Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres

PURPOSE: To determine efficacy, safety, and requirements for adjunctive embolization or surgery in the treatment of symptomatic arteriovenous malformations (AVMs) with superabsorbent polymer microsphere (SAP-MS) particles. MATERIALS AND METHODS: SAP-MS particles (sodium acrylate and vinyl alcohol copolymer) are nonbiodegradable spheres with a precisely calibrated diameter. SAP-MS particles swell by absorbing fluids and become soft and deformable. Twenty-five patients (16 men, nine women; mean age, 32 y; range 12-66 y) with symptomatic facial (n = 5), upper- (n = 8) and lower- (n = 12) extremity AVMs were treated primarily (n = 23) or preoperatively (n = 2) by transarterial embolization (TAE) treatment with use of SAP-MS particles. Direct puncture embolization (DPE; n = 4) and/or surgical intervention (n = 5; ie, skin graft, resection, or amputation) were required. Surgical specimens from the resected (n = 2) and the amputated (n = 2) patients were evaluated histologically. Follow-up study, including clinical findings and imaging studies, was performed at intervals ranging from 3 months to 1 year. Clinical outcome was evaluated retrospectively, depending on the subjective improvement of symptoms and signs, according to the medical records. RESULTS: Seventy-two TAEs (range, 1-11; mean, 2.8) and 12 DPEs (range, 1-3; mean, 2.4) were performed during the mean follow-up period of 38 months (range, 7-110 mo). Twenty patients (80%) experienced symptom improvement by embolotherapy alone (n = 17) or in combination with surgery (n = 3). One lip and two finger AVMs were totally removed by surgical excision or amputation after TAE treatment. In diffuse upper- (n = 1) and lower- (n = 1) extremity AVMs, the symptoms were uncontrolled. No nerve injury or skin necrosis was observed after TAE treatment with SAP-MS particles. Mucosal necrosis was induced by DPE with ethanol in one patient. Histologically, SAP-MS particles penetrated intralesional vessels and conformed to the vessel lumen, resulting in tight vessel occlusion. Minimal perivascular reaction was observed. CONCLUSION: SAP-MS particles were used safely in TAE treatment of AVM. TAE treatment with use of SAP-MS particles was suitable for certain symptomatic AVMs, but diffuse AVMs remain a challenge and a combination of alternative methods will be necessary for further strategy.     

The effect of initial graft tension in anterior cruciate ligament reconstruction on the mechanical behaviors of the femur-graft-tibia complex during cyclic loading

BACKGROUND: Initial graft tension influences clinical results of anterior cruciate ligament reconstruction. HYPOTHESIS: Under repetitive loading conditions, the effect of initial graft tension on the biomechanical behavior of the femur-graft-tibia complex may depend on the graft and the fixation. STUDY DESIGN: Ex vivo biomechanical laboratory study. METHODS: After anterior cruciate ligament reconstruction, initial graft tension of 20, 80, or 140 N was applied to the complex for 2 minutes. Then, a cyclic force-relaxation test was performed for 5000 cycles so that the graft was stretched by 2 mm. RESULTS: In a patellar tendon graft with interference screws, the average peak load values at the 5000 th cycle were 105, 157, and 205 N for the complexes with initial tension of 20, 80, and 140 N, respectively. In a flexor tendon graft with interference screws, the values were 27, 41, and 39 N. In a flexor tendon graft with Endobutton fixation, the values were 17, 40, and 77 N. CONCLUSIONS: Considering the tension of the normal anterior cruciate ligament (16 to 87 N), an initial tension of 20 N appears to be high enough for a patellar tendon graft. For a flexor tendon graft with interference screws, an increase in initial tension above 80 N has no biomechanical advantages.     

Spontaneously stabilized severe dysplastic spondylolisthesis without operation: long-term follow-up of a preteenage patient

