[Two cases of EGFR-mutated lung adenocarcinoma treated with bronchial recanalization and first-line therapy with afatinib.] / Due casi di adenocarcinoma del polmone EGFR mutati trattati con ricanalizzazione bronchiale e terapia di prima linea con afatinib.

In 2019, we admitted two non-smoking patients with severe dyspnea from invasion of the main airway due to lung cancer. The patients were 57 and 67 years old; both presented with critical stenosis due to infiltration of the right main bronchus and in both cases, due to severe respiratory insufficiency, an indication of unclogging of the right stenotic main bronchus with rigid bronchoscope and Laser yttrium aluminum perovskite (YAP)-Nd in the operating room was given. At the end of the recanalization operation, a tracheobronchial prothesis, the GSS-Y 40x30x30 mm by Novatech, was positioned in Case 1; a nitinol self-expanding prothesis, the SILMET® 14x40 mm by Novatech, was positioned in Case 2. Once the histological diagnosis of EGFR-mutated adenocarcinoma was established, we started first-line treatment with afatinib 40 mg die tablets.

Surgical approach in thymectomy: Our experience and review of the literature.

AIM: Thymectomy is the main treatment for thymoma and patients with myasthenia gravis (MG). The traditional approach is through a median sternotomy, but, recently, thymectomy through minimally invasive approaches is increasingly performed. Our purpose is an analysis and discussion of the clinical presentation, the diagnostic procedures and the surgical technique. We also consider post-operative complications and results, over a period of 5 years (May 2011-June 2016), in thymic masses admitted in our Thoracic Surgery Unit. METHODS: We analyzed 8 patients who underwent surgical treatment for thymic masses over a period of 5 years. 6 patients (75%) had thymoma, 2 patients (25%) had thymic carcinomas. 2 patients with thymoma (33%) had myasthenia gravis. We performed a complete surgical resection with median sternotomy as standard approach. RESULTS: One patient (12%) died in the postoperative period. The histological study revealed 6 (75%) thymoma and 2 (25%) thymic carcinomas. Post-operative morbidity occurred in 2 patients (25%) and were: pneumonia in 1 case (12%), atrial fibrillation and pleural effusion in 2 patients (25%). One patient with thymoma type A recurred at skeletal muscle 2-years after surgery. CONCLUSIONS: Thymic malignancies are rare tumors. Surgical resection is the main treatment, but a multimodal approach is useful for many patients. Radical thymectomy is completed removing all the soft tissue in the anterior mediastinum between the two phrenic nerves and this is the most important factor in controlling myasthenia and influencing survival in patients with thymoma. Open (median sternotomy) approach has been the standard approach for thymectomy for the better visualization of the anatomical structures. Actually, video-assisted thoracoscopic surgery (VATS) thymectomy and robotic video-assisted thoracoscopic (R-VATS) approach versus open surgery has an equal if not superior oncological efficacy, better perioperative complications and survival outcomes.

Cushing's like syndrome in typical bronchial carcinoid a case report and review of the literature.

Cushing's syndrome occurred in 1-5% of cases of bronchial carcinoids. In this paper we describe a case of typical bronchial carcinoid in a nonsmoker young male with clinical manifestations mimicking a Cushing's syndrome. The patient performed chest radiograph and computed tomography. Fiberoptic bronchoscopy revealed the presence of an endobronchial mass occluding the bronchus intermedius. A rigid bronchoscopy was necessary for the conclusive diagnosis and for partial resection of the intraluminal tumor. Despite of the presence of Cushingoid features, the normal blood levels of ACTH and cortisol excluded the coexistence of a Cushing's syndrome.

The diagnostic accuracy of fine-needle cytology of Hurthle cell lesions; A comprehensive cytological, clinical and ultrasonographic experience.

