Enhancement of neural crest formation by mechanical force in Xenopus development.

In vertebrate development, ectoderm is specified into neural plate (NP), neural plate border (NPB), and epidermis. Although such patterning is thought to be achieved by molecular concentration gradients, it has been revealed, mainly by in vitro analysis, that mechanical force can regulate cell specification. During in vivo patterning, cells deform and migrate, and this applies force to surrounding tissues, shaping the embryo. However, the role of mechanical force for cell specification in vivo is largely unknown. In this study, with an aspiration assay and atomic force microscopy, we have demonstrated that tension on ectodermal cells decreases laterally from the midline in Xenopus early neurula. Ectopically applied force laterally expanded the neural crest (NC) region, a derivative of the NPB, whereas force relaxation suppressed it. Furthermore, force application activated both the FGF and Wnt pathways, which are required for NC formation during neuroectodermal patterning. Taken together, mechanical force is necessary for NC formation in order to regulate signaling pathways. Furthermore, molecular signals specify the NP and generate force on neighboring tissue, the NPB, with its closure. This force activates signals, possibly determining the appropriate width of a narrow tissue, the NC.

Evaluation of Pancreatic ß-cell Differentiation Efficiency of Human iPSC Lines for Clinical Use.

BACKGROUND: Transplantation of pancreatic ß-cells generated from human induced pluripotent stem cells (hiPSCs) has great potential as a root treatment for type 1 diabetes. However, their current level of efficiency to differentiate into ß-cells is still not at par for clinical use. Previous research has shown that differentiation efficiency varies among human embryonic stem cells and mouse-induced pluripotent stem cell lines. Therefore, selecting a suitable cell line for efficient induction into desired tissues and organs is crucial. METHOD: In this study, we have evaluated the efficiency of 15 hiPSC lines available for clinical use to differentiate into pancreatic ß-cells. RESULTS: Our investigation has revealed induction efficiency to differ among the hiPSC lines, even when derived from the same donor. Among the hiPSC lines tested, the 16A01 cell line exhibited the highest insulin expression and low glucagon expression, suggesting that this cell line is suitable for differentiation into ß-cells. CONCLUSION: Our study has demonstrated the importance of selecting a suitable hiPSC line for effective differentiation into ß-cells.

Identification of tumor-related genes via RNA sequencing of tumor tissues in Xenopus tropicalis.

Cancer treatment is still challenging because the disease is often caused by multiple mutations. Although genomic studies have identified many oncogenes and tumor suppressor genes, gene sets involved in tumorigenesis remain poorly understood. Xenopus, a genus of aquatic frogs, is a useful model to identify gene sets because it can be genetically and experimentally analyzed. Here, we analyzed gene expression in tumor tissues of three individuals in Xenopus tropicalis and identified 55 differentially expressed genes (DEGs). Gene ontology (GO) analysis showed that the upregulated genes in the tumor tissues were enriched in GO terms related to the extracellular matrix and collagen fibril organization. Hierarchical clustering showed that the gene expression patterns of tumor tissues in X. tropicalis were comparable to those of human connective, soft, and subcutaneous tissue-derived cancers. Additionally, pathway analysis revealed that these DEGs were associated with multiple pathways, including the extracellular matrix, collagen fibril organization, MET signaling, and keratan sulfate. We also found that the expression tendency of some DEGs that have not been well analyzed in the cancer field clearly determines the prognosis of human cancer patients. This study provides a remarkable reference for future experimental work on X. tropicalis to identify gene sets involved in human cancer.

The Helicobacter pylori CagA oncoprotein disrupts Wnt/PCP signaling and promotes hyperproliferation of pyloric gland base cells.

