Elderly onset atypical Lemierre's syndrome concurrent with a rheumatoid vasculitis sacral ulcer infection: a case report.

BACKGROUND: Typical Lemierre's syndrome is usually secondary to an oropharyngeal infection. Recently, several cases following a primary infection site other than the oropharynx have been reported as atypical Lemierre's syndrome; although, these primary lesions are limited to the head and neck. This is the first case potentially sequential to infectious foci outside the head and neck. CASE PRESENTATION: We describe an atypical Lemierre's syndrome in a 72-year-old woman with rheumatoid arthritis, which occurred during the treatment of Streptococcus anginosus bacteremia acquired from a sacral ulcer infection related to rheumatoid vasculitis. At first, the symptoms resolved after the initial administration of vancomycin for the bacteremia caused by methicillin-resistant Staphylococcus aureus and Streptococcus anginosus that entered via a sacral ulcer. On the 8th day, the patient developed a fever of 40 °C and unexpectedly required 10 L of oxygen due to rapid deterioration of oxygenation temporarily. Immediately contrast-enhanced computed tomography was performed to investigate systemic thrombosis including pulmonary embolism. Afterward, the newly formed thrombi at the right external jugular vein, bilateral internal jugular veins, and the right small saphenous vein were detected, and apixaban was started. On the 9th day, the patient again had an intermittent fever of 39.7 °C, and continuous Streptococcus anginosus bacteremia was revealed; subsequently, clindamycin was administered. On the 10th day, she developed a left hemothorax; consequently, apixaban was discontinued, and a thoracic drain was inserted. She repeatedly had an intermittent fever of 40.3 °C, and contrast-enhanced computed tomography detected an abscess formation at the left parotid gland, pterygoid muscle group, and masseter muscle. After Lemierre's syndrome was diagnosed in combination with the abovementioned jugular vein thrombus, clindamycin was replaced with meropenem, and vancomycin was increased. Swelling of the lower part of the left ear became prominent with delay and peaked at approximately the 16th day. The subsequent treatment course was favorable, and she was discharged on the 41st day. CONCLUSION: Clinicians should consider Lemierre's syndrome as the differential diagnosis of internal jugular vein thrombosis occurring during sepsis, even though an antibiotic is administered or a primary infection site is anything besides the oropharynx.

Surgical Repair of Pleuroperitoneal Communication with Continuous Ambulatory Peritoneal Dialysis.

BACKGROUND: Pleuroperitoneal communication is a serious complication in patients receiving continuous ambulatory peritoneal dialysis. However, few single-institutional reports discuss the details of pleuroperitoneal communication in continuous ambulatory peritoneal dialysis patients regarding the intraoperative findings, postoperative course, and outcomes. METHODS: We retrospectively reviewed the records of consecutive pleuroperitoneal communication patients who were treated surgically from September 2008 to March 2016. RESULTS: All four patients had right-sided hydrothorax. The time from introduction of continuous ambulatory peritoneal dialysis to the diagnosis of hydrothorax ranged from 1 to 12 months (average: 5.5 months). Case 1 and case 4 had bleblike lesions near the center of the diaphragm; case 2 had a small hole located near the cardiophrenic angle, and case 3 had thinning of the diaphragm near the cardiophrenic angle. All lesions except for case 3 were directly closed with absorbable suture and reinforced by fibrin glue and a polyglycolic acid sheet. In case 3, the thinned diaphragm was reinforced using fibrin glue, a sealing sheet, and pericardial fat pad tissue. Continuous ambulatory peritoneal dialysis was reinitiated an average period of 11 days (range: 4-15 days) postoperatively. During postoperative follow-up, there was no recurrence of hydrothorax. Continuous ambulatory peritoneal dialysis was continued for an average of 16.7 months (range: 3-34 months) after surgical treatment. CONCLUSIONS: Surgical treatment for pleuroperitoneal communication is a safe and acceptable procedure and could greatly benefit continuous ambulatory peritoneal dialysis patients.

HMGB1 blockade significantly improves luminal fibrous obliteration in a murine model of bronchiolitis obliterans syndrome.

