Hemosuccus pancreaticus - Multidisciplinary therapy for a splenic artery aneurysm, ruptured into the pancreatic duct.

BACKGROUND: Numerous conditions may lead to gastrointestinal bleeding (GIB). Compared with common causes, hemosuccus pancreaticus (HP) is a scarce and potentially life-threatening condition. CASE PRESENTATION: We report the case of a 45-year-old female patient who suffered from hematemesis and subsequent hemorrhagic shock. In repeat esophagogastroduodenoscopies, bleeding from the major duodenal papilla was detected. To stop the acute bleeding, an ERCP was performed, and a plastic stent was inserted into the pancreatic duct (PD). Subsequently, MR and CT scans demonstrated a pseudoaneurysm of the splenic artery (SA) with a fistula to the PD. An interventional therapy approach failed due to a highly twisted course of the SA. Thus, the patient underwent surgery with ligation of the SA. The stent from the PD was removed postoperatively, and the patient recovered well. A histological examination of the SA revealed fibromuscular dysplasia. A lifelong ASA therapy was prescribed, and the patient was discharged on the 14th postoperative day in good condition. CONCLUSION: The diagnosis and treatment of HP might be impeded due to its multiple causes, ambiguous symptoms, and challenging diagnostic verification. Being a potentially life-threatening condition, the knowledge of this rare entity and the provision of multidisciplinary and multimodal therapy are mandatory for the successful treatment of patients with obscure GIB and proven HP.

[Late Open Semi-conversion with Endograft Preservation for (Type II) Endoleaks with Late Aneurysm Sac Enlargement after EVAR - Indications, Method and Results in Our Own Patient Collective]. / Die späte offene Semikonversion mit Prothesenerhalt bei (Typ II­)Endoleckagen mit spätem Aneurysmasackwachstum nach EVAR - Indikationen, Methode und Ergebnisse im eigenen Patientenkollektiv.

EVAR (endovascular aortic repair) is the most common method for treating an abdominal aortic aneurysm, but according to the latest findings it carries the risk of subsequent complications. These can be caused by (late) aneurysm sac growth. If conservative and surgical therapies fail to treat the aneurysm sac growth, open conversion is necessary to prevent aneurysm rupture. There are several options for open conversion, in which the EVAR prosthesis can be completely preserved or is (partially) removed. Late open semi-conversion with complete in-situ preservation of the EVAR-prosthesis and gathering of the aneurysm sac are a less invasive method than complete conversion and may be performed instead for selected patients. The aim of the present work is to present the surgical method, including indications and technical information, as well as the presentation of the results in our recent patient collective.All patients semi-converted in our department of vascular surgery and phlebology due to (type II) endoleak were included. All data are presented as n (%) or median (range).Between 6/2019 and 3/2023, 13 patients underwent semi-conversion 6 (2-12) years (median, range) after the initial EVAR. The aneurysm sac diameter at the time of semi-conversion was 69 mm (58-95 mm), the operating time was 114 min (97-147 min), the blood loss was 100 ml (100-1500 ml). Five (38%) patients received blood transfusion intraoperatively and 2 (15%) postoperatively. The stay in the intensive care unit lasted 1 (1-5) days, the hospitalisation time was 8 (6-11) days. Postoperative complications were intestinal atony (3 [23%], 1 [8%] with nausea/emesis and gastric tube insertion), anaemia (2 [15%]), hyponatraemia (2 [15%]), delirium (1 [8%]), COVID-19 infection (1 [8%]) and 1 [8%] intra-abdominal postoperative bleeding with the indication for surgical revision and the transfusion of 8 erythrocyte concentrates.Semi-conversion is a safe and practicable surgical method with few severe complications for a selected group of patients, which should be considered as an alternative to more invasive methods with (partial) removal of the EVAR-prosthesis. Further long-term studies comparing semi-conversion to full conversion are needed to demonstrate its benefits.

Adductor Canal Compression Syndrome in a 46-Year-Old Female Patient Leading to Acute External Iliac, Femoral, and Popliteal Artery Thrombosis and Critical Ischemia: A Case Report.