Helicobacter pylori strains that deliver the oncoprotein CagA into gastric epithelial cells are the major etiologic agents of upper gastric diseases including gastric cancer. CagA promotes gastric carcinogenesis through interactions with multiple host proteins. Here, we show that CagA also disrupts Wnt-dependent planar cell polarity (Wnt/PCP), which orients cells within the plane of an epithelium and coordinates collective cell behaviors such as convergent extension to enable epithelial elongation during development. Ectopic expression of CagA in Xenopus laevis embryos impaired gastrulation, neural tube formation, and axis elongation, processes driven by convergent extension movements that depend on the Wnt/PCP pathway. Mice specifically expressing CagA in the stomach epithelium had longer pyloric glands and mislocalization of the tetraspanin proteins VANGL1 and VANGL2 (VANGL1/2), which are critical components of Wnt/PCP signaling. The increased pyloric gland length was due to hyperproliferation of cells at the gland base, where Lgr5+ stem and progenitor cells reside, and was associated with fewer differentiated enteroendocrine cells. In cultured human gastric epithelial cells, the N terminus of CagA interacted with the C-terminal cytoplasmic tails of VANGL1/2, which impaired Wnt/PCP signaling by inducing the mislocalization of VANGL1/2 from the plasma membrane to the cytoplasm. Thus, CagA may contribute to the development of gastric cancer by subverting a Wnt/PCP-dependent mechanism that restrains pyloric gland stem cell proliferation and promotes enteroendocrine differentiation.

Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells.

Islet transplantation, including pancreatic beta cells, has become an approved treatment for type I diabetes. To date, the number of donors limits the availability of treatment. Induction of pancreatic endocrine cells from pluripotent stem cells including iPSCs in vitro offers promise as a solution, but continues to face problems including high reagent costs and cumbersome differentiation procedures. In a previous study, we developed a low-cost, simplified differentiation method, but its efficiency for inducing pancreatic endocrine cells was not sufficient: induction of endocrine cells is non-uniform, resulting in colonies containing relatively high ratio of non-pancreatic-related cells. Here, we applied cyclin-dependent kinase inhibitors (CDKi) within a specific time window, which improved the efficiency of pancreatic endocrine cell induction. CDKi treatment reduced the prevalence of multi-layered regions and enhanced expression of the endocrine progenitor-related marker genes PDX1 and NGN3 resulting in enhanced production of both INSULIN and GLUCAGON. These findings support a step forward in the field of regenerative medicine of pancreatic endocrine cells.

Thrombus formation at the stump of the pulmonary vein after lobectomy: a prospective multi-institutional study.

PURPOSE: Recent reports suggest that postoperative cerebral infarction following lung cancer surgery is caused by thrombus formation at the stump of the pulmonary vein and that the risk is highest after left upper lobectomy (LUL). Thrombosis at the stump of the pulmonary vein and the incidence of cerebral infarction was investigated prospectively in patients who underwent lobectomy for lung cancer. METHODS: Lung cancer patients undergoing planned pulmonary lobectomy were enrolled. The endpoint was to confirm if there is a higher incidence of thrombus formation (primary) and a higher incidence of cerebral infarction (secondary) in patients undergoing LUL. We planned to accrue 600 patients. An interim analysis was scheduled for just after the data center received the final clinical review form of the 300th patient. RESULTS: The interim analysis revealed a significant difference in the primary endpoint. In the final analysis, thrombus was identified in 16 of 88 LUL patients (20.5%), and in 4 of 247 patients who underwent other types of lobectomy (1.6%) (p < 0.05). Cerebral infarction was identified in 1 of the LUL patients (1.3%) and in 9 of the other patients (3.6%) (p = 0.318). CONCLUSIONS: Thrombus frequently forms at the stump of the left superior pulmonary vein after LUL. However, our study did not identify a relationship between thrombosis and cerebral infarction.

Ndst1, a heparan sulfate modification enzyme, regulates neuroectodermal patterning by enhancing Wnt signaling in Xenopus.

