Nonrecurrent laryngeal nerve during carotid artery surgery: case report and literature review.

The anomalous position of a nonrecurrent inferior laryngeal nerve predisposes it to injury during surgery in the neck. We present the case of a patient who underwent a carotid endarterectomy in which a rare left nonrecurrent laryngeal nerve was found intraoperatively. This abnormality, which occurs much less often on the left than the right side of the neck, should be familiar to vascular surgeons. Historical, embryologic, and surgical significance of this anomaly is addressed.

"Cobrahead" graft for intercostal artery implantation during descending aortic replacement.

A technique for a separate sidearm graft ("cobrahead") to facilitate reattachment of intercostal arteries in descending aortic replacement is described. The technique allows for very prompt restoration of spinal cord blood flow (via a Y attachment from the arterial perfusion circuit). The technique permits a simple, quick, and fully accessible anastomosis, technically more facile than the traditional side-to-side anastomosis. None of 7 patients treated with this technique had early or late paraplegia. Preliminary computed tomographic follow-up scans confirm patency of the cobrahead graft.

Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections.

The natural history of thoracic aortic aneurysms and dissections is diverse, reflecting a broad spectrum of etiologies which include increasing aortic size, hypertension, and genetic factors. The pathogenesis is related to defects or degeneration in structural integrity of the adventitia, not the media, which is required for aneurysm formation. The ascending and descending aorta appear to have separate underlying disease processor that lead to a weakened vessel wall and an increased susceptibility for dissection. Etiologic factors for aortic aneurysms and dissections are multifactorial, reflecting genetic, environmental, and physiologic influences.

Pathologic variants of thoracic aortic dissections. Penetrating atherosclerotic ulcers and intramural hematomas.

This article confirms the existence of two variants of acute aortic pathology, the penetrating atherosclerotic ulcer (PAU) and the intramural hematoma (IMH), which are radiologically distinct from classic aortic dissection. Table 4 reviews the characteristics distinguishing PAU from classic aortic dissection and IMH. We took as a matter of definition that classic aortic dissection involves a flap which traverses the aortic lumen. We defined PAU and IMH as nonflap lesions, with PAU demonstrating a crater extending from the aortic lumen into the space surrounding the aortic lumen. This categorization can be summarized with the expression, "no flap, no dissection." With these definitions made, re-review of the imaging studies for the present report identified 36 such lesions out of 214 cases originally read as aortic dissection. Therefore, these variant lesions accounted for over 1 out of 8 acute aortic pathologies. Besides confirming the existence of the conditions, PAU and IMH, as distinct radiographic lesions, this series strongly suggests that these two conditions constitute distinct clinical entities as well. Table 4 summarizes the clinical patterns of these two entities as apparent from the present study, and contrasts them with classic aortic dissections. In particular, the following observations, some of which are consonant findings in smaller series, can be made regarding the typical patient profiles of PAU and IMH from the present study: The patients with PAU and IMH are distinctly older than those with type A aortic dissection (74.0 and 73.9 versus 56.5 years, P = 0.0001). Although not statistically significant, PAU and IMH patients tend to be older than patients with type B aortic dissections as well. For PAU and IMH, unlike aortic dissection, the concentration in the elderly is manifested in a very small standard deviation of the mean age (see Fig. 13); these two entities, PAU and IMH, are essentially diseases of the seventh, eighth, and ninth decades of life. Patients with PAU and IMH are almost invariably hypertensive (about 94% of cases). The pain of PAU and IMH mimics that of classic aortic dissection, with anterior symptoms in the ascending aortic lesions and intrascapular or back pain with descending aortic lesions. Unlike classic dissection, PAU and IMH do not produce branch vessel compromise or occlusion and do not result in ischemic manifestations in the extremities or visceral organs. PAU and IMH are more focal lesions than classic aortic dissection, which frequently propagates for much or the entire extent of the thoracoabdominal aorta. PAU is uniformly associated with severe aortic arteriosclerosis and calcification, whereas classic dissection often occurs in aortas with minimal arteriosclerosis and calcification. PAU and IMH tend to occur in even larger aortas than classic aortic dissection (6.2 and 5.5 versus 5.2 cm, P = 0.01). PAU and IMH are strongly associated with AAA, which is seen concomitantly in 42.1% of PAU patients and 29.4% of IMH patients. PAU and IMH are largely diseases of the descending aorta (90% for PAU and 71% for IMH). Although our pathology data is limited, we do feel that an inherent difference in the histologic intramural level of the hematoma may underlie the pathophysiologic process that determines which patient develops a typical dissection and which develops an intramural hematoma. In particular, we feel that the level of blood collection is more superficial, closer to the adventitia, in IMH than in typical aortic dissection. This may explain why the inner layer does not prolapse into the aorta on imaging studies or when the aorta is opened in the operating room. This more superficial location would also explain the high rupture rates as compared to classic aortic dissection (Fig. 14, Table 3). We did find PAU and IMH to behave much more malignantly than typical descending aortic dissection. As seen in Figure 6, the rupture rate is much higher than for aortic dissection. Docume