BACKGROUND: Fine-needle cytology (FNC) diagnosis and pre-operative classification of Hurthle cells (HC) lesions may be difficult. Rapid on-site evaluation (ROSE) enhances the efficiency of FNC, mainly when utilized in close combination to clinical and ultrasound (US) data. OBJECTIVE: to describe an experience on HC FNC with contextual clinical,US and ROSE evaluation and assess if this comprehensive approach improves the FNC accuracy of HC lesions. METHODS: FNC of 112 HC lesion were diagnosed and classified, according to the Bethesda system, by clinical, US and ROSE in one year. All the cases were controlled by follow-up and histology when performed. RESULTS: Eighty-five cases were diagnosed HC rich goiter or Hashimoto thyroiditis and were classified THY2; 5 cases were diagnosed hyperplastic nodular goiter and classified THY3A. Eight cases were diagnosed suspect neoplasia and classified THY3B. Two cases were diagnosed suspect HC papillary thyroid carcinoma (PTC) and classified THY4 and 2 cases were diagnosed HC-PTC and classified THY5. THY3B, THY4, THY5 and 1 THY3A were histologically controlled. FNC were confirmed in 14 out of the 17 THY3-THY5 cases. CONCLUSIONS: A comprehensive diagnostic approach that include FNC, clinical data, US and ROSE improves the diagnosis and classification of HC lesions.

Role of FDG-PET scan in staging of pulmonary epithelioid hemangioendothelioma.

In this report we describe a case of pulmonary epithelioid hemangioendothelioma (PEH) in a young woman. The neoplasm manifested with dry cough, chest pain, finger clubbing, and multiple bilateral pulmonary nodules on chest x-ray and computed tomographic (CT) scan. She underwent thoracoscopy, and the histological features of the lung biopsies were initially interpreted as consistent with a not-well-defined interstitial lung disease. Our patient was clinically and radiologically stable over a period of four years, after which the disease progressed to involve not only the lung but also mediastinal lymph nodes, liver and bone. Fiberoptic bronchoscopy showed subtotal occlusion of the right middle and lower lobe bronchi. The histologic examination of bronchial biopsies revealed a poorly differentiated neoplasm immunohistochemically positive for vimentin and vascular markers CD31, CD34 and Factor VIII. A diagnosis of malignant hemangioendothelioma was made. Positron emission tomography (PET) is more sensitive than CT scan and bone scintigraphy in detecting PEH metastases. Furthermore, 18-fluorodeoxyglucose (FDG) uptake seems to be related to the grade of malignancy of PEH lesions. Therefore, we suggest that FDG-PET should be included in the staging system and follow-up of PEH.

Sternal reconstruction by extracellular matrix: a rare case of phaces syndrome.

Congenital defects of the sternum are rare and due to a failure of midline development and fusion of the sternal bones. Surgical correction of a sternal cleft should be preferred during infancy for functional reasons. Chest wall reconstruction represented a complex problem in the last decades. We report our successful outcome of sternal reconstruction in a rare case of PHACES syndrome, in which the patient was submitted to reconstruction of the sternum and complete closure of the thoracic defect by the employ of an extracellular matrix XCM Biologic tissue matrix. We promote the use of extracellular matrix in surgical reconstruction of chest defects for its maneuverability, plasticity, tolerability and the possibility of growing with the children's chest getting a good compliance and optimal cosmetic results.

Prenatal diagnosis, 3-D virtual rendering and lung sparing surgery by ligasure device in a baby with "CCAM and intralobar pulmonary sequestration".

Congenital cystic lung lesions are a rare but clinically significant group of anomalies, including congenital cystic adenomatoid malformation (CCAM), pulmonary sequestration, congenital lobar emphysema (CLE) and bronchogenic cysts. Despite the knowledge of these lesions increasing in the last years, some aspects are still debated and controversial. The diagnosis is certainly one aspect which underwent many changes in the last 15 years due to the improvement of antenatal scan and the introduction of 3-D reconstruction techniques. As it is known, a prompt diagnosis has an essential role in the management of these children. The new imaging studies as 3D Volume rendering system are the focus of this paper. We describe our preliminary experience in a case of hybrid lung lesion, which we approached by thoracoscopy after a preoperative study with 3D VR reconstruction. Our final balance is absolutely positive.

Idiopathic pleural panniculitis with recurrent pleural effusion not associated with Weber-Christian disease.

A 82-year-old patient with dyspnea and a recurrent history of pleural effusion was admitted into our unit. He performed a Chest computed tomography showing right pleural effusion. Video-assisted thoracoscopy (VATS) exploratory showed parietal pleural thickening of adipose tissue. The surgical procedure consisted, therefore, in the execution of multiple biopsies of the parietal pleura which appeared covered, on the whole surface, by islands of adipose tissue, without macroscopic pathological aspects. After the procedure was performed pleurodesis with talc. The definitive histological examination consisted of normal mesothelial cells surrounded by fatty tissue infiltrated by small lymphocytes in a patient without skin lesions or visceral or systemic signs of inflammatory involvement of the adipose tissue. We reported a rare case of idiopathic pleural panniculitis with recurrent pleural effusion not associated with Weber-Christian disease.

Human lung cancer-derived immunosuppressive plasmacytoid dendritic cells release IL-1α in an AIM2 inflammasome-dependent manner.

Plasmacytoid dendritic cells (pDCs) highly populate lung tumor masses and are strictly correlated to bad prognosis, yet their role in lung cancer is controversial. To understand their role in lung cancer, we isolated pDCs from human samples of lung obtained from non-small cell lung cancer patients undergoing thoracic surgery. Tumor masses presented a higher percentage of pDCs than healthy tissues; pDCs were in the immunosuppressive phenotype, as determined by higher levels of CD33 and PD-L1. Despite higher HLA-A and HLA-D expression, cancerous pDCs did not exert cytotoxic activity against tumor cells but instead promoted their proliferation. In this scenario, cancerous pDCs were able to produce high levels of IL-1α. This effect was observed on the specific activation of the inflammasome absent in melanoma 2 (AIM2), which led to higher cytoplasmic calcium release responsible for calpain activation underlying IL-1α release. The blockade of type I interferon receptor and of AIM2 via the addition of LL-37 significantly reduced the release of IL-1α, which was still high after Nod-like receptor P3 inhibition via glibenclamide. More important, mitochondrial-derived reactive oxygen species sequester diminished AIM2-dependent IL-1α release. Our data demonstrate that lung tumor-associated pDCs are responsive to the activation of AIM2 that promotes calcium efflux and reactive oxygen species from mitochondria, leading to calpain activation and high levels of IL-1α, which facilitate tumor cell proliferation in the lung.

Bacterial Epidemiology and Antimicrobial Resistance in the Surgery Wards of a Large Teaching Hospital in Southern Italy.

OBJECTIVES: Surgical infections represent an increasingly important problem for the National Health System. In this study we retrospectively evaluated the bacterial epidemiology and antimicrobial susceptibility of the microorganisms concerned as well as the utilization of antibiotics in the General and Emergency Surgery wards of a large teaching hospital in southern Italy in the period 2011-2013. METHODS: Data concerning non-duplicate bacterial isolates and antimicrobial susceptibility were retrieved from the Vitek 2 database. The pharmacy provided data about the consumption of antibiotics in the above reported wards. Chi-square or Fisher's exact test were used. RESULTS: In all, 94 Gram-negative were isolated in 2011, 77 in 2012, and 125 in 2013, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa always being the most frequently isolated microorganisms. A. baumannii showed high rates of resistance to carbapenems (with values of 100% in 2011 and 2012) and low rates of resistance to tigecycline, colistin and amikacin. In the same years, there were respectively 105, 93, and 165 Gram-positive isolated. The rate of MRSA isolates ranged from 66% to 75% during the study period. CONCLUSIONS: Our results show no significant increase in antimicrobial resistance over the period in question, and a higher rate of both MRSA isolates and resistance to carbapenems in A. baumannii compared with other European data.

Pharmacological inhibition of caspase-8 limits lung tumour outgrowth.