Neural tissue is derived from three precursor regions: neural plate, neural crest, and preplacodal ectoderm. These regions are determined by morphogen-mediated signaling. Morphogen distribution is generally regulated by binding to an extracellular matrix component, heparan sulfate (HS) proteoglycan. HS is modified by many enzymes, such as N-deacetyl sulfotransferase 1 (Ndst1), which is highly expressed in early development. However, functions of HS modifications in ectodermal patterning are largely unknown. In this study, we analyzed the role of Ndst1 using Xenopus embryos. We found that ndst1 was expressed in anterior neural plate and the trigeminal region at the neurula stage. ndst1 overexpression expanded the neural crest (NC) region, whereas translational inhibition reduced not only the trigeminal region, but also the adjacent NC region, especially the anterior part. At a later stage, ndst1 knocked-down embryos showed defects in cranial ganglion formation. We also found that Ndst1 activates Wnt signaling pathway at the neurula stage. Taken together, our results suggest that N-sulfonated HS accumulates Wnt ligand and activates Wnt signaling in ndst1-expressing cells, but that it inhibits signaling in non-ndst1-expressing cells, leading to proper neuroectodermal patterning.

The heparan sulfate modification enzyme, Hs6st1, governs Xenopus neuroectodermal patterning by regulating distributions of Fgf and Noggin.

The nervous system has various types of cells derived from three neuroectodermal regions: neural plate (NP), neural crest (NC), and preplacodal ectoderm (PPE). Differentiation of these regions is regulated by various morphogens. However, regulatory mechanisms of morphogen distribution in neural patterning are still debated. In general, an extracellular component, heparan sulfate (HS), is essential to regulate morphogen gradients by modulating morphogen binding. The present study focused on an HS modification enzyme, heparan sulfate 6-O-sulfotransferase 1 (Hs6st1), which is highly expressed during the neurula stage in Xenopus. Our present in situ hybridization analysis revealed that Hs6st1 is expressed in the lateral sensorial layer of neuroectoderm. Overexpression of Hs6st1 expands Sox3 (NP marker gene) expression, and slightly dampens FoxD3 (NC marker) expression. Hs6st1 knockout using the CRISPR/Cas9 system also expands the neural plate region, followed by retinal malformation. These results imply that 6-O sulfation, mediated by Hs6st1, selectively regulates morphogen distribution required for neuroectodermal patterning. Among morphogens required for patterning, Fgf8a accumulates on Hs6st1-expressing cells, whereas a secreted BMP antagonist, Noggin, diffuses away from those cells. Thus, cell-autonomous 6-O sulfation of HS at the sensorial layer of neuroectoderm also affects neuroectodermal patterning in neighboring regions, including neural plate and neural crest, not only through accumulation, but also through dispersal of specific morphogens.

Postoperative pain and quality of life after lung cancer surgery: a prospective observational study.

BACKGROUND: We aimed to identify the factors associated with postoperative pain, quality of life, and development of chronic pain after lung cancer surgery, including pain sensation threshold, fentanyl sensitivity, and surgical procedures. METHODS: We conducted a single-center prospective observational study involving lung cancer patients. Brief pain inventory, including nine items concerning pain and quality of life, was investigated at 1 week, 1 month, and 3 months postoperatively. Pain sensation threshold and fentanyl sensitivity were assessed preoperatively. RESULTS: Of the 146 patients who were enrolled, 100 who met our criteria were analyzed. Thoracoscopic surgery was performed in 42 patients and minimally invasive thoracotomy in 58 patients. Pain sensation threshold and fentanyl sensitivity were normally distributed among the patients and were not significantly associated with brief pain inventory scores at each postoperative time-point. The average pain score 1 week after the operation was significantly higher in the thoracotomy group than in the thoracoscopic surgery group (P<0.050). The worst pain scores did not differ between the groups at all the examination periods. Pain sensation threshold, fentanyl sensitivity, and surgical procedures were not related to the incidence of post-thoracotomy pain syndrome. CONCLUSIONS: Individual pain sensation threshold and fentanyl sensitivity were not associated with subjective postoperative pain score, quality of life score, or development of post-thoracotomy pain syndrome.

