 genotypes seem to be promising parameters to predict the pharmacokinetics with flip-flop phenomenon of EC-MPS in transplant recipient having stable renal function. This model on clinical practice may help prevent overexposure and achieve a proper AUC in the Korean population.

Squamous cell carcinoma of the lung with simultaneous metastases to peritoneum and skeletal muscle.

Skeletal muscle and peritoneum are rare sites of metastases from lung cancer. We report a case of squamous cell lung cancer with concurrent metastases to skeletal muscle and peritoneum. A 71-year-old man was diagnosed with squamous cell carcinoma of the right lower lobe with metastasis to the right hilar lymph node at clinical stage T3N1M0. Because of poor performance status and comorbidity, he only received radiation therapy. Positron emission tomography-computed tomography for mid-assessment of response showed two abnormal hypermetabolic lesions in the peritoneum of the left upper quadrant area and the left thigh muscle. We performed a needle-approach biopsy in each lesion and found both of the lesions were metastases from lung cancer. The patient died after two months.

A case of fulminant community-acquired Acinetobacter baumannii pneumonia in Korea.

Acinetobacter baumannii (AB) is a common pathogen found in patients with hospital-acquired pneumonia all over the world. Community-acquired AB pneumonia, however, is very rare and has seldom been reported in Asia-Pacific countries. Community-acquired AB pneumonia has a fulminant course and is associated with a higher mortality than hospital-acquired AB pneumonia. In Korea, no case of fatal community-acquired AB pneumonia has been reported to date. Here, we describe the first fatal case of fulminant community-acquired AB pneumonia in Korea.

Bronchomediastinal fistula detected accidently during palliative radiation therapy.

Bronchomediastinal fistula is an extremely rare complication resulting from diseases such as mediastinitis or mediastinal malignancies. In patients with lung cancer, bronchomediastinal fistula formation has rarely been reported, except during post-chemotherapy or post-radiation therapy complications. An 84-year-old visited our hospital to receive palliative radiation therapy for squamous cell carcinoma of the right main bronchus T4N2M1a. During an early course of radiation therapy, chest computed tomography (CT) scans revealed bronchomediastinal fistula between the right main bronchus and the enlarged sub-carinal lymph nodes. Radiation therapy was, therefore, discontinued and the patient received only supportive care.

A Case of Streptococcus suis Infection Causing Pneumonia with Empyema in Korea.

Streptococcus suis causes meningitis and sepsis in pigs, but human infection has increased over the past few years in those who are exposed to pigs or raw pork. Most cases have occurred in Southeast Asia, but only two cases have been reported in South Korea, presenting with arthritis and meningitis. Here, we report a rare case of S. suis infection, a 60-year-old sailor, who visited the emergency room presenting septicemia, pneumonia with empyema and meningitis, showed full recovery; however, neurologic sequale of severe cognitive dysfunction was present after the usage of antibiotics and percutaneous drainage. S. suis was isolated from blood and pleural fluid and the strain was susceptible to penicillin and vancomycin. Increased awareness of S. suis infection and prevention are warranted.

Change in body compositions of Asian recipients after kidney transplantation.

Kidney transplantation and accompanying medical conditions may result in changes in body composition. Such changes have been evaluated in Caucasian recipients, but not in Asian recipients. Herein, we conducted a study on Asian recipients because Asians have a different body composition from Caucasians. A total of 50 Asian recipients was enrolled as a prospective cohort. Using bioelectrical impedance analysis, body composition (muscle and fat mass) was assessed after 2 weeks (baseline), and at 1, 3, 6, 9, and 12 months following kidney transplantation. To find predictors related to changes, the data were analyzed by multivariate analysis using forward selection. All of the patients had good graft function during the study period. Patients gained approximately 3 kg within 1 yr of kidney transplantation. The proportion of muscle mass significantly decreased (P(trend) = 0.001) and the proportion of fat mass significantly increased over time (P(trend) = 0.002). The multivariate results revealed that male recipients, deceased donor type, and low protein intake were associated with an increase in fat mass and a decrease in muscle mass. The results from this study may help to investigate differences in body composition changes between races, as well as the factors related to these changes.

Long-term outcomes of kidney allografts obtained by transplant tourism: observations from a single center in Korea.

