Diagnostic value and complication rate of ultrasound-guided transthoracic core needle biopsy in mediastinal lesions.

BACKGROUND: Ultrasound-guided transthoracic core needle biopsy (US-TCNB) is a promising method for establishing the correct diagnosis of mediastinal masses. However, the existing studies in this area are scant and with small samples. PURPOSE: To evaluate the diagnostic value and the complication rate of US-TCNB, particularly large bore cutting biopsy in patients with mediastinal lesions. MATERIAL AND METHODS: This retrospective study includes 566 patients with mediastinal lesions suspicious of malignancy evaluated between March 2004 and December 2018. Inclusion criteria: 1. Patients with mediastinal lesions detected on thoracic CT scan; 2. Lesions more than 15 mm; 3. Negative histological diagnosis after bronchoscopic biopsy; 4. Normal coagulation status; 5. Cooperative patient; 6. Written informed consent. US visualization of the mediastinal lesions was successful in 308 (54.4%). In all of them, US-TCNB was performed. All patients with mediastinal lesions unsuitable for US visualization were evaluated for a CT-guided transthoracic needle biopsy (CT-TTNB), which was done if the presence of a safe trajectory was available (n = 41, 7.2%). All patients inappropriate for image-guided TTNB were referred to primary surgical diagnostic procedures (n = 217, 38.3%). RESULTS: The US-TCNB is a highly effective (accuracy 96%, sensitivity 95%) and safe tool (2.6% complications) in the diagnosis of all subgroups mediastinal lesions. It is non-inferior to CT-TTNB (90%) and comes close to the effectiveness of surgical biopsy techniques (98.4%), but is less invasive and with a lower complication rate. CONCLUSION: US-TCNB of mediastinal lesions is highly effective and safe tool which is particularly helpful in critically ill patients.

Migration of Bare-Metal Stent Placed in the Right Iliac Vein Into the Right Pulmonary Artery.

Stent migration is a rare event with potentially serious complications including cardiac arrhythmias and heart failure. We report a case of migration of arterial stent placed in the right iliac vein into the right pulmonary artery; it was diagnosed there and subsequently not removed for at least 3 years. Despite reports in the literature for the removal of migrated stents by minimally invasive interventional methods, in our case, that was not possible because of the long period during which the foreign body was in the right pulmonary artery and the proximal partial occlusion of organized mural thrombus.

Bardet-Biedl Syndrome with a Kidney Transplant, Esophageal Adenocarcinoma, and Postoperative Complications.

The authors present a rare clinical case of a patient with Bardet-Biedl syndrome and chronic kidney disease, who reached end-stage renal disease (ESRD) and underwent a long-term hemodialysis treatment, during which infections with Hepatitis C Virus (HCV) infection and Cytomegalovirus (CMV) infection were established. Kidney transplantation from an alive unrelated donor was performed. Later, an adenocarcinoma of the esophagus was diagnosed at an early stage, treated surgically with resection of the esophagus and gastroesophagoplasty afterward. Seven months later, a rare complication of the immunosuppressive therapy with Cyclosporin A occurred, which consisted of spontaneous bilateral pleural hemorrhage. The same, as well as the postoperative ventral hernia, was successfully resolved. Concomitant HCV was also treated. Rare autosomal recessive syndrome with severe complications, adenocarcinoma of the esophagus, spontaneous bilateral pleural hemorrhage after the operation, and successful treatment were discussed.

Treatment Optimization of Post-pneumonectomy Pleural Empyema.

INTRODUCTION: Pleural empyema after pneumonectomy still poses a serious postoperative complication. A bronchopleural fistula is often detected. Despite various therapeutic options developed during the last five decades it remains a major surgical challenge. RESULTS: There is no widely accepted treatment for post-pneumonectomy pleural empyema (PPE) and the management depends mostly on the presence or absence of broncho-pleural fistula (BPF) and the patient's general condition. In the absence of BPF, the role of surgery is still not clear because of its high morbidity and impossibility to prevent recurrences. In the earlier period, the definitive treatment consisted of open window thoracostomy followed by obliteration of the pleural cavity with antibiotic solution at the time of chest wall closure. Subsequently, the proposed different methods and modifications improved the outcome. There is an association between hospital volume and operative mortality after the lung resection. Hospital volume and the surgeon's specialty have more influence on the outcome than the individual surgeon's volume. CONCLUSIONS: Treatment management of PPE should be individualized. Definitive treatment options comprise aggressive surgery that is not possible in quite a high proportion of impaired patients. Hospital volume, surgeon's volume and surgeon's specialty may influence the prognosis.