Predicting pathological highly invasive lung cancer from preoperative [18F]FDG PET/CT with multiple machine learning models.

PURPOSE: The efficacy of sublobar resection of primary lung cancer have been proven in recent years. However, sublobar resection for highly invasive lung cancer increases local recurrence. We developed and validated multiple machine learning models predicting pathological invasiveness of lung cancer based on preoperative [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomic features. METHODS: Overall, 873 patients who underwent lobectomy or segmentectomy for primary lung cancer were enrolled. Radiomics features were extracted from preoperative PET/CT images with the PyRadiomics package. Seven machine learning models and an ensemble of all models (ENS) were evaluated after 100 iterations. In addition, the probability of highly invasive lung cancer was calculated in a nested cross-validation to assess the calibration plot and clinical usefulness and to compare to consolidation tumour ratio (CTR) on CT images, one of the generally used diagnostic criteria. RESULTS: In the training set, when PET and CT features were combined, all models achieved an area under the curve (AUC) of ≥ 0.880. In the test set, ENS showed the highest mean AUC of 0.880 and smallest standard deviation of 0.0165, and when the cutoff was 0.5, accuracy of 0.804, F1 of 0.851, precision of 0.821, and recall of 0.885. In the nested cross-validation, the AUC of 0.882 (95% CI: 0.860-0.905) showed a high discriminative ability, and the calibration plot indicated consistency with a Brier score of 0.131. A decision curve analysis showed that the ENS was valid with a threshold probability ranging from 3 to 98%. Accuracy showed an improvement of more than 8% over the CTR. CONCLUSION: The machine learning model based on preoperative [18F]FDG PET/CT images was able to predict pathological highly invasive lung cancer with high discriminative ability and stability. The calibration plot showed good consistency, suggesting its usefulness in quantitative risk assessment.

Positive feedback regulation of frizzled-7 expression robustly shapes a steep Wnt gradient in Xenopus heart development, together with sFRP1 and heparan sulfate.

Secreted molecules called morphogens govern tissue patterning in a concentration-dependent manner. However, it is still unclear how reproducible patterning can be achieved with diffusing molecules, especially when that patterning concerns differentiation of thin tissues. Wnt is a morphogen that organizes cardiac development. Wnt6 patterns cardiogenic mesoderm to induce differentiation of a thin tissue, the pericardium, in Xenopus. In this study, we revealed that a Wnt receptor, frizzled-7, is expressed in a Wnt-dependent manner. With a combination of experiments and mathematical modeling, this receptor-feedback appears essential to shape a steep gradient of Wnt signaling. In addition, computer simulation revealed that this feedback imparts robustness against variations of Wnt ligand production and allows the system to reach a steady state quickly. We also found that a Wnt antagonist sFRP1, which is expressed on the opposite side of the Wnt source, accumulates on N-acetyl-rich heparan sulfate (HS). N-acetyl-rich HS concentration is high between the sources of Wnt and sFRP1, achieving local inhibition of Wnt signaling via restriction of sFRP1 spreading. These integrated regulatory systems restrict the Wnt signaling range and ensure reproducible patterning of the thin pericardium.

Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm.

Pre-placodal ectoderm (PPE), a horseshoe-shaped narrow region formed during early vertebrate development, gives rise to multiple types of sensory organs and ganglia. For PPE induction, a certain level of FGF signal activation is required. However, it is difficult to reproducibly induce the narrow region with variations in gene expression, including FGF, among individuals. An intracellular regulatory factor of FGF signaling, Dusp6, is expressed by FGF signal activation and inactivates a downstream regulator, ERK1/2, in adult tissues; however, its role in early development is not well known. Here, we reveal that Dusp6 is expressed in an FGF-dependent manner in Xenopus PPE. Gain- and loss-of-function experiments showed that Dusp6 is required for expression of a PPE gene, Six1, and patterning of adjacent regions, neural plate, and neural crest. To reveal the importance of Dusp6 in variable FGF production, we performed Dusp6 knockdown with FGF-bead implantation, which resulted in varying Six1 expression patterns. Taken together, these results suggest that Dusp6 is required for PPE formation and that it contributes to the robust patterning of PPE by mediating FGF signaling.