The adductor canal compression syndrome is one of the several rare nontraumatic causes of arterial occlusions, which may lead to critical ischemia of the lower limb. We report the case of a 46-year-old athletic woman, who suffered from activity-related paresthesia and sharp pain in the left upper and lower leg for 2 years. Imaging and neurological investigations of the spine remained without pathological findings that would explain the patient's complaints. Actually, the patient presented with symptoms of critical lower limb ischemia. Magnetic resonance angiography revealed nearly complete thrombotic occlusion of the common femoral artery and the arteries of the lower leg. An emergency surgery was performed, revealing an external compression of the superficial femoral artery in the adductor canal. Subsequently, a thrombectomy was performed and a venous bypass graft was installed. No postoperative complications occurred, the patient recovered well and could return to her activities of daily living about 3 weeks after the surgery. The adductor canal compression syndrome results from a local anomalous musculotendinous band or hypertrophic musculature surrounding the passing structures. It mainly occurs in athletes exposed to repetitive stress, especially runners and skiers, and may lead to thrombosis followed by critical lower extremity ischemia. The lack of obvious symptoms during routine physical examination often impedes rapid diagnosis and timely therapy. Considering the high thrombotic risk, attention should be paid to this rare cause of lower limb pain to prevent the patient from critical lower extremity ischemia and potential limb loss due to consecutive acute thrombotic occlusions.

Successful Management of an Infected Aortic Stent Graft in a Liver Transplanted Patient.

We report on a 57-year-old female liver transplanted patient who underwent endovascular aneurysm repair because of an infrarenal abdominal aortic aneurysm. Two months later, she developed an infection, and positron emission tomography computed tomography detected a paraprosthetic abscess. Explantation of the endoprosthesis and aortic reconstruction with a Y-shaped silver graft was made. The patient was discharged on the 12th postoperative day and shows up regularly in our outpatients department in a good clinical condition. After meticulous research of the current literature, this is the first published case of the successful management of an infected endovascular aortic stent in a liver transplanted patient.

Antithrombin reduces inflammation and microcirculatory perfusion failure in closed soft-tissue injury and endotoxemia.

BACKGROUND: Closed soft-tissue trauma leads to activation of the coagulation cascade and is often complicated by systemic inflammation and infection. Previous investigations have shown potent anti-inflammatory properties of antithrombin. We herein report on the action of antithrombin on skeletal muscle injury in experimental endotoxemia. MATERIALS AND METHODS: By using a pneumatically driven computer-controlled impact device, closed soft-tissue trauma was applied on the left hind limb of pentobarbital-anesthetized rats. Six hours later, endotoxemia was induced by intraperitoneal injection of Escherichia coli lipopolysaccharide. An equivalent volume of physiological saline was given in controls. At the same time point, treatment of animals was started by intravenous injection of antithrombin (250 IU/kg body weight) or vehicle solution. Twenty-four hours after trauma, the extensor digitorum longus muscle was microsurgically exposed and analyzed by means of high-resolution multifluorescence microscopy. RESULTS: Traumatic soft-tissue injury with additional endotoxemia was characterized by nutritive perfusion failure (functional capillary density: 379±20cm/cm;), tissue hypoxia (nicotinamide adenine dinucleotide autofluorescence: 77±4 aU), and enhanced leukocyte-endothelial cell interaction (773±35 cells/mm;). Therapeutic intervention with antithrombin 6 hrs after trauma restored nutritive perfusion and tissue oxygenation (functional capillary density: 469±22cm/cm; nicotinamide adenine dinucleotide autofluorescence: 61±5 aU [p < 0.05]) and reduced inflammatory leukocyte adherence (237±20 cells/mm; [p < 0.05]) toward values found in nontraumatized controls (functional capillary density: 573±13cm/cm; nicotinamide adenine dinucleotide autofluorescence: 56±2 aU; leukocyte adherence: 204±20 cells/mm;). CONCLUSION: Antithrombin ameliorates microcirculatory dysfunction and tissue injury in traumatized animals during endotoxemia. Furthermore, a reduced inflammatory cell response helps to prevent leukocyte-dependent secondary tissue injury.

Antithrombin therapy in pancreas retransplantation and pancreas-after-kidney/pancreas-transplantation-alone patients.

Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities. AT reduces ischemia/reperfusion injury and has been successfully used in patients with simultaneous pancreas kidney transplantation. This study retrospectively analyzes prophylactic high-dose AT application in patients with solitary pancreas transplantation traditionally related to suboptimal results. In our center, 31 patients received solitary pancreas transplantation between 7/1994 and 7/2005 (pancreas retransplantation, PAK/PTA). The perioperative treatment protocol was modified in 5/2002 now including application of 3000 IU. AT was given intravenously before pancreatic reperfusion (AT, n = 18). Patients receiving standard therapy served as controls (n = 13). Daily blood sampling was performed during five postoperative days. Standard coagulatory parameters and number of transfused red blood cell units were not altered by AT. In AT patients serum amylase (p < 0.01) and lipase (p < 0.01) on postoperative days 1, 2 and 3 were significantly reduced. Our actual perioperative management protocol including high dose AT application in human solitary pancreas transplantation reduced postoperative liberation of pancreatic enzymes in this pilot study. Prophylactic AT application should deserve further clinical testing in a randomized controlled trial.

Atypical and rare cause of myocardial infarction: coronary subclavian steal syndrome (CSSS) treated by a carotid-subclavian bypass in a 71-year-old female patient.

BACKGROUND: The coronary subclavian steal syndrome (CSSS) is a rare complication after coronary arterial bypass graft operations (CABG) using the left or right internal mammary artery ((L/R)IMA). It results from a retrograde blood flow from the IMA into the subclavian artery (SA) due to a stenosis or occlusion of the SA proximal to the IMA origin. This "steal phenomenon" leads to a decreased blood flow in the IMA and may result in myocardial ischemia (MIS) and even myocardial infarction (MIN). Treatment options include interventional and surgical therapy. CASE PRESENTATION: We report the case of a 71-year old woman, who suffered from an acute non-ST elevation myocardial infarction (NSTEMI) 11 years after LIMA-CABG surgery and who was treated successfully with a carotid-subclavian bypass (CSB) after failed interventional therapy. CONCLUSION: CSB may be regarded as a viable treatment option for patients suffering CSSS in the case of MIS and even an acute MIN/NSTEMI, especially in the case of missing or failed interventional therapy attempts. Specialists in cardiothoracic and vascular surgery should be aware of possible CSSS conditions and know about appropriate diagnostic and therapeutic options.

Intraoperative use of transit time flow measurement improves patency of newly created radiocephalic arteriovenous fistulas in patients requiring hemodialysis.

BACKGROUND: The autologous arteriovenous fistula is the primary choice to establish hemodialysis access without high failure rates. Intraoperative ultrasound flow measurements of newly created autologous arteriovenous fistulas represent a possibility of quality control and may therefore be a tool to assess their functionality. The aim of our study was to correlate intraoperative blood flow with access patency. METHODS: Between March 2012 and March 2015, intraoperative transit time flow measurements were collected on 89 patients. Measurements were performed 5-10 min after the creation of a standardized anastomosis using 3-6 mm flow probes. To examine the correlation between intraoperative blood flow and access patency, groups of patients with high (> 200 mL/min) versus low flow (< 200 mL/min) were enrolled. Patients were assessed clinically and with ultrasound every 3 months. Data were analyzed retrospectively. RESULTS: In the current short-term follow-up, including 89 patients (age 62 ± 3 years), 61 (68.5%) of the autologous arteriovenous fistulas were currently being used in an observation period ranging from 3 months to 3 years (mean observation period 546 ± 95 days) postoperatively. The intraoperative blood flow in patients with functioning autologous arteriovenous fistula (78) was significantly higher than that of patients without functioning autologous arteriovenous fistulas (407 ± 25 vs 252 ± 42 mL/min, respectively; p < 0.005) (11). CONCLUSION: The intraoperative measurement of blood flow is a useful tool to predict the outcome of maturation in autologous arteriovenous fistula. With this method, technical problems can be detected and corrected intraoperatively. Routine implementation of intraoperative flow measurements has to be examined by prospective controlled trials.

Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding.

INTRODUCTION: Prothrombin complex concentrates are recommended for rapid reversal of vitamin K anticoagulants. As they normalize levels of vitamin K dependent clotting factors and re-establish hemostasis, they may also be used as adjunctive therapy in patients with major bleeding. The aim of this study was to retrospectively evaluate the efficacy of prothrombin complex concentrates in the surgical setting. METHODS: The case notes of 50 patients requiring urgent oral anticoagulation reversal (n = 12) or with severe perioperative coagulopathic bleeding (n = 38) who received an infusion of prothrombin complex concentrate (Beriplex P/N(R) 500) at the surgical department of the University of Munich Hospital, Germany were retrospectively reviewed. Efficacy of prothrombin complex concentrate application was evaluated using the Quick test, reported as an international normalized ratio, hemodynamic measurements and requirement for blood products. Safety assessments included whole blood hemoglobin levels and specific parameters of organ dysfunction. RESULTS: Baseline characteristics were comparable, except that mean baseline international normalized ratio and hemoglobin levels were significantly higher (P < 0.01) in anticoagulation reversal than in bleeding patients. In anticoagulation reversal, the international normalized ratio was significantly reduced (from 2.8 +/- 0.2 at baseline to 1.5 +/- 0.1, P < 0.001) after one prothrombin complex concentrate infusion (median dose 1500 IU; lower quartile 1,000, upper quartile 2,000). No major bleeding was observed during surgery after prothrombin complex concentrate administration. Only one patient received platelets and red blood cell transfusion after prothrombin complex concentrate administration. In bleeding patients, infusion of prothrombin complex concentrate (median dose 2,000 IU; lower quartile 2,000, upper quartile 3,000) significantly reduced the INR from 1.7 +/- 0.1 at baseline to 1.4 +/- 0.1 (P < 0.001). This decrease was unrelated to fresh frozen plasma or vitamin K administration. Bleeding stopped after prothrombin complex concentrate administration in 4/11 (36%) patients with surgical bleeding and 26/27 (96%) patients with diffuse bleeding. Hemoglobin levels increased significantly from baseline in bleeding patients (P < 0.05) and mean arterial pressure stabilized (P < 0.05). No thrombotic events or changes in organ function were reported in any patient. CONCLUSIONS: Prothrombin complex concentrate application effectively reduced international normalized ratios in anticoagulation reversal, allowing surgical procedures and interventions without major bleeding. In bleeding patients, the improvement in coagulation after prothrombin complex concentrate administration was judged to be clinically significant.

Efficacy of antithrombin in the prevention of microvascular thrombosis during endotoxemia: an intravital microscopic study.

INTRODUCTION: The KyberSept trial in septic patients showed that antithrombin (AT) reduced 90-day mortality significantly in a subgroup of patients not receiving concomitant heparin for thrombosis prophylaxis. Microvascular thrombosis is a key pathophysiologic mechanism during sepsis, ischemia/reperfusion and disseminated intravascular coagulation (DIC). Therefore, this study investigated the antithrombotic property of AT as potential monotherapy in an experimental endotoxemia model in order to omit concomitant heparin. MATERIALS AND METHODS: Using a light/dye injury model in the ear and the cremaster muscle preparation of mice, we quantitatively assessed microvascular thrombus formation in a total of 30 endotoxemic mice by means of intravital fluorescence microscopy. Before thrombus induction animals received a single i.v. bolus of AT (100 or 250 IU/kg), heparin (100 IU/kg) or saline (NaCl). RESULTS: In NaCl-treated endotoxemic animals, light/dye exposure led to complete thrombotic occlusion in arterioles and venules within <450 s in the ear model. Heparin delayed thrombotic vessel occlusion by more than 50%. AT significantly prolonged times until thrombotic vessel occlusion in a dose-dependent manner and more effectively than heparin (p<0.05 vs. NaCl and heparin). This anti-coagulative effect of AT was especially pronounced in arterioles. Upon light/dye exposure to cremaster muscle preparations in endotoxemic mice AT also caused a 4-fold delay in microvascular thrombus growth with 827+/-77 s until complete thrombotic occlusion. CONCLUSIONS: We could characterize for the first time AT-mediated antithrombotic activity during endotoxemia in two models of phototoxicity-induced microvascular thrombosis. Our results clearly demonstrate an additional AT mechanism of action that may be responsible for beneficial effects observed during endotoxemia and DIC. This AT profile may allow future high-dose AT application without giving heparin for thrombosis prophylaxis, an intriguing strategy that is to be tested under clinical conditions.

Antithrombin and hypercoagulability in sepsis: insights from thrombelastography?

Antithrombin (AT) has been used for over 25 years to successfully treat disseminated intravascular coagulation (DIC). A four-day AT therapy in patients with DIC in the KyberSept trial has been related to a clear survival benefit in patients not receiving concomitant heparin. Gonano and coworkers performed thrombelastography (TEG) measurements in patients with severe sepsis and clearly showed hypercoagulability, as defined by five TEG parameters, compared to healthy controls. In the AT group they found a trend towards normalization of TEG parameters after treatment, although this did not reach statistical significance. This first clinical evaluation of hypercoagulability during AT treatment could not provide evidence for an attenuation of coagulopathy, an effect that might be due to high inter-individual variability.