BACKGROUND: Although high-mobility group box-1 (HMGB1), which is a nuclear protein, was reported to enhance the allogeneic responses in transplantation, the effect of HMGB1 on bronchiolitis obliterans syndrome (BOS) is unknown. METHODS: A murine heterotopic tracheal transplantation model was used. Protein concentrations of HMGB1, interferon-γ (IFN-γ), interleukin (IL)-10, and IL-17 were analyzed in the isografts, allografts, controls, and HMGB1-neutralizing antibody administered allografts (n = 6; Days 1, 3, 5, 7, 14, 21, and 28). The luminal fibrous occlusion was analyzed (n = 6; Days 7, 14, 21, and 28). Infiltrating CD8 and CD4 T lymphocytes around the allografts and serum levels of IFN-γ and IL-10 were evaluated (n = 6; Day 7). RESULTS: The HMGB1 levels in the allografts were significantly increased compared with the isografts at Day 7. HMGB1 blockade did not change the IL-17 level, but decreased the IFN-γ/IL-10 ratio in the early phase (Days 5 and 7) and significantly improved the fibrous occlusion in the late phase (Days 14, 21, and 28). HMGB1 blockade significantly suppressed the CD8 T lymphocytes infiltration and decreased the serum IFN-γ/IL-10 ratio compared with the control at Day 7. CONCLUSIONS: HMGB1 may be a trigger of the BOS pathogenesis and candidate target for the treatment of the disease.

Impact of Preoperative Ultrasonography Screening for Carotid Artery Stenosis in Lung Cancer Patients.

BACKGROUND: Stroke is a major cause of morbidity or death after lung operations. Carotid artery screening (CAS) is useful for detecting carotid artery stenosis, which is one of the causes of stroke. This study investigated the frequency of and risk factors for preoperative carotid artery stenosis to determine whether CAS with ultrasonography contributes to preventing postoperative stroke or cardiovascular comorbidities in lung cancer patients. METHODS: This retrospective study included 1,676 consecutive lung cancer patients who underwent surgical resection. RESULTS: Of the 1,342 patients who underwent CAS, 173 (12.9%) had carotid artery stenosis. Significant associations with carotid artery stenosis were found for older patients (p < 0.0001), men (p < 0.0001), smoking history (p < 0.0001), history of stroke (p = 0.0037), cardiovascular diseases (p < 0.0001), hypertension (p = 0.0353), diabetes mellitus (p = 0.0037), and peripheral vascular diseases (p < 0.0001). Patients with the three independent risk factors of age, male sex, and history of cardiovascular diseases had a 6.43-fold higher prevalence of carotid artery stenosis (odds ratio, 6.43; 95% confidence interval, 3.80 to 10.89) than those with none of these factors. Propensity score-matched analysis showed that incidences of postoperative stroke and cardiovascular comorbidities were both lower in patients who underwent CAS and received appropriate anticoagulant therapy than in those who did not (p = 0.0619 and p = 0.0319, respectively). CONCLUSIONS: Preoperative CAS is a simple and useful tool for detecting carotid artery stenosis. Administration of perioperative anticoagulant therapy to preoperative patients with lung cancer and carotid artery stenosis identified by CAS may prevent postoperative stroke and cardiovascular events.

Postoperative Management of Multiple Primary Cancers Associated with Non-small Cell Lung Cancer.

BACKGROUND/AIM: Modern treatment for primary cancers has improved survival. Therefore, increased numbers of patients with multiple primary cancers (MPC) associated with lung cancer may be expected. The aim of the present study was to report MPC associated with lung cancer and discuss patients' characteristics and postoperative management. PATIENTS AND METHODS: Overall, 973 consecutive patients who underwent surgery for non-small cell lung cancer (NSCLC) were retrospectively studied. RESULTS: NSCLC with MPC was observed in 148 patients (15.2%). MPC comprised 24 synchronous (2.5%) and 124 metachronous (12.7%) diseases. Of the 124 metachronous patients, NSCLC was detected before cancers were detected in other organs (lung cancer first (LCF)) in 25 (20.2%) patients and subsequently in other organs after treatment (other organs, primary cancer-first (OCF)) in 99 (79.8%) patients. MPC was significantly associated with advanced age (p<0.0001) and chronic obstructive pulmonary disease (COPD) (p=0.0040). The leading sites of MPC in patients with synchronous tumors and those with OCF were the digestive organs. In contrast, the leading site of MPC in patients with LCF was the lung. In the latter, at least two primary lung cancers were detected within 5 years as well as 5 years after surgery for the treatment of the first detected lung cancer, while primary cancers of other organs were detected within 5 years. CONCLUSION: Advanced age and COPD may represent a high-risk of MPCs. Therefore, we recommend careful follow-up to detect MPC in the lung as well as the digestive organs beyond 5 years after treatment of the first cancer.

