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Abstract: Objective: To report on the experience with radical surgery, with emphasis on the long-term outcome, for malignant pleural mesothelioma (MPM) at a single institution. Methods: From our prospective database over a 17-year period, we reviewed 83 consecutive patients undergoing radical surgery for MPM in a multimodality programme. The long-term overall survival was analysed using the Kaplan–Meier method. Results: A total of 83 patients (65 males, median age: 60 years) underwent an extra-pleural pneumonectomy (EPP) with a curative intent. Epitheliod MPM was the most frequent (82%) cause. A right-sided disease was present in half of the cases (n =42). The International Mesothelioma Interest Group (IMIG) stage of the disease was 2 in 36%, 3 in 45% and 4 in 9% of the cases. Preoperative chemotherapy consisting of a doublet cisplatin–pemetrexed (mean of three cycles) was offered to 10 patients (12%). Postoperative therapies, either chemotherapy or radiotherapy, were given in 25 patients (30%). The 30-day and 90-day mortality rates were 4.8% and 10.8%, respectively. Postoperative complications occurred in 39.8% and were major in 23 patients (27.7%). Re-operation was necessary in 12 cases (14.5%) for one of the following reasons: broncho-pleural fistula (n =4), bleeding (n =3), diaphragmatic patch rupture (n =3), oesophago-pleural fistula (n =1) and empyaema (n =1). The mean hospital stay was 43 days. The median survival was 14.5 months, while the overall 1-, 2- and 5-year survival rates were 62.4%, 32.2% and 14.3%, respectively. Conclusions: These results concur with the published data of the most experienced centre with regards to the mortality and morbidity after EPP for MPM. In line with the biggest series reported in the past, the observed 5-year survival rate of almost 15% is disappointing. [Copyright &y& Elsevier]

Abstract: Objective: Some patients with localised oesophageal cancer are treated with definitive chemoradiotherapy (CRT) rather than surgery. A subset of these patients experiences local failure, relapse or treatment-related complication without distant metastases, with no other curative treatment option but salvage oesophagectomy. The aim of this study was to assess the benefit/risk ratio of surgery in such context. Methods: Review of a single institution experience with 24 patients: 18 men and 6 women, with a mean age of 59 years (±9). Histology was squamous cell carcinoma in 18 cases and adenocarcinoma in 6. Initial stages were cIIA (n =5), cIIB (n =1) and cIII (n =18). CRT consisted of 2–6 sessions of the association 5-fluorouracil/cisplatin concomitantly with a 50–75Gy radiation therapy. Salvage oesophagectomy was considered for the following reasons: relapse of the disease with conclusive (n =11) or inconclusive biopsies (n =7), intractable stenosis (n =3), and perforation or severe oesophagitis (n =3), at a mean delay of 74 days (14–240 days) following completion of CRT. Results: All patients underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy. Thirty-day and 90-day mortality rates were 21% and 25%, respectively. Anastomotic leakage (p =0.05), cardiac failure (p =0.05), length of stay (p =0.03) and the number of packed red blood cells (p =0.02) were more frequent in patients who received more than 55Gy, leading to a doubled in-hospital mortality when compared to that of patients having received lower doses. A R0 resection was achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was observed in 3 patients (12.5%). Overall and disease-free 5-year survival rates were 35% and 21%, respectively. There was no long-term survivor following R1–R2 resections. Functional results were good in more than 80% of the long-term survivors. Conclusion: Salvage surgery is a highly invasive and morbid operation after a volume dose of radiation exceeding 55Gy. The indication must be carefully considered, with care taken to avoid incomplete resections. Given that long-term survival with a fair quality of life can be achieved, such high-risk surgery should be considered in selected patients at an experienced centre. [Copyright &y& Elsevier]

