The Role of Adjuvant Therapy Following Surgical Resection of Small Cell Lung Cancer: A Multi-Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This multi-center, retrospective study was conducted to evaluate the long-term survival in patients who underwent surgical resection for small cell lung cancer (SCLC) and to identify the benefit of adjuvant therapy following surgery. @*Materials and Methods@#The data of 213 patients who underwent surgical resection for SCLC at four institutions were retrospectively reviewed. Patients who received neoadjuvant therapy or an incomplete resection were excluded. @*Results@#The mean patient age was 65.29±8.93 years, and 184 patients (86.4%) were male. Lobectomies and pneumonectomies were performed in 173 patients (81.2%), and 198 (93%) underwent systematic mediastinal lymph node dissections. Overall, 170 patients (79.8%) underwent adjuvant chemotherapy, 42 (19.7%) underwent radiotherapy to the mediastinum, and 23 (10.8%) underwent prophylactic cranial irradiation. The median follow-up period was 31.08 months (interquartile range, 13.79 to 64.52 months). The 5-year overall survival (OS) and disease-free survival were 53.4% and 46.9%, respectively. The 5-year OS significantly improved after adjuvant chemotherapy in all patients (57.4% vs. 40.3%, p=0.007), and the survival benefit of adjuvant chemotherapy was significant in patients with negative node pathology (70.8% vs. 39.7%, p=0.004). Adjuvant radiotherapy did not affect the 5-year OS (54.6% vs. 48.5%, p=0.458). Age (hazard ratio [HR], 1.032; p=0.017), node metastasis (HR, 2.190; p < 0.001), and adjuvant chemotherapy (HR, 0.558; p=0.019) were associated with OS. @*Conclusion@#Adjuvant chemotherapy after surgical resection in patients with SCLC improved the OS, though adjuvant radiotherapy to the mediastinum did not improve the survival or decrease the locoregional recurrence rate.

ABT-737, a BH3 Mimetic, Enhances the Therapeutic Effects of Ionizing Radiation in K-ras Mutant Non-Small Cell Lung Cancer Preclinical Model

Purpose@#Tumor radioresistance and dose-limiting toxicity restrict the curative potential of radiotherapy, requiring novel approaches to overcome the limitations and augment the efficacy. Here, we investigated the effects of signal transducer and activator of transcription 3 (STAT3) activation and autophagy induction by irradiation on antiapoptotic proteins and the effectiveness of the BH3 mimetic ABT-737 as a radiosensitizer using K-ras mutant non-small cell lung cancer (NSCLC) cells and a Kras G12D :p53 fl/fl mouse (KP mouse) model. @*Materials and Methods@#A549 and H460 cells were irradiated, and the expression of Bcl-2 family proteins, JAK/STAT transcriptional pathway, and autophagic pathway were evaluated by immunoblotting. The radiosensitizing effects of ABT-737 were evaluated using A549 and H460 cell lines with clonogenic assays and also by a KP mouse model with microcomputed tomography and immunohistochemistry. @*Results@#In A549 and H460 cells and mouse lung tissue, irradiation-induced overexpression of the antiapoptotic molecules BclxL, Bcl-2, Bcl-w, and Mcl-1 through JAK/STAT transcriptional signaling induced dysfunction of the autophagic pathway. After treatment with ABT-737 and exposure to irradiation, the number of surviving clones in the cotreatment group was significantly lower than that in the group treated with radiation or ABT-737 alone. In the KP mouse lung cancer model, cotreatment with ABT-737 and radiation-induced significant tumor regression; however, body weight changes in the combination group were not significantly different, suggesting that combination treatment did not cause systemic toxicity. @*Conclusion@#These findings supported the radiosensitizing activity of ABT-737 in preclinical models, and suggested that clinical trials using this strategy may be beneficial in K-ras mutant NSCLC.

