Chronic intestinal pseudo-obstruction in a child with Treacher Collins syndrome.

BACKGROUND: Treacher Collins syndrome (TCS) mainly presents with severe craniofacial developmental abnormalities characterized by a combination of bilateral downward-slanting palpebral fissures, colobomas of the lower eyelids, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. It is due to mutations in Treacher Collins syndrome 1 (TCOF1) (5q32-q33.1) and Polymerase RNA 1 polypeptides D and C (POLR1D [13q12.2], and POLR1C [6p21.1]) genes, which are responsible for increased neuroepithelial apoptosis during embryogenesis resulting in the lack of neural crest cells involved in facial bone and cartilage formation. Altered function of the upper digestive tract has been reported, whereas severe dysmotility disorders have never been reported. We describe here the first case of TCS associated with histologically proven chronic intestinal pseudo-obstruction (CIPO) in humans. Case presentatios A 12-year-old boy with TCS due to TCOF1 gene deletion experienced nutritional difficulties and digestive intolerance from birth. CIPO was suspected during childhood because of severe intestinal dysmotility leading to enteral-jejunal nutrition intolerance and dependence on total parenteral nutrition. Diagnosis of CIPO with nervous abnormalities was histologically confirmed on a surgical rectal biopsy that showed enlarged ganglionic myenteric plexus. At the age of 9 years, an isolated colonic stenosis without dilatation responsible for severe abdominal pain and altered quality of life led to digestive derivation contributing to rapid disappearance of chronic abdominal pain. At the age of 12 years, the patient was still dependent on total home parenteral nutrition 7 days a week to maintain regular growth velocity. CONCLUSION: Recently, mice studies have pointed out the role played by TCOF1 in ganglionic cell migration in the foregut, suggesting that the synergistic haploinsufficiency of Tcof1 and Pax3, a transcription factor regulating the RET gene involved in disorders of neural crest cell development, probably results in colonic aganglionosis and may explain the association described here between TCS and CIPO. This case may correspond to this possible mechanism in humans. These findings and our clinical report suggest that CIPO may be assessed as unusual digestive manifestations in TCS with TCOF1 deletion.

[A pseudotumoral lesion revealing Meckel's diverticulum]. / Lésion pseudo-tumorale révélatrice d'un diverticule de Meckel.

INTRODUCTION: Meckel's diverticulum is a common malformation in children, usually asymptomatic, with complications in only 20% of cases. Exceptionally, a tumor can develop in Meckel's diverticulum in children, particularly Burkitt's lymphoma; in adults it can develop into a gastrointestinal stromal tumor, a leiomyosarcoma, or a neuroendocrine tumor such as a carcinoid tumor. The diagnosis of inflammatory pseudotumor following an insidious perforation is rare. OBSERVATION: We report the case of a 14-month-old boy who presented with fever, asthenia, food refusal, and digestive complaints such as vomiting and tender abdomen suggesting appendicitis. Computed tomography showed an ileal mass of 3cm in diameter, which led to the suspicion of Burkitt's lymphoma. Laparoscopy showed Meckel's diverticulum with a mass of 3×2.8×2cm. Histological examination confirmed the diagnosis of Meckel's diverticulum with gastric heterotopia and showed a proliferation of spindle cells in a myxoid background, with an inflammatory infiltrate made of lymphocytes and plasmocytes. Immunostaining ruled out a malignant tumor. The diagnosis of an inflammatory pseudotumor developing on a Meckel diverticulum with gastric heterotopias was made. The outcome was favorable after surgical resection. CONCLUSION: While perforation of a Meckel diverticulum with gastric heterotopia is a common finding, the discovery of an inflammatory pseudotumor following a perforation is rare; the differential diagnosis should include Burkitt's lymphoma.

Unusual outer ear swelling: Childhood auricular rhabdomyosarcoma.