Antithrombin is as effective as heparin and hirudin to prevent formation of microvascular thrombosis in a murine model.

A recently published post-hoc analysis of a trial using high-dose antithrombin (AT) in septic patients (KyberSept) revealed significant reduction of lethality when no concomitant heparin was administered, whereas patients with the combination of heparin and AT did not benefit in terms of survival. Therefore, it seems feasible to study the capability of AT in prevention of microvascular thrombus formation to avoid concomitant application of heparin and AT. Using fluorescence microscopy and a light/dye-injury mouse ear model, the kinetics of thrombus formation were analyzed quantitatively in vivo upon single iv bolus of saline (control), heparin (100 IU/kg), hirudin (1 mg/kg) or AT (25, 50, 100 or 250 IU/kg) (N = 7 animals per group each). In controls, light/dye-injury induced complete thrombotic occlusion in all arterioles and venules studied. Heparin and hirudin prevented thrombotic vessel occlusion in 62% and 43% of arterioles and 11% and 28% of venules. AT-250 was found to be more effective than heparin and hirudin, because thrombus formation was completely banned in all arterioles and venules. AT-100 and AT-50 were also capable of significantly blocking thrombus formation in both arterioles and venules. In blood vessels, which finally clogged, the time for development of complete vessel occlusion was delayed after heparin, hirudin and AT-25, but in particular after AT-50 and AT-100. In conclusion, AT-mediated antithrombotic activity has been characterized in a model of phototoxicity-induced microvascular thrombosis formation, demonstrating that AT delays and prevents thrombus formation in arterioles and venules at least comparably effective as heparin and hirudin.

Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin.

A randomised, prospective, placebo-controlled phase III multicentre clinical trial (KyberSept) has been performed to test the efficacy of high-dose antithrombin therapy in patients with severe sepsis. Concomitant low-dose heparin has been routinely given in two thirds of patients for deep vein thrombosis prophylaxis. This study analyses heparin - antithrombin interactions in terms of long-term mortality, adverse events, and thromboembolic events. From a total of 2,314 patients with severe sepsis (placebo: n = 1,157; antithrombin: n = 1,157) 1,616 patients (placebo: 811, antithrombin: 805) received heparin concomitantly with study drug (antithrombin 30,000 IU) over four days, whereas 698 patients (346 and 352, respectively) did not. In patients with no concomitant heparin, 28-day mortality was lower with antithrombin than with placebo (37.8% vs. 43.6%; absolute reduction: 5.8%; risk ratio: 0.860 [0.725-1.019]), which increased until day-90 (44.9% vs. 52.5%; absolute reduction: 7.6%; risk ratio: 0.851 [0.735-0.987]). In patients with concomitant heparin, no effect of antithrombin on mortality was seen (28-day mortality: 39.4% vs. 36.6%; absolute increase: 2.8%; risk ratio: 1.08 [0.96-1.22]). Frequency of use of concomitant heparin increased during conduct of the study. Increased bleeding incidences were reported with antithrombin plus concomitant heparin as compared to antithrombin alone. Rates of thromboembolic events were similar when antithrombin was given with or without concomitant heparin. In the treatment of severe sepsis, high-dose antithrombin may sufficiently protect against development of venous thromboembolism when no concomitant heparin is given. Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin.

Microcirculatory alterations in ischemia-reperfusion injury and sepsis: effects of activated protein C and thrombin inhibition.

Experimental studies in ischemia-reperfusion and sepsis indicate that activated protein C (APC) has direct anti-inflammatory effects at a cellular level. In vivo, however, the mechanisms of action have not been characterized thus far. Intravital multifluorescence microscopy represents an elegant way of studying the effect of APC on endotoxin-induced leukocyte-endothelial-cell interaction and nutritive capillary perfusion failure. These studies have clarified that APC effectively reduces leukocyte rolling and leukocyte firm adhesion in systemic endotoxemia. Protection from leukocytic inflammation is probably mediated by a modulation of adhesion molecule expression on the surface of leukocytes and endothelial cells. Of interest, the action of APC and antithrombin in endotoxin-induced leukocyte-endothelial-cell interaction differs in that APC inhibits both rolling and subsequent firm adhesion, whereas antithrombin exclusively reduces the firm adhesion step. The biological significance of this differential regulation of inflammation remains unclear, since both proteins are capable of reducing sepsis-induced capillary perfusion failure. To elucidate whether the action of APC and antithrombin is mediated by inhibition of thrombin, the specific thrombin inhibitor hirudin has been examined in a sepsis microcirculation model. Strikingly, hirudin was not capable of protecting from sepsis-induced microcirculatory dysfunction, but induced a further increase of leukocyte-endothelial-cell interactions and aggravated capillary perfusion failure when compared with nontreated controls. Thus, the action of APC on the microcirculatory level in systemic endotoxemia is unlikely to be caused by a thrombin inhibition-associated anticoagulatory action.

