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Introduction: Lung cancer is one of the most prevalent cancers worldwide. Dickkopf-1 (DKK-1) and -2 (DKK-2) are important proteins for the regulated Wnt signalling pathway. Alternations in the Wnt pathway are associated with tumour progression. The aim of the study was to analyse the concentration of DKK-1 and DKK-2 in tumour and matched non-tumour (NT) samples of 65 patients with non-small cell lung cancer (NSCLC), including 3 subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Material and methods: The protein concentration was measured by enzyme-linked immunosorbent assay (ELISA) in homogenates. Results: The difference between the level of DKK-1 in tumour and NT specimens was not significant for the whole NSCLC group and SCC and LCC subtype, while in AC samples they were significantly higher (p = 0.028). The highest concentration of DKK-1 was found in the advanced NSCLC samples, with the T4 parameter as well as stage III. Significantly decreased DKK-2 concentrations were detected in all NSCLC subtypes (p < 0.05). Moreover, the DKK-2 level was higher in non-smokers than in smokers. The results indicate that concentrations of DKKs were different in relation to subtypes as well as clinical and socio-demographic parameters. The concentration of DKKs could be associated with the progression of NSCLC. Conclusions: We suggest that DKK-1 could play an oncogenic role in AC, while DKK-2 could be a tumour suppressor in all NSCLC subtypes. Dickkopf-1 and DKK-2 proteins could have differential roles in the Wnt signalling pathway, which is important in many cellular processes, such as proliferation and apoptosis.
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BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. METHODS: The cohorts were: gastroenteropancreatic NEN (GEP-NEN; n = 253), bronchopulmonary NEN (BPNEN; n = 64), thymic NEN (n = 1), colon cancer (n = 37), non-small-cell lung cancer (NSCLC; n = 63), benign lung disease (n = 59), and controls (n = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, n = 135) or were image-negative but resection-margin/biopsy-positive (n = 29), and were graded as G1 (n = 106), G2 (n = 49), G3 (n = 7), or no data (n = 2). The remainder (n = 71) had no evidence of disease (NED). In the BPNEN group, 43/64 (67%) had IPD. Histology revealed typical carcinoids (TC, n = 14), atypical carcinoids (AC, n = 14), small-cell lung cancer (SCLC, n = 11), and large-cell neuroendocrine carcinoma (LCNEC, n = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (n = 563) and NETest/CgA analysis matched samples (n = 178). NETest was performed by PCR (on a scale of 0-100), with a score ≥20 reflecting a disease-positive status and >40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. RESULTS: In the GEPNEN group, NETest was significantly higher (34.4 ± 1.8, p < 0.0001) in disease-positive patients than in patients with NED (10.5 ± 1, p < 0.0001), colon cancer patients (18 ± 4, p < 0.0004), and controls (7 ± 0.5, p < 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 ± 3 vs. 32 ± 2, p = 0.02) and correlated with stage (localized: 26 ± 2 vs. regional/distant: 40 ± 3, p = 0.0002) and progression (55 ± 5 vs. 34 ± 2 in stable disease, p = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 ± 1.3) who had IPD than in controls (7 ± 0.5, p < 0.0001), patients with NED (24.1 ± 1.3, p < 0.005), and NSCLC patients (17 ± 3, p = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 ± 7) than in those with BPC (30 ± 1.3, p = 0.0005) or progressive disease (57.8 ± 7), compared to those with stable disease (29.4 ± 1, p < 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (p < 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (n = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test χ2 = 87, p < 0.0001). In the BPNEN group (n = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar's test χ2 = 30, p < 0.0001). CONCLUSIONS: The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.
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Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/normas , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias del Colon/diagnóstico , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias del Timo/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/sangre , Estudios de Cohortes , Neoplasias del Colon/sangre , Femenino , Neoplasias Gastrointestinales/sangre , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/sangre , Neoplasias Pancreáticas/sangre , Sensibilidad y Especificidad , Neoplasias del Timo/sangre , Adulto JovenRESUMEN
BACKGROUND: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. AIM: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. MATERIAL AND METHODS: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. RESULTS: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). CONCLUSIONS: Elevated -NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.
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Biopsia Líquida/normas , Neoplasias Pulmonares/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The synchronous primary lung tumors is a rare condition and presented patient is the first reported case of simultaneous two distinct neuroendocrine lung cancer lesions in the same lobe. We present the case of a 55-year-old woman with synchronous two distinct neuroendocrine lung cancer lesions in the right upper lobe. Initially she showed no signs or symptoms related to lung lesions and was admitted to Thoracic Surgery Ward for the investigation of two oval, solitary pulmonary nodules (11 and 19 mm in diameter) detected on a chest X-ray performed three months earlier. The radiological imaging showed a variability of growth of both lesions (smaller tumor has enlarged while the larger one remained unchanged). After the CT-guided lung biopsy, patient underwent right upper lobectomy. Histological examination revealed a small cell carcinoma in one of the tumors and a large cell neuroendocrine carcinoma in the other one. The patient was discharged in good condition and lung inflation in chest X-ray and qualified for adjuvant chemotherapy with a combination of cisplatin and etoposide and the prophylactic cranial irradiation. Very important issues, having impact on outcome of patients with multiple lung tumours is differentiation whether the lesions are metastases or synchronous primary lung tumors and the optimal management of these patients.
