Tracheal atypical solitary carcinoid in a so called "difficult asthma": a diagnostic challenge.

This report describes the case of a 46-year-old non-smoker housewife. She presented to our attention having a diagnosis of "difficult asthma" from another center in the previous two years. She had no allergies and had not been exposed to an excessive amount of noxious stimuli. Her chronic respiratory symptoms (dyspnea on exertion with wheezing) remained uncontrolled despite maximal anti-asthmatic inhaled therapy. An HRCT scan was performed to further investigate other pulmonary diseases that mimic asthma. It revealed a pedunculated endotracheal lesion with regular borders that obstructed 90% of the tracheal lumen. The lesion was removed via rigid bronchoscopy with laser endobronchial; histological examination revealed the presence of atypical carcinoid. Atypical carcinoids are a rare subtype of neuroendocrine lung tumor that accounts for 2% of all thoracic malignancies. They frequently arise from the central airways and cause obstructive symptoms such as coughing, wheezing, chest pain, or recurrent obstructing pneumonia, which is caused by central airway obstruction. Clinical onset is gradual and characterized by non-specific symptoms, which frequently result in misdiagnosis. As a result, in a young patient with progressive dyspnea, chronic cough, and wheezing that is not responding to anti-asthmatic treatment, second-level investigations are required and may lead to a definite diagnosis, allowing the appropriate course of treatment to begin.

Effect of repeated intakes of a neonicotinoid insecticide on the foraging behaviours of Apis mellifera in field trials.

Evaluating the effects of neonicotinoids on forager bees in conditions as near as possible to those in nature presents a considerable challenge. Tackling this challenge is, however, necessary to establish their negative side effects on these pollinators. For instance, it is still under debate the mechanism by which bees seem to recognize low-level contaminations of neonicotinoid insecticides in nectar and pollen of the flowers they visit and limit collection to protect themselves and their hive from a possible intoxication. In this study, we propose an experimental system that involves the use of foragers in free flight foraging repeatedly on artificial feeders containing a sucrose solution contaminated with clothianidin, as well as foragers feeding at adjacent control feeders, allowing us to observe changes in their foraging activity. The progressive disappearance of foragers from the contaminated feeders became increasingly clear and rapid with the increase in clothianidin concentration. The lowest concentration at which we observed an effect was around 10 µg/L, which corresponds to the maximum residual concentration (10 ng/g) observed in pollen and nectar of flowers close to open fields sown with seeds coated with insecticides. At the highest concentrations tested (80 µg/L), there was an almost total abandonment of the feeders. The estimated quantity of contaminated sucrose solution collected by foragers showed an almost linear relationship inversely proportional to clothianidin concentration, whilst the estimated quantity of insecticide collected by a forager increased and then stabilised at the highest concentrations tested of 40 and 80 µg/L. Irregular mortality was not observed in front of the hives, furthermore, foragers did not show evident memory of the position of the treated units in the trials on the 2 consecutive days. The decrease in foraging activity in the presence of a few µg/L of insecticide in the sucrose solution appears to limit the introduction of elevated amounts of toxic substances into the hives, which would have serious consequences for the young bees and the brood. At the same time, in the absence of an alternative energy source, even reduced feeding of the hive can compromise colony health.

Multidimensional 3-Month Follow-Up of Severe COVID-19: Airways beyond the Parenchyma in Symptomatic Patients.

SARS-CoV-2 may lead to a large spectrum of respiratory manifestations, including pulmonary sequelae. We conducted a single-center longitudinal study of survivors from severe COVID-19 cases who underwent a chest CT during hospitalization (CTH). Three months after being discharged, these patients were evaluated by a clinical examination, pulmonary function tests and a chest-CT scan (CTFU). Sixty-two patients were enrolled. At follow-up, 27% complained of exertional dyspnoea and 12% of cough. Dyspnoeic patients had a lower forced expiratory flow (FEF)25-75 (p = 0.015), while a CT scan (p = 0.016 showed that patients with cough had a higher extent of bronchiectasis. Lung volumes and diffusion of carbon monoxide (DLCO) at follow-up were lower in patients who had been invasively ventilated, which correlated inversely with the length of hospitalization and ground-glass extension at CTH. At follow-up, 14.5% of patients had a complete radiological resolution, while 85.5% presented persistence of ground-glass opacities, and 46.7% showed fibrotic-like alterations. Residual ground-glass at CTFU was related to the length of hospitalization (r = 0.48; p = 0.0002) and to the need for mechanical ventilation or high flow oxygen (p = 0.01) during the acute phase. In conclusion, although patients at three months from discharge showed functional impairment and radiological abnormalities, which correlated with a prolonged hospital stay and need for mechanical ventilation, the persistence of respiratory symptoms was related not to parenchymal but rather to airway sequelae.