Analysis of the influence of antithrombin on microvascular thrombosis: anti-inflammation is crucial for anticoagulation.

PURPOSE: Microvascular thrombosis during septic conditions is of essential clinical relevance, but the pathomechanisms are not yet completely understood. The purpose of this study was to study the distinguished differentiation of the interactions of inflammation and coagulation using antithrombin (AT), a mediator of anticoagulation and anti-inflammation. METHODS: Using a thrombosis model in a cremaster muscle preparation of male C57Bl/6J mice (n = 83), we quantitatively assessed microvascular thrombus formation by using intravital fluorescence microscopy. Experimental groups consisted of animals treated with AT or with tryptophan(49)-blocked AT (TrypAT), which exerts only anticoagulant but no anti-inflammatory effects. To further see whether endothelial glycosaminoglycan (GAG) binding with consecutive prostacyclin (PGI2) release is mandatory for the anticoagulant process of AT, animals were administered heparin or indomethacin either alone or in combination with AT. RESULTS: The antithrombotic capacity of AT significantly differs in the experimental groups in which anti-inflammation was antagonized. This is given by the significantly prolonged occlusion times (p < 0.05) and higher patency rates in case of application of AT alone; while all other groups in which the anti-inflammatory action of AT was blocked by TrypAT, heparin or indomethacin revealed thrombus kinetics comparable to controls. CONCLUSIONS: The anti-inflammatory influence of AT is essentially linked to its anticoagulant effect in the microvascular system. Those specifications of the active profile of AT characterize the intimate interactions of the anticoagulant and anti-inflammatory pathways. This might be of relevance for AT as a therapeutic agent in critically diseased patients and the clinical understanding of microvascular thrombosis.

Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms.

A recent clinical sepsis trial reported a significant reduction in 90-day mortality by antithrombin (AT) exclusively in the subgroup of patients without simultaneous heparin prophylaxis. Patients additionally receiving heparin did not benefit from AT treatment. Herein, we studied the microhemodynamic and cellular mechanisms of this adverse effect of heparin on AT actions by the use of intravital microscopy and granulocyte culturing. In Syrian golden hamsters normotensive endotoxemia was induced by 2 mg/kg endotoxin (LPS, E. coli) i.v. In a first group of animals, AT (AT, 250 IU/kg i.v., n = 6) was given 5 min before LPS administration. A second group of animals (Heparin + AT, n = 5) received AT (250 IU/kg i.v.) combined with unfractionated heparin (sodium heparin, 100 IU/kg/24 h, i.v.). Additional animals (LMWH + AT, n = 5) received AT (250 IU/kg i.v.) combined with LMWH (nadroparin 47.5 IU anti-Xa/kg, s.c., 2 h before LPS). LPS-treated animals, which received only saline, served as controls (control, n = 6). Using dorsal skinfold fold preparations, LPS-induced microvascular leukocyte-endothelial cell interaction (LE) and alteration of functional capillary density (FCD) were studied by intravital video fluorescence microscopy. In controls, LPS induced a massive increase in LE with a maximum at 8 h and an impressive decrease in FCD over a 24-hour period. Both LPS effects were effectively prevented by AT treatment (p < 0.01), whereas Heparin + AT and LMWH + AT animals showed microcirculatory alterations comparable to that in controls. In additional in vitro chemotaxis assays. AT blocked neutrophil chemotaxis, an effect reversed by both unfractionated heparin and LMWH. Thus, our study elucidates a relevant in vivo and in vitro unfractionated heparin and LMWH adverse effect in the microcirculatory actions of AT during endotoxemia. These results indicate that heparin should be avoided to permit AT to modulate LPS-induced inflammatory responses.

Latent antithrombin does not affect physiological angiogenesis: an in vivo study on vascularization of grafted ovarian follicles.