Abstract: Objective: To review the long-term results of redo gastro-esophageal reflux disease (GERD) surgery with special emphasis on residual acid-suppressing medications, pH monitoring results, and quality of life. Methods: Retrospective analysis of 52 patients (24 males) who underwent redo GERD surgery between 1986 and 2006 through a transthoracic (n =14), or a transabdominal (n =38) approach. Indications were recurrent GERD in 41 patients, and complication of the initial surgery in 11. Quality of life was evaluated by telephone enquiry using a validated French questionnaire (reflux quality score, RQS). Results: Postoperative complications occurred in 18 patients (35%), resulting in one death (2%). Reoperation was required in seven patients. At 1 year, 26 patients (51%) had 24h pH monitoring, among whom 2 (8%) were proved to have recurrence of GERD. RQS values were calculated in 38 patients with a mean follow-up of 113 months. Fifty percent of this subgroup had a RQS value beyond 26/32, indicating an excellent quality of life. Among these 38 patients, 20 (53%) had acid-suppressing medications whatever their RQS values. Patients who underwent transthoracic GERD surgery had the highest RQS values (p =0.02), a lower rate of complications (p =0.06) and a lower rate of reoperation (p =0.04). Conclusion: Our experience confirms that selection of candidates for redo GERD surgery is a challenging issue. A transthoracic approach seems to produce better results and lower rates of complications. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the clinical relevance of preoperative airway colonisation in patients undergoing oesophagectomy for cancer after a neoadjuvant chemoradiotherapy. Methods: From 1998 to 2005, 117 patients received neoadjuvant chemoradiotherapy for advanced stage oesophageal cancer. Among them, 45 non-randomised patients underwent a bronchoscopic bronchoalveolar lavage (BAL group) prior to surgery to assess airways colonisation. The remaining patients (n =72) constituted the control group. The two groups were similar with respect to various clinical or pathological characteristics. Results: Thirteen of the 45 BAL patients (28%) had a preoperative bronchial colonisation by either potentially pathogenic micro-organisms (PPMs) (n =7, 16%) or non-potentially pathogenic micro-organisms (n =6, 13%). Cytomegalovirus (CMV) was cultured from BAL in four patients. Pre-emptive therapy was administrated in seven patients: four antiviral and three antibiotic prophylaxes. Postoperatively, 14 patients (19%) developed acute respiratory distress syndrome (ARDS) in the control group and three (7%) in the BAL group (p =0.064). The cause of ARDS was attributed to CMV pneumonia in six control group patients on the basis of the results of open lung biopsies (n =3) or BAL cultures (n =3) versus none of the BAL group patients (p =0.08). Timing for extubation was shorter in the BAL group (mean 13±3h) as compared with the control group (mean 19.5±14h; p =0.039). In-hospital mortality was not significantly lower in BAL group patients when compared to that of control group patients (8% vs 12.5%). Conclusions: Airway colonisation by PPMs after neoadjuvant therapy is suggested as a possible cause of postoperative ARDS after oesophagectomy. Pre-emptive treatment of bacterial and viral (CMV) colonisation seems an effective option to prevent postoperative pneumonia. [Copyright &y& Elsevier]

Abstract: Objective: T4-disease for non-small cell lung cancer (NSCLC) includes different conditions: mediastinal invasion, neoplastic pleural cytology, and multifocal disease in the same lobe; regarding the last category, no strict criteria allow to differentiate satellite nodules from synchronous multiple primary tumours. Methods: Retrospective study of 56 patients who underwent a complete resection from 1985 to 2006 of a NSCLC graded pT4N0 due to multifocal disease. A small nodule (<1cm) closed to the primary tumour, in a same pulmonary segment with an identical histology was considered as a satellite nodule (pT4sn). Multiple tumours, sized more than 1cm, with an identical histology, located in the same lobe but in different segment were considered as synchronous cancers (pT4sc). Results: There were 44 males and 12 females: 35 patients were graded T4sn and 21 patients T4sc. The median age was 62.5 years. The two groups were similar for sex, age, tobacco consumption, ASA score, NYHA, Charlson''s index, spirometric parameters, cardiovascular comorbidity and history of previous extra-thoracic malignancies. All had a complete anatomic resection with mediastinal lymphadenectomy. Thirty-day mortality rate was 3.6%. Overall 5-year and 10-year survival rates were 48.2% and 29.9%, respectively. There was a non-significant trend for a worse survival in T4sn group patients when compared to that of T4sc group patients: 42.9% vs 52.3% at 5 years, and 25% vs 34.9% at 10 years (p =0.62). Conclusions: Multifocal T4 stage IIIB disease is a heterogeneous category where overall prognosis is far better than those of other T4 subgroups. Survival rates associated with pT4sn and pT4sc look roughly similar because of the small size of the subgroups usually submitted to comparison in most series. In the present experience, respective survival figures diverge, suggesting different biological behaviours. [Copyright &y& Elsevier]

Abstract: Objective: Induction Therapy (IT) before surgery emerged as a widely used strategy for IIIAN2 and selected IIIB NSCLC patients. However, IT is associated with a possible increase in postoperative complications. Consequently, selection of patients with the best chances to benefit from combined treatment is mandatory. Methods: Study recorded demographics, treatment and outcome of consecutive patients treated with IT plus surgery for IIIAN2 or IIIB NSCLC. Survival was analysed by Kaplan–Meier and prognostic factors were analysed by log-rank and Cox regression. Results: From 1993 to 2003, 155 patients (IIIAN2=95/IIIB=60) were treated. Complete resection was associated with a significant prolonged median survival both for IIIAN2 (20 vs 16 months, P=0.05) and IIIB (20 vs 15 months, P=0.02) patients. A lower risk of death for IIIAN2 patients was independently associated with postoperative mediastinal lymph node clearance (HR=0.45, 95%CI [0.25–0.81], P=0.009) and absence of postoperative complication (HR=0.54, 95%CI [0.31–0.93], P=0.02). Absence of blood vessel invasion only was identified as an independent predictor of a lower risk of death (HR=0.27, 95%CI [0.12–0.59], P=0.01) for stage IIIB patients. Conclusions: Besides similarities as the role of a complete R0 resection, treatment-related factors influence outcome of IIIAN2 patients while disease-related factors prevail on survival of IIIB patients, in whom the benefit of IT is unclear. [Copyright &y& Elsevier]