INTRODUCTION: Rhabdomyosarcoma (RMS) is the most frequent soft-tissue sarcoma in children and makes up 5% of all pediatric malignant tumors. The main head and neck locations are the base of the skull, nasopharynx, nasal cavity and orbit. An outer ear location is considered extremely rare. We present 3 cases of children, aged 6 to 14 years, presenting with auricular RMS. CASE REPORTS: The first child, aged 6, was managed by 4 chemotherapy cycles followed by surgical resection of the tumor bed, completed by 5 further cycles of chemotherapy. The second, aged 14, was managed by 4 chemotherapy cycles followed by external radiation therapy of the tumor bed and lymph node areas, completed by 5 further cycles of chemotherapy. The third, aged 13, was managed by 4 chemotherapy cycles followed by surgery, completed by 5 further cycles of chemotherapy. DISCUSSION: In these 3 patients, the treatment program achieved complete disease control. Prognosis was good, thanks to good surgical access. Diagnosis should be considered in case of unusual progressive swelling in the outer ear.

[Eosinophilic gastroenteritis and colitis in pediatric patients: Increasingly frequent diseases]. / Les gastro-entéro-colites à éosinophiles chez l'enfant : des maladies de plus en plus fréquentes.

Eosinophilic gastrointestinal disorders are a heterogeneous group of disorders characterized by no specific digestive symptoms associated with dense eosinophilic inflammation of the gastrointestinal tract in the absence of known causes for such tissue eosinophilia. Among these diseases, eosinophilic gastroenteritis (EGE) and colitis (EC) are less common than esophagitis, but their incidence and prevalence have been increasing over the past decade due in part to increased disease recognition. The exact pathophysiology is not clear: EGE and EC are immune-mediated diseases implicating adaptive T-helper cell type 2 immunity. According to the site of eosinophilic infiltration, there is a wide spectrum of digestive symptoms ranging from food refusal, nausea, vomiting, abdominal pain, weight loss, gastrointestinal bleeding (anemia), protein loosing enteropathy, ascites, bowel obstruction or perforation for EGE and diarrhea ± bleeding for CE. Endoscopic lesions are not specific: friability, erythematous mucosa with superficial erosions, or ulceration is often observed. Histologically, markedly increased numbers of mucosal eosinophils are seen in biopsy specimens. However, no standards for the diagnosis of EGE or CE exist and few findings support the diagnosis: intraepithelial eosinophils, eosinophil crypt abscesses, and eosinophils in muscularis mucosa and/or submucosa. Other organs are not involved. The other causes of tissue eosinophilia (infections, inflammatory bowel diseases) should be excluded. Food allergy appears to play a central role in driving inflammation in EGE and CE, as evidenced by symptomatic improvement with initiation of food exclusion or elemental diets. Dietary treatment should be the first therapeutic option in children. If the elimination diet fails, corticosteroids are currently the best characterized treatment but appropriate duration is unknown and relapses are frequent. In severe forms, immunomodulators or biologic agents (anti-IL5, anti-IgE, or anti-TNFa) can potentially play a role in the treatment of EGE and CE.

Intraosseous haemangioma: semantic and medical confusion.

The literature is rich in case reports of intraosseous haemangioma, although most of these are actually cases of venous or capillary malformations. To illustrate this confusion in terminology, we present three cases of slow-flow vascular malformations misnamed as intraosseous haemangioma. A retrospective study of children diagnosed with intraosseous haemangioma was conducted. Clinical and radiological data were evaluated. Histopathological examinations and immunohistochemical studies were redone by three independent pathologists to classify the lesions according to the International Society for the Study of Vascular Anomalies (ISSVA) and World Health Organization (WHO) classifications. Three children who had presented with jaw haemangiomas were identified. Computed tomography scan patterns were not specific. All tumours were GLUT-1-negative and D2-40-negative. The lesions were classified as central haemangiomas according to the WHO, and as slow-flow malformations according to the ISSVA. The classification of vascular anomalies is based on clinical, radiological, and histological differences between vascular tumours and malformations. Based on this classification, the evolution of the lesion can be predicted and adequate treatment applied. The binary ISSVA classification is widely accepted and should be applied for all vascular lesions.

Ongoing and prolonged response in adult low-grade gliomas treated with radiotherapy.