Latent antithrombin (L-AT), a heat-denatured form of native antithrombin (AT), is a potent inhibitor of pathological tumor angiogenesis. In the present study, we have investigated whether L-AT has comparable antiangiogenic effects on physiological angiogenesis of ovarian tissue. For this purpose, preovulatory follicles of Syrian golden hamsters were mechanically isolated and transplanted into dorsal skinfold chambers chronically implanted in L-AT- or AT-treated hamsters. Non-treated animals served as controls. Over 14 days after transplantation neovascularization of the follicular grafts was assessed in vivo by quantitative analysis of the newly developed microvascular network, its microvessel density, the diameter of the microvessels, their red blood cell velocity and volumetric blood flow as well as leukocyte-endothelial cell interaction using fluorescence microscopic techniques. In each group, all of the grafted follicles were able to induce angiogenesis. At day 3 after transplantation, sinusoidal sacculations and capillary sprouts could be observed, finally developing complete glomerulum-like microvascular networks within 5 to 7 days. Overall revascularization of grafted follicles did not differ between the groups studied. Interestingly, follicular grafts in L-AT- and AT-treated hamsters presented with higher values of microvessel diameters and volumetric blood flow, when compared to non-treated controls, which may be best interpreted as a reactive response to an increased release of vasoactive mediators. In conclusion, the present study demonstrates, that L-AT has no adverse effects on physiological angiogenesis of freely transplanted ovarian follicles. Thus, L-AT may be an effective drug in tumor therapy, which blocks tumor growth by selective suppression of tumor vascularization without affecting new vessel formation in the female reproductive system.

Tumescent and dry liposuction of lower extremities: differences in lymph vessel injury.

Lipectomy is a standard procedure in plastic surgery. Until now, however, there was no definite information about the influence of different liposuction techniques (tumescent versus dry liposuction) on the integrity of lymph collectors during this procedure. To study the effect of these liposuction techniques on the incidence of lymph vessel injury, postmortem lymphatic preparations were done in nine human cadavers (18 lower extremities). Conventional liposuction with a blunt 4-mm cannula in the dry technique (n = 29 regions) was compared with the tumescent technique (n = 26). Liposuction was performed in parallel to the superficial lymph vessels (longitudinal suction) or transversally in an 80-degree to 90-degree angle to the extremity (vertical suction). Careful surgical preparation of different regions followed. A specific macroscopic lymph vessel injury score was applied to differentiate three degrees of lymph vessel lesions according to the extravasation of patent blue. In all lower extremities, postmortem lymph flow occurred as indicated by patent blue staining of the lymph vessels. Injection of fluid that is obligatory during tumescent suction did not result in grade 2 injury. On the contrary, tumescent suction overall produced significantly fewer lymph vessel lesions when compared with the dry technique (p < 0.05). Longitudinal liposuction produced significantly less injury when compared with vertical suction (p < 0.05). Tumescent suction and dry suction were equally effective in removing adipose aspirates, as verified by circumference measurements. In addition, tumescent liposuction is unlikely to cause major lesions of epifascial lymph vessels during suction procedures vertical to the extremity axis. Therefore, in this respect, this technique is superior to dry suction.

Chromogranin a as serum marker for gastroenteropancreatic neuroendocrine tumors: a single center experience and literature review.

The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA), urinary 5-hydroxyindoleacetic acid (5-HIAA) and alkaline phosphatase (AP) in neuroendocrine tumors (NETs) of the GastroEnteroPancreatic-(GEP-) system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62) and pancreatic (n = 48) NETs. CgA levels were analyzed by a commercially-available immunoradiometric assay (CIS-bio) during routine follow-up in the years 2000-2009. CgA showed a higher sensitivity for midgut (68%) than pancreatic (54%) NETs. A higher CgA sensitivity and significantly higher median CgA values were found in patients with liver metastases than in those without, and in patients with hepatic and additionally extra-hepatic metastases than in those with hepatic and nodal metastases alone, respectively. We found an overall sensitivity for elevated 5HIAA excretion of 69% for midgut NETs and a significant correlation between median CgA and 5-HIAA values. The sensitivity of AP and the correlations of AP/CgA-data-pairs were low in both midgut and pancreatic NETs, although highest for metastatic pancreatic NETs. The sensitivity of CgA measurement depends on the NET primary location and spread of disease. 5-HIAA and CgA showed comparable sensitivity in midgut NETs, while AP does not seem to be useful as a tumor marker in GEP-NETs.