Abstract: Objective: Controversy continues over the optimal extent of lymphadenectomy for the surgical treatment of Adenocarcinoma of the oesophagus. Methods: From 1996 to 2003, 102 transthoracic en-bloc esophagectomy were performed for adenocarcinoma. Based on the 1994 consensus conference of the International Society of Disease of Esophagus, 35 patients underwent standard lymphadenectomy whereas 67 underwent extended lymphadenectomy. Mortality, morbidity and long-term survival were reviewed in each group. Results: Extended lymphadenectomy increased the number of resected lymph nodes and improved the healthy/invaded lymph node ratio. It allowed to detect skip nodal metastasis in 36.4% of the N+ patients. Morbidity was higher following extended lymphadenectomy, with respect to pulmonary complications, and blood transfusions requirement (P=0.04). However, operative mortality was similar in both groups (9 vs. 11%). Overall disease-free survival was 28% at 5 years. Median of survival was higher in N0 than in N+ patients (55 months vs. 20 months; P=0.02). Extended lymphadenectomy was associated with an improving of disease-free survival when compared to standard lymphadenectomy (41 vs. 10% at 5 years; P&#60;0.05), especially in the subgroup of patients with a N0 disease (median of survival 44 months vs. 17 months; P=0.001). Based on multivariable analyses, predictive factors of recurrence affecting disease free-survival were the pT status (P=0.02), standard lymphadenectomy (P=0.05) and extracapsular lymph node involvement (0.04). Conclusions: These results indicate that extended 2-field lymphadenectomy is an important component of the surgical treatment of patients with adenocarcinoma of the oesophagus. It increases the likelihood of proper staging and affects patient outcome, while it does not enhance the operative mortality. However, extended lymphadenectomy increases non-fatal morbidity, especially the incidence of pulmonary complications and the need for blood transfusion. [Copyright &y& Elsevier]

Abstract: Objective: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). Methods: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. Results: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (±SD) numbers of removed lymph nodes were 7±6.1 per patient following LS vs.18.6±9.3 following LA (P=0.001). An average mean of 1±0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7±0.8 following LA (P&#60;10−6). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00–2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. Conclusions: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy. [Copyright &y& Elsevier]

Objective: To assess the role of video-assisted thoracoscopic surgery (VATS) in the management of a recurrent primary spontaneous pneumothorax after a prior talc pleurodesis. Methods: From 1996 to 2002, we retrospectively reviewed all patients who were treated for a recurrent primary spontaneous pneumothorax after a previous talc pleurodesis. Data on the talc procedure and the recurrent pneumothorax, delay between both, and operative features were studied. Conversion rate to a thoracotomy and postoperative complications as well as long-term outcome were reported. Results: We collected 39 patients (28 male) with a median age of 25 years (15–41 years). The initial procedure consisted of thoracoscopic talc poudrage in all cases. The median delay between the talc procedure and the recurrence was 23 months [10 days–13 years]. Size of recurrence involved 10–80% of the hemithorax. The VATS procedure was successfully achieved in 27 patients (69%) while 12 required conversion to a thoracotomy. The main cause for conversion was the presence of dense pleural adhesion at the mediastinal part of the pleural cavity. Postoperative morbidity was limited to pleural complications in the VATS group (n=6, 22%). Median follow-up was 26 months [10–38 months]. One patient treated by VATS developed a partial recurrent pneumothorax at 12 months with a favorable outcome without further surgery. Conclusions: Feasibility, safety and efficacy of VATS for management of recurrent primary spontaneous pneumothorax following thoracoscopic talc poudrage are strongly suggested. [Copyright &y& Elsevier]

