Combining PD-L1 Expression and Standardized Uptake Values in FDG-PET/CT Can Predict Prognosis in Patients With Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: This study aimed to determine the relationship of programmed death-ligand 1 (PD-L1) expression and standardized uptake values in fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) with prognosis in non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 328 NSCLC patients who underwent lobectomy/segmentectomy with lymph node dissection. PD-L1 expression was detected by immunohistochemically stained using the murine monoclonal antibody clone 22C3. The preoperative maximum standardized uptake value (SUVmax) of FDG-PET/CT at the primary lesion; pathological factors including histological type, microscopic lymphatic, venous, and pleural invasion; and lymph node metastases in resected specimens was determined. Significant prognostic clinicopathologic factors were analyzed by univariate and multivariate analyses. RESULTS: PD-L1 expression was higher in men, smokers, squamous cell carcinoma, advanced pathologic stages, positive venous invasion, positive pleural invasion, and high preoperative SUVmax (≥3). Postoperative survival analysis showed that both PD-L1 expression and preoperative SUVmax were significantly negative prognostic factors in univariate analysis for overall survival (OS) (P = 0.0123 and P < 0.0001) and relapse-free survival (RFS) (P = 0.0012 and P < 0.0001). Kaplan-Meier survival curves showed that the OS and RFS were the best in patients with negative PD-L1 expression and SUVmax < 3, intermediate in patients with positive PD-L1 expression and SUVmax < 3 and those with negative PD-L1 expression and SUVmax ≥ 3, and poor in patients with positive PD-L1 expression and SUVmax ≥ 3. CONCLUSION: Combining PD-L1 expression and preoperative FDG-PET/CT SUVmax in primary tumor might help in accurate prediction of postoperative prognosis in NSCLC patients.

Survival outcomes of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected nonsmall cell lung cancer: FAST-nab.

The relatively low toxicity profile of nab-paclitaxel plus carboplatin and its feasibility as an adjuvant administration was reported previously. This study aimed to evaluate the survival efficacy for completely resected patients with stage IB, II, and IIIA nonsmall cell lung cancer (NSCLC). Twenty-nine eligible patients with NSCLC who received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-paclitaxel (nab-P) (100 mg/m) on days 1 and 8 followed by carboplatin area (area under the curve = 6) on day 1 were prospectively enrolled and assessed for survival outcomes against patients with the same stages who received other postoperative adjuvant chemotherapy regimens during the same period. There were no significant differences in clinicopathological features, including age, gender, smoking status, performance status, surgical procedures, tumor histology, and pathological stage between the two groups. The cumulative overall survival (OS) rates at 5 years of the experimental and control groups in pathological stage IB-IIIA were 85.4% and 63.9%, respectively (P = 0.598), while recurrence-free survival (RFS) rates in these groups at 5 years were 65.2% and 34.8%, respectively (P = 0.344). Moreover, the cumulative OS rates of the experimental and control groups in pathological stage II-IIIA were 83.6% and 63.6%, respectively (P = 0.970), while RFS rates in these groups at 5 years were 61.1% and 37.3%, respectively (P = 0.460). This new regimen was considered an attractive alternative postoperative adjuvant chemotherapy option with relatively low toxicity and moderate survival outcomes for completely resected NSCLC.

Feasibility study of adjuvant chemotherapy with modified weekly nab-paclitaxel and carboplatin for completely resected non-small-cell lung cancer: FAST-nab.

The aim of this study was to determine the feasibility of adjuvant administration of nab-paclitaxel (nab-P) plus carboplatin and for completely resected patients with stage IB, II, and IIIA non-small-cell lung cancer (NSCLC) (FAST-nab study, UMIN000011225). Twenty-nine eligible NSCLC patients received surgical resection for pathological stage IB, II, or IIIA, followed by postoperative adjuvant chemotherapy with modified 3-week cycles of either nab-P (100 mg/m) on days 1 and 8, followed by carboplatin area (area under the curve=6) on day 1. Twenty-two (75.9%) of the 29 patients enrolled completed four cycles of this regimen. The most common grade 3 or 4 adverse event experienced during the nab-P plus carboplatin was neutropenia (34.5%), followed by anemia (13.8%). No grade 3 or 4 nonhematologic adverse event was observed during this chemotherapy. The median time to disease recurrence survival was 21 (95% confidence interval: 16-26) months. The administration of modified nab-P plus carboplatin was considered an attractive alternative regimen that was safe and well tolerated as a postoperative adjuvant chemotherapy for completed resected NSCLC.