Interpreting data on thoracic aortic aneurysms. Statistical issues.

Reliable information on growth rates and risk factors for growth of thoracic aortic aneurysms (TAA) is important for managing patients with this potentially lethal condition. This article reviews existing procedures for ascertaining TAA growth rates and describes improved statistical methodologies. Using data from the Yale Center for Thoracic Aortic Disease, the article demonstrates that the statistical procedure of instrumental variables (IV) estimation leads to substantially more precise and robust estimates of TAA growth rates and associated risk factors. We recommend that IV estimation be routinely employed in estimating the progression of thoracic aortic aneurysms and in identifying risk factors for growth. The article also discusses the issue of sample selection effects that arise when patients receive graft surgery and therefore are removed from the data set, and describes statistical procedures fro addressing this issue.

Developing surgical intervention criteria for thoracic aortic aneurysms.

In summary, the development of intervention criteria is a complex and challenging endeavor. Specific examination of this issue is crucial to the appropriate clinical care of patients. With these objectives in mind, we have drawn upon our clinical experience to design, by way of statistical analysis, reasoned size criteria for intervention. These intervention criteria must be carefully weighed against the patient's age, overall physical condition, and anticipated life expectancy. We have approached the development of criteria for intervention using statistical methodology from the standpoint of preventing complications (i.e., dissection and rupture). Symptomatic states, organ compression, concomitant aortic insufficiency, and acute ascending aortic dissection are well-accepted general indications for surgical intervention regardless of aortic size. The appendix incorporates the size criteria developed in the present study as an integral component within a comprehensive strategy for managing patients with TAA. This study confirms that aneurysms of the thoracic aorta are potentially lethal, that attentive follow-up is critical, and that adverse events can be anticipated based on size criteria. As we continue to expand our database, we hope to refine further statistically-based recommendations for surgical intervention. Multi-institutional patient enrollment, with the concomitant statistical power of larger patient numbers, would considerably strengthen this type of analysis.

Surgical intervention criteria for thoracic aortic aneurysms: a study of growth rates and complications.

BACKGROUND: Evidence regarding the behavior of thoracic aortic aneurysm (TAA) is limited. This study reviews our ongoing efforts to understand the factors influencing aortic growth rates and the complications of rupture and dissection in order to define scientifically sound criteria for surgical intervention. METHODS: Data from 370 patients with TAA treated at Yale University School of Medicine from January 1985 to June 1997 were analyzed. This computerized data base included 1063 imaging studies (magnetic resonance imaging, computed tomography, and echocardiography). RESULTS: The mean size of the thoracic aorta in these patients at initial presentation was 5.2 cm (range 3.5-10). The mean growth rate was 0.10 cm/year. Median size at the time of rupture or dissection was 5.9 cm for ascending and 7.2 cm for descending aneurysms. The incidence of dissection or rupture increased with aneurysm size. Multivariable regression analysis to isolate risk factors for acute dissection or rupture revealed that size > or = 6.0 cm increased the probability of these devastating complications by 25.2% for ascending aneurysms (p = 0.006 compared with aneurysms 4.0-4.9 cm). For descending aneurysms > or = 7.0 cm, risk of dissection or rupture was increased by 37.3% (p = 0.031). CONCLUSIONS: If the median size at time of dissection or rupture had been used as the indication for intervention, half the patients would have suffered a devastating complication before surgery. Accordingly, a criterion lower than the median is appropriate. We recommend 5.5 cm as an acceptable size for elective resection of ascending aortic aneurysms because this operation can be performed with relatively low mortality. For aneurysms of the descending aorta, where perioperative complications are greater and the median size at the time of complication is larger, we recommend intervention at 6.5 cm.

Management of descending aortic dissection.

