TYPE: Abstract Publication TOPIC: Diffuse Lung Disease PURPOSE: Transbronchial cryobiopsy is an emerging technique for diagnostic biopsies on lung parenchyma. The preliminary experience of the Thoracic Endoscopy Department of the University Hospital of Pisa is reported. METHODS: During 2019, 10 patients (8M/2F) underwent transbronchial cryobiopsy; median age 65 years (range 45-76 years). The cases were discussed by a multidisciplinary team (pneumologist, radiologist, thoracic endoscopist and surgeon, rheumatologist, anatomo-pathologist). Patients met the eligibility criteria (PaP<40 mmHg, PLT>70.000, FEV1>0.8 l, FVC>50% of the predicted, DLCO>35%, PaO2>50 mmHg, oxygen therapy <2 l/min) . The procedures were performed under general anesthesia, using rigid bronchoscope, Fogarty catheter and assisted by fluoroscopy. RESULTS: In two cases, the procedure was performed in the right upper lobar bronchus (anterior and apical segment); in five cases in the right lower lobar bronchus (lateral segment); in 1 patient in the middle lobar bronchus (lateral segment); in last 2 patients in the left lower lobar bronchus (lateral segment). In 4 cases the 1.9 mm probe was used, in 6 cases the 2.4 mm probe. The median dimensions of the samples correspond to 0.8x0.5x0.3 cm (range 2.4-0.5x0.8-0.4x0.2-0.5 cm). One patient presented post-procedural right pneumothorax (chest tube) and needed 4 days hospital stay. Six patients had 1 day hospital stay, while 3 patients 2 days, without any complication. CONCLUSIONS: All the samples were diagnostic (2 fibrosis, 2 silicosis, 2 NSIP, 2 lung adenocarcinoma, 2 chronic hypersensitivity pneumonia). CLINICAL IMPLICATIONS: Transbronchial cryobiopsy proves valid for diagnosis of diffuse lung disease and comparable to surgery, also it is burdened by fewer complications, although further studies are needed. DISCLOSURE: No significant relationships. KEYWORDS: diagnosis, Lung, cryobiopsy

Objective The majority of patients with lung cancer are treated on the basis of a diagnosis made from the analysis of a small tumour biopsy or a cytological sample and histotype is becoming a critical variable in clinical workup as it has led to the introduction of newer biologically targeted therapies. Consequently, simply classifying cancers as small cell lung cancers or non‐small cell lung cancers is no longer sufficient. Methods From 2009 to 2011, a review of the histo‐cytological database was conducted to identify all small biopsy and cytology specimens collected for diagnostic purposes in patients with a thoracic lesion. In total, 941 patients were studied by examining exfoliative and/or aspirative cytological samples. To establish the accuracy of these methods, cytological and biopsy diagnoses were compared with each other and with subsequent resection specimens when available. Moreover, during the diagnostic workup, we examined a validated panel of immunohistochemical markers. Results The diagnostic concordance of pre‐operative diagnoses with surgical samples was high in both cytology and biopsy samples [κ = 0.71, confidence interval (CI) = 0.6–0.81; P < 0.0001 and κ = 0.61, CI = 0.41–0.82; P < 0.0001 respectively; good agreement] but concordance between cytology and biopsy was moderate (κ = 0.5, CI = 0.43–0.54; P < 0.0001). Immunohistochemistry‐aided diagnoses were definitive for histotype in 92.8% of both cytology (206/222) and biopsy (155/167) specimens. Conclusion We found that lung cancer diagnosis and subtyping of cytology and biopsy samples are highly feasible and concordant; thus, the diagnostic approach to lung cancer does not require more invasive procedures.

Aim Since World Health Organization (WHO) histologic typing of tumors of the thymus publication in 1999 only a few studies correlated this classification with the clinical features of the patients. We present the results of a retrospective analysis on patients, operated on for a thymoma, whose specimens were available, to compare the WHO thymoma histologic classification to the clinical behavior of the tumors. Methods The specimens of 69 patients, who underwent surgical treatment between 1983 and 1998, were analyzed, comparing the clinical features of the patients and the hystological typing of the neoplasm, according to the WHO classification. A survival analysis of clinical and pathological prognostic factors was carried out. Results The incidence of thymus-related syndrome was related to the histological subtype and increases progressively from A to B3, while in C subtype the incidence was nihl. With a mean follow-up of 108 months (range 54-239 months), we experienced 6 intrathoracic recurrencies, 3 of those were intrapleuric and 3 mediastinal. At the last follow-up, 52 patients were alive; 1 with disease. Five deaths were related to the tumor (2 mediastinal and 3 intrapleuric relapses). Actuarial five-year and ten-year survival was 95% and 88.9%. Because of the absence of deaths related to thymomas in most samples it was not possible to perform a comparison among different histological types and different clinical stages. Conclusions The WHO histologic classification seems to correlate with the incidence of thymus related syndromes and the clinical stage of Masaoka. Despite the higher incidence of recurrences in type B3 and C thymoma the WHO classification did not prove to be a prognostic factor.

a history of medical or surgical therapy for tuberculosis.