The aim of the present study was to evaluate the impact of first-line radiotherapy on low-grade gliomas (LGGs) growth kinetics. The mean tumor diameter (MTD) of 39 LGGs was retrospectively measured on serial magnetic resonance images before (n = 16) and after radiotherapy onset (n = 39). After radiotherapy, a decrease of the MTD was observed in 37 patients. Median duration of the MTD decrease was 1.9 years (range 0-8.1 years). According to RANO criteria, the rates of partial and minor responses were 15 and 28 % at the first evaluation after radiotherapy and 36 and 34 % at the time of maximal MTD decrease. The presence of a 1p19q codeletion and the absence of p53 expression were associated with longer durations of MTD decrease (5.3 vs 1 years, p = 0.02 and 2.4 vs 1.8 years, p = 0.05, respectively) while no association was observed between IDH1-R132H expression and duration of MTD decrease. In most patients, MTD decrease after radiotherapy occurred in two phases: an initial phase of rapid MTD decrease followed by a second phase of slower MTD decrease. Patients with a high rate of MTD decrease during the initial phase (>7 mm/year) had both a shorter duration of response (1.9 vs 5.3 years, p = 0.003) and a shorter overall survival (5.5 vs 11.6 years, p = 0.0004). LGGs commonly display a prolonged and ongoing volume decrease after radiotherapy. However, patients who respond rapidly should be carefully monitored because they are at a higher risk of rapid progression.

[Paraganglioma of the cauda equina region: Report of six cases and review of the literature]. / Paragangliomes de la queue de cheval : à propos de six cas et revue de la littérature.

BACKGROUND AND PURPOSE: Paragangliomas of the cauda equina are rare tumors. The standard treatment is surgical resection. Our study aims to compare our clinical, radiological, prognostic data to the literature and to offer management and follow-up recommendations. METHODS: In this retrospective study, six patients with paraganglioma of the cauda equina region were treated. Symptoms included radicular nerve pain and low back pain with occasional sphincter dysfunction and motor deficit. MRI showed well-circumscribed lesions with homogeneous enhancement following gadolinium injection. Treatment involved complete surgical resection of the tumor under electrophysiological control. In addition to the characteristics of the tumor, we assessed operating results as well as postoperative morbidity and follow-up. RESULTS: All patients had complete removal of the tumor, which required in most cases the resection of the carrying root. The intervention allowed a regression of the initial symptoms, with possible postoperative regressive sphincter disorders. Clinical and radiological follow-up (19 months on average), showed no tumor recurrence. CONCLUSIONS: The reference treatment of these tumors is complete surgical resection, usually requiring the sacrifice of the carrying nerve root. Intra-operative nerve roots stimulation is recommended to reduce the risk of motor deficit linked to this radical treatment. A long-term clinical and radiological follow-up is recommended.

Human or animal homograft: could they have a future as a biological scaffold for engineered heart valves?

Tissue-engineered heart valves (TEHVs) promise to be the ideal heart valve replacement: they have the potential to grow and repair within the host, to minimise inflammatory and immunological responses and to limit thromboembolism. Viable cells included in TEHVs can theoretically adapt to a growing and changing environment exactly as a native biological structure. This could be extremely important in case of paediatric applications, where reoperations are frequently required to replace failed valve substitutes or to accommodate the growth of the patient. At present time the biological matrix from allogenic or xenogenic decellularized valves represents an appropriate valve scaffold in TEHVs, showing theoretically an ability to grow and repair within the host. Viable cells included in extracellular valve matrix can theoretically adapt to a growing and changing environment like the native biological structure. The aim of this paper is to present a review concerning the use of homograft and allograft valves as an ideal substrate for cardiac engineered tissue valves that represent an exciting possibility for in situ regeneration and repair of heart valves.

Abdominal aortic aneurysm repair in octogenarians: outcomes and predictors.