Surgical management is the accepted treatment choice for grade III or IV spondylolisthesis, and many satisfactory clinical and radiologic follow-up results have been reported. Very little, however, has been written about long-term results in preteenage patients in whom dysplastic spondylolisthesis has been treated nonoperatively, especially in those who have > or =50% displacement of the fifth lumbar vertebra on the sacrum. We report an unusual case of spontaneous stabilization of severe dysplastic spondylolisthesis in an 8-year-old girl who presented with grade III spondylolisthesis of L5-S1 and was followed up for >14 years in the absence of surgical intervention. On presentation, she complained of a restriction in forward bending and tightness of hamstrings, but she was undisturbed in her daily activities. Initial radiographs showed severe dysplastic spondylolisthesis; however, magnetic resonance imaging (MRI) performed at age 9 years showed that the amount of listhesis was much less than that seen in the initial radiograph. Routine radiographic follow-ups were chosen over early operative measures until she became a teenager. There was no change in the slip, and unusually a gradual ossification of the cartilaginous promontory of the S1 and the posterior lip of the L5 was observed. At 22 years old, the patient is asymptomatic and not conscious of her cosmetic appearance. Surgical treatment has generally been indicated for patients with grade III or IV spondylolisthesis, because slippage progression has been noted in most reported cases. However, MRI may be a tool for predicting which dysplastic spondylolisthesis cases are more likely to progress and therefore circumvent surgical intervention, while maintaining an excellent outcome.     

Preoperative chemotherapy increases cytokine production after lung cancer surgery.

OBJECTIVE: Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality. However, little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention. We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker. METHODS: The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003. Nineteen patients received a single cycle of cisplatin (80 mg/m(2)) and docetaxel (60 mg/m(2)) chemotherapy prior to surgery (neoadjuvant group), and 19 patients underwent surgery without any previous chemotherapy (control group). White blood cell and neutrophil counts and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (GCSF) were determined before surgery and on postoperative days 1 and 3. Postoperative complications were reviewed. Differences were assessed by repeated analysis of variance. RESULTS: Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group, but white blood cell count, neutrophil count, and CRP did not differ between the groups. No major complication occurred in either group. CONCLUSIONS: A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients.     

Peculiar mechanisms of graft recovery through anti-inflammatory responses after rat lung transplantation from donation after cardiac death

BackgroundAlthough lung transplantation from donation after cardiac death (DCD), especially uncontrolled DCD, is limited by warm ischemic periods, the molecular mechanism of warm ischemia–reperfusion-injury (IRI) has not been well elucidated. The purpose of this study was to clarify the particular longitudinal mechanisms of molecular factors involved in warm IRI.MethodsCold ischemic-time (CIT)-group lungs were retrieved and subjected to 3-h of cold preservation, whereas warm ischemic-time (WIT)-group lungs were retrieved after 3-h of warm ischemia. Orthotopic rat lung transplantation was performed and the grafts were reperfused for 1 or 4-h. The graft functions, gene expression, and activation of inflammatory molecules in the grafts were analyzed. Exhaled-carbon-monoxide-concentration (ExCO-C) was measured during reperfusion.ResultsOnly the WIT-group showed obvious primary graft dysfunction at 1-h reperfusion, but the graft function was recovered during 4-h reperfusion. Most of pro-inflammatory cytokines and stress-induced molecules showed different expression and activation patterns between CIT and WIT groups. In the WIT-group, the expressions of anti-inflammatory molecules, IL-10 and HO-1, were significantly increased at 1-h reperfusion compared to the CIT-group, and these high levels were maintained through 4-h reperfusion. Furthermore, ExCO-C levels in the WIT-group increased immediately after reperfusion compared to the CIT-group.ConclusionsThis study indicates that warm IRI may involve a different mechanism than cold IRI and anti-inflammatory pathways may play important roles in the graft recovery after lung transplantation from uncontrolled DCD.     

Improvement of porcine islet isolation by inhibition of trypsin activity during pancreas preservation and digestion using α1-antitrypsin

Porcine islets are considered to be a promising resource for xenotransplantation. However, it is difficult to isolate porcine islets because of the marked fragility and rapid dissociation. Endogenous trypsin is one of the main factors to damage islets during the isolation procedure. Recent studies have suggested that trypsin inhibitors during the preservation of pancreas or the collagenase digestion can improve the result of islet isolation. In this study, we examined whether α1-antitrypsin (Aralast?), which inhibits several endogenous proteases and has immunomodulatory properties, can protect islets from the proteases and improve the results of porcine islet isolation. Twelve porcine pancreata were divided into three groups: without Aralast group (standard, n = 5), preserved with Aralast using the ductal injection (DI) method (DI, n = 3), and with Aralast using the DI method and in the collagenase solution (DI+C, n = 4). Efficacy of islet isolation was assessed by islet yields, purity, and viability. The trypsin activity of the preservation and the digestion solution during the isolation procedure was measured. During islet isolation, the trypsin activity in DI+C group was significantly inhibited compared to the standard group, whereas DI group showed less effect than DI+C group. The average of postpurification islet equivalents (IEQ) per pancreas weight in the DI+C group was significantly higher than the standard group (standard: 3516 ± 497 IEQ/g, DI: 4607 ± 1090 IEQ/g, DI+C: 7097 ± 995 IEQ/g; p = 0.017 between standard and DI+C). In the DI+C group, stimulation index was higher than in other groups, although there was no significant difference. The presence of Aralast in both DI solution and collagenase solution markedly inhibited trypsin activity during pancreas digestion procedure and improved the porcine islet isolation. Inhibition of trypsin activity by Aralast could improve porcine islet isolation.     