The significant influence of having children on the postoperative prognosis of patients with nonsmall cell lung cancer: A propensity score-matched analysis.

The aim of this study was to elucidate the relationship between family-associated factors and the postoperative prognosis in patients with nonsmall cell lung cancer (NSCLC). Additionally, we investigated whether having children was associated with the postoperative maintenance of the nutritional status. We selected 438 NSCLC patients who had undergone curative lung resection between 2004 and 2011 at Kyushu University (Fukuoka, Japan), whose family-associated factors were available. Nutritional indices, including the prognostic nutritional index (PNI), were used to estimate the change in the nutritional status for 1 year after surgery. A propensity score analysis was conducted after adjusting the following variables: sex, age, smoking history, performance status, pathological stage, and histological type. Three hundred patients (68.5%) had both children and partners. Forty-nine patients (11.2%) only had children, and 56 (12.8%) patients only had a partner. Thirty-three patients (7.5%) did not have a partner or children. The overall survival (OS) and disease-free survival (DFS) of the partner-present and partner-absent patients did not differ to a statistically significant extent (P = .862 and P = .712, respectively). However, childless patients showed significantly shorter OS and DFS in comparison with patients with children (P = .005 and P = .002, respectively). The postoperative exacerbation of PNI was significantly greater in childless patients than in patients with children (P = .003). These results remained after propensity score matching. Childless patients had a significantly poorer postoperative prognosis than those with children. Surgeons caring for childless NSCLC patients should be aware of the poorer postoperative outcomes in this population.

Clinical Impact and Risk Factors for Skeletal Muscle Loss After Complete Resection of Early Non-small Cell Lung Cancer.

BACKGROUND: A relationship between sarcopenia diagnosed by skeletal muscle area (SMA) and poor prognosis in cancer patients has recently been reported. This study aimed to clarify the clinical significance of postoperatively decreased SMA in patients with early non-small cell lung cancer (NSCLC). METHODS: This study selected 101 patients with pathologic stage 1 NSCLC who had undergone pre- and postoperative (~ 1 year) computed tomography scans and lobectomy between 2005 and 2010 at Kyushu University Hospital. The post/pre ratio was defined as the postoperative normalized SMA (cm2/m2) at the 12th thoracic vertebra level divided by the preoperative normalized SMA. The cutoff value for the post/pre ratio was set at 0.9. RESULTS: The study classified 31 patients (30.7%) as having decreased SMA. Poor performance status (PS) was significantly associated with decreased SMA (p = 0.048). The patients with decreased SMA had a significantly shorter disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001) than the other patients. Decreased SMA was found to be an independent prognostic factor for DFS (p = 0.010) and OS (p = 0.0072). The independent risk factors for skeletal muscle loss included poor PS (PS ≥ 1) and obstructive ventilatory impairment [forced expiratory volume (FEV) 1% < 70%]. CONCLUSIONS: Skeletal muscle loss after surgery is significantly associated with postoperative poor outcomes for patients with early NSCLC. Patients with poor PS, obstructive ventilatory impairment, or both need careful support to maintain their skeletal muscle mass. Future prospective studies may clarify whether physical activity and nutritional support improve postoperative prognosis.

Invasive features of small-sized lung adenocarcinoma adjoining emphysematous bullae.

