Risk Factors for Unplanned Early Implantable Port Catheter Removal in Adult Hematology Cancer Patients Receiving Chemotherapy: A Propensity Score Matching Study.

Purpose: Implantable port catheter is a reliable vascular access for chemotherapy infusion in cancer patients. However, patients with hematology malignancies usually present with a myriad of blood cell abnormalities that put them at risk of infection and mechanical problems requiring catheter removal. This study aims to determine the risk factors associated with unplanned (catheter removal other than completion of treatment plan) early (within 90 days of catheter implantation) implantable port catheter removal. Patients and Methods: A retrospective, propensity score-matched study of 386 patients with hematology malignancies who received implantable venous access ports between January 2015 and December 2022. We conducted a univariate analysis to select the variables for propensity score matching. Patients with unplanned early implantable port catheter removal (early group) were matched 1:1 to patients without unplanned early removal (non-early group). Results: Univariate analysis demonstrated a statistically significant difference between early and non-early groups for age (p = 0.048), hemoglobin level (p = 0.028), thrombocytopenia (p = 0.025), and PG-SGA (p < 0.001). Thrombocytopenia was the only independent risk factor with a statistically significant difference in Cox proportional hazard analysis, HR 2.823, 95 CI 1.050-7.589, p = 0.040. The median catheter survival for patients with thrombocytopenia was 61 days (95% CI 28.58-93.42) compared to 150 days (95% CI 9.81-290.19) for patients without thrombocytopenia, p = 0.015. Patient survival is not affected by early catheter removal. The median survival for patients in the early group was 28.28 months (95% CI 27.43-29.15) compared to 32.39 months (95% CI 24.11-40.68), for the non-early group, p = 0.709. Conclusion: Hematology malignancy patients with thrombocytopenia are at high risk for unplanned early port catheter removal without survival difference.

Pseudomonas aeruginosa Infections Are Associated with Infection Recurrence in Arteriovenous Grafts Treated with Revision.

Background and Objectives: This study was conducted to investigate whether Pseudomonas aeruginosa (PA) infections of arteriovenous grafts (AVGs) recur more frequently than other bacterial infections following treatment with revision. Materials and Methods: Operative procedures, including total excision, subtotal excision, and revision, were performed on 60 patients to treat 65 AVG infections. Final outcomes were classified as no infection recurrence, infection recurrence, and death without prior recurrence. In the competing risk setting, the cumulative incidence was estimated using the cumulative incidence function and Gray's test, and the associations between outcomes and different variables were estimated using a subdistribution hazard (SDH) model. Results: Comparing AVG infections with and without recurrence, PA infection was not associated with a higher risk of infection recurrence (p = 0.13); however, the first operative procedure type was associated with infection recurrence (p = 0.04). AVGs with PA infection were associated with a higher total number of surgical interventions (p < 0.05) than AVGs without PA infection. Regarding the cumulative incidences of outcomes, for AVGs treated with subtotal excision or revision, the cumulative incidence of recurrent infection was 3.3-fold higher for those with PA infection than without one year after the first surgery. However, when AVGs were treated with revision alone, the cumulative incidence was 4.1-fold. After excluding AVGs treated with total excision, the SDH model was applied, obtaining a hazard ratio for infection recurrence of 16.05 (p = 0.02) for AVGs with PA infection compared with AVGs without PA infection. No other variables were significantly associated with infection recurrence. Conclusions: For subtotal resection and revision, AVGs infected with PA had a higher recurrence rate than those infected with other species. However, revision surgery may aggravate the recurrence rate.

Appraisal of lung cancer survival in patients with end-stage renal disease.