Islet purification method using large bottles effectively achieves high islet yield from pig pancreas

Porcine islets are a promising resource for xenotransplantation. However, low efficacy of islet isolation because of their marked fragility remains a problem. Recently we found that the standard purification method using COBE 2991 cell processor (COBE) with Ficoll density gradient solution damaged islets mechanically by high shearing force. In this study, we evaluated our new purification method using large plastic bottles for the efficacy of islet purification. Ten porcine pancreata were used. The average warm ischemic time was over 40 min; therefore, these pancreata were considered to be in a marginal condition. After digestion, the digested tissue was divided into three groups. Each group was purified using either top loading method with bottle (top group) or bottom loading method with bottle (bottom group) or standard COBE method (COBE group). Islet yield per pancreas weight (IEQ/g) and the rate of postpurification recovery in the top group were significantly higher than the COBE group (top: 8060 ± 1652 IEQ/g, bottom: 4572 ± 614 IE/g, COBE: 3900 ± 734 IE/g. p < 0.02 in top vs. COBE; top percentage of recovery: 99.3 ± 12.3%, bottom: 62.6 ± 8.8%, COBE: 49.5 ± 6.7%, p < 0.02 in top vs. bottom and COBE). The average sizes of purified islets in the top and bottom groups were significantly larger than COBE group (Average diameter top: 156 ± 8 μm, bottom: 147 ± 6 μm, COBE: 119 ± 6 μm, p < 0.01 in top vs. COBE and in bottom vs. COBE), which indicated that bottle method can reduce shear force during purification. Our new purification using top loading bottle method enabled us to obtain a high yield of porcine islets from marginal pancreata.     

Comparison of ulinastatin, gabexate mesilate, and nafamostat mesilate in preservation solution for islet isolation

For islet transplantation, maintaining organ viability after pancreas procurement is critically important for optimal graft function and survival. We recently reported that islet yield was significantly higher in the modified ET-Kyoto (MK) solution, which includes a trypsin inhibitor (ulinastatin), compared with the UW solution, and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with other trypsin inhibitors, gabexate mesilate, and nafamostat mesilate, in preservation solution for islet isolation. Ulinastatin was easily dissolved in ET-Kyoto solution, while ET-Kyoto with gabexate mesilate and nafamostat mesilate became cloudy immediately after addition. Although there were no significant differences in islet yield among the three groups, viability was significantly higher for the MK group than for the GK group or the NK group. The stimulation index was significantly higher for the MK group than for the GK group. In summary, there are no other trypsin inhibitors that are more effective than ulinastatin. Based on these data, we now use ET-Kyoto solution with ulinastatin for clinical islet transplantation.     

A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces nasal morbidity for nasotracheal intubation

We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved tube with a conventional diagonal bevel for nasotracheal intubation. Eighty anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal intubation for tonsillectomy were randomly allocated into two equal-sized groups for airway management with the silicone tracheal tube or PVC tracheal tube. Intubation was subdivided into three phases: 1). passage through the nose into the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3). laryngoscope-guided passage into the trachea. A specific sequence of airway maneuvers was followed at each stage if it was unsuccessful. The number of attempts and intubation time were documented by an unblinded observer. The frequency of epistaxis and postoperative nasal complications was documented by blinded observers. There were no intubation failures. The number of attempts at pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005) placement was smaller for the silicone tracheal tube, but the number of attempts at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis were less for the silicone tracheal tube. The total number of postoperative nasal symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We conclude that the pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with the silicone tracheal tube than the PVC tracheal tube but that the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical bevel than with a polyvinyl chloride-based precurved tracheal tube with a conventional diagonal bevel, but the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube.     

Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.