Ex vivo Immuno-modulatory effect of Echinococcus granulosus laminated layer during allergic rhinitis and allergic asthma: A study in Algerian Patients.

The effect of helminthic infections on allergic diseases and asthma is still inconclusive. Moreover, there is considerable evidence suggesting that nitric oxide (NO), metalloproteinases and pro-inflammatory cytokines play a significant role in the physiopathology of these diseases. In this sense, the aim of our study is to investigate the ex vivo immunomodulatory effect of the laminated layer (LL, outside layer of parasitic cyst) of the helminth Echinococcus granulosus on NO, IL-17A and IL-10 production. In the first step of our study, we evaluated in vivo the NO, MMP-9, IL-17A, IL-10 levels in Algerian patients with allergic asthma and allergic rhinitis and their changes in relation with exacerbation status of the patients. In the principal part of our work, we assessed NO, IL-10 and IL-17A levels in supernatants of patients PBMC cultures before and after stimulation with LL. Our results indicate a significant reduction in NO production by PBMC of patients with allergic rhinitis and allergic asthma whether mild, moderate or severe after stimulation with LL. Interestingly, LL induces a significant decrease in the production of NO and IL17-A levels as well as an increase in the production of IL-10 in the cultures performed with PBMC of patients with severe allergic asthma. Importantly, our data indicate that LL exert a down-modulatory effect on inflammatory mediators (NO, IL-17A) and up immune-regulatory effect on IL-10 production. Collectively, our study supports the hygiene hypothesis suggesting that Echinococcus granulosus infection like other helminths could prevent and/or modulate inflammation responses during inflammatory diseases.

In vitro immunoregulatory activity and anti-inflammatory effect of Echinococcus granulosus laminated layer.

The Laminated layer of Echinococcus granulosus (LL) is the outer layer of the hydatic cyst. It plays a pivotal role in protecting the metacestode from host immunity. In our current study, we investigated the immunomodulatory effect of the LL on mouse spleen cells in presence of Lipopolysaccharide (LPS). Mouse spleen cells were cultured with or without LL in presence of LPS. After 24 h, the nitrites level representative of Nitric oxide (NO) production was measured in the culture supernatant by Griess-modified method. In addition, the mRNA expression levels of cytokines (IFN-γ, IL-1ß, TGF-ß, IL-10), Foxp3, and CTLA-4 were measured by quantitative Real-Time Polymerase chain reaction (qRT-PCR). Interestingly, our results showed a significant decrease (p< 0.01) in NO production and IFN-γ mRNA level (p< 0.001) from LPS- induced spleen cells in response to LL after 24h of culture. Moreover, LPS induced high level of IL-1ß that was significantly (p<0.05) down regulated by LL. Importantly, mRNA levels of TGF-ß (p< 0.01), Foxp3 and IL-10 (p< 0.05) were significantly upregulated by LL. In conclusion, our data indicated the in vitro immuno-regulatory and anti-inflammatory effects of the hydatic Laminated Layer on mouse spleen cells. These effects are related to an innate response implicating up-regulation of Foxp3, IL-10 and TGF-ß expression and down-regulation of IFN-γ and IL-1ß expression. LL could constitute a potential candidate for controlling inflammation during inflammatory disease.

Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: revisiting exploratory thoracotomies and incomplete resections.

OBJECTIVES: Only patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations. METHODS: A total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections. RESULTS: ET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1 extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade. CONCLUSIONS: ET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.

Microscopic residual disease after resection for lung cancer: a multifaceted but poor factor of prognosis.

BACKGROUND: Many studies focus on bronchial microscopic residual disease (R1) after resection for lung cancer, although R1 also concerns vascular and soft tissues. Our purpose was to study the R1 prognosis at different resection margins and to compare it with the prognosis for those having complete resection (R0). METHODS: We reviewed the clinical records of 4,026 patients from two centers who underwent surgery in view of cure. Despite perioperative frozen section, 216 patients (5.4%) proved R1 and were classified into seven types according to R1 anatomic site: bronchus, peribronchus, great vessels and atrium, mediastinum and pericardium, chest wall, lung tissue, and lymph nodes. Patients who were classified as R0 and R1 were compared, and R1 patients were further studied according to R1 margins. RESULTS: Frequency of R1 increased with the T and N values and type of resection (lobectomies, 3.3% [70 of 2,041 patients]; pneumonectomies, 8.8% [126 of 1,308 patients]; p < 10(-6)). Five-year survival rates for R1 patients were lower than those for R0 patients (20% versus 46%; p < 10(-6)), and were not modified by the degree of T and N involvement or adjuvant therapy, but were better in bronchial and peribronchial (48.4% of R1 patients) than in extrabronchial R1 (26.3% versus 15.6%; p = 0.023). Multivariate analysis confirmed R1 to be an independent factor of poor prognosis (p = 0.0008), after N, T, and age. CONCLUSIONS: Long-term survival is possible in case of an R1 margin, but 5-year survival rates are jeopardized. Poor efficacy of adjuvant therapy and global outcome indicate advanced disease or reflect tumor cell aggressiveness, rather than surgical insufficiency, when prevention of R1 margins is guided by frozen-section examination and scrupulously respected.