Spontaneous histological transformation of lung squamous-cell carcinoma to large cell neuroendocrine carcinoma and small cell lung cancer.

BACKGROUND: Histopathological transformation between different types of lung cancer cells has been reported following a variety of anti-tumor treatments. Examples include transformation from lung adenocarcinoma to squamous-cell carcinoma (SCC) and transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC). CASE REPORT: A patient with intermittent hemoptysis for 2 days underwent a computed tomography (CT) scan that revealed interstitial pneumonia in addition to two enlarged paratracheal lymph nodes: one on the right (4R) and one on the left (4L) measuring 10 and 7 mm in diameter, respectively (Fig. 1). There was no evidence of a lung or bronchial mass. Bronchoscopy identified an endoluminal primary mass in a superior segmental bronchus of the left lower lobe and pathological examination following surgery confirmed it to be SCC. At 15 months post operation, a CT scan detected that the 4R lymph node had increased in size from 10 to 16 mm in diameter. At the next follow-up 7 months later, a CT scan showed that the R4 lymph node had further increased in size from 16 to 40 mm in the short axis, making it difficult for a surgeon to resect it "en bloc" immediately. The maximum standardized uptake value was 7.5 on PET-CT images. One month following completion of one cycle of neoadjuvant chemotherapy with gemcitabine and nedaplatin, a further CT scan indicated that the lymph node had decreased in size from 40 to 30 mm in the short axis. A complete mediastinal lymphadenectomy via open thoracotomy was performed and the lymph node was resected. Histological examination identified a main large cell neuroendocrine carcinoma (LCNEC) component with a small fraction of small cell carcinoma, confirmed by immunohistochemical analysis and genetic evidence. CONCLUSION: Histopathological transformation from SCC to LCNEC with a small fraction of SCLC may have occurred spontaneously without any treatment.

Benign but fatal: management of endotracheal Rosai-Dorfman disease with acute onset.

Rosai-Dorfman disease (RDD) is a non-malignant condition mainly manifesting as a proliferation of histiocytes in lymph nodes. Endotracheal RDD (ERDD) with an acute onset presentation is extremely rare. There are few case reports of ERDD mainly concerning its pathology, diagnostics and bronchoscopic treatment, without providing sufficient clinical information from a comprehensive perspective. As a novel and challenging technique, tracheal resection and reconstruction (TRR) with spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS) has been reported as feasible and safe in highly selected patients, but few centres have shared their experience with this approach. This case-based discussion includes not only practical issues in the management of a life-threatening ERDD patient, but also specialists' views on the management of acute obstructive airway, and the surgeons' reflection on TRR with SV-VATS.

Fluoroscopic removal of fractured, retained, embedded Z self-expanding metal stent using a guidewire lasso technique: A case report.

BACKGROUND: There are few reports of a fractured esophageal self-expanding metallic stent (SEMS) and the lasso retrieval technique, forming a guidewire loop by directing the guidewire back up the external stent for retrieval. CASE SUMMARY: A 74-year-old man complained of dysphagia approximately 6 mo after radical resection of esophageal cancer. Benign anastomotic stenosis was diagnosed, and a 20 mm in diameter and 60 mm in length esophageal covered SEMS was inserted after repeated balloon dilatation. About 13.5 mo after stenting, dysphagia recurred and esophagography showed severe stenosis above the proximal stent and stent removal was performed. One-third of the stent was removed and the fractured stent remained in the proximal esophagus. A suction tube was introduced through the guidewire and then the guidewire was grabbed, acting like a "lasso" on tightening. The remaining fractured stent was successfully removed by slowly pulling back the guidewire, with no fragments of stent wires retained. CONCLUSION: The guidewire lasso technique is a simple, effective method of removing esophageal SEMS in rare cases of stent fracture.

Endobronchial Metastasis of Renal Carcinoma: A Case Report and Review of Previous Literature.

The definition of endobronchial metastasis (EBM) lacks clarity because it is currently based on the judgments of surgeons; it is rare in patients with nonpulmonary malignancies. Although EBM represents an advanced stage of malignancy, it does not necessarily indicate a poorer prognosis than that for its primary tumors. The present study defines EBM as bronchoscopy-visible lesions with histologically confirmed primary extrapulmonary tumors, excluding those primary lung tumors with involvement of the bronchial lumen. A bronchoscopy and biopsy provide strong proof for diagnosis. Complete surgical resection is the best choice for patients with EBM. This study analyzed the case of a 69-year-old male patient who had undergone a radical left nephrectomy several years previously after the identification of a bronchoscopy-visible lesion in the left main bronchus. The lesion was initially diagnosed as an angiogenic tumor but was eventually confirmed by surgical biopsy as EBM from the left kidney. After diagnosis, the patient underwent a left pneumonectomy. The analysis of this case focused on diagnosis, symptoms, radiographic findings, treatment, and prognosis. A review of the previous literature relating to EBM was also conducted.

Illumina Sequencing of 18S/16S rRNA Reveals Microbial Community Composition, Diversity, and Potential Pathogens in 17 Turfgrass Seeds.

The increasing need for turfgrass seeds is coupled with the high risk of dangerous microbial pathogens being transmitted through the domestic and international trade of seeds. Concerns continue to be raised about seed safety and quality. Here, we show that next-generation sequencing (NGS) of DNA represents an effective and reliable tactic to monitor the microbial communities within turfgrass seeds. A comparison of DNA sequence data with reference databases revealed the presence of 26 different fungal orders. Among them, serious plant disease pathogens such as Bipolaris sorokiniana, Boeremia exigua, Claviceps purpurea, and Rhizoctonia zeae were detected. Seedborne bacteria, including Erwinia persicina and Acidovorax avenae, were identified from different bacterial orders. Our study indicated that the traditional culturing method and the NGS approach for pathogen identification complement each other. The reliability of culturing and NGS methods was further validated by PCR with specific primers. The combination of these different techniques ensures maximum sensitivity and specificity for turfgrass seed pathogen testing assay.

Predictive Factors for Level V Lymph Node Metastases in Papillary Thyroid Carcinoma with BRAFV600E Mutation and Clinicopathological Features.

BACKGROUND: Therapeutic lateral neck dissection (LND) is recommended in papillary thyroid carcinoma (PTC) patients with clinically lateral lymph node metastasis (LLNM), whether underwent level V LND remains controversial for lacking of sensitive predicting system. BRAFV600E mutation is associated with aggressive tumor behavior, recurrence, and disease-specific mortality of PTC. However, the relationship between BRAFV600E mutation and level V LNM is unclear. METHODS: Univariate and multivariate analyses were retrospectively conducted on the potential predictive factors of 252 PTC patients who underwent initial treatment of neck lymph node dissection from September 2015 to October 2018 in our institute. BRAFV600E mutation and the clinicopathological characteristics of the two groups were compared. RESULTS: LLNM was presented in 208 (82.5%) patients and level II-V LNM was present in 42.8%, 71.2%, 85.1%, 17.8% patients, respectively. BRAFV600E mutation was observed in 188 (74.6%) patients and was significantly associated with patients' age, lymphocytic thyroiditis, capsule invasion, bilateral central lymph node metastasis (CLNM) and level V LNM in PTC. Univariate analysis revealed that lymphocytic thyroiditis, tumor size, number of CLNM, Level II LNM, Level III LNM, simultaneous Level II+III, simultaneous Level III+IV and simultaneous Level II+III+IV were significantly correlated with Level V LNM. In addition, multivariate analysis revealed that tumor size ≥2.5 cm, number of CLNM≥3, level II metastases and BRAFV600E mutation were independent Level V LNM predictors (odds ratio 3.910, 3.660, 8.410, 0.439; 95% CI 1.737-10.135, 1.054-12.713, 1.233-57.355, 0.280-0.827, respectively). CONCLUSION: In summary, we presented several independent predictive factors for level V LNM in PTC patients. We constructed a risk prediction model consisting of tumor size ≥2.5 cm, number of CLNM≥3 and level II metastases and BRAFV600E mutation that may guide surgeons to evaluate the nodal status in PTC and perform tailored therapeutic LND.