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Carcinoma Neuroendocrino/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/radioterapia , Carcinoma de Células Pequeñas , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Persona de Mediana Edad , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/radioterapia , Neoplasias Primarias Secundarias/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
Although a growing body of evidence emphasizes the superiority of VATS over conventional thoracotomy, little is still known about early postoperative diaphragm muscle function after lobectomy via these two approaches. To fill the gap in existing literature, we conducted a comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, the magnitude of effort and potential risk of dysfunction such as atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled in this study. The control group consisted of 28 health subjects without medical conditions that could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function-compared to baseline data. Postoperative reduction in diaphragm contraction was demonstrated in most of the 59 patients. In the case of the control group, the differences between measurements were not observed. We noted that lobectomy via thoracotomy was linked with a greater percentage of patients with diaphragm paralysis and/or atrophy than VATS. Similar findings were observed in referring to diaphragm magnitude effort, as well as diaphragm contraction strength, where minimally invasive surgery was associated with better diaphragm function parameters-in comparison to thoracotomy. Disturbance of diaphragm work was reported both at the operated and non-operated side. Upper-right and left lobectomy were connected with greater diaphragm function impairment than other segments. In conclusion, the VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of the main respiratory muscle.
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One-lung ventilation is also used in some thoracic or cardiac surgery, vascular surgery and oesophageal procedures. We conducted a search of the literature for relevant studies in PubMed, Web of Science, Embase, Scopus and Cochrane Library. The final literature search was performed on 10 December 2022. Primary outcomes included the quality of lung collapse. Secondary outcome measures included: the success of the first intubation attempt, malposition rate, time for device placement, lung collapse and adverse events occurrence. Twenty-five studies with 1636 patients were included. Excellent lung collapse among DLT and BB groups was 72.4% vs. 73.4%, respectively (OR = 1.20; 95%CI: 0.84 to 1.72; p = 0.31). The malposition rate was 25.3% vs. 31.9%, respectively (OR = 0.66; 95%CI: 0.49 to 0.88; p = 0.004). The use of DLT compared to BB was associated with a higher risk of hypoxemia (13.5% vs. 6.0%, respectively; OR = 2.27; 95%CI: 1.14 to 4.49; p = 0.02), hoarseness (25.2% vs. 13.0%; OR = 2.30; 95%CI: 1.39 to 3.82; p = 0.001), sore throat (40.3% vs. 23.3%; OR = 2.30; 95%CI: 1.68 to 3.14; p < 0.001), and bronchus/carina injuries (23.2% vs. 8.4%; OR = 3.45; 95%CI: 1.43 to 8.31; p = 0.006). The studies conducted so far on comparing DLT and BB are ambiguous. In the DLT compared to the BB group, the malposition rate was statistically significantly lower, and time to tube placement and lung collapse was shorter. However, the use of DLT compared to BB can be associated with a higher risk of hypoxemia, hoarseness, sore throat and bronchus/carina injuries. Multicenter randomized trials on larger groups of patients are needed to draw definitive conclusions regarding the superiority of any of these devices.
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Changes in smoking trends and changes in lifestyle, together with worldwide data regarding the incidence of lung cancer in the group of patients with no previous history of smoking, leads to consideration of the differences in the course of the disease, the time of cancer diagnosis, the survival rate, and the occurrence of comorbidities in this group of patients. This study aimed to determine the occurrence of non-smokers among patients undergoing anatomical resection of the lung tissue due to lung carcinoma and to investigate the differences between the course of lung cancer, survival, and the comorbidities in the groups of patients with lung cancer depending on the history of tobacco smoking. The study included a cohort of 923 patients who underwent radical anatomical resection of the lung tissue with lung primary adenocarcinoma or squamous cell carcinoma. The Chi2 Pearson's test, the t-test, the Mann-Whitney U test, the Kaplan-Meier method, the Log-rank test with Mantel correction, and the Cox proportional hazard model were used for data analysis. We observed a significantly higher mean age of smoking patients compared to the mean age of non-smoking patients. The coexistence of former neoplastic diseases was significantly more frequent in the group of non-smokers compared to the group of smoking patients. We did not observe differences depending on smoking status in the tumor stage, grade, vascular and pleural involvement status in the diagnostic reports. We did not observe differences in the survival between smokers vs. non-smokers, however, we revealed better survival in the non-smoker women group compared to the non-smoker men group. In conclusion, 22.11% of the patients undergoing radical anatomical resection of the lung tissue due to lung cancers were non-smokers. More research on survival depending on genetic differences and postoperative treatment between smokers and non-smokers is necessary.