The Assessment and Outcomes of Crossmatching in Lung Transplantation in Korean Patients

Background@#In lung transplantation, human leukocyte antigen (HLA) compatibility is not included in the lung allocation score system or considered when placing donor allografts.However, HLA matching may affect the outcomes of lung transplantation. This study evaluated the current assessment status, prevalence, and effects of HLA crossmatching in lung transplantation in Korean patients using nationwide multicenter registry data. @*Methods@#Two hundred and twenty patients who received lung transplantation at six tertiary hospitals in South Korea between March 2015 and December 2019 were retrospectively reviewed. Clinical data, including general demographic characteristics, primary diagnosis, and pretransplant status of the recipients and donors registered by the Korean Organ Transplant Registry, were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier method with log-rank tests. @*Results@#Complement-dependent cytotoxic crossmatch (CDC-XM) was performed in 208 patients (94.5%) and flow cytometric crossmatch (flow-XM) was performed in 125 patients (56.8%). Among them, nine patients (4.1%) showed T cell- and/or B cell-positive crossmatches. The incidences of postoperative complications, including primary graft dysfunction, acute rejection, and chronic allograft dysfunction in positively crossmatched patients, were not significant compared with those in patients without mismatches.Moreover, Kaplan-Meier analyses showed poorer 1-year survival in patients with positive crossmatch according to CDC-XM (P < 0.001) and T lymphocyte XM (P = 0.002) than in patients without mismatches. @*Conclusion@#Positive CDC and T lymphocyte crossmatching results should be considered in the allocation of donor lungs. If unavailable, the result should be considered for postoperative management in lung transplantation.

Basiliximab Induction with Delayed Calcineurin Inhibitors for High-Risk Lung Transplant Candidates

Purpose@#Calcineurin inhibitor (CNI) use has improved lung transplantation outcomes. However, significant perioperative complications in patients receiving CNI can deteriorate the early course of lung transplantation. To date, there is no consensus regarding the optimal agent for the induction regimen after lung transplantation. We aimed to determine the efficacy of basiliximab induction with delayed CNI initiation in the prevention of acute complications without compromising immunosuppression in high-risk patients. @*Materials and Methods@#Between January 2013 and December 2019, 236 patients at a single lung transplant center were retrospectively reviewed. Forty-one patients (17.4%) received basiliximab induction, and 195 patients (82.6%) received a routine triple-drug regimen without induction. The primary endpoint was postoperative acute kidney injury with several other postoperative outcomes as secondary end-points. @*Results@#Preoperatively, the induction group had a higher proportion of patients who were admitted before transplantation (95.1% vs. 47.7%, p<0.001) and received intensive unit care (90.2% vs. 33.8%, p<0.001) and extracorporeal membrane oxygenation (ECMO) (87.8% vs. 20.0%, p<0.001) compared to the non-induction group. No significant differences were observed in the incidence of acute rejection between groups (p=0.657), although lower incidence of postoperative complications, including acute kidney injuries or culture-proven infections, were observed in the induction group. However, the differences were not statistically significant. A subgroup analysis of high-risk and preoperative ECMO support groups showed similar results. @*Conclusion@#Basiliximab induction with delayed CNI initiation for high-risk patients might decrease the incidence of perioperative complications, including acute renal failure, without increasing the risk of acute rejection.

Factors Affecting the Number of Stapler Cartridges in Complete Video-Assisted Thoracoscopic Surgery Lobectomy for Non-small Cell Lung Cancer

Background@#Video-assisted thoracoscopic surgery (VATS) lobectomy has become the major surgical option for the treatment of non-small cell lung cancer (NSCLC). Endoscopic instruments such as stapler cartridges are essential for VATS procedures. In this study, we investigated the factors that affect the number of stapler cartridges used in VATS lobectomy. @*Methods@#A retrospective analysis was conducted of patients who underwent complete VATS lobectomy for NSCLC from January 2013 to December 2015. @*Results@#In total, 596 patients underwent complete VATS lobectomy. The average number of stapler cartridges used for VATS lobectomy was 5.3±1.9. The number of stapler cartridges used for VATS lobectomy was higher in men (5.5±1.9 vs. 5.0±18, p=0.006), those aged older than 70 years (5.5±2.1 vs. 5.1±1.7, p=0.038), those who underwent upper or middle lobectomy procedures (5.7±1.9 vs. 4.1±1.2, p<0.001), those with a higher fissure sum average (p<0.001), and those in whom surgery was performed by a surgeon with a preference for staplers (5.6±2.0 vs. 4.9±1.6, p<0.001). @*Conclusion@#The number of stapler cartridges required to perform VATS lobectomy in NSCLC patients appears to be influenced by sex, age, the location of the tumor, the degree of fissure development, and the surgeon’s preference.

Incidental Lung Cancer of Explanted Lungs from Lung Transplant Recipients:Incidence, Characteristics, and 5-Year Survival

Purpose@#Recent history of malignancy without 5-year disease-free interval is an absolute contraindication for lung transplantation (LTx). However, in rare cases, lung cancer may be incidentally diagnosed in the explanted lung of recipients. We evaluated the prevalence, 5-year survival, and prognosis of incidental lung cancer after LTx. @*Materials and Methods@#Medical records of patients who underwent LTx at Severance Hospital between January 1, 2012 and June 30, 2019 were reviewed. Patients with incidental lung cancer were included, and those with histologically proven pre-transplant lung cancer were excluded. @*Results@#Of the 247 patients who underwent LTx, 6 (2.4%) were diagnosed with incidental lung cancer. Interstitial lung disease (ILD) was the underlying lung disease in all patients. The median interval from the last preoperative computed tomography (CT) screening to LTx was 26 days. The most common histological type of incidental lung cancer was adenocarcinoma (n=4, 66.7%).All Stage IV cases were misdiagnosed as fibrosis on preoperative chest CT. Patients with incidental lung cancer showed lower 5-year survival than those without malignancy (median survival: 8.5 months vs. not reached, p=0.047, respectively). Patients with Stage III or IV demonstrated lower 5-year survival than those with Stage I or II and those without malignancy (median survival: 5 months, 19 months, and not reached, respectively, p=0.011). @*Conclusion@#Multidisciplinary preoperative screening and serial imaging studies within short intervals are required to differentiate lung malignancy from fibrotic foci. Furthermore, active pathologic examination of suspicious lung lesions is required in patients at high risk for lung cancer.

Panel-Reactive and Donor-Specific Antibodies before Lung Transplantation can Affect Outcomes in Korean Patients Receiving Lung Transplantation

Purpose@#Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. @*Materials and Methods@#This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. @*Results@#Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). @*Conclusion@#Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

Clinical significance of postoperative atrial arrhythmias in patients who underwent lung transplantation

Background/Aims@#Atrial arrhythmia (AA) occasionally occurs after lung transplantation (LT); however, risk factors for AA and their impact on clinical outcomes are inconsistent. We aimed to investigate the incidence, predisposing factors, and clinical outcomes of AA after LT. @*Methods@#We retrospectively evaluated 153 consecutive patients who underwent LT between January 2010 and August 2016. An AA episode was defined as a documented atrial fibrillation (AF), atrial flutter, or atrial tachycardia on 12-lead electrocardiography or episodes lasting ≥ 30 seconds on telemetry monitoring. @*Results@#The mean follow-up time was 22.0 ± 19.1 months. Postoperative AA occurred in 46 patients (30.1%) after LT. Patients with postoperative AA were older, had larger body surface area, and had an increased incidence of paroxysmal AF prior to transplantation, idiopathic pulmonary fibrosis, and postoperative tracheostomy than patients without AA. Preoperative right atrial pressure (RAP) (odds ratio [OR], 1.19; p = 0.005) and longer periods of mechanical ventilation (OR, 1.03; p = 0.008) were found to be independent risk factors for AA after surgery. Development of AA was a significant predictor of long-term overall mortality (hazard ratio, 2.75; p = 0.017). @*Conclusions@#Patients with elevated preoperative RAP and long-term ventilator care had a higher risk of AA after LT. Further, AA after LT was associated with poor long-term survival.

Characteristics of Lung Allocation and Outcomes of Lung Transplant according to the Korean Urgency Status

PURPOSE: We investigated the characteristics of lung allocation and outcomes of lung transplant (LTx) according to the Korean urgency status. MATERIALS AND METHODS: LTx registration in the Korean Organ Transplantation Registry (KOTRY) began in 2015. From 2015 to June 2017, 86 patients who received LTx were enrolled in KOTRY. After excluding one patient who received a heart-lung transplant, 85 were included. Subjects were analyzed according to the Korean urgency status. RESULTS: Except for Status 0, urgency status was classified based on partial pressure of oxygen in arterial blood gas analysis and functional status in 52 patients (93%). The wait time for lung allograft was well-stratified by urgency (Status 0, 46.5±59.2 days; Status 1, 104.4±98.2 days; Status 2 or 3, 132.2±118.4 days, p=0.009). Status 0 was associated with increased operative times and higher intraoperative blood transfusion. Status 0 was associated with prolonged extracorporeal membrane oxygenation use, postoperative bleeding, and longer mechanical ventilation after operation. Survival of Status 0 patients seemed worse than that of non-Status 0 patients, although differences were not significant. CONCLUSION: The Korean urgency classification for LTx is determined by using very limited parameters and may not be a true reflection of urgency. Status 0 patients seem to have poor outcomes compared to the other urgency status patients, despite having the highest priority for donor lungs. Further multi-center and nationwide studies are needed to revise the lung allocation system to reflect true urgency and provide the best benefit of lung transplantation.

Preoperative Corticosteroid Use and Early Postoperative Bronchial Anastomotic Complications after Lung Transplantation

BACKGROUND: Airway anastomotic complications are a leading cause of mortality after lung transplantation. Among the factors that cause airway complications, preoperative steroid use has been considered to be related with postoperative airway healing. We analyzed the influence of preoperative steroid use on postoperative airway complications. METHODS: The medical records of 66 double-lung transplant recipients from January 2014 to December 2015 were reviewed. Forty patients were prescribed steroids preoperatively. The daily steroid dose was standardized using the patient’s body mass index (BMI). Patients who received preoperative steroids were sub-divided into high-dose (HD) and low-dose (LD) groups (cut-off value, 1.6 mg/BMI/day). RESULTS: Thirteen patients suffered from airway complications postoperatively (bronchopulmonary fistula, 9; bronchial stenosis, 4). There was a tendency for early development of airway complications in the steroid use group compared to the non-steroid use group, but it was not significant (percentage free from airway complications in year 1: non-steroid group, 90.9% vs. steroid group, 79.2%; p=0.43). The percentage of patients in the LD and HD groups who were free from airway complications in year 1 was not significantly different (84.0% vs. 77.8%, p=0.39). CONCLUSION: The airway complication rate did not vary significantly according to steroid use. Additionally, in patients who received preoperative steroids, the dose did not affect the rate of development of airway complications.

Factors Associated with Lung Function Recovery at the First Year after Lung Transplantation

PURPOSE: Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs. < 80%). We compared the two groups and analyzed factors associated with lung function recovery. RESULTS: Fifty-eight patients were enrolled in this study: 28 patients (48%) recovered to a FEV1 ≥80% of the predicted value, whereas 30 patients (52%) did not. Younger recipients [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.87–0.98; p=0.010], longer duration of mechanical ventilator use after surgery (OR, 1.14; 95% CI, 1.03–1.26; p=0.015), and high-grade primary graft dysfunction (OR, 8.08; 95% CI, 1.67–39.18; p=0.009) were identified as independent risk factors associated with a lack of full recovery of lung function at 1 year after lung transplantation. CONCLUSION: Immediate postoperative status may be associated with recovery of lung function after lung transplantation.

Surgical Repair of a Traumatic Tracheobronchial Injury in a Pediatric Patient Assisted with Venoarterial Extracorporeal Membrane Oxygenation

Tracheobronchial rupture due to blunt chest trauma is a rare but life-threatening injury in the pediatric population. Computed tomography (CT) is not always reliable in the management of these patients. An additional concern is that ventilation may be disrupted during surgical repair of these injuries. This report presents the case of a 4 -year-old boy with an injury to the lower trachea and carina due to blunt force trauma that was missed on the initial CT scan. During surgery, he was administered venoarterial extracorporeal membrane oxygenation (ECMO). Although ECMO is not generally used in children, this case demonstrated that the short-term use of ECMO during pediatric surgery is safe and can prevent intraoperative desaturation.

Surgical Repair of a Traumatic Tracheobronchial Injury in a Pediatric Patient Assisted with Venoarterial Extracorporeal Membrane Oxygenation

Tracheobronchial rupture due to blunt chest trauma is a rare but life-threatening injury in the pediatric population. Computed tomography (CT) is not always reliable in the management of these patients. An additional concern is that ventilation may be disrupted during surgical repair of these injuries. This report presents the case of a 4 -year-old boy with an injury to the lower trachea and carina due to blunt force trauma that was missed on the initial CT scan. During surgery, he was administered venoarterial extracorporeal membrane oxygenation (ECMO). Although ECMO is not generally used in children, this case demonstrated that the short-term use of ECMO during pediatric surgery is safe and can prevent intraoperative desaturation.

Tacrolimus-induced, Transplant-associated Thrombotic Microangiopathies after Lung Transplantation / 대한이식학회지

We report a case of tacrolimus-induced transplant-associated thrombotic microangiopathies (TA-TMA) after lung transplantation. A 71-year-old man underwent lung transplantation secondary to idiopathic pulmonary fibrosis. After 4 months, he presented with abdominal discomfort and dyspnea, and was diagnosed with hemolytic anemia and thrombocytopenia. Tacrolimus was considered the cause of the TMA. Tacrolimus was stopped and several sessions of plasma exchange were performed immediately after diagnosis of TA-TMA. However, his platelet count did not normalize, gastrointestinal bleeding was recurrent, and severe pneumonia developed, following which he died. TA-TMA are rare but severe, life-threatening complications in lung transplant recipients. Therefore, the possibility of TA-TMA should be considered in posttransplant recipients.

Successful Management of Delayed Esophageal Rupture with T-Tube Drainage Using Video-Assisted Thoracoscopic Surgery

Spontaneous perforation of the esophagus after forceful vomiting is known as Boerhaave syndrome, a rare and life-threatening condition associated with a high rate of mortality. The management of Boerhaave syndrome is challenging, especially when diagnosed late. Herein, we report the successful management of late-diagnosed Boerhaave syndrome with T-tube drainage in a 55-year-old man. The patient was transferred to our institution 8 days after the onset of symptoms, successfully managed by placing a T-tube, and was discharged on postoperative day 46 without complications.

Combined Bilateral Lung Transplantation and Off-Pump Coronary Artery Bypass

Coronary artery disease has historically been a contraindication to lung transplantation. We report a successful combined bilateral lung transplantation and off-pump coronary artery bypass in a 62-year-old man. The patient had a progressive decline in lung function due to idiopathic pulmonary fibrosis and a history of severe occlusive coronary artery disease.

Three-Dimensional Ground Glass Opacity Ratio in CT Images Can Predict Tumor Invasiveness of Stage IA Lung Cancer

PURPOSE: We investigated the relationship between various parameters, including volumetric parameters, and tumor invasiveness according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with completely resected stage IA lung adenocarcinoma. The correlation between several parameters [one-dimensional ground glass opacity (1D GGO) ratio, two-dimensional (2D) GGO ratio, three-dimensional (3D) GGO ratio, 1D solid size, 2D solid size, and 3D solid size] and tumor invasiveness according to IASLC/ATS/ERS classification was investigated using receiver operating characteristic (ROC) analysis. Adenocarcinoma in situ and minimally invasive adenocarcinoma were referred to as noninvasive adenocarcinoma. RESULTS: The areas under the curve (AUC) to predict invasive adenocarcinoma for the 1D, 2D, and 3D GGO ratios were 0.962, 0.967, and 0.971, respectively. The optimal cut-off values for the 1D, 2D, and 3D GGO ratios were 38%, 62%, and 74%, respectively. The AUC values for 1D, 2D, and 3D solid sizes to predict invasive adenocarcinoma were 0.933, 0.944, and 0.903, respectively. The optimal cut-off values for 1D, 2D, and 3D solid sizes were 1.2 cm, 1.5 cm2, and 0.7 cm3, respectively. The difference in the ROC curves for 3D GGO ratio and 3D solid size was significant (p=0.01). CONCLUSION: Computed tomography image-related parameters based on GGO were well correlated with and predictive of invasiveness according to IASLC/ATS/ERS classification. 3D GGO ratio was more strongly correlated with pathologic invasiveness than 3D solid size.

Comparison of Predicted Total Lung Capacity and Total Lung Capacity by Computed Tomography in Lung Transplantation Candidates

PURPOSE: Lung size mismatch is a major cause of poor lung function and worse survival after lung transplantation (LTx). We compared predicted total lung capacity (pTLC) and TLC measured by chest computed tomography (TLC(CT)) in LTx candidates. MATERIALS AND METHODS: We reviewed the medical records of patients on waiting lists for LTx. According to the results of pulmonary function tests, patients were divided into an obstructive disease group and restrictive disease group. The differences between pTLC calculated using the equation of the European Respiratory Society and TLC(CT) were analyzed in each group. RESULTS: Ninety two patients met the criteria. Thirty five patients were included in the obstructive disease group, and 57 patients were included in the restrictive disease group. pTLC in the obstructive disease group (5.50±1.07 L) and restrictive disease group (5.57±1.03 L) had no statistical significance (p=0.747), while TLC(CT) in the restrictive disease group (3.17±1.15 L) was smaller than that I the obstructive disease group (4.21±1.38 L) (p<0.0001). TLC(CT)/pTLC was 0.770 in the obstructive disease group and 0.571 in the restrictive disease group. CONCLUSION: Regardless of pulmonary disease pattern, TLC(CT) was smaller than pTLC, and it was more apparent in restrictive lung disease. Therefore, we should consider the difference between TLC(CT) and pTLC, as well as lung disease patterns of candidates, in lung size matching for LTx.

Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

BACKGROUNDS/AIMS: Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. METHODS: Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. RESULTS: Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). CONCLUSIONS: Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.

The Effects of N-acetylcystein and Epigallocatechin-3-Gallate in Ischemia-Reperfusion Injury of Rat Lungs / 대한이식학회지

BACKGROUND: Ischemia-reperfusion injury (IRI) is a major cause of early graft dysfunction after lung transplantation. The aim of this study was to assess the effects of N-acetylcystein (NAC) and epigallocatechin-3-gallate (EGCG) on IRI of rat lungs. METHODS: Sprague-Dawley rats were divided into four groups. Sham group (n=6) did not receive IRI. Rats in the control group (n=6), NAC group (n=6), and EGCG group (n=6) were treated with an intraperitoneal injection of normal saline, NAC, and EGCG, respectively, prior to IRI. In the latter three groups, IRI was induced by clamping the left pulmonary artery, vein, and main stem bronchus for a period of 60 minutes. After ischemia, reperfusion and ventilation of the lung was allowed for a period of 180 minutes. The expression levels of inducible nitric oxide synthase (iNOS), hemeoxygenase-1 (HO-1), AMP-activated protein kinase-alpha (AMPK), and caveolin-1 in lung tissues were evaluated by Western blot. The pathological findings and the extent of pulmonary edema after IRI were compared among the groups. RESULTS: The expression levels of iNOS decreased in the Sham and EGCG groups. The expression level of HO-1 was significantly higher in the EGCG group (P=0.0001). Although the expression levels of AMPK and caveolin-1 showed no differences, the extent of phosphorylation of AMPK and caveolin-1 was higher in the EGCG and NAC groups, respectively. In hematoxylin-eosin staining, the lungs in the NAC and EGCG groups showed fewer alveolar injuries and less hemorrhagic congestion compared with the control group. CONCLUSIONS: NAC and EGCG enhanced the phosphorylation of caveolin-1 and AMPK, respectively, and attenuated lung injury induced by ischemia-reperfusion.