Tracheal repair with sternocleidomastoid flap in mediastinoscopic surgery for esophageal cancer.

Tracheal injury during mediastinoscopic esophagectomy is a life-threatening complication that is challenging to manage. However, no precise treatment has been defined. An 80-year-old male patient with upper esophageal cancer underwent a mediastinoscopic esophagectomy and gastric tube reconstruction through the posterior mediastinal route. When the esophagus was separated from the trachea using a bipolar vessel sealing system, the left side of the membranous trachea incurred a 3-cm defect 7 cm below the sternal notch. We successfully repaired the tracheal injury not by directly suturing the defect but by reinforcing it with a pedicle sternocleidomastoid flap. The gastric tube was placed over the tracheal repair for esophageal reconstruction via a posterior mediastinal route. As a result, the patient recovered well and was discharged. A sternocleidomastoid flap might be another surgical option for reinforcement flaps in tracheal injuries.

Recurrence-free survival curve for pulmonary metastasectomy in colorectal cancer plateaus at 3 years.

Pulmonary metastasectomy in colorectal cancer (CRC) has encouraging results; however, specific criteria for lung resection and the timing of resection remain undetermined. Therefore, in this study, we aimed to examine the long-term prognosis and 10-year survival rates and analyze poor prognostic factors in patients who underwent resection of pulmonary metastases from CRC. This retrospective, single-institution study included 156 patients with controlled primary CRC and metastases confined to the lungs or liver who underwent pulmonary metastasectomy between 2005 and 2022. Statistical analyses were conducted using the X2 and two-tailed Student's t test to compare variables. The receiver operating characteristic (ROC) curve was used to determine the appropriate cut-off point for tumor size as a predictive factor of survival. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and non-parametric group comparisons were performed using log-rank tests. The 5- and 10-year OS rates were 67% and 59%, respectively. Further, there was no recurrence 38 months post-surgery, and the RFS curve plateaued. Moreover, by 88 months post-surgery, no deaths occurred, and the OS curve plateaued. Multivariate analysis revealed that a pulmonary metastatic tumor >14 mm and disease-free interval <2 years indicated poor prognosis. The RFS curve for pulmonary metastasectomy may plateau approximately 3 years after surgery. Pulmonary metastasectomy can achieve long-term survival in selected patients with CRC. Furthermore, surgical resection of recurrence after pulmonary metastasectomy may lead to better results. Thus, tumor size and disease-free interval may be independent prognostic factors.

Siglec10 Expression on Tumor-associated Macrophages Is an Independent Prognostic Factor in Stage I Lung Adenocarcinoma.

BACKGROUND/AIM: Prognostic indicators for postoperative lung adenocarcinoma are elusive. The interaction between CD24 on tumor cells and sialic-acid-binding Ig-like lectin 10 (Siglec10) on tumor-associated macrophages (TAMs) is implicated in immune evasion in distinct tumors. However, the therapeutic significance of phagocytic checkpoints in lung adenocarcinoma remains unknown. We aimed to investigate the clinical relevance and prognostic significance of phagocytosis checkpoints mediated by Siglec10 in TAMs of patients with lung adenocarcinoma who underwent curative resection. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed the data of 423 patients with stage I lung adenocarcinoma resected between 1999 and 2016. Tissue microarrays were constructed, and CD24, CD68, and Siglec10 immunohistochemistry was performed. Additionally, we assessed the clinical significance and prognostic associations of these markers. RESULTS: CD24 expression was higher in the Siglec10-high expression group than that in the -low expression group. Multivariate analysis showed that combined high Siglec10 and CD24 expression was an independent predictor of recurrence-free probability. The combined high Siglec10 and CD68 expression was a significant independent predictor of overall survival. Univariate analysis demonstrated that the 5-year probability of post-recurrence survival of patients with combined high Siglec10 and CD68 expression was lower than that of the other patients. CONCLUSION: High TAM Siglec10 expression and tumor CD24 expression are correlated, and the high Siglec10+CD24 combination is a major risk factor for recurrence. CD68+Siglec10 TAMs are important prognostic factors. Siglec10 expression on TAMs is essential for tumor microenvironment immunoregulation and offers a promising new immunotherapeutic approach for lung adenocarcinoma.

(Pro)renin Receptor Down-regulation Is Associated With a Higher Risk of Recurrence in Lung Adenocarcinoma.