OBJECTIVES: This study was undertaken to evaluate predictors and outcomes of octogenarians who underwent abdominal aortic aneurysm repair. DESIGN: A prospective observational study. MATERIALS AND METHODS: Between January 1st, 1997 and April 15th, 2005, 31 octogenarians were admitted to our Department with the diagnosis of abdominal aortic aneurysm. Mean follow-up time was 53.7+/-27.2 months. All patients were in good clinical condition and represented a selected healthy group of octogenarians. RESULTS: The overall perioperative (30-days) mortality rate was 3.1%. The total in-hospital morbidity rate was 22.6%. Overall survival estimates at 48 and 96 months were 81+/-8% and 46+/-21%, respectively. The actuarial freedom from aneurysm-related death at 48 and 96 months was 96+/-4% and 96+/-4%, respectively. The actuarial freedom from aneurysm-unrelated death at 48 and 96 months was 84+/-7% and 48+/-21%. Only coronary artery disease was a significant predictor of survival using multivariate stepwise logistic regression analysis. CONCLUSIONS: In this series, AAA surgery was carried out in selected octogenarians without affecting long-term survival.

A preoperative index of mortality for patients undergoing surgery of type A aortic dissection.

BACKGROUND: The aim of this study was to identify and stratify the most important preoperative factors for in-hospital death after surgery for type A aortic dissection. METHODS: From January 1985 to June 1998, 108 patients underwent surgery for type A aortic dissection. 89.9% of the patients had an acute type A dissection (AD), whereas 11.1% had a chronic dissection (CD). Cardiac tamponade and shock occurred in 22% and 14.8% of the patients, respectively. The location of the primary intimal tear was in the ascending aorta in 71.2% of the cases, in the arch in 16.6% and in the descending aorta in 7.4%. Univariate and multivariate analyses were conducted to identify non-embolic variables independently correlated to in-hospital death. A predictive model of in-hospital mortality was then constructed by means of a mathematical method with the variables selected from logistic regression analysis. RESULTS: The overall in-hospital mortality rate was 20.3% (22/108 patients), being 9% for CD and 21.6% for AD. Emergent procedures had an in-hospital mortality rate of 47.6%, whereas non-emergent operations had an in-hospital mortality rate of 13.7% (p<0.01). Univariate analysis revealed among 39 preoperative and operative variables, age (years), age >70 years, remote myocardial infarction, cerebrovascular dysfunction, diabetes, preoperative renal failure, shock, cardiopulmonary bypass time (minutes), emergency operation as factors associated to in-hospital death (p<0.05). Stepwise logistic regression analysis selected as independent predicting variables (p<0.05), remote myocardial infarction (p=0.006), preoperative renal failure (p=0.032), shock (p=0.001), age >70 years (p=0.007). Finally, a probability table of death risk was obtained with the logistic regression coefficients. The lower death probability (10.6%) was calculated in absence of risk variables; the higher one in presence of all of them (79.7%). Between these extremes, a total of 64 combinations of death risk were obtained. CONCLUSIONS: Increasing age, shock, coronary artery disease and renal failure are variously associated to a high risk of in-hospital death after surgical correction of type A aortic dissection. This predictive model of death probability allows to collocate preoperatively patients with type A aortic dissection at different levels of risk for in-hospital death.

Centrifugal pump and reduction of neurological risk in adult cardiac surgery.

This study was performed to assess if the kind of pump used for CPB (roller vs. centrifugal) can influence neurological outcomes of adult cardiac surgery patients. Between 1994 and 1998, 3438 patients underwent coronary and/or valve surgery at our hospital; of these, 1805 (52.5%) underwent surgery with the use of a centrifugal pump, and 1633 (47.5%) were operated with a roller pump. The effect of the type of the pump and of common preoperative and intraoperative risk factors for five different neurological outcomes (permanent neurological deficit, coma, delirium, transient neurological deficit, overall neurological complications) were assessed with univariate and multivariate analyses in the whole patients population, in patients > or = 75 years old and in patients with histories of previous neurological events. Centrifugal pump use was the only protective factor for perioperative permanent neurological deficit in multivariable models developed for the whole patient population and for patients > or = 75 years old. In addition, it resulted as the only protective factor for perioperative coma occurrence in multivariable models developed for patients > or = 75 years old, and for patients with histories of previous neurological events. The use of the centrifugal pump provided a risk reduction for the considered events ranging from 23 to 84%. Centrifugal pump use can be helpful in reducing the occurrence of some of the most feared neurological complications of adult cardiac surgery patients.

Cardiopulmonary bypass and oxygen consumption: oxygen delivery and hemodynamics.

BACKGROUND: This study was undertaken to investigate the relations between whole body oxygen consumption (VO2), oxygen delivery (DO2), and hemodynamic variables during cardiopulmonary bypass. METHODS: One hundred one patients were studied during cooling, hypothermia, and rewarming. Oxygen consumption, DO2, hemodynamics, and DO2crit were measured at these times. RESULTS: There was a direct linear relation between DO2 and VO2 during all three times. No relation between VO2 and hemodynamics was detected during cooling; during hypothermia, an inverse linear relation with peripheral arterial resistance was found. Finally, during rewarming, there was a direct relation with pump flow rate, and an inverse relation with arterial pressure and arterial resistance. The same relations among the variables were found at delivery levels above or below DO2crit. CONCLUSIONS: During cardiopulmonary bypass there is a direct linear relation between DO2 and VO2; the relations with hemodynamic variables depend on the phases of cardiopulmonary bypass. This suggests that increasing delivery levels may recruit and perfuse more vascular beds, and higher delivery levels are advisable during perfusion. During rewarming and hypothermia, lower arterial resistances are also desirable to optimize VO2.

Quick, simple clamping technique in descending thoracic aortic aneurysm repair.

BACKGROUND: Although significant advances have been made in the surgical treatment of diseases affecting the descending thoracic aorta, paraplegia remains a devastating complication. We propose the quick, simple clamping technique to prevent spinal cord ischemic injury. METHODS: From 1983 to 1998, 143 patients had descending thoracic aorta aneurysm repair. We divided the patients into the following three groups according to the surgical technique used: selective atriodistal bypass was used in group 1 (66 patients); simple clamping technique in group 2 (28 patients); and quick simple clamping technique in group 3 (49 patients). Mean aortic cross clamp time was 39+/-13 minutes in group 1, 37+/-11 minutes in group 2, and 17+/-6 minutes in group 3 (p<0.01 group 3 versus group 1 and group 2). RESULTS: The overall incidence of paraplegia was 4.8% (7 patients), 4.5% (3 patients) in group 1, 14.3% (4 patients) in group 2, and 0 in group 3 (p<0.05 group 3 versus group 2). The overall in-hospital mortality rate was 5.5%. Multivariate logistic regression analysis showed a powerful effect of aortic cross-clamping time as risk factor for both paraplegia (p<0.008), with an odds ratio of 1.03 per minute, and in-hospital mortality (p<0.001), with an odds ratio of 2.5 per minute. The mean follow-up time was 65 months with a lower overall mortality rate in group 3 than in group 1 and group 2 (p<0.05). CONCLUSION: In descending thoracic aortic aneurysm repair, spinal cord perfusion can be maintained adequately without reimplantation of segmental vessels or use of atriodistal bypass when the aortic cross-clamp time is short (<15 to 20 minutes).

Endothelial-dependent dynamic and antithrombotic properties of porcine aortic and pulmonary valves.