AIM: Organ shortages lead end stage renal disease patients to seek overseas kidney transplantations (OTs), but the long-term outcomes of OTs have not been evaluated extensively. METHODS: Patients who received OT and were followed at Seoul National University Hospital (SNUH) from 2000 to 2009 (n = 87) were compared with patients who received kidneys from local donors (LTs) and were followed at SNUH (n = 577). Furthermore, we matched OT patients and LT patients via a propensity score using operation date, age, renal replacement therapy duration, and donor sources (n = 87 vs 87). RESULTS: The recipient age was older in the OT group (48 vs 41 years), and donor age was younger in the OT group (29 vs 39 years). The estimated glomerular filtration rates (eGFR) of functioning grafts between the groups were not different throughout the follow-up period. Biopsy-proven acute rejection, infectious disease, and hospitalization were more frequent in the OT group (27/87 vs 141/577, log-rank P < 0.001; 39/87 vs 28/577, log-rank P < 0.001; 66/87 vs 99/577, log-rank P < 0.001). The graft survival rate was lower in the OT group (82/87 vs 542/577, log-rank P = 0.003). Patient survival rate, however, was similar between the groups. After propensity score matching, the donor age was still younger in the OT group (29 vs 38 years). The risks of biopsy-proven acute rejection, infectious disease, and hospitalization were still higher in the OT group (27/87 vs 36/87, log-rank P = 0.04; 39/87 vs 3/87, log-rank P < 0.001; 66/87 vs 19/87, log-rank P < 0.001). CONCLUSION: Overseas kidney transplantation connotes risk factors that may negatively affect the long-term graft outcome.

Graft volume as the surrogate marker for nephron number affects the outcomes of living-donor kidney transplantation.

Post-transplant outcome of kidney allografts depends on various factors, one of which may be the compatibility in volume between graft and recipient. However, previous studies adjusted the graft volume only for recipient's size. As the adjusted graft volume for donor's size would be substituted of nephron number more accurately, we adjusted the graft volume for both recipient's and donor's sizes. In 351 cases of living-donor kidney transplantation, we found that the adjusted graft volume for both recipient's and donor's body surface areas (BSAs) yielded larger area under the curves for the transplant outcomes than looking only at the adjusted volume for the recipient's BSA. The recipients were separated into two groups according to the low and high adjusted graft volumes. During the follow-up period (mean 55.6 months), the low-graft-volume group conferred greater risk of rejection, chronic change, glomerulonephritis, and graft loss than the high-graft-volume group (all p's < 0.05). However, the frequency of T-cell infiltration, as evaluated in protocol biopsy, was not different between the two adjusted graft volume groups. In conclusion, the graft volume as the surrogate marker for nephron number should be considered in kidney transplantation, especially in otherwise similar donor conditions.

Acute hemodynamic effects of recruitment maneuvers in patients with acute respiratory distress syndrome.

BACKGROUND: The recruitment maneuver (RM) in acute respiratory distress syndrome (ARDS) can cause hemodynamic derangement. We evaluated circulatory and cardiac changes during RMs. METHODS: We performed sustained inflation (SI) with a pressure of 40 cm H(2)O for 30 seconds as an RM on 22 patients with ARDS. Blood pressure (BP) and heart rate were recorded immediately before, every 10 seconds during, and 30 seconds after the RM. Ventricular dimensions were obtained simultaneously using M-mode echocardiography, and tissue Doppler imaging was performed on the left ventricular wall. RESULTS: Mean, systolic, and diastolic BP decreased at 20 and 30 seconds during 30-second RMs (mean BP: 92 +/- 12 at baseline to 83 +/- 18 mm Hg at the end of the RM, P < .05) and subsequently recovered. Heart rate decreased at 10 and 20 seconds during the RM, and tended to increase afterward. Both ventricular dimensions decreased significantly during the RM. The left ventricular ejection fraction and peak velocity of the left ventricle during systole remained stable. The fractional changes in mean BP and left ventricular end-diastolic dimension during the RMs were correlated significantly with each other (r(s) = 0.59). Static compliance of the respiratory system (Crs) was lower in patients with mean BP change > or =15% than in patients in whom the change was <15% (P < .05). CONCLUSIONS: A transient decrease in mean BP was observed during the RM, and its degree was correlated with the preload decrease, while cardiac contractility was maintained.