OBJECTIVES: Radiologically small-sized adenocarcinomas are special entities of lung cancer, as their radiological and pathological invasiveness determines the surgical procedures applied; however, the clinicopathological features of small-sized lung adenocarcinoma adjoining cystic airspaces (Ca-ADJ) have yet to be fully clarified. The aim of this study was to elucidate the clinicopathological characteristics, including the programmed death ligand 1 (PD-L1) expression, in patients with Ca-ADJ ≤3.0 cm. METHODS: A total of 283 patients with resected adenocarcinoma, whose radiological tumour size was ≤3.0 cm without lymph node or distant metastases on preoperative high-resolution computed tomography, were analysed for their clinicopathological and radiological features. Furthermore, the PD-L1 expression was evaluated by immunohistochemistry using an anti-human PD-L1 rabbit monoclonal antibody (clone SP142). RESULTS: Among the 283 patients, 31 (11.0%) patients were reported to have Ca-ADJ. The Fisher's exact test demonstrated that Ca-ADJ was significantly associated with male gender (P < 0.001), a history of smoking (P < 0.001), a high consolidation/tumour ratio (P = 0.026), advanced pathological stage (P < 0.001), the presence of pleural (P < 0.001) and vessel invasion (P < 0.001), histological invasive subtypes (P < 0.001) and wild-type epidermal growth factor receptor (P = 0.001). The patients with Ca-ADJ had a significantly higher maximum standardized uptake value than those without Ca-ADJ (8.4 vs 4.1, P < 0.001). Furthermore, Ca-ADJ was significantly associated with the PD-L1 expression (P < 0.001). Log-rank test showed that patients with Ca-ADJ had a significantly shorter disease-free survival than those without Ca-ADJ (P = 0.001). CONCLUSIONS: This study showed that patients with radiologically small-sized Ca-ADJ might exhibit radiologically and pathologically invasive features.

Programmed Death-Ligand 1 Expression and EGFR Mutations in Multifocal Lung Cancer.

BACKGROUND: Little is known about the programmed death-ligand 1 (PD-L1) expression in multifocal lung cancer, such as the expression in multiple primary lung cancer and pulmonary metastasis. In this translational study, we investigated PD-L1 expression and its relationship with the epidermal growth factor receptor (EGFR) mutation status in resected multifocal lung cancer. METHODS: The PD-L1 expression in 152 samples of multifocal lung cancer from 59 patients was evaluated by an immunohistochemical analysis. RESULTS: Among the 152 lung cancer lesions of 59 patients, PD-L1 expression was observed in 29 lesions (19.1%) of 20 patients (33.9%). Among 43 patients with 112 multiple primary lung cancer lesions, 15 lesions (13.4%) of 13 patients (30.2%) were PD-L1 positive; and among 16 patients with 40 pulmonary metastatic lesions, 14 lesions (35.0%) of 7 patients (43.8%) were PD-L1-positive. Among 43 patients with multiple primary lung cancer, there was disagreement of PD-L1 expression in 12 patients (27.9%, κ = 0.104). On the contrary, among 16 patients with pulmonary metastasis, disagreement of PD-L1 expression was observed only in 1 patient (6.3%, κ = 0.871). In pulmonary metastatic lesions, the frequency of PD-L1 positivity among lesions with wild-type EGFR was significantly higher than among lesions with mutated EGFR (66.7% versus 0%: p < 0.001). CONCLUSIONS: This study provides important evidence of higher levels of agreement of PD-L1 expression in pulmonary metastasis compared with in multiple primary lung cancer, and high positivity of PD-L1 expression in pulmonary metastatic lesions with wild-type EGFR in an Asian population.

Prognostic significance of immune-nutritional parameters for surgically resected elderly lung cancer patients: a multicentre retrospective study.

OBJECTIVES: The world's population is rapidly ageing, and the age of patients with lung cancer will increase as well. The prognostic nutritional index, controlling nutritional status and the geriatric nutritional risk index (GNRI) are useful parameters for evaluating immune-nutritional status. We aimed to perform a multicentre retrospective study to investigate the correlations of these immune-nutritional parameters with postoperative comorbidities or surgical outcomes of elderly patients with non-small-cell lung cancer (NSCLC). METHODS: We selected 272 consecutive patients with NSCLC aged >75 years treated from January 2005 to December 2012 and evaluated 3 preoperative immune-nutritional parameters as potential predictive factors of postoperative comorbidities or as prognostic factors for surgically resected elderly patients with NSCLC. RESULTS: Prognostic nutritional index, GNRI, sex and preoperative respiratory comorbidities were significantly associated with postoperative comorbidities. Multivariate analyses revealed that preoperative GNRI, sex, preoperative serum carcinoembryonic antigen levels, preoperative serum cytokeratin 19 fragment levels, pathological N factor and pleural invasion were significantly associated with overall survival (OS). Abnormal GNRI was significantly associated with histology and outcomes. The Kaplan-Meier analysis of OS as a function of preoperative GNRI revealed that patients with an abnormal GNRI experienced significantly shorter OS compared with those with normal GNRI (5-year OS, 45.15% vs 64.10%, respectively; P = 0.0007, log-rank test). The controlling nutritional status score was not significantly associated with postoperative comorbidities or surgical outcomes. CONCLUSIONS: Preoperative GNRI is a novel preoperative predictor of postoperative comorbidities and a prognostic factor that may identify high-risk elderly patients with NSCLC.

Correlation between CXCR4/CXCR7/CXCL12 chemokine axis expression and prognosis in lymph-node-positive lung cancer patients.

The CXCR4/CXCR7/CXCL12 chemokine axis plays important roles in the migration of tumor cells during cancer development by modulating site-specific distant metastasis including to regional lymph nodes. We investigated the correlation of these chemokine expressions to prognosis in lymph-node-positive non-small-cell lung cancer (NSCLC) patients. A total of 140 surgically resected specimens of primary site (PS) and metastatic lymph nodes (MLN) of NSCLC involving hilar and/or mediastinal lymph nodes (N1-2) were collected. CXCR4, CXCR7 and CXCL12 expressions were evaluated. Cox regression analysis was performed to determine whether these chemokines were independent prognostic factors in N1-2 NSCLC. High expression of CXCR4 in PS and CXCL12 in MLN was associated with poor overall survival (OS) (P = .025 and .033, respectively). Significant correlations between CXCR4 expression in PS and CXCL12 expression in MLN were observed (P = .040). There was significant difference in OS between 2 groups according to expressions of CXCR4 in PS and CXCL12 in MLN (P = .0033). Expression of CXCL12 in MLN was identified as an independent prognostic factor (HR 1.79, 95% CI 1.08-3.04, P = .023). CXCL12 in MLN was mainly expressed by tumor cells compared with stromal cells (56% vs 25%, respectively, P < .0001). CXCR4/CXCL12 may play roles in tumor progression in MLN and is associated with poor prognosis of lymph-node-positive NSCLC patients.

Relationship Between Preoperative Sarcopenia Status and Immuno-nutritional Parameters in Patients with Early-stage Non-small Cell Lung Cancer.

BACKGROUND: Although the skeletal muscle in the region of the third lumbar vertebra (L3) is generally assessed in order to judge sarcopenia, not every patient with non-small cell lung cancer (NSCLC) undergoes computed tomography including the L3 region. We hypothesized that immuno-nutritional parameters could predict the existence of sarcopenia in patients with NSCLC. AIM: The aim of this study was to retrospectively investigate the correlation between preoperative sarcopenia and immuno-nutritional parameters in patients with early-stage NSCLC. PATIENTS AND METHODS: We selected 147 of patients with pathological stage I NSCLC who underwent preoperative measurement of immuno-nutritional parameters and CT including the L3 region. RESULTS: Preoperative sarcopenia was significantly associated with female gender (p=0.0003) and poor prognosis (p=0.0322). In Kaplan-Meier analysis of overall survival (OS) by preoperative sarcopenia status, the sarcopenic group had significantly shorter OS than the non-sarcopenic group (5-year OS: 87.27% vs. 77.37%, p=0.0131, log-rank test). In multivariate analysis, the preoperative sarcopenia status (hazard ratio=5.138; 95% confidence interval=2.305-11.676; p<0.0001) was an independent prognostic factor. Preoperative sarcopenia status was significantly related to controlling nutritional status score (p=0.0071) and Geriatric Nutritional Risk Index (GNRI) (p<0.0001). Spearman's correlation test showed good significant correlation between preoperative sarcopenia status and GNRI (r=0.348, p<0.0001). CONCLUSION: The preoperative GNRI is a simple and useful predictor for existence of preoperative sarcopenia which was associated with poor outcome in patients with early-stage NSCLC.

Prognostic impact of controlling nutritional status score in resected lung squamous cell carcinoma.

BACKGROUND: The preoperative immune-nutritional status has been shown to predict the postoperative prognosis in various types of cancer; however, the prognostic significance of the controlling nutritional status (CONUT) score in resected lung squamous cell carcinoma (SCC) has yet to be elucidated. METHODS: A total of 108 patients with resected lung SCC were analyzed for their clinicopathological factors, including the CONUT score, which can be calculated from the serum albumin, total cholesterol, and total peripheral lymphocyte count. The patients were divided into two groups: CONUT low (0 or 1) or high (≥2). RESULTS: Among 108 patients, 76 (70.4%) were CONUT low, while 32 (29.6%) were CONUT high. No significant association between the CONUT score and the clinicopathological factors was found. Patients with CONUT high exhibited significantly shorter disease-free and overall survivals (DFS and OS) than those with CONUT low (P=0.016 and P=0.006, respectively). Multivariate analyses showed that the CONUT score [hazard ratio (HR): 1.902, 95% confidence interval (CI): 1.045-3.373, P=0.036], age (HR: 2.286, 95% CI: 1.246-4.304, P=0.007), pathological stage (HR: 2.527, 95% CI: 1.391-4.644, P=0.002), and lymphatic invasion (HR: 2.321, 95% CI: 1.110-4.493, P=0.027) were independent prognostic factors for the DFS. Furthermore, in a multivariate analysis, the CONUT score (HR: 1.909, 95% CI: 0.902-3.860, P=0.081), age (HR: 2.455, 95% CI: 1.208-5.178, P=0.013), pathological stage (HR: 2.488, 95% CI: 1.201-5.306, P=0.014), and lymphatic invasion (HR: 3.409, 95% CI: 1.532-7.240, P=0.004) were shown to be independent prognostic factors for the OS. CONCLUSIONS: The current study showed that the CONUT score was an independent prognostic factor for the DFS and OS in patients with resected lung SCC.

Successful resection of a tracheal metastasis of rectal cancer: a case report.

A tracheal metastasis (TM) from non-pulmonary malignancy is extremely rare, and there are very few reports regarding TM. Here, we report a case of the successful tracheal resection of TM of colorectal cancer. A 36-year-old man underwent a surgical resection for the rectal cancer. Approximately 5 years after the surgical resection of the primary rectal cancer, an isolated TM was identified. The patient was successfully treated with a tracheal resection. In conclusion, the current case suggested that the best treatment of the isolated TM might be a surgical resection.

Preoperative Geriatric Nutritional Risk Index: A predictive and prognostic factor in patients with pathological stage I non-small cell lung cancer.

BACKGROUND: Surgical outcomes of early-stage non-small cell lung cancer (NSCLC) are poor. The Geriatric Nutritional Risk Index (GNRI) is a useful parameter for evaluating nutritional status. We aimed to investigate if preoperative GNRI could be a predictive factor for pathological stage I NSCLC patients. PATIENTS AND METHODS: We retrospectively selected 141 consecutive pathological stage I NSCLC patients treated from August 2005 to August 2010. We analyzed their preoperative GNRI in univariate and multivariate Cox regression analyses for postoperative recurrence-free survival (RFS). RESULTS: A preoperative abnormal GNRI was significantly associated with postoperative recurrence (P = 0.0107). Univariate analyses showed that serum carcinoembryonic antigen (CEA) levels (P = 0.0013), preoperative serum albumin level (P < 0.0001), preoperative GNRI (P = 0.0009), pleural invasion (P < 0.0001) and blood vessel invasion (P = 0.0137) significantly affected RFS. In multivariate analysis, preoperative GNRI (P = 0.0084), CEA level (P = 0.0031), preoperative serum albumin level (P = 0.0041) and pleural invasion (P = 0.0018) were independent prognostic factors. In Kaplan-Meier analysis of RFS, cancer-specific survival (CS), and overall survival (OS) by preoperative GNRI, the abnormal GNRI group had significantly shorter RFS, CS, and OS (5-year RFS, CS, and OS: 52.81% vs. 89.15%; P < 0.0001, 81.73% vs. 94.73%; P = 0.0014 and 50.84% vs. 89.57%; P < 0.0001, log-rank test, respectively). CONCLUSIONS: Preoperative GNRI is a novel prognostic factor for pathological stage I NSCLC patients, which can identify high-risk patients for postoperative recurrence and cancer-related death.

Metabolic characteristics of programmed cell death-ligand 1-expressing lung cancer on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography.

Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18 F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18 F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC.

Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression.

Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher's exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.

Discrepancy in Programmed Cell Death-Ligand 1 Between Primary and Metastatic Non-small Cell Lung Cancer.

AIM: To investigate the discordance in the programmed cell death-ligand 1 (PD-L1) expression between primary and metastatic tumors and analyze the association between the discordance and the clinical factors in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Twenty-one NSCLC patients who underwent surgery or biopsy for paired primary and metastatic lesions at our Institution from 2005 to 2016 were analyzed. Lesions with the PD-L1 expression being ≥5% were considered PD-L1-positive. RESULTS: The metastatic sites included the brain (n=16), adrenal gland (n=3), spleen (n=1) and jejunum (n=1). Negative conversion of the primary PD-L1-positive NSCLC and positive conversion of the primary PD-L1-negative NSCLC were observed in 3 (14%) and 2 (10%) cases, respectively. Radiotherapy for the metastatic brain lesion before its resection showed a significant relationship with the positive conversion of the primary PD-L1-negative NSCLC (p=0.048). CONCLUSION: Radiotherapy-derived effects may contribute to the positive conversion of the primary PD-L1-negative NSCLC.

Association of MTH1 expression with the tumor malignant potential and poor prognosis in patients with resected lung cancer.

OBJECTIVES: The oxidized purine nucleoside triphosphatase, mutT homolog 1 (MTH1), physiologically sanitizes 8-oxo-dGTP in the nucleotide pool. Previous studies indicated that MTH1 is associated with tumor proliferation and invasion in non-small cell lung cancer (NSCLC) cell lines; however, the role of MTH1 in patients with NSCLC remains unclear. MATERIALS AND METHODS: Two patient cohorts that underwent surgery for NSCLC in our institution were investigated retrospectively. In one cohort consisting of 197 patients, the associations between MTH1 expression and clinicopathological factors or prognosis were analyzed. In another cohort consisting of 41 patients, the relationship between MTH1 expression in the tumors and serum oxidative stress levels (evaluated by the diacron-reactive oxygen metabolites [d-ROMs] test) or antioxidant capacity in the patients (evaluated by the biological antioxidant potential (BAP) test) was analyzed. A total of 238 patients were assessed for MTH1 protein levels using immunohistochemistry. RESULTS: Among the 197 patients in the former cohort, 111 (56.3%) exhibited high MTH1 expression, while 86 (43.7%) exhibited low MTH1 expression. Male sex, smoking habit of ≥20 pack-years, squamous cell carcinoma, pathological stage ≥ II, tumor diameter ≥30mm, lymph node metastases, pleural invasion, lymphatic permeation and vascular infiltration were significantly associated with high MTH1 expression (p<0.05). The high MTH1 expression group had a significantly worse prognosis than that of the low MTH1 expression group (5-year overall survival: 81.6% vs. 92.3%, p=0.0011; 5-year disease-free survival: 55.0% vs. 83.7%, p=0.0002). d-ROMs and BAP test values were significantly higher in the high than in the low MTH1 expression group (p<0.05). CONCLUSION: This study showed that MTH1 protein expression was closely related to factors associated with a high malignant potential and poor patient survival. MTH1 may be a novel therapeutic target for NSCLC.

Significance of the Preoperative CONUT Score in Predicting Postoperative Disease-free and Overall Survival in Patients with Lung Adenocarcinoma with Obstructive Lung Disease.

BACKGROUND: The usefulness of the controlling nutritional status (CONUT) score for preoperative nutritional assessment has been reported in resected colorectal and esophageal cancer, but not in lung cancer with obstructive lung disease. PATIENTS AND METHODS: We retrospectively reviewed 109 patients with adenocarcinoma with obstructive pulmonary disease. We set 1 as the cut-off value for the CONUT score and classified patients into high (≥1) and low (0) CONUT groups. RESULTS: Among 109 patients, 35 (32.1%) had low CONUT scores, and 74 (67.8%) had high CONUT scores. The high-CONUT group was significantly associated with a lower body mass index (p=0.025) and wild-type epidermal growth factor receptor mutation status (p=0.011). A multivariate analysis showed that the CONUT score was independently associated with disease-free and overall survival. CONCLUSION: The results of this study suggest that the CONUT score was an independent prognostic factor for disease-free and overall survival in patients with lung adenocarcinoma with obstructive lung disease.