BACKGROUND: Experience with 100 consecutive patients with acute dissection of the descending aorta seen at the Yale Center for Thoracic Aortic Disease over a 10-year period is reported. METHODS: Clinical records from the Yale Center for Thoracic Aortic Disease from 1988 to 1998 were analyzed. This computerized data base included information regarding patients' demographics, history, presenting symptomatology, diagnostic imaging, early hospital course, treatment strategy, and long term follow up (office visits, echocardiography, computerized tomography, magnetic resonance imaging, and home phone calls). RESULTS: The average size of the aorta at the time of dissection was 5.05 cm. Nine patients died (six of complications directly related to the thoracic aorta). Sixty of the 91 surviving patients had a benign course, and 31 had a course complicated by rupture (8), vascular occlusion (17), early expansion or extension (12), and continued pain (4); multiple complications were seen in some patients. Forty-two patients came to operation (22 early and 20 late): 32 direct aortic replacements, 6 fenestration procedures, and 4 thromboexclusions. There were six postoperative deaths and six paraplegias. Clinical experience with the alternative procedures of fenestration and thromboexclusion found both procedures safe and effective for selected categories of patients. Review of the literature indicated that direct aortic replacement in the setting of acute descending aortic dissection continues to carry a very high mortality (28%-65%) and paraplegia rate (30%-35%), leaving room for consideration of alternative procedures. CONCLUSIONS: We recommend a "complication-specific" approach to acute descending aortic dissection: medical management with "antiimpulse therapy" for uncomplicated acute descending dissections and surgical intervention for complicated dissections. Surgical therapy varies for the specific complication: for rupture, direct aortic replacement is recommended; for vascular occlusion, fenestration; and for acute expansion or impending rupture, direct aortic replacement, with thromboexclusion as an option. Chronic descending aortic dissection is treated according to general guidelines for descending aortic aneurysms, with operation for symptoms or enlargement > 6.5 cm.

Dominant negative suppression of major histocompatibility complex genes occurs in trophoblasts.

BACKGROUND: Polymorphic class I and II major histo-: compatibility complex (MHC) genes are not transcribed in trophoblasts although many immune system cells express these genes constitutively. To study the molecular biology of MHC suppression for the purposes of potential transgenic animal development, we examined the effect on MHC expression in B cells by fusing them with trophoblasts. METHODS: Trophoblasts and B cells with separate selection markers were fused with polyethylene glycol. After growth in double selection media, the hybrids were analyzed for HLA-A, -B, -C, -DR, -DP, and -DQ expression by fluorescence-activated cell scanning and class I and II mRNA by Northern blotting. Class II promoter activity in trophoblasts was then analyzed by transfection of a lethal reporter construct and subsequently, the class II transactivator. RESULTS: Class I and II surface antigens and their corresponding mRNA were completely suppressed in the hybrids. The lethal reporter construct demonstrated that class II suppression resulted from lack of activation of the class II promoter. This in turn was caused by lack of functional class II transactivator. CONCLUSIONS: These data indicate that dominant negative trophoblast factors, either directly or indirectly, suppress expression of the MHC genes. If these factors can be cloned, the potential exists for developing transgenic animals that cannot express MHC or peptide antigen to T cell receptors through the MHC system.

Familial patterns of thoracic aortic aneurysms.

