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Ermanno Ancona

Publications and source records attributed to Ermanno Ancona.

At least 19 recordsLinked to original sources
PubMed2006

Hybrid cardiomyocytes derived by cell fusion in heterotopic cardiac xenografts.

Cardiomyocytes expressing host markers, such as the Y chromosome in sex-mismatched transplants, have been described in human allografts, suggesting that circulating cells can contribute to cardiac regeneration. It has not been established, however, whether host-derived cardiomyocytes result from transdifferentiation of stem cells or cell fusion. To address this issue, we used heterotopic heart xenografts and looked for markers of donor and recipient cells. Golden Syrian hamsters or transgenic mice expressing nuclear beta-galactosidase under the control of the cardiac troponin I promoter served as organ donors, while GFP+ transgenic rats were used as recipients. GFP+ cells, including abundant CD-45+ inflammatory cells and rare undifferentiated cells expressing early cardiac markers (GATA-4 or MEF2C), were found in xenografts harvested two weeks after surgery. In addition, rare GFP+ mature cardiomyocytes were found in 7 of 8 hamster xenografts and 6 of 6 mouse xenografts. The proportion of these cells was very low (0.0001% to 0.0344% in hamster xenografts) but similar to the one observed in control rat heart allografts. Without exception, all GFP+ cardiomyocytes also expressed donor markers, i.e., hamster membrane antigens or lacZ, so they must derive from cell fusion, not transdifferentiation.

Animals↗
PubMed2006

Surgical complications do not affect longterm survival after esophagectomy for carcinoma of the thoracic esophagus and cardia.

BACKGROUND: Surgical resection is the only real chance of cure for carcinoma of the esophagus and esophagogastric junction, although it carries considerable postoperative morbidity and mortality. The longterm prognosis for patients undergoing operation depends largely on the pathologic stage of the disease. The real impact of postoperative complications on survival is still under evaluation. STUDY DESIGN: A retrospective analysis was performed on patients with squamous cell carcinoma and adenocarcinoma of the thoracic esophagus and esophagogastric junction, undergoing surgical resection between January 1992 and December 2002. For the 522 patients considered for esophagogastroplasty, we analyzed comorbidities, preoperative staging, neoadjuvant treatments, surgical data, histopathology, postoperative surgical or medical complications, and survival. RESULTS: Surgical complications occurred in 85 of 522 patients (16.3%); their survival rate was entirely similar to that of the group of patients without surgical complications (p=0.9). The survival rate was worse for patients with concurrent surgical and medical complications. Analysis of the 99 patients (19%) who had only medical complications postoperatively revealed a survival rate comparable (p=0.9) with that of the 338 patients (63.7%) with an uneventful postoperative course. The median postoperative hospital stay was 14 days for all 522 patients, and 18 days for patients with medical or surgical postoperative complications. Multivariate analysis of the predictive factors showed that surgical complications do not affect longterm prognosis. CONCLUSIONS: Surgical complications have no negative impact on survival rates, which seem to depend exclusively on the pathologic stage of the tumor.

Adenocarcinoma↗
PubMed2006

Xenotransplantation-current status and future perspectives.

Research efforts have shed light on the immunological obstacles to long-term survival of pig organs transplanted into primates and allowed the identification of targets for specific immune intervention. Accordingly, the development of genetically engineered animals has overcome the hyperacute rejection barrier, with acute humoral xenograft rejection (AHXR) currently remaining the most important immunological obstacle. At this stage, a better control of the elicited anti-pig humoral immune response and avoidance of coagulation disorders are the two primary research fronts being pursued in order to overcome AHXR. Nonetheless, it is encouraging that porcine xenografts can sustain the life of non-human primates for several months. Proactive research aimed at the development of a safer organ source is also underway. It is anticipated that ongoing research in several fields, including accommodation, tolerance, immune suppression and genetic engineering, will result in further improvements in non-human primate survival. However, until convincing efficacy data and a more favourable risk/benefit ratio can be established in relevant animal models, progression to the clinic should not be viewed as an option.

Animals↗
PubMed2006

Erosion of an esophageal endoprosthesis into the trachea.

Acquired benign non-neoplastic tracheoesophageal fistulas are unusual, demanding clinical entities. Surgical technique and final outcome depends on fistula size. A one-stage procedure with esophageal resection is preferred when the fistula is located in the upper third of the trachea and is less than 1 cm long.

Adult↗
PubMed2006

Understanding of and attitude to xenotransplantation among Italian university students: impact of a 3-yr university course.

BACKGROUND: Young people, and students in particular, generally have a positive attitude to xenotransplantation. We reported previously that university students attending their first year approved of the idea of transplanting animal organs into humans. The aim of this study was to evaluate the impact of a 3-yr course at various faculties on the university students' understanding of and attitude to xenotransplantation. METHODS: University students in their fourth year at five different faculties of Padua University (Italy), who had previously been surveyed in exactly the same way 3 yr earlier, were re-administered an anonymous 19-item questionnaire on their attitude to xenotransplantation. RESULTS: A total of 453 students completed the fourth year questionnaire (84 males, 369 females; mean age 24.6 yr, range 21-36 yr). Students were attending courses in Medicine (22.1%), Veterinary Science (16.5%), Agriculture (10.4%), Educational Sciences (22.1%) and Psychology (28.9%). In their fourth year, 85% of the students knew that animal organs could, at some stage, be transplanted into humans, 81.5% approved of this idea and 84% would accept an animal organ to save their life if necessary (these percentages were 88%, 78% and 76%, respectively 3 yr earlier). A significantly larger proportion of the students who approved of xenotransplantation were attending science courses rather than art courses, while no differences emerged as regards gender. Those who refused xenotransplantation justified their position mainly on ethical-moral (41.7%) and immunological (35.7%) grounds. CONCLUSION: As in their first year, so too in their fourth, University students were well informed about the feasibility of transplanting animal organs into human beings and those attending science courses were more likely to accept this idea than art students. Approval of xenotransplantation was much the same among fourth year males and females, whereas in the first year, male students had approved more than female students.

Adult↗
PubMed2005

Effects of long-term administration of high-dose recombinant human antithrombin in immunosuppressed primate recipients of porcine xenografts.

BACKGROUND: Fibrin deposition is central to the acute humoral rejection process occurring in the presence of consumptive coagulopathy when pig organs are transplanted into primates. METHODS: To assess whether strategies aimed at preventing fibrin formation may extend xenograft survival, we administered high daily doses of recombinant human antithrombin (rhAT) (500 U/kg twice daily) to obtain both anticoagulant and anti-inflammatory effects in immunosuppressed primate recipients of porcine kidneys. RESULTS: Some degree of consumptive coagulopathy developed in both rhAT-treated (n=3) and untreated (n=3) primates. No major differences in the coagulation parameters analyzed were observed between the 2 groups. Similarly, no difference in survival was seen between rhAT-treated (20.6+/-4 days; range: 15-23 days) and untreated animals (17.3+/-11.6 days; range: 7-30 days), although the rhAT-treated primates had a higher bleeding tendency. Despite the high daily dose of rhAT, considerable fibrin deposition was observed in the graft as early as 2 weeks after transplantation. CONCLUSIONS: These results suggest that a high daily dose of rhAT fails to influence survival or prevent fibrin formation and deposition in the graft in our pig-to-primate model. However, the potential role of rhAT administered in combination with heparins or other clotting inhibitor concentrates in this model remains to be determined.

Animals↗
PubMed2005

Host-derived circulating cells do not significantly contribute to cardiac regeneration in heterotopic rat heart transplants.

OBJECTIVES: The aim of this study was to investigate the contribution of host-derived circulating cells to cardiac repair after tissue damage using the model of heterotopic heart transplantation between transgenic recipient rats expressing green fluorescent protein (GFP) and wild-type donors. METHODS: Unlabeled donor rat hearts, some of which underwent prolonged cold ischemia pretreatment, were transplanted into the abdominal cavity of GFP+ transgenic recipient rats and were analyzed 15 and 90 days after surgery. An additional experimental group underwent heart transplantation following administration of granulocyte-colony stimulatory factor (G-CSF) to mobilize bone marrow cells. RESULTS: Most transplants contained GFP+ mature cardiomyocytes. However, systematic counting in the transplants showed that the proportion of GFP+ cardiomyocytes was only 0.0005% to 0.008% of all cardiomyocytes. These relative proportions did not change after G-CSF treatment, despite evidence for sustained marrow cell mobilization. Confocal image analysis showed that the majority of GFP+ cardiomyocytes contained a high number of nuclei, suggesting that these cells may derive from fusion events. Very rarely, small GFP+ undifferentiated cells, expressing GATA-4, were also identified. Occasionally, GFP+ endothelial cells, but not smooth muscle cells, were detected in blood vessels of some transplants. CONCLUSIONS: Our results demonstrate that cardiomyocytes expressing a host transgenic marker are detectable in heterotopic heart transplants; however, they do not significantly contribute to repopulation of the damaged myocardium.

Animals↗
PubMed2005

Heterotopic cardiac xenotransplantation in rodents: report of a refined technique in a hamster-to-rat model.

Hamster-to-rat heterotopic cardiac xenotransplantation is widely used as an experimental model to study xenograft rejection, accommodation, and tolerance, as well as in studies aimed at developing immunosuppressive strategies in xenotransplantation. Despite its widespread application, no detailed description of a surgical technique for this model has been provided in the literature. Indeed, all publications so far on the use of this species combination refer to the rat allotransplantation technique. Hence the present paper provides a detailed, up-to-date description of the surgical method adopted at our center for the hamster-to-rat heterotopic cardiac xenotransplantation model. Considerable effort went into developing a reliable, reproducible experimental model in rodents, and the description given here is enriched with "tips" that we learned in the process. The discussion of the technique also addresses several significant related issues, e.g., the anesthesia and organ preservation solution used (aspects that, in our experience, are crucial to a good surgical outcome).

Animals↗
PubMed2005

Barrett's epithelium after antireflux surgery.

Barrett's epithelium (BE), defined as endoscopically visible, histologically proved intestinal-type epithelium in the esophagus, is considered the ultimate consequence of long-standing gastro(duodeno)esophageal reflux disease (GERD). Recent reports suggest that effective antireflux therapy may promote the regression of this metaplastic process. This study aimed to establish whether antireflux surgery (laparoscopic fundoplication) can induce any endoscopic and/or histologic changes in BE. Thirty-five consecutive cases of BE (11 short-segment [SBE] and 24 long-segment [LBE]) were considered. All patients underwent extensive biopsy sampling before and after surgery (mean follow-up, 28 months; range, 12-99 mo). In all cases, (a) intestinal metaplasia (IM) extension (H&E), (b) IM phenotype (high-iron diamine [HID]), and (c) Cdx2 immunohistochemical expression were histologically scored in the biopsy material obtained before and after fundoplication. After surgery, a significant decrease in IM extension and a shift from incomplete- to complete-type IM were documented in SBE. No significant changes occurred in the LBE group in terms of IM extension or histochemical phenotype. A drop in the immunohistochemical expression of Cdx2 protein was also only documented in the SBE group. Antireflux surgery significantly modifies the histologic phenotype of SBE, but not of LBE.

Adult↗
PubMed2005

Long-term outcome of laparoscopic Heller-Dor surgery for esophageal achalasia: possible detrimental role of previous endoscopic treatment.

Laparoscopic Heller myotomy has recently emerged as the treatment of choice for esophageal achalasia. Previous unsuccessful treatments (pneumatic dilations or botulinum toxin [BT] injections) can make surgery more difficult, causing a higher risk of mucosal perforation and jeopardizing the outcome. The study goal was to evaluate the effects of prior endoscopic treatments on laparoscopic Heller myotomy. Between January 1992 and February 2005, 248 patients (130 males and 118 females; median age, 43 years) underwent a laparoscopic Heller-Dor operation for achalasia: 203 underwent primary surgery (group A), 19 had been previously treated with pneumatic dilations (group B), and 26 had BT injections (alone [22] or with dilations [4] (group C)). Median duration of the operation and rate of intraoperative mucosal lesions were not different in the three groups. Median follow-up was 41 months. The 5-year actuarial of control of dysphagia was similar in groups A (86%) and B (94%), whereas only 75% of group C patients were symptom free at 5 years (P = 0.02). On logistic regression analysis, prior treatment with two BT injections or BT combined with dilation was associated with poor outcome of surgery. Further, dilations for surgical failure patients were effective in 80% of group A but in only 33% of group B or C patients. Heller-Dor surgery is safe and effective as a primary or a second-line treatment (after pneumatic dilations or BT injections) for achalasia. However, long-term results seem less satisfactory in patients previously treated with BT.

Adolescent↗
PubMed2005

Antibody mediated rejection in pig-to-nonhuman primate xenotransplantation models.

Antibody-mediated mechanisms are central to the rejection that occurs when pig organs are transplanted into primates. In this article, the histopathological features of the humoral rejection process in these species combinations, namely hyperacute rejection and acute humoral xenograft rejection, will be illustrated. The profile of the natural and elicited antibodies involved will also be discussed. It has now been demonstrated that the natural immune response to a porcine xenograft is primarily directed to Galalpha1-3Gal (alphaGal) specificities, whilst the elicited immune response is directed to both alphaGal and non-alphaGal antigens. The principal characteristics of anti-alphaGal, anti-non-alphaGal and polyreactive antibodies will be described, together with the identification of the molecules recognised by natural and elicited xenoreactive antibodies. The role of the humoral immune response in the rejection of porcine islets in the primate is still uncertain and the current views on the subject will be discussed. Finally, a concise but comprehensive review of the different strategies that have been attempted to prevent the onset of antibody-mediated rejection is presented. These strategies encompass approaches aimed at interfering with the binding of xenoreactive antibodies with their targets, the use of conventional or novel immunosuppressants and splenectomy. It is undeniable that significant progress has been recently achieved in understanding the humoral rejection process of pig organs transplanted into primates. It is expected that a more comprehensive elucidation of the mechanisms underlying accommodation and tolerance may, in the not too distant future, further extend survival of pig organs transplanted into primates.

Animals↗
PubMed2004

The role of botulinum toxin injection and upper esophageal sphincter myotomy in treating oropharyngeal dysphagia.

The aims of this study were to assess the efficacy and safety of botulinum toxin (BoTox) injection in the cricopharyngeus muscle (CP) and CP myotomy in patients with oropharyngeal dysphagia (OPD) and to identify factors predicting the outcome of these treatments. The study involved patients with persistent OPD despite 2-6 months of rehabilitation, who all underwent clinical evaluation, esophageal manometry, upper gastrointestinal endoscopy, and videofluoroscopy (VFS). Patients received 5-10 BoTox units injections in the CP, identified by electromyography. Surgical myotomy of the upper esophageal sphincter was performed when dysphagia persisted after two BoTox injections. After treatment, patients were reevaluated with clinical interviews and VFS. The study population included 21 patients (15 mean and 6 women; median age, 68 years), classified into three groups, based on the etiology of their OPD: eight (38%) had central nervous system abnormalities, five (24%) had peripheral nerve disease, and eight (38%) were classified as idiopathic. The median time since the onset of dysphagia was 18 months. Thirteen of 21 patients (62%) needed supplemental/total gastrostomy feeding, and 5 of 21 (24%) had tracheostomy. One patient died, on posttreatment day 7, due to massive aspiration. No other BoTox-related complications were observed. After BoTox injection, dysphagia improved in 9 of 21 (43%) patients. Severely altered VFS findings and CP incoordination or low activity predicted BoTox failure at multivariate analysis. Dysphagia improved in 8 of 11 (72.7%) patients who failed to respond to BoTox and underwent myotomy. A mild impairment of VFS findings and a higher pressure of pharyngeal contractions best predicted response to BoTox with or without myotomy. BoTox injection can be used as the first therapeutic option in patients with OPD: it is safe and simple and relieves dysphagia in 43% of cases. If BoTox fails, CP myotomy can be offered to patients with preserved oral and tongue activity at VFS and an intact bolus propulsion ability on manometry.

Aged↗
PubMed2004

Barrett's esophagus: management of high-grade dysplasia and cancer.

Esophagectomy remains the treatment of choice for the appropriate patient with Barrett's adenocarcinoma invading beyond the mucosa, without evidence of distant metastasis or invasion of adjacent organs. On the other hand, therapeutic management of patients with Barrett's high-grade dysplasia (HGD) or mucosal adenocarcinoma should be individualized, taking into account the patient's preferences, willingness to return for frequent endoscopic biopsies, and medical fitness to undergo esophagectomy. Surgery has to be considered the best treatment for HGD or superficial carcinoma, unless contraindicated by severe comorbidities, because it has proven to be the only treatment that is successful in curing the condition and preventing recurrent HGD or the development of invasive cancer. Nonsurgical treatment by photodynamic therapy or endoscopic mucosal resection may be a less invasive and organ-sparing option for elderly, poor-risk patients but it is still to be considered an investigational therapy that should only be conducted under a clinical trial protocol. Finally, intensive endoscopic biopsy surveillance of patients with HGD is another investigational option that may allow prompt treatment of cancer if it develops. However, few data document the safety of this observational approach.

Adenocarcinoma↗
PubMed2004

Oesophageal diverticula.

Oesophageal diverticula are rare. They are most commonly seen at the pharyngo-oesophageal junction (Zenker's diverticula) or at the distal oesophagus (epiphrenic diverticula). In both cases they are caused by altered motility which results in abnormal intraluminal pressure and the pushing of the oesophageal mucosa through focal weaknesses of the muscular wall (pulsion diverticula). The established surgical treatment for these diverticula therefore consists of eliminating the functional obstruction causing the disease (myotomy), associated with resection of the diverticulum (diverticulectomy) or its suspension (diverticulopexy). Recently, the spread of minimally invasive surgery has also led the application of such techniques to the treatment of oesophageal diverticula. Endoscopic diverticulostomy with stapler, laser or coagulation, through a rigid or flexible endoscope, has been demonstrated to be a valid treatment for Zenker's diverticula-as an alternative to surgery-especially in high-risk patients. On the other hand, laparoscopic treatment of epiphrenic diverticula has recently been introduced with encouraging results. However, because the disease is rare, more experience is required in order to allow definitive conclusions.

Diverticulum, Esophageal↗
PubMed2004

Alterations in the coagulation profile in renal pig-to-monkey xenotransplantation.

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model. Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded. There was no consumption of the main clotting inhibitors (including antithrombin) or a progressive, severe drop in fibrinogen levels and platelet counts, although grafts were left in situ. After transplantation, D-dimer levels remained persistently high, so they were of limited value in defining this coagulopathy. At post mortem, no cases of multiorgan involvement typical of overt DIC were observed. The lack of a rapid postoperative recovery of clotting inhibitor levels after transplantation was invariably associated with early poor outcome. This study shows that AHXR is associated with various degrees of compensated consumptive coagulopathy in our pig-to-primate model. No clear relationship was found between coagulation parameter levels and graft outcome.

Animals↗
PubMed2004

Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia.

OBJECTIVE: To compare laparoscopic cardia myotomy and fundoplication with botulinum toxin (BoTx) injection in patients with esophageal achalasia. SUMMARY BACKGROUND DATA: Although myotomy is thought to offer better results, recent studies have reported 80% success rates after 2 BoTx injections a month apart. No randomized controlled trials comparing the 2 treatments have been published so far. MATERIALS AND METHODS: Newly diagnosed achalasia patients were randomly assigned to BoTx injection or laparoscopic myotomy. Symptoms were scored; lower esophageal sphincter resting and nadir pressures were measured by manometry; barium swallow was used to assess esophageal diameter pre- and post-treatment. Eight to one hundred units of BoTx were injected twice, a month apart, at the esophagogastric junction. Myotomy included anterior partial (Dor) or Nissen fundoplication. RESULTS: Eighty patients were involved in the study: 40 received BoTx and 40 underwent myotomy. Mortality was nil. One surgical patient bled from the trocar site. Median hospital stay was 6 days for surgery; BoTox patients were treated as day-hospital admissions. All patients completed the follow-up. After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76-89 vs. 66% CI 57-75, P < 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13-26 vs. 5% CI 2-11, P < 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P < 0.05). CONCLUSION: Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx should be reserved for patients who are unfit for surgery or as a bridge to more effective therapies, such as surgery or endoscopic dilation.

Adolescent↗
PubMed2004

Evaluation of 84 elderly donors in renal transplantation.

BACKGROUND: The use of elderly donors (ED) and dual kidney transplantation (DKT) procedures have become common in clinical practice. A correct evaluation of kidneys from ED is crucial to avoid unsuccessful transplantation or the use of DKT when a single transplant (ST) would be equally successful. The aim of this investigation was to assess the role of renal biopsy (RB) in the assessment of kidneys from ED. PATIENTS AND METHODS: A total of 84 ED aged > or = 60 yr were evaluated. In 19 cases, the kidneys were not used, mainly because of atherosclerotic vascular lesions. A histological score (HS) from 0 to 12 was awarded, considering the proportion of glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arterial and arteriolar narrowing. On the basis of the HS, 37 donors were selected for 40 ST and 21 for DKT, three were discarded. All recipients received triple-drug therapy based on calcineurin inhibitors, mycophenolate mofetil and steroids. RESULTS: Primary non-function was observed in three of 40 ST and one of 21 DKT. Acute tubular necrosis occurred in 22/40 ST and in 11/21 DKT. Acute rejection occurred in 16/40 ST and four of 21 DKT. Renal function was satisfactory in both groups, with 1-yr S-Cr = 171 micromol/L and 137 micromol/L, respectively in the ST and DKT groups. One-year patient survival was 92% in ST and 100% in DKT; 1-yr graft function was 87% in ST and 95% in DKT. CONCLUSION: The histological assessment of kidneys from ED enables a correct selection of kidneys for ST or DKT and prevents the transplantation of high-risk kidneys.

Age Factors↗