A simple method of hiPSCs differentiation into insulin-producing cells is improved with vitamin C and RepSox.

Human induced pluripotent stem cells (hiPSCs) are considered a promising source of pancreatic ß-cells for the treatment of diabetes. However, this approach is limited by issues such as low efficiency and high cost. Here, we have developed a new protocol to induce insulin-producing cells. To reduce costs, we decreased the number of reagents and replaced protein reagents with chemical compounds. In this method, we increased induction efficiency with ascorbic acid (vitamin C) and an ALK5 inhibitor, RepSox. In 2D culture, the majority of cells were immature ß-cells with low glucose-stimulated insulin secretion. Transferring to 3D culture immediately after endocrine progenitor cell differentiation, however, improved glucose-stimulated insulin secretion. This simplified method will contribute to realizing transplantation therapy of ß-cells using iPSCs.

Evolution of hes gene family in vertebrates: the hes5 cluster genes have specifically increased in frogs.

BACKGROUND: hes genes are chordate homologs of Drosophila genes, hairy and enhancer of split, which encode a basic helix-loop-helix (bHLH) transcriptional repressor with a WRPW motif. Various developmental functions of hes genes, including early embryogenesis and neurogenesis, have been elucidated in vertebrates. However, their orthologous relationships remain unclear partly because of less conservation of relatively short amino acid sequences, the fact that the genome was not analyzed as it is today, and species-specific genome duplication. This results in complicated gene names in vertebrates, which are not consistent in orthologs. We previously revealed that Xenopus frogs have two clusters of hes5, named "the hes5.1 cluster" and "the hes5.3 cluster", but the origin and the conservation have not yet been revealed. RESULTS: Here, we elucidated the orthologous and paralogous relationships of all hes genes of human, mouse, chicken, gecko, zebrafish, medaka, coelacanth, spotted gar, elephant shark and three species of frogs, Xenopus tropicalis (X. tropicalis), X. laevis, Nanorana parkeri, by phylogenetic and synteny analyses. Any duplicated hes5 were not found in mammals, whereas hes5 clusters in teleost were conserved although not as many genes as the three frog species. In addition, hes5 cluster-like structure was found in the elephant shark genome, but not found in cyclostomata. CONCLUSION: These data suggest that the hes5 cluster existed in the gnathostome ancestor but became a single gene in mammals. The number of hes5 cluster genes were specifically large in frogs.

Surgical outcomes of pulmonary metastasectomy for head and neck cancer in the current era of advances in chemotherapy and immunotherapy.

OBJECTIVE: The innovation of novel systemic chemo/immunotherapy for metastatic head and neck cancer might contribute to prognostic improvement. We aimed to clarify the recent characteristics and outcomes of pulmonary metastasectomy for head and neck cancer. METHODS: Twenty-five patients who underwent pulmonary metastasectomy from January 2011 to December 2016 were included. The clinicopathological factors and survival were assessed by retrospective chart reviews. RESULTS: The median follow-up period was 39 months (range, 7-94 months). The median age was 66 years (range, 20-89 years), and 23 males were included. The primary tumor locations were as follows: pharynx (n = 12), nasal/paranasal cavity (n = 5), larynx (n = 4), and others (n = 4). The 5-year overall survival rate was 49%. In the univariate analysis, a history of local recurrence before pulmonary metastasis was an independent predictor of a poor prognosis. In 90% of patients with recurrence after pulmonary metastasectomy, the site of recurrence was the lung. Eight patients achieved long-term survival without any evidence of recurrence (median: 45 months). Molecular targeting chemotherapy and immune-checkpoint inhibitors were used in five patients with systemic recurrence after pulmonary metastasectomy, leading to preferable survival. CONCLUSIONS: In the current era of advances in systemic chemotherapy and immunotherapy, surgical indication has not changed for resectable pulmonary metastases and selected patients can still benefit from pulmonary metastasectomy. Further investigation is needed to clarify the significance of systemic therapy in patients with pulmonary metastasis of head and neck cancer.