Selectively decreased expression of peroxiredoxins induced by silica in pulmonary epithelial cells.

BACKGROUND/AIMS: Peroxiredoxin (Prx) belongs to a ubiquitous family of antioxidant enzymes that regulates many cellular processes through intracellular oxidative signal transduction pathways. Silica-induced lung damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses in alveolar epithelial cells resulting in fibrosis. Therefore, we investigated the role of Prx in the development of lung oxidant injury caused by silicosis, and determined the implication of ROS in that process. METHODS: Lung epithelial cell lines A549 and WI26 were treated with 1% silica for 0, 24, or 48 hours, following pretreatment of the A549 cells with N-acetyl-L-cysteine and diphenylene iodonium and no pretreatment of the WI26 cells. We transfected an HA-ubiquitin construct into the A549 cell line and then analyzed the cells via Western blotting and co-immunoprecipitation. RESULTS: Silica treatment induced cell death in the A549 lung epithelial cell line and selectively degraded Prx I without impairing protein synthesis in the A549 cells, even when the ROS effect was blocked chemically by N-acetyl-L-cysteine. A co-immunoprecipitation study revealed that Prx I did not undergo ubiquitination. CONCLUSIONS: Silica treatment induces a decrease of Prx I expression in lung epithelial cell lines regardless of the presence of ROS. The silica-induced degradation of Prx does not involve the ubiquitin-proteasomal pathway.

Low expression of Bax predicts poor prognosis in resected non-small cell lung cancer patients with non-squamous histology.

OBJECTIVE: The present study evaluated the prognostic significance of apoptosis-related proteins p53, Bax and galectin-3 in patients with non-small cell lung cancer (NSCLC) treated with surgical resection. METHODS: We investigated the expression of these proteins and their association with clinicopathologic characteristics including disease-free survival (DFS) and overall survival (OS) in 205 NSCLC patients who underwent surgical resection (Stage I, 97; II, 46; IIIA, 45; IIIB, 17) using immunohistochemistry. Eighty-eight patients (43%) received adjuvant treatment (chemotherapy: 8, radiotherapy: 24, both: 56). RESULTS: High expressions of Bax, p53 and galectin-3 were observed in 48 (23%), 81 (40%) and 105 (51%) patients, respectively. Low expression of Bax was significantly associated with male gender, squamous cell histology and low expression of galectin-3. Five-year DFS and OS of total patients were 37 and 46%, respectively. High expressions of p53 and galectin-3 were not associated with poor DFS or OS, and no significant correlation existed between low expression of Bax and outcome of patients. However, in patients with non-squamous histology (108 patients), low expression of Bax was a significant independent predictor of poor DFS (P = 0.017) and OS (P = 0.037). In addition, in patients with Stage II or III disease, low expression of Bax significantly correlated with poor DFS (P = 0.004). It was also the most significant independent poor prognostic factor second only to a large primary tumor size in Stage II or III patients with non-squamous histology. CONCLUSIONS: Low expression of Bax was significantly associated with poor prognosis in resected NSCLC patients with non-squamous histology.

Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis.

BACKGROUND: Apoptosis is thought to play an important role in the development of acute respiratory distress syndrome (ARDS). We evaluated the bronchoalveolar lavage (BAL) fluid from ARDS patients focusing on apoptosis. METHODS: The study enrolled 31 ARDS patients and 20 healthy controls. BAL fluid levels of caspase-cleaved cytokeratin-18 (CK-18) and soluble mediators such as interleukin-8 (IL-8), soluble Fas (sFas), soluble Fas ligand (sFasL), growth-related oncogene-alpha (GRO-alpha), granulocyte colony-stimulating factor (G-CSF), and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The BAL fluid caspase-cleaved CK-18 levels in ARDS patients were higher than those in controls, reflecting increased epithelial apoptosis, and were correlated with lung injury scores (rs=0.49). The BAL fluid levels of all mediators were significantly higher in ARDS patients than in controls. In ARDS patients, the BAL fluid IL-8 level was positively correlated with the levels of sFas (rs=0.57), GRO-alpha (rs=0.47), and TRAIL (rs=0.45). The BAL fluid IL-8 (rs=0.61), sFas (rs=0.57), G-CSF (rs=0.44), and TRAIL (rs=0.33) levels were correlated with the BAL fluid neutrophil count. The G-CSF levels were significantly higher in non-surviving than in surviving ARDS patients [median 183.4 pg/mL (interquartile range 76.7-315.9) vs. 63.8 pg/mL (36.2-137.2); p<0.05]. The sFas levels were positively correlated with the PaO2/FiO2 ratio (rs=0.40), and the TRAIL levels were negatively correlated with the multiple organ dysfunction scores (rs=-0.37). CONCLUSIONS: Among the mediators in BAL fluid from ARDS patients, G-CSF had the most significant prognostic implications, and the sFas and TRAIL levels were correlated with clinical severity.

