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10
result(s) for
"Nicola Santelmo"
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Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases
by
Beau-Faller, Michèle
,
Santelmo, Nicola
,
Reeb, Jérémie
in
692/699/67/1612/1350
,
692/699/67/1857
,
692/700/1750
2015
Background:
Identifying patients who will experience lung cancer recurrence after surgery remains a challenge. We aimed to evaluate whether mutant forms of epidermal growth factor receptor (
EGFR
) and Kirsten rat sarcoma viral oncogene homolog (
KRAS
) (
mEGFR
and
mKRAS
) are useful biomarkers in resected non-small cell lung cancer (NSCLC).
Methods:
We retrospectively reviewed data from 841 patients who underwent surgery and molecular testing for NSCLC between 2007 and 2012.
Results:
mEGFR
was observed in 103 patients (12.2%), and
mKRAS
in 265 (31.5%). The median overall survival (OS) and time to recurrence (TTR) were significantly lower for
mKRAS
(OS: 43 months; TTR: 19 months) compared with
mEGFR
(OS: 67 months; TTR: 24 months) and wild-type patients (OS: 55 months; disease-free survival (DFS): 24 months). Patients with
KRAS
G12V exhibited worse OS and TTR compared with the entire cohort (OS:
KRAS
G12V: 26 months
vs
Cohort: 60 months; DFS:
KRAS
G12V: 15 months
vs
Cohort: 24 months). These results were confirmed using multivariate analyses (non-G12V status, hazard ratio (HR): 0.43 (confidence interval: 0.28–0.65),
P
<0.0001 for OS; HR: 0.67 (0.48–0.92),
P
=0.01 for TTR). Risk of recurrence was significantly lower for non-
KRAS
G12V (HR: 0.01, (0.001–0.08),
P
<0.0001).
Conclusions:
mKRAS
and
mEGFR
may predict survival and recurrence in early stages of NSCLC. Patients with
KRAS
G12V exhibited worse OS and higher recurrence incidences.
Journal Article
Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis
by
Villegas, José A.
,
Berrih-Aknin, Sonia
,
Truffault, Frédérique
in
Analysis
,
Animals
,
Autoantibodies
2023
Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR
+
autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR
+
MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects.
Journal Article
Early postoperative prophylactic noninvasive ventilation after major lung resection in COPD patients: a randomized controlled trial
by
Jean-François Regnard
,
Laurent Quinquis
,
Benjamin Planquette
in
Acute respiratory distress syndrome
,
Analysis
,
Anesthesiology
2014
Objectives
To investigate whether prophylactic postoperative NIV prevents respiratory complications following lung resection surgery in COPD patients.
Methods
In seven thoracic surgery departments, 360 COPD patients undergoing lung resection surgery were randomly assigned to two groups: conventional postoperative treatment without (
n
= 179) or with (
n
= 181) prophylactic NIV, applied intermittently during 6 h per day for 48 h following surgery. The primary endpoint was the rate of acute respiratory events (ARE) at 30 days postoperatively (ITT analysis). Secondary endpoints were acute respiratory failure (ARF), intubation rate, mortality rate, infectious and non-infectious complications, and duration of ICU and hospital stay.
Measurements and main results
ARE rates did not differ between the prophylactic NIV and control groups (57/181, 31.5 vs. 55/179, 30.7 %,
p
= 0.93). ARF rate was 18.8 % in the prophylactic NIV group and 24.5 % in controls (
p
= 0.20). Re-intubation rates were similar in the prophylactic NIV and control group [10/181 (5.5 %) and 13/179 (7.2 %), respectively,
p
= 0.53]. Mortality rates were 5 and 2.2 % in the control and prophylactic NIV groups, respectively (
p
= 0.16). Infectious and non-infectious complication rates, and duration of ICU and hospital stays were similar between groups.
Conclusions
Prophylactic postoperative NIV did not reduce the rate of ARE in COPD patients undergoing lung resection surgery and did not influence other postoperative complications rates, mortality rates, and duration of ICU and hospital stay.
Journal Article
Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma
by
Guerrera, Francesco
,
Beau-Faller, Michèle
,
Santelmo, Nicola
in
Adenocarcinoma
,
Clonal deletion
,
Epidermal growth factor receptors
2018
BackgroundThe prognostic value of exon 19 and 21 EGFR mutations in stage IV non-small cell lung cancer (NSCLC) is well established.ObjectiveWe aimed to evaluate the prognostic value of the mutations in surgically resected NSCLC.MethodsWe retrospectively reviewed data from 1798 surgically resected NSCLC adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was known. Overall survival (OS) was evaluated using log-rank and Cox proportional hazard models.ResultsEGFR exon 19 deletion was observed in 108 patients (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In stage I, the median OS was not significantly different between exons 19 and 21 (p = 0.54), while, in stage II, the median OS reached 65 months [95% confidence interval (CI) 41.67–88.33] for exon 19 mutations and decreased to 48 months for exon 21 mutations (95% CI 44.21–51.79; p = 0.027). In multivariate analysis, exon 19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95% CI 0.098–0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI 44.67–87.32) for exon 19 mutations and decreased to 32 months for exon 21 mutations (95% CI 29.86–34.14; p = 0.03). In multivariate analysis, exon 19 deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI 0.027–0.999; p = 0.05).ConclusionThe prognostic value of EGFR exon 19 and 21 mutations appears to be different according to disease stage in surgically resected NSCLC.
Journal Article
Video-assisted thoracoscopic surgery is a safe option for benign lung diseases requiring lobectomy
2017
Background
Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated.
Methods
We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the
χ
2
test and Student’s
t
test; any
p
value ≤0.05 was considered as significant.
Results
Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (
p
< 0.001), history of cancer (
p
< 0.001), history of stroke (
p
= 0.05), and the presence of pleural adhesions (
p
= 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate.
Conclusions
We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context.
Journal Article
Superior sulcus non small cell lung carcinoma: retrospective analysis of 42 patients
2014
Aims
Retrospective, monocentric analysis of localized superior sulcus non-small cell cancer (SS-NSCLC), article management.
Materials and methods
Between 2000 and 2010, 42 patients have been treated for a SS-NSCLC. Median age was 54.7 years (34.5-86.8). Nineteen tumors (45.2%) were stage IIB, 18 were stage IIIA (42.9%) and 5 were stage IIIB (11.9%). Twenty-two patients were treated by pre-operative radiotherapy or chemoradiotherapy, 20 received exclusive radiotherapy or chemoradiotherapy. Preoperative and exclusive median radiotherapy doses were 46 Gy (40–47 Gy) and 51.8 Gy (40–70 Gy), respectively. All patients treated with chemotherapy received at least platinum. Mean follow up was 44.1 months (0–128 months).
Results
Local, loco-regional and metastatic relapses occurred in 11 (26.2%), 2 (4.8%) and 15 patients (35.7%), respectively. Most common metastatic site was cerebral (7 patients, 46.7%). Median disease-free survival (DFS) was 9.7 months (8.9-10.4). One-, 2- and 5- years DFS rates were 44%, 33% and 26.5%, respectively. No prognostic factor was identified.
Median overall survival (OS) was 22.6 months (10.4-34.8). One-, 2- and 5- years OS rates were 61.9%, 44.9% and 30.1%, respectively. Univariate prognostic factors for OS were WHO (p = 0.027) and tumoral response (p = 0.05). In multivariate analysis, independent favorable prognostic factors were WHO 0–1 (p = 0.017; OR = 0.316 [CI95% 0.123-0.81) and complete response to treatment (p = 0.035; OR = 0.312 [IC95% 0.106-0.919]).
Conclusion
This study highlighted that a good performans status and complete response to treatment are independent factors of OS, whatever the delivered treatment. Brain was the most common metastatic relapse site.