BACKGROUND AND PURPOSE: Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. EXPERIMENTAL APPROACH: To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced lung cancer. KEY RESULTS: Healthy and cancerous NSCLC samples had similar levels of the active form of caspase-8. Similarly, lung tumour-bearing mice had high levels of the active form of caspase-8. Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduced tumour outgrowth and this was closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-α, IL-18, IL-1α, IL-33, but not IL-1ß. Furthermore, inhibition of caspase-8 reduced the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice. However, despite the well-known role of caspase-8 in cell death, the apoptotic cascade (caspase-3, caspase-9 and Bcl-2 dependent) was not active in lungs of z-IETD-treated tumour-bearing mice, but instead higher levels of the short segment of c-FLIP (c-FLIPs) were detected. Similarly, human healthy lung samples had higher levels of c-FLIPs than cancerous samples. CONCLUSIONS AND IMPLICATIONS: Our data suggest that caspase-8 is an important orchestrator of cancer-associated inflammation and the presence of short segment of c-FLIP determines whether caspase-8 induces tumour proliferation or tumour arrest/regression in the lung.

Pulmonary arterovenous malformation causing hemothorax in a pregnant woman without Osler-Weber-Rendu syndrome.

Pulmonary arteriovenous malformations (PAVMs), although most commonly congenital, are usually detected later in life. CASE REPORT: We present a case of a 19-year-old woman with no previous history of AVM or telangiectasia, who presented dyspnea and hypoxia by massive left hemothorax in the 34th week of gestation. After emergent cesarean delivery, a chest computed tomography (CT) with i.v. contrast showed a likely 3 cm area of active contrast in left lower lung. Chest tube placement revealed about 2 liters of blood. The patient was subsequently found to have pulmonary AVM. A successful embolisation of AVM followed by lung atipic resection involving AVM and decortication for lung re-expansion were the treatments provided. CONCLUSIONS: Women with known pulmonary AVM should be maximally treated prior to becoming pregnant, and the physician should be alert to complications of pulmonary AVM during pregnancy.

Age as a risk factor in the occurrence of pneumothorax after transthoracic fine needle biopsy: our experience.

Transthoracic needle biopsy (TTNB) of the lung is a well-established technique for diagnosing many thoracic lesions, and is an important alternative to more invasive surgical procedures. Complications of TTNB include pneumothorax, hemoptysis, hemothorax, infection, and air embolism, with the most common complication as pneumothorax. From June 2011 to June 2014 we performed a prospective study of 188 patients who underwent TTNB with CT guidance at University Hospital of Salerno, Italy. Pneumothorax occurred in 14 of 188 biopsies (7.45%). With the respect of age of patients pneumothorax occurred more frequently in patients aged 60-70 years, while it was less frequent in younger (<60 years) and older patients (>70 years). In conclusion, data of our prospective study documented that CT-guided TTNB is a safe and reliable procedure in elderly patients with suspected chest malignancy and is well tolerated.

Neuroendocrine differentiation in breast carcinoma with osteoclast-like giant cells. Report of a case and review of the literature.

Osteoclast-like giant cells (OGCs) may occur in several types of breast carcinomas (BS). Neuroendocrine differentiation may be present in BS but, associated with OGCs, neuroendocrine differentiation has been rarely reported. A case of invasive ductal carcinoma with OGCs and neuroendocrine differentiation diagnosed by fine needle cytology (FNC) is described. A 72-year-old woman with a nodular lesion of the right breast underwent to fine-needle cytology (FNC) The smears showed a dissociated cell population of monomorphous, mononucleated atypical cells with interspersed multinucleated giant cells osteoclast-like. The mononuclear cell component showed plasmacytoid features and frequent vacuoles of secretion. Immunostaining (IHC) performed on cell block sections showed oestrogen receptor positivity in the mononucleated cells and OGCs positivity for LCA and CD68. Histologically the tumour showed cell nests or cords separated by thin fibrovascular septa. The neoplastic cells were monomorphic, with round-oval nuclei, granular chromatin and evident nucleoli. The cytoplasm was indistinct and eosinophilic, finely granular, often containing eosinophilic globules that were positive at the PAS and mucicarmine stainings. Numerous non-neoplastic OGCs were also detected in the interstitial septa. The ICH showed positivity of the tumoral cells for E-Cadherin, oestrogen and progesterone receptors and c-ErbB2 negativity. Mitotic index was inconspicuous with a low Ki67 positivity rate (<10%). OCGs were CD68 and LCA positive. IHC also showed strong positivity for the chromogranin and synaptophysin. A diagnosis of invasive ductal BC with OGCs and neuroendocrine differentiation was performed. The expression of chromogranin and synaptophysin was then retrospectively assessed on CB sections too. The identification of OGCs component on breast FNA samples is not difficult, depending on a good sampling only. On contrary, the neuroendocrine differentiation still represents still a challenge in breast FNC.