Serum angiopoietin-2 as a clinical marker for lung cancer.

BACKGROUND: Angiopoietins play a critical role in the angiogenesis related to tumor growth in concert with vascular endothelial growth factor (VEGF), and enhanced expression of angiopoietin-2 has been reported in lung cancer tissue. METHODS: Patients with lung cancer (n = 136) and healthy volunteers (n = 40) were enrolled. Serum angiopoietin-2 and VEGF concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: Patients with lung cancer had higher serum angiopoietin-2 (2,046.3 +/- 1,171.3 pg/mL vs 1,269.8 +/- 494.1 pg/mL, p < 0.001) and VEGF (542.9 +/- 445.8 pg/mL vs 364.7 +/- 185.9 pg/mL, p < 0.05) [mean +/- SD] levels than the control group. Serum angiopoietin-2 and VEGF levels correlated with each other in patients with lung cancer (Spearman r = 0.30, p < 0.001), specifically in non-small cell lung cancer (NSCLC) [n = 110; r = 0.34; p < 0.001] but not in small cell lung cancer (n = 26). With stage progression in NSCLC, serum angiopoietin-2 levels increased, and patients with distant metastasis had higher levels than those without metastasis (p < 0.005). By contrast, serum VEGF level did not increase with stage progression, and only had a trend toward elevation in distant metastasis (p = 0.05). In NSCLC, the low angiopoietin-2 group (< 1,605.5 pg/mL) had a better overall survival compared to the high angiopoietin-2 group (> or = 1,605.5 pg/mL; p < 0.05), although this survival benefit was not maintained after controlling for stage in a multivariate analysis. The angiopoietin-2 levels were higher in NSCLC patients with postoperative recurrence than in those without. CONCLUSIONS: Our study suggests that serum angiopoietin-2 is a useful clinical marker for detecting NSCLC with distant metastasis and is of potential prognostic value.

Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung.

BACKGROUND: Peroxiredoxins (Prxs) have been implicated in regulating many cellular processes including cell proliferation, differentiation and apoptosis. However, the pathophysiological significance of Prx proteins, especially in lung disease, has not been defined. Therefore, the authors investigated the distribution and expression of various Prx isoforms in lung cancer and compared this with normal lung from human and mouse. METHODS: Patients diagnosed with lung cancer who underwent surgery at Ajou Medical Center were enrolled. Expression of Prxs, thioredoxin and thioredoxin reductase was analysed by proteomic techniques. Immunohistochemistry was performed to localize Prx proteins. RESULTS: Immunohistochemical staining showed that the isoforms of Prx I, II, III and V were predominantly expressed in bronchial and alveolar epithelium as well as in alveolar macrophages of the normal mouse lung. The isoforms I, III and thioredoxin were overexpressed in lung cancer tissues compared with normal lungs. There was also an increased amount of oxidized form of Prx I and a putative truncated form of Prx III in lung cancer samples when analysed on two-dimensional electrophoresis. In addition, a 40-kDa intermediate MW protein band and high MW bands of over 20 kDa, recognized by anti-Prx (a-Prx) I antibody, were present in tissue extracts of lung cancer patients on one-dimensional electrophoresis. CONCLUSION: The upregulation of Prx I, Prx III and thioredoxin in lung cancer tissue may represent an attempt by tumour cells to adjust to the microenvironment in a manner that is advantageous to survival and proliferation.