Introduction: The survival outcome of lung cancer patients with end-stage renal disease has been poorly studied in the literature. In this study, we evaluated the effect of end-stage renal disease on lung cancer survival. Material and methods: A retrospective, multicenter, matched-cohort study of lung cancer patients with end-stage renal disease under renal replacement therapy (WITH-ESRD) and without end-stage renal disease (WITHOUT-ESRD) was performed. One WITH-ESRD patient was matched to four WITHOUT-ESRD patients. Results: Baseline clinical characteristics did not differ statistically significantly after matching between the WITH-ESRD and WITHOUT-ESRD groups. WITH-ESRD included 133 patients and WITHOUT-ESRD included 532 patients. Kaplan-Meier survival analysis demonstrated no significant difference in median overall survival between WITH-ESRD patients and WITHOUT-ESRD patients (7.36 months versus 12.25 months, respectively, p = 0.133). Lung cancer WITH-ESRD patients receiving medical treatment had a median overall survival of 5.98 months (95% CI: 4.34-11.76) compared to 14.13 months (95% CI: 11.30-16.43) for WITHOUT-ESRD patients, p = 0.019. Although patients receiving surgical treatment compared to those receiving medical treatment had an improvement of survival by 46% (HR = 0.54, 95% CI: 0.19-1.53, p = 0.243), the difference did not reach statistical significance. Cox regression analysis revealed that male gender and stage IIIA-IV were independent factors associated with poor outcome for WITH-ESRD patients. Conclusions: In our limited experience, the survival for lung cancer with ESRD is not inferior to lung cancer patients without ESRD. The reasons for poor survival for the WITH-ESRD medical treatment group and late diagnosis despite frequent medical visits merit further investigation.

The role of venous pressure variability during hemodialysis in the prediction of impending arteriovenous graft occlusion.

BACKGROUND: Elevated venous pressure during hemodialysis (VPHD) is associated with arteriovenous graft (AVG) stenosis. This study investigated the role of VPHD variations in the prediction of impending AVG occlusion. METHODS: Data were retrieved from 118 operations to treat AVG occlusion (occlusion group) and 149 operations to treat significant AVG stenosis (stenosis group). In addition to analyzing the VPHD values for the three hemodialysis (HD) sessions prior to the intervention, VPHD values were normalized to mean blood pressure (MBP), blood flow rate (BFR), BFR × MBP, and BFR2 × MBP to yield ratios for analysis. The coefficient of variation (CV) was used to measure relative variations. RESULTS: The within-group comparisons for both groups revealed no significant differences in the VPHD mean and CV values among the three HD sessions prior to intervention. However, the CVs for VPHD/MBP, VPHD/(BFR × MBP), and VPHD/(BFR2 × MBP) exhibited significant elevation in the occlusion group during the last HD session prior to intervention compared with both the penultimate and antepenultimate within-group HD data (p < 0.05). In the receiver operating characteristic curve analysis, the CV for VPHD/(BFR2 × MBP) was the only parameter able to discriminate between the last and the penultimate HD outcomes (p < 0.001). According to a multivariate analysis, after controlling for covariates, CV for VPHD/(BFR2 × MBP) >8.76% was associated with a higher risk of AVG thrombosis (odds ratio: 3.17, p < 0.001). CONCLUSIONS: Increasing the variation in VPHD/(BFR2 × MBP) may increase the probability of AVG occlusion.

The potential and limitation of targeted chromosomal breakpoint sequencing for the ROS1 fusion gene identification in lung cancer.

ROS1 fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each ROS1 fusion variant are still largely unknown and require further investigation. RNA is the preferable template for the ROS1 fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the ROS1 fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that ROS1-altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in ROS1 fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all ROS1 fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with ROS1 alterations.

Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma.

Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.

Survival of Patients with Lung Cancer in the Setting of Liver Cirrhosis: A Multicenter Propensity Score Matching Study.

