Advances in Endoscopic Management of Endobronchial Carcinoid.

INTRODUCTION: Bronchial carcinoid (BC) tumors represent between 1% and 5% of all lung cancers and about 20-30% of carcinoid tumors; they are classified into two groups: typical and atypical bronchial carcinoids. The aim of the present study was to review the results of endoscopic treatments as an alternative to surgical treatment in selected patients. MATERIALS AND METHODS: The present study was a retrospective and multicentric study, in which all data were reviewed for patients with BC in the central airways, referred to the Thoracic Surgery Units of Luigi Vanvitelli University of Naples and Sant'Andrea Hospital in Rome between October 2012 and December 2022 Overall, 35 patients, 13 of whom were female, were included in the study (median age, 53 years; range, 29-75 years). All patients underwent rigid bronchoscopy combined with flexible bronchoscopy. Tumor clearance was mostly performed by use of Argon Plasma Coagulation or Thulep Laser, mechanical debridement and excision with the use of forceps and aspirator through the working channel of the 8.5 mm-sized rigid bronchoscope. There were no complications during the treatment. RESULTS: Endobronchial treatment provided complete tumor eradication in all patients; two patients had controlled bleeding complications; however, bleeding was well controlled without patient desaturation, and only one patient died of renal failure during the follow-up period. We found two recurrences in the left and right main bronchus, in patients with atypical carcinoma during fiberoptic bronchoscopy follow-up. Only one patient died of renal failure. At the first analysis, there were no significant differences between the patients receiving endobronchial treatment and patients receiving surgical treatment in the present study (p-value > 0.05-it means statistically insignificant). CONCLUSIONS: Endobronchial treatment is a valid and effective alternative for patients with BC unsuitable for surgery.

Intraoperative lung ultrasound improves subcentimetric pulmonary nodule localization during VATS: Results of a retrospective analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) resection of deep-seated lung nodules smaller than 1 cm is extremely challenging. Several methods have been proposed to overcome this limitation but with not neglectable complications. Intraoperative lung ultrasound (ILU) is the latest minimally invasive proposed technique. The aim of the current study was to analyze the accuracy and efficacy of ILU associated with VATS to visualize solitary and deep-seated pulmonary nodules smaller than 1 cm. METHODS: Patients with subcentimetric solitary and deep-seated pulmonary nodules were included in this retrospective study from November 2020 to December 2022. Patients who received VATS aided with ILU were considered as group A and patients who received conventional VATS as group B (control group). The rate of nodule identification and the time for localization with VATS alone and with VATS aided with ILU in each group were analyzed. RESULTS: A total of 43 patients received VATS aided with ILU (group A) and 31 patients received conventional VATS (group B). Mean operative time was lower in group A (p < 0.05). In group A all the nodules were correctly identified, while in group B in one case the localization failed. The time to identify the lesion was lower in group A (7.1 ± 2.2 vs. 13.8 ± 4.6; p < 0.05). During hospitalization three patients (6.5%; p < 0.05) in group B presented air leaks that were conservatively managed. CONCLUSION: Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.

Intraoperative ventilatory leak: Real-time guidance for management of air leak in lung cancer patients undergoing VATS lobectomy.

BACKGROUND: Persistent air leak (PAL) is a common complication after video-assisted thoracoscopic surgery (VATS) lobectomy. We aimed to evaluate whether the intraoperative quantitative measurement of air leaks using a mechanical ventilation test could predict PAL and identify those patients needing additional treatment for the prevention of PAL. METHODS: This was an observational, retrospective, single-center study that included 82 patients who underwent VATS lobectomy with a mechanical ventilation test for VL. Only 2% of patients who underwent lobectomy surgery had persistent air leaks. RESULTS: At the end of lobectomy performed in patients with non-small cell lung cancer, the lung was reinflated at a 25-30 mmH2O pressure and ventilatory leaks (VL) were calculated and in relation to the entity of the air leaks, we evaluated the most suitable intraoperative treatment to prevent persistent air leaks. CONCLUSION: VL is an independent predictor of PAL after VATS lobectomy; it provides a real-time intraoperative guidance to identify those patients who can benefit from additional intraoperative preventive interventions to reduce PAL.

Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection.

BACKGROUND: The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study's focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. METHODS: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. RESULTS: Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1-2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3-0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3-0.7), PM = 0.0005, PMC = 0.005]. CONCLUSIONS: The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation.

BACKGROUND: Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity. METHODS AND FINDINGS: A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate. CONCLUSIONS: KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.

Role of human leukocyte antigen-G 14-base pair polymorphism in kidney transplantation outcomes.

BACKGROUND: Both the membrane-bound and soluble forms of human leukocyte antigen-G (HLA-G) molecules exhibit a multitude of immunomodulatory properties that can potentially obviate or delay graft rejection. The 14-base pair (14-bp) polymorphism in the 3'-untranslated region of the HLA-G gene is thought to have a role in soluble HLA-G (sHLA-G) expression. METHODS: In this study, we retrospectively investigated a large cohort of 418 kidney transplant recipients with the aim of establishing whether the HLA-G 14-bp insertion/deletion polymorphism could serve as an effective genetic risk marker for acute and/or chronic deterioration of transplanted kidney function. RESULTS: A statistically significant higher incidence of chronic kidney dysfunction leading to allograft loss was observed in transplant recipients homozygous for the HLA-G 14-bp deletion polymorphism. This difference increased over time and was confirmed by progressive decline in the glomerular filtration rate. CONCLUSIONS: These results suggest that alongside other factors previously consolidated in clinical practice, recipient HLA-G 14-bp genotype may serve as an adjuvant independent predictor of long-term outcome of kidney transplantation.

HLA-G gene polymorphism in human placentas: possible association of G*0106 allele with preeclampsia and miscarriage.

Definite causes for several pathologies of pregnancy remain unknown. In light of several recent studies, however, diminished or aberrant HLA-G expression may be associated with certain complication of pregnancy and be linked to HLA-G polymorphism. We analyzed DNA from 60 normal placentas (controls), 140 placentas from miscarriage, 36 placentas from preeclampsia, 76 placentas from fetal hypotrophy, and 34 placentas with hypoxia for variations in coding regions (allelic groups G*0101 to G*0107) and the 14-bp deletion/insertion into the 3'-untranslated region. No statistically significant differences were observed in the distribution of allelic group between pathological placentas and controls with the exception of G*0106 allele frequency in preeclamptic compared with control placentas (21.2% and 6.6%, respectively). A greater frequency of this allele also was observed in the two subgroups of miscarriage and hypoxia compared with that in controls. In addition, presence of the 14-bp sequence was prominent in preeclampsia compared with controls (60.8% vs. 35%, respectively), and homozygotes with deletion were not detected in the pathology. The results suggest that the G*0106 allele, which is coupled with the presence of the 14-bp sequence, contributes and/or is a relevant marker in some specific complications of pregnancy, especially preeclampsia.

The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia.

The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30.2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (-14-bp/-14-bp vs +14-bp/+14-bp: Relative Risk = 15.0; 95% confidence interval 1.59-141.24; P = 0.008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation.