Colistin-based Treatment of Multidrug-resistant Gram-negative Bacterial Pulmonary Infections After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is a viable option for a select group of patients with end-stage lung disease. However, infections are a major complication after LT, accounting for significant morbidity and mortality. Several germs may be responsible; multidrug-resistant Gram-negative (MDR-GN) bacteria are emerging. Colistin is widely used in the treatment of these infections and is administered by inhalation and/or parenterally. At our institution, in patients with tracheostomy, colistin is administered by direct instillation in the airway during bronchoscopy. We reviewed a series of patients who underwent LT complicated by postoperative MDR-GN bacterial pulmonary infection. METHODS: From January 2015 to May 2017, 26 lung transplants were performed. In the postoperative course, 14 (54%) developed MDR-GN bacterial infection; respiratory specimen culture, blood tests, and chest X-ray were considered. Colistin was the only antibiotic usable. Thirteen patients received intravenous (IV) colistin; in the subgroup of patients with tracheostomy, colistin was instilled directly in the airway, and 6 patients received inhaled colistin. RESULTS: Seven patients needed tracheostomy. Pseudomonas aeruginosa was the predominant infection (86%), with Acinetobacter baumanii seen in 2 cases (14%). An early clinical-laboratory response was observed in 9 patients (64%). White blood cell count and C-reactive protein values improved (P = .02 and P = .001, respectively). A significant reduction in bacterial load was observed on microbiologic bronchoalveolar lavage specimens. CONCLUSION: Colistin instilled directly in the airway did not show side effects. The combination of IV and inhaled/instilled colistin could be a useful treatment option for MDR-GN infections after LT.

Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV1) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV1 range after treatment between -6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence. DISCUSSION: ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.

Evaluation of Renal Function in Patients Undergoing Lung Transplantation.

BACKGROUND: Acute kidney injury and chronic kidney failure are serious complications after lung transplantation. Glomerular filtration rate (GFR) is the primary indicator of renal function. Several equations have been proposed to evaluate the estimated GFR (eGFR). We compared three different equations to determine which has the better correlation with the development of acute and chronic renal failure in lung recipients. METHODS: Twenty-two patients with a mean age of 54.4 ± 8.5 years underwent lung transplantation from 2010 to 2015. Thirteen (59%) had pulmonary fibrosis, 7 (32%) emphysema, 1 (4.5%) bronchiectasis, and 1 (4.5%) lymphangioleiomyomatosis. In all patients, eGFR was measured preoperatively using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Levey's Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. In 20 patients (90%) eGFR was calculated at 1, 3, and 6 months. RESULTS: According to CKD-EPI and MDRD, eight patients (36.3%) had preoperative reduction in eGFR, whereas 6 patients (27.2%) had preoperative reduction according to the CG (P = .04). The mean values were higher for the CG (103.2 vs. 102 vs. 94.4). Five patients (22.7%) developed perioperative acute renal failure requesting a dialysis treatment; four of these showed a preoperative eGFR to the highest CG (P = .05). At 1 and 6 months after lung transplantation, the CG, MDRD and CKD-EPI eGFR values were, respectively, 86.6, 84.1 and 76.6 mL/min/1.73m2 and 75.8, 72.7, and 72.3 mL/min/1.73m2. CKD-EPI eGFR values are more predictable than the other equations of AKI. CONCLUSIONS: Preoperative assessment of eGFR using the MDRD and CKD-EPI seems to correlate better than the CG to the prediction of acute renal failure, whereas for the chronic form the three equations seem equivalent.

Selection of Candidates for Lung Transplantation: The First Italian Consensus Statement.

Lung transplantation is a well-established treatment for selected patients with advanced chronic respiratory insufficiency. Recognizing those patients with end-stage lung disease who might benefit from lung transplantation is a crucial task. Considering the presence of inadequate evidence-based practice, international and national scientific societies provided consensus opinions regarding the appropriate timing of listing. The Study Group for Thoracic Organs Transplantation (branch of the Italian Society for Organs Transplantation) promoted and realized a Delphi conference among the Italian lung transplantation centers to provide guidance to clinical practice based on international recommendations. The experts from the nine Italian centers completed two rounds of standardized questionnaires (answer rate, 100%): 42 statements received a consensus ≥80%. The selected statements presented in this article are intended to assist Italian clinicians in selecting patients for lung transplantation.