PURPOSE: The survival outcome of lung cancer patients with coexisting liver cirrhosis has thus far received limited attention in the literature. In this study, we evaluated whether liver cirrhosis is an independent risk factor for the survival of patients with lung cancer. MATERIALS AND METHODS: We conducted a retrospective, multicenter, propensity-matched study of lung cancer patients with and without liver cirrhosis. To determine differences in survival, we sought to identify risk factors associated with poor outcomes using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: There were no statistically significant differences in the baseline clinical characteristics of patients between the cirrhosis and non-cirrhosis groups. The median overall survival of patients with and without cirrhosis was 13.07 months (95% confidence interval [CI]: 10.56-16.84) and 13.67 months (95% CI: 10.42-16.91), respectively (p=0.76). Cox proportional hazards regression analysis revealed that liver cirrhosis was not an independent risk factor for poor outcome (hazard ratio [HR]: 1.057, 95% CI: 0.805-1.388, p=0.690). In patients with cirrhosis, lower serum albumin levels, higher Charlson Comorbidity Index score, advanced-stage lung cancer, and treatment modality were factors associated with poor outcome. Increase in serum albumin by 1 g was associated with a 30% reduction in the risk of mortality (HR: 0.700, 95% CI: 0.494-0.993, p=0.045). While every point increase in the Charlson Comorbidity Index score by 1 point was linked to a 9% higher risk of mortality (HR: 1.090, 95% CI: 1.023-1.161, p=0.007). CONCLUSION: The survival rates of lung cancer patients with and without cirrhosis did not differ significantly. Higher serum albumin levels and lower Charlson Comorbidity Index scores were associated with improved survival.

Porphyromonas gingivalis promotes tumor progression in esophageal squamous cell carcinoma.

PURPOSE: Increasing evidence indicates that the microbiome may influence tumor growth and modulate the tumor microenvironment of gastrointestinal cancers. However, the role of oral bacteria in the development of esophageal squamous cell carcinoma (EsoSCC) has remained unclear. Herein, we investigated the relationship between the periodontal pathogen Porphyromonas gingivalis and EsoSCC. METHODS: To identify bacterial biomarkers associated with EsoSCC, we analyzed microbiomes in oral biofilms. The presence of P. gingivalis in esophageal tissues and relationships of P. gingivalis infection with clinicopathologic characteristics in 156 patients with EsoSCC were assessed using immunohistochemistry. The role of P. gingivalis infection in in vitro and in vivo EsoSCC progression was also assessed. RESULTS: Microbiota profiles in oral biofilms revealed that P. gingivalis abundance was associated with an increased risk of EsoSCC development. In total, 57% of patients with EsoSCC were found to be infected with P. gingivalis. The presence of P. gingivalis was found to be associated with advanced clinical stages and a poor prognosis. It was also found to be associated with an elevated esophageal cancer incidence in a 4-nitroquinoline 1-oxide-induced mouse model and with an increased xenograft tumor growth. P. gingivalis infection increased interleukin (IL)-6 production and it promoted epithelial-mesenchymal transition and the recruitment of myeloid-derived suppressor cells. Furthermore, inhibited IL-6 signaling attenuated the tumor-promoting effects of P. gingivalis in 4-nitroquinoline 1-oxide-treated mice and xenograft mouse models. CONCLUSIONS: Our data indicate that P. gingivalis may promote esophageal cancer development and progression. Direct targeting of P. gingivalis or concomitant IL-6 signaling may be a promising strategy to prevent and/or treat EsoSCC associated with P. gingivalis infection.

A highly sensitive and specific real-time quantitative PCR for BRAF V600E/K mutation screening.

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

Do the Paths of Sequential Vein Grafts Influence the Outcomes of Coronary Artery Bypass Surgeries?