Genetic alterations in squamous cell lung cancer associated with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are at higher risk of developing lung cancers including squamous cell lung carcinoma (SCC), which typically carries a poor prognosis. Although the molecular basis of cancer development subsequent to IPF has not been fully investigated, we recently reported two epigenetic phenotypes characterized by frequent and infrequent DNA hypermethylation in SCC, and an association of the infrequent hypermethylation phenotype with IPF-associated SCCs. Here, we conducted targeted exon sequencing in SCCs with and without IPF using the Human Lung Cancer Panel to investigate the genetic basis of IPF-associated SCC. SCCs with and without IPF displayed comparable numbers of total mutations (137 ± 22 vs 131 ± 27, P = .5), nonsynonymous mutations (72 ± 14 vs 69 ± 16, P = .5), indels (3.0 ± 3.5 vs 3.0 ± 3.9, P = 1) and synonymous mutations (62 ± 9.1 vs 60 ± 12, P = .5). Signature 1 was the predominant signature in SCCs with and without IPF. SETD2 and NFE2L2 mutations were significantly associated with IPF (44% vs 13%, P = .03 for SETD2; 38% vs 10%, P = .04 for NFE2L2). MYC amplification, assessed by copy number variant analysis, was also significantly associated with IPF (18.8% vs 0%, P = .04). Mutations in TP53 and CDKN2A were observed relatively frequently in SCCs with frequent hypermethylation (P = .02 for TP53 and P = .06 for CDKN2A). Survival analysis revealed that the SETD2 mutation was significantly associated with worse prognosis (P = .04). Collectively, we found frequent involvement of SETD2 and NFE2L2 mutations and MYC amplification in SCCs with IPF, and an association of a SETD2 mutation with poorer prognosis.

Management of thoracic empyema with broncho-pulmonary fistula in combination with negative-pressure wound therapy.

OBJECTIVE: Intrathoracic negative-pressure wound therapy (NPWT) has been introduced as a novel therapeutic device for the management of empyema. NPWT is expected to reduce the empyema cavity more rapidly than standard treatments; however, no objective analysis of the function of NPWT has yet been conducted. The study objective was to evaluate the efficacy of NPWT in the management of thoracic empyema. METHODS: Ten patients with stage II or III thoracic empyema treated with NPWT were retrospectively analyzed. The volume of the empyema cavity was measured, and the volume change after the administration of NPWT was calculated. A comparison with the institutional historical controls was also performed. RESULTS: The patients had initially undergone fenestration of the chest wall for empyema, and eight had bronchopleural fistula and required procedures to close the fistula. The mean duration of NPWT was 71.1 days (4-190 days). The mean volume of the empyema cavity decreased from 230.2 ml (42.8-788.4 ml) to 78.5 ml (5.2-185.3 ml) by applying NPWT (P = 0.02), and the mean % decrease was 58.7% (0-87.9%). Ultimately, the empyema cavity was able to be cleaned in nine, including seven who were cured by subsequent thoracoplasty and two who were cured without thoracoplasty. The current study group had a tendency toward an early cure with less chest wall destruction, a less hospital stay after open window thoracotomy compared to historical control. CONCLUSIONS: NPWT enables the effective volume reduction and cleaning of the empyema cavity and achieves an early cure and reduced destruction of the chest wall.

Endobronchial ultrasound-guided transbronchial needle aspiration in patients with previously treated lung cancer.