Should heart transplantation be considered as a treatment option for patients aged 70 years and older?

Background: Surgery is the choice treatment for symptomatic tracheal obstruction due to malignant thyroid disease. Few additional therapeutic alternatives are available: radiotherapy (RT), chemotherapy (CT) or radioiodine therapy (131I). Only few studies on interventional bronchoscopy (IB) as well as alternative or palliative procedures have been reported so far. This study is a retrospective report of results of IB performed in patients with severe tracheal obstruction due to advanced thyroid cancer. Setting: Pulmonary and Endocrinology Units of a University Hospital. Patients and interventions: From January 2, 2000 to March 1, 2004 14 consecutive patients [5 males, mean age: 62.2±10.7 (SD) yr] underwent IB due to tracheal obstruction for anaplastic (ATC: 7 patients), differentiated (DTC: 5), medullary (MTC: 1) and non-epithelial malignant (NEMN: 1) thyroid cancer. Eight out of 14 patients had local advanced inoperable disease, 6 had local relapse after surgery, 131I or RT. Ten out of 14 patients sufferedfrom severe dyspnea. In 4 patients airway patency was maintained by insertion of a stent; in 3 the tracheal lesion was removed by Nd-YAG laser; in 7 both procedures were performed. Results: All 10 patients with dyspnea showed an improvement in symptoms. Early and late complications were observed in 4 and in 3 patients, respectively. All but 4 DTC patients died 11.9±14.2 months after the diagnosis (4.20±5.1 after IB). In 4 DTC patients still alive 90.7±59.2 since diagnosis and 16.7±9.2 months since IB, the airway dilatations allowed further treatments like 131-I and/or RT. Conclusions: Interventional bronchoscopy, including Nd-YAG laser and airways stenting are alternatives to surgery in inoperable thyroid-induced tracheal obstruction. Moreover, airway dilatation improves dyspnea and may allow further treatment.

Objectives: Tumor angiogenesis. expressed by the microvessel count (MVC), and its mediators (i.e. vascular endothelial growth factor) significantly correlate with metastases in surgically treated non-small cell lung carcinoma/cancer (NSCLC). SCLC is rarely treated by surgery, as a consequence. few specimens are available to perform a biological characterization. We reviewed our experience in the surgical treatment of SCLC with particular reference to the angiogenetic expression and its correlation to the stage of disease and prognosis. Methods: We retrospectively investigated a homogenous cohort of 87 patients with SCLC, who were primarily operated on and then underwent adjuvant chemotherapy between 1980 and 1998. Their median age was 62 years (range 34-73). All the patients were completely staged. The surgical procedures included: 32 pneumonectomies and 55 lobectomies. There were 46 NO. 17 NI and 24 N2-disease. The adjuvant chemotherapy consisted of four to six courses of cyclophosphamide, epidoxorubicine and etoposide. The MVC was determined highlighting the microvessels with anti-CD34 monoclonal antibodies. Immunostaining for VEGF was performed using the ABC method with anti-VEGF monoclonal antibodies. The p53 protein expression was assessed by NCL-DO7 anti-p53 monoclonal antibody. Results: With a median follow-up of 109.6 months (range 25-238). 37 patients are alive and well, two are alive with systemic metastases. Forty-four patients died of local (n = 5) or systemic (n = 39) relapse. while four patients died from other causes. The median MVC was 59 (range 18-145). Among the clinico-pathological parameters, metastatic nodal-involvement (P = 0.002) and advanced stage of disease (P = 0.005) were associated with a worse overall survival (OS). MVC and VEGF protein expression significantly affected the survival (P < 0.001 and P = 0.0008, respectively), No statistical association was found between p53 alterations and OS as well as no association was found among p53 alterations, MVC and VEGF expression. On multivariate analysis only the VEGF expression (P = 0.003) was an independent prognostic factor. Conclusions: Angiogenesis plays a role in the metastatic process of the SCLC as well as NSCLC. SCLC has a higher vascularization than NSCLC as results from the higher number of microvessels however, tumor angiogenesis tested by the MVC and the VEGF protein expression correlates with the prognosis also in SCLC. SCLC may be an ideal field to test new antiangiogenic drugs associated to chemotherapy. (C) 2002 Elsevier Science B.V. All rights reserved.