BACKGROUND/AIM: The (pro)renin receptor [(P)RR] plays a role not only in cardiovascular and renal diseases, but also in tumorigenesis. (P)RR contributes to the activation of the Wnt/ß-catenin signaling pathway, independent of the renin-angiotensin system. Accumulating evidence has shown that (P)RR is expressed in various human cancers. However, its clinical impact in lung carcinomas remains unclear. This study aimed to clarify the associations between (P)RR expression and clinical outcomes in patients with non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We analyzed the data of 913 patients with NSCLC who underwent resection between 1999 and 2016. Tissue microarrays were constructed and the expression of (P)RR and ß-catenin was investigated using immunohistochemistry. Recurrence-free probability and overall survival were analyzed using a log-rank test and Cox proportional hazards model. RESULTS: In adenocarcinomas, (P)RR down-regulation correlated significantly with high-grade tumors (p=0.026) and a higher risk of recurrence in all patients (p=0.001). Among patients with (P)RR-positive tumors, the nuclear expression of ß-catenin was associated with a higher risk of recurrence (p=0.001). Multivariate analysis revealed that (P)RR down-regulation was an independent predictor of disease recurrence (p=0.031). Conversely, in squamous cell carcinoma, (P)RR was not associated with patient outcomes. CONCLUSION: (P)RR down-regulation is associated with a higher risk of recurrence in lung adenocarcinomas, thereby characterizing a prognostic subset within high-grade tumors.

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas.

CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

Synthesis and anti-tumor activities in human leukemia-derived cells of polyenylpyrroles with a methyl group at the conjugated polyene terminus.

To develop novel drugs for treating T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) which are highly malignant hematological tumors, a series of analogs having a polyenylpyrrole structure of natural compounds (rumbrin and auxarconjugatin B) were synthesized and investigated their structure-activity relationships (SAR) of in vitro anti-T-ALL and anti-AML activities. We obtained three findings: (1) introduction of a methyl group at the conjugated polyene terminus enhanced anti-T-ALL activity, (2) analogs with a 3-chloropyrrole moiety had even higher selectivity for T-ALL cells, and (3) some analogs were effective against AML-derived cells. Among the studied compounds, 3-chloro-2-(8-ethoxycarbonylnona-1,3,5,7-tetraenyl) pyrrole 4e was the most promising candidate of T-ALL- and AML-treating drug. This study provides useful structural information for designing novel drugs treating T-ALL and AML.

Identification of compounds that preferentially suppress the growth of T-cell acute lymphoblastic leukemia-derived cells.

T-cell acute lymphoblastic leukemia (T-ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large-scale screening of natural compound libraries to identify potential drugs against T-ALL. We identified three low-molecular-weight compounds (auxarconjugatin-B, rumbrin, and lavendamycin) that inhibited the proliferation of the T-ALL cell line CCRF-CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin-B and rumbrin commonly contained a polyenyl 3-chloropyrrol in their chemical structure, therefore we chose auxarconjugatin-B for further analyses. Auxarconjugatin-B suppressed the in vitro growth of five human T-ALL cell lines and two T-ALL patient-derived cells, but not that of adult T-cell leukemia patient-derived cells. Cultured normal T cells were several-fold resistant to auxarconjugatin-B. Auxarconjugatin-B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF-CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti-T-ALL drugs.

MMP-7 expression is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas.

OBJECTIVES: The spread through air spaces (STAS) of adenocarcinoma (ADC) is a unique pattern for local invasion, which comprises the spread of tumor cells within air spaces beyond the tumor edge without a direct connection with the primary tumor. Matrix metalloproteinase-7 (MMP-7), a secreted proteolytic enzyme that degrades various extracellular matrix components and other substrates, regulates several pathophysiological processes as well as the occurrence and development of cancers in humans. Here, we retrospectively analyzed a cohort of Japanese patients with treatment-naive, surgically-resected lung ADC to assess whether MMP-7 is associated with STAS development and if it could be used as a predictor of STAS. MATERIALS AND METHODS: We performed histological evaluation using hematoxylin and eosin staining and immunohistochemical analysis using microarrays. Thereafter, we scored the examined tissues for immune markers to identify significant tumor STAS predictors. RESULTS: We identified that high MMP-7 expression is an independent predictor of a high STAS incidence. Multivariate analysis revealed that MMP-7 expression was correlated with tumor behavior and poor prognosis. Furthermore, STAS remained significantly associated with a higher risk of ADC recurrence. CONCLUSION: The development of tumor STAS could be promoted by the functioning of MMP-7. This study could be a crucial basis for future investigations on the detection of tumor STAS.