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Non-small cell lung carcinoma (NSCLC) is the most common lung cancer worldwide. Secreted frizzled-related proteins (SFRPs) are important tumour suppressors and antagonists of the Wnt signalling pathway, which is linked with cancer development. The aim of this study was to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 proteins in tumour and non-tumour (NT) samples obtained from 65 patients with primary NSCLC. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of SFRPs in the tissue homogenates. A significantly lower SFRP2 protein concentration was found in the total NSCLC tumour samples and the following NSCLC subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC) (p > 0.05, p = 0.028 and p = 0.001, respectively). AC tumour samples had a higher SFRP1 level than NT samples (p = 0.022), while the highest SFRP1 concentration was found in NSCLC samples from patients with clinical stage T4 cancer. Increased concentrations of SFRP1 and SFRP5 were present in stage III NSCLC samples, while the tumour samples with high pleural invasion (PL2) had an increased level of SFRP2. The results from this study suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. The levels of SFRPs varied according to the clinicopathological parameters of NSCLC.
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Adenocarcinoma , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Relacionadas con Frizzled Secretadas , Metilación de ADN , Neoplasias Pulmonares/patologíaRESUMEN
We report a 49-year-old patient with COVID-19 who developed lung abscess, pleural empyema, and tracheo-esophageal fistula. He underwent cervicotomy, segmental tracheal resection, esophageal-tracheal fistula excision, and suturing the esophagus, and a classic thoracotomy was performed. Despite the severe infection, the patient was discharged home after successful surgical treatment.
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The development of the SARS-CoV-2 pandemic caused a common appearance of severe pulmonary complications, rarely seen as a result of the other infections. These are pneumothorax, pneumomediastinum, emphysematous bullae, cavitary lung lesions, or subcutaneous emphysema. Their formation is influenced by both-the natural course of the disease and the treatment strategy adopted.
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Tietze's syndrome is a benign, self-limiting arthropathy, without purulent character. The disease most often involves articulations: sternocostal, sternoclavicular, or costochondral joints. The characteristic symptoms are tenderness, pain and edema involving one of the aforementioned joints on one side. Diagnosis of Tietze's syndrome is based on physical examination (increase of palpation tenderness in the affected joint), laboratory tests (increase of inflammatory parameters) and imaging studies (USG, MRI). Differential diagnosis of Tietze's syndrome is based on exclusion of costal cartilage inflammation, coronary syndrome and inflammatory changes in the lung and pleura. Most commonly the treatment is conservative, in resistant cases surgical.
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Spontaneous perforation of the esophagus (Boerhaave syndrome) is a rare disease that poses a serious surgical challenge. The analysis of literature concerning the Boerhaave syndrome reveled cases of recurrent spontaneous perforation of the esophagus. The incidental nature of this condition calls for more accurate assessment of all such cases. The authors made a detailed evaluation of the data obtained from eight reports of recurrent Boerhaave syndrome. The data is presented as a summary table comparing the clinical course and outcomes of patients with the primary Boerhaave syndrome as well as recurrent Boerhaave syndrome.
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Procedimientos Quirúrgicos del Sistema Digestivo/historia , Perforación del Esófago/historia , Esofagectomía/historia , Rotura Espontánea/historia , Perforación del Esófago/cirugía , Femenino , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Masculino , Radiografía Torácica/historia , SíndromeRESUMEN
The authors of the present report review the etiology and clinical symptoms of malignant pleural mesothelioma (MPM) as well as diagnostic techniques (both radiological and biomarkers) used for its detection. Subsequently, they present methods of multimodal treatment (surgery, chemotherapy, and radiotherapy) recommended by the International Mesothelioma Interest Group (IMIG). Finally, they discuss complications and long-term results associated with these methods of MPM treatment.
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The diaphragm is the primary muscle involved in active inspiration and serves also as an important anatomical landmark that separates the thoracic and abdominal cavity. However, the diaphragm muscle like other structures and organs in the human body has more than one function, and displays many anatomic links throughout the body, thereby forming a 'network of breathing'. Besides respiratory function, it is important for postural control as it stabilises the lumbar spine during loading tasks. It also plays a vital role in the vascular and lymphatic systems, as well as, is greatly involved in gastroesophageal functions such as swallowing, vomiting, and contributing to the gastroesophageal reflux barrier. In this paper we set out in detail the anatomy and embryology of the diaphragm and attempt to show it serves as both: an important exchange point of information, originating in different areas of the body, and a source of information in itself. The study also discusses all of its functions related to breathing.