Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues.

BACKGROUND: Non-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard. METHODS: In the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs). RESULTS: NEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs. CONCLUSIONS: The observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.

Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer.

Despite the advances in cancer therapy, lung cancer still remains the most leading cause of cancer death worldwide. The long non-coding RNAs (lncRNAs) are recently introduced as novel regulators of human cancers. SOX2 overlapping transcript (SOX2OT) is a cancer-associated lncRNA gene that encodes different alternatively spliced transcripts. Here, we investigated the alterations in the preferential expression of different SOX2OTs in twenty non-small cell lung cancer (NSCLC) patients by real-time quantitative reverse transcription PCR (qRT-PCR) method. We observed preferential expression of SOX2OT4 and SOX2OT7 in lung tumor tissues. The quantitative gene expression analysis revealed that >30 % of NSCLC tumors express SOX2OT4 (mean = 7.6 times) and SOX2OT7 (mean = 5.9 times) more than normal tissues, with higher expression in squamous cell carcinoma. Further, we observed overexpression of pluripotency-associated transcription factor, SOX2 in 47 % of our samples concordant with SOX2OT (R = 0.62, P value <0.05). Overexpression of OCT4A gene was also observed in 36.8 % of tumor tissues. Then, we investigated the effects of SOX2OT suppression in lung adenocarcinoma cell line, by means of RNAi. Cell characteristics of colony formation, apoptosis, 2-D mobility, and cell cycle progression were measured in control and treated A549 cells. The SOX2OT knockdown significantly reduced the colony formation ability of cancer cells; however, no alterations in the rate of apoptosis were detected. On the other hand, SOX2OT-suppressed cells had elevated accumulation in G2/M phase of cell cycle and exhibited limited mobility. Altogether, our findings support a potential oncogenic role for SOX2OT in non-small cell lung cancer tumor genesis and SOX2OT seems a promising therapeutic candidate for NSCLC.

Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation.

Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways.

Primary Spontaneous Pneumothorax: Open Thoracotomy vs. Video-assisted Thoracoscopic Surgery: A Single-center Retrospective Cohort Study.

Background: Primary spontaneous pneumothorax (PSP) is a spontaneous pneumothorax without underlying lung disease. The main goals of this study were to compare the outcomes of video-assisted thoracoscopic surgery (VATS) and open thoracotomy in patients with PSP. Methods: The current study is a retrospective cohort study of patients who were admitted to the emergency department or general surgery ward at Dr. Masih Daneshvari Hospital (Tehran, Iran) with the diagnosis of PSP and underwent surgery by open or VATS approach from 2006 to 2012. The groups were compared in terms of the length of operation, the length of hospitalization, recurrence, and postoperative complications. Data were analyzed using SPSS version 18.0, and Student's t test, analysis of variance (ANOVA), Chi square, and Fisher's exact test were employed. P values less than 0.05 were considered statistically significant. Results: PSP was diagnosed in 90 patients who underwent surgery. Open thoracotomy and VATS procedures were performed in 65 (72.2%) and 25 (27.8%) patients, respectively. VATS was converted to open in seven cases (7.7%). Recurrent pneumothorax was the most common surgical indication for PSP. There was no significant difference between the two groups in terms of mean age, sex, smoking, side of the involved lung, previous pneumothorax history, mean length of hospitalization for recurrence, post-operation bleeding, and failure of lung expansion. However, the length of surgery (P=0.011) and air leakage (P=0.048) significantly differed between the two groups. Conclusion: When compared to open thoracotomy, VATS could be the primary treatment option in the surgical treatment of PSP due to the shorter length of surgery and decreased complications such as air leakage.

Post-intubation tracheal stenosis in pediatric age group: single-center experiences of 24 years.