Objective: Analysis of a single institution experience with completion pneumonectomy. Methods: From 1989 to 2002, 55 consecutive cancer patients received completion pneumonectomy (mean age 62 years; 25–79). Indications were bronchogenic carcinoma in 38 patients (4 first cancers, 8 recurrent cancers, 26 second cancers), lung metastases in three (one each from breast cancer, colorectal neoplasm and lung cancer), lung sarcoma in one, and miscellaneous non-malignant conditions in 13 patients having been surgically treated for a non-small cell lung cancer previously (bronchopleural fistula in 4, radionecrosis in 3, aspergilloma in 2, pachypleura in 1, massive hemoptysis in 1 and pneumonia in 2). Before completion pneumonectomy, 50 patients had had a lobectomy, three a bilobectomy, and two lesser resections. The mean interval between the two procedures was 51 months for the whole group (1–469), 60 months for lung cancer (12–469), 43 months for pulmonary metastases (21–59) and 29 months for non-malignant disorders (1–126). Results: There were 35 right (64%) and 20 left (36%) resections. The surgical approaches were a posterolateral thoracotomy in 50 cases (91%) and a lateral thoracotomy in five cases (9%). Intrapericardial route was used in 49 patients (89%). Five patients had an extended resection (2 chest wall, 1 diaphragm, 1 subclavian artery and 1 superior vena cava). Operative mortality was 16.4% (n=9): 11.9% for malignant disease (n=5) and 30.8% for benign disease (n=4). Operative mortality was 20% for right completion pneumonectomies (n=7) and 10% for left-sided procedures (n=2). Twenty-three patients (42%) experienced non-fatal major complications. Actuarial 3- and 5-year survival rates from the time of completion pneumonectomy were 48.4 and 35.2% for the entire group. Three- and five-year survival for patients with bronchogenic carcinoma were 56.9 and 43.4%, respectively. Conclusions: These results suggest that completion pneumonectomy in the setting of lung malignancies can be done with an operative risk similar to the one reported for standard pneumonectomy. In contrast, in cancer patients, completion pneumonectomy for inflammatory disorders is a very high-risk procedure. [Copyright &y& Elsevier]

Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma with pure bronchoalveolar growth pattern and no evidence of stromal, vascular or pleural invasion (1999 WHO criteria), that seems to increase in incidence actually. BAC has its proper clinical spectrum, occurring more frequently in women and in younger patients. BAC also seems to be less dependent on tobacco exposure. Furthermore, original feature of this type of lung cancer is its intrapulmonary spreading and being infrequently systemic. Thus, surgical resection appears to have a pivotal role. This review of the literature attempted to assess whether or not patients with BAC should be treated according to the same oncological principles as those recommended for other non-small cell lung cancers, i.e. performance of anatomical resection combined with lymphadenectomy, and development of multimodality therapeutic strategies. Unilateral multinodular or pneumonic forms are best removed by lobectomy, or pneumonectomy when appropriate, combined with lymphadenectomy. Segmentectomy or wedge resection is a valuable option for the treatment of solitary lung nodules with pure pathological BAC patterns, provided specific conditions based upon computed tomography scan findings are present. The place of multimodality strategies is still unexplored. Treatment of bilateral BAC is challenging. Incomplete resection may be performed to palliate a severe intrapulmonary shunting. However, one hope of cure is provided by lung transplantation, even though disappointing results with disease recurrence on the grafts have been reported. The lack of large studies including only pure BAC gives a place for future biological and clinical research on this cancer. [Copyright &y& Elsevier]

: Background:The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB.: Methods:Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA).: Results:Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 ± 164 days and 307 ± 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 ± 323 and 152 ± 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups.: Conclusions:These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered. [Copyright &y& Elsevier]

Objective: Bronchoalveolar lavage (BAL) fluid provides a crucial tool for investigation of the cellular component of the deep lung spaces and hence to approach the alloreactive response following lung transplantation. This study investigated whether BAL cell profiles can assist for the diagnosis of certain postoperative complications. Methods: We conducted a retrospective analysis of both transbronchial biopsy and bronchoalveolar lavage materials in a series of 26 consecutive lung transplant recipients (LTR) in relationship with their clinical status at the time of the procedure. BAL fluid was subjected to cell morphology as well as flow cytometric phenotypic analyses. The samples were labeled as follows: normal transplant in clinically stable and healthy recipients, n=58; acute rejection (AR), n=58; infection (INF), n=31; and obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS) n=27. Results: Total BAL cell counts were the highest in INF. Lymphocytic alveolitis was suggestive of both acute allograft rejection and CMV viral infection, with a combined significant increased HLA-DR positive cells in AR. Alveolar neutrophilia with an increased CD4/CD8 ratio was correlated with the diagnosis of OB. The neutrophil percentages, HLA-DR and CD57 positive cells were significantly higher when an infection was present. Conclusion: These findings suggest that BAL cell analysis could give complementary information of histological data and further insight into immunologic events after lung allograft. A longitudinal surveillance of BAL cell profiles in an individual patient may be suggestive for a preclinical state of posttransplant acute rejection, bacterial infection and obliterative bronchiolitis. [Copyright &y& Elsevier]