Search

Castleman disease is a rare and benign disorder, characterized by enlarged lymph nodes and angiofollicular lymphoid hyperplasia. We report a case of a 57-year-old male, who was admitted to our surgical department because of a retroperitoneal nodular mass measuring about 4 cm in maximum diameter, incidentally discovered on a radiologic exam performed for the onset of vague abdominal pain with posterior irradiation. The patient was subdue to laparoscopic removal of the mass and no intra- and post-operative complications were recorded. Histologic diagnosis of hyaline-vascular variant of the Castleman disease was confirmed. Only two cases have been found in the literature reporting the paraduodenal unicentric Castleman disease localization like our case. Although rare, the Castleman disease must be considered in the differential diagnosis among all the lymph nodes diseases, for avoiding improper therapies., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Introduction: Purtscher's retinopathy causes sudden loss of vision of varying severity, secondary to head injury or chest compression. Its pathophysiology is unclear. Purtscher's-like retinopathy has more attenuated clinical and objective features and can be associated with many non-neoplastic pathologies. Otherwise, an association of this kind of retinopathy with malignancies has been described once in the Literature. We present a case report on a unique association between pancreatic cancer and Purtscher-type retinopathy., Case Presentation: A 79-year-old man with reduced central vision in both eyes required an ophthalmic evaluation. Visual acuity was 20/40 in the right eye and 20/50 in the left eye. Fundus examination showed yellow-white peripapillary spots and bilateral retinal hemorrhages in the superficial retina. The patient complained of abdominal pain and received a CT scan of the abdomen, which showed a pancreatic mass extending into the spleen. A percutaneous needle biopsy sample showed mucinous pancreatic adenocarcinoma., Clinical Discussion: This case report should warn of a possible association between pancreatic adenocarcinoma and Purtscher's-like retinopathy., Conclusion: Patients with this kind of retinopathy should be evaluated to rule out not only benign associated disease, but also malignant tumors of the pancreas., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although still debated, post-operative modification of hemostasis seems to be less pronounced after laparoscopy compared to open surgery. Antiphospholipid antibodies might play a role in the post-operative thromboembolic risk, although their evaluation in surgical patients has never been performed. Post-operative modification of antiphospholipid antibodies could be related to the surgical approach (laparoscopic or open). In this prospective study, the authors statistically compared the pre-operative values and post-operative modification of antiphospholipid antibodies in two homogeneous groups of patients operated on by laparoscopic and open surgery. No statistical differences within each group and between the two groups were shown comparing mean values of pre-operative and post-operative antiphospholipid antibodies. In the open group, there was a significant difference between pre-operative and post-operative LAC means (P < 0.01). In the laparoscopic group, on the contrary, no significant change in LAC values between pre- and post-operative tests (P = 0.55) was observed. Since LAC could be related to coagulation disorders, this study seems to support that laparoscopic surgery might induce a less risk of post-operative thromboembolic disease.

Purpose: Presently, laparoscopic splenectomy (LS) is being performed for several indications in clinical practice. However, conversion to open surgery is occasionally required in some patients. We analyzed the intraoperative indications and potential preoperative predictors associated with conversion to open surgery in those presenting for LS., Methods: We reviewed 107 patients who underwent LS. We analyzed the surgical indications, spleen size, surgical procedure performed, operative time, rate of and indications for conversions, as well as postoperative complications., Results: Among the 15 patients (14.0%) who underwent conversion, the conversion was related to the occurrence of a splenic lymphoma in 10, severe bleeding in 3, a lack of anatomic definition in 1, and splenic candidiasis in 1 patient. A comparison between the results obtained in the initial 30 patients (LS performed during the learning curve) and those obtained in the remaining 77 patients, showed that conversions appeared to be related to the experience/expertise of the surgical team excluding patients with splenic malignancies. Conversion was not associated with a higher morbidity-mortality rate, but only a longer length of hospitalization., Conclusions: LS is a gold standard procedure when performed by experienced and competent surgeons. However, careful patient selection is recommended before using the laparoscopic approach in those presenting with splenic malignancies.

Background: Hereditary spherocytosis is a benign hematologic disease, which needs surgical treatment when medical therapy fails. Currently, the surgical strategies consist mainly in total or partial splenectomy, which can be performed either in open or in laparoscopic fashion. In this study, we analyzed our series of splenectomies for hereditary spherocytosis and we discuss about the surgical management, reviewing the Literature., Material and Methods: Twenty-seven patients (mean age 16.5 years, range 8 - 30 years) affected by hereditary spherocytosis were retrospectively evaluated. Indication to surgery was based on hemolysis severity. Thirteen patients were submitted to laparoscopic splenectomy and 14 to open splenectomy, after preventive specific vaccinations. Cholecystectomy for associated cholelithiasis was performed during the same operation in 4 laparoscopic patients and in 6 open patients., Results: Main reasons for performing splenectomy were anemia unresponsive to iron supplementation in 7 patients (42%), splenomegaly in 6 patients (37%), and jaundice in 4 cases (21%). All the patients had a severe disease with hemoglobin level below 80 g/L, median reticulocytes count 6,5%, median value of indirect bilirubin concentration 2,0 mg/dL. Indications to splenectomy were increased need for red cell transfusions in 11 patients (66%) and symptoms related to cholelithiasis in 6 patients (34%). A post-operative early complication was observed after open splenectomy, consisting in a pancreatic fistula, which was treated conservatively. No post-operative complications were observed after laparoscopic splenectomy. Neither intra-operative complications nor conversions to open surgery were recorded during the laparoscopic approach. In a long-term follow- up, no infective complications were recorded., Conclusions: According to our results, total splenectomy is associated with good results and few complications. In our opinion, it remains the best therapeutic option in selected adult patients non-responder to the medical treatment., Key Words: Hereditary spherocytosis, Laparoscopic splenectomy, Partial splenectomy.