Dual Image Navigation to Secure Surgical Margins in Thoracoscopic Segmentectomy.

PURPOSE: Video-assisted thoracoscopic surgery (VATS) segmentectomy is being increasingly used for the management of non-small cell lung cancer. For non-palpable lesions, surgeons frequently find difficulty in ensuring a sufficient surgical resection margin. OBJECTIVE: The purpose of this study was to evaluate the role of intraoperative dual image navigation in combination with the infrared thoracoscopy with intravenous injection of indocyanine green (IRT-ICG) method and intraoperative computed tomography (CT) in detecting oncological margins. METHODS: This study involved 34 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy between October 2017 and July 2021. The intersegmental line on the visceral pleura was visualized using the IRT-ICG method. The intersegmental line was marked by clipping, and an intraoperative CT scan was performed under bilateral lung ventilation. Intraoperative CT or three-dimensional CT reconstruction images were used by surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 91.2% of patients. In eight cases, the surgeon needed to make some modifications to the resection line to secure a sufficient surgical margin. The mean surgical margin assessed on gross examination by the pathologist was 23.4 ± 9.0 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Intraoperative dual image navigation combined with the IRT-ICG method and intraoperative CT scan enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study.

This study assessed the immunogenicity and safety of the BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment. We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 ± 1 weeks after the second vaccination. Anti-severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant and Elecsys Anti-SARS-CoV-2 S assays. Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody concentration, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p < .001 on Architect; 4.0 vs 1.2 U/mL, p < .001 on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p = .005 on Architect; 213 vs 573 A/mL, p = .002 on Elecsys). The adjusted odds ratio (aOR) for seroprotection was significantly lower (p < .05) in lung cancer patients than that in non-cancer patients. Analysis of the anticancer treatment types showed that the aOR for seroprotection was significantly lower (p < .05) in lung cancer patients receiving cytotoxic agents. They showed no increase in adverse reactions. BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased (p < .05) antibody titers and showed acceptable safety. Immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

Tumor-associated CD163+ macrophage as a predictor of tumor spread through air spaces and with CD25+ lymphocyte as a prognostic factor in resected stage I lung adenocarcinoma.

OBJECTIVE: Lung cancer can spread in numerous ways, including spread through air spaces (STAS). A high number of CD68+ tumor-associated macrophages (TAMs), which creates a favorable microenvironment for tumor progression, is an independent predictor of increased STAS rate and is used as a pan-macrophage marker, whereas CD163 is used as an M2 macrophage marker. A high number of CD25+ tumor-infiltrating lymphocytes (TILs) is associated with the frequency of STAS. This study investigated the influence of M2 macrophages and CD25+ TILs on STAS and postoperative recurrence in patients with stage I lung adenocarcinoma who underwent curative resection. METHODS: We analyzed data from 485 patients with stage 0-I lung adenocarcinoma who underwent resection between 1999 and 2016. Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, CD68, and CD163. Three tumor areas with the highest density of immune cells were photographed, and the immune cells were quantified. Associations between variables were analyzed using chi-square tests and Mann-Whitney U tests. Recurrence-free probability (RFP) was analyzed using log-rank tests and Cox proportional hazards models. RESULTS: CD163+ TAMs were identified as an independent predictor of a higher rate of STAS (P < 0.001). Analysis of biologically relevant immune cell combinations revealed that patients with high CD25+ TILs and high CD163+ TAMs had a significantly lower RFP (5-year RFP, 74%) than those with other combinations of CD25 and CD163 (5-year RFP, 90%; P < 0.001). Multivariate analysis showed that high CD25+/high CD163+ immune cell infiltration was an independent predictor of RFP. CONCLUSION: We demonstrated that a higher density of M2 macrophages is an independent predictor of a higher STAS incidence. A high CD25+/high CD163+ immune cell infiltration ratio is a significant prognostic factor for stage 0-I lung adenocarcinoma.

Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma.

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p < 0.001) and worse OS (hazard ratio [HR]: 1.75, p = 0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.

High-grade tumor classified by new system is a prognostic predictor in resected lung adenocarcinoma.