Epidemiology, Etiology and Prevention of Postpneumonectomy Pleural Empyema.

BACKGROUND: Pleural empyema after pneumonectomy still poses a serious postoperative complication. A broncho-pleural fistula is often detected. Despite various therapeutic options developed over the last five decades it remains a major surgical challenge. MATERIALS AND METHODS: A literature search in MEDLINE database was carried out (accessed through PubMed), by using a combination of the following key-words and MeSH terms: pneumonectomy, postoperative, complications, broncho-pleural fistula, empyema, prevention. The following areas of intervention were identified: epidemiology, etiology, prevention. RESULTS: Pleural empyema in a post-pneumonectomy cavity occurs in up to 16% of patients with a mortality of more than 10%. It is associated with broncho-pleural fistula in up to 80% of them, usually in the early postoperative months. Operative mortality could reach 50% in case of broncho-pleural fistula. Unfavourable prognostic factors are: benign disease, COPD, right-sided surgery, neoadjuvant and adjuvant therapy, time of chest tube removal, long bronchial stump and mechanical ventilation. Bronchial stump protection with vascularised flaps is of utmost importance in the prevention of complications. CONCLUSION: Postpneumonectomy pleural empyema is a common complication with high mortality. The existing evidence confirms the role of bronchopleural fistula prevention in the prevention of life-threatening complications.

Surgery and pleuro-pulmonary tuberculosis: a scientific literature review.

Tuberculosis (TB) is still a major public health concern, mostly affecting resource-constrained settings and marginalized populations. The fight against the disease is hindered by the growing emergence of drug-resistant forms whose management can be rather challenging. Surgery may play an important role to support diagnosis and treatment of the most complex cases and improve their therapeutic outcome. We conducted a non-systematic review of the literature based on relevant keywords through PubMed database. Papers in English and Russian were included. The search was focused on five main areas of intervention as follows: (I) diagnosis of complicated cases; (II) elimination of contagious persisting cavities, despite appropriate chemotherapy; (III) treatment of destroyed lung; (V) resection of tuberculomas; (VI) treatment of tuberculous pleural empyema. Although specific practical guidelines concerning surgical indications and approaches are currently unavailable, a summary of the evidence emerged from the scientific literature was elaborated to help the clinician in the management of severely compromised TB patients. The decision to proceed to surgery is usually individualized and a careful assessment of the patient's risk profile is always recommended before performing any procedure in addition to appropriate chemotherapy.

Spotlight on esophageal perforation: A multinational study using the Pittsburgh esophageal perforation severity scoring system.

OBJECTIVE: The Pittsburgh group has suggested a perforation severity score (PSS) for better decision making in the management of esophageal perforation. Our study aim was to determine whether the PSS can be used to stratify patients with esophageal perforation into distinct subgroups with differential outcomes in an independent study population. METHODS: In a retrospective study cases of esophageal perforation were collected (study-period, 1990-2014). The PSS was analyzed using logistic regression as a continuous variable and stratified into low, intermediate, and high score groups. RESULTS: Data for 288 patients (mean age, 59.9 years) presenting with esophageal perforation (during the period 1990-2014) were abstracted. Etiology was spontaneous (Boerhaave; n = 119), iatrogenic (instrumentation; n = 85), and traumatic perforation (n = 84). Forty-three patients had coexisting esophageal cancer. The mean PSS was 5.82, and was significantly higher in patients with fatal outcome (n = 57; 19.8%; mean PSS, 9.79 vs 4.84; P < .001). Mean PSS was also significantly higher in patients receiving operative management (n = 200; 69%; mean PSS, 6.44 vs 4.40; P < .001). Using the Pittsburgh strata, patients were assigned to low PSS (≤2; n = 63), intermediate PSS (3-5; n = 86), and high PSS (>5; n = 120) groups. Perforation-related morbidity, length of stay, frequency of operative treatment, and mortality increased with increasing PSS strata. Patients with high PSS were 3.37 times more likely to have operative management compared with low PSS. CONCLUSIONS: The Pittsburgh PSS reliably reflects the seriousness of esophageal perforation and stratifies patients into low-, intermediate-, and high-risk groups with differential morbidity and mortality outcomes.

Whole genome microarray analysis in non-small cell lung cancer.

Lung cancer is a serious health problem, since it is one of the leading causes for death worldwide. Molecular-cytogenetic studies could provide reliable data about genetic alterations which could be related to disease pathogenesis and be used for better prognosis and treatment strategies. We performed whole genome oligonucleotide microarray-based comparative genomic hybridization in 10 samples of non-small cell lung cancer. Trisomies were discovered for chromosomes 1, 13, 18 and 20. Chromosome arms 5p, 7p, 11q, 20q and Хq were affected by genetic gains, and 1p, 5q, 10q and 15q, by genetic losses. Microstructural (<5 Mbp) genomic aberrations were revealed: gains in regions 7p (containing the epidermal growth factor receptor gene) and 12p (containing KRAS) and losses in 3p26 and 4q34. Based on high amplitude of alterations and small overlapping regions, new potential oncogenes may be suggested: NBPF4 (1p13.3); ETV1, AGR3 and TSPAN13 (7p21.3-7p21.1); SOX5 and FGFR1OP2 (12p12.1-12p11.22); GPC6 (13q32.1). Significant genetic losses were assumed to contain potential tumour-suppressor genes: DPYD (1p21.3); CLDN22, CLDN24, ING2, CASP3, SORBS2 (4q34.2-q35.1); DEFB (8p23.1). Our results complement the picture of genomic characterization of non-small cell lung cancer.

Lung resection for lung cancer after pleural empyema.

BACKGROUND: The association of pleural empyema and lung cancer has traditionally been considered as a contraindication for lung resection. However, several aspects of this problem still remain controversial. MATERIALS AND METHODS: A retrospective study was conducted including 15 patients (12 pneumonectomies and 3 lobectomies) who underwent a lung resection for primary lung cancer after previous pleural empyema. RESULTS: In all but one patient, empyema was treated by chest tube for 15 to 40 days. In only two patients, the diagnosis of empyema preceded the diagnosis of lung cancer. Among patients with pneumonectomy, a good intrapleural cleavage plane existed in only one patient with no signs of infection. In each patient with a lobectomy, preoperative chest tube aspiration took 20 to 30 days and in none of them intraoperative signs of infection existed. In patients with pneumonectomy, empyema without bronchopleural fistula occurred in two patients, while in one patient, empyema was associated with fistula. The operative morbidity after pneumonectomy was 33.3%. CONCLUSION: Association of pleural empyema and lung cancer is not an absolute contraindication for surgery. Potentially curative operation is possible, provided a full control of infection is achieved.

Expression analysis of angiogenesis-related genes in Bulgarian patients with early-stage non-small cell lung cancer.

AIMS AND BACKGROUND: Angiogenesis is a key process in the early stages of tumor development. In this study we aimed to evaluate the expression of a panel of angiogenesis-related genes in a group of Bulgarian patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND STUDY DESIGN: We analyzed the expression of 84 genes associated with the angiogenic process in 12 NSCLCs of two histological subtypes: 7 adenocarcinomas and 5 squamous cell carcinomas. Eight peripheral nontumorous tissues were used as controls. We performed real-time PCR on pathway-specific gene arrays (SABiosciences). RESULTS: Our pilot study identified upregulated genes in early-stage NSCLC including growth factors (TGFA and EFNA3), the adhesion molecule THBS2, cytokines and chemokines (MDK, CXCL9, CXCL10), and the serine protease PLAU. Several genes showed downregulation including one growth factor (FIGF), the receptors for growth factors TEK and S1PR1 as well as adhesion molecules (COL4A3 and CDH5), the cytokine IL6, the matrix protein LEP and the transcription factor NOTCH4. The study demonstrated deregulated genes specific for the two histological subtypes including the transcription factor HAND2, which was overexpressed in squamous cell carcinomas but not adenocarcinomas. CONCLUSIONS: Despite the limited number of patients, our results demonstrated the potential of angiogenesis-related genes as biomarkers in the early stages of NSCLC development.

Expression profile of the small heat-shock protein alpha-B-crystallin in operated-on non-small-cell lung cancer patients: clinical implication.

OBJECTIVE: Alpha-B-crystallin, a small heat-shock protein, recently gained major interest because of its differential expression during tumourigenesis and metastasis in various epithelial tumours. The purpose of this study was to investigate the expression of alpha-B-crystallin and its biologic and prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Immunohistochemical analysis was performed on a tissue microarray slide containing samples from 146 NSCLC patients who were operated on between 2004 and 2005. RESULTS: Cytoplasmic and nuclear staining was detected. Squamous cell carcinomas and adenocarcinomas had a distinctive profile of expression. The cytoplasmic staining of the tumours, however, is related to the local invasion - T-factor (p=0.044). Nuclear staining was more commonly detected in advanced stages, and was a biomarker of an aggressive tumour biology (p=0.042). Kaplan-Meier analysis showed that patients with positive nuclear staining had shorter overall survival (log-rank p=0.002). Using Cox's proportional hazards model, we performed multivariate analyses to assess the independent prognostic value of nuclear staining. The variables used included age, histology, gender and stage. Alpha-B-crystallin was an independent negative prognostic factor of survival in addition to clinical stage. CONCLUSIONS: Alpha-B-crystallin plays an essential role in NSCLC biology and its nuclear staining is an independent factor of poor survival. Its clinical application in molecular biologic substaging of NSCLC patients needs further validation.

Clinical usefulness of alpha-crystallin antibodies in non-small cell lung cancer patients.

The non-invasive approach of finding biomarkers in peripheral blood of cancer patients makes it useful for clinical application and cancer screening. The aim of the study was to explore the clinical utility of alpha-crystallin antibodies as markers for diagnosis of non-small cell lung cancer (NSCLC) and screening among high-risk groups. Alpha-crystallin antibodies were detected with enzyme-linked immunosorbent assay (ELISA) in 51 NSCLC patients, 38 high-risk chronic obstructive pulmonary disease (COPD) patients and 52 age and sex matched healthy volunteers. Alpha-crystallin IgG antibodies differed significantly between the groups of cancer patients and the healthy volunteers (P<0.001). A cut-off value of 0.317 discerned NSCLC patients with sensitivity 62%, and specificity 72% among the control group. The assay was effective in distinguishing the patients with and without lymphogenic metastatic spread of the disease (P=0.045): sensitivity 60%, and specificity 70%. The clinical significance of this marker has a modest implication in lung cancer diagnosis and screening in high-risk groups. Its importance as a prognostic marker or a marker of disease recurrence and lymph node micrometastasis should be further explored.

EGFR and hTERT Expression as a Diagnostic Approach for Non-small Cell Lung Cancer in High Risk Groups.

OBJECTIVE: The early detection of NSCLC is of importance because it provides chances for better outcomes. The aim of the study was to explore the clinical utility of EGFR and hTERT mRNA expression as markers for diagnosis of NSCLC. METHODS: EGFR and hTERT mRNA were quantified by quantative reverse transcription real time polymerase chain reaction in plasma of 45 non-small cell lung cancer (NSCLC) and 40 chronic obstructive pulmonary disease (COPD) patients, selected by certain spirometric characteristics that made them at high risk of developing lung cancer in future. RESULTS: The gene expression level of each gene was calculated and given as a relative quantity-RQ. EGFR gene expression was found in all lung cancer patients. The mean level of expression was RQ = 29.39. hTERT mRNA could be detected in 88% of patients. The mean expression ratio in them was RQ = 17.31. Only 50% of the high risk patients turned to be positive for EGFR. The level of their expression was RQ = 2.09. The plasma levels of hTERT could be detected in 17 (42.5%) patients of the high risk COPD group. Their mean level of expression was RQ = 1.02. A statistically significant difference in EGFR and hTERT mRNA expression could be observed between the two groups of patients-p = 0.0001. CONCLUSION: EGFR and hTERT mRNA are potential markers for lung cancer diagnosis, whose clinical importance should be replicated in a larger cohort of patients.

Epidermal growth factor receptor gene copy number changes in lung cancer.

OBJECTIVE: The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor (EGFR) in lung cancer pathogenesis. MATERIALS AND METHODS: We used the highly reliable method of FISH, applied on tissue microarray (TMA), containing 306 lung tumors of different histological types, grades and tumor stage, in order to analyze the correlations between gene copy number changes and tumor phenotype. RESULTS: The frequency of EGFR copy number changes was 22.2%-2.8% amplifications and 19.4% gains. EGFR gains occurred more commonly in the squamous cell cancers (23.5%) than in adenocarcinomas (11.8%). Amplifications of EGFR were found only in the squamous cell cancers. Regarding cancer phenotype, there was a statistically significant correlation between EGFR copy number changes and histological grade (p = 0.001). No statistically significant relation could be observed with the metastatic spread of the tumors (lymphogenic and haematogenic) (p = 0.082 and p = 0.1, respectively). In our study EGFR could not be determined as a prognostic factor of survival (p = 0.6115). CONCLUSION: EGFR copy number changes could supplement the clinical significance of EGFR as a marker related to its pathogenesis and targeted therapy.

Thymic epithelial cells of human patients affected by myasthenia gravis overexpress IGF-I immunoreactivity.

Accumulating evidence shows that several kinds of thymic cells express insulin-like growth factor-I (IGF-I), which is known to play an important role in T cell ontogeny under both physiological and pathological conditions. Still, little is known about the mechanisms of IGF-I involvement in the pathological transformation of the thymocyte microenvironment. The present study focuses on a comparative analysis of the IGF-I immunoreactivity of thymic epithelial cells (EC) from human patients with hyperplasia-associated myasthenia gravis (MG) versus physiological thymic tissue from healthy controls using immunohistochemistry and immunoelectron microscopy. We show that myasthenic EC overexpress IGF-I in comparison to EC from control subjects. The IGF-I immunoreactivity in the medullary and cortical EC from MG patients was stronger than in the normal gland. The increased expression of IGF-I and more frequent distribution of IGF-I and IGF-I-receptor (IGF-IR) immunopositive EC correlated with modulation in the immunoreactivity of double (IGF-I/IGF-IR) positive EC. Our data provide new immunocytochemial evidence for alterations of IGF-I and IGF-IR immunoreactivity in EC from pathological thymi. The persisting expression of IGF-I and IGF-IR most likely indicates that the myasthenic thymus is still capable of governing IGF-I signaling pathways, which are involved in the local regulation of T cell development and plasticity.

Structural and ultrastructural localization of NGF and NGF receptors in the thymus of subjects affected by myasthenia gravis.

We have previously reported that the thymus of patients affected by myasthenia gravis (MG) is characterized by an elevated level of nerve growth factor (NGF), an endogenous polypeptide which plays a marked role in the cell biology of nervous and immune system. A consistent number of studies has shown altered expression of NGF in diseases associated with inflammatory and/or autoimmune responses. To evaluate the biochemical and molecular mechanisms implicated in NGF action in human myasthenic thymus, it is important to identify the cellular and structural organization of NGF receptors. To address this question, we investigated, both at light and electron microscopic levels, the cellular distribution of immunoreactivity for NGF and its low-affinity receptors, (p75) and its high-affinity receptor (TrkA) in the thymus of patients with MG. The present investigation shows that NGF and NGF receptors are overexpressed in the thymic cells of patients with MG compared to control subjects.