BACKGROUND AND AIM: Post-intubation tracheal stenosis (PITS) is an iatrogenic injury that involves some patients. Given the importance of this issue and the referral of a significant number of children with tracheal stenosis to Masih Daneshvari Hospital in Tehran, Iran, the present study investigated tracheal stenosis following prolonged intubation in the pediatric age group. METHODS: In this observational retrospective study, from 1994 to 2018, the medical records of all children under 14 years of age with a history of PITS were reviewed. Demographic and clinical characteristics including signs and symptoms, the underlying condition that leads to intubation, duration of intubation, type of stenosis, and the therapeutic approach, type of surgery, and follow-up were collected and analyzed using SPSS. RESULTS: Among 161 patients with a mean age of 9.8 ± 4.2 years, 69% were male. The site of stenosis was limited to the trachea in 47% and others both trachea and subglottic area were involved. The most common cause of intubation was trauma. The most common symptoms were dyspnea and wheezing. Success rates of reconstruction were 93.75% in type I, 82.15% in type II, and 35.70% in type III. Among the 16 patients who underwent Type III surgery, decannulation was not performed in 11 patients. Traction in the anastomosis and complications were stated in 26 and 10% of the patients respectively, a mortality rate of 8.7% was also reported. CONCLUSION: In the case of endotracheal intubation, PITS should be considered in the differential diagnosis of dyspnea in children as well as adults.

Medical management of pancreatic neuroendocrine tumors in patients with MEN 1: case report.

Objectives: Multiple endocrine neoplasia type 1 (MEN-1) is a rare inherited autosomal dominant disease which manifests itself with at least one clinical scenario before 45 years of age. The value of somatostatin analogue therapy is unknown in the treatment of non-functioning pancreatic tumours and a few studies have been published in this field. Case presentation: We report a young patient with MEN-1 with multiple gastric and pancreatic neuroendocrine tumors that was treated with the monthly injection of Sandostatin LAR before and After Distal Pancreatectomy and partial gastrectomy. Conclusions: Now she is well after four years of treatment with Sandostatin LAR.

Investigation the Role of Autophagy in Non-Small Cell Lung Cancer.

OBJECTIVE: Recent studies have shown the role of autophagy in different types of cancer including lung cancer. MicroRNAs are considered as key factors in regulation of autophagy related genes. miR-30d, miR-204-5p and miR-20a are regulatory markers which can suppress the expression of beclin1, LC3, bcl2 and ULK1 as their target genes and they lead to decrement of autophagy in human cancer cells. Moreover, epigenetic modifications DNA methylation has been indicated in regulation of autophagy in different stages of cancer. METHODS: In this study, the expression levels of miR-30d, miR-204-5p and miR-20a as well as their target genes were analyzed in 30 non-small cell lung cancers (NSCLCs) patients sample and adjacent normal tissues by real-time qPCR. In addition, DNA methylation of beclin1, LC3, bcl2 and ULK1 genes were assessed by MS-HRM method. RESULTS: MiR-30d (p value= 0.01) and miR-204-5p (P=0.048) significantly down-regulated in tumor samples compared to normal adjacent tissues, while there was no significant change in expression level of miR-20a. On the other hand, target genes expression level was significantly increased in NSCLC tissues, however methylation pattern of the target gene promoters, did not show any significant alteration. CONCLUSION: These results indicate roles for miR-30d, miR-204-5p as tumor suppressor genes as well as target genes as oncogenes in NSCLC patients. Although these factors may have a significant role in NSCLC progression, further studies are necessary to investigate the implications of these findings for treatment of lung cancer. 
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Postintubation Multisegmental Tracheal Stenosis: A 24-Year Experience.

BACKGROUND: Management of multisegmental tracheal stenosis is challenging. In this 24-year longitudinal single-center study, we present an algorithmic treatment approach. METHODS: A retrospective analysis of 2167 patients with postintubation tracheal stenosis indicated 83 (3.83%) patients with multisegmental tracheal stenosis. Patients were assigned to 4 management groups according to the length, location, and severity of stenoses; tracheal infection/mucositis; laryngeal function; symptoms; general condition; and comorbid diseases. Type 1 (n = 13): 1-stage resection of both strictures, Type 2 (n = 6): 2-stage resection of both strictures, Type 3 (n = 40): resection of 1 stricture and nonresectional management of the other, Type 4 (n = 24): nonresectional management of both strictures. Outcomes were categorized as Good, Acceptable, or Poor. Univariate analyses for factors predictive of recurrence and outcome were performed. RESULTS: Follow-ups were completed in 70 (84.34%) patients (median, 22.5 months). Outcome was assessed as Good in 56 (82.35%), Acceptable in 10 (14.71%), Poor in 2 (2.94%), and mortality in 2 (2.94%) patients. The median length of airway resection was 46, 67.5, and 40 mm in Types 1-3, respectively. Only 11 (13.25%) patients had no history of tracheostomy or tracheal surgery. By univariate analysis, a shorter intubation period was associated with Good outcome (P = .017). No factors predictive of recurrence or outcome were ascertained. CONCLUSIONS: Multisegmental tracheal stenosis, generally caused by performing an inappropriate tracheostomy, is an iatrogenic disease that can be prevented. Although resection of both strictures may be feasible and is associated with Good results, in the majority of cases, a combination of surgical resection and non-resectional methods are sufficient to achieve Good results.