Pneumothorax and/or Pneumomediastinum Worsens the Prognosis of COVID-19 Patients with Severe Acute Respiratory Failure: A Multicenter Retrospective Case-Control Study in the North-East of Italy.

Pneumothorax (PNX) and pneumomediastinum (PNM) are potential complications of COVID-19, but their influence on patients' outcomes remains unclear. The aim of the study was to assess incidence, risk factors, and outcomes of severe COVID-19 complicated with PNX/PNM. METHODS: A retrospective multicenter case-control analysis was conducted in COVID-19 patients admitted for respiratory failure in intermediate care units of the Treviso area, Italy, from March 2020 to April 2021. Clinical characteristics and outcomes of patients with and without PNX/PNM were compared. RESULTS: Among 1213 patients, PNX and/or PNM incidence was 4.5%. Among these, 42% had PNX and PNM, 33.5% only PNX, and 24.5% only PNM. COVID-19 patients with PNX/PNM showed higher in-hospital (p = 0.02) and 90-days mortality (p = 0.048), and longer hospitalization length (p = 0.002) than COVID-19 patients without PNX/PNM. At PNX/PNM occurrence, one-third of subjects was not mechanically ventilated, and the respiratory support was similar to the control group. PNX/PNM occurrence was associated with longer symptom length before hospital admission (p = 0.005) and lower levels of blood lymphocytes (p = 0.017). CONCLUSION: PNX/PNM are complications of COVID-19 associated with a worse prognosis in terms of mortality and length of hospitalization. Although they are more frequent in ventilated patients, they can occur in non-ventilated, suggesting that mechanisms other than barotrauma might contribute to their presentation.

Medical thoracoscopy without pleural fluid: How I do it.

Thoracoscopy is a commonly used minimally invasive procedure in the field of interventional pulmonology. While medical thoracoscopy is the widely preferred modality, modifications to the technique and expansion in the scope of its utility have always challenged the conventional approach. We describe a modified technique of medical thoracoscopy in absence of pleural effusion also known as dry thoracoscopy under sedation and local anaesthesia.

A case report on expanding horizon of endobronchial ultrasound through esophagus.

Endobronchial ultrasound has revolutionized the field of bronchoscopy and has become one of the most important tools for the diagnosis of intrathoracic lymphadenopathy and para-bronchial structures. The reach of this technique has not been limited to these structures and pleural lesions have been at times accessible. To our knowledge, pleural fluid collections have not been accessed with endobronchial ultrasound (EBUS) through oesophageal approach and rationale behind using this approach. We report a case of 70 years old man who has been referred from physician for the EBUS in view of hilar mass with mediastinal lymphadenopathy with pleural effusion. The endobronchial ultrasound through oesophagus (EUS-B) was done for thoracocentesis and lymph node cytology evaluation and ultimately endobronchial biopsy of hilar mass was done as rapid on-site (ROSE) analysis of lymph node was suggestive of necrotic tissue. The cytology report of lymph node and pleural effusion was positive for malignant cells. The final diagnosis was metastatic poorly differentiating adeno-squamous carcinoma.

Esophageal ultrasound with ultrasound bronchoscope (EUS-B) guided transvascular needle aspiration (TVNA).

We have described a 67-year-old man, diagnosed to have adenocarcinoma of lung by transvascular approach with esophageal ultrasound using ultrasound bronchoscope (EUS-B). To the best of our knowledge this is the first case where EUS-B has been used for transvascular fine needle aspiration cytology to diagnose lung carcinoma.

Inhibition of epoxyeicosatrienoic acid production in rats with cirrhosis has beneficial effects on portal hypertension by reducing splanchnic vasodilation.

UNLABELLED: In cirrhosis, 11,12-epoxyeicosatrienoic acid (EET) induces mesenteric arterial vasodilation, which contributes to the onset of portal hypertension. We evaluated the hemodynamic effects of in vivo inhibition of EET production in experimental cirrhosis. Sixteen control rats and 16 rats with carbon tetrachloride-induced cirrhosis were studied. Eight controls and eight rats with cirrhosis were treated with the specific epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH; 20 mg/kg/day) for 3 consecutive days. Portal blood flow and renal and splenic resistive indexes were calculated through echographic measurements, while portal and systemic pressures were measured through polyethylene-50 catheters. Small resistance mesenteric arteries were connected to a pressure servo controller in a video-monitored perfusion system, and concentration-response curves to phenylephrine and acetylcholine were evaluated. EET levels were measured in tissue homogenates of rat liver, kidney, and aorta, using an enzyme-linked immunosorbent assay. Urinary Na(+) excretion function was also evaluated. In rats with cirrhosis, treatment with MS-PPOH significantly reduced portal blood flow and portal pressure compared to vehicle (13.6 ± 5.7 versus 25.3 ± 7.1 mL/min/100 g body weight, P < 0.05; 9.6 ± 1.1 versus 12.2 ± 2.3 mm Hg, P < 0.05; respectively) without effects on systemic pressure. An increased response to acetylcholine of mesenteric arteries from rats with cirrhosis (50% effect concentration -7.083 ± 0.197 versus -6.517 ± 0.73 in control rats, P < 0.05) was reversed after inhibition of EET production (-6.388 ± 0.263, P < 0.05). In liver, kidney, and aorta from animals with cirrhosis, treatment with MS-PPOH reversed the increase in EET levels. In both controls and rats with cirrhosis, MS-PPOH increased urinary Na(+) excretion. CONCLUSION: In rats with cirrhosis, in vivo inhibition of EET production normalizes the response of mesenteric arteries to vasodilators, with beneficial effects on portal hypertension. (Hepatology 2016;64:923-930).

Changes in gene expression of cytochrome P-450 in liver, kidney and aorta of cirrhotic rats.

INTRODUCTION: Liver cirrhosis is characterized by structural and hemodynamic changes that affect mainly the liver, the kidney and the vascular system. Cytochrome P-450 (CYP) is a variegated family of enzymes that, among many other activities, metabolize arachidonic acid to the vasoactive epoxyeicosatrienoic acids (EETs). AIM: To investigate in an animal model of cirrhosis the m-RNA expression of CYPs in liver, kidney and aorta and to evaluate the effect of epoxygenase inhibition by N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH). METHODS: In aorta, liver and kidney from 3 control, 3 cirrhotic and 6 cirrhotic rats treated with MS-PPOH, quantitative real-time PCR reactions were performed and the m-RNA expression of CYP2J3, CYP2J4, CYP2J10, CYP2C11, CYP2C12 and CYP2C23 was calculated. RESULTS: In cirrhotic rats, the gene expression of hepatic CYP2C11 and CYP2J10 was increased, of aortic CYP2J4 was increased, of aortic CYP2C12 was reduced and of renal CYP2C11 was increased. In cirrhotic rats, MS-PPOH reduced CYP2J10 hepatic and CYP2C11 renal gene expression to levels similar to the ones of control rats. CONCLUSIONS: Changes in CYPs gene expression may contribute to the hemodynamic alterations typical of cirrhosis. The altered gene expression of CYPs can, in some cases, be reversed by epoxygenase inhibition.

Mesenteric arteries responsiveness to acute variations of wall shear stress is impaired in rats with liver cirrhosis.

OBJECTIVE: In liver cirrhosis, excessive splanchnic vasodilation is due to abnormal synthesis of endogenous vasodilators and to decreased sensitivity to vasoconstrictors. The role of mechanical stimuli such as wall shear stress (WSS) on splanchnic circulation remains unclear. The aim of this study was to assess the vasodilation induced by wall shear stress (WSS) and acute changes in blood flow in the mesenteric arteries in an experimental model of liver cirrhosis. MATERIALS AND METHODS: The effect of acute changes in intraluminal flow (0, 10, and 20 µl/min) and WSS on the diameter of the mesenteric arteries (diameters <500 µm) of control and cirrhotic rats was assessed, at baseline and after the inhibition of nitric oxide synthase, cyclooxygenase and hemeoxygenase. Concentration-response curves to phenylephrine were also obtained. RESULTS: In controls, the increase in intraluminal flow led to a significant increase in arterial diameter (p < 0.05), while WSS remained stable; the effect was maintained in vessels pre-constricted with phenylephrine, blocked by the exposure to indomethacin and L-NAME and restored by the subsequent addition of chromium mesoporphyrin (p < 0.05). In cirrhotic arteries, arterial diameters did not change in response to acute increase in flow, neither at baseline nor after exposure to indomethacin and L-NAME, while WSS increased (p < 0.01). Responsiveness to flow was partially restored (p < 0.05) after exposure of the arteries to chromium mesoporphyrin in addition to indomethacin and L-NAME. CONCLUSIONS: Arteries from cirrhotic rats showed an abolished responsiveness to acute variations in flow, which exposes the mesenteric endothelium to sudden variations in WSS.

Increased myoendothelial gap junctions mediate the enhanced response to epoxyeicosatrienoic acid and acetylcholine in mesenteric arterial vessels of cirrhotic rats.

BACKGROUND: Cirrhotic portal hypertension is characterized by mesenteric arterial vasodilation and hyporeactivity to vasoconstrictors. AIM: We evaluated the role of epoxyeicosatrienoic acid (EET) and of myoendothelial gap junctions (GJ) in the haemodynamic alterations of experimental cirrhosis. METHODS: Thirty-five control rats and 35 rats with carbon tetrachloride (CCl(4))-induced cirrhosis were studied. Small resistance mesenteric arteries (diameter <350 µm) were connected to a pressure servo controller in a video-monitored perfusion system. Concentration-response curves to acetylcholine (ACh) were evaluated in mesenteric arteries pre-incubated with indomethacin, N(G)-nitro-L-arginine-methyl-ester and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one before and after the epoxygenase inhibitor miconazole or 18α-glycyrrhetinic acid (18α-GA) (GJ inhibitor). EC(50) was calculated. Concentration-response curves to 11,12-EET were also evaluated. mRNA and protein expression of connexins (Cxs) in the mesenteric arteries was evaluated by real-time PCR and immunohistochemistry. RESULTS: The ACh response was increased in cirrhotic rats (EC(50): -6.55±0.10 vs. -6.01±0.10 log[M]; P<0.01) and was blunted by miconazole only in cirrhotic animals. 18α-GA blunted the response to ACh more in cirrhotic than that in control rats (P<0.05). Concentration-response curves to 11,12-EET showed an increased endothelium-dependent vasodilating response in cirrhotic rats (P<0.05); the BK(Ca) inhibitor Iberiotoxin (25 nM) blocked the response in normal rats but not in cirrhotic rats, while 18α-GA blunted the response in cirrhotic rats but not in control rats. An increased mRNA and protein expression of Cx40 and Cx43 in cirrhotic arteries was detected (P<0.05). CONCLUSIONS: The increased nitric oxide/PGI(2)-independent vasodilation of mesenteric arterial circulation in cirrhosis is because of, at least in part, hyperreactivity to 11,12-EET through an increased expression of myoendothelial GJs.

Primary role of multiparametric flow cytometry in the diagnostic work-up of indolent clonal mast cell disorders.

BACKGROUND: According to the World Health Organization (WHO) classification the diagnosis of systemic mastocytosis (SM) relies on bone marrow (BM) examination and is based on one major and four minor criteria. Herein, we used WHO criteria to compare flow cytometry (FC) with other available techniques in the diagnosis of SM after BM examination. METHODS: We analyzed a cohort of 95 patients with suspect SM. All patients underwent comprehensive BM examination by using cytology, immunohistochemistry, FC and molecular study for mutation of c-Kit and serum tryptase dosage. FC evaluation was based on a combination of monoclonal antibodies, specifically CD25/CD2/CD45/CD34/CD117. RESULTS: Seventy-four out of ninety-five patients were diagnosed with indolent SM (n = 59) or monoclonal mast cell activation syndrome (n = 15) because satisfying less than 3 minor criteria. Thirty-nine out of these seventy-four patients fulfilled the major histological criterion, whereas the presence of a minor criterion was assessed by FC, molecular study, cytology, and tryptase level in 70/74, 52/67, 56/74, and 42/74 patients, respectively. FC showed higher sensitivity than IHC in detection of CD25+ mast cells (MC) (92.9% vs. 73.8%; P = 0.019), especially in the absence of the major histological criterion (90.5% vs. 47.6%; P = 0.003). Moreover, CD2 expression was documented by FC and IHC in 97.1% and 35.3% of cases, respectively (P < 0.001). CONCLUSIONS: FC showed the best sensitivity for identifying abnormal MC compared to other techniques, especially in cases with low MC burden. Therefore, we hope for a major role of FC in the diagnostic work-up of clonal MC disorders.

A proliferation-inducing ligand (APRIL) serum levels predict time to first treatment in patients affected by B-cell chronic lymphocytic leukemia.

PURPOSE: A proliferation-inducing ligand (APRIL), a tumor necrosis factor superfamily member involved in B-lymphocytes differentiation and survival, plays a role in protecting B-Cell Chronic lymphocytic leukemia (B-CLL) cells from apoptosis. Having observed that APRIL serum (sAPRIL) levels were higher in B-CLL patients with CLL at diagnosis as compared to healthy donors (14.61±32.65 vs. 4.19±3.42 ng/mL; P<0.001), we tested the correlation existing in these patients between sAPRIL, clinical-biological parameters and disease progression. EXPERIMENTAL DESIGN: sAPRIL levels were measured by ELISA in 130 patients with B-CLL at diagnosis and in 25 healthy donors. RESULTS: sAPRIL levels did not correlate with gender, age, clinical stage, blood cell counts, ß2-microglobulin (ß2M) levels, ZAP-70 and CD38 expression. Using median sAPRIL natural logarithm (ln) as cutoff, we distinguished two groups of patients (APRIL(LOW) and APRIL(HIGH) ) who were comparable with regard to clinical-biological parameters and overall survival, but different with regard to time to the first treatment (TTFT; P=0.035). According to univariate analysis, high lymphocyte count, high ß2M, Binet stage B-C, ZAP-70 expression and ln(sAPRIL) above median were associated with earlier TTFT. Advanced clinical stage, high ß2M, ZAP-70 expression and ln(sAPRIL) above median remained independently predictive of shorter TTFT at multivariate analysis. Moreover, sAPRIL increased its prognostic significance when patients were stratified according to independent favorable clinical-biological characteristics (low ß2M, stage A and lack of ZAP-70 expression). CONCLUSIONS: sAPRIL is a novel indicator of shorter TTFT in B-CLL and a predictor of progression especially in patients otherwise considered at low risk according to validated prognostic factors.

Heme oxygenase regulates renal arterial resistance and sodium excretion in cirrhotic rats.

BACKGROUND & AIMS: Heme oxygenase (HO) catabolizes heme into biliverdin, carbon monoxide (CO), and free iron. CO generated in endothelial and smooth muscle layers of blood vessels modulates vascular tone by inducing relaxation of vascular smooth muscle cells. The aim of this study was to verify the role played by HO in regulating renal arterial resistance and Na(+) excretion in cirrhosis. METHODS: Twenty control rats and 20 rats with CCl(4)(-) induced cirrhosis, 10 of which were chronically treated with the HO inducer cobalt-protoporphyrin (CoPP), were studied. Pressurized renal interlobar arteries were challenged with increasing doses of phenylephrine (PE) and acetylcholine (ACh). Dose-response curves were evaluated under basal conditions and after inhibition of HO with chromium-mesoporphyrin (CrMP). HO-1 (inducible form) and HO-2 (constitutive form) expression was measured in the main and interlobar renal arteries. Serum and urinary levels of Na(+) and creatinine were also evaluated. RESULTS: In renal interlobar arteries from cirrhotic rats, the response to PE was increased, while that to ACh was blunted. After HO inhibition, the responsiveness to these vasoactive substances was comparable in the two groups. In cirrhotic rats, HO-1 expression was impaired in the main and the interlobar renal arteries. Chronic HO induction normalized the response to the vasoconstrictor, but not to the vasodilator. Cirrhotic rats treated with CoPP showed higher urinary Na(+) concentration and fractional Na(+) excretion, compared to both untreated cirrhotic and control rats. CONCLUSIONS: In cirrhotic rats, an impaired HO-1 expression promotes vasoconstriction of renal interlobar arteries. Chronic HO induction normalizes the sensitivity to PE and promotes Na(+) excretion.

