Guglielmo Ferrari

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.

Fluorescence confocal microscopy for pathologists

Confocal microscopy is a non-invasive method of optical imaging that may provide microscopic images of untreated tissue that correspond almost perfectly to hematoxylin- and eosin-stained slides. Nowadays, following two confocal imaging systems are available: (1) reflectance confocal microscopy, based on the natural differences in refractive indices of subcellular structures within the tissues; (2) fluorescence confocal microscopy, based on the use of fluorochromes, such as acridine orange, to increase the contrast epithelium–stroma. In clinical practice to date, confocal microscopy has been used with the goal of obviating the need for excision biopsies, thereby reducing the need for pathological examination. The aim of our study was to test fluorescence confocal microscopy on different types of surgical specimens, specifically breast, lymph node, thyroid, and colon. The confocal images were correlated to the corresponding histological sections in order to provide a morphologic parallel and to highlight current limitations and possible applications of this technology for surgical pathology practice. As a result, neoplastic tissues were easily distinguishable from normal structures and reactive processes such as fibrosis; the use of fluorescence enhanced contrast and image quality in confocal microscopy without compromising final histologic evaluation. Finally, the fluorescence confocal microscopy images of the adipose tissue were as accurate as those of conventional histology and were devoid of the frozen-section-related artefacts that can compromise intraoperative evaluation. Despite some limitations mainly related to black/white images, which require training in imaging interpretation, this study confirms that fluorescence confocal microscopy may represent an alternative to frozen sections in the assessment of margin status in selected settings or when the conservation of the specimen is crucial. This is the first study to employ fluorescent confocal microscopy on surgical specimens other than the skin and to evaluate the diagnostic capability of this technology from pathologists’ viewpoint.

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.

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.

Contralateral risk reducing mastectomy in Non-BRCA-Mutated patients

Abstract The use of contralateral risk reducing mastectomy (CRRM) is indicated in women affected by breast cancer, who are at high risk of developing a contralateral breast cancer, particularly women with genetic mutation of BRCA1, BRCA2 and P53. However we should consider that the genes described above account for only 20-30% of the excess familiar risk. What is contralaterally indicated when genetic assessment results negative for mutation in a young patient with unilateral breast cancer? Is it ethically correct to remove a contralateral “healthy” breast? CRRM rates continue to rise all over the world although CRRM seems not to improve overall survival in women with unilateral sporadic breast cancer. The decision to pursue CRRM as part of treatment in women who have a low-to-moderate risk of developing a secondary cancer in the contralateral breast should consider both breast cancer individual-features and patients preferences, but should be not supported by the surgeon and avoided as first approach with the exception of women highly worried about cancer. Prospective studies are needed to identify cohorts of patients most likely to benefit from CRRM.

Breast conserving treatment for ductal carcinoma in situ in the elderly: Can radiation therapy be avoided? Our experience

INTRODUCTION Ductal Carcinoma In Situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 15-20% of all new breast cancers. If appropriately managed, DCIS has a small chance of impacting on patient life expectancy. Despite the possibility of a further recurrence or of a development in an invasive form, we are unable to select treatment of choice especially in the elderly. In particularly we risk an overtreatment of women at low risk of progression to invasive breast cancer. The aim of this study was to retrospectively evaluate the outcome of elderly patients affected by DCIS not undergoing Radiation Therapy (RT) after Breast Conserving Surgery (BCS). MATERIAL AND METHODS We reviewed our prospectively-maintained database from 1998 to 2013, selecting all women over 65 years old diagnosed with DCIS who did not receive RT for personal choice. We considered two groups, according to the risk of local recurrence (Low Risk (Group 1) vs. High Risk (Group 2)). RESULTS We identified 44 cases of DCIS treated with surgery alone or with surgery followed by adjuvant tamoxifen. 24 patients presented low risk of local recurrence (Group 1) and 20 had characteristics associated to high risk of local recurrence (Group 2). At a median follow-up of 66.3 months, no local recurrences have been described in group 1. No patients presented distant metastases, while 4 patients died for other causes. At a median follow-up of 72 months we observed 5 local recurrences in the second group (p < 0.05). CONCLUSION Our results suggest that radiation therapy can be safely avoided in a selected group of elderly patients affected by DCIS.