Langerhans cell histiocytosis of the lung and thyroid, co-existing with papillary thyroid cancer.

A 24-year-old man presented to our center with a huge goiter compressing his airway. He had a previous diagnosis of Langerhans cell histiocytosis (LCH) of the lung. Core needle biopsy was consistent with histiocytosis. Thyroidectomy was performed. A very invasive mass was encountered at the time of surgery. Histopathology result was consistent with an invasive papillary cancer of thyroid co-occurring with LCH. Although association of LCH with different malignancies has been reported, co-existing invasive papillary thyroid cancer and LCH is a rare combination.

Pulmonary artery stenosis shortly after lung transplantation: successful balloon dilation and stent insertion in one case.

BACKGROUND: Pulmonary artery stenosis after lung transplantation is a rare complication. It usually requires surgical correction but even after that the outcome is not favorable.
CASE REPORT: The patient was a 53-years-old woman who was candidate for lung transplantation surgery due to pulmonary fibrosis. After 7 months on waiting list, with severe limitations in daily living activities, she received a single lung transplant in 2007. The surgery was performed without any complication. One day after surgery and after extubation, the patient needed oxygen supplementation through mask with reservoir bag. In bronchoscopy, black-and-white exudate and black membrane that blocked the main bronchus in the transplanted lung was observed. By bronchial lavage the membrane and exudate were successfully removed and patient received antibiotics for documented Aspergillus infection and methylprednisolone pulse therapy for evidences of graft rejection. Despite success in treatments of the mentioned complications, the condition of the patient deteriorated and she became totally dependent to supplemental oxygen. Oxygen consumption level had increase and pulmonary artery pressure was increasing gradually. With suspicion to pulmonary artery stenosis, bronchial CT-Scan with contrast was performed 13 days after transplantation surgery which showed a 50% stenosis. Trans-esophageal echocardiography also showed a stenosis with 40 mmHg gradient. 18 days after transplantation surgery, percutaneous balloon angioplasty was performed which was initially successful but re-stenosis occurred. Seven days later, another balloon angioplasty with stent insertion was performed. After the procedure, the gradient has been removed. Patient was discharged 30 days after transplantation. Follow-up after 10 months revealed no stenosis and the stent was working properly.
CONCLUSIONS: Stent angioplasty can be performed with no problem or complication if pulmonary artery stenosis is seen after lung transplantation.

Identifying and Localizing of the In-depth Pulmonary Nodules Using Electrical Bio-Impedance.

Intraoperative localization of small and in-depth pulmonary nodules particularly during video-assisted thoracoscopic surgery (VATS), is one of the main challenges for Thoracic surgeons. Failure to determine the location of nodules may lead to a large incision in the normal lung tissue or the conversion of the minimally invasive surgery to an open thoracotomy. The aim of this study is to evaluate the use of electrical bio-impedance measurement to precisely determine the position of in-depth pulmonary nodules and tumors, which are not visible during thoracoscopic surgeries or even are not palpable during open thoracic surgeries. With this regard, a suitable bio-impedance sensor similar to a biopsy forceps has been designed in order to measure the lung tissue bio-impedance. Using the available data on the electrical properties recorded from lung tissue during inhalation and exhalation, combined with the tumor modeling in COMSOL software, the effect of different parameters including the size and depth of tumor and the relative difference of electrical properties between healthy and tumoral tissue has been assessed. Furthermore, the geometric characteristics of the proposed sensor are considered. The results generally verify that larger size of nodules results in an easier distinguishing process. Additionally, it is worthy to note that applying a larger geometrically sensor is essential to detect the small and in-depth nodules.

Identification of Pulmonary Nodules by Sweeping the Surface of the Lung with an Electrical Bioimpedance Probe: A Feasibility Study.

