Biomechanical strength dependence on mammalian airway length.

BACKGROUND: The trachea is the uppermost respiratory airway element connecting the larynx to the bronchi Airway reconstructions in humans are often developed from animal models but there is limited knowledge comparing tracheal biomechanics between species. We aimed to assess the structure and biomechanics of porcine, canine, caprine and human airways. METHODS: Tracheas from pigs (n=15), goats (n=9) and canines (n=9) were divided into three groups (4, 6 and 8-ringswhile human left principal brochi (n=12) were divided into two groups (3and-rings). Airway structures were compared using histology and scanning electron microscopy. Biomechanical properties were measured subjecting samples to uniaxial tension and compression, recording the elastic modulus and (tensile and compressive) strengths. RESULTS: The structures of animal tracheal and human bronchia appeared similar. Biomechanical testing revealed that the elastic modulus of 8-ring tracheas was 1,190.48±363.68, 2,572.00±608.19 and 1,771.27±145.54 kPa, for porcine, canine and caprine samples, respectively, while corresponding tensile strengths were 437.63±191.41, 808.38±223.48 and 445.76±44.00 kPa. Comparable measures of anterior-posterior (A-P) compression strengths were 7.94±0.82, 7.54±0.07 and 8.10±1.87 N, respectively, whereas lateral compression strengths were 8.75±0.82, 14.55±2.29 and 11.12±0.40 N. Compression testing of human samples showed significant differences (P<0.05) between the 3-ring (A-P, 1.06±0.02 N; lateral, 0.55±0.06 N) and 5-ring groups (A-P, 1.08±0.64 N; lateral, 2.32±1.95 N). CONCLUSIONS: The tensile and compressive strengths of mammalian airways show positive correlations with the cartilage ring number (length). On the basis of structural and biomechanical comparisons, porcine, canine and caprine species appear suitable models for the study of airway reconstruction in human.

Aberrantly High Expression Of NOK/STYK1 Is Tightly Associated With The Activation Of The AKT/GSK3ß/N-Cadherin Pathway In Non-Small Cell Lung Cancer.

PURPOSE: High metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms. PATIENTS AND METHODS: We investigate the expression of NOK, p-Akt, p-GSK-3ß, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3ß. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3ß pathway. RESULTS: Statistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3ß (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3ß. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3ß pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3ß pathway. CONCLUSION: Our results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3ß/N-cadherin pathway in NSCLC.

Knockdown of MALAT1 expression inhibits HUVEC proliferation by upregulation of miR-320a and downregulation of FOXM1 expression.

Regulation of cancer angiogenesis could be a useful strategy in cancer therapy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA), and can induce cancer cell proliferation, while lncRNAs, generally are able to act as microRNA (miRNA) sponges. The latter is a type of competitive endogenous RNA (ceRNA) that regulates expression of the targeting miRNAs and protein-coding genes. This study investigated the proliferative role of MALAT1 in human umbilical vein endothelial cells (HUVECs) and the underlying molecular events. The data showed that knockdown of MALAT1 expression using MALAT1 siRNA inhibited HUVEC proliferation and also significantly decreased levels of FOXM1 mRNA and protein in vitro, while knockdown of FOXM1 expression reduced HUVEC proliferation. Annotation of HUVEC microarray data revealed that seven miRNAs, including miR-320a, were upregulated after knockdown of MALAT1 expression in HUVECs. MALAT1 was shown to reciprocally interact with miR-320a, i.e., expression of one negatively regulated levels of the other, whereas knockdown of MALAT1 expression promoted miR-320a levels. Furthermore, miR-320a could directly target and inhibit FOXM1 expression in HUVECs. Knockdown of MALAT1 expression enhanced miR-320a expression but reduced FOXM1 expression resulting in downregulation of HUVEC proliferation. However, such an effect was inhibited by miR-320a depletion. In conclusion, this study demonstrates that miR-320a plays an important role in mediating the effects of MALAT1 on HUVEC proliferation by suppression of FOXM1 expression. Thus, targeting of this gene pathway could be a novel strategy in cancer therapy.

Effect of cauterizing esophageal mucosa in "double-patch" treatment for acquired benign tracheoesophageal fistula/bronchogastric stump fistula.

BACKGROUND: The management of acquired benign tracheoesophageal fistula (TEF) and bronchogastric stump fistula (BGSF) is a challenge. This study aimed to assess the "double-patch" technique with or without esophageal mucosa in treating nonmalignant TEF and BGSF. MATERIALS AND METHODS: We established a dog model with TEF by incising the esophageal and tracheal membranes and suturing them together. The dogs were divided into three groups (n = 12 per group). Groups A and B received a double-patch 7 d later. The esophageal mucosa of the patches was cauterized in the group A dogs, kept intact in group B dogs, and group C dogs did not receive surgical intervention. Tissue healing was measured using hydroxyproline levels. RESULTS: Morphologic and histopathologic changes of the esophagus were assessed by gross observation of the specimens, hematoxylin and eosin staining, tracheal stenosis index, and hydroxyproline levels. On day 56 after surgery, group A showed a tracheal stenosis index comparable with that of group C (0.140 ± 0.009 versus 0.138 ± 0.014, P = 1.00), whereas group B showed a higher stenosis index (0.170 ± 0.007) than group C (P = 0.029). The hydroxyproline levels were higher in group A than in B and C on day 7 (P = 0.029), and this difference was statistically significant on days 14 and 56 (all P < 0.001). CONCLUSIONS: The use of an esophageal "double-patch" technique without mucosa showed faster and more stable recovery than patches with mucosa in the repair of acquired nonmalignant complicated TEF and BGSF.

Inhibiting CREPT reduces the proliferation and migration of non-small cell lung cancer cells by down-regulating cell cycle related protein.

It has been reported that CREPT acts as a highly expressed oncogene in a variety of tumors, affecting cyclin D1 signal pathways. However, the distribution and clinical significance of CREPT in NSCLC remains poorly understood. Our study focused on the role of CREPT on the regulation ofnon-small cell lung cancer (NSCLC). We found that CREPT mRNA and protein expression was significantly increased in NSCLC compared with adjacent lung tissues and was increased in various NSCLC cell lines compared with the normal human bronchial epithelial (HBE) cell line. siRNA-induced knockingdown of CREPT significantly inhibited the proliferation and migration of NSCLC cell lines by arresting cell cycle in S phase. Moreover, CREPT knocking down affected the expression of cell cycle proteins including c-mycand CDC25A. Finally, we found there were obvious correlations between CREPT with c-myc expression in histological type, differentiation, and pTNM stages of NSCLC (P<0.05, rs>0.3). Immunohistofluorescence studies demonstrated a co-localization phenomenon when CREPT and c-myc were expressed. Thus, we propose that CREPT may promote NSCLC cell growth and migration through the c-myc and CDC25A signaling molecules.

A novel surgical method for acquired non-malignant complicated tracheoesophageal and bronchial-gastric stump fistula: the "double patch" technique.

BACKGROUND: To manage the acquired benign complicated tracheoesophageal fistula (TEF) and bronchial-gastric stump fistula (BGSF) are clinical technical challenge. The purpose of this study is to retrospectively review a surgical "double patch" technique in treating nonmalignant complicated TEF and BGSF, and then clarify the long-term curative effect of the technique. METHODS: Clinical records of 30 patients with non-malignant complicated TEF and BGSF treated by "double patch" technique in Tangdu Hospital between August 2004 and August 2014, were analyzed and summarized retrospectively. RESULTS: Thirty patients (19 males and 11 females) underwent "double patch" surgical repair of acquired benign complicated TEF and BGSF. The median age of the patients was 40.2±21.1 years. The most common causes were the following: TEF [22], BGSF [8]. Post-intubation injury [6], trauma [5], foreign body and stents [10], complications from prior esophageal surgery [8], and caustic ingestion [1]. The follow-up was completed for 24 months in all the patients (100%). The operative mortality was 0% (0/30). Twenty-six patients (86.7%) recovered uneventfully while four patients (13.3%) exhibited some major complications in the perioperative and postoperative periods. One patient (3.3%) developed recurrence of tracheal fistula in situ, two patients (6.7%) showed pneumonia, and one patient (3.3%) developed fistula esophageal anastomosis. All the 30 patients resumed oral intake finally. CONCLUSIONS: The double patch technique is an effective and safe method to repair the acquired non-malignant complicated TEF and BGSF.

Clinicopathologic features and prognostic implications of Gankyrin protein expression in non-small cell lung cancer.