Carbon monoxide-mediated activation of large-conductance calcium-activated potassium channels contributes to mesenteric vasodilatation in cirrhotic rats.

Large-conductance calcium-activated potassium channels (BK(Ca)s) are important regulators of arterial tone and represent a mediator of the endogenous vasodilator carbon monoxide (CO). Because an up-regulation of the heme oxygenase (HO)/CO system has been associated with mesenteric vasodilatation of cirrhosis, we analyzed the interactions of BK(Ca) and of HO/CO in the endothelium-dependent dilatation of mesenteric arteries in ascitic cirrhotic rats. In pressurized mesenteric arteries (diameter, 170-350 microm) of ascitic cirrhotic rats, we evaluated the effect of inhibition of BK(Ca), HO, and guanylyl-cyclase on dilatation induced by acetylcholine and by exogenous CO; and HO-1 and BK(Ca) subunit protein expression. Inhibition of HO and of BK(Ca) reduced acetylcholine-induced vasodilatation more in cirrhotic rats than in control rats, whereas inhibition of guanylyl-cyclase had a similar effect in the two groups. CO was more effective in cirrhotic rats than in control rats, and the effect was hindered by BK(Ca) inhibition. The expression of HO-1 and of BK(Ca) alpha-subunit was higher in mesenteric arteries of cirrhotic rats compared with that of control animals, whereas the expression of the BK(Ca) beta1-subunit was lower. In conclusion, an overexpression of BK(Ca) alpha-subunits, possibly due to HO up-regulation with increased CO production, participates in the endothelium-dependent alterations and mesenteric arterial vasodilatation of ascitic cirrhotic rats.

Methodological approach to minimal residual disease detection by flow cytometry in adult B-lineage acute lymphoblastic leukemia.

A flow cytometric approach to minimal residual disease (MRD) monitoring useful in childhood B-lineage acute lymphoblastic leukemia (ALL) is discussed here in the context of ALL in adults. Of 64 leukemia samples analyzed, 95.3% had at least one abnormal phenotype (57.3% had two or more) as compared to physiologic B-cell precursors in adult bone marrow. The method was sensitive enough to detect one leukemic cell among 10,000 normal cells in 16/19 experiments (84.2%). Blast phenotypes were stable in culture and at relapse, and were useful for MRD monitoring in patients. Marker combinations for childhood ALL are also applicable to adult cases.

Thymic epithelial cells promote survival of human T-cell acute lymphoblastic leukemia blasts: the role of interleukin-7.

BACKGROUND AND OBJECTIVES: T-cell lymphoblastic leukemia (T-ALL) cells originate within the thymus from the clonal expansion of T cell precursors. Among thymic stromal elements, epithelial cells (TEC) are known to exert a dominant inductive role in survival and maturation of normal, immature T-cells. In this study we explored the possible effect of TEC on T-ALL cell survival and analyzed the role of interleukin-7 (IL-7) within the microenvironment generated by T-ALL-TEC interactions. DESIGN AND METHODS: T-ALL blasts derived from 10 adult patients were cultured with TEC obtained from human normal thymuses. The level of blast apoptosis was measured by annexin V-propidium iodide co-staining and flow cytometry. The proliferative response of leukemic cells to interaction with TEC was evaluated by thymidine incorporation at various time intervals of culture. To assess the role of IL-7, lympho-epithelial co-cultures were carried out in the presence of anti-IL-7 or anti IL-7R blocking antibodies and the level of apoptosis of T-ALL blasts was analyzed. RESULTS: When T-ALL cells were cultured in the presence of TEC monolayers, the percentage of viable cells increased significantly and this survival was sustained with time in culture. In addition, the interaction with TEC induced a considerable proliferative response in T-ALL cells (15-fold greater than that of the control cells after 7 days of culture). The presence of IL-7 or IL-7R blocking antibodies in lympho-epithelial co-cultures consistently reduced the TEC-mediated apoptosis inhibition in T-ALL blasts (70% decrease). INTERPRETATION AND CONCLUSIONS: These results point to the role of thymic epithelium in the regulation of T blast survival. In addition, they show that interaction between IL-7 and its receptor has the major role in modulating T-ALL survival within the microenvironment generated by the T-ALL/TEC interaction.