A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.

Independent lung ventilation in the postoperative management of single lung transplantation: case report.

Independent lung ventilation (ILV) is a ventilation strategy used in patients with significant differences in respiratory mechanics between the 2 lungs owing to asymmetric or unilateral lung diseases. We report the case of a 66-year-old patient treated with ILV for a primary graft dysfunction occurred early after single lung transplantation. On intensive care unit admission, the patient was ventilated with pressure-controlled mechanical ventilation. Despite efforts to optimize ventilation and medical therapy, his clinical condition progressively worsened, manifesting hypoxemia, hypercapnia, and radiologic evidence of hyperinflation of the native lung, collapse of the graft, and mediastinal shift. The ventilation was therefore switched to ILV. A constant improvement in clinical conditions, arterial blood gas parameters, and radiologic findings was then obtained. The patients was weaned from mechanical ventilation and finally successfully extubated.

Extracorporeal membrane oxygenation as bridge to lung transplantation.

Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in selected patients with satisfactory long-term results. However, the paucity of available donors engenders a prolonged stay on the waiting list with progressive decline of lung function. In cases of sudden respiratory failure, admission to an intensive care unit with institution of extracorporeal membrane oxygenation (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we started ECMO because of acute decline of lung function. Eleven patients had cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral OLT was performed after a mean waiting time of 6 days from ECMO institution; 5 patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2 patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient died in the perioperative period and 1-year survival was 85.7%. ECMO represents a valid option as a bridge to urgent OLT for selected candidates.

Low-flow venovenous CO2 removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. METHODS: From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. RESULTS: No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. CONCLUSION: The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation.

Lung transplantation for cystic fibrosis: outcome of 101 single-center consecutive patients.

Bilateral sequential lung transplantation (BSLT) is nowadays considered a valid therapeutic option for patients with end stage cystic fibrosis. We report our experience with 104 BSLTs in 101 patients. The overall survivals at 1, 3, 5, 10 years were 79%, 65%, 58%, and 42%, respectively. Perioperative mortality was 14.8% (n = 15). The leading causes of perioperative mortality were primary graft dysfunction and sepsis. Three patients were retransplanted owing to obliterative bronchiolitis. In 70 cases (69%), patients displayed ≥ 1 additional risk factors: previous lung resections, colonization by Burkholderia cepacia, diabetes, pneumothorax, or noninvasive ventilatory support. The mean preoperative 1-second forced expiratory volume of 0.69 ± 0.2 L (22%) increased to 85% at 1 year after the operation. The mean time on the waiting list was 12 ± 5 months. The 5 patients treated with extracorporeal membrane oxygenation before urgent transplantation were operated after 3, 5, 6, 30, and 3 days respectively. During the procedure, cardiopulmonary bypass was required in 33 patients (32%). Lung transplantation represents a unique opportunity to ameliorate the quality and improve the survival of patients affected by cystic fibrosis. Timing of referral and patient selection remain crucial for success.

Pulmonary hypertension is associated with higher mortality in cystic fibrosis patients awaiting lung transplantation.

AIM: Pulmonary hypertension (PH) is frequently found in patients with advanced parenchymal lung diseases. In advanced stages, cystic fibrosis (CF) patients can develop PH and eventually cor pulmonale. Little is known about the prevalence of PH in CF patients and its impact on outcome. METHODS: We retrospectively studied a large cohort of CF patients evaluated for lung transplantation between 1995 and 2010. All the patients underwent right heart catheterization as part of the evaluation. We included 179 unique consecutive adult CF patients. Age was 24±9 years and 45.8% were women. RESULTS: Eighty-seven patients were transplanted (48.6%) and 65 died (36.3%) while waiting for LT. By right heart catheterization, 38.5% of the patients had PH (mean ≥25 mm Hg). PaCO(2) (P=0.045) and forced vital capacity (P=0.023) were independent predictors of PH in CF patients. The median survival (free of lung transplantation) was 13.4 months. After adjusting for several covariates, the presence of PH significantly increased mortality (hazard ratio, HR) (P<0.001). Pulmonary vascular resistance was associated with mortality (P=0.03). When both PH and PVR were included in the model, only PH predicted mortality. CONCLUSION: Pulmonary hypertension of mild degree is frequently found in CF patients with advanced lung disease and its presence significantly worsens survival.

Pulmonary hypertension is associated with higher mortality in cystic fibrosis patients awaiting lung transplantation.

AIM:Pulmonary hypertension (PH) is frequently found in patients with advanced parenchymal lung diseases. In advanced stages, cystic fibrosis (CF) patients can develop PH and eventually cor pulmonale. Little is known about the prevalence of PH in CF patients and its impact on outcome. METHODS: We retrospectively studied a large cohort of CF patients evaluated for lung transplantation between 1995 and 2010. All the patients underwent right heart catheterization as part of the evaluation. We included 179 unique consecutive adult CF patients. Age was 24±9 years and 45.8% were women. RESULTS:Eighty-seven patients were transplanted (48.6%) and 65 died (36.3%) while waiting for LT. By right heart catheterization, 38.5% of the patients had PH (mean ≥25 mm Hg). PaCO2 (P=0.045) and forced vital capacity (P=0.023) were independent predictors of PH in CF patients. The median survival (free of lung transplantation) was 13.4 months. After adjusting for several covariates, the presence of PH significantly increased mortality (hazard ratio, HR) (P<0.001). Pulmonary vascular resistance was associated with mortality (P=0.03). When both PH and PVR were included in the model, only PH predicted mortality. CONCLUSION: Pulmonary hypertension of mild degree is frequently found in CF patients with advanced lung disease and its presence significantly worsens survival.

Lung transplantation for cystic fibrosis after thoracic surgical procedures.

During their life, cystic fibrosis (CF) patients may require thoracic surgical procedures for a number of reasons before undergoing lung transplantation. In the past, this has been considered to be a contraindication to lung transplantation. However, a meticulous surgical technique and careful intraoperative management allows one to perform the transplantation safely. Herein we have reported our experience with CF patients undergoing lung transplantation after previous surgical treatment for pneumothorax or bronchiectasis.

Treatment of complex airway lesions after lung transplantation with self-expandable nitinol stents: early experience.

Airway complications (AC) are considered a serious cause of morbidity after lung transplantation (LT). Mechanical dilatation, laser vaporization, and silicone stent placement usually solve it. However, the use of self-expandable metallic stents (SENS) may be indicated in selected cases. Ten lung transplant recipients with AC were treated with SENS. Six patients underwent LT for cystic fibrosis, 2 for idiopathic pulmonary fibrosis, 1 for bronchiectasis, and 1 for emphysema. All patients received at least 1 treatment attempt with dilatation and silicone stent placement. The indications for SENS placement were the presence of a tortuous airway axis with stenosis and malacia of the right main bronchus in 5 patients; a long stenosis of the main and intermediate right bronchus involving the upper lobe orifice in 3 patients; or malacia that could not be stabilized with silicone stents in 3 cases. In 1 patient the procedure was bilateral. Functional improvement was immediate with a mean forced expiratory volume at 1 second (FEV(1)) gain of 35%. No stent dislocation was observed. Symptoms did not occur again in 5 patients with previous recurrent episodes of pneumonia. One stenosis, which was due to the ingrowth of granulation tissue occurred at 6 months after the procedure, was successfully treated with mechanical dilatation and laser vaporization. The deployment of SENS in a selected group of patients with AC after LT was easy, safe, and effective.

Extracorporeal circulatory support for lung transplantation: institutional experience.

Lung transplantation (LT) represents the only available therapy for selected patients affected by end-stage pulmonary disease. Cardiopulmonary bypass (CPBP) is used, when required, during single and sequential double lung transplantation; however, it increases the risk of bleeding, early graft dysfunction, failure, and other potential side effects. We report our experience with 145 patients who underwent lung transplantations, among whom 34 required intraoperative CPBP. The indications for LT among these 34 patients were cystic fibrosis (n = 22), chronic obstructive pulmonary disease (n = 3), bronchiectasis (n = 2), primary pulmonary hypertension (n = 1), fibrosis (n = 2), pulmonary microlithiasis (n = 1), and retransplantation for obliterative bronchilitis (n = 3). CPBP was planned in 12 cases (group I) and unplanned in 22 (group II). The main reason for planning CPBP was primary and secondary pulmonary hypertension (mean pulmonary artery pressure >or=25 mm Hg). Acute right ventricular failure, hemodynamic instability, arterial desaturation, and increased pulmonary artery pressure were mandatory for unplanned CPBP. Among the 34 CPBP patients, the 30-day mortality rate was 35% (12/34) including 9 (70%) in group II (unplanned CPBP). The leading cause of death was multiorgan failure. The 1-year survival rates were 67% and 36%, and the 3-year survival rates were 47% and 18% for groups I and II, respectively. In conclusion, even if it represents a useful tool in the management of critical events, the use of unscheduled CPBP during LT procedures is associated with an increased postoperative morbidity and mortality.

Surgical treatment of redundancy after retrosternal esophagocoloplasty.

Redundancy is a well-recognized complication of esophageal replacement with colonic interposition, occurring several years after surgery. In a small number of patients, symptoms are disabling and might require reoperation. This article describes the surgical treatment of a 54-year-old male presenting with severe dysphagia, malnutrition and recurrent aspiration pneumonia, progressively developed 30 years after esophageal replacement with retrosternal ileocolonic interposition for caustic strictures.

Sub-lobar lung resection of peripheral T1N0M0 NSCLC does not affect local recurrence rate.

BACKGROUND AND AIMS: The use of sub-lobar resection versus lobectomy for stage I non small cell lung cancer is still controversial. This study was undertaken to compare the results of limited resection in terms of survival and local recurrence rate to lobectomy in patients with peripheral stage I non small cell lung cancer. MATERIAL AND METHODS: During the 8 year period from 1999 to 2007, 152 consecutive patients with stage I non-small cell lung cancer underwent lung resection at our thoracic surgery unit. In 116 cases we performed a standard lobectomy while in the remaining 36 cases we did sub lobar resection through mini-thoracotomy or video-assisted thoracoscopy. The survival, local recurrence rate and the clinical outcome were analyzed and compared. RESULTS: Fifty-one patients were staged as T1 N0 M0, 22 in the sub-lobar resection group (61,1%) and 29 (25%) in the lobectomy group. The remaining were staged as T2 N0 M0. Although the patient population undergone to sub-lobar resection was older, with poorer lung function and more co-morbidities, the Kaplan-Meier survival proportion at 5 year did not differ significantly between the two groups: 64% for lobectomy group vs 66,7% for sub-lobar resection group. Overall local recurrence did approach significance in favour of lobectomy group but analyzing only T1 patients, no differences in terms of survival and local recurrence rate were observed. CONCLUSIONS: The results of this study indicate that in patients with peripheral T1N0M0 non small cell lung cancer the outcome of limited resection is comparable with that of pulmonary lobectomy.

Lung transplantation for cystic fibrosis: ten years of experience.

Lung transplantation represents the only therapeutic option for patients affected by end-stage cystic fibrosis (CF). We performed 76 lung transplantations in 73 patients from 1996-2007. The mean time on the waiting list was 10+/-6 months. The median follow-up after the transplantation was 69.3 months. Twenty-one transplants (27.6%) were performed under cardiopulmonary bypass. Perioperative mortality, excluding retransplants, was 16.4% (12 patients) and the causes of death were sepsis, primary graft failure, and myocardial infarction. The overall survival was 74.5%+/-5%, 62.9%+/-5%, 54.1%+/-6%, and 43.4%+/-6% at 1, 3, 5, and 10 years, respectively. The accurate selection of potential recipients and the correct timing of referral and transplantation are factors that play crucial roles to obtain satisfactory results in term of improvement of quality of life and long-term survival.

Non-Hodgkin's lymphoma, presenting as an isolated endobronchial mass after bilateral lung transplantation: a case report.