OBJECTIVES: A grading system for pulmonary adenocarcinoma has not been established; hence, the International Association for the Study of Lung Cancer (IASLC) pathology panel developed a new grading system for invasive adenocarcinoma. We aimed to evaluate the prognostic significance of the IASLC grading system for invasive pulmonary adenocarcinoma. METHODS: We conducted a retrospective analysis of 471 Japanese patients with resected lung adenocarcinoma. Tumors were classified in accordance with the IASLC grading system and 2015 World Health Organization classification. We analyzed recurrence-free probability (RFP) and overall survival (OS) using the log-rank test and compared the two grading systems using the Cox proportional hazards model. RESULTS: Grade 3 tumors of the IASLC system and high-grade tumors of the 2015 World Health Organization classification were present in 38% and 17% of patients, respectively. The 5-year RFP was lower in patients with IASLC Grade 3 tumors (45%) than in patients with IASLC Grade 1 and 2 tumors (91% and 83%, respectively). The 5-year RFP of patients with IASLC Grade 2 tumors (83%) was higher than of those with 2015 World Health Organization intermediate tumors (69%). On multivariate analysis for recurrence, IASLC Grade 3 was an independent prognostic factor of worse RFP. We showed similar results on analysis for the OS. CONCLUSIONS: The prognostic significance of IASLC Grade 3 tumors on recurrence-free probability was confirmed through both univariate and multivariate analyses. Thus, the IASLC Grade 3 tumor is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.

Preoperative monocyte count is a predictor of recurrence after Stage I lung adenocarcinoma resection.

OBJECTIVES: High-grade tumours are observed even in Stage I lung adenocarcinomas. Tumour spread through air spaces (STAS) is a risk factor for recurrence after resection. However, there is no ideal predictive biomarker for STAS in high-grade Stage I lung adenocarcinoma. This study assessed the prognostic impact of the preoperative peripheral monocyte count in lung adenocarcinoma. METHODS: We retrospectively analysed the data of 444 patients with resected Stage I lung adenocarcinoma during 2006-2016. Univariable and multivariable Cox proportional analyses of recurrence-free probability (RFP) and overall survival (OS) were used to analyze preoperative complete peripheral blood cell count data. Since monocyte count was associated with poor prognosis, the relationship between preoperative peripheral monocyte count and clinicopathological factors, including STAS, was assessed. In addition, immunohistochemical CD68 staining was performed to evaluate tumour-associated macrophages (TAMs). RESULTS: A higher preoperative peripheral monocyte count was a predictor of lower RFP (P = 0.004) and lower OS (P < 0.001). In multivariable analysis, a higher peripheral monocyte count was an independent prognostic factor for RFP and OS (hazard ratio: 1.88, 95% confidence interval: 1.07-3.31, P = 0.029; hazard ratio: 2.13, 95% confidence interval: 1.22-3.75, P = 0.008, respectively). A higher peripheral monocyte count was associated with a higher frequency of STAS (P = 0.017) and higher number of CD68+ TAMs (P = 0.013). CONCLUSIONS: A higher preoperative peripheral monocyte count was an independent marker for a poor prognosis in Stage I lung adenocarcinoma and was associated with a higher frequency of STAS.

Tumor-associated macrophage infiltration is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas.

OBJECTIVE: Lung cancer can spread in numerous ways, one of which has been suggested to be spread through air spaces (STAS). The tumor immune microenvironment appears to play a significant role in this spread. Particularly, tumor-associated macrophages (TAMs) can create a favorable microenvironment for tumor progression. In this study, we analyzed data from 709 patients with stage 0-IIIA lung adenocarcinoma, resected between 1999 and 2016, and investigated whether immune cell infiltration was associated with the occurrence of STAS and clinical outcome of the disease. MATERIALS AND METHODS: Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, and CD68. The three tumor areas with the highest density of immune cells were photographed, and the immune cells were quantified. Associations between variables were analyzed using chi-square tests and Mann-Whitney U tests. Recurrence-free probability and overall survival were analyzed using log-rank tests and Cox proportional hazards models. RESULTS: After analyzing the associations between STAS and each type of immune cell infiltration, high density of CD68 + TAMs was identified as an independent predictor of a high STAS rate (p =  0.014) and was found to be associated with a high risk of recurrence, using univariate analysis (p =  0.008). After adjusting for CD68+ TAMs, pathological stage, and lymphovascular invasion, STAS remained significantly associated with a high risk of recurrence (HR = 3.50, p < 0.001). CONCLUSION: We demonstrated that a high density of CD68 + TAMs is an independent predictor of an increased STAS rate. Additionally, STAS is correlated with aggressive tumor behavior characteristics.