A large membranous wall laceration of the thoracic trachea was surgically treated. The surgical approach consists on a low collar incision followed by a longitudinal tracheotomy. The membranous tear was repaired with a running suture and tracheotomy sutured with interrupted crossed stitches. The procedure was effective and endoscopic follow-up showed a perfect healing process with no signs of tracheal stenosis. This new technique proved to be a reliable, quick and safe procedure, which allows to repair membranous lacerations as far as the carina, avoiding thoracotomy.

Objective: Patients with an acute major airway injury are coming at our attention with increasing frequency. Despite of its nature, post-traumatic or iatrogenic, these lesions may be life-threatening. An early diagnosis and a prompt treatment reduce morbidity and mortality, Materials and methods: In the last 10 years, on a total of 55 patients treated in our institution for benign lesions of the major airway, 20 were with an acute injury; eleven females and nine males with a mean age of 58 years (range of 24-92). Twelve lesions were iatrogenic (orotracheal intubation) and eight were post-traumatic (three blunt traumas, five penetrating traumas). The cervical trachea was involved in 13 cases tone associated to an incomplete esophageal transection and two associated to laryngeal injuries), the thoracic trachea in six cases (four extended to the right mainstem one and to the left), Sixteen patients underwent immediate surgical repair (13 direct sutures of the tear and three complex restorations of the airway): 11 by cervicotomy and five by thoracotomy. In six cases the suture of a posterior tracheal wall tear was achieved through a new approach which provides for a small collar incision and a longitudinal tracheotomy, Results: All the patients were discharged healed with a normal patency of the airway. At a mean follow up of 49 months (range of 9-122 endoscopy showed a perfect healing process of the lesions. One patient, treated in a conservative fashion, required endoscopic laser Nd-YAG removal of a granuloma, Conclusion: Early diagnosis and surgical repair are the goals to persescute to achieve the best outcome in this potentially lethal lesions, The surgical approach should be the thoracotomy if the trauma involves the 1/3 inferior trachea and/or a mainstem. the cervicotomy in the case it was injured the 2/3 superior trachea and the larynx. Posterior tracheal wall tears may be repaired via the new transcervical/transtracheal technique. The conservative treatment should be reserved to those patients with minimal signs and symptoms. anti with an adequate potency of the airways. (C) 2001 Elsevier Science B.V. All rights reserved.

Background: Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. Patients and Methods: From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. Results: There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease’s progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). Conclusion: The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.

Background: Smaller postintubation tracheal tears are often misdiagnosed and, when recognized, they are effectively managed in a conservative fashion. Large membranous lacerations, especially if associated with important manifestations, require immediate surgical repair. We report our experience over the past 7 years.Methods: From 1993 to 1999, 11 patients with a postintubation posterior tracheal wall laceration were treated in our institution. One patient was male and 10 were female, with a mean age of 68 years. Ten patients underwent orotracheal intubation under general anesthesia for elective surgery, 4 of whom were treated with a double-lumen selective tube. One patient underwent emergency intubation because of anaphylactic shock. In 9 cases the tracheal tear was promptly repaired, by way of a thoracotomy in 4 and by way of a cervicotomy and longitudinal tracheotomy in 5. In 2 cases the tear was small and was consequently managed conservatively.Results: All surgical procedures proved effective in repairing the laceration, and there was no mortality or morbidity in the perioperative period. Early and late endoscopic follow-up showed no signs of tracheobronchial stenosis.Conclusions: When repair of membranous tracheal laceration is required, the surgical approach should be through a thoracotomy if the tear involves the distal trachea, a main stem, or both, and through a cervicotomy when the laceration is located in the proximal two thirds of the trachea. Performing a longitudinal tracheotomy to reach and suture the posterior tracheal wall is a reliable, quick, and safe procedure, and it avoids lateral and posterior dissection of the trachea.

Objective: We analyzed our experience in the period January 1975-December 1995 aiming to confirm the role of surgery in the multimodality treatment of small cell lung cancer (SCLC). Methods: 127 patients (5.28% of the overall lung resections for carcinoma) underwent surgery for SCLC. The median age was 60 years (range 34-73). In 87 patients (68.5%) a pre-operative tissue diagnosis was effected and those patients underwent a complete staging procedure. Fifteen patients received up to six complete courses of neoadjuvant and adjuvant chemotherapy. The surgical procedures included: 50 pneumonectomies, 71 lobectomies and six wedge resections. Two patients experienced a local recurrence and a completion pneumonectomy was performed. Results: The median follow-up is 66 months (range 6-214). The 5-year actuarial survival rate is 22.6% (median 18 months). Twenty-three patients are still alive, 21 of them being disease-free. Considering the most conspicuous group of patients (n = 92) treated by surgery and adjuvant chemotherapy, the survival data were 47.2, 14.8 and 14.4% for Stage I, II and III, respectively (P = 0.001). N0 patients had a significantly better survival than N1 and N2 patients (P = 0.035). Conclusions: Surgery and adjuvant chemotherapy might represent an effective form of treatment of limited SCLC without lymph-node involvement. The role of surgery is yet to be verified as regards N1 and N2 status, where even neoadjuvant chemotherapy has not achieved the hoped-for results (no patient reaching a 2-year survival). (C) 1997 Elsevier Science B.V.

Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count (MC), as a measure of tumor angiogenesis, has been significantly correlated with metastatic disease in cutaneous, mammary, prostatic, head and neck, and early stage lung carcinoma.

Over a period of eleven years (1983-1993), the role of adjuvant chemo and/or radiotherapy was evaluated on 222 resected patients (pts) with NSCLC at atage IIIA(N2). All the patients underwent an attentive mediastinal limphoadenectomy. Fifty-five patients had a clinical mediastinal node involvement. 174 pts had a single mediastinal node station involved while 48 had two or more stations involved. One hundred and seventy-one pts (77%) underwent adjuvant therapies, consisting of citotoxic chemotherapy in 40 pts, radioterhapy in 97 pts and chemoradioterhapy in 34 pts. Follow-up lasted until September 1994. Overall 5-yr survival was 17.5%, the median being 17 months. Forty-two pts were, at that moment, still living (median 43.5 months, min 11-max 120) with 37 disease free. We verified a significant difference concerning survival among the three histologic types (p = 0.03), with the squamous achieving the best result (21.3% at 5-yrs). Surgical N2 had a better survival (20/5% at 5-yrs) than the clinical one (9%), (p = 0.01). In particular, if only one nodal station was involved, survival was 21.3% compared to 4.5% when metastases were present at two or more nodal station (p = 0.0001). Considering the level of mediastinal node involvement, the worst prognosis was linked to the carina node metastases (p = 0.02). Survival benefits were obtained by means of adjuvant therapies (20/2% vs 8.1%), (p = 0.0002). Analyzing all the pts, the best survival was achieved in those treated by surgery plus chemo-radiotherapy (32.4%), (p = 0.0001). As regards the squamous cell tumors, pts who underwent surgery plus radiotherapy had the best prognosis (24.2%), (p = 0.0026). Further, in non-squamous cell tumor, chemo-radiotherapy increased survival (45%), (p = 0.0001). At multivariate analysis, only the level of nodal involvement and the adjuvant therapy maintained their statistical significance. Our results prompt us to conclude that: 1) Squamous cell tumors and single nodal station involvement are linked to the best prognosis; 2) Squamous cell carcinoma should be treated by adjuvant radiotherapy; 3) Non-squamous tumors should undergo to chemo-radiotherapy; 4) Clinical N2 (according to our recent experience) may benefit from neoadjuvant chemotherapy.

During a 14-year period (1980-1993) second primary lung cancer or relapse was treated in 44 consecutive patients, Thirty-seven patients had synchronous (n = 18) or metachronous (n = 19) second primary lung cancer, Ten synchronous tumors were ipsilateral and treated contemporarily with five pneumonectomies, three lobectomies and two double wedge resections. The bilateral synchronous lesions (8 patients) were treated by staged bilateral thoracotomy (mean interval; 2 months). The first resection consisted of a lobectomy in six patients and wedge resection in two, The second one was a wedge resection in six patients and a lobectomy in two, In the metachronous presentation 15 patients (79%) were asymptomatic and detected by follow-up chest X-ray, In this group the first operation was a lobectomy in 12 patients, a wedge resection or segmentectomy in 6 and a pneumonectomy in 1, The second one was a wedge resection in nine patients, a lobectomy in six and completion pneumonectomy in four, Seven patients, all of them asymptomatic, had local recurrence from their primary lung cancer, The first lung resection was a lobectomy in five patients and a wedge resection in two, The second one was completion pneumonectomy in five patients and completion lobectomy in two, We had no operative death, The actuarial overall 5-year survival rate after the second pulmonary resection for second primary lung cancer was 38.3% with a median survival time of 13.5 months, The synchronous presentation had a better survival than the metachronous one (46.2% and 25.9%), respectively), The actuarial overall 5-year survival rate for patients with relapse was 38.1% with a median survival time of 37 months, We may conclude that an aggressive surgical approach is safe, effective and warranted in patients with either a second primary lung cancer or relapse from their primary lung cancer, Moreover, for early detection of the second lesions, follow-up at a maximum of 6-monthly intervals should be continued for more than 5 years after the first resection.