Glucose Uptake Values in Positron Emission Tomography Are Useful to Predict Survival after Sublobar Resection for Lung Cancer.

Background To assess the reliability of maximum standardized uptake values (SUVmax) at the primary lesion in 18-fluorodeoxyglucose positron emission tomography combined with computed tomography (18FDG-PET/CT) for identifying patients with lung cancer who were most likely to be cured by sublobar resection (SR). Methods We retrospectively reviewed the medical records of 120 patients who underwent SR for clinical (c)-stage IA + IB lung cancer after 18FDG-PET/CT. Various factors, including tumor size, SUVmax at the primary site, and microscopic tumor invasion, were examined to identify their association with postsurgical survival. Prognoses of patients undergoing SR were compared with those of 272 patients undergoing lobectomy and lymphadenectomy during the same period. Results The 5-year recurrence-free survival (RFS) and overall survival (OS) rates in all patients undergoing SR for c-stage IA + IB disease were 79.5% and 82.2%, respectively. In multivariate analysis, a lack of microscopic pleural invasion and SUVmax ≤ 3.0 significantly correlated with better RFS and OS in patients undergoing SR. Though there were no significant differences in RFS and OS following SR and lobectomy for c-stage IA + IB or IA disease, RFS was significantly inferior in nonintentional SR (NISR) than in lobectomy in c-stage IA disease (p < 0.01). However, in NISR identified based on SUVmax ≤ 2.0, RFS was comparable to those in lobectomy (p = 0.5371). Conclusion When certain subgroups of patients are accurately identified based on preoperative SUVmax, SR can be a highly curative surgical method for lung cancer.

[CURRENT STATUS AND FUTURE DIRECTION OF SURGICAL MANAGEMENT FOR ELDERLY PATIENTS WITH NON-SMALL CELL LUNG CANCER].

According to the 2012 annual report of the Japanese Association for Thoracic Surgery, the total number of surgical procedures performed for the treatment of lung cancer had reached 35,667. Patients over 70 years of age comprised 52% of those surgical cases, and those over 80 years 12%. This tendency has been increasing annually. Although hospital mortality rates in elderly patients over 80 years of age and others were almost the same, 30% of elderly patients died from other diseases, as reported by the Japanese Joint Committee of the Lung Cancer Registry in 1999. Therefore, current preoperative physiological and oncological risk evaluations of elderly patients do not appear to be sufficient. The Japanese Association for Chest Surgery planned and performed a multiinstitutional prospective cohort study of elderly patients with lung cancer who underwent thoracic surgery to answer clinical questions surrounding such risk evaluations.

Standardized Uptake Values in the Primary Lesions of Non-Small-Cell Lung Cancer in FDG-PET/CT Can Predict Regional Lymph Node Metastases.

PURPOSE: Maximum standardized uptake values (SUVmax) at the primary lesions of non-small-cell lung cancer in (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT), and the microscopic local extension of tumors were examined to develop reliable criteria to determine candidates for sublobar resection. METHODS: We retrospectively analyzed 209 patients who underwent lobectomy, bilobectomy, or pneumonectomy with systematic lymph node dissection. Preoperative SUVmax at the primary lesion, microscopic lymphatic, venous, and pleural invasion in addition to lymph node metastases in the resected specimens were examined. Receiver operating characteristic analyses were used to predict an optimal cutoff for lymph node metastases. RESULTS: With receiver operating characteristic analysis, the areas under the curve for SUVmax and tumor size were 0.693 and 0.545, respectively, suggesting SUVmax superiority for prediction of lymph node metastases with a cutoff of 2.9. When a tumor was ≤2.0 cm (n = 41, 19.6 %), the percentages of microscopic lymphatic invasion, venous invasion, pleural invasion, and lymph node metastases were 12.2, 7.3, 4.9, and 17.1 %, respectively. When SUVmax was <3.0 (n = 91, 43.5 %), these percentages were 15.4, 3.3, 7.7, and 8.8 %, showing that SUVmax could efficiently exclude nodal metastases in more cases than tumor size. The postoperative 5-year survival rate was 86.6 % in patients with SUVmax < 3.0 and 58.1 % in patients with SUVmax ≥ 3.0 (p < 0.001). CONCLUSIONS: (18)F-FDG uptake value was more useful than tumor size for selecting patients with non-small-cell lung cancer suitable for intentional sublobar resection.