Is Age over 70 Years a Risk Factor for Pneumonectomy

The lengthening of life expectancy has led to more surgical procedures in elderly patients. The aim of this work was to determine whether age >70 years is a risk factor for pneumonectomy. All cases of pneumonectomy from January 1999 to December 2006 were retrospectively reviewed. The 40 patients aged > 70 years were compared with a group of 70 patients aged 40-68 years matched for sex, physical status, respiratory function, side of pneumonectomy, and pathologic stage. Postoperatively, significantly more older patients had atrial fibrillation (24% vs. 5.6%). There was a low incidence of respiratory complications in both groups, and reduced respiratory function did not increase respiratory morbidity. Thirty-day mortality was not significantly different (2.5% in older vs. 1.4% in younger patients), but long-term mortality rates evaluated at December 31, 2007 were 50% for those aged <70 years (35 patients) and 72.5% for the older group. Although age is a risk factor for morbidity and mortality in pneumonectomy, the risk is acceptable.

Nipple Areola Complex Management and Reconstruction in Subareolar Breast Abscess

Breast abscesses can be divided in puerperal and not puerperal. Puerperal breast abscess is defined as breast abscess associated with pregnancy, or during the first 3 months after labor without lactation, during lactation, or during the first 3 months after cessation of lactation. Non-puerperal breast abscesses are divided into subareolar breast abscesses, located in the subareolar area or within 1 cm from the areola, and non-subareolar breast abscesses that are located in different areas of the breast. The authors discuss pathogenesis, clinical presentation, radiological features and treatment of Nipple Areola Complex (NAC) subareolar breast abscess.

Intramuscular Nodular Fasciitis of the Pectoralis Major

A 31-year old woman, with no history of trauma, presented with a progressively enlarging mass in correspondence of the right axillary tail that had present for 2 months. Physical examination revealed a 1 cm well-defined firm nodule located in the right upper anterior-lateral margin of pectoralis major muscle. Axillary lymphadenopathy and skin infiltration were not observed. The ultrasonography examination showed a hypoechoic, homogeneous, solid nodule (sizes: 18 9 10 9 10 mm) within the pectoralis major muscle with no posterior acoustic enhancement (Fig. 1). Using Color Doppler some peripheral penetrating vessels were evident. A magnetic resonance imaging was performed for further evaluation. Magnetic resonance imaging showed an oval, intramuscular nodule that involved the major pectoralis muscle and its deep fascia without a surgical plain. This nodule was hypointense relative to muscle tissues on spin-echo T1-weighted imaging, hyperintense on spinechoT2weighted imaging (Fig. 2a) and higher hyperintense on (selective partial T1 inversion recovery) after contrast agent somministration (Fig. 2b). The lesion was considered as benign according to instrumental features however a tru-cut biopsy was performed for further confirmation. Histologic aspect was consistent with nodular fasciitis (NF). Instead of conservative management, the lesion was excised because of unaesthetic location and persistent pain. The procedure alleviated symptoms, corrected the unaestethic deficiency and allowed a definitive histopatolgic diagnosis (Fig. 3). Nodular fasciitis is a benign, rapid and self-limiting fibroblastic proliferation that is often mistaken for a malignant disease, especially sarcoma, due to its rapid growth. Reports have described the lesion as typically solitary, commonly occurring in younger adults in the third to fourth decades, particularly affecting subcutaneous tissue of upper and lower extremities, trunk, head and neck. Most of lesions have a spontaneous regression in 1 month or less and are 2 cm or less in greatest dimension. The etiology of NF is still unknown. Intramuscular NF is not common and it affects mainly vastus medialis and gluteus medius muscle in the lower extremities, hand volar aspect of the forearm in the upper extremities. Rare cases have been reported as case report also within the breast parenchyma, showing the same features of the soft tissue counterpart. We presented, to the best of our knowledge, the first case of NF in the major pectoralis muscle to offer to the breast surgeons more familiarity with this kind of benign lesion, that usually does not necessitate surgery because of the tendency toward spontaneous regression within 1 month. However, the conservative approach requires not only the presence Figure 1. Ultrasound. Longitudinal sonogram shows a intramuscular hypoechoic homogeneous solid nodule with no posterior attenuation that involved major pectoralis muscle.