BACKGROUND: In the present study, the endothelium-dependent antithrombotic and dynamic properties of porcine aortic (AoV) and pulmonary valves (PuV) were investigated. METHODS: Fifteen fresh AoV and 15 fresh PuV were obtained from 25 9-month-old swines. The valves were examined for endothelial function by pharmacologic evaluation (with and without endothelium) of both the endothelial-releasing capacity of prostacyclin and the endothelial-dependent dynamic response to relaxing (acetylcholine from 10[-10] mol/L to 10[-4] mol/L in AoV and PuV segments precontracted with norepinephrine [3 x 10(-6) mol/L]) and contracting (endothelin-1, from 10[-11] mol/L to 10[-5] mol/L; and NG-monomethyl-L-arginine, 10[-4] mol/L) drugs. The ultrastructural integrity of the endothelial valve layer was also examined with transmission electron microscopy. RESULTS: Acetylcholine caused potent relaxation in both AoV and PuV specimens with, but not in those without, endothelium. Endothelin-1 produced a concentration-dependent tension increase in AoV and PuV with and without endothelium. However, the intrinsic activity of the peptide significantly increased in tissues without endothelium. NG-monomethyl-L-arginine evoked a progressive increase in resting tension of the preparations, but the AoV and PuV without endothelium were less sensitive to the inhibition of the nitric oxide generation. Aortic and pulmonary valves with an intact endothelium showed a spontaneous ability to release prostacyclin. The basal release of this lipidic autacoid significantly decreased in cardiac valves without endothelium. This phenomenon was observed in both basal conditions, and under stimulation with the aforementioned drugs. Transmission electron microscopy showed the perfect preservation of endothelial cells in all the preparations examined. CONCLUSIONS: Valvular endothelium of AoV and PuV seems to have similar antithrombotic and dynamic functions of vascular endothelium, actively participating in valvular homeostasis.

[Oxygen consumption during cardiovascular surgery conducted under extra-corporeal circulation]. / Il consumo di ossigeno nella chirurgia cardiovascolare condotta con l'utilizzo della circolazione extracorporea.

Whole-body oxygen consumption (VO2) is universally considered both a measure of the metabolic activity of the body and an indicator of the adequacy of tissue perfusion during cardiopulmonary bypass as well. There is little agreement in the literature about the main determinants of oxygen consumption during CPB, except for the role of temperature in reducing the metabolic activity of the body. Many studies, which have been performed both on animals and in humans, have reached some contradictory conclusions about the role of delivery and perfusion flow rates, of haemodynamic variables, of the acid-base status, and of drugs influencing the variations of oxygen consumption during CPB. Aim of this paper is to review the evidences in literature about the determinants of whole-body oxygen consumption during cardiopulmonary bypass in man.

[Surgery of the ascending aorta: the 1984-1995 experience of the cardiac surgery teaching unit in the University of Milan. Multivariate analysis of its risk factors for hospital mortality and reduced long-term survival]. / Chirurgia dell'aorta ascendente: esperienza 1984-1995 della Cattedra di Cardiochirurgia dell'Università di Milano. Analisi multivariata sui fattori di rischio per mortalità ospedaliera e ridotta sopravvivenza a distanza.

Between 1984 and 1995, 183 patients underwent an ascending aorta procedure at our institution. Their mean age was 60 +/- 12.3 years; 116 (63.4%) patients were male, 35 (19.1%) had a history of congestive heart failure, 72 (39.3%) presented acute type A dissection, 23 (12.6%) were redos and 63 (34.4%) were operated on an emergency basis. In-hospital mortality was 10% (12/120) in elective procedures and 36.5% (23/63) in emergency operations (p < 0.0001). Multivariate stepwise logistic regression analysis identified cardiopulmonary by-pass time, emergency operation, arch replacement and the need for femoral vein cannulation at surgery as independent predictors of in-hospital death. Mean follow-up time was 54 +/- 30 months (median 50 months), with a Kaplan-Meier survival of 69 +/- 4% and of 60 +/- 5% at 5 and 7 years, respectively. Cox regression analysis identified arch replacement, perioperative myocardial infarction, preoperative NYHA class, acute type A aortic dissection, the need for femoral vein cannulation at intervention and redo operations as independent predictors of reduced survival at follow-up. When this kind of analysis was performed on hospital survivors only, postoperative tracheostomy, reexploration for bleeding, and the occurrence of postoperative ventricular arrhythmias emerged as risk factors. In conclusion, multiple factors affect both early and long-term outcome following ascending aorta surgery. Preoperative clinical status of patients, priority of surgery and aortic dissection are the main determinants of the short-term results. Otherwise, in hospital survivors, the main determinant for long-term outcome seems to be the immediate postoperative course.