Early chest tube removal within 6 hours after thoracic surgery results in improved postoperative prognosis and no adverse effects.

Background: Advances in minimally invasive surgery and drainage systems have caused earlier chest-tube-removal. This retrospective study aimed to assess the safety of early chest tube removal using the institution's new criteria 6 hours after thoracic surgery. Methods: Elective thoracic surgery patients from 2017 to 2023 were reviewed for meeting or not meeting the newer institutional requirement for early chest tube removal; (I) no air leak detected under the digital drainage device observation; (II) no fluid drainage of ≥100 mL/h; (III) no ≥3 combined risks [male, chronic obstructive pulmonary disease (COPD), body mass index (BMI) of <18.5 kg/m2, severe pleural adhesion, upper lobe lobectomy, or left upper division segmentectomy]. The incidence of adverse events, including chest tube replacement, subcutaneous tube placement, and postoperative thoracentesis, were investigated for 1 month postoperatively. Perioperative outcomes and factors involved in conventional chest tube removal were also assessed. Results: Of the 942 patient charts reviewed, 244 (25.9%) met the criteria for chest tube removal within 6 hours postoperatively. This patient group did not experience adverse events. They also demonstrated shorter postoperative hospital stay (4 vs. 6 days, P<0.001), and lesser postoperative complications (7.4% vs. 25.6%, P<0.001) compared to those for whom early chest tube removal was not done. A correlation with thoracotomy, COPD, and steroid and/or immunosuppressant use was observed for patients in the conventional chest tube removal group. Conclusions: Early chest tube removal after 6 postoperative hours was deemed safe for a selected group of patients who met the criteria for early chest tube removal. This study would support the potential expansion of our early removal criteria.

Minichromosome maintenance 2 is an independent predictor of survival in patients with lung adenocarcinoma.

Minichromosome maintenance (MCM) protein deregulation is associated with tumor formation, progression and malignant transformation. MCM2 is frequently expressed during premalignant lung cell proliferation and is a sensitive marker for the early detection of pulmonary malignant lesions. The present study was undertaken to investigate whether MCM2 expression is of clinical and prognostic value in patients who have undergone lung adenocarcinoma resection. Between January 2009 and December 2010, 102 consecutive patients underwent complete pulmonary resection (involving lobectomy or more extensive resection) for lung adenocarcinoma at St. Marianna Medical University Hospital (Kanagawa, Japan). Among those, 73 patients, who had a final pathological diagnosis of lung adenocarcinoma measuring ≥10 mm, were enrolled in the present study. High MCM2 expression was found in 35 patients (48.0%). Univariate analysis of the overall survival (OS) revealed that pathological stage and MCM2 expression were significant prognostic factors in lung adenocarcinoma (P<0.001 and P<0.002, respectively). Univariate analysis of the recurrence-free survival (RFS), the significant prognostic factors included pathological stage, EGFR mutation status and MCM2 expression (P<0.001, P<0.034 and P<0.003, respectively). On multivariate survival analysis, high MCM2 expression and pathological stage II-III were identified as independent strong prognostic factors (OS: HR=5.084, 95% CI: 1.715-15.080, P=0.003; RFS: HR=2.761, 95% CI: 1.090-6.998, P=0.032). Therefore, the findings of the present study demonstrated that MCM2 may serve as a potential biomarker and therapeutic target for lung adenocarcinoma.

Solid histological component of adenocarcinoma might play an important role in PD-L1 expression of lung adenocarcinoma.