BACKGROUND: Lymphoma is a serious complication following solid organ transplantation. Endobronchial involvement of non-Hodgkin's lymphoma (NHL) is rare usually occurring in the setting of widely disseminated disease. Only a few cases of isolated endobronchial NHL have been reported. They were mostly confined to the main bronchi. METHODS: Herein we have described a case of an obstructive endobronchial NHL lesion in a young patient, which developed 6 years after bilateral lung transplantation for cystic fibrosis. RESULTS: Successful treatment was obtained with endoscopic resection of the lesion followed by chemotherapy. CONCLUSIONS: In rare cases NHL may present as an isolated endobronchial mass in the main bronchi. Because in these cases the prognosis seems to be better, early diagnosis is essential. Rigid bronchoscopy offers the opportunity to safely obtain large amounts of tissue for complete histological diagnosis and to de-obstruct the airway to relieve the symptoms.

Preoperative anaemia does not affect the early postoperative outcome in patients with lung cancer.

AIM: Several prognostic factors like age, gender, histology, stage, type of operation, associated disorders and administration of induction therapy have been evaluated to assess the risk of postoperative complications and outcome in patients with resectable lung cancer. Anemia is a frequent condition in this subset of patients being estimated up to 50%. The aim of this retrospective study was to evaluate the effect of preoperative anemia on early outcome after lung cancer resection. METHODS: One-hundred thirty nine consecutive patients undergoing surgery for non small cell lung cancer were retrospectively considered. The mean age was 64.8+/-11.6 years. No patient received blood transfusions or administration of erythropoetin preoperatively. Overall, we performed 96 lobectomies, 14 pneumonectomies, 2 bilobectomies and 27 atypical resections. A subset of 27 patients (19.4%) (group I) had a preoperative value of Hb less than 12 g/dl (10.4+/-1.9 g/dL). Seven patients of them were stage IA (26%), 9 stage IB (33.3%), 2 stage IIA (7.4%), 6 stage IIB (22.2%), 2 stage IIIA (7.4%) and 1 stage IIIB (3.7%). Age, gender, stage, type of operation, induction chemotherapy, comorbidities were evaluated by univariate analysis comparing patients with and without preoperative anaemia. The two groups were homogenous regarding demographic characteristics. RESULTS: Three patients (11.1%) in group I and 2 (1.8%) in group II required blood transfusions after surgery (P=0.01); 4 of them received pneumonectomy (P<0.0001). The overall morbidity was 17.9% (25/139); the most frequent complication was persistent air leakage, followed by retention of secretions. No statistically significant difference was observed between the 2 groups about early mortality (1 patient-3.7% in group I and 2 patients-1.8% in group II) and postoperative complications (5 patients-18.5% in group I and 20 patients-17.9% in group II). CONCLUSION: Preoperative anaemia is not a risk factor for an increased rate of postoperative complications and should not be considered a contraindication to surgery.

Malignancies following lung transplantation.

During the last 2 decades, long-term survival after lung transplantation has significantly improved. However, among the complications related to the continuous administration of immunosuppressive drugs, malignancy plays an important role. We retrospectively revisited our series of patients to report our experience. From January 1991 we performed 134 lung transplantations in 128 recipients (mean age, 33.4 +/- 13.5 years). In all patients the first-line immunosuppressive regimen was based on a calcineurin inhibitor (cyclosporine or tacrolimus), an antimetabolic agent (azathioprine), and steroids. Five patients (4.2%) developed malignancy and the mean time of occurrence after the transplantation was 46.4+/-23 months. The mean age was 41 +/- 16 years (P = not significant [ns]). The tumors were as follows: laryngeal cancer (radiotherapy), colon cancer (surgery plus adjuvant chemotherapy), gastric cancer (surgery plus adjuvant chemotherapy), endobronchial non-Hodgkin lymphoma (NHL) (endoscopic resection plus chemoradiotherapy), and cutaneous and visceral Kaposi's sarcoma (KS) (chemotherapy). All patients have reduced the dose of immunosuppressive drugs; in 1 of them, tacrolimus was changed to rapamycin. Two patients died because of neoplastic dissemination, another 1 due to obliterans bronchiolitis. The 2 patients with NHL and KS are alive at 6 and 9 months, respectively, without signs of recurrence. Malignancies after lung transplantation represent an important problem. A multidisciplinary approach is mandatory to obtain satisfactory results in terms of improved quality of life and long-term survival.