Purpose: Identifying and localizing the invisible and nonpalpable pulmonary nodules are among the main challenges surgeons face during open and thoracoscopic surgeries. This in vitro study explores the feasibility of utilizing a simple and safe electrical bioimpedance probe in locating the pulmonary nodules by sweeping the surface of the lung tissue. Methods: A probe was designed with four spherical electrodes that were used for recording the bioimpedance spectrum of the lung tissue in a frequency range of 50 kHz to 5 MHz. In each of the 10 resected surgical specimens, the bioimpedance of normal lung tissue as well as the tumoral lung tissue were recorded and compared with each other. Results: By drawing the Nyquist curves, it was determined that the amplitude of the electrical impedance measured by moving the probe from the healthy point to the region of the pulmonary nodule decreases and the frequency characteristics of the bioimpedance spectrum increases. Conclusion: This method could be potentially beneficial in the localization of invisible and even nonpalpable in-depth pulmonary nodules in thoracic surgeries.

Idiopathic Subglottic Tracheal Stenosis in Identical Twin Sisters.

INTRODUCTION: Idiopathic subglottic tracheal stenosis is a rare inflammatory disease of the trachea; most commonly affects females within the age range of 20-50 years. No etiologic factor has yet been identified for this rare tracheal disease and therefore it should be diagnosed after the exclusion of other inflammatory, traumatic, and autoimmune diseases of the trachea. The familial or genetic predisposition to this disease is still unknown although one published report in the literature showed some familial predisposition. CASE REPORT: A 41-year old woman presented with progressive dyspnea and stridor. The bronchoscopic evaluation revealed subglottic tracheal stenosis; however, there was no significant etiology of this disease after complete evaluations. Therefore, the idiopathic subglottic stenosis was the final diagnosis. After two years, her identical twin sister presented with the same signs and symptoms. There was also no etiology for her tracheal stenosis. The first patient was managed surgically through cricotracheal resection. However, the second sister didn't need surgical resection due to the mild to moderate tracheal stenosis. CONCLUSION: The obtained results of our cases along with the previously reported family cases can potentiate the hypothesis that there is some genetic predisposition to the development of this disease.

The Development of a Four-Electrode Bio-Impedance Sensor for Identification and Localization of Deep Pulmonary Nodules.

Identifying and localizing of deep pulmonary nodules are among the main challenges that thoracic surgeons face during operations, particularly in thoracoscopic procedures. To facilitate this, we have tried to introduce a non-invasive and safe method by measuring the lung electrical bio-impedance spectrum with a four-electrode array sensor. To study the feasibility of this method, since any change in the depth or diameter of the nodule in the lung tissue is not practical, we used the finite element modeling of the lung tissue and pulmonary nodule to allow changes in the depth and diameter of the nodule, as well as the distance in between the injection electrodes. Accordingly, a bio-impedance sensor was designed and fabricated. By measuring the electrical impedance spectrum of pulmonary tissues in four different specimens with a frequency band of 50 kHz to 5 MHz, 4 pulmonary nodules at four different depths were identified. The obtained bio-impedance spectrum from the lung surface showed that the magnitude and phase of electrical bio-impedance of the tumoral tissue at each frequency is smaller than that of the healthy tissue. In addition, the frequency characteristic varies in the Nyquist curves for tumoral and healthy lung tissues.

In-vivo characterization of a 3D hybrid scaffold based on PCL/decellularized aorta for tracheal tissue engineering.

INTRODUCTION: As common treatments for long tracheal stenosis are associated with several limitations, tracheal tissue engineering is considered as an alternative treatment. AIM OF STUDY: This study aimed at preparing a hybrid scaffold, based on biologic and synthetic materials for tracheal tissue engineering. MATERIALS AND METHODS: Three electrospun polycaprolactone (PCL) scaffolds, namely E1 (pure PCL), E2 (collagen-coated PCL) and E3 (PCL blended with collagen) were prepared. Allogeneic aorta was harvested and decellularized. A biodegradable PCL stent was fabricated and inserted into the aorta to prevent its collapse. RESULT: Scaffold characterization results revealed that the 2-h swelling ratio of E2 was significantly higher than those of E1 and E3. In the first 3months, E2 and E3 exhibited almost equal degradabilities (significantly higher than that of E1). Moreover, tensile strengths of all samples were comparable with those of human trachea. Using rabbit's adipose-derived mesenchymal stem cells (AMSCs) and primary chondrocytes, E3 exhibited the highest levels of GAG release within 21days as well as collagen II and aggrecan expression. Fot the next step, AMSC-chondrocyte co-culture seeded scaffold was sutured to the acellular aorta, implanted into rabbits' muscle, and finally harvested after 4weeks of follow up. CONCLUSION: Harvested structures were totally viable due to the angiogenesis created by the muscle. H&E and alcian blue staining results revealed the presence of chondrocytes in the structure and GAG in the produced extracellular matrix. Since tracheal replacement using biologic and synthetic scaffolds usually results in tracheal collapse or granulation formation, a hybrid construct may provide the required rigidity and biocompatibility for the substitute.

