Nicola Santelmo

Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum coinfection after lung and liver transplantation in a cystic fibrosis patient.

ABSTRACT Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient.

Risk factors for early mortality and morbidity after pneumonectomy: a reappraisal.

BACKGROUND Pneumonectomy remains a high-risk procedure. Comprehensive patient selection should be based on analysis of proven risk factors. METHODS The records of 323 pneumonectomy patients were retrospectively reviewed. Multiple demographic data were collected. End points were operative mortality at 30 and at 90 days, major procedurally related complications, and cardiovascular events. Univariate and multivariate statistical analyses were performed. RESULTS Smoking habits, chronic obstructive pulmonary disease (COPD) status, induction chemotherapy status, diabetes, and obesity had no statistical influence on short-term outcomes. After right pneumonectomy, 30-day mortality (p = 0.045) and the incidence of bronchopleural fistulas (p = 0.009) were increased. Multivariate analysis for postoperative bronchopleural fistulas discovered that right pneumonectomies are the sole risk factor (p = 0.015). Univariate analysis for postoperative atrial fibrillation showed that male gender, age 70 and older, hypertension, and dyslipidemia are risk factors. Multivariate analysis found no definite risk factor. Patients with coronary artery disease had more postoperative cardiovascular events (p = 0.003). Among patients free of coronary artery disease, COPD led to an increased 90-day mortality rate (p = 0.028). CONCLUSIONS Patients with right pneumonectomies are at increased risk. Postoperative cardiovascular events are more frequent in coronary artery disease patients. COPD is a risk factor in patients free of coronary disease.

Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response §

INTRODUCTION Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. PATIENTS AND METHODS Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1-1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20mg/m2 d1-d5 and etoposide 50mg/m2 d1-d5, d1-5 d29-33. Within 3-4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4-6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20-25 Gy boost +/-1 extra-cycle of cisplatinum+etoposide. RESULTS From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median=26.7 months) for all the intention-to-treat population (n=107), 62% and 51% (median=36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median=19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio=0.50 and 0.48, p=0.006 and 0.038, respectively). CONCLUSION Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0-1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.

Does the use of extended criteria donors influence early and long-term results of lung transplantation?

A best evidence topic was constructed according to a structured protocol. The question addressed was whether the presence of extended criteria donors influences the early and long-term results in patients referred for lung transplantation. Of the 30 papers found using a report search, 14 presented the best evidence to answer the clinical question. The authors, journal, date, country of publication, study type, group studied, relevant outcomes and results of these papers are given. In total, we recorded 10 retrospective studies that considered all the donor criteria for comparing marginal donors (MDs) and standard donors. On the one hand, six of them showed no difference between the two groups in terms of early and long-term results. On the other hand, four studies demonstrated a negative impact of MDs on various early outcomes (mortality, primary graft dysfunction, duration of mechanical ventilation, length of stay in intensive care unit), whereas no significant negative influence on survival has ever been described when screening MD results. More precisely, when analysing the role of individual factors of marginality, as done in two of the 14 studies, a significant negative impact was observed for a low level of PaO(2) at the time of harvesting, positive bronchoscopy and smoking history. More specifically, the first two criteria have been validated by several authors, both in multicentre and cohort studies. Finally, the importance of avoiding the donation of the lung from an MD to a high-risk recipient emerged, whereas the association with single or bilateral transplants remains more controversial. Hence, current evidence suggests that there are no contraindications-given the absence of negative impact on survival-for the use of MDs for the transplant of a proposed standard receiver. However, given the low level of evidence of published studies, caution is necessary in order to avoid organ shortage, despite these encouraging results.

Intra-operative paravertebral block for postoperative analgesia in thoracotomy patients: a randomized, double-blind, placebo-controlled study

OBJECTIVE Epidural analgesia is the gold standard for post-thoracotomy pain relief but is contraindicated in certain patients. An alternative is paravertebral block. We investigated whether ropivacaine, administered through a paravertebral catheter placed by the surgeon, reduced postoperative pain. METHODS In a randomized double-blind study, adult patients with a paravertebral catheter placed by the thoracic surgeon after thoracotomy were randomly assigned to receive through this catheter, either a 0.1 mlkg(-1) bolus of 0.5% ropivacaine, followed by a continuous infusion of 0.1 mlkg(-1)h(-1) for 48 h, or saline at the same scheme of administration. Patients also benefited from patient-controlled analgesia with intravenous morphine (bolus 1mg, lockout time 7 min), paracetamol, and nefopam. The primary endpoint was pain intensity on a visual analog scale at rest and on coughing. Secondary endpoints were total morphine consumption and side effects during the first 48 postoperative hours. Surgeons, anesthesiologists, and all the nurses and caring staff involved in this study were blinded. Solutions of saline and ropivacaine were prepared identically by the central pharmacy, without any possible identification of the product. RESULTS Forty-seven patients with contraindications to epidural anesthesia were included. There were no significant differences between the groups receiving ropivacaine and saline in terms of pain severity at rest and on coughing, mean postoperative morphine consumption (45.7 mg for ropivacaine, 43.2mg in controls), and incidence of morphine-related side effects (nausea and vomiting, urinary retention, pruritus, respiratory rate, and sedation). CONCLUSIONS Paravertebral block using a catheter placed by the thoracic surgeon was ineffective on postoperative pain after thoracotomy and did not confirm the analgesic effect that has been observed after percutaneous catheter placement. A direct comparison of these two placement methods is required.