BACKGROUND: The use of a sequential vein graft (SVG) in coronary artery bypass grafting (CABG) in multi-vessel coronary disease is common. This study aimed to investigate the influence of the paths of SVGs on the outcomes of CABG. METHODS: From January 2011 to June 2017, 126 patients underwent elective isolated CABG. If the path of the SVG was from the aorta to the right coronary artery (RCA)/ posterior descending artery (PDA) to the left circumflex artery (LCX)/obtuse marginal artery (OM), the patients were included in Group R. If the path was from the aorta to the LCX/OM to the RCA/PDA, the patients were included in Group L. The in-hospital and follow-up outcomes were analyzed. RESULTS: Group R had 69 patients, and Group L had 57 patients. Univariate analysis showed that Group L had a higher number of grafts (P < .001) and less aortic cross-clamping time (P < .001) and total bypass time (P = .001). Otherwise, Group L had 14 patients (19.3%), who received first diagonal branch (D1) bypass grafting, while Group R had none (P < .001). In the multivariate analysis, in- hospital mortality from heart failure, postoperative acute kidney injury, medium-term mortality, and readmission for cardiac incidents were not associated with the SVG path. CONCLUSION: The SVG path from the aorta to the LCX/OM to the RCA/PDA facilitated the additional D1 bypass grafting, but the outcomes for this approach were not significantly different from those for the other path.

MET exon 14 skipping mutations and gene amplification in a Taiwanese lung cancer population.

Somatic mutations of MET gene are emerging as important driver mutations for lung cancers. To identify the common clinicopathological features of MET exon 14 skipping mutations and amplification and clarify whether the two MET gene alterations cause protein overexpression were investigated using 196 lung cancer samples of Taiwan through real time-qPCR/sequencing, fluorescence in situ hybridization, and immunohistochemistry. The two MET gene alterations are both present in low frequency, ~1%, in the studied lung cancer population of Taiwan. MET exon 14 skipping mutations were identified from two early-stage patients, who were both relatively advanced in age, and did not carry other driver mutations. One was an adenocarcinoma and the other was a rare carcinosarcoma. Three gene amplifications cases were identified. Neither of the two MET gene alterations would lead to protein overexpression; hence, direct detection in nucleic acid level would be a preferred and straightforward solution for the identification of skipping mutations. The presence of MET exon 14 mutations in minor histological types of lung cancers urge to extend screening scope of this mutation in lung cancer and treatment response evaluation in clinical trials. These would be important next steps for the success of MET target therapy in clinical practice.

Does Interhospital Transfer Influence the Outcomes of Patients Receiving Surgery for Acute Type A Aortic Dissection? Type A Aortic Dissection: Is Transfer Hazardous or Beneficial?

INTRODUCTION: The progression of acute type A aortic dissection may cause immediate death, such that, in the event of its diagnosis, emergency surgery is indicated. Relatedly, an interhospital transfer may prolong the time from diagnosis to surgery. This study therefore investigated how interhospital transfers impact surgical outcomes for acute type A aortic dissection. MATERIALS AND METHODS: After excluding those patients who received deferred surgery for acute type A aortic dissection, 112 patients who received emergency surgery for the condition at our hospital from January 2011 to January 2018 were enrolled. These patients were divided into two groups, one consisting of the patients who were sent directly to our emergency department (group 1) and the other consisting of the patients who were transferred from another hospital after first being diagnosed with type A aortic dissection (group 2). The collected data included the patient demographics, clinical characteristics, operative findings and methods, postoperative outcomes, latest follow-up time, and most recent status. RESULTS: There were 59 patients in group 1 and 53 patients in group 2. Univariate analysis revealed that group 1 had significantly more patients with a previous stroke (p = 0.007). Moreover, the average length of time from receiving a computed tomography (CT) scan to entering the operating room (OR) was shorter for the group 1 patients (p < 0.001). However, except for the incidence of postoperative acute kidney injury (14.5% versus 33.3%, p = 0.024), there was no statistical difference between the groups in terms of the operative findings and outcomes, such as hypotension before cardiopulmonary bypass, hemopericardium, other complications, and survival rate. Multivariate analysis showed that the independent predictors of hospital mortality included age > 61.5 years (p = 0.017), respiratory rate upon admission > 18.5 breaths/minute (p = 0.046), and total bypass time > 265.6 minutes (p = 0.015). For the patients who survived to discharge, log-rank analysis demonstrated similar cumulative survival rates for the two groups (p = 0.62). Further multivariate analysis showed that the risk of death after discharge was associated with the interval between the CT scan and OR entry (hazard ratio = 0.97 per minute; 95% confidence interval, 0.950-0.998; p = 0.037). CONCLUSION: In this study, it was found that interhospital transfer did not influence the surgical outcomes of patients with acute type A aortic dissection. As such, it can be concluded that the transfer of the patients with type A aortic dissection to tertiary hospitals with experienced cardiac surgical teams may not increase the surgical risk.

Lung cancer outcome in the setting of chronic kidney disease: Does the glomerular filtration estimation formula matter?

BACKGROUND: The survival outcomes of lung cancer patients with coexisting chronic kidney disease (CKD) reported in the literature have been conflicting. We evaluate whether the survival of lung cancer patients with and without CKD differ significantly using two different formulas. METHODS: A retrospective, multicenter, propensity-matched study of lung cancer patients with and without CKD was conducted. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/minute. Kaplan-Meier survival analysis was used to determine survival differences between CKD and non-CKD patients using the Cockcroft-Gault formula (CKD-CG) compared to the Chronic Kidney Disease Epidemiology Collaboration Formula (CKD-EPI). RESULTS: Baseline clinical characteristics did not differ statistically significantly between the groups. The CKD-CG formula demonstrated median survival of 10.61 months (95% confidence interval [CI] 9.33-11.89) for the non-CKD group compared to 10.58 months (95% CI 9.03-12.13) for the CKD group (P = 0.76). The CKD-EPI formula demonstrated median survival of 9.10 months (95% CI 8.01-10.20) for the non-CKD group compared to 7.59 months (95% CI 6.50-8.68) for the CKD group (P = 0.19). Cox regression analysis using both models revealed that CKD is not an independent risk factor for mortality in lung cancer patients. Although the CKD-EPI formula revealed an increased risk of mortality and the CKD-CG formula revealed decreased survival, these results were not statistically significant. CONCLUSION: Lung cancer survival did not differ significantly between CKD and non-CKD patients using either formula.

Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment.

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC.

Survival benefit of surgery to patients with esophageal squamous cell carcinoma.

To assess if surgery provided survival benefit to patients with esophageal squamous cell carcinoma (SCC), we performed a retrospective review of 1230 patients who were newly diagnosed with stage T2-T4 esophageal SCC from 2007 to 2014 in our hospital. There were greater than 70% of patients with age under 65 years, and more than 85% were stage T3-T4 at the time of diagnosis. The median survival time was 1.06 year (95% CI 0.99-1.1 yrs). Survival analyses showed that survival time was significantly associated with age, T stage, clinical lymph node involvement and treatment modality (surgery versus definite chemoradiotherapy). Surgery still possessed a powerful impact on overall survival by multivariable analysis. Death risk of patients treated with curative surgery was significantly lower than those with definite chemoradiotherapy. Furthermore, for patients of stage T3N(+) and T4, surgery combined with (neo-)adjuvant treatment were significantly associated with higher survival rate than surgery alone or definite chemoradiotherapy. In conclusion, the patients who undergo surgery were significantly associated longer survival, therefore, curative resection should be considered for esophageal cancer patients who are medically fit for surgery. Moreover, combined with (neo-)adjuvant treatment is recommended for surgically resectable stage T3-T4 esophageal SCC.

Is chronic kidney disease an adverse factor in lung cancer clinical outcome? A propensity score matching study.