PURPOSE: The sampling and accurate diagnosis of lymph nodes during the clinical history of lung cancer are essential for selecting the appropriate treatment strategies. This study aims to evaluate the feasibility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with previously treated lung cancer. METHODS: Patients who underwent EBUS-TBNA after treatment for lung cancer were retrospectively reviewed. We classified the patients into two groups; Group 1 (G1): Indicated to have a recurrence of new lesions after radical surgery or chemo/radiotherapy with a curative intent; and Group 2 (G2): Indicated to have residual tumor cells after undergoing primary treatment for chemo/radiotherapy or re-staging after induction therapy prior to surgery. RESULTS: Seventy previously treated lung cancer cases (G1, n = 52; G2, n = 18) were enrolled. Thirty-two cases (61.5%) had recurrent disease in G1, and 9 cases (50.0%) had nodal metastasis in G2. The diagnostic accuracy was 95.2% in G1 and 88.9% in G2. Twenty-four cases were examined for epidermal growth factor receptor (EGFR) mutations, and 9 (37.5%) cases had mutations, including two cases with a T790M mutation. Furthermore, in one case, a re-biopsy revealed that the initial adenocarcinoma had transformed into small cell lung cancer. CONCLUSION: Performing EBUS-TBNA during lung cancer treatment showed a high diagnostic yield. Samples obtained by EBUS-TBNA were helpful in determining when to perform repeat biomarker testing as well as for making pathological re-evaluations.

Is needle biopsy a risk factor of pleural recurrence after surgery for non-small cell lung cancer?

BACKGROUND: Tumor seeding, whereby malignant cells are deposited along the needle tract, is considered to be a potential hazard of needle biopsies. The aim of this study is to elucidate the relationship between needle biopsies for lung tumor, such as a preoperative computed tomography-guided needle biopsy (PCTGNB) or an intraoperative fine-needle aspiration biopsy (IFNAB), and ipsilateral pleural recurrence (PR) after lung cancer surgery. METHODS: Between 2008 and 2017, 1,047 patients with non-small cell lung cancer (NSCLC) underwent curative lung resection in our institution. They were divided into two groups: those in whom the first recurrent site was the ipsilateral pleural cavity (PR group) and the others (control group). Risk factors of PR were investigated retrospectively. RESULTS: Recurrence was observed in 191 patients (18.2%), 25 of whom were categorized to the PR group (17 malignant effusion, 10 dissemination). Pathological tumor [2-4], lymph nodes [1-2], pleural, lymphatic and vascular invasion (each ≥1) factors and patients who underwent PCTGNB were more frequently observed in the PR group than in the control group (each P<0.01) whereas the proportion of patients who underwent IFNAB was not significant. A multivariate analysis identified pathological lymph node factor and the frequency of PCTGNB as independent risk factors for PR with hazard ratios of 7.33 (95% CI, 2.93-19.8; P<0.01) and 6.92 (95% CI, 2.25-17.8; P<0.01), respectively. CONCLUSIONS: PCTGNB is a risk factor of PR but IFNAB is not. Indications for PCTGNB should be carefully determined.

Emergency surgery for hemothorax due to a ruptured pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformation (PAVM) is a potential cause of hemothorax. The risk of PAVM rupture is reported to be higher during pregnancy for several reasons, including increased body fluid and a change in hormonal conditions. A 34-year-old pregnant woman suddenly felt right chest pain and dyspnea in the 28th week of gestation. Chest X-ray and computed tomography showed massive right pleural effusion. Her vital signs gradually deteriorated with hemorrhagic shock, necessitating emergency surgery. During exploratory thoracoscopy, active bleeding from the middle lobe was noticed and gauze packing was required to maintain her blood pressure. Following conversion to major thoracotomy, wedge resection of the middle lobe was performed with a linear stapler, and finally, her general condition became stable. Her postoperative course was uneventful. A histological examination of the resected specimen confirmed the diagnosis of ruptured PAVM. Her baby was successfully delivered at the 38th week of gestation.