BACKGROUND: In this study we aimed to clarify the PD-L1 positive expression in lung adenocarcinoma, including various adenocarcinoma subtypes paying particular attention to its component. METHODS: A total of 307 lung adenocarcinoma patients who underwent lobectomy or segmentectomy, as well as systematic lymph node dissection (ND2a), from February 2008 to March 2020 at our hospital, were enrolled into the study. A final diagnosis of adenocarcinoma was obtained from the resected lung specimens of all 307 patients to determine the histological type, adenocarcinoma subtype, and component of adenocarcinoma by ethics of 5%. PD-L1 was immunohistochemically stained using the murine monoclonal antibody clone 22C3. RESULTS: When PD-L1 expression-positive was defined by tumor proportion score (TPS) ≥1%, the positive cases were 6/33 in adenocarcinoma (Ad) in situ (AIS), 2/26 in minimally invasive Ad (MIA), 12/60 in lepidic predominant Ad (LPA), 44/91 in papillary predominant Ad (PPA), 24/49 in acinar predominant Ad (APA), 23/28 in solid predominant Ad (SPA), 4/7 in micropapillary predominant Ad (MPA), and 0/13 in invasive mucinous Ad (IMA). In the high proportion group (APA, PPA, SPA, and MPA) of PD-L1 expression, SPA was the only subtype which was statistically significant when both PD-L1 expression-positive was defined by TPS ≥ 1% (p < 0.0001) and TPS â‰§ 50% (p < 0.0001). We then considered the solid component. We investigated 279 cases of the other subtype group excluding SPA. The group containing a solid component (≥5%) tended to be PD-L1 expression-positive both when defined by TPS ≥1% (p < 0.0001) and TPS â‰§50% (p = 0.0049). CONCLUSIONS: The PD-L1 expression tended to be positive when a solid component was confirmed (≥5%) in specimens of lung adenocarcinoma patients.

Thoracic mesenchymal malignant tumors and programed cell death ligand-1 status: Clinicopathologic and prognostic analysis of eight pulmonary sarcomatoid carcinomas and eight malignant mesotheliomas.

BACKGROUND: The current study aimed to evaluate the significance of clinicopathological factors, particularly the immunohistochemistry of programed cell death ligand-1 (PD-L1), in eight cases each of pulmonary sarcomatoid carcinoma (PSC) and malignant pleural mesothelioma (MPM) at our hospital. METHODS: From January 2004 to December 2020, a total of 16 consecutive patients (eight with PSC and eight with MPM diagnosed via surgical resection or biopsy) were included in this study. After retrospectively reviewing the patient characteristics, the associations between PD-L1 status and age, sex, stage, histological type, and prognosis were investigated. RESULTS: PD-L1-positive staining was observed in four (50%) PSC cases and one (12.5%) MPM case. Among the four PD-L1-positive PSC cases, two showed high PD-L1 expression in the vimentin-positive sarcomatoid compartment. Moreover, among those with PSC, two survived for about 10 years, whereas the others died within 5 years. No clear correlation was found between PD-L1 expression and prognosis. Among the patients with MPM, four survived for more than 2 years, with the longest being 9 years. Among MPM cases who received nivolumab, one patient with positive PD-L1 staining in the sarcomatoid survived, whereas the other with negative PD-L1 staining did not. CONCLUSION: The present study showed that sarcomatoid carcinoma had a higher PD-L1 expression compared to non-small-cell lung cancer and that both PSC and MPM tended to exhibit PD-L1 positivity in the sarcomatoid compartment. Moreover, while immune checkpoint inhibitors may somewhat prolong the prognosis of both tumors, further studies with a larger cohort are necessary to confirm our results.

Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer: An Unusual Case Involving a Pulmonary Tumor.

Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.

Successful treatment with nivolumab in a patient with lung adenocarcinoma complicated by pulmonary aspergilloma.

Immune checkpoint inhibitors (ICIs) are the key drugs used in patients with non-small cell lung cancer (NSCLC). However, anti-PD-1 therapy might worsen chronic infection by reactivating the immune response to infectious diseases. Here, we describe a case of successful treatment with nivolumab in a patient with NSCLC complicated by pulmonary aspergilloma, which was safely treated by surgical resection before administration of nivolumab. In conclusion, to safely treat patients with locally limited chronic pulmonary aspergillosis (CPA), surgical resection should be considered before ICI therapy.

Three-dimensional culture using a radial flow bioreactor induces matrix metalloprotease 7-mediated EMT-like process in tumor cells via TGFbeta1/Smad pathway.

