Lung Cancer Surgery in Octogenarians: Implications and Advantages of Artificial Intelligence in the Preoperative Assessment.

The general world population is aging and patients are often diagnosed with early-stage lung cancer at an advanced age. Several studies have shown that age is not itself a contraindication for lung cancer surgery, and therefore, more and more octogenarians with early-stage lung cancer are undergoing surgery with curative intent. However, octogenarians present some peculiarities that make surgical treatment more challenging, so an accurate preoperative selection is mandatory. In recent years, new artificial intelligence techniques have spread worldwide in the diagnosis, treatment, and therapy of lung cancer, with increasing clinical applications. However, there is still no evidence coming out from trials specifically designed to assess the potential of artificial intelligence in the preoperative evaluation of octogenarian patients. The aim of this narrative review is to investigate, through the analysis of the available international literature, the advantages and implications that these tools may have in the preoperative assessment of this particular category of frail patients. In fact, these tools could represent an important support in the decision-making process, especially in octogenarian patients in whom the diagnostic and therapeutic options are often questionable. However, these technologies are still developing, and a strict human-led process is mandatory.

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients.

We investigated humoral and T-cell response to a SARS-CoV-2 mRNA vaccine in solid organ transplant recipients (SOT-Rs) and healthy donors (HDs) before (T0) and after two (T1) and twelve months (T2) since the third dose administration. SOT-Rs were stratified according to the transplanted organ and to the time elapsed since the transplant. In SOT-Rs, detectable levels of anti-S antibodies were observed in 44%, 81% and 88% at T0, T1 and T2, respectively. Conversely, anti-S antibody levels were detected in 100% of HD at all time points. Lower antibody titers were observed in SOT-Rs compared to HDs, even stratifying by transplanted organs and the time elapsed since transplant. Lower percentages of responding and polyfunctional T-cells were observed in SOT-Rs as well as in each subgroup of SOT-Rs compared to HDs. At both T0 and T1, in SOT-Rs, a predominance of one cytokine production shortly was observed. Conversely, at T2, a dynamic change in the T-cells subset distribution was observed, similar to what was observed in HDs. In SOT-Rs, the third dose increased the rate of seroconversion, although anti-S levels remained lower compared to HDs, and a qualitatively inferior T-cell response to vaccination was observed. Vaccine effectiveness in SOT-Rs is still suboptimal and might be improved by booster doses and prophylactic strategies.

Torque teno virus (TTV): A gentle spy virus of immune status, predictive marker of seroconversion to COVID-19 vaccine in kidney and lung transplant recipients.

To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and nonresponsive patients was observed, considering a 5 log10 TTV copies/mL threshold to discriminate between the two groups. Moreover, for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/mL threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients.

Evaluation of Immunogenicity to Three Doses of the SARS-CoV-2 BNT162b2 mRNA Vaccine in Lung Transplant Patients.

The aim of the study was to explore the humoral and T-cell response in lung transplant (LuT) patients. Two-time points were considered, before (T0) and after (Tpost) the third dose of the BNT162b2 mRNA vaccine, comparing LuT with healthy donors (HD). LuT patients showed a lower serologic response against SARS-CoV-2 compared with HD at both time-points (p = 0.0001 and p = 0.0011, respectively). A lower percentage of IFNγ+orIL2+orTNFα+CD4+ and CD8+ T-cells LuT patients was observed in LuT patients compared with HD at T0 (CD4+: p = 0.0001; CD8+: p = 0.0005) and Tpost (CD4+: p = 0.0028; CD8+: p = 0.0114), as well as in the percentage of IFNγ+IL2+TNFα+CD4+ T-cells (T0: p = 0.0247; Tpost: p = 0.0367). Finally, at Tpost, a lower percentage of IFNγ+IL2+TNFα+ CD8+ T-cells in LuT patients compared with HD was found (p = 0.0147). LuT patients were stratified according to the lowest cut-off value for the detection of a humoral response (4.81 BAU/mL) at T0, into responder (R) and non-responder (NR) groups. In the R group, no differences in the percentage of IFNγ+or IL2+orTNFα+ and IFNγ+IL2+TNFα+CD4+ and CD8+ T-cells compared with HD at both time-points were observed. Otherwise, in the NR group, lower percentages of IFNγ+IL2+TNFα+CD4+ T-cells compared with the R group (T0: p = 0.0159; Tpost: p = 0.0159), as well as compared with the HD, at both time-points, were observed (T0: p = 0.0064; Tpost: p = 0.0064). These data seem to confirm that some LuT patients can mount cellular responses even in the absence of a positive humoral response (>33.8 BAU/mL), although this cellular response is dysfunctional and partially detrimental.

Use of Ceftazidime-Avibactam and Ceftolozane-Tazobactam After Lung Transplantation.