Post-pneumonectomy broncho-pleural fistula successfully closed by open-window thoracostomy associated with V.A.C. therapy.

Broncho-pleural fistula (BPF), is a dramatic complication that may occur after lung resection. The treatment is challenging due to its high rate of morbidity and mortality. Herein, a case of BPF associated with empyema, occurred in an elderly patient who had undergone to left pneumonectomy for non-small cell lung cancer (NSCLC), is reported. After various treatments including chest drainage and endoscopic procedures, BPF was successfully closed by open-window thoracotomy associated with vacuum assisted closure (V.A.C.) device therapy. The authors conclude that V.A.C. is a convenient and safe measure in the management of empyema with BPF. Moreover, in similar clinical contexts, V.A.C. may be the only option available that may assure the survival of the patient and the avoiding any later-phases of residual cavity.

Bone and soft tissue non-Hodgkin lymphoma of the maxillofacial area: report of two cases, literature review and new therapeutic strategies.

Primary mandibular non-Hodgkin lymphoma (NHL) and soft tissues NHL of the maxillofacial are extremely rare representing a minimal percentage of the head and neck tumors. Two cases of bone and soft tissue maxillofacial NHL are reported. Clinical, radiological and pathological features are described and the therapeutic procedures are discussed accordingly. Mandibular radiologic features have been carefully analyzed and discussed to achieve an early and accurate diagnosis avoiding improper dental therapies.

The influence of body mass index and weight loss on outcome of elderly patients undergoing lung cancer resection.

BACKGROUND: The aim of the study was to evaluate the influence of nutritional status on outcome of elderly patients resected for lung cancer. MATERIALS AND METHODS: A total of 117 consecutive patients aged ≥ 70 years undergoing lung cancer resection were enrolled. In addition to routine preoperative evaluations, other variables such as body mass index, weight loss, serum albumin, lymphocytes, and transferrin were counted. According to the body mass index value, patients were divided into Group A (≤ 18.5, underweight) and Group B (> 18.5) and risk factors for morbidity and mortality were analyzed. RESULTS: Group A and Group B counted 21 and 96 patients, respectively. The mean age was 74.9 ± 2.6; body mass index of Group A was significantly lower than that of Group B (16.7 ± 1.3 vs. 23.5 ± 1.7, respectively, p < 0.0001). On multivariate analysis, significant risk factors for complications were pneumonectomy (p = 0.001), stage (p = 0.006), predictive postoperative flow expiratory volume in 1 second (ppoFEV1%) (p = 0.003), and coronary disease (p = 0.04) and significant risk factors for early mortality were pneumonectomy (p = 0.0002), ppoFEV1% (p < 0.0001), BMI (0.02), and weight loss (0.007). The median survival time of Group A and Group B was 41 versus 54 months, respectively (p = 0.1). However, body mass index of less than 18.5 (p = 0.01) and weight loss of > 5% before operation (p = 0.01) were independent risk factors for 1 year mortality. CONCLUSIONS: In elderly patients, malnutrition was a significant additional risk factor for early death. Nutritional assessment should be included in the routine preoperative selection. In malnourished patients, nutritional support before and after operation and a careful postdischarge care might be beneficial, but it should be corroborated by further prospective studies.

Detection of RAS mutation by pyrosequencing in thyroid cytology samples.

INTRODUCTION: Fine-needle aspiration cytology (FNAC) is the primary means to distinguish benign from malignant thyroid nodules. However, adjunctive diagnostic tests are needed as 20-40% of FNAC are inconclusive. RAS mutations have been described in differentiated thyroid cancer and they could be used as tumor markers. However, their prevalence varies widely among studies, probably as a result of the detection methods used. We investigated whether the pyrosequencing method can be applied to detect NRAS and KRAS mutations in thyroid aspirates. PATIENTS AND METHODS: A total of 37 thyroid aspirates, including benign hyperplastic nodules (HBN, N = 16) and follicular thyroid carcinomas (FTC, N = 21) were analyzed for the presence of NRAS(61) and KRAS(13) mutations. RESULTS: A RAS mutation was found in 31% and 62% of BN and FTC respectively. Most samples displayed a percentage of mutated alleles lower than 50% (median = 30.8% and 15.3% in FTC and HBN respectively), a result compatible with the presence of extra-nodular cells contaminating the FNA or with the subclonal nature of both types of thyroid nodules. DISCUSSION: Pyrosequencing is a reliable assay to detect RAS mutations in fine-needle thyroid aspirates. CONCLUSIONS: The low specificity and sensitivity limit the power of this test to distinguish between FTC and benign nodules in inconclusive FNACs.

Quantitative assessment of emphysematous parenchyma using multidetector-row computed tomography in patients scheduled for endobronchial treatment with one-way valves†.

OBJECTIVES: To investigate the role of volume quantitative assessment using multidetector-row computed tomography to select patients scheduled for endobronchial one-way valves treatment. METHODS: Twenty-five consecutive patients (15 with heterogeneous emphysema and 10 with giant emphysematous bulla) undergoing endobronchial valves treatment were enrolled. All patients were studied pre- and postoperatively with standard pulmonary functional tests and quantitative volume assessment of target lobe and entire lung. Emphysematous parenchyma was obtained applying density thresholds of -1.024/-950 Hounsfield units. Among different subtype of patients, we evaluated: (i) the differences between preoperative versus postoperative data; (ii) the correlation between functional and volumetric quantification changes and (iii) the critical threshold value of volumetric quantification of the target lobe in close association with clinical effects. RESULTS: Among heterogeneous emphysematous and giant emphysematous bulla patients, a significant improvement of flow-expiratory volume in 1 s (from 36.9 ± 15.3 to 43.9 ± 10.4; P = 0.01; and from 35.8 ± 6.0 to 47.5 ± 7.9; P < 0.0001, respectively); and of forced vital capacity (from 41.9 ± 5.9 to 47.3 ± 9.3; P = 0.0009 and from 40.7 ± 5.9 to 48.8 ± 4.9; P = 0.0002, respectively); and a significant reduction of residual volume (from 185 ± 14 to 157 ± 14.7; P = 0.005; and from 196 ± 13.5 to 137 ± 21; P < 0.0001, respectively) and of total lung volume (from 166.7 ± 13 to 137 ± 18 ; P = 0.0003, and from 169 ± 15 to 134 ± 18; P < 0.0001, respectively) were seen after treatment. The volumetric measurements showed a reduction of volume of the treated lobe among heterogeneous emphysematous patients (from 1448 ± 204 to 1076 ± 364; P = 0.0008); and in those with giant emphysematous bulla (from 1668 ± 140 to 864 ± 199; P < 0.0001). The entire lung and target lobe volume changes were inversely correlated with change in forced expiratory volume in 1 s in patients with heterogeneous emphysematous (r = -0.7; P = 0.0006; and r = -0.7; P = 0.0009, respectively) and giant emphysematous bulla (r = -0.8; P = 0.001; and r = -0.7; P = 0.009, respectively). Among patients with heterogenous emphysematous and giant emphysematous bulla, the value of sensitivity and specificity were 66.6 and 83%, respectively (for a volumetric qunatification >1.5239), and of 60 and 100%, respectively (for a volumetric qunatification >1.762). CONCLUSIONS: Our study showed that the volumetric quantification adds further informations to the routine evaluation for optimizing the selection of patients scheduled for endobronchial valve treatment.