To confirm the usefulness of the radial flow type bioreactor (RFB) for a three-dimensional (3D) culture system, which provides a tissue architecture and molecular function mimicking the in vivo environment, molecular expression in the A431 human squamous carcinoma cell line during culture were analyzed under the physically different environments of 3D culture in the RFB, 2D culture in a monolayer as well as in nude mice. Time-dependent accumulation of autocrine transforming growth factor (TGF) beta1 was found in spent culture media obtained only from 3D cultured A431 cancer cells, which grew well with a stratified-sheet morphology. Cells in the RFB overexpressed matrix metalloproteinase 7 (MMP7) and showed an increased release of soluble 80-kDa fragments of E-cadherin into the media time-dependently, resulting in the reduction of E-cadherin protein at the cell surface without down-regulation of the mRNA. beta-Catenin and its nuclear partner, LEF1, were up-regulated and Wnt protein secretion was also accelerated. Additional up-regulation of the transcriptional factors, HMGA2 and down-stream Slug, was noted. TGFbeta1-dependent, MMP7-mediated up-regulation of beta-catenin/LEF1 signaling and TGFbeta1-activated HMGA2 pathways consequently converged with Slug overexpression, due to disassembly and further repression of E-cadherin expression, which was reproducible in the epithelial mesenchymal transition process without any manipulation. Other transcriptional factors, Notch/HEY1 and NF-kappaB, were also up-regulated in 3D-cultured cells. These signals recruited molecules related to extracellular matrix-cell remodeling and angiogenesis. Expression of several representative molecules in the 3D cultured cells was parallel with that in xenotransplanted A431 tumor tissues in nude mice. 3D culture of tumor cells in the RFB is a useful tool for cancer experimental biology and evaluation of cancer therapeutic-like systems in nude mice.

Importance of preoperative imaging with 64-row three-dimensional multidetector computed tomography for safer video-assisted thoracic surgery in lung cancer.

PURPOSE: Video-assisted thoracic surgery (VATS) has recently been adopted for complicated anatomical lung resections. During these thoracoscopic procedures, surgeons view the operative field on a two-dimensional (2-D) video monitor and cannot palpate the organ directly, thus frequently encountering anatomical difficulties. This study aimed to estimate the usefulness of preoperative three-dimensional (3-D) imaging of thoracic organs. METHODS: We compared the preoperative 64-row three-dimensional multidetector computed tomography (3DMDCT) findings of lung cancer-affected thoracic organs to the operative findings. RESULTS: In comparison to the operative findings, the branches of pulmonary arteries, veins, and bronchi were well defined in the 3D-MDCT images of 27 patients. CONCLUSION: 3D-MDCT imaging is useful for preoperatively understanding the individual thoracic anatomy in lung cancer surgery. This modality can therefore contribute to safer anatomical pulmonary operations, especially in VATS.

Video-assisted thoracic surgery for recurrent primary spontaneous pneumothorax in reoperated chests.

PURPOSE: There are few reports on video-assisted thoracic surgery (VATS) for recurrent primary spontaneous pneumothorax (PSP) in reoperated chests. We report our experience of performing redo VATS for recurrent PSP in reoperated chests. METHODS: Between July 1, 2005 and December 31, 2007, 55 patients at Jikei University Kashiwa Hospital and 80 patients at Jikei University Hospital underwent VATS for PSP. In this period, no patient underwent thoracotomy for PSP. Ten of these patients underwent surgery for recurrent PSP in a reoperated chest: five from our hospital and five who were referred from other institutions. RESULTS: Video-assisted thoracic surgery revealed minimal to strong adhesions in all ten patients. Nine patients underwent bullectomy using endoscopic staplers, and seven had covering pleural adhesions. There were no major complications or mortality, and no patient showed any sign of recurrence of PSP in the follow-up period. CONCLUSION: Redo VATS on a reoperated chest is a promising technique for treating recurrent PSP.

Temporary claviculectomy approach for plexiform neurofibroma of the first intercostal nerve.

