Clinical and Prognostic Significance of Glutathione Peroxidase 2 in Lung Adenocarcinoma.

BACKGROUND: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. RESULTS: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. CONCLUSIONS: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

Maximum resistance pressure at the time of lung tissue rupture after porcine lung transection using automatic linear staplers with different reinforcement methods.

PURPOSES: Polyglycolic acid (PGA) sheets, fibrin glue, and staple line reinforcement are frequently used to prevent air leakage during lung resection. However, the optimal staple-line reinforcement method remains unclear. METHODS: Cranial lung lobes of pigs were used to evaluate different staple line reinforcement methods (n = 6). Ventilator-assisted manometry was used to measure the maximum resistance pressure at the time of rupture of the lung tissue after stapling. RESULTS: The mean maximum resistance pressures at the time of lung tissue rupture after using the stapler alone, stapler with PGA sheet and fibrin glue, and stapler with reinforcement were 38.0 cmH2O, 51.3 cmH2O, and 62.7 cmH2O, respectively. A significant increase in the maximum resistance pressure was observed with stapler reinforcement (P < 0.001), while the differences between the other groups were not statistically significant (P = 0.055, P = 0.111). A histological assessment revealed disruption of alveolar structures near the needle-stitching site in the stapler alone, and in the stapler with PGA sheet and fibrin glue groups. Pleural rupture near the staple line was observed in the stapler with reinforcement group. CONCLUSIONS: The maximum resistance pressure before air leakage was significantly higher when using a stapler with reinforcement than when using a stapler alone.

The Clinical Role of Adjuvant Chemotherapy after Sublobar Resection for Non-Small-Cell Lung Cancer ≤ 20 mm with Lymph Node Metastases: A Propensity-Matched Analysis of the National Cancer Database.

Sublobar resection is a standard surgical procedure for small-sized non-small-cell lung cancer (NSCLC). However, the clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. The National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. The Kaplan-Meier method with a log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. The samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

CD155 Expression in Early-Stage Lung Adenocarcinoma.

BACKGROUND: Cluster of differentiation (CD) 155 is a transmembrane protein that belongs to the nectin-like molecule family, which is widely overexpressed in several types of cancer. However, the clinical significance of CD155 in pathologic stage I lung adenocarcinoma remains poorly understood. METHODS: We analyzed 320 patients diagnosed with pathologic stage I lung adenocarcinoma who underwent surgical treatment at Kyushu University Hospital between 2006 and 2015. The number of tumor cells expressing CD155 was assessed by immunohistochemistry, and patients were categorized into high and low CD155 expression groups. We compared the clinical and pathologic characteristics and clinical outcomes between these groups. RESULTS: Mutation status of the epidermal growth factor receptor gene (EGFR) was determined in 237 patients. A total of 106 patients (33.1%) had EGFR wild-type, and 131 patients (40.9%) had EGFR mutant-type. CD155 expression was classified as high in 77 patients (24.1%) and as low in 243 (75.9%) as low. Multivariate analysis identified pleural invasion and EGFR wild-type as independent predictors of high CD155 expression. The Kaplan-Meier plot demonstrated significantly poorer recurrence-free survival and overall survival in the high CD155 group compared with the low CD155 group. Multivariate analysis showed high CD155 expression was an independent poor prognostic factor for recurrence-free and overall survival. Subgroup analyses revealed that a prognostic difference related to CD155 expression was observed only in patients with EGFR wild-type but not in those with EGFR mutant-type. CONCLUSIONS: Our findings suggest that high expression of CD155 is associated with EGFR wild-type and could serve as a valuable prognostic marker in pathologic stage I lung adenocarcinoma, particularly in cases without EGFR mutation.

Role of Pathologic Single-N and Multiple-N Descriptors in Resected Non-Small Cell Lung Cancer.

BACKGROUND: The eighth edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single-N and multiple-N descriptors. RESEARCH QUESTION: Do the single-N and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? STUDY DESIGN AND METHODS: Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. RESULTS: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio [HR], 1.22 [P < .0001] for N1 and 1.39 [P < .0001] for N2). After adjusting age, sex, and histologic findings, the HR for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P = .0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P < .0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. INTERPRETATION: Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic.

Prognostic significance of preoperative creatine kinase in resected thymic epithelial tumors.

Background: The preoperative serum creatine kinase (CK) concentration is a prognostic factor for malignant diseases. We investigated the significance of CK in surgically resected thymic epithelial tumors and the relationship between CK and clinicopathological factors. Methods: We retrospectively evaluated the relationship between preoperative CK levels and prognosis in 120 patients with thymic epithelial tumors who underwent surgical resection at two centers. The cutoff for CK was determined by the standard value in our institution (<62 IU/L for men and <45 IU/L for women). The paravertebral muscle at the Th12 level was used to assess skeletal muscle area to investigate sarcopenia. Results: Eighteen patients (15.0%) were categorized into the low CK group. The CK level was not associated with age, sex, performance status, myasthenia gravis, and pathological findings. Preoperative serum albumin and total cholesterol concentrations were significantly lower in the low CK group than in the normal CK group (both P<0.001). Moreover, the Th12 muscle index was lower in the low CK group (P=0.03), indicating that low CK was related to sarcopenia. Kaplan-Meier curve analysis illustrated that patients in the low CK group had significantly shorter disease-free survival (DFS) and overall survival (OS) than those in the normal CK group (P=0.03 and P=0.002, respectively). Multivariate analysis identified low CK as an independent prognostic factor for DFS (P=0.03) and OS (P=0.005). Conclusions: Preoperative serum CK might reflect the host nutritional status in patients with resected thymic epithelial tumors; therefore, CK could be a biomarker of postoperative prognosis.