Giorgio Sgarbi

Circulating plasma DNA as diagnostic biomarker in non-small cell lung cancer

OBJECTIVES The presence of circulating DNA in plasma of patients with malignant neoplasm has been a known fact for over 30 years. Since then, the concentration of free circulating plasma DNA has been studied as well as the genetic alterations and epigenetic alterations of tumour DNA of patients that suffer from various types of tumours. The analysis of circulating plasma DNA may be a useful marker to get an early diagnosis on malignant neoplasms. This study has been specifically designed to validate the quantification of circulating DNA in order to design a test useful for the early identification of non-small cell lung cancer patients and the monitoring of lung cancer progression. A second aim of this work is the sensibility and specificity evaluation of such method for future applications. METHODS The quantity of plasma DNA was determined using quantitative Real-Time PCR with amplification of the human telomerase reverse transcriptase (hTERT) gene in 151 patients that suffer from lung cancer and 79 healthy controls. The performance of the test was evaluated with a ROC curve. The relationship between the DNA concentration and main demographic, clinical and pathological variables was examined with logistic regression models as well as multiple linear regression models. RESULTS The concentration of circulating plasma DNA was about four times higher in patients with lung cancer with respect to the controls (12.8 vs 2.9 ng/mL). The area under the ROC curve was 0.79 (95% CI, 0.710-0.83). The concentration of circulating DNA proved to be an important risk factor for the presence of the illness and a prognostic index in the follow-up. CONCLUSIONS The use of quantitative Real-Time PCR revealed that higher values of circulating DNA can be found in patients with lung neoplasm compared to the healthy controls. This could have practical implications such as the use in screening programs and a possible prognostic significance in the follow-up.

PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids

Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.

Preoperative localization of indeterminate pulmonary nodules before videothoracoscopic resection

Background: The management of a solitary pulmonary nodule is the subject of debate and minimally invasive diagnostic approaches have low sensitivity for small peripheral nodules. We discuss the role of video-assisted thoracoscopic surgery (VATS) in the management of solitary pulmonary nodules (SPNs) ?1 cm performed with a preoperatory computed tomography-guided wire localization. Methods: Thirty-five selected patients underwent VATS resection for SPN, with localization by guide wire before surgery. Results: Seven patients, after VATS exploration, underwent thoracotomy because of pleuropulmonary adhesions, depth or dimensions. Histological diagnosis was obtained in all procedures; there was no postoperative morbility or morbidity. Conclusion: Preoperative computed tomography hook-wire localization is a suitable strategy for peripheral nodules ?1 cm in diameter.

The role of diagnostic VATS in penetrating thoracic injuries.

BackgroundPenetrating chest injuries account for 1–13% of thoracic trauma hospital admissions and most of these are managed with a conservative approach. Nevertheless, 18–30% of cases managed only with tube thoracostomy have residual clotted blood, considered the major risk factor for the development of fibrothorax and empyema. In addition, 4–23% of chest injury patients present persistent pneumothorax and 15–59% present an injury to the diaphragm, which is missed in 30% of cases. In order to make a correct diagnosis, reduce the number of missed injuries, chronic sequelae and late mortality we propose performing surgical exploration of all patients with a penetrating injury of the pleural cavity.Methods1270 patients who sustained thoracic trauma were admitted to our hospital between 1994 and 2004. Of these, 16 patients had penetrating injuries: thirteen were surgically explored by means of Video Assisted Thoracic Surgery (VATS), and 3 with thoracotomy due to hemodynamic instability or suspected lesion of the heart or great vessels.ResultsIn the 13 patients who underwent VATS, 5 injuries to the diaphragm, 3 lesions to an intercostal artery, and 1 lesion to the diaphragmatic artery were detected. In 12 of these patients a laceration of the pulmonary parenchyma was also present. A conversion to thoracotomy was necessary due to a broad laceration of the diaphragm and due to hemostasis of an intercostal artery. In all but one case, which was later converted, diagnostic imaging missed the diagnosis of laceration of the diaphragm. There was no intra- or postoperative mortality, and average hospital stay was five days.ConclusionVATS is a safe and effective way to diagnose and manage penetrating thoracic injuries, and its extensive use leads to a reduction in the number of missed, potentially fatal lesions as well as in chronic sequelae.