Plexiform neurofibroma at the thoracic inlet has rarely been reported and to our knowledge, the use of a temporary middle claviculectomy approach for thoracic inlet tumors has never been reported. We report a case of plexiform neurofibroma of the first intercostal nerve resected using a temporary claviculectomy approach. An abnormal shadow detected radiographically in a 16-year-old boy led to a diagnosis of neurofibromatosis 1 (NF-1) with a chest wall tumor at the thoracic inlet. The patient underwent resection of the tumor with the right first rib. The resected clavicle was reapproximated with a plate and postoperative shoulder function was satisfactory. The tumor was diagnosed pathologically as a plexiform neurofibroma and the patient's postoperative course was uneventful. The temporary middle claviculectomy approach provides excellent exposure of the subclavian vessels and brachial plexus before resection of the tumor. We recommend this approach for tumors of the anterior thoracic inlet.

PD-L1 Expression in Non-Small-Cell Lung Cancer Including Various Adenocarcinoma Subtypes.

PURPOSE: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes. METHODS: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3. RESULTS: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS). CONCLUSION: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.

Hepatic reconstruction from fetal porcine liver cells using a radial flow bioreactor.

AIM: To examine the efficacy of the radial flow bioreactor (RFB) as an extracorporeal bioartificial liver (BAL) and the reconstruction of liver organoids using embryonic pig liver cells. METHODS: We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day (E) 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed administration of a high concentration hepatocyte growth factor (HGF) was examined. RESULTS: Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin (Cx) 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION: Our system can potentially be applied in the fields of BAL and transplantation medicine.

Survival significance of coexisting chronic obstructive pulmonary disease in patients with early lung cancer after curative surgery.

BACKGROUND: The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early-stage lung cancer (NSCLC) has not been sufficiently elucidated. METHODS: We retrospectively reviewed 250 consecutive patients who underwent lobectomy with lymph nodal dissection for pathological stage I-II NSCLC. RESULTS: Among the COPD patients, 28 were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 21 as GOLD 2, and one as GOLD 3. The cumulative overall survival (OS) of the non-COPD, GOLD 1, and GOLD 2-3 groups at five years was 90.7%, 85.7%, and 55.3%, respectively, (P < 0.0001), while recurrence-free survival (RFS) between the groups at five years was 84.7%, 80.7%, and 72.9%, respectively. Although RFS in the GOLD 2-3 group tended to indicate a poor prognosis, there was no statistical difference between the groups (P = 0.385). In multivariate analysis, age ≥75 years, pN1, and GOLD 2-3 COPD were independent factors for a poor prognosis (P = 0.034, P = 0.010, and P = 0.030, respectively). CONCLUSIONS: Our results indicate that early stage NSCLC patients with COPD had a significantly increased risk of poorer OS and potentially an increased risk of poor RFS.

Accuracy of the cobas EGFR Mutation Assay in Non-small-cell Lung Cancer Compared With Three Laboratory-developed Tests.

BACKGROUND: The reliability of the cobas EGFR assay to detect epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) as an in vitro diagnostic test was compared with 3 laboratory-developed tests (LDTs). MATERIALS AND METHODS: After screening for EGFR mutations using formalin-fixed-paraffin-embedded NSCLC tissue sections using the cobas EGFR assay, 151 samples were further tested with 3 LDTs; the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PCR) clamp, PCR invader, and Cycleave assays. The cobas EGFR assay performance was evaluated by determining the concordance rate and κ-coefficient between the assays. In samples exhibiting discrepancies in the EGFR mutation status in the 4 assays, next-generation sequencing was performed to confirm mutated sequences. RESULTS: Concordance rates and κ-coefficients between the cobas EGFR assay and the other tests were 96.0% and 0.921 for the peptide nucleic acid-locked nucleic acid PCR clamp assay, 94.0% and 0.881 for the PCR invader assay, and 96.7% and 0.934 for the Cycleave assay, respectively. Data showed very good agreement with the other assays. Precise mutated sequences or exons in the EGFR gene matched in 137 samples (90.7%). Different results were obtained in 4 samples (2.6%), owing to systemic limitations of the assay. Next-generation sequencing of 10 (6.6%) samples with discordant results exhibited a concordance rate of 60% to 80% in each assay. CONCLUSIONS: The cobas EGFR assay showed high concordance rates and κ-coefficients between the 3 compared LDTs and can be used to select patients who would benefit from EGFR-tyrosine kinase inhibitors.