An Overview of Tracheal Stenosis Research Trends and Hot Topics.

BACKGROUND: Tracheal stenosis remains a challenge in the thoracic surgery field. Recognizing the hot topics and major concepts in this area would help the health policy makers to determine their own priorities and design the effective research plans. The present study analyzed and mapped the topics and trends of tracheal stenosis studies over time as well as authors' and countries' contributions. MATERIALS AND METHODS: Search results were obtained employing Bibexcel. To determine cold and hot topics, co-occurrence analysis was applied using three international databases 'Web of Science', 'PubMed' and 'Scopus'. Appropriately, different categories in the articles such as keywords, authors, and countries were explored via VOSviewer and NetDraw. Afterward, the trends of research topics were depicted in four time-intervals from 1945 to 2015 by ten co-occurrence terms. RESULTS: The majority of articles were limited to case series and retrospective studies. The studies had been conducted less frequently on prevention, risk factors and incidence determination but extensively on treatment and procedures. Based on the articles indexed in WOS, 45 countries and 8,260 authors have contributed to scientific progress in this field. The highest degree of cooperation occurred between the USA and England with 15 common papers. CONCLUSIONS: Most of the published literature in tracheal stenosis research field was about surgical and non-surgical treatments. Conducting the screening and prevention studies would diminish the burden of this disease on the health system as well as the patients and their families' well-being.

Colopharyngoplasty in Patients with Severe Pharyngoesophageal Corrosive Injury: A Complicated but Worthwhile Procedure to Restore GI Tract Continuity, A Case Series.

BACKGROUND: Pharyngoesophageal strictures (PES) after corrosive injury impose a problematic condition for both physicians and patients in terms of their management and patients' quality of life. Colopharyngoplasty is a complex procedure, which is used to restore swallowing in these severely disabled patients. We describe our experience in treating nine patients with severe PES after corrosive injuries in a referral center. MATERIALS AND METHODS: A retrospective analysis of our database from 2009 to 2014 showed nine patients (seven men; age range: 18 to 47 years) with severe PES who underwent colopharyngoplasty ∼6 months (range: 4-10) after caustic material ingestion. All patients had a feeding jejunostomy tube before reconstruction. Esophagectomy with or without gastrectomy was performed in all patients, except for one; thereafter, an isoperistaltic segment of the left colon was pulled up, and a pharyngocolic anastomosis was performed. Eight patients had a tracheostomy created either before reconstruction due to respiratory symptoms or at the time of definitive surgery to prevent aspiration in the early post-operative period. RESULTS: Almost all survivors had a satisfactory swallowing at the end of the follow-up (range: 4-60 months). The jejunostomy tube could be removed in all of the patients after a median of 5 months. One patient died of sepsis due to graft necrosis in the immediate post-operative period. Another patient died 5 months after the first surgery following a revision surgery for intractable dysphagia. At the end of the follow-up, only one patient tolerated tracheostomy tube decannulation. Two patients required laryngotracheal dissociation because of massive aspiration and recurrent episodes of pneumonia. Five patients still had a tracheostomy because of an severely destroyed larynx (two patients) and aspiration (three patients). CONCLUSION: Colopharyngoplasty is considered a complicated but trustworthy procedure to restore gastrointestinal tract continuity after severe corrosive injury. Undeniably, laryngeal involvement adversely affects the functional outcome. The post-operative course is frequently protracted, accompanied with several problems. Aspiration is nearly the most problematic event in the early post-operative period, which mandates a multidisciplinary approach to manage it.