Objective: The Authors report their experience with the routine use of surgical drainage in a large series of splenectomies., Summary of Background Data: Benefits and risks related to surgical drains have been always discussed, with some surgeons in favor of them and skeptic others considering not physiological their use. After splenectomy, their use is also largely debated, especially because of susceptibility of operated patients to infections., Patients and Methods: Two thousand nine cases have been reviewed. Indications for splenectomy, performed either by open or laparoscopic approach, included idiopathic thrombocytopenic purpura in 137 patients (65,4%), splenic lymphoma in 36 (17,2%), hereditary spherocytosis in 15 (7,4%), β-thalassemia in 8 (3,7%), other diseases in 13 (6,1%)., Results: "Active" or "passive" drains were placed in 80% and 20% of cases, respectively. Drains were removed 2-3 days after surgery in 90,2%, within 10 days in 4,3%, within 2 months in 0,4% of cases. In 2 cases a post-operative bleeding, detected through the drainage, required re-operation. One patient developed a subphrenic abscess, successfully treated by a percutaneous drainage. One case of pancreatic fistula was observed., Conclusions: In Authors' experience, the use of drains after splenectomy does not affect the risk of subsequent infectious complications, independently on the type of the drainage system used. Early removal of drains in this series might have played an important role in the very low incidence of abdominal infections reported. The use of surgical drains after splenectomy might play an important role to early detect post-operative bleeding, as it happened in 2 cases of this series.

Background: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count., Materials and Methods: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ≤30,000/μL (study group: 22 patients) and >30,000/μL (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ≥100,000/μL or in patients with a postoperative platelet count ≥30,000/μL and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test., Results: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = -0.41; P = .089), whereas a significant negative correlation (r = -0.68; P = .0004) was found in the study group., Conclusions: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count.

Background and Objectives: The aim of this study was to evaluate the results of laparoscopic surgery performed for coexisting spleen and gallbladder surgical diseases., Methods: Between May 2004 and October 2012, 12 patients underwent concomitant laparoscopic splenectomy and cholecystectomy. Indications for surgery included idiopathic thrombocytopenic purpura in 5 patients, hereditary spherocytosis in 4 patients, and thalassemia intermedia in 3 patients., Results: The mean operative time was 100 minutes (range, 80 -160 minutes), and the blood loss ranged from 0 to 150 mL (mean, 50 mL). The mean longitudinal diameter of the spleen was 14 cm. One patient required conversion to open procedure. An accessory spleen was detected and removed in one case. The mean length of hospital stay was 5 days. No deaths or other major intraoperative and/or postoperative complications occurred., Conclusion: Provided that the technique is performed by an experienced surgical team, concomitant laparoscopic splenectomy and cholecystectomy is a safe and feasible procedure and may be considered for coexisting spleen and gallbladder diseases.

Hereditary spherocytosis is an inherited hemolytic anemia caused by a deficiency in erythrocyte membrane proteins. Removal of the spleen may reduce the intra-splenic hemolytic process of the disease and, therefore, may correct the anemia. Furthermore, it seems to decrease the levels of serum bilirubin, thus reducing the formation of gallbladder stones. Indications and timing of splenectomy, however, are still debated. Twelve patients with severe hereditary spherocytosis operated on with laparoscopic splenectomy were retrospectively reviewed. Median age at diagnosis was 13.8 years (range 8-25 years). Male to female ratio was 5/7. Indications for laparoscopic removal of the spleen included anemia unresponsive to iron supplementation in eight patients (66.6 %) with increase need for red cells transfusions, and jaundice with symptoms related to cholelitiasis in four patients (33.3 %). Laparoscopic splenectomy was associated in four cases to laparoscopic cholecystectomy. Mean operative time was 50 min (range 40-75 min) with no conversion to open surgery. Mean hospital stay ranged from 3 to 7 days. In a 16-month follow-up, no complications were recorded and a persistent correction of anemia was observed. With the advent of laparoscopic surgery, splenectomy has been performed by this mini-invasive approach in referral centers. Laparoscopic splenectomy is an effective technique, when performed in patients with hereditary spherocytosis. Low complication rate and persistent correction of the hematologic disorders can be expected after the laparoscopic splenectomy, provided that a proper technique is performed and an experienced surgical team is available.