Synchronous bilateral bronchial carcinoid diagnosed with combined dual tracer ( 18F-FDG and 68Ga-DOTATOC) PET/CT scans

A 38-year-old non-smoker female with unremarkable history presented with an insidious onset of dry cough. Computed tomography revealed two solid round pulmonary lesions, curiously symmetrically located in the middle lobe and in the lingular segment, respectively (Fig. 1). Trans-bronchial needle biopsy was limited by a profuse bleeding and the diagnosis was inconclusive. The radiological differential diagnosis consisted of non-neoplastic disease, synchronous/multifocal bronchial carcinoids and pulmonary metastases from unknown neoplasm.

Ultrasonically guided biopsy of anterior mediastinal masses.

The various techniques used to perform biopsies of mediastinal masses--mediastinoscopy, mediastinotomy, extended cervical mediastinoscopy, and assisted video-thoracoscopy--have already been amply described. In this study the authors give particular attention to ultrasonically guided percutaneous biopsy. Between January 1998 and July 2001 42 patients underwent anterior mediastinal core needle biopsy with ultrasonic guidance. An accurate diagnosis was made for all the patients, with a sensitivity and specificity of 100%. Two cases of pneumothorax were seen, with pleural drainage and a 5-day hospitalization necessary in one of the cases. The remaining 40 patients were treated as outpatients and were discharged within 4 h of the procedure. Ultrasonically guided percutaneous core-needle biopsy is a safe procedure for the diagnosis of the anterior mediastinal masses.

Intra pulmonary migration of a Kirschner wire after glenohumeral fixation.

A 79-year-old asymptomatic woman underwent arthrodesiswith a double K-wire insertion for a posttraumatic invet-erate right glenohumeral dislocation. After removal of thefirst K-wire, chest X-ray showed intrathoracic migration ofthe foreign body, and the CT scan confirmed the pulmonarypenetration of the device within the right upper lobe withintraparenchymal surrounding hematoma (Fig. 1).Although the vital parameters were substantially within therange, the patient underwent urgent surgery. A combinedapproach was attempted: the K-wire was mobilized fromthe glenoid cavity to resect the distal hook and, at the sametime, a right lateral thoracotomy was performed to removesafely the device deeply slipped into the lung and suture theparenchyma (Fig. 2). The postoperative course wasuneventful, and the patient was discharged on the eighthpostoperative day.Improper uses or positioning of K-wires are widelydescribed in the literature and may expose patients toinsidious but potentially life-threatening complications [1];therefore, regular radiological follow-up may be advisablein patients with foreign body at risk of dislodgement intovital structures.

Mediastinal Castleman’s disease mimicking thoracic paravertebral schwannoma

A 51-year-old female underwent resection of a solid lesion in the posterior mediastinum, preoperatively interpreted at imaging as thoracic schwannoma, requiring double sequential surgical procedure to be resected. The histologic examination of the resected mass diagnosed a hyaline-vascular Castlemans disease.

Endobronchial Hamartoma Subtotally Occluding the Right Main Bronchus and Mimicking Bronchial Carcinoid Tumor

AbstractHamartomas are very rarely identified as an endobronchial lesion.Herein, we describe a peculiar case of a 55-year-old woman with persistent cough and increasing dyspnea and radiological detection of a solid lesion subtotally occluding the main right bronchus. Despite the radiological and radiometabolic (18-fluoro-2-deoxy-d-glucose positron emission tomography/computer tomography scan) features were highly suspected for bronchial carcinoid, the definitive diagnosis after endoscopic removal was indicative of an endobronchial hamartoma.When considering differential diagnosis of an endobronchial lesion, the physicians should take firmly in mind such rare entity and, accordingly, bronchoscopy and bronchoscopic biopsy should be done as first step in management of all cases presenting with endobronchial lesions.

Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura

Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity.