Davide Tosi

Extracorporeal membrane oxygenation with spontaneous breathing as a bridge to lung transplantation

OBJECTIVES A large number of transplantation centres consider extracorporeal membrane oxygenation as an inappropriate option for bridging critical patients to lung transplantation. Technical improvements such as the introduction of a polymethylpentene membrane, new centrifugal pumps and heparin-coated circuits have led to a safer application of extracorporeal membrane oxygenation, and an increasing number of centres are reporting their positive experiences. The aim of this study was to review our practice in bridging critical candidates to lung transplantation with extracorporeal membrane oxygenation, by comparing patients with invasive mechanical ventilation with patients with spontaneous breathing. METHODS The records of candidates for lung transplantation treated with extracorporeal membrane oxygenation have been revised. RESULTS From February 2008 to 2012, 11 patients who experienced an abrupt worsening of their respiratory conditions were treated with extracorporeal membrane oxygenation; mean age: 33.9 ± 13.2 years, male/female ratio: 5/6, 6 patients were affected by cystic fibrosis, 2 had chronic rejection after transplantation, 2 had pulmonary fibrosis and 1 had systemic sclerosis. Seven patients were awake, while 4 patients received invasive mechanical ventilation. The sequential organ failure assessment score significantly increased during bridging time and this increase was significantly higher in the intubated patients. All the patients had bilateral lung transplantation. Spontaneously breathing patients showed a tendency to require a shorter duration of invasive mechanical ventilation, intensive care unit stay and hospital stay after transplantation. One-year survival rate was 85.7% in patients with spontaneous breathing vs 50% in patients with invasive mechanical ventilation. CONCLUSIONS Extracorporeal membrane oxygenation in spontaneously breathing patients is a feasible, effective and safe bridge to lung transplantation.

Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low‐flow, open atrium and low hematocrit technique. Thirty‐five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X‐ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

Muscle sparing versus posterolateral thoracotomy for pulmonary lobectomy: randomised controlled trial

Muscle sparing thoracotomy (MST) has been proposed as an alternative to posterolateral thoracotomy (PLT) for pulmonary lobectomy. This issue has been addressed by few clinical reports. To explore that subject, a prospective, controlled randomised, double-blind trial comparing MST through the auscultatory triangle and PLT was planned. The study included patients scheduled for pulmonary lobectomy for stage I or II non-small-cell lung cancer and were followed for three years. The primary endpoints were pain, analgesic consumption and post-thoracotomy pain syndrome. The secondary endpoints included morbidity plus shoulder and pulmonary functions. The trial randomised 100 patients into two groups. Postoperative pain results were similar, although analgesic consumption was higher in the PLT group (P=0.001). The MST group had a shorter hospital stay (P=0.003). Three years post-thoracotomy syndrome was unaffected by the type of incision. The women suffered more than men during the early and late postoperative time. An inverse correlation between incision length and pain was found. Immediate shoulder strength was significantly better in the MST group (P=0.004) but postoperative pulmonary function and complications were comparable. The two incisions results were very similar in the patient outcome, however, few aspects indicated the MST as the more suitable incision for pulmonary lobectomy.

Alveolar adenoma of the lung: unusual diagnosis of a lesion positive on PET scan. A case report.

The authors report a clinical case of alveolar adenoma presenting as a solitary pulmonary nodule which was positive to PET and deeply located in the lung. Few cases of alveolar adenomas have been reported in literature; these lesions are considered pulmonary neoplasms with benign behaviour, usually presenting as a peripheral or subpleural coin lesion; the PET activities of such neoplasms were unknown.The present clinical case was singular for the deep location of the nodule and its tight adhesion to left inferior pulmonary vein requiring a lobectomy. In addition, alveolar adenoma PET behaviour has been reported as light positivity.

Sternal reconstruction for unusual chondrosarcoma: innovative technique

The authors report a clinical case of a primary sternal chondrosarcoma, presented as a mass in the anterior mediastinum. The patient was treated with subtotal sternectomy and sternal transplantation followed by radiotherapy. Twelve months after surgery, the patient is in good clinical condition, without any sign of tumor relapse and with normal respiratory mechanics.Primary malignant tumors of the sternum are uncommon and a presentation mimicking thymoma is rare and unreported. The stermal replacement with a cryopreserved allograft sternum is an innovative technique that overcomes the problems related to the prosthetic biocompatibility or to the bone autograft.

Leukocyte subsets dynamics following open pulmonary lobectomy for lung cancer: a prospective, observational study.

This study was planned to observe prospectively the effects of standard open pulmonary lobectomy on leukocyte subsets and their connection with oncological outcome. Leukocyte subsets from 200 patients undergoing pulmonary lobectomy were analyzed: 151 patients had non-small-cell lung cancer, and 49 had non-malignant diseases. Blood samples were taken for leukocyte flow cytometry before and five, 30 and 60 days after operation. The end points were: observation of postoperative leukocyte subsets that are dynamic in patients with lung cancer vs. patients without malignant disease; correlations between leukocyte subsets trend and disease-free interval or survival; and identification of prognostic factors related to preoperative leukocyte subsets. Lymphocyte counts significantly decreased at five days after lobectomy while monocyte counts increased, and complete recovery of the preoperative leukocyte setting was documented at 30 and 60 days. The patients with lung cancer showed a significant low percentage of human leukocyte antigens on their monocytes before surgery (P=0.0017), followed by a peculiar disarrangement of leukocytes subsets compared with patients without malignant disease at the five-day control point. There was no correlation between leukocyte subset dynamics and disease free interval or survival. This study proves reductions of T-, B and natural killer cells, and the expression of DR on T-lymphocyte after pulmonary lobectomy; oncological patients were significantly less affected by surgery than non-cancer patients.

Genetic susceptibility variants for lung cancer: replication study and assessment as expression quantitative trait loci.

Many single nucleotide polymorphisms (SNPs) have been associated with lung cancer but lack confirmation and functional characterization. We retested the association of 56 candidate SNPs with lung adenocarcinoma risk and overall survival in a cohort of 823 Italian patients and 779 healthy controls, and assessed their function as expression quantitative trait loci (eQTLs). In the replication study, eight SNPs (rs401681, rs3019885, rs732765, rs2568494, rs16969968, rs6495309, rs11634351, and rs4105144) associated with lung adenocarcinoma risk and three (rs9557635, rs4105144, and rs735482) associated with survival. Five of these SNPs acted as cis-eQTLs, being associated with the transcription of IREB2 (rs2568494, rs16969968, rs11634351, rs6495309), PSMA4 (rs6495309) and ERCC1 (rs735482), out of 10,821 genes analyzed in lung. For these three genes, we obtained experimental evidence of differential allelic expression in lung tissue, pointing to the existence of in-cis genomic variants that regulate their transcription. These results suggest that these SNPs exert their effects on cancer risk/outcome through the modulation of mRNA levels of their target genes.

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.

VATS lobectomy combined with limited Shaw-Paulson thoracotomy for posterolateral Pancoast tumor.

Purpose Several techniques have been proposed for the challenging surgical resection of Pancoast tumors. We describe a hybrid approach that combines video-assisted thoracic surgery (VATS) lobectomy and limited Shaw-Paulson thoracotomy. Methods We report a case of Pancoast tumor in a 57-year-old man, staged as cT3N0M0, that was treated with induction chemoradiotherapy prior to the hybrid surgical approach. After thoracoscopic pleural cavity inspection, an upper right VATS lobectomy by a 3-port standard approach was performed. The chest wall was resected through a limited paravertebral incision, allowing the extraction of the lobe together with the rib segments. The posterior chest wall defect was repaired with a synthetic patch. Results The postoperative period was uneventful and the pain never exceed a score of 3 on a visual analogue scale. Pathological examination revealed nonvital tumor cells in the specimen (ypT0N0M0). The patient is disease free at 6 months’ follow-up. Conclusions With this approach we experienced excellent access to both the apical and hilar structures. Further experiences are needed to validate the role of VATS lobectomy in the multidisciplinary management of posterior Pancoast tumor.

Autoimmune hepatitis: an uncommon presentation of thymoma

Purpose In a substantial proportion of patients with thymoma, many different types of paraneoplastic syndromes are observed. The association between thymoma and autoimmune liver diseases, however, has been found in very few cases. Methods We report the case of a 31-year-old man affected by autoimmune hepatitis associated with myasthenia gravis and thymoma, successfully treated with extended thymectomy. Results The patient is free from neoplastic and hepatic disease 4 years after surgery. Eighteen months after thymectomy, an exacerbation of hepatitis was successfully treated with steroids. Conclusions To the authors’ knowledge, only 7 cases of myasthenia gravis associated with thymoma and autoimmune hepatitis have been reported in the English-language literature. The exact role of thymoma in immune-mediated hepatitis is unclear. It seems likely that thymoma-associated T-cell abnormalities, due to the presence of thymoma, may have a role in the development of this rare clinical triad of autoimmune hepatitis, thymoma and myasthenia gravis.