BACKGROUND: Comorbidity has a great impact on lung cancer survival. Renal function status may affect treatment decisions and drug toxicity. The survival outcome in lung cancer patients with coexisting chronic kidney disease (CKD) has not been fully evaluated. We hypothesized that CKD is an independent risk factor for mortality in patients with lung cancer. METHODS: A retrospective, propensity-matched study of 434 patients diagnosed between June 2004 and May 2012 was conducted. CKD was defined as estimated glomerular filtration rate <60 mL/minute. Lung cancer and coexisting CKD patients were matched 1:1 to patients with lung cancer without CKD. RESULTS: Age, gender, smoking status, histology, and lung cancer stage were not statistically significantly different between the CKD and non-CKD groups. Kaplan-Meier survival analysis demonstrated a median survival of 7.26 months (95% confidence interval [CI] 6.06-8.46) in the CKD group compared with 7.82 months (95% CI 6.33-9.30) in the non-CKD group (P = 0.41). Lung cancer stage-specific survival is not affected by CKD. Although lung cancer patients with CKD presented with an increased risk of death of 6%, this result was not statistically significant (hazard ratio 1.06, 95% CI 0.93-1.22; P = 0.41). CONCLUSION: According to our limited experience, CKD is not an independent risk factor for survival in lung cancer patients. Clinicians should not be discouraged to treat lung cancer patients with CKD.

Clinical outcome in lung cancer with a second malignancy: The time sequence matters.

The aim of the study was to determine the clinical outcome of lung cancer patients with a secondary malignancy according to the time sequence between the lung cancer and the secondary malignancy.Retrospective review of all lung cancer patients with any secondary cancer treated from June 2004 to July 2012. The survival of patients with a secondary malignancy was compared to those patients without a secondary malignancy. According to the time sequence between the lung cancer and the secondary malignancy, patients were divided into 4 groups. Group I: lung cancer without any other malignancy, Group II: lung cancer with a secondary malignancy at follow-up, Group III: lung cancer with a pre-existing malignancy, Group IV: synchronous malignancies (diagnosis interval between lung cancer and a secondary malignancy of less than 3 months).Patients with any secondary cancer in their history or at follow up included 157 patients (9.5%). Collectively; the median survival was significantly better for patients with a secondary malignancy, 19.09 months, compared to those without a secondary malignancy, 9.53 months, P < 0.001, HR 0.66 (95% CI 0.55 - 0.79). However, the survival differed significantly according to the time sequence between the lung cancer and the secondary malignancy. The median survival was 47.9 months for group II patients, 12.19 months for group III, 17.51 months for group IV, and 9.53 months for group I; P = 0.001. In Cox proportional hazard analysis, the risk of dying decreased by 68% in group II patients compared to group I patients, HR 0.32 (95% CI 0.21-0.5), P < 0.001. Although the risk of dying for group III and IV decreased by 19% and 16% respectively compared to group I patients, it did not reach statistical significance.Nowadays, secondary malignancy in lung cancer patients is a frequent finding. Better survival was observed for patient with secondary malignancy following lung cancer.

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

Long-term outcomes after thoracoscopic resection of stage I and II thymoma: a propensity-matched study.

PURPOSE: The use of video-assisted thoracoscopic surgery (VATS) in patients with thymoma remains controversial. We sought to evaluate the perioperative and oncological outcomes after VATS resection for stage I and II thymoma and to compare the outcomes with those obtained after median sternotomy (MST). METHODS: Between 1991 and 2007, a total of 140 patients with stage I and II thymoma underwent surgery at the Chang Gung Memorial Hospital. Of them, 58 underwent MST, 61 VATS, and 21 thoracotomy. Using a propensity score based on four variables (myasthenia gravis, tumor size on CT images, age, and Masaoka stage), 48 VATS-treated patients were matched to 48 patients who received MST. Outcomes compared included perioperative complications, length of stay, tumor recurrence, and survival. RESULTS: No operative deaths occurred in this study. VATS was associated with fewer intraoperative blood loss, and more patients in the VATS group were extubated in the operating room after surgery compared with the MST group (37.5 vs. 12.5 %, respectively, P = 0.005). The mean length of stay was shorter in the VATS group than in the MST group (5.8 vs. 7 days, respectively; P = 0.008). After a median follow-up of 53 months, five patients developed recurrent tumors (four pleural and one pericardial). No statistically significant differences were found in the 5-year survival rates between the two study groups. CONCLUSIONS: VATS appears feasible for patients with stage I and II thymoma and is associated with better perioperative outcomes than MST. The oncological outcomes are also similar.