Patients with chronic obstructive pulmonary disease (COPD) are prone to clinical exacerbations that are associated with increased airway inflammation, a potent pro-thrombotic stimulus. Limited information is available on the mechanisms underlying the putative alterations of the endothelial-coagulative system during acute exacerbations. The aim was to investigate whether the activation of the endothelial-coagulative system occurs in association with the acute inflammatory response of COPD exacerbation. We monitored the blood levels of surrogate markers of inflammation: interleukin-6 (IL-6); endothelium damage: von Willebrand's factor (vWF); clotting activation: D-dimer (D-D), and prothrombin fragment 1+2 (F1+2); fibrinolytic response: plasminogen activator inhibitor 1 (PAI-1), in COPD subjects, during hospital admission and after clinical resolution. In 30 COPD subjects, IL-6, vWF, D-D and F1+2 levels were elevated during exacerbation and decreased significantly at clinical stability (IL-6, p = 0.005; vWF, p < 0.001; D-D, p < 0.001; F1+2, p < 0.001). PAI-1 levels did not change at exacerbation compared to clinically stable situations. Positive correlations were observed between several of the markers measured. Elevation of IL-6, vWF, D-D and F1+2 levels during COPD exacerbations implies a strict association between acute inflammation, endothelial activation and clotting initiation. This was not associated with a change in PAI-1, implying an increase in the fibrinolytic response to inflammation. The pro-thrombotic nature of COPD exacerbations sustained by enhanced clotting activation appears to be mitigated by excessive fibrinolysis.

Background: Cigarette smoking is associated with cardiovascular morbidity and mortality. Exposure to cigarette smoke can cause endothelial dysfunction with impaired endothelium-dependent vasodilation and 'endothelial activation', which predispose to atherothrombosis. The effects of continued smoking and smoking cessation on the level of endothelial, platelet and clotting activation have not been described previously. Here, we prospectively monitored changes in circulating endothelial-coagulative activation markers in smokers undertaking smoking cessation., Method: This 12-month prospective study of 174 smokers with no commonly acquired atherothrombotic risk factors underwent an intensive smoking-cessation programme investigating the effect of quitting on circulating levels of von Willebrand's Factor Antigen (vWF:Ag), soluble Thrombomodulin (sTM), d-Dimer (d-D), prothrombin fragment F1+2 (F1+2), platelet factor-4 (PF4) and β-Thromboglobulin (β-TG). Blood samples and study measures were collected and compared at baseline and at 2, 6 and 12months after smoking cessation from quitters and relapsers'., Results: No significant differences in demographic or laboratory parameters at baseline were observed between the study groups. Significant changes in von Willebrand's Factor activity were observed at 2months after smoking cessation, with levels decreasing from 141·8% to 113·6%. Substantial modifications in d-Dimer, prothrombin fragment F1 +2, platelet factor-4 and β-thromboglobulin concentrations were observed only at 6 and 12months after smoking cessation. Positive associations between baseline levels of these biomarkers and number of pack per years have been demonstrated., Conclusions: Chronic exposure to cigarette smoke sustains the activation of the endothelial-coagulative system and abstinence may result in the improvement of several endothelial-coagulative abnormalities in regular smokers. This may translate into an overall decline in cardiovascular risk., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Pediatric surgery is now in the forefront of minimal access procedures. Although pediatric surgeons have been skeptic about laparoscopic splenectomy, recently minimally invasive approach for spleen removal has been revaluated also in young patients. Purpose of this study was to report Authors' personal experience in patients under eighteen who underwent laparoscopic splenectomy. Results of the procedure were evaluated., Patients and Methods: A retrospective review was undertaken in 18 splenectomised patients under the age of eighteen. Indications were hereditary spherocytosis in 10 patients, β-thalassemia in 4, idiopathic thrombocytopenic purpura in 3 and a splenic cyst in 1 child., Results: No intra-operative complications occurred. No conversion to open surgery was reported. During the follow-up one case of portal vein thrombosis, treated by medical therapy, was encountered and no other postoperative complications were observed., Conclusions: Laparoscopic approach has to be preferable for all those children undergoing spleen surgery. In experienced hands, it is of beneficial effects with a very reasonable rate of complications.

Endothelial activation/injury following exposure to cigarette smoke may explain incidence of atherosclerosis and cardiovascular disease in smokers. We investigated cigarette smoke extract (CSE) effects relative to activation, injury, and survival of human umbilical vein endothelial cells (HUVEC) and compared circulating levels of specific endothelial activation markers between smokers and healthy non-smokers before and after smoking cessation. Viability and toxicity of HUVEC were tested by MTT and LDH assay. Release (by endothelial cells) and circulating levels (in smokers) of von Willebrand Factor (vWF), thrombomodulin (TM), was evaluated by ELISA. Incubation with increasing concentrations of CSE reduced the percentage of viable cells, being 33.9%, 23.9% after CSE 4%, 6% respectively. Dose- and time-dependent release of LDH was observed after incubation with CSE. vWF, TM release were assayed after CSE 2% HUVEC stimulation. Significant 42%, 61%, 76% increase in vWF concentration was detected respectively at 30', 60', 120'. Reduction in circulating levels of vWF, from a median value of 144.0% to 123.7%, was observed in the quitters group after smoking cessation. Exposure to cigarette smoke is cytotoxic and induces activation/injury of endothelium in vitro and in vivo. These findings may provide pathogenetic basis by which smoking can predispose to development of atherothrombosis and cardiovascular disease.