INTRODUCTION: After lung transplantation (LTx), infections caused by multidrug-resistant (MDR) bacteria are frequent and difficult to treat. Some new antibiotics seem to be effective in treating these infections. MATERIAL AND METHODS: We describe our experience in treatment of Klebsiella pneumoniae MDR and Pseudomonas aeruginosa MDR infections with ceftazidime-avibactam (CEF-AVI) and ceftazidime-tazobactam (CEFT-TAZ) in patients who underwent LTx. RESULTS: In 3 patients who underwent double LTx and in 4 patients who underwent single LTx, strains of K. pneumoniae and P. aeruginosa were isolated from bronchoalveolar lavage. All patients showed worsening of respiratory functions, increasing in inflammation indexes, and, in some cases, onset of pulmonary consolidation. P. aeruginosa was treated with CEFT-TAZ for 10 days average (7-15 days) and K. pneumoniae with CEF-AVI for 14 days average (4-24 days). One patient developed a septic state caused by K. pneumoniae, requiring 24 days of therapy. None had shown side effects caused by drugs administration. One patient died after 15 days from lung transplant owing to primary graft dysfunction. CONCLUSIONS: CEF-AVI and CEFT-TAZ seems to be effective in treatment of infections caused by MDR bacteria after lung transplant.

Inflammatory Myofibroblastic Tumor After Lung Transplant-A Rare and Aggressive Complication: A Case Report.

INTRODUCTION: Malignant diseases are well-known complications after lung transplantation (LT). Among these, inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with a not well-known and often aggressive biological behavior. MATERIAL AND METHODS: We hereby describe 2 cases of cystic fibrosis patients who underwent bilateral sequential LT (BSLT) complicated by IMT. RESULTS: A 26-year-old man presented a right endobronchial lesion 6 months after BSLT. Two consecutive fiber bronchoscopic biopsies showed granulation tissue. For the persistent lesion growth, the patient underwent a transthoracic biopsy showing histologic diagnosis of IMT. Therefore, he underwent to right pneumonectomy that was unfortunately complicated after 6 months with a late bronchopleural fistula and empyema with exitus 6 months later. A 31-year-old woman 1 year after BSLT presented with a left voluminous pleural-parenchymal lesion; the histologic examination after biopsy revealed an IMT. She underwent a removal of the lesion with a macroscopic R0 resection. Histologic, immunophenotypic, and cytogenetic examinations showed a strong overexpression of anaplastic lymphoma kinase requiring biological adjuvant therapies; however, the patient refused it. Four years later, she presented a recurrence treated with debulking procedure and adjuvant radiotherapy. At last follow-up, the patient was alive with stable disease and optimal graft function. CONCLUSIONS: Although IMT is a rare complication after lung transplant, to obtain a careful diagnosis, an early and aggressive treatment is mandatory.

Bronchoscopic treatment of emphysema: an update.

Chronic obstructive pulmonary disease (COPD) is the major causes of disability and mortality. The efficacy of maximal medical treatment, although effective at the early stages of the disease, becomes limited when extensive alveolar destruction is the main cause of respiratory failure. At this stage of the disease more aggressive options, when feasible, should be considered. Lung transplantation and lung volume reduction surgery (LVRS) are currently available for a selected group of patients. Endoscopic alternatives to LVRS have progressively gained acceptance and are currently employed in patients with COPD. They promote lung deflation searching the same outcome as LVRS in terms of respiratory mechanics, ameliorating the distressing symptom of chronic dyspnea by decreasing the physiological dead space.

Pulmonary metastasectomy in uterine malignancies: outcome and prognostic factors.

BACKGROUND: This retrospective study is designed to evaluate factors affecting survival in a population of patients receiving pulmonary metastasectomy after gynecologic cancers. METHODS: Nineteen patients with isolated lung metastases (one or two) were surgically treated with R0 resection. Four of them underwent lobectomies. RESULTS: Six patients (31.6%) received adjuvant therapy and 11 (58%) experienced recurrences after metastasectomy. Five- and ten-year survival were 40.9% and 31.4%, respectively. Five-year survival in patients receiving adjuvant therapy was 52.4%. At multivariate analysis factors negatively influencing survival were a disease-free interval (DFI) of less than 24 months and recurrence after pulmonary metastasectomy. CONCLUSIONS: Pulmonary resection for metastatic gynecologic cancer is feasible and effective; adequate selection of patients is mandatory to achieve satisfactory results and long-term survival.

Multimodality treatment of stage II thymic tumours.