Drug coated balloon angioplasty for renal artery stenosis due to Takayasu arteritis: Report of five cases.

BACKGROUND: Takayasu arteritis is a rare but intractable chronic disease in young female patients. Percutaneous transluminal angioplasty of the involved renal arteries has been reported; however, few studies have reported the use of drug coated balloon angioplasty in the treatment of Takayasu arteritis. We aimed to demonstrate five young female patients who presented with a history of hypertension due to Takayasu arteritis. CASE SUMMARY: From April 2017 to October 2018, five female patients were diagnosed with hypertension due to Takayasu arteritis by computed tomography angiography (CTA) and laboratory tests. Four patients had a complaint of headache with or without dizziness, and one patient showed no symptom. There was no significant family or past history of hypertension or kidney disease, and the physical examinations were almost normal on admission. We performed a treatment by drug coated balloon angioplasty. Blood pressure decreased dramatically in all patients after balloon angioplasty, and the patency of treated renal artery was demonstrated with CTA over 5 months after the angioplasty procedure. CONCLUSION: Drug coated balloon angioplasty is safe and effective for renal artery stenosis due to Takayasu arteritis. A prospective study with a larger sample size is necessary to further demonstrate the effectiveness of the treatment.

Surgical repair of graft aneurysm following ascending-to-abdominal aortic bypass.

Graft aneurysm after ascending aorta to abdominal aorta bypass is a rare complication of repair of coarctation of the aorta. We present a case of an aneurysm measuring 75 mm in diameter at the midportion of the prosthetic graft in a 33-year-old man. To prevent aneurysm rupture, redo ascending-to-abdominal aortic bypass was performed through an upper ministernotomy and upper midline laparotomy. No postoperative complications occurred. The patient was successfully discharged on postoperative day 6. Although ascending-to-abdominal aortic bypass can achieve long-term patency, the prosthetic graft still has the rare risk of aneurysm formation, as highlighted in this case. Early diagnosis and timely management of this rare complication are essential in preventing aneurysm rupture.

The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by unrelenting polymorphonuclear neutrophil (PMN) inflammation and vascular permeability. The matrikine proline-glycine-proline (PGP) and acetylated PGP (Ac-PGP) have been shown to induce PMN inflammation and endothelial permeability in vitro and in vivo. In this study, we investigated the presence and role of airway PGP peptides in acute lung injury (ALI)/ARDS. Pseudomonas aeruginosa-derived lipopolysaccharide (LPS) was instilled intratracheally in mice to induce ALI, and increased Ac-PGP with neutrophil inflammation was noted. The PGP inhibitory peptide, arginine-threonine-arginine (RTR), was administered (it) 30 min before or 6 h after LPS injection. Lung injury was evaluated by detecting neutrophil infiltration and permeability changes in the lung. Pre- and posttreatment with RTR significantly inhibited LPS-induced ALI by attenuating lung neutrophil infiltration, pulmonary permeability, and parenchymal inflammation. To evaluate the role of PGP levels in ARDS, minibronchoalveolar lavage was collected from nine ARDS, four cardiogenic edema, and five nonlung disease ventilated patients. PGP levels were measured and correlated with Acute Physiology and Chronic Health Evaluation (APACHE) score, PaO2 to FIO2 (P/F), and ventilator days. PGP levels in subjects with ARDS were significantly higher than cardiogenic edema and nonlung disease ventilated patients. Preliminary examination in both ARDS and non-ARDS populations demonstrated PGP levels significantly correlated with P/F ratio, APACHE score, and duration on ventilator. These results demonstrate an increased burden of PGP peptides in ARDS and suggest the need for future studies in ARDS cohorts to examine correlation with key clinical parameters.

PPARGC1A is upregulated and facilitates lung cancer metastasis.

Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.

Male tarsi specific odorant-binding proteins in the diving beetle Cybister japonicus sharp.

Odorant binding proteins (OBPs) play critical roles in chemical communication of insects, as they recognize and transport environmental chemical signals to receptors. The diving beetle Cybister japonicus Sharp shows a remarkable sexual dimorphism. The foreleg tarsi of males are equipped with large suction cups, believed to help holding the female during underwater courtship and mating. Here, we identified two OBPs highly and specifically expressed in male tarsi, suggesting important functions of these structures in chemical communication. The first protein, CjapOBP1, exhibits the 6 conserved cysteines motif of classic OBPs, while the second, CjapOBP2, contains only four cysteines and can be assigned to the sub-class of C-minus OBPs. Both proteins were expressed in a bacterial system and the purified recombinant proteins were used to for antibodies preparation. Western Blot analysis showed that CjapOBP1 is predominantly expressed in male tarsi and could be also detected in antennae and palpi of both sexes, while CjapOBP2, besides male tarsi, is also present in testis. Ligand-binding experiments showed a good binding affinity between CjapOBP1, CjapOBP2 and citral and coniferyl aldehyde, respectively. These results support a possible function of these two OBPs in the male foreleg tarsi of diving beetles in chemical communication.

Differential expression of IQGAP1/2 in Hepatocellular carcinoma and its relationship with clinical outcomes.

PURPOSE: To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. METHODS: IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. RESULTS: IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). CONCLUSION: Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.

Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis.

BACKGROUND: Chronic kidney disease (CDK) is a worldwide health problem, but there is currently no effective treatment that can completely cure this disease. Recently, studies with mesenchymal stem cells (MSCs) on treating various renal diseases have shown breakthroughs. This study is to observe the homing features of MSCs transplanted via kidney artery and effects on renal fibrosis in a reversible unilateral ureteral obstruction (R-UUO) model. METHODS: Thirty-six Balb/c mice were divided into UUO group, UUO-MSC group, and sham group randomly, with 12 mice in each group. The MSCs had been infected by a lentiviral vector to express stably the luciferase reporter gene and green fluorescence protein genes (Luc-GFP-MSC). Homing of MSCs was tracked using in vivo imaging system (IVIS) 1, 3, 14, and 28 days after transplantation. Imaging results were verified by detecting GFP expression in frozen section under a fluorescence microscope. E-cadherin, α-SMA, TGF-ß1, and TNF-α mRNA expression in all groups at 1 and 4 weeks after transplantation were analyzed by quantitative PCR. RESULTS: Transplanted Luc-GFP-MSCs showed increased Luciferase expression 3 days after transplantation. The expression decreased from 7 days, weakened thereafter and could not be detected 14 days after transplantation. Quantitative PCR results showed that all gene expressions in UUO group and UUO-MSC group at 1 week had no statistical difference, while at 4 weeks, except TGF-ß expression (P > 0.05), the expression of E-cadherin, α-SMA, and TNF-α in the above two groups have statistical difference (P < 0.01). CONCLUSION: IVIS enables fast, noninvasive, and intuitive tracking of MSC homing in vivo. MSCs can be taken home to kidney tissues of the diseased side in R-UUO model, and renal interstitial fibrosis can be improved as well.

SMC1A knockdown induces growth suppression of human lung adenocarcinoma cells through G1/S cell cycle phase arrest and apoptosis pathways in vitro.

SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that down-regulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.

Overexpression of MMSET is correlation with poor prognosis in hepatocellular carcinoma.

The multiple myeloma SET domain (MMSET) involved in the t(4;14)(p16;q32) chromosomal translocation encodes a histone lysine methyltransferase. High expression of MMSET is common translocation in multiple myeloma (MM) and is associated with the worst prognosis. Recent studies have shown that overexpression of MMSET is significant in other tumor types compared to their normal tissues. However, little is known about its role in hepatocellular carcinoma (HCC). In these study we investigate the expression of MMSET in HCC and to make correlations with clinicopathologic features. Twenty-eight pairs of HCC and adjacent non-tumor tissues, and eight normal liver tissues were collected for MMSET detection by western blotting and real time-PCR analysis. Immunohistochemistry was used to determine the expression of MMSET in HCC and adjacent non-tumor tissues from 103 patients. Overexpression of MMSET was significantly associated with Edmondson stage, vascular invasion. Moreover, Kaplan-Meier curves showed that MMSET upregulated was associated with shorter overall survival and disease-free survival in HCC patient. In conclusion, our study demonstrates for the first time that overexpression of MMSET is an independent prognostic factor and is correlated with poor survival in HCC patients.

A standard approach to expose the recurrent laryngeal nerve during endoscopic thyroidectomy.

PURPOSE: Exposing the recurrent laryngeal nerve (RLN) during all types of thyroid surgery is essential to protect this nerve. Endoscopic thyroidectomy (ET) has gained acceptance from both patients and physicians, in part due to the cosmetic benefits. Therefore, the avoidance of intraoperative RLN impairment during ET is of critical significance. We have developed a standard approach to expose the RLN during ET that prevents RNL impairment. PATIENTS AND METHODS: ET was performed in 120 consecutive patients with thyroid disease. In order to develop a standard procedure that protects the RLN, several steps that differed from the traditional open procedure were introduced. First, the thyroid gland was freed from the isthmus instead of the superior pole. Then, the inferior pole of the thyroid gland was meticulously freed, and the lateral side of the thyroid gland was freed followed by the superior pole. At this point, the RLN was easily visualized in the tracheoesophageal groove. The thyroidectomy was then performed simultaneously with exposure of the RLN from the inferior to superior aspects. All RLNs were exposed when hemithyroidectomies, subtotal thyroidectomies, or total thyroidectomies were performed. The operative time and parathyroid hormone (PTH) and calcium levels were recorded prospectively and analyzed. RESULTS: Using this method, all RLNs were easily exposed within 15 minutes. Only one case of transient RLN palsy occurred due to accidental contact of the harmonic scalpel to the nerve. Postoperative hypocalcemia occurred in 23 cases (19.2%), and the PTH level decreased significantly in 33 cases (27.5%). The PTH levels returned to normal within 3 months. CONCLUSION: Use of the described approach to expose and protect the RLN when performing ET is safe and feasible.

MED19 promotes proliferation and tumorigenesis of lung cancer.

MED19 is a subunit of Mediator that is an essential component of RNA polymerase II-mediated transcription machinery. High expression levels of MED19 were examined in human lung adenocarcinoma tissues by immunohistochemical assay. MED19-specific short hairpin RNA (shRNA) expressing lentivirus was constructed and infected lung cancer cell line A549. MED19 mRNA and protein expression levels were downregulated in A549 cells as evidenced by real-time PCR and western blot assays. Importantly, MED19 inhibition resulted in impaired proliferation and colony formation, and induced accumulation of G1-phase cells and mitigated invasiveness of cells. More importantly, downregulation of MED19 expression reduced the tumorigenicity of A549 cells in vivo. It was suggested that MED19 is a novel proliferation regulator that promotes growth of lung cancer cells, thereby indicating that MED19 may serve as a new molecular target for lung cancer therapy.

Perfusion computed tomography evaluation of angiogenesis in liver cancer.

OBJECTIVE: To investigate the value of computed tomography (CT) perfusion imaging for assessment of angiogenesis in liver cancer. METHODS: Twenty-one patients with histologically proven liver cancer underwent CT perfusion examination. We compared the following perfusion parameters in the tumour area versus the non-tumour area: total blood flow (TBF), hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP) and hepatic arterial perfusion index (HAPI). Slices of postoperative specimen were stained with haematoxylin-eosin and anti-CD34 immunohistochemistry. The slices were evaluated with emphasis on the CD34-positive neovasculature in the tumour parenchyma. Tumour microvascular density (MVD) was calculated according to the Weidner method. Pearson correlation was used to detect correlations between tumour MVD and tumour perfusion parameters. RESULT: TBF and HPP in the tumour area were lower than in the non-tumour area (P < 0.05). HAP and HAPI in the tumour area were higher than those of the non-tumour area (P < 0.05). TBF and HAP in the tumour area correlated with MVD in the tumour (P < 0.05), with correlation coefficients of 0.849 and 0.829, respectively. CONCLUSION: CT perfusion imaging can quantitatively assess the blood supply and its distribution in liver cancer. TBF or HAP may be a useful parameter in assessing angiogenesis of liver cancer.