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Background Pulmonary vein stump thrombosis may occur after left upper lobectomy (LUL) and is a potential risk factor for cerebral infarction. However, there are few reports on the role of pulmonary vein stump thrombosis in the development of cerebral infarction. We aimed to clarify the correlation between pulmonary vein stump thrombosis and cerebral infarction following LUL. Methods We evaluated 296 patients who underwent contrast-enhanced computed tomography (CT) after LUL for lung cancer at the Shizuoka Cancer Center Hospital in Shizuoka, Japan, between September 2002 and December 2015. The cerebral infarction in patients with pulmonary vein stump thrombosis was examined, and the risk factors for cerebral infarction were identified via a univariate analysis of the clinicopathological and surgical variables. Results Overall, 179 men and 117 women (median age: 68 years; range: 36–88 years) were included. The median observation period was 68 months. Pulmonary vein stump thrombosis occurred in 21 (7%) patients and cerebral infarction occurred in 15 (5%) patients. None of the 21 patients with pulmonary vein stump thrombosis developed cerebral infarction. Most cerebral infarctions (12/15) were diagnosed in the late phase (> 3 months). The pathological stage of cancer was found to be the only significant risk factor for cerebral infarction by the univariate analysis. Conclusion Pulmonary vein stump thrombosis following LUL was not necessarily associated with cerebral infarction, including the late phase. A prospective observational study with contrast-enhanced chest CT would be required to investigate the risk factors for cerebral infarction in each phase of the postoperative period. [ABSTRACT FROM AUTHOR]

Decellularized extracellular matrix (dECM) hydrogels have cytocompatibility, and are currently being investigated for application in soft tissues as a material that promotes native cell infiltration and tissue reconstruction. A dECM hydrogel has broad potential for application in organs with complex structures or various tissue injury models. In this study, we investigated the practical application of a dECM hydrogel by injecting a kidney‐derived dECM hydrogel into a rat partial nephrectomy model. The prepared dECM hydrogel was adjustable in viscosity to allow holding at the excision site, and after gelation, had an elastic modulus similar to that of kidney tissue. In addition, the migration of renal epithelial cells and vascular endothelial cells embedded in dECM hydrogels was observed in vitro. Four weeks after injection of the dECM hydrogel to the partial excision site of the kidneys, infiltration of renal tubular constituent cells and native cells with high proliferative activity, as well as angiogenesis, were observed inside the injected areas. This study is the first to show that dECM hydrogels can be applied to the kidney, one of the most complex structural organs and that they can function as a scaffold to induce angiogenesis and infiltration of organ‐specific renal tubular constituent cells, providing fundamental insights for further application of dECM hydrogels. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Although pulmonary emphysema is a component of chronic obstructive pulmonary disease, the prognostic significance of the quantitative severity of emphysema in patients with primary lung cancer is unclear. This study aimed to identify the association between the quantitative severity of emphysema detected by the low-attenuation area on computed tomography and the prognostic outcome of early non-small-cell lung cancer. METHODS A consecutive series of 1062 patients who underwent lobectomy for clinical stage I and II non-small-cell lung cancer were enrolled in this study. The clinicopathological features and long-term outcomes of patients with primary lung cancer in emphysema were investigated. The extent of emphysema in the lobe where the tumour was present was measured by preoperative computed tomography as a percentage of the low-attenuation area (LAA%). RESULTS LAA% ≥ 1.0% was detected in 145 (13.7%) patients. LAA% was associated with pleural invasion (P  < 0.0001), vascular invasion (P  < 0.0001) and a larger tumour size (P  = 0.001). The overall survival and recurrence-free survival in patients with LAA% ≥ 1.0% and with LAA% < 1.0% at 5 years were 78.6% and 92.1% (P  < 0.0001) and 68.7% and 85.2% (P  < 0.0001), respectively. According to the Cox proportional hazards model, LAA% was an independent prognostic factor for overall survival and recurrence-free survival (P  = 0.0004 and P  = 0.003, respectively). CONCLUSIONS The quantitative severity of pulmonary emphysema was found to be associated with poor prognosis and clinicopathological aggression in early non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cells (hiPSCs) are a promising cell source for elucidating disease pathology and therapy. The mass supply of hiPSC-derived cells is technically feasible. Carriers that can contain a large number of hiPSC-derived cells and evaluate their functions in vivo-like environments will become increasingly important for understanding disease pathogenesis or treating end-stage organ failure. hiPSC-derived hepatocyte-like cells (hiPSC-HLCs; 5 × 108) were seeded into decellularized organ-derived scaffolds under circumfusion culture. The scaffolds were implanted into immunodeficient microminiature pigs to examine their applicability in vivo. The seeded hiPSC-HLCs demonstrated increased albumin secretion and up-regulated cytochrome P450 activities compared with those in standard two-dimensional culture conditions. Moreover, they showed long-term survival accompanied by neovascularization in vivo. The decellularized organ-derived scaffold is a promising carrier for hiPSC-derived cells for ex vivo and in vivo use and is an essential platform for regenerative medicine and research. [ABSTRACT FROM AUTHOR]

Positive preresection pleural lavage cytology (PLC+) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC+ for the different pathologic stages (p-stages) of NSCLC. A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC+ on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC+ was compared using the Kaplan-Meier method with the log-rank test for comparison. PLC+ was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P <.001), a pathologic tumor size larger than 3 cm (P =.033), the presence of pleural invasion (P <.001), and adenocarcinoma (P =.038). In patients with PLC+, the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC−) (P <.001). On multivariate analysis, the PLC+ status was an independent prognostic factor of DFS (hazard ratio 1.70; P =.013). Among the 818 patients with p-stage I NSCLC, PLC+ was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC+ was equal to that in patients with p-stage IIIA NSCLC with PLC− (5-year DFS, 40.4% and 39.0%). PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC+, especially for patients with p stage I. [ABSTRACT FROM AUTHOR]

Background and objective: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. Methods: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole‐exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. Results: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1–64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. Conclusion: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values. Patients with NSCLC and ILD did not have high TMB and could develop severe pneumonitis if immune checkpoint inhibitors are used. Therefore, immune checkpoint inhibitors should not be used based on expectations of high TMB in patients with NSCLC and ILD. See relatedEditorial [ABSTRACT FROM AUTHOR]

• We describe a pulmonary LCNEC with bronchial intraepithelial recurrence. • Because of its rarity, the mechanism of tumor progression of LCNEC is still unknown. • Endobronchial metastases usually showed the presence of polypoid lesions. • This is the first case of metastasis with bronchial intraepithelial recurrence. • Clinicians should be aware of this unique recurrence type in pulmonary LCNEC. We encountered a case of a large cell neuroendocrine carcinoma with bronchial intraepithelial spread, a unique form of recurrence. A 63-year-old man underwent middle lobectomy and systematic lymph node dissection for lung cancer. The pathological diagnosis was a large cell neuroendocrine carcinoma, and the pathological stage of the tumor was T2aN0M0, stage IB. At 30 months after surgery, the patient complained of continuous cough, and computed tomography revealed a thickened right upper bronchus. Transbronchial biopsy revealed a large cell neuroendocrine carcinoma with bronchial intraepithelial recurrence. The patient died of disease 24 months after recurrence was diagnosed. In cases of centrally located small cell lung carcinoma, it is well known that tumor cells progress along the sub-bronchial mucosa. In contrast, the mechanism of tumor progression of large cell neuroendocrine carcinoma is not fully elucidated because of the rarity of such cases. Endobronchial metastases usually show the presence of polypoid lesions. To the best of our knowledge, this is the first case of endobronchial metastasis from a pulmonary large cell neuroendocrine carcinoma showing bronchial intraepithelial recurrence. Clinicians should be aware of this unique form of recurrence in patients with large cell neuroendocrine carcinoma of the lungs. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.09.003 Byline: Kana Unuma (a)(b), Kazuki Harada (a), Makoto Nakajima (a), Hiromi Eguchi (c), Kensuke Tsushima (d), Takako Ito (a)(e), Kaori Shintani-Ishida (a), Hideaki Kojima (c)(f), Ken-ichi Yoshida (a) Keywords: Central pontine myelinolysis; Digoxin; Vomiting; Autopsy Abstract: An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na.sup.+) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration. Author Affiliation: (a) Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan (b) Research Fellow of the Japan Society for the Promotion of Science, Japan (c) Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Japan (d) Department of Cardiovascular Medicine, University of Tokyo Hospital, Japan (e) Department of Health Services Management and Policy, Graduate School of Medicine Sciences, Kyushu University, Japan (f) Department of Pathology and Clinical Cytology, Mitsubishi Chemical Medience, Japan Article History: Received 26 September 2008; Revised 21 April 2009; Accepted 1 September 2009

Objectives The objective of this study was to investigate clinicopathological risk factors for local recurrence in patients who underwent either complete resection with lobectomy or more extensive resection with hilar and mediastinal lymph node dissection for non-small cell lung cancer (NSCLC). The role of adjuvant therapy was also explored. Materials and methods We reviewed the records of 1012 consecutive stage I–III NSCLC patients who underwent complete resection. The median follow-up time was 59 months. The risk factors for local recurrence were investigated by multivariate analysis using Cox’s proportional hazards regression model. Results Local recurrence was identified in 9.4% of the patients. The most significant risk factor for local recurrence was lymph node metastasis (N1: hazard ratio [HR] = 2.27, p = 0.009; N2: HR = 6.85, p < 0.0001). For the subgroup of patients with lymph node metastasis (n = 289), the independent risk factors for local recurrence were N2 disease with N1 metastasis (N2 with N1; HR = 3.46, p < 0.0001) and non-receipt of adjuvant platinum-based chemotherapy (HR = 1.91, p = 0.018). The 5-year freedom from local recurrence rates were 96.1%, 84.1%, 85.0%, and 53.5% for N0, N1, skip N2, and N2 with N1 stages ( p < 0.0001). Conclusion Local recurrence is significantly associated with poor overall survival. Therefore, local control is essential for radical cure of NSCLC. N2 with N1 status was the primary risk factor for local recurrence, while adjuvant chemotherapy improved local control. These data have important implications for postoperative radiotherapy and highlight the need to devise more effective eligibility criteria for this modality in patients with lymph node metastasis. [ABSTRACT FROM AUTHOR]

Background: Thoracic epidural analgesia (EDA) is the gold standard for pain control after thoracotomy. However, because of its severe side effects, it is contraindicated in patients taking anticoagulant or antiplatelet drugs. In addition, some patients' anatomy can make epidural catheter insertion challenging. We therefore investigated the safety and efficacy of paravertebral block (PVB) using a thoracoscopic insertion technique, which avoids damage to the parietal pleura, for postoperative pain after thoracotomy.Methods: Patients who underwent thoracotomy with thoracic PVB in our hospital between March 2013 and March 2014 were examined retrospectively. Prior to creating the thoracotomy incision, a catheter for PVB was inserted percutaneously into the paravertebral space under thoracoscopic guidance. A matched-pair control group was selected at a 1:2 ratio from patients who underwent thoracotomy with thoracic EDA in our hospital from April 2011 to February 2013. Pain control and side effects were compared between groups and the results statistically analyzed.Results: Thoracic PVB was performed in 56 patients during this period, and 112 patients were selected as matched controls. Numeric Rating Scale scores on postoperative day 2 did not differ significantly between the PVB group (3.25 ± 1.80) and the EDA group (3.56 ± 2.05) (p = 0.334). In terms of side effects, urinary retention occurred less frequently in thoracic PVB patients (p = 0.03).Conclusion: Under the conditions of the present study, continuous thoracic PVB was at least as effective as epidural analgesia for postoperative pain control after thoracotomy with lung resection. [ABSTRACT FROM AUTHOR]

We report an autopsy case of multiple anomalies with severe micrencephaly, bilateral microphthalmos, and hypoplastic endocrine organs. We examined expressions of calcium-binding proteins and hypothalamic and pituitary hormones. A female proband presented with microcephaly, microphthalmia, and psychomotor development delay. At the age of 23 years, she died of cardiorespiratory failure. The endocrine organs demonstrated severe underdevelopment, and the hypoplastic eyeballs had remnant lens, vitreous hemorrhage, and retinal detachment. The brain weighed 260 g; the cerebrum, cerebellum, and brain stem were extremely small; and the tertiary sulci were absent in the cerebral surface. The cross-sectional area of cerebral cortex was reduced to about one third of those in the control, although six-layered lamination, density of pyramidal neurons, and expressions of calcium-binding proteins were comparatively preserved in the cerebral cortex. The third ventricle was hypoplastic, and the bilateral thalami appeared to be fused and the hippocampus was unrolled, whereas the corpus callosum was preserved. In the hypothalamus, the paraventricular nucleus was only identified, and the adenohypophysial somatotrophs were reduced. This may be the first autopsy report of Micro syndrome, which is characterized by microcephaly, brain malformations, optic atrophy, and hypogenitalism, although the case lacked agenesis of the corpus callosum. (J Child Neurol 2003;18:54-57). [ABSTRACT FROM AUTHOR]