Lobar Lung Transplantation From Deceased Donor: Monocentric Experience.

INTRODUCTION: Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation. METHODS: The aim of the current study was to analyze the outcome of lobar lung transplantation from deceased donors in our Lung Transplant Center. Overall survival, perioperative mortality and morbidity, problem on bronchial anastomosis, and chronic rejection were prospectively recorded in a 5-year time-frame. RESULTS: From November 2010 to October 2015, we performed 100 lung transplantations; 6 of which (6%) were lobar transplantations from deceased donors. Three recipients were on an emergency list due to preoperative extracorporeal support. The causes of lobectomy leading to lobar transplantation were: size mismatch (3), iatrogenic vascular damage (2), and chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and 5 patients were alive at the study end (median follow-up: 17.5 months). Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient developed bronchial stenosis. No cases of chronic rejection were recorded. CONCLUSIONS: Lobar transplantation can be considered a valid tool to overcome the donor pool shortage in selected cases; such a technique has proved particularly useful in critically ill patients who were scheduled in an emergency transplant program.

Successful Transplantation of Lungs From an Uncontrolled Donor After Circulatory Death Preserved In Situ by Alveolar Recruitment Maneuvers and Assessed by Ex Vivo Lung Perfusion.

We developed a protocol to procure lungs from uncontrolled donors after circulatory determination of death (NCT02061462). Subjects with cardiovascular collapse, treated on scene by a resuscitation team and transferred to the emergency room, are considered potential donors once declared dead. Exclusion criteria include unwitnessed collapse, no-flow period of >15 min and low flow >60 min. After death, lung preservation with recruitment maneuvers, continuous positive airway pressure, and protective mechanical ventilation is applied to the donor. After procurement, ex vivo lung perfusion (EVLP) is performed. From November 2014, 10 subjects were considered potential donors; one of these underwent the full process of procurement, EVLP, and transplantation. The donor was a 46-year-old male who died because of thoracic aortic dissection. Lungs were procured 4 h and 48 min after death, and deemed suitable for transplantation after EVLP. Lungs were then offered to a rapidly deteriorating recipient with cystic fibrosis (lung allocation score [LAS] 46) who consented to the transplant in this experimental setting. Six months after transplantation, the recipient is in good condition (forced expiratory volume in 1 s 85%) with no signs of rejection. This protocol allowed procurement of lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia.

Graft downsizing during ex vivo lung perfusion: case report and technical notes.

Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation.

Variations of thoracoabdominal volumes after lung transplantation measured by opto-electronic plethysmography.

BACKGROUND: Lung function after lung transplantation (LTx) has been widely studied. On the contrary, the thoracoabdominal volume rearrangement after LTx has yet to be investigated. METHODS: Patients with cystic fibrosis and listed for double LTx at our institution were enrolled for the prospective study to explore the effects of LTx on the rearrangement of respiratory volumes in patients affected by cystic fibrosis, by utilizing the opto-electronic plethysmography (OEP), a noninvasive method to study the volume and motion of the human trunk. Rib cage and abdominal volumes were tested with OEP (OEP system, BTS, Milano, Italy). RESULTS: Eight patients were enrolled (male-to-female ratio: 1:3; mean age 29.3 ± 7.8 years). After LTx the volume changes analyzed with OEP revealed a significant decrease of the total lung capacity (TLC) as well as the functional residual capacity and residual volume when the chest wall volume was considered. Dividing the whole respiratory volume in the three compartments showed different trends. CONCLUSIONS: We consider OEP a particularly useful device in patients with severe respiratory disease, in that it allows a noninvasive estimate of the volume change of the chest wall. This study demonstrates a significant reduction of thoracoabdominal volumes in patients affected by cystic fibrosis treated with bilateral LTx. Abdomen and upper rib cage were congruent with the volume reduction, while the lower rib cage showed an opposite tendency.

Extracorporeal lung perfusion and ventilation to improve donor lung function and increase the number of organs available for transplantation.

INTRODUCTION: Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation. MATERIAL AND METHODS: After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal membrane oxygenation (ECMO) bridge to transplantation with rapid functional deterioration. Using Steen solution with packed red blood cells oxygenated with 21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of approximately 40% predicted cardiac output. Once normothermic, the lungs were ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory rate of 7 bpm. Lungs were considered to be suitable for transplantation if well oxygenated [P(v-a) O(2) > 350 mm Hg on FiO(2) 100%], in the absence of deterioration of pulmonary vascular resistance and lung mechanics over the perfusion time. RESULTS: From March to September 2011, six lung transplantations were performed, including two with EVLP. The functional outcomes were similar between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP versus conventional). Intensive care unit ICU and hospital length of stay were similar (P = .533 and P = .663, respectively) with no mortality at 60 days in both groups. EVLP donors were older (49 ± 6 y versus 21 ± 7 y, P < .05), less well oxygenated (184 ± 6 mm Hg versus 570 ± 30, P < .05), displaying higher Oto scores (9.5 ± 0.7 versus 1.7 ± 1.5, P < .05). CONCLUSIONS: The first 6 months of the EVLP program allowed us to increase the number of organs available for transplantation with short-term outcomes comparable to conventional transplantations.

Use of the Oto lung donor score to analyze the 2010 donor pool of the Nord Italia Transplant program.

INTRODUCTION: The feasibility and utility of a lung donor score that has been recently proposed was tested among a pool of lung donors referred to the Nord Italia Transplant program (NITp) organ procurement organization. MATERIAL AND METHODS: Each lung donor was assigned an Oto score including, age, smoking history, chest X-ray, secretions and ratio of arterial oxygen tension to inspired oxygen fraction (PaO(2)/FiO(2)). Based on clinical compromise, each variable received a score between 0 and 3, except for PaO(2)/FiO(2), which was scored between 0 and 6 given its overall relevance. RESULTS: Throughout 2010, 201 multiorgan donors were initially considered to be potential lung donors. Among these, 59 (29.4%) eventually yielded 67 lung transplantations (named "Used group"). Among the 142 (70.6%) refused lungs, 28 were not used due to logistic or medical problems ("general exclusion" group, GE) and 114, because of poor lung function ("lung exclusion" group, LE). Median lung donor scores were 1 (range, 0 to 3), 4 (range, 2.5 to 6.5), and 7 (range, 5 to 9) in the Used, GE, and LE groups, respectively (one-way analysis of variance, P < .001). Some donors with Oto scores ≤7 worsened over time so that the score had significantly increased by the time of organ retrieval. Overall, subjects who died after lung transplantation were characterized by higher lung donor scores, (2 [1-4] versus 0.5 [0-3], P = .003). CONCLUSION: Our analysis suggested that the use of a donor score as a dynamic tool over the donation process was of great utility to describe and analyze a pool of lung donors.

Lung transplantation and posterior reversible encephalopathy syndrome: a case series.

Posterior reversible encephalopathy syndrome is a neurological problem characterized by headache, altered mental status, focal neurological deficits, visual disorders, and seizures. The disorder is related to a number of diseases including calcineurin inhibitor therapy in solid organ transplantation. The incidence of posterior reversible encephalopathy syndrome in lung transplantation patients is unclear; probably the majority of the cases are unreported. The authors have described a case series constituted of four patients presenting posterior reversible encephalopathy syndrome after bilateral lung transplantation. The cases had in common complicated surgery and a posttransplant course characterized by hypertension, hypomagnesemia and acidosis. Invasive mechanical ventilation, calcineurin inhibitor discontinuation, aggressive antihypertensive therapy, and electrolyte regulation led to near complete recovery of symptoms.

Early lung retransplantation in a patient affected by cystic fibrosis correlated with donor cause of death: a case report.

The relationship between donor cause of death and lung transplantation outcomes remains unclear. We report a case of lung transplantation in a young patient affected by cystic fibrosis. Immediately after lung reperfusion a pulmonary hypertension was observed that was intractable with maximal medical therapy requiring surgical resection of the left lower lobe which became congested after a few days. The donor had died from suicidal hanging; the authors attributed the posttransplantation pulmonary hypertension which is an uncommon form of primary graft dysfunction to this cause of death. The patient was treated with early bilateral lung retransplantation which required a long, troublesome hospital stay. In conclusion, the authors warn against the use of lungs from donors who die due to hanging even when the gas exchanges were ideal.

Late lung retransplantation using extracorporeal membrane oxygenation as a bridge: case report.

Lung retransplantation is the only therapeutic option for acute and chronic graft failure, but only a few cases have been described to have been performed with extracorporeal membrane oxygenation (ECMO) support. We describe the successful case of a 46-year-old man treated with right lung transplantation and left lung retransplantation supported by venovenous ECMO. Lung retransplantation is the only therapeutic option to treat severe primary graft dysfunction, major technical problems, and refractory chronic rejection following pulmonary transplantation. Despite a number of comprehensive studies on lung retransplantation, only a few works have addressed the use of extracorporeal membrane oxygenation (ECMO) as a bridge to the surgical reoperation. Herein we have presented a patient treated with pulmonary bilateral retransplantation subsequent to ECMO therapy for progressive deterioration of pulmonary function in single lung transplantation.

The consumption of glucose during ex vivo lung perfusion correlates with lung edema.

INTRODUCTION: Ex vivo lung perfusion (EVLP) has been recently proposed to recondition organs before transplantation from donors with marginal or unacceptable features. The aim of our investigation was to explore glucose consumption during EVLP. MATERIALS AND METHODS: We investigated 8 domestic pigs (mean weight, 21 ± 0.8 kg). After perfusion with Perfadex, retrieval, and back table surgery, we initiated EVLP. The lungs were perfused with Steen solution with added methylprednisolone, cefazoline, and heparin. The blood flow was gradually increased with a target of 40% of the estimated cardiac output (or less if the pulmonary artery pressure was >15 mm Hg), while keeping the left atrial pressure between 3 and 5 mm Hg. The temperature of the perfusate was increased from 25 °C to 37 °C. Once the temperature of the lung outflow was >32 °C, we began gas flow (4 L/min, 5%-8% CO(2) in air) and mechanical ventilation. EVLP parameters and blood gases were measured throughout the experiment; glucose consumption was calculated as (glucose initial-glucose final)/time. The wet to dry ratio was also calculated as an index of lung edema. RESULTS: When stratified by median glucose consumption (0.237 mg/min), high glucose consumers (0.588 ± 0.17) were characterized by worse lung function, as assessed by oxygenation (partial pressure of oxygen/inspiratory fraction of oxygen [PaO(2)/FiO(2)] 326 ± 63 mm Hg vs 218 ± 84; P=.083 low vs high, respectively), and lung edema (wet/dry ratio 6.5 ± 0.7 vs 8.6 ± 0.9; P=.012). Glucose consumption correlated with wet to dry ratio (R(2)=0.663; P=.014). CONCLUSIONS: We found that the worse the lung function, the greater the consumption of glucose during EVLP. This observation suggests the need to explore lung metabolism during EVLP to possibly obtain metrics for evaluation.

Primary pulmonary glomangioma: a coin lesion negative on PET study. Case report and literature review.

Glomus tumor is an uncommon perivascular lesion usually located in the dermis of the extremities. It rarely involves the respiratory tract or the lungs. We present the clinical and pathological features of a 39-year-old man who was evaluated for an incidental radiological finding of a pulmonary nodule. A chest computed tomography (CT) confirmed the presence of an upper left lobe coin lesion. Bronchoscopy and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) were negative. An intraoperative frozen section examination was interpreted as a neuroendocrine tumor; therefore a left upper lobectomy with lymphadenectomy was performed. An immunohistochemical examination supported the diagnosis of a primary pulmonary glomangioma. The patient was free of disease at the 51-month follow-up. Due to its uncertain behavior we stress the usefulness of typical lung resection, lymph node dissection, and accurate follow-up.

Bridge to lung transplantation by venovenous extracorporeal membrane oxygenation: a lesson learned on the first four cases.

Extracorporeal membrane oxygenation (ECMO) is the only therapeutic option for patients with ventilation-refractory hypercapnia while awaiting lung transplantation. Moreover, there is increasing success using ECMO for definitive respiratory failure in formerly healthy patients. This report describes the use of membrane oxygenation as a bridge to lung transplantation in 2 patients on the waiting list and in 2 previously healthy patients. Our experience showed that coagulation management, critical illness myopathy, and psychological disorders were the most critical problems. One patient died at 2 days after transplantation, 1 at 3 months, and 2 returned to their pretransplantation activities. We concluded that ECMO is an adequate bridge to lung transplantation but, especially in formerly healthy patients, an awake procedure is advisable for a successful outcome.

Use of venovenous extracorporeal membrane oxygenation as a bridge to urgent lung transplantation in a case of acute respiratory failure.

Several transplant centers consider pretransplant extracorporeal membrane oxygenation (ECMO) as a contraindication for lung transplantation because of the poor outcomes. However, some technical improvements have changed the scenario; there is increasing evidence of ECMO efficacy as a bridge to lung transplantation. This report describes the successful use of venovenous ECMO as a bridge to an urgent bilateral lung transplantation and as treatment for primary graft dysfunction in a case of hyperacute pulmonary fibrosis in a 58-year-old man. Our experience demonstrated that ECMO, using Quadrox, supported respiratory functions for 28 days without any detrimental effects, serving as a successfully bridge to urgent lung transplantation.

Immunocytochemical detection of occult tumor cells in the bone marrow: prognostic impact on early stages of lung cancer.

OBJECTIVES: This study was designed to verify the prognostic impact of occult tumor cells in the bone marrow of stage I and II non-small-cell lung cancer patients using cytokeratin as a micrometastatic marker. METHODS: One hundred and fifty-two patients with stage I and II non-small-cell lung cancer, who underwent radical surgery by pulmonary lobectomy, were entered into the study. Bone marrow from fragments of resected ribs, and primary tumors were stained by anti-cytokeratin 18 antibody. Fourteen bone marrow specimens from patients without malignancy were used as a control group. Cancer recurrence was the study end point. RESULTS: All the primary tumors were positive for cytokeratin; occult tumor cells were detected in 38 bone marrow specimens (25%). The prevalence of the occult tumor cells was not related to age, gender, tumor stage, histological differentiation or grade. The mean follow-up time was 35.3 months; 68 patients developed recurrence; the mean time for recurrence was 21.2 months. The general disease-free interval was not related to the presence of occult tumor cells in the bone marrow. This result did not change when grouping the patients by tumor stage. The stage was the best predictor of cancer recurrence (Cox proportional hazards model ratio: 2.09; p = 0.0026). CONCLUSIONS: This study confirms that immunocytochemical analysis detects occult tumor cells in the bone marrow of at least 25% of patients surgically treated for stage I and II non-small-cell lung cancer. These occult tumor cells do not have any impact on the disease-free interval.

Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line.

We have previously reported that the peptide a-melanocyte stimulating hormone (alpha-MSH) has antiproliferative effects in human malignant mesothelioma cells. To determine the molecular mechanisms underlying such effects, we investigated the changes in gene expression profile induced by the alpha-MSH analog [Nle4 -DPhe7 ]-alpha-MSH (NDP-alpha-MSH) in a human malignant mesothelioma cell line. The cDNA macroarray technique revealed changes in expression of genes involved in cell growth, adhesion, signal transduction, and transcription. In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer. Further, NDP-alpha-MSH exerted a favorable transcriptional regulation of certain integrins and their signaling pathways. Finally, peptide treatment was associated with a prominent inhibition of IL-13, a cytokine with tumor-promoting effects. The data indicate that the influences of alpha-MSH extend beyond the established anti-inflammatory effects in normal cells to include cell cycle regulatory properties in malignant cells.

Unusual presentation of a transparietal cavernous hemangioma of the esophagus.

Hemangiomas are tumors of vascular origin and represent less than 3% of benign neoplasm of the esophagus. We herein report a case of a 55-year-old man, who presented transitory dysphagia and weight loss. A malignancy could not be excluded by a complete work-up, including esophagogram, endoscopic biopsies, CT scan, esophageal endoscopic ultrasonography, PET and thoracoscopic biopsies. Only after partial esophagectomy with laparoscopic gastric mobilization was histological diagnosis obtained. In fact, on microscopic observation of the specimen, the neoplasm appeared to be a cavernous hemangioma of the esophageal submucosa with transparietal extension.

[Various genetic cardiac diseases predispose to arrhythmias and the risk of sudden death]. / Sindromi aritmiche ereditarie: importanza in anestesia e rianimazione.

Identification of underlying genetic factors has added to understanding of arrhythmogenic triggers and determinants of sudden death. Many factors (medications, bradycardia, temperature changes) during general anesthesia could precipitate malignant dysrhythmia in these patients. Criteria for risk stratification for surgical patients are not available: we can only extrapolate information collected from medical patients. We describe 4 patients with suspected Brugada syndrome (only one was confirmed) during genera anesthesia and propose an anesthesiologic management during operation and for the postoperative period (36 hours).

Positive end-expiratory pressure applied to the dependent lung during one-lung ventilation improves oxygenation and respiratory mechanics in patients with high FEV1.

BACKGROUND AND OBJECTIVE: The aim of this study was to test the efficacy of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation, taking into consideration underlying lung function in order to select responders to PEEP. METHODS: Forty-six patients undergoing open-chest thoracic surgical procedures were studied in an operating room of a university hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP) or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral decubitus. The patients were stratified according to preoperative forced expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above 72%). Oxygenation was measured in the supine position, in the lateral decubitus with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system pressure-volume curve of the dependent hemithorax was measured in supine and open-chest lateral decubitus positions with a super-syringe. RESULTS: Application of 10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did not occur in ZEEP group, considered as a time matched control. PEEP improved oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P < 0.05). There was no significant change in the low FEV1 group. Dependent hemithorax compliance decreased in lateral decubitus, more in patients with high FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). CONCLUSIONS: During one-lung ventilation in lateral decubitus, PEEP applied to the dependent lung significantly improves oxygenation and respiratory mechanics in patients with rather normal lungs as assessed by high FEV1.