Synthesis of polyenylpyrrole derivatives with selective growth inhibitory activity against T-cell acute lymphoblastic leukemia cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a hardly curable disease with a high relapse rate. 20 analogs were synthesized based on the structures of two kinds of fungi-derived polyenylpyrrole products (rumbrin (1) and auxarconjugatin-B (2)) to suppress the growth of T-ALL-derived cell line CCRF-CEM and tested for growth-inhibiting activity. The octatetraenylpyrrole analog gave an IC50 of 0.27 µM in CCRF-CEM cells, while it did not affect Burkitt lymphoma-derived cell line Raji and the cervical cancer cell line HeLa, or the oral cancer cell line HSC-3 (IC50 > 10 µM). This compound will be a promising compound for developing T-ALL-specific drugs.

The epithelial-mesenchymal transition phenotype is associated with the frequency of tumor spread through air spaces (STAS) and a High risk of recurrence after resection of lung carcinoma.

OBJECTIVES: The prognostic value of spread through air spaces (STAS) in lung carcinoma has been validated in independent cohorts. Epithelial-mesenchymal transition (EMT) is a biological process that promotes the migration and invasiveness of tumor cells. To investigate the role of the EMT phenotype in the occurrence of STAS, we analyzed patients with therapy-naive lung adenocarcinoma and squamous cell carcinoma undergoing lobectomy (n = 635). MATERIALS AND METHODS: STAS was defined by the presence of tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The expression of E-cadherin, vimentin, and ®-catenin was evaluated by immunohistochemistry using tissue microarray. Tumors were classified into three EMT phenotypes (epithelial, intermediate, and mesenchymal). Recurrence-free probability and overall survival were analyzed using the log-rank test and the Cox proportional hazards model. RESULTS: STAS was less frequently observed in tumors with epithelial phenotype than in those with non-epithelial phenotype (p = 0.034), and more frequent in patients with nuclear ß-catenin-positive tumors (p < 0.001). The EMT phenotype was an independent prognostic factor of recurrence (mesenchymal vs. epithelial: hazard ratio [HR] = 2.27, p = 0.014; mesenchymal vs. intermediate: HR = 2.13, p = 0.019). CONCLUSION: We have demonstrated that in patients with resected lung carcinoma, STAS was less frequent in tumors with an epithelial phenotype than in those with non-epithelial phenotype, and that the nuclear translocation of ß-catenin was associated with a higher rate of STAS. The mesenchymal state was an independent predictor of high risk of recurrence in patients with STAS.

Development of Three-Dimensional Cell Culture Scaffolds Using Laminin Peptide-Conjugated Agarose Microgels.

Three-dimensional (3D) cell scaffolds are essential for tissue engineering. So far, various polymer hydrogels have been utilized to design 3D scaffolds as a biomaterial. In this study, we focused on a biocompatible polysaccharide, agarose, as a potential biomaterial candidate. We have previously established a laminin-derived cell adhesive peptide library, and these peptides are useful for incorporating cell adhesiveness into inert materials. We synthesized aldehyde-functionalized agarose (CHO-agarose) by (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of agarose and developed peptide-agarose scaffolds using two laminin peptides, CGG-A99 (CGGAGTFALRGDNPQG, binds to αvß3 integrin) and CGG-AG73 (CGGRKRLQVQLSIRT, binds to syndecan). The peptides were effectively loaded onto the CHO-agarose gels via thiazolidine formation without coupling reagents. Two-dimensional (2D) cell culture assay using human dermal fibroblasts (HDFs) showed that the peptide-agarose gels have potent cell adhesion activity and promoted cell proliferation. Furthermore, we developed a simple preparation method of 3D cell culture scaffolds using peptide-agarose microgels. HDFs cultured in a 3D environment of the A99-agarose microgel scaffold exhibited cell spreading morphology and proliferated significantly. These results suggest that 3D cell culture systems using peptide-agarose microgel scaffolds are promising as a biomaterial for tissue engineering.

[Thoracoscopic Diaphragmatic Stitching for the Catamenial Pneumothorax].

A 46-year-old woman experienced an initial episode of right-sided spontaneous pneumothorax at the time of menstruation. The findings of thoracoscopic examination suggested catamenial pneumothorax. Thoracoscopic surgery revealed multiple blueberry spots on the diaphragm. Considering the patient to be premenopausal within several years and expecting postoperative hormonal therapy, we stitched all lesions without resection for detailed histopathological diagnosis. The patient is well 5 months postoperatively.