Re-focusing on Agnathia-Otocephaly complex.

OBJECTIVES: Agnathia-otocephaly complex is a rare condition characterized by mandibular hypoplasia or agnathia, ear anomalies (melotia/synotia) and microstomia with aglossia. This severe anomaly of the first branchial arch is most often lethal. The estimated incidence is less than 1 in 70.000 births, with etiologies linked to both genetic and teratogenic factors. Most of the cases are sporadic. To date, two genes have been described in humans to be involved in this condition: OTX2 and PRRX1. Nevertheless, the overall proportion of mutated cases is unknown and a significant number of patients remain without molecular diagnosis. Thus, the involvement of other genes than OTX2 and PRRX1 in the agnathia-otocephaly complex is not unlikely. Heterozygous mutations in Cnbp in mice are responsible for mandibular and eye defects mimicking the agnathia-otocephaly complex in humans and appear as a good candidate. Therefore, in this study, we aimed (i) to collect patients presenting with agnathia-otocephaly complex for screening CNBP, in parallel with OTX2 and PRRX1, to check its possible implication in the human phenotype and (ii) to compare our results with the literature data to estimate the proportion of mutated cases after genetic testing. MATERIALS AND METHODS: In this work, we describe 10 patients suffering from the agnathia-otocephaly complex. All of them benefited from array-CGH and Sanger sequencing of OTX2, PRRX1 and CNBP. A complete review of the literature was made using the Pubmed database to collect all the patients described with a phenotype of agnathia-otocephaly complex during the 20 last years (1998-2019) in order (i) to study etiology (genetic causes, iatrogenic causes…) and (ii), when genetic testing was performed, to study which genes were tested and by which type of technologies. RESULTS: In our 10 patients' cohort, no point mutation in the three tested genes was detected by Sanger sequencing, while array-CGH has allowed identifying a 107-kb deletion encompassing OTX2 responsible for the agnathia-otocephaly complex phenotype in 1 of them. In 4 of the 70 cases described in the literature, a toxic cause was identified and 22 out the 66 remaining cases benefited from genetic testing. Among those 22 patients, 6 were carrying mutation or deletion in the OTX2 gene and 4 in the PRRX1 gene. Thus, when compiling results from our cohort and the literature, a total of 32 patients benefited from genetic testing, with only 34% (11/32) of patients having a mutation in one of the two known genes, OTX2 or PRRX1. CONCLUSIONS: From our work and the literature review, only mutations in OTX2 and PRRX1 have been found to date in patients, explaining around one third of the etiologies after genetic testing. Thus, agnathia-otocephaly complex remains unexplained in the majority of the patients, which indicates that other factors might be involved. Although involved in first branchial arch defects, no mutation in the CNBP gene was found in this study. This suggests that mutations in CNBP might not be involved in such phenotype in humans or that, unlike in mice, a compensatory effect might exist in humans. Nevertheless, given that agnathia-otocephaly complex is a rare phenotype, more patients have to be screened for CNBP mutations before we definitively conclude about its potential implication. Therefore, this work presents the current state of knowledge on agnathia-otocephaly complex and underlines the need to expand further the understanding of the genetic bases of this disorder, which remains largely unknown. CLINICAL RELEVANCE: We made here an update and focus on the clinical and genetic aspects of agnathia-otocephaly complex as well as a more general review of craniofacial development.

IL11RA-related Crouzon-like autosomal recessive craniosynostosis in 10 new patients: Resemblances and differences.

By describing 10 new patients recruited in centres for Human Genetics, we further delineate the clinical spectrum of a Crouzon-like craniosynostosis disorder, officially termed craniosynostosis and dental anomalies (MIM614188). Singularly, it is inherited according to an autosomal recessive mode of inheritance. We identified six missense mutations in IL11RA, a gene encoding the alpha subunit of interleukin 11 receptor, 4 of them being novel, including 2 in the Ig-like C2-type domain. A subset of patients had an associated connective tissue disorder with joint hypermobility and intervertebral discs fragility. A smaller number of teeth anomalies than that previously reported in the two large series of patients evaluated in dental institutes points toward an ascertainment bias.

Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogénétique Hématologique.

The NUP98 gene is fused with 19 different partner genes in various human hematopoietic malignancies. In order to gain additional clinico-hematological data and to identify new partners of NUP98, the Groupe Francophone de Cytogénétique Hématologique (GFCH) collected cases of hematological malignancies where a 11p15 rearrangement was detected. Fluorescence in situ hybridization (FISH) analysis showed that 35% of these patients (23/66) carried a rearrangement of the NUP98 locus. Genes of the HOXA cluster and the nuclear-receptor set domain (NSD) genes were frequently fused to NUP98, mainly in de novo myeloid malignancies whereas the DDX10 and TOP1 genes were equally rearranged in de novo and in therapy-related myeloid proliferations. Involvement of ADD3 and C6ORF80 genes were detected, respectively, in myeloid disorders and in T-cell acute lymphoblastic leukemia (T-ALL), whereas the RAP1GDS1 gene was fused to NUP98 in T-ALL. Three new chromosomal breakpoints: 3q22.1, 7p15 (in a localization distinct from the HOXA locus) and Xq28 were detected in rearrangements with the NUP98 gene locus. The present study as well as a review of the 73 cases previously reported in the literature allowed us to delineate some chromosomal, clinical and molecular features of patients carrying a NUP98 gene rearrangements.

Doppler echocardiography for the diagnosis of acute cardiac allograft rejection.

To evaluate the changes in left ventricular filling associated with acute cardiac rejection, serial Doppler echocardiographic examinations were prospectively performed on the same day as endomyocardial biopsy in 55 consecutive patients who successfully underwent orthotopic transplantation and were free of a previous episode of rejection. On average, 8.6 Doppler studies per patient were performed within a 6 month period after transplantation. Recordings of mitral flow were made with pulsed Doppler and two-dimensional echocardiography from an apical four chamber view; isovolumic relaxation time, peak early mitral flow velocity and pressure half-time were measured. The patients were classified into two groups on the basis of the histopathologic findings: group I (25 patients with at least one episode of mild or moderate rejection) and group II (30 patients without rejection). In group I, rejection was associated with a significant decrease of isovolumic relaxation time (p less than 0.005) and especially pressure half-time (p less than 0.0005) with no change in heart rate and peak early mitral flow velocity. In group II, Doppler indexes remained unchanged. These changes were not associated with alterations in left ventricular systolic function assessed by echocardiography. Isovolumic relaxation time and pressure half-time both returned to values similar to baseline values after immunosuppressive therapy (p less than 0.05 and p less than 0.0005, respectively). With 20% decrease in pressure half-time as a criterion for acute rejection, sensitivity was 88%, specificity 87% and positive predictive value 85%. Thus, Doppler echocardiographic evaluation of left ventricular diastolic function provides an excellent tool for early detection of acute rejection and noninvasive monitoring of the cardiac transplant recipient.

Cytogenetic study of 75 erythroleukemias.

Chromosomal abnormalities of erythroleukemia (EL) are often described as complex and unspecific. A retrospective study of 75 EL defined following the WHO classification was performed by the Groupe Francophone de Cytogénétique Hématologique (GFCH) in order to reexamine the cytogenetics of this infrequent leukemia subtype. Clonal chromosomal abnormalities were found in 57 patients (76%), distributed in 4 subgroups according to their ploidy status: pseudodiploid (16%), hypodiploid (47%), hyperdiploid (19%), and 18% mixed cases associating 2 different clones (hypodiploid+hyperdiploid) or (pseudodiploid+hyperdiploid). Complex rearrangements and hypodiploid chromosome number were widely dominant (50%). Partial or entire monosomies represented 56% of abnormalities. Chromosomes 5 and 7 were the most frequently involved (41 and 33 times, respectively), followed by chromosomes 8, 16, and 21 (19 times each). Unbalanced abnormalities were more frequent than balanced. All these kinds of abnormalities were observed in de novo as well as in secondary EL. Four out of 7 cases of "pure erythroid" leukemia were associated with a BCR-ABL fusion. Lastly, no chromosome abnormality specific to EL could be established. However, the large overlap of chromosomal abnormality patterns of EL (pure erythroid form excepted) and refractory anemia with excess of blasts in transformation (RAEB-t) favors the hypothesis of similarities between these 2 hematologic disorders.

Implications of de novo ELAM-1 and VCAM-1 expression in human cardiac allograft rejection.