HYPOTHESIS: To provide evidence that genetic factors contribute to the development of thoracic aortic aneurysms (TAA) by demonstrating familial patterns of the disease. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS AND METHODS: We sought to identify familial patterns of TAA from a database of 598 patients evaluated or treated for TAA at the Yale Center for Thoracic Aortic Disease, New Haven, Conn, from January 1985 to August 1998. Of the 598 patients, 45 patients had a diagnosis of Marfan syndrome and 553 patients had no known history of any collagen vascular disorder. Of the 553 patients in the latter category, 398 patients had confirmed TAA, 66 had TAA with concomitant aortic dissections, and 89 had aortic dissections. From the group of 464 patients with TAA with or without concomitant aortic dissections, 2 interviewers attempted to contact 150 randomly selected patients for telephone screening to determine the presence of familial patterns of aortic disease. Fifteen of these patients were lost to follow-up. Complete medical and family histories of the remaining 135 patients (85 men, 50 women) were reviewed. Of the 135 individuals screened, 26 (18 men, 8 women) (19.3%) were found to belong to multiplex pedigrees. These 26 patients with familial nonsyndromic TAA were compared with the remaining 109 patients with sporadic TAA and the 45 patients with Marfan syndrome-associated TAA. MAIN OUTCOME MEASURES: Groups were examined for statistical differences in age and aortic size at the time of diagnosis, growth rates of TAA, and rates of concomitant diseases. Nonsyndromic family pedigrees were analyzed and potential modes of inheritance were determined. RESULTS: The mean age at presentation for patients with familial nonsyndromic TAA (56.8 years) was significantly younger than the mean age of presentation in sporadic cases (64.3 years, P< or =.03), and significantly older than that of patients with Marfan syndrome (24.8 years, P< or =.001). Patients with a family history of aortic aneurysms had faster growth rates (0.22 cm/y) compared with patients with sporadic TAA (0.03 cm/y) (P< or =.001) and patients with Marfan syndrome (0.10 cm/y) (P< or =.04). Familial nonsyndromic TAA in patients with a concomitant aortic dissection had a growth rate of 0.33 cm/y, which was greater than that of patients with sporadic TAA (0.10 cm/y) and patients with Marfan syndrome (0.08 cm/y) with associated aortic dissection. This growth of 0.33 cm/y was significantly faster than the overall growth rate estimate of aneurysms in patients with aortic dissection (0.14 cm/y) (P< or =.05). Ten pedigrees (38.5%) showed direct father to son transmission, consistent with an autosomal dominant mode of inheritance. Six family pedigrees (23.1%) suggested an autosomal dominant or X-linked mode of inheritance. Seven pedigrees (26.9%) suggested a recessive mode of inheritance; 2 an autosomal recessive mode, and 5 an X-linked recessive or autosomal recessive mode. The remaining 3 pedigrees displayed more complex modes of inheritance. CONCLUSIONS: This study supports the role of genetic factors influencing familial aggregation of TAA. Thoracic aortic aneurysms in association with multiplex pedigrees represent a new risk factor for aneurysm growth. Pedigree analysis suggests genetic heterogeneity. The primary mode of inheritance seems to be autosomal dominant, but X-linked dominant and recessive modes are also evident.

Interval or permanent nonoperative management of acute type A aortic dissection.

HYPOTHESIS: Selected patients with acute type A (ascending) aortic dissection who are treated with delayed operation or nonoperative therapy may have better early and short-term outcomes than was previously expected. DESIGN AND SETTING: Retrospective cohort at a university hospital. SUBJECTS: Data on 75 patients with acute or chronic type A aortic dissection treated at one institution from January 1, 1985, to November 30, 1997, were analyzed. Of these 75 patients, 34 (21 male and 13 female, with a mean age of 65.5 years) did not undergo initial operative treatment, and 15 (10 male and 5 female, with a mean age of 72.6 years) never underwent surgery. For the 19 patients who underwent delayed surgery, the mean period between aortic dissection and intervention was 11.4+/-4.83 days. The follow-up period ranged from 0.27 to 149 months, with a mean of 20.2 months. MAIN OUTCOME MEASURES: Vascular complications, hospital mortality, and early survival. RESULTS: Reasons for interval delay in surgical treatment included initial misdiagnosis or delay in diagnosis (13 [68%] of 19), need to address significant comorbidity (4 [21%] of 19), and initial refusal of operative intervention (2 [11%] of 19). For the 15 patients treated entirely by medical therapy, reasons for electing nonoperative management included extensive comorbidity (5 [33%] of 15), refusal of surgical intervention (6 [40%] of 15), and misdiagnosis or long delay in diagnosis (4 [27%] of 15). Of the 34 patients, 15 (44%) presented with moderate or severe aortic insufficiency, 5 (14%) had evidence of pericardial effusion, 6 (21%) had evidence of concomitant coronary ischemia on electrocardiogram, and 8 (24%) had extension of the dissection into the descending aorta. Four patients (11.8%) died while in the hospital. Of the 34 patients, 30 (88%) who underwent either delayed or no surgery received aggressive medical treatment (beta-adrenergic blocking agents and afterload-reducing agents) and were discharged from the hospital. All patients who were operative candidates in the interval treatment group survived to reach definitive operation. There was no statistically significant difference in short-term survival between the group of patients undergoing delayed surgery or medical treatment only and the group of 41 patients undergoing early operation (P = .42). CONCLUSIONS: Immediate surgical therapy is still recommended for acceptable operative candidates with acute type A aortic dissection who seek immediate treatment. However, this study permits the following 2 conclusions: (1) patients with type A aortic dissection who are referred or whose conditions are diagnosed several days after presentation have survived