Journal Article
Bronchioloalveolar Lung Carcinoma
by
Santelmo, Nicola
,
Dulmet, Elisabeth
,
Romdhani, Noureddine
in
bronchioloalveolar adenocarcinoma
,
lung neoplasms
,
pathology
1998
To determine the long-term results after surgical treatment of bronchioloalveolar lung carcinoma (BALC) and to identify prognostic factors.
A retrospective study of 70 patients (49 men, 21 women), mean age 61 ±10 years, was carried out. Their carcinomas were classified into three clinicopathologic types: nodular or tumoral, pneumonic, and diffuse types. All the diagnosed BALC cases were reviewed and were classified into histologic types: mucinous, nonmucinous (including fibrotic center), and mixed tumors. Univariate and multivariate analyses were carried out.
The nodular or tumoral type was identified in 42 patients, pneumonic in 21, and diffuse in seven. Histologically, there were 36 mucinous, 25 nonmucinous, and nine mixed tumors. Resection was complete in 61 instances (87%) and incomplete in five. The 5-year survival rate was 34% in patients with curative resections. Five prognostic factors were identified by univariate analysis, but in multivariate analysis, only three factors remained significant: the absence of symptoms, the TNM stage, and completeness of resection. Thirty-six patients with curative resection (59%) developed recurrences (in the lung in 26 patients; mediastinal lymph nodes, four; distant metastases, nine). The frequency of recurrence was significantly greater in patients with pneumonic-type BALC than in nodular or tumoral types (p<0.01), and pulmonary recurrences were significantly more frequent in pneumonic than in tumoral types (p<0.02).
This study confirmed that the overall prognosis of BALC is not significantly different from that of the other non-small cell lung cancers. We found that the lungs are the predominant site of recurrence in BALC, especially in the pneumonic types. The complete surgical resection of localized BALC offers the best chances of long-term survival.
Journal Article
Bronchioloalveolar lung carcinoma: Results of surgical treatment and prognostic factors
by
DULMET, M. E
,
BOURCEREAU, M. J
,
GHARBI, N
in
Adenocarcinoma, Bronchiolo-Alveolar - classification
,
Adenocarcinoma, Bronchiolo-Alveolar - pathology
,
Adenocarcinoma, Bronchiolo-Alveolar - secondary
1998
To determine the long-term results after surgical treatment of bronchioloalveolar lung carcinoma (BALC) and to identify prognostic factors.
A retrospective study of 70 patients (49 men, 21 women), mean age 61+/-10 years, was carried out. Their carcinomas were classified into three clinicopathologic types: nodular or tumoral, pneumonic, and diffuse types. All the diagnosed BALC cases were reviewed and were classified into histologic types: mucinous, nonmucinous (including fibrotic center), and mixed tumors. Univariate and multivariate analyses were carried out.
The nodular or tumoral type was identified in 42 patients, pneumonic in 21, and diffuse in seven. Histologically, there were 36 mucinous, 25 nonmucinous, and nine mixed tumors. Resection was complete in 61 instances (87%) and incomplete in five. The 5-year survival rate was 34% in patients with curative resections. Five prognostic factors were identified by univariate analysis, but in multivariate analysis, only three factors remained significant: the absence of symptoms, the TNM stage, and completeness of resection. Thirty-six patients with curative resection (59%) developed recurrences (in the lung in 26 patients; mediastinal lymph nodes, four; distant metastases, nine). The frequency of recurrence was significantly greater in patients with pneumonic-type BALC than in nodular or tumoral types (p<0.01), and pulmonary recurrences were significantly more frequent in pneumonic than in tumoral types (p<0.02).
This study confirmed that the overall prognosis of BALC is not significantly different from that of the other non-small cell lung cancers. We found that the lungs are the predominant site of recurrence in BALC, especially in the pneumonic types. The complete surgical resection of localized BALC offers the best chances of long-term survival.
Journal Article