PURPOSE: The expression of Gankyrin, a liver cancer-related oncoprotein, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of Gankyrin expression in NSCLC remains unclear. METHODS: Gankyrin expression was assessed using immunohistochemical (IHC) methods in 166 paired paraffin-embedded NSCLC specimens and adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were employed to measure the expression of Gankyrin in 24 paired fresh NSCLC specimens and the corresponding normal tissues. The association of Gankyrin expression with clinicopathological parameters was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Gankyrin expression on survival. RESULTS: Data showed that Gankyrin was expressed in 78.3% (130/166) and 28.9% (48/166) of cancer lesions and corresponding adjacent normal tissue, respectively. And the Gankyrin overexpression in tumor tissue occurred in 53.6% (89/166) of patients, while overexpression of Gankyrin in normal tissue occurred only in 4.8% (8/166) of patients (P<0.001). Semi-quantitative RT-PCR and Western blotting showed that NSCLC specimens had increased Gankyrin mRNA and protein expression compared to the corresponding normal tissues. Out of all the clinicopathological factors analyzed, Gankyrin overexpression was significantly correlated with lymphatic metastasis (P<0.001) and p-TNM stage (P<0.001). Gankyrin-overexpressed NSCLC patients had a significantly shorter survival time (P<0.001, Log-rank test), and the prognostic significance of Gankyrin overexpression was apparent in both squamous cell carcinoma patients (P=0.028) and adenocarcinoma patients (P<0.001). Multivariate analysis indicated that Gankyrin overexpression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.51; P=0.041). CONCLUSION: Our results indicate that Gankyrin overexpression is of clinical significance and can serve as a prognostic biomarker in NSCLC.

Effect of Intravascular Ultrasound-assisted Thoracic Endovascular Aortic Repair for "Complicated" Type B Aortic Dissection.

BACKGROUND: Intravascular ultrasound (IVUS) examination can provide useful information during endovascular stent graft repair. However, its actual clinical utility in thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (type B-AD) remains unclear, especially in complicated aortic dissection. We evaluated the effect of IVUS as a complementary tool during TEVAR. METHODS: From September 2011 to April 2012, we conducted a prospective cohort study of 47 consecutive patients with "complicated" type B-AD diagnosed. We divided the patients into two groups: IVUS-assisted TEVAR group and TEVAR using angiography alone group. The general procedure of TEVAR was performed. We evaluated the perioperative and follow-up events. Patient demographics, comorbidities, preoperative images, dissection morphology, details of operative strategy, intraoperative events, and postoperative course were recorded. RESULTS: A total of 47 patients receiving TEVAR were enrolled. Among them (females, 8.51%; mean age, 57.38 ± 13.02 years), 13 cases (27.66%) were selected in the IVUS-assisted TEVAR group, and 34 were selected in the TEVAR group. All patients were symptomatic. The average diameter values of IVUS measurements in the landing zone were greater than those estimated by computed tomography angiography (31.82 ± 4.21 mm vs. 30.64 ± 4.13 mm, P < 0.001). The technique success rate was 100%. Among the postoperative outcomes, statistical differences were only observed between the IVUS-assisted TEVAR group and TEVAR group for total operative time and the amount of contrast used (P = 0.013 and P < 0.001, respectively). The follow-up ranged from 15 to 36 months for the IVUS-assisted TEVAR group and from 10 to 35 months for the TEVAR group (P = 0.646). The primary endpoints were no statistical difference in the two groups. CONCLUSIONS: Intraoperative IVUS-assisted TEVAR is clinically feasible and safe. For the endovascular repair of "complicated" type B-AD, IVUS may be helpful for understanding dissection morphology and decrease the operative time and the amount of contrast used.

Clinicopathologic features and prognostic implications of NOK/STYK1 protein expression in non-small cell lung cancer.

BACKGROUND: The expression of novel oncogenic kinase (NOK), a member of the protein tyrosine kinase (PTK) family, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of NOK expression in NSCLC remains unclear. METHODS: In this study, NOK expression in tumor cells was assessed using immunohistochemical methods in 191 patients with resected NSCLC. The association of NOK expression with clinicopathological parameters, including the Ki-67 labeling index (LI), was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of NOK expression on survival. RESULTS: Data showed that NOK was expressed in 75.4% and 14.1% of cancer lesions and corresponding adjacent non-cancerous tissue, respectively. Out of all the clinicopathological factors analyzed, NOK expression was significantly correlated with the grade of tumor differentiation (P=0.035), pTNM stage (P=0.020), lymphatic metastasis (P=0.005) and high Ki-67 LI (P<0.001). NOK positive NSCLC patients had a significantly shorter survival time (P=0.004, Log-rank test) and the prognostic significance of NOK expression was apparent in squamous cell carcinoma patients (P=0.022). Multivariate analysis indicated that NOK expression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.731; P=0.043). CONCLUSIONS: Our results indicate that NOK expression is of clinical significance and can serve as a prognostic biomarker in NSCLC.

Management of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair.

We reported a case of multiple type II endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair. The patient was undergoing warfarin therapy. Duplex ultrasound was applied as the sole surveillance method during follow-up and provided the concerned information for reintervention. The endoleaks were successfully repaired by coil embolization of the collaterals from the internal iliac artery feeding the fourth lumbar artery.

[Analysis of contrast medium induced pancreatitis].

OBJECTIVE: To report the contrast medium induced pancreatitis after angiography or endovascular therapy, analyze the possible cause of this complication, the treatment specialty and the prognosis. METHOD: The patients suffered from contrast medium induced pancreatitis after angiography or endovascular therapy during last 10 years were retrospectively analyzed. The patients' comorbidity, the onset time of the pancreatitis, the specialty of the pancreatitis, the treatment method and the prognosis were documented. The relative literature was retrieved and reviewed. The clinical data was compared with the relative literature and analyzed. RESULTS: Three cases of contrast medium induced pancreatitis were documented. One case was a young man, received angiography because of renal artery stenosis. He was suffered from moderate abdominal pain 2 hours after the procedure. Pancreatitis of edema type was confirmed by CT scan. He recovered thoroughly after the medical treatment. One case was an old man, underwent angiography for renal artery stenosis and abdominal aortic aneurysm. He was suffered from acute abdominal pain during the procedure. The CT scan revealed as edema pancreatitis. He died from cardiac infarction during the treatment. The last case was an old female, suffered from sustained abdominal distension after endovascular treatment of endoleak post AAA EVAR. Edema pancreatitis was confirmed by CT scan. The symptom was not alleviated well after the treatment. Finally she was died from MOSF. CONCLUSION: The incidence of contrast medium induced pancreatitis is relatively low. It's not easy to detect in early stage. Early diagnosis and treatment is the key to improve the therapeutic effect. The prognosis of patient with multiple comorbidity is poor.

[Endovascular repair of descending thoracic aortic aneurysm: preliminary experience].

OBJECTIVE: To report an initial experience with the endovascular repair of descending thoracic aortic aneurysm (DTAA). METHODS: Endoprostheses were placed into 41 patients with DTAA between January 2001 and July 2007 which were retrospectively analyzed. The preliminary right-left carotid and left carotid-subclavian bypass was performed in 4 cases in which the distances from the proximal aneurysm to the origin of the left common carotid artery were no longer than 15 mm. EVAR was conducted 1 week after the bypass or immediately. RESULTS: All stent grafts were deployed in proper position. There were two deaths (4.9%) during perioperative period, resulting from multiorgan failure and acute cardiac infarction, respectively. Eighteen endoleaks occurred immediately after EVAR (43.9%), four disappeared after balloon dilatation. There were two acute renal insufficiencies (4.9%), one requiring hemodialysis for more than 30 days. Follow-up, which ranged from 1 to 60 months [median, (18.6 +/- 4.2) months] was carried out in 26 patients (63.4%). Type-I endoleak and type-III endoleak were detected in two patients in 4 years and 2 years after EVAR, might because of migration, and were corrected using another stent-graft each. Two patients died of other diseases during follow-up. Complete thrombosis of the thoracic aneurysm sac with no late migration or endoleaks was revealed on CT at 3 months postoperatively in the remaining patients. The decrease in maximal aneurysm diameter was 0-22 mm [median, (8.3 +/- 4.5) mm] and the prosthetic vascular grafts in four patients with preliminary carotid subclavian bypass surgery were patent during the follow-up period. CONCLUSIONS: The treatment of descending thoracic aortic aneurysm with an endovascular approach is feasible with less trauma, quick recovery and less complications. It may offer the best means of therapy for high risk patients.