Both cytokines produced by activated monocytes and T cells and direct cell-to-cell contact with antigen-primed T cells during inflammatory reactions are known to induce the expression of several adhesion proteins on endothelial cells. In this prospective longitudinal study, we analyzed the expression of ELAM-1, VCAM-1, and ICAM-1 on myocardial allograft biopsy specimens taken from 16 cardiac allograft recipients either for routine monitoring or for the investigation of suspected rejection. Infiltrating T cells were identified using anti-CD3 antibodies. Three to six sequential biopsies taken at one-week intervals were analyzed by means of conventional histology and immunohistochemistry. Seven patients did not develop rejection during the study; their biopsies were negative for VCAM-1 and ELAM-1, although faint ICAM-1 staining was present on capillaries, reflecting constitutive expression. Three patients entered the study with clear-cut clinical and histologic signs of acute rejection. Intense VCAM-1 and ICAM-1 expression was detected on capillary and postcapillary venules, together with a heavy CD3+ T cell infiltrate; VCAM-1 was also expressed on arteriolar endothelial cells. ELAM-1 was undetectable in all three cases. Six patients developed acute rejection during the course of the study. In four, ELAM-1 and VCAM-1 were expressed on both capillary and postcapillary venules one or two weeks before the histological diagnosis of rejection (heavy CD3+ cell infiltrate). Importantly, ELAM-1 expression was short-lived and had disappeared by the time CD3+ cellular infiltrate was detected, thus extending in vivo the finding that ELAM-1 expression is usually transient in vitro. Only VCAM-1 expression was observed in the other two patients, one week prior to the histological diagnosis of rejection. These results suggest that ELAM-1 and VCAM-1 might represent early predictive markers of acute cardiac allograft rejection. ELAM-1 expression is, however, usually transient, necessitating frequent testing.

Prevention of atrial fibrillation or flutter by acebutolol after coronary bypass grafting.

Supraventricular tachyarrhythmias are common after coronary artery bypass graft surgery (CABG) and may have deleterious hemodynamic consequences. To determine if acebutolol, a cardioselective beta-blocking drug, prevents such tachyarrhythmias after CABG, 100 consecutive patients, aged 30 to 77 years (mean +/- standard deviation 53 +/- 9), were entered into a randomized, controlled study. Exclusion criteria were: contraindications to beta-blocking drugs, left ventricular aneurysm, major renal failure, history of cardiac arrhythmia and cardiac arrhythmia during the immediate postoperative period. From 36 hours after surgery until discharge (usually on the seventh day), 50 patients were given 200 mg of acebutolol (or 400 mg if weight was more than 80 kg) orally twice a day (dosage than modified to maintain a heart rate at rest between 60 and 90 beats/min). The 50 patients in the control group did not receive beta-blocking drugs after CABG. The 2 groups were comparable in angina functional class, ejection fraction, number of diseased vessels, antianginal therapy before CABG, number of bypassed vessels and duration of cardiopulmonary bypass All patients were clinically evaluated twice daily and had continuous electrocardiographic monitoring and daily electrocardiograms. A 24-hour continuous electrocardiogram was recorded in the last 20 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic hypertension after cardiac transplantation: effect of cyclosporine on the renin-angiotensin-aldosterone system.

Fifteen patients who had undergone cardiac transplantation and who had hypertension (164 +/- 14/112 +/- 13 mm Hg), aged 16 to 57 years (mean 39), were treated with cyclosporine, 8 +/- 3 mg/kg/day, and prednisolone, 0.27 +/- 0.1 mg/kg/day, for 63 to 788 days (mean 288) after transplantation. They were not given antihypertensive drugs. Before treatment, the mean urinary sodium level was 104 +/- 48 mEq/day. Two discrete abnormalities accompanied their high blood pressure (BP): an increase in serum creatinine levels (p less than 0.05) to values exceeding those measured just before transplantation (2.1 +/- 1.0 vs 1.35 +/- 0.54 mg/dl) with low creatinine clearance (61 +/- 28 ml/min X 1.73 m2), and a 15% increase in plasma volume (+445 +/- 686 ml, p less than 0.02). Urinary excretion of vanilmandelic acid and total metanephrines was normal. Supine plasma renin activity was also normal (0.78 +/- 0.32 nmol/ml/hour). The stimulation of renin release after acute inhibition of converting enzyme by captopril was less marked than is usual in hypertensive subjects (0.86 +/- 0.54 nmol/liter/hour). Captopril induced a smaller drop in BP than nifedipine (-8 +/- 13/-6 +/- 10 mm Hg vs -14 +/- 11/-15 +/- 10 mm Hg). Levels of plasma aldosterone, angiotensinogen and converting enzyme activity were all normal, 308 +/- 147 pmol/liter, 712 +/- 164 nmol/ml and 30 +/- 6 mU/ml, respectively. It is concluded that hypertension is common in cardiac transplantation patients treated with cyclosporine, since 13 of our 15 subjects were normotensive before transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytogenetic study in a mentally retarded child with Bloom syndrome and acute lymphoblastic leukemia.

Bloom syndrome (BS) was diagnosed in a 7-year-old boy during hospitalization for acute lymphoblastic leukemia (ALL). The patient had most of the signs of BS along with some atypical manifestations: absence of telangiectases, obesity, and moderate mental retardation. Results of the cytogenetic studies were fully consistent with the diagnosis of BS: the occurrence of quadriradial figures and a very high incidence of sister-chromatid exchanges (SCE). This child's ALL was of non-B, non-T type with the presence, at the time of diagnosis, of a marrow clone including two markers. A Yq - chromosome was detected in about 10% of PHA-stimulated lymphocytes but neither in bone marrow cells nor in skin fibroblasts. This case is the fifth instance of ALL out of 104 registered cases of BS.

Long-term results with total replacement of the ascending aorta and reimplantation of the coronary arteries.

From November, 1976, to June, 1983, 100 patients, 84 male and 16 female patients ranging in age from 13 to 74 years, were operated on for aortic insufficiency associated with an aneurysm of the ascending aorta. Twenty patients were in New York Heart Association Class I, 22 in Class II, 51 in Class III, and seven in Class IV. The surgical treatment in all cases consisted of total replacement of the ascending aorta with a tube graft containing a prosthetic aortic valve and reimplantation of the coronary arteries by an intermediate tube graft according to the technique already reported. In 68 patients an uncomplicated annulo-aortic ectasia existed, and in 32, an aortic dissection; nine of the latter group were operated on during the acute phase. The operative mortality for the entire group was 4% (four deaths). One patient has been lost to follow-up during a period ranging from 18 months to 8 years (average 54 months). The late mortality has been 11/96. Among the 84 survivors, clinical improvement is readily apparent (89% are in Class I or II). Twenty-five patients have been restudied by angiography, which revealed a satisfactory coronary and aortic appearance in all cases with neither stenosis nor aneurysm. The actuarial survival rate is 75% at 8 years. In conclusion, the treatment of aortic insufficiency associated with an aneurysm of the ascending aorta by insertion of a composite graft and reimplantation of the coronary arteries through an intermediate Dacron tube is a reliable method with low mortality and excellent long-term results.

Intraoperative coronary artery endarterectomy with excimer laser.

Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater. A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis. Laser power was increasingly delivered up to the clearing of the stenosis or occlusion. Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram. In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow. In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent. The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter. We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes.

Cardiac echinococcosis. Surgical treatment and results.

During the last 15 years, eight patients with a diagnosis of hydatid cysts of the heart and one patient with a diagnosis of alveolar hydatid disease with intracardiac parasitic thrombus underwent successful operation at La Pitié Hospital. Only five cases had symptoms, and the remaining four cases were diagnosed incidentally. Serologic tests achieved a variety of results and were not determinant. All patients were examined with echocardiography and angiography, and almost all patients underwent magnetic resonance scanning. Sternotomy was the approach used, and all patients underwent operation with cardiopulmonary bypass. Surgical treatment included puncture and aspiration of the cyst content, previous sterilization with hypertonic saline solution, and excision of the cyst with closure of the cavity in seven patients with different concomitant procedures. No case of intraoperative rupture was reported, and the only complication was an atrioventricular block in a patient with a cyst of the left ventricular wall invading the intraventricular septum. There was no operative mortality, and only one late death was observed. No recurrences or associated complications were reported in the late follow-up.

Prosthetic valve endocarditis with ring abscesses. Surgical management and long-term results.

From January 1978 to December 1988, 71 patients underwent surgical intervention at our institution for prosthetic valve endocarditis with ring abscesses. These procedures involved 59 aortic prostheses and 12 mitral prostheses. No causative agent could be identified in 19 patients (26.7%). The operation was performed during antibiotic therapy in 63 patients and after a planned course of antibiotic therapy in 8 patients. At the aortic level, abscesses were remedied by suturing in 3 cases, by pericardial patches in 34 cases, and by complex procedures in 22 cases (subcoronary valved conduit in 11 cases, supracoronary valved conduit with coronary bypass grafts in 10 cases, apicoaortic valved conduit in 1 case). At the mitral level, ring abscesses were cured in 10 cases by intraatrial implantation of the prosthesis. In one case, the prosthesis was anchored inside the left ventricle; and in one case the valve could be seated on the anulus. The overall operative mortality rate was 17%. Long-term survival was 54% +/- 8% at 6 years. Fifteen (26%) of the survivors needed a third valve replacement (four operative deaths); a complex reconstruction was performed in seven patients. Better detection of ring abscesses and earlier surgical intervention before annular destruction and hemodynamic failure can improve the operative mortality rate for prosthetic valve endocarditis. When it is necessary, complex reconstruction, in spite of a high mortality rate, seems to eradicate the infectious seat, and the outlook for the patient's condition appears good.

Heart and unilateral lung transplantation in patients with end-stage cardiopulmonary disease and previous thoracic operations.

Orthotopic en bloc transplantation of the heart and one lung has been done in two patients with end-stage cardiopulmonary disease and a prior thoracic operation. The first patient had undergone right pulmonary thromboembolectomy with caval ligation 5 years earlier, and the second had had left lower lobectomy for bronchiectasis 15 years before the heart and contralateral lung transplantation. Surgical procedures followed the techniques that had been developed in animals. Transplantation of the unoperated contralateral lung made it possible to avoid dissection in the obliterated pleural space and to minimize bleeding, which simplified the procedure considerably. Dramatic reduction in pulmonary artery pressure and improved respiratory function allowed both patients to be weaned from cardiopulmonary bypass without problems. Although the first patient died of liver and renal failure soon after the operation, an intact cough reflex facilitated recovery in the second patient, who has been discharged with essentially normal respiratory function. This report describes heart and unilateral lung transplantation as a procedure of choice for patients with extensive pleural adhesions that made total cardiopulmonary replacement unfeasible.

Hemodynamic evaluation of heterotopic heart transplantation.

To assess the relative contribution of native and donor hearts to total circulatory performance after heterotopic transplantation, we used cardiac catheterization to examine 10 patients. Left and right ventricular filling pressures significantly decreased by 41% and 36%, respectively, cardiac index increased by 25%, and pulmonary arteriolar resistance was reduced by 61%. Patients were subdivided into two groups according to the presence of one (group I) or two (group II) peaks on the aortic pressure curve. In group I, the donor left ventricle assumed total left ventricular work and 80% of right ventricular work. Because the native left ventricle could not generate enough pressure to open the aortic valve, its entire stroke volume was ejected into the common left atrium. In addition, in all four patients a native aortic regurgitation occurred in diastole and systole. In contrast, in group II, native left ventricular systolic pressure always exceeded aortic diastolic pressure. The donor left ventricle contributed 68% to systemic blood flow and the donor right ventricle 51% to pulmonary blood flow. Mild native aortic regurgitation was demonstrated in two patients only. Native left ventricular function deteriorated postoperatively in all patients (ejection fraction decreased from 0.22 +/- 0.09 to 0.14 +/- 0.08), but this deterioration was more marked in group I. Postoperative depression of native left ventricular function could not be ascribed to progression of coronary artery disease but was mainly due to reduced preload (competitive filling) and increased afterload. Thus in group I patients with more severe preoperative left ventricular dysfunction, the donor heart behaved like a total biventricular assist device. In contrast, in group II patients the donor heart acted like a partial biventricular assist device.

Heart-lung transplantation in situs inversus. A case report in a patient with Kartagener's syndrome.

After a long history of recurrent chronic pulmonary infections in a 25-year-old woman with Kartagener's syndrome, a heart-lung transplantation was performed. A modified surgical procedure was needed to perform transplantation because of the presence of a situs inversus, which is usually associated with bronchiectasis and sinusitis in this congenital syndrome. A large single atrium was created with both the right and left recipient atria used to facilitate anastomosis with the donor's right atrium. The patient was discharged after resolution of early ventilatory complications and is in good condition 8 months after transplantation.

Orthotopic transplantation after implantation of a Jarvik 7 total artificial heart.

A total artificial heart was used to support the circulation in 33 heart transplantation candidates who were expected to die before procurement of a donor heart. Twelve of these patients (mean age 35 +/- 10 years) underwent cardiac transplantation. Another patient is still being supported with the total artificial heart 90 days after implantation. The other 20 patients died during mechanical support because their condition could not be stabilized for transplantation, despite blood flow restoration. Fifty-six percent of the patients younger than 40 years underwent successful transplantation and six of nine patients are long-term survivors. By comparison, in the older group, 17.6% of patients underwent transplantation and one of three survived long term. Forty-four percent of patients in the acute decompensation group had successful transplantation and four of seven patients are long-term survivors. In the chronic decompensation group these figures were 29.4% and three of five patients. All patients who were heavily immunosuppressed (n = 4) died of sepsis. Transplantation was considered and performed only when the patient's condition was correct and stable. In six patients an infection developed in the immediate posttransplant period. Three of the infections were resolved with antibiotic therapy. One originated in the mediastinum and is still unresolved, although the patient's condition is improving. Another patient died of an anoxic coma caused by ventilatory problems. There were two late deaths at 14 and 19 months, one resulting from a combination of toxoplasmosis and rejection and the other from a Kaposi sarcoma caused by azathioprine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic disease of the ascending aorta. Surgical treatment and long-term results.

Between January 1979 and December 1991, we operated on 339 patients for chronic disease of the ascending aorta. The operation was elective in all. Endocarditis and its sequelae have been excluded. Thirty-one patients had a previous operation on the ascending aorta or the aortic valve; 268 patients had aneurysms of the ascending aorta without dissection; 72 had chronic aortic dissections, of whom 33 had a preexistent aneurysm. The patients included 272 men and 67 women. Mean age was 53.58 +/- 7 years. Eight percent of the patients had clinical stigmata of Marfan's disease. A tubular graft replacement was used in 7 patients, a tubular graft and valve replacement in 72 patients, and a composite valve graft replacement with reattachment of the coronary arteries using a 8 mm Dacron graft was performed in 260 patients. Concomitant procedures were used in 74 patients: coronary artery bypass grafts in 25, mitral valve replacement in 9, and aortic arch reconstruction in 40. The 30-day mortality rate was 7.6% (n = 26). For the whole group, multivariate analysis using stepwise logistic regression showed that operative risk factors were concomitant coronary artery bypass grafting, age (increased), aortic valve regurgitation, and previous cardiac surgery. Follow-up was conducted in 303 patients, and risk factors for late mortality were studied. Long-term survival was 59.6% +/- 3.7% at 9 years. It was 67% +/- 3.5% at 9 years for patients without aortic arch reconstruction and 56% +/- 4.5% for patients with aortic arch reconstruction (p = 0.0018). Reoperation was needed in 14 patients. Actuarial freedom from reoperation was 90% +/- 0.2% at 9 years for all the patients. Only one patient with composite valve graft replacement and reattachment of the coronary arteries had required reoperation for problems related to this procedure. This technique is used routinely by our team, especially in patients with large chronic aneurysms, dissected or not, and in those who had previous operations. The long-term results are good.

Complete replacement of the ascending aorta with reimplantation of the coronary arteries: new surgical approach.

Thirty patients had total replacement of the ascending aorta with reimplantation of the coronary arteries, 20 for a fusiform aneurysm of the ascending aorta and 10 because of a dissection of the ascending aorta, of which there were acute. All had associated aortic insufficiency. The technique consists of implantation, within the aneurysmal sac, of a Dacron prosthesis containing a Björk-Shiley aortic valve. The coronary orifices are anastomosed to the tubular Dacron prosthesis by means of a second smaller Dacron tube. The aneurysmal pouch is then closed over the entire appliance and a fistula between the aneurysmal sac and the right atrial appendage is created to drain oozing from the prosthesis. The operative mortality was 10% (three deaths) and the late mortality has been 14.8% (four deaths). The deaths, early and late, have been confined to the first 10 cases, during which time the technique was being developed. There has been no mortality among the last 20 patients. The 23 survivors followed for an average of 19 1/2 months (range 6 months to 5 1/2 years) are in NYHA Functional Class I (21) or II (two). The technical modifications utilized in this series have simplified the operation and permit the proposal of this technique for aneurysm involving the entire ascending aorta.