BACKGROUND: Complete resection for stage II thymic tumors can be easily accomplished even if the capsula and adjacent mediastinal tissue are macroscopically involved; however, also at this stage, recurrence may occur, particularly for B2, B3 and thymic carcinoma. The criteria for the administration of adjuvant therapy remain controversial and it is unclear whether patients at this stage may benefit from it. We reviewed a series of patients at this stage receiving adjuvant chemo-radiotherapy (chemo-RT) based on histology. METHODS: Eighty-eight consecutive patients with stage II thymic tumors were reviewed; 59 patients (67%) with B thymoma or thymic carcinoma received adjuvant treatment with mediastinal irradiation (40-55 Gy), chemotherapy (CH) (PAC regimen) or a combination of both. RESULTS: Complete resection was achieved in all patients. Fifty-four patients (61%) received post-operative chemo-RT, 2 (2%) patients received adjuvant CH only and 3 (3%) post-operative RT only; they all had B2, B3 histology or thymic carcinoma. The median follow up was 107±83 months. 5-year and 10-year survival were 96%±2% and 83.4%±5%. Recurrence was observed in 5 patients (5.7%). Disease-free 5 and 10-year survival was 94%±2% and 92%±3% respectively. Five patients (5.7%) had recurrence. CONCLUSIONS: The administration of adjuvant chemo-RT to patients with stage II type B thymoma and thymic carcinoma contributes to reduce the recurrence rate and to increase long-term survival.

Devastating fast-growing lung cancer after single lung transplantation.

Patients receiving lung transplantation are at increasing risk for the development of cancer due to the administration of immunosuppressive drugs. We hereby report the case of a patient with a devastating fast-growing lung cancer after single lung transplantation for pulmonary fibrosis.

Uniportal video assisted thoracoscopic lobectomy: going directly from open surgery to a single port approach.

Uniportal video-assisted thoracoscopy (VATS) has gaining a special place in the thoracic surgery scenario; nowadays even major pulmonary resections can be performed through this approach. We hereby review our initial experience with uniportal VAT lobectomy, performed passing directly from the open approach to a single port approach. We attempted 26 lobectomies through VATS with a single incision of about 5 cm and 22 of them were completed: eight left lower lobectomies, six right upper lobectomies, five left upper lobectomies and three right lower lobectomies. At pathological staging all but four patients were stage I; three patients were T2N1M0 and one had a micrometastasis in a lymph node of station 7 (T1N2M0-Stage IIIA) and they all underwent adjuvant chemotherapy. No perioperative mortality was observed. One patient had a myocardial infarction in the first postoperative day requiring placement of four stents and another one required thoracentesis after drainage removal. The mean time for drainage removal was 3 days and the length of hospitalization was 4.2±1.1. Pain as measured by the visual analogical scale (VAS) scale was graded as 4.9, 2.6 and 0.5 during the first postoperative day, at discharge and after 1 month respectively.

Correlation between collateral ventilation and interlobar lung fissures.

BACKGROUND: New bronchoscopic techniques for end-stage emphysema treatment are nowadays available; the presence of interlobar collateral ventilation (CV) and interlobar lung fissures (ILF) is crucial for patient selection. OBJECTIVES: Assessment of these variables has been reported previously, but it has never been anatomically validated in vivo. This is the purpose of our study. METHODS: Twenty-one patients undergoing lung resection for lung cancer were prospectively enrolled in this study. At operation, CV was assessed by the Chartis catheter system. ILF completeness at high-resolution computed tomography (HRCT) was retrospectively reviewed. The ILF status at HRCT and at surgery was compared; furthermore, the relationship between CV and ILF status was assessed. RESULTS: At HRCT, ILF were incomplete in 18 cases; at catheter evaluation, CV was present in 11 cases; 15 patients had incomplete ILF at operation. HRCT specificity, sensitivity and accuracy were 33, 93 and 76% compared with ILF status at surgery. HRCT accuracy was 90% on the right and 63% on the left. We demonstrated a high grade of probability of CV presence and incomplete ILF at surgery (odds ratio = 10.0). CONCLUSIONS: There is a correlation between ILF status and CV. Both catheter evaluation of CV and HRCT assessment of ILF show some limitations. However, the cumulative information provided by these techniques allows to reliably assess the anatomical ILF status.

Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema.

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV(1)) was 0.88 L · s(-1) (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of >12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV(1), RV, 6MWT and MRC score showed a statistically significant improvement (p ≤ 0.0001, p = 0.004, p = 0.03, p = 0.003 and p<0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.

Bilateral simultaneous inflammatory myofibroblastic tumor of the lung with distant metastatic spread.

Inflammatory myofibroblastic tumors (IMT) of the lung are considered rare and benign; however, involvement of adjacent thoracic organs, local recurrence and distant metastases have been described. The potential presence of distant metastases supports the hypothesis that those tumors should not be considered 'clinically' benign, although histological features suggest this attitude; thus, complete resection and careful follow-up are mandatory. We present a case of a bilateral pulmonary IMT with left adrenal gland metastasis in a patient with dyspnea and cough.