Does nodal status influence survival? Results of a 19-year systematic lymphadenectomy experience during lung metastasectomy of colorectal cancer

OBJECTIVES Resection of pulmonary metastases originating from colorectal cancer is increasingly considered. While several adverse risk factors for long-term outcome are known, the selection of patients who may benefit from surgery remains unclear. In particular, few studies have addressed the impact of lymph node involvement, and signification of the hilar or mediastinal level of extent. METHODS We retrospectively reviewed the data of 320 patients operated in two thoracic departments between 1992 and 2011. Appropriate statistical tests were used to compare groups at risk. RESULTS There were 105 women and 215 men with a mean age of 63.3 years (range: 27-86) at the time of metastasectomy. Lymph node involvement appeared as a significant prognostic factor in both the univariate and multivariate analyses [median survival: 94 months N0 vs 42 months N+, P < 0.0001; OR = 0.573 (0.329-1), P = 0.05]. Survival was similar for hilar and mediastinal locations (median survival: 47 months vs 37 months, respectively, P = 0.14). Associated hepatic metastases had a negative impact on survival in both univariate and multivariate analyses [median survival: 74 months vs 47 months, P < 0.01; OR = 0.387 (0.218-0.686), P = 0.001]. Multiple lung metastases significantly decreased survival in univariate analysis only (median survival: 81 months vs 55 months, P < 0.01). Disease-free survival and preoperative carcinoembryonic antigen had no impact on survival. CONCLUSIONS While lymph node involvement was associated with decreased survival, the impact of mediastinal location on survival did not differ from that of hilar location. Consequently, these patients should not be excluded from surgical treatment.

Double lumen bi-cava cannula for veno-venous extracorporeal membrane oxygenation as bridge to lung transplantation in non-intubated patient

Extracorporeal membrane oxygenation (ECMO) is used for refractory respiratory failure. Normally, ECMO is implanted in intubated patients as a last resort. We report the case of a non-intubated patient who benefited from veno-venous (VV) ECMO. A 35-year old cystic fibrosis man presented a severe respiratory decompensation with refractory hypercapnia. We opted for an ECMO instead of mechanical ventilation (MV). We implanted a double lumen bi-cava cannula (DLC) (Avalon Elite(TM)) in the right jugular vein. Before ECMO implantation, the patient presented refractory respiratory failure (pH = 7.1, PaO(2) = 83 mmHg, PaCO(2 )= 103 mmHg). We proposed that the patient be placed on the high emergency lung transplantation waiting list after failure to wean him from ECMO. This registration was effective 10 days after ECMO implantation. The patient was grafted the next day. Under ECMO, mean PaO(2), PaCO(2) and TCA were 80.6 ± 14.2, 53.8 ± 6.4 mmHg and 56.2 ± 9.7 s, respectively. The patient could eat, drink, talk and practice chest physiotherapy. The evolution was uneventful under ECMO. Weaning from ECMO was done in the operating theatre after transplantation. VV ECMO with DLC is safe and feasible in non-intubated patients. It avoids potential complications of MV, and allows respiratory assistance as bridge to transplantation.

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.Methods:Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.Results:Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.Conclusions:mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.

Surgery for aspergilloma: time trend towards improved results?

Surgery of aspergilloma has been renowned to be technically challenging and has a high complication rate. We have already demonstrated an improved outcome as a result of a reduction in complex cases related to history of tuberculosis. In this paper we will evaluate whether this time trend has continued during recent years. Initial presentation and postoperative outcome of 33 patients who underwent surgical treatment between 1998 and 2009 were reviewed and compared with two previous reports (group 1: 55 patients from 1974 to 1991; group 2: 12 patients from 1992 to 1997). Underlying disease was tuberculosis in 15% of patients (57% in group 1, 17% in group 2), and 12% of patients had complex aspergillomas (80% in group 1, 41% in group 2). Postoperatively, there was no mortality (5% in group 1, 0% in group 2). Morbidity decreased progressively in terms of bleeding (44% in group 1, 9% in group 2, and 6% in recently, accrued patients), of pleural space problems (47%, 18% and 12%, respectively), and of prolonged hospital stay (32%, 8% and 6%, respectively). With a decreased postoperative complications rate after resection, contemporary surgery of aspergilloma is safe and offers satisfactory early and long-term results.

Persistent N2 Disease After Induction Therapy Does Not Jeopardize Early and Medium Term Outcomes of Pneumonectomy

BACKGROUND Operative management of patients with persistent N2 disease after induction therapy is still debated. METHODS One hundred fifty-three consecutive patients underwent pneumonectomy from January 1999 until July 2005; 28 patients (18.3%) had persistent N2 disease after induction therapy (group 1), 32 patients (20.9%) had pathologic stage N0 or N1 after induction therapy (group 2), and 93 patients (60.8%) with pathologic N2 disease underwent immediate surgery (group 3). Short-term end points were operative mortality at 30 and 90 days and major complications. Long-term end points were 5-year survival and disease-free survival rates. RESULTS Demographics of the three groups were similar (age, sex, side of operation, type of chemotherapy, smoking status, and comorbidity such as coronary artery disease, diabetes, and chronic obstructive pulmonary disease). Thirty-day postoperative mortality was 10.7% in group 1, 3.1% in group 2 (p = 0.257), and 4.3% in group 3 (p = 0.201); 90-day postoperative mortality was 10.7% in group 1, 12.5% in group 2 (p = 0.577), and 9.7% in group 3 (p = 0.558). Incidence of major postoperative complications was similar. Five-year survival rate was 32.2% (median, 28 months; 95% confidence interval, 7 to 43) in group 1, 34.8% (median, 27 months; 95% confidence interval, 7 to 47) in group 2 (p = 0.685), and 12.4% (median, 15 months; 95% confidence interval, 11 to 19) in group 3 (p = 0.127). No statistical difference was found in terms of 5-year event-free survival, or regarding the side of pneumonectomy. CONCLUSIONS Our results suggest that pneumonectomy is justified in patients with persistent N2 disease after induction chemotherapy.