Introduction: Portal vein thrombosis (PVT) could be a life-threatening complication after splenectomy if not diagnosed promptly and treated properly. Risk factors of PVT are not completely clarified. Spleen size and underlying hematologic diseases are main potential risk factors for this complication. Laparoscopic surgery might increase the risk of developing PVT, as it reduces the blood flow in the portal system due to the pneumoperitoneum but, on the other hand, it seems to be associated with less postoperative modifications of coagulation parameters than open surgery, thus preventing PVT itself. The authors reviewed their series on open and laparoscopic splenectomies, pointing out their experience on PVT and discussing their surveillance and prophylaxis programs to prevent this complication., Materials and Methods: In this series, the authors report their experience on postsplenectomy PVT in 162 patients who have been splenectomised (102 operated on laparoscopically and 60 by open surgery)., Results: PVT was clinically observed in 1 case out of 60 open splenectomies and in 3 cases out of 102 laparoscopic procedures. Patients were treated with conservative anticoagulation therapy. In one case, additional ileal resection was needed. Mortality was 0%., Conclusion: Low-molecular-weight heparin should be administered to all patients who have been splenectomised, especially if they are at high risk of PVT. If symptoms appear, patients need to be treated with high-dose heparin followed, after at least 3 weeks, by oral anticoagulant therapy.

There is evidence that leukocytosis is associated with an increased risk of first thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Whether it is a risk factor for recurrent thrombosis too is currently unknown. In the frame of a multicenter retrospective cohort study, we recruited 253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who were not receiving cytoreduction at the time of thrombosis. The probability of recurrent thrombosis associated with the leukocyte count recorded at the time of the first thrombosis was estimated by a receiver operating characteristic analysis and a multivariable Cox proportional hazards regression model. Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12-4.18) in patients with a leukocyte count that was >12.4 x 10(9)/L at the time of the first thrombotic episode. The prognostic role for leukocytosis was age-related, as it was only significant in patients that were aged <60 years (HR for arterial recurrence 3.35, 95% CI 1.22-9.19).

Evidence suggests that the JAK2 V617F mutation is associated with an increased risk of first thrombosis in patients with essential thrombocythemia (ET). Whether this mutation is also a risk factor for recurrent thrombosis is currently unknown. To investigate the impact of the JAK2 V617F mutation on the risk of recurrent thrombosis in patients with ET, we carried out a multicentre retrospective cohort study. We recruited 143 patients with previous arterial (64.4%) or venous major thrombosis (34.8%) or both (0.8%); 98 of them (68.5%) carried the mutation. Thrombosis recurred in 43 of the patients (30%); overall, after adjustment for sex, age, presence of vascular risk factors, and treatment after the first thrombosis, the presence of the JAK2 mutation did not predict recurrence (multivariable hazard ratio, HR, 0.88, 95% CI 0.46-1.68). Indeed, the individuals homozygous for the JAK2 V617F (allele burden >50%) mutation had an increased risk of recurrence in comparison with wild-type patients (HR 6.15, 95% CI 1.51-24.92). In conclusion, a homozygous JAK2 V617F mutation is an independent risk factor for recurrent thrombosis in patients with ET.

Since its introduction in 1992 laparoscopic splenectomy (LS) has become the technique of choice for surgical removal of the spleen in several centres. The procedure, however, is associated with risks and complications, either during surgery or in the postoperative phase. Although the incidence of intraoperative complications is unknown, intraoperative risks in patients undergoing laparoscopic splenectomy are not uncommon. In this article, we reviewed the literature on risks and complications during LS, and we point out, based on our personal series and on the experiences reported by other Authors, how to prevent, whenever possible, these complications.

Background: Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence., Design and Methods: We retrospectively estimated the rate of recurrence in a multicenter cohort of 494 patients (poly-cythemia vera/essential thrombocythemia 235/259) with previous arterial (67.6%) or venous thrombosis (31%) or both (1.4%). First thrombosis was cerebrovascular disease in 191 cases, acute coronary syndrome in 106, peripheral arterial thrombosis in 44, and venous thromboembolism in 160. Microcirculatory events were not computed., Results: Thrombosis recurred in 166 patients (33.6%), with an incidence of 7.6% patient-years. Sex, diagnosis (polycythemia vera or essential thrombocythemia), and presence of vascular risk factors did not predict recurrence, whereas age >60 years did (multivariable hazard ratio [HR], 1.67; 95% confidence interval [CI] 1.19-2.32). Increased leukocyte count at the time of the first thrombosis was a risk factor for recurrence in patients <60 years old (HR 3.55; 95% CI 1.02-12.25). Cytoreduction halved the risk in the overall cohort (HR 0.53; 95% CI 0.38-0.73) and the combination with antiplatelet agents or oral anticoagulants was more effective than administration of single drugs. Significant prevention of rethrombosis was independently achieved in patients with venous thromboembolism by both oral anticoagulants (HR 0.32; 95% CI 0.15-0.64) and antiplatelet agents (HR 0.42; 95% CI 0.22-0.77), in those with acute coronary syndrome by cytoreduction (HR 0.30; 95% CI 0.13-0.68), and in those with cerebrovascular disease by antiplatelet agents (HR 0.33; 95% CI 0.16-0.66). The overall incidence of major bleeding was 0.9% patient-years and rose to 2.8% in patients receiving both antiplatelet and anti-vitamin K agents., Conclusions: In patients with polycythemia vera and essential thrombocythemia, cytoreduction protects against recurrent thrombosis, particularly after acute coronary syndrome. The contemporary use of oral anticoagulants (after venous thromboembolism) or antiplatelet agents (after cerebrovascular disease or venous thromboembolism) further improves the protective effect. Such findings call for prospective studies aimed at investigating whether strategies tailored according to the type of first thrombosis could improve prevention of recurrences.

Cigarette smoking plays a major role in the development of atherosclerosis and is associated with increased morbidity and mortality for coronary heart disease, stroke and peripheral vascular disease. In spite of the abundance of epidemiological evidence that links cigarette smoking to vascular disease, the pathologic mechanisms for such interaction are not clear. The endothelium is a major target organ that undergoes activation when exposed to common vascular triggers, including hypertension, hypercholesterolemia, hyperglycaemia and smoking. Changes in endothelial function may lead to a dysfunctional vascular phenotype characterized by anomalous responses of the vascular tone, abnormal endothelial proliferation and prothrombotic activation. Several studies have demonstrated that smoking may alter endothelial function by a direct toxic effect and consequently trigger haemostatic activation and thrombosis. In this article we will review the evidence that loss of normal endothelial function may result in a loss of the balance of the haemostatic system and in changes of the platelet physiology that may be relevant for the pathogenic effect of smoking on the development of atherothrombosis.

We prospectively evaluated the effect of anagrelide (ANA) on platelets, PF4, F1+2, PAP, PAI-1, and TFPI and erythromelalgia in patients with essential thrombocythemia (ET) receiving anti-aggregants both pre- and post-ANA. At first, we observed a successful reduction of platelets, which was associated with normalization of platelet coagulant and endothelial function and disappearance of erythromelalgia. Secondly, we found a correlation between PF4 and TFPI and between TFPI and thrombosis, suggesting that erythromelalgia may be caused by platelet-mediated endothelial activation. These data may indicate that ANA may be efficacy in the treatment of symptomatic patients with ET., (Copyright 2005 Wiley-Liss, Inc.)

Background: Previous studies have shown that inhaled heparin attenuated the airway responses to allergen, exercise, and AMP bronchial provocation, possibly through an inhibition of mast cell activation., Objective: The aim of this study was to provide the evidence of in vivo inhibition of human mast cell activation by heparin in a noninvasive model., Methods: Nine atopic and 6 nonatopic subjects received placebo and unfractionated heparin sodium (5000 IU/mL) 15 minutes before an AMP nasal provocation in a double-blind crossover study design. The nasal lavage was collected from these subjects before or 3, 5, 15, or 30 minutes after the AMP nasal challenge, and concentrations of histamine and tryptase in the nasal lavage were measured., Results: AMP nasal provocation produced considerable sneezing and induced a transient increase in histamine and tryptase release, with peak values achieved at 3 to 5 minutes after the challenge in all atopic subjects. Compared with placebo, inhaled heparin significantly attenuated the release of histamine and tryptase induced by AMP challenge (P=.012 and.004, respectively). Moreover, the AMP-induced sneezing was also inhibited by pretreatment with heparin (P=.016). In nonatopic subjects, AMP did not induce a significant increase in histamine and tryptase release on placebo-treated or heparin-treated days., Conclusion: These data suggest that AMP nasal provocation and AMP bronchial provocation cause mast cell mediator release in a similar fashion. In addition, the data support the hypothesis that inhaled heparin plays a protective role against AMP provocation by inhibition of mast cell activation.

Background: Ozone is a photochemical oxidant pollutant that is an important public health hazard. Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood., Objective: Because the epidermal growth factor receptor (EGFR) is a central regulator of epithelial function, we tested the hypothesis that nasal epithelial cells respond to ozone-induced oxidant stress by modulating expression of the EGFR and its ligands, EGF and transforming growth factor-alpha (TGF-alpha)., Methods: Normal volunteers were exposed to air or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF-alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF-alpha; mediator release was measured by ELISA and cellular EGFR expression by immunoblotting and fluorescence-activated cell sorting analysis., Results: Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P <.05) increased in the nasal biopsy specimens after ozone exposure, and there was a significant positive correlation between EGFR expression and the increase in neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR expression, even though IL-8 release was enhanced. In contrast, exposure to TNF-alpha caused EGFR levels to increase significantly., Conclusion: These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha.

Background: The incidence of deep vein thrombosis and pulmonary embolism following laparoscopic surgery is unknown and studies on alterations of hemostasis after laparoscopy are inconclusive., Methods: In this study we prospectively evaluated changes in prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (Fg), antithrombin III (ATIII), prothrombin fragment F 1 + 2, beta-thromboglobulin (betaTG) and D-dimer (D-D), preoperatively and 24 h after laparoscopic surgery in 16 patients., Results: Comparing pre- and postoperative values, no statistical differences were observed in aPTT, F1 + 2, and ATIII measurements. Postoperative PT values increased slightly (p approximately 0.05) after surgery. Conversely, Fg, betaTG, and D-D values were statistically higher in the 24-h evaluation (p = 0.008, 0.01, and 0.045, respectively)., Conclusions: These data suggest that laparoscopic surgery induces activation of coagulation and fibrinolytic pathways and, additionaly, betaTG elevation, which has never been reported and might account for postoperative platelet activation and a greater risk of thrombogenicity. Therefore, routine thromboembolic prophylaxis in patients undergoing laparoscopic surgery is recommended.

Laparoscopic splenectomy (LS) is now considered the procedure of choice for removal of the spleen in several hematologic and traumatic splenic conditions. Perisplenitis is still considered a relative contraindication. We report a rare case of isolated splenic candidiasis treated by laparoscopic splenectomy. The technical challenges of the laparoscopic approach in cases of perisplenitis are outlined. Because of dense adhesions to the diaphragm, the LS was converted to open splenectomy, and the procedure was completed through a small subcostal incision. This case report suggests the need for and effectiveness of splenectomy in patients whose fungal infection is suspected to be localized to the spleen. Laparoscopic removal of the spleen in these cases is very difficult to accomplish because of the risk for diaphragm injuries and the technical problems encountered.

Background: Airway hyperresponsiveness (AHR) to pharmacologic stimuli and sputum eosinophils might be useful in the individual adjustment of long-term asthma management. However, it is not clear whether inhaled glucocorticosteroids (GCSs) provide greater protection against specific surrogate markers of airways inflammation than other means. In addition, detailed longitudinal assessment of changes in airway response with inhaled GCSs has never been carried out., Objectives: We compared changes in AHR to inhaled methacholine and adenosine 5'-monophosphate (AMP) after budesonide treatment in a randomized, double-blind, placebo-controlled, crossover study of patients with mild-to-moderate asthma. Subsequently, we undertook a separate study to examine the time course of the changes in AHR in more detail and the changes in sputum cell counts in relation to budesonide treatment., Methods: In the phase 1 of the study, patients undertook bronchial provocation studies with increasing doubling concentrations of methacholine (0.06 to 16 mg/mL) and AMP (3.125 to 800 mg/mL) before and after budesonide 0.8 mg/daily for 3 weeks. The bronchial responses to the inhaled agonists were expressed as the provocative concentration causing a 20% decline in FEV(1) (PC(20)). In phase 2 of the study, patients attended the laboratory on 12 separate occasions to investigate changes in PC(20) methacholine, PC(20) AMP, and sputum cell counts before, during, and after withdrawal of therapy with inhaled budesonide 0.8 mg/daily for 6 weeks., Results: Budesonide treatment for 3 weeks significantly attenuated the constrictor response by 0.8 +/- 0.3 doubling doses for methacholine and by 2.6 +/- 0.5 doubling doses for AMP. These changes were significantly different from each other (P =.003). Significant variation in PC(20) methacholine (P <.05) value, PC(20) AMP (P <.001) value, percentage of sputum eosinophils (P <.001), and percentage of sputum epithelial cells (P <.001) were observed throughout the longitudinal assessment of changes in airway response to budesonide. Compared with the other surrogate markers, PC(20) AMP appears to be useful in promptly detecting early inflammatory changes of the asthmatic airways; a significant change of 1.6 +/- 0.3, 2.2 +/- 0.3, and 2.8 +/- 0.3 doubling doses of PC(20) AMP was observed at 1, 4, and 6 weeks, respectively, in the course of budesonide treatment., Conclusions: The present findings underline the exquisite selectivity of diverse surrogate markers of airway inflammation in response to inhaled budesonide. When compared with that to the other markers, AHR to inhaled AMP is an early and sensitive indicator of the beneficial anti-inflammatory effects of topical GCSs.

Presacral myelolipoma is a rare benign tumour composed of fat and haemopoietic tissue. Ultrasound, computed tomography and magnetic resonance imaging are of help to achieve the diagnosis, but pathologic confirmation is mandatory. The Authors report an asymptomatic case whose diagnosis has been achieved by means of CT scan-guided percutaneous needle biopsy. Unnecessary surgical treatment was avoided in this case. Clinical approach and role of surgery are discussed.

Clinical guidelines are statements designed to help physicians make decisions about appropriate health care for specific circumstances. The constant rise in the number of published guidelines has been accelerated by the need of healthcare organizations to integrate evidence from clinical research with rational health policy, with the prospect of improving the quality and reducing the costs of health care at a local level. The best guidelines are developed from a systematic examination and appraisal of good evidence from well conducted trials, supported by appropriate clinical expertise, and leading to unambiguous recommendations. Great care needs to be taken both to maximize the validity of guidelines and to ensure their use within clinical practice. Moreover, the evidence on which clinical guidelines are based can change with time and therefore they should be reviewed regularly. The critical approaches to making high-quality guidelines, the value of implementation strategies, and how healthcare organizations and individual physicians can use medical guidelines to enhance clinical effectiveness will be discussed.

Cholecystectomy is a common surgical procedure performed in patients with sickle cell disease (SCD). Postoperative complications, including acute painful vaso-occlusive crisis and acute chest syndrome, have been described frequently after either traditional or laparoscopic cholecystectomy (LC). It's still not clear if preoperative blood transfusion, hyperhydration, intraoperative body temperature conservation may reduce complications rate. The Authors reviewed the charts of seven patients with SCD operated on LC for symptomatic gallbladder lithiasis and describe their perioperative management. In 3 patients preoperative endoscopic removal of stones was achieved. Five patients with HB lower than 9 g/dl and/or HbS higher than 40% were transfused preoperatively and all the patients were hyperhydrated. Intraoperative monitoring was achieved for early recognition of ventilation to perfusion mismatch and acid-base balance or temperature modifications. The Authors reported only one case of postoperative lower extremities pain. This study suggests that LC is a safe procedure in SCD if appropriate monitoring and perioperative management are achieved.

A total of 26 surgical patients with chronic idiopathic thrombocytopenic purpura (ITP) were reviewed and results of splenectomy were statistically related to age and sex, length of and response to pre-operative corticosteroid therapy, pre-operative platelet count and time interval between diagnosis and surgery. Median age was 37 years (range, 17-81 years) and the male:female ratio was 1.16. Pre-operative platelet count ranged from 2-70 x 10(9)/l. The length of pre-surgical corticosteroid therapy (prednisone 1-2 mg/kg/day) varied from 2 weeks to 3 years. Steroid therapy was unsuccessful in 15 patients and only achieved temporary remission in the remaining 11 cases. The time interval between diagnosis and splenectomy ranged from 4-60 months. There were 21 responders (80.4%) and 5 non-responders (19.6%) to splenectomy. Using the chi-square test, differences in age, length and response to pre-operative steroid therapy and diagnosis-to-splenectomy interval did not achieve statistical significance when responder and non-responder groups to splenectomy were compared. Conversely, a significant difference was found comparing male to female groups, since 92.9% of males and only 66.7% of females were successfully treated by surgery (P approximately 0.01). In addition, patients with a pre-operative platelet count less than 30 x 10(9)/l responded at an higher rate (100% versus 70.6%; P approximately 0.05) to splenectomy.

In the hemopoietic system, interactions between stem cells and components of the bone marrow microenvironment play a pivotal role in blood cell proliferation and differentiation. Among the adhesion molecules, the integrins of the beta 1-subfamily are known to direct cell-cell and cell-matrix interactions and evidence has been provided that CD34-positive stem cells bind either to the bone marrow stroma or to the extracellular matrix proteins through the beta 1-integrins. It seems that changes in their expression pattern or signalling function are likely to reflect disturbances at the hemopoietic bone marrow microenvironmental level. Any alteration of their biological functions makes them attractive candidates for playing decisive roles in the leukemic processes. In this view, beta 1-integrins have been recognized to mediate those cellular interactions and migrations that are important in the biology of leukemia. In this paper we review some aspects of the role played by beta 1-integrins, especially VLA-4 and VLA-5, in adult acute lymphoblastic leukemia in relation with the expression rate of the stem cell antigen CD34.

Kinins may affect lung mucociliary clearance in man by interacting with specific surface receptors designated B1 and B2. To evaluate this possibility, we have compared the effect of inhaled bradykinin and [desArg9]-bradykinin on mucociliary clearance in healthy volunteers. Four subjects attended the laboratory on three separate occasions to undertake tracheobronchial clearance studies, by a noninvasive radioisotopic technique, followed by inhalation with either bradykinin (8 mg.mL-1), [desArg9]-bradykinin (8 mg.mL-1), or vehicle placebo 30 min after radioaerosol inhalation. Half-hourly whole lung counts were measured for 6 h with two collimated scintillation counters and a tracheobronchial clearance curve was plotted for each subject on each occasion. In all the subjects studied, mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first 6 h (AUCo-6h) was enhanced after inhaling bradykinin and prolonged following exposure with [desArg9]-bradykinin when compared to placebo. The median values (range) for AUCo-6h were significantly reduced from 123 (83-152)%.h to 92 (51-133)%.h with placebo and bradykinin, respectively, and significantly augmented to 269 (144-331)%.h after exposure with [desArg9]-bradykinin. This small study suggests that acute exposure with inhaled bradykinin accelerates, whilst [desArg9]-bradykinin delays, tracheobronchial clearance in normal human airways.

The use of recombinant erythropoietin for treatment of anemia in myelodysplastic patients has so far produced poorer results than expected. Most clinical studies have been conducted without any selection of patients. In the present study we report our experience with the use of rhEPO in a population of selected MDS subjects. Only patients affected by refractory anemia according to FAB criteria, without significant WBC and platelets reduction, with normal LDH and short history of disease were eligible for the study and were treated with rhEPO at a dosage of 150 mg/kg three times a week for 2 months. Among the 12 so treated patients, 7 (58.3%) achieved complete remission, 2 partial remission and 3 failed to respond. This high response rate makes more than acceptable the cost/benefit ratio for rhEPO in RA patients and may identify a subgroup of patients that can be treated successfully with rhEPO alone.

Cutaneous vasculitis has been described in association with various hematological malignancies, but it seems to be very uncommon among non Hodgkin's lymphomas (NHL). For this reason no attention has been given to the peculiarity of this rare association. We identified 5 cases of cutaneous vasculitis among 315 NHL patients examined at our Institution from 1984 through 1990 and after the appearance of vasculitis, we observed some heterogeneity in either the degree of activity or in the clinical outcome of the NHL. The onset of cutaneous vasculitis appeared to mark two different clinical patterns: a vasculitis present from diagnosis characterized an indolent course of the neoplasia, while a late-appearing vasculitis was followed by rapid lymphoma progression and short survival.

The expression of the pluripotent stem cell antigen CD34 was evaluated at diagnosis in forty-five adult patients with de novo ALL. Comparison of clinical and hematological features between CD34 positive (24/45) and CD34 negative (21/45) patients showed that the former were of older age, had more pronounced lymphoid organ involvement and higher serum LDH levels. Immunophenotypic analysis of marrow blast cells revealed a significant predominance of the 'null' phenotype in the CD34 positive group, together with a strong expression of the VLA-4 and VLA-5 integrins (fibronectin receptors). CD34 positive ALL were also more frequently associated with either aberrant myeloid-related antigens (CD13, CD33) or the P-gp/MDR-1 phenotype. Only 11 out of 24 (45%) CD34 positive patients achieved complete remission after induction chemotherapy, compared to 20/21 (95%) CD34 negative cases. Furthermore, survival was significantly shorter in the CD34 positive group (6.6 mo. vs 13.5 mo.). These results suggest that in ALL, as in AML, CD34 positivity may predict a poor prognosis.

Kinins (i.e. bradykinin, kallidin and [desArg9]-bradykinin) are vasoactive oligopeptides which may contribute as mediators in the pathogenesis of asthma by interacting with specific receptors designated as B1 and B2. The aim of the present study was to investigate the airway response to inhaled histamine, bradykinin, kallidin and [desArg9]-bradykinin in normal and asthmatic subjects. Changes in airway caliber were followed as FEV1 (forced expiratory volume in 1 sec) and as Vp30 (maximum expiratory flow at 30% of the vital capacity). Neither histamine, bradykinin, kallidin nor [desArg9]-bradykinin had any measurable bronchoconstrictor effect in the normal subjects. However, in the asthmatic subjects, histamine, bradykinin and kallidin, but not [desArg9]-bradykinin, produced prompt concentration-related bronchoconstriction. The geometric mean PC20FEV1 (provocation-concentration of inhaled agonist reducing the FEV1 by 20% from baseline) values were 0.027, 0.082 and 0.44 mg/mL for bradykinin, kallidin and histamine respectively. Because bradykinin and kallidin are agonists of B2 receptors and [desArg9]-bradykinin is an agonist for B1 receptors, our data suggest that asthmatic, but not normal, airways are hyperresponsive to kinins and that this potent bronchoconstrictor response is due to a specific pharmacologic effect compatible with the stimulation of B2 receptors.

In the present study the effects on the polyclonal Ig synthesis of peripheral MM T gamma and T non-gamma cell fractions when cocultured with autologous and normal allogenic B-lymphocytes have been reported. Five untreated MM patients (three IgG-kappa, two IgG-lambda) were studied employing a five-day PWM-stimulated co-culture technique, in which the percentage of cells with detectable amounts of cytoplasmic Ig was evaluated by direct immunofluorescence. Our results indicated that depressed polyclonal Ig synthesis in human MM could be ascribed not only to an increased "suppressive" activity of T gamma cells but also to an impaired "inducer" function of T non-gamma lymphocytes and to an intrinsic B-lymphocyte disfunction as well. In addition, it was noteworthy that MM T gamma cells showed on normal Ig synthesis a selective suppressive effect mainly for those Ig chains corresponding to the monoclonal Ig which characterizes the own myeloma type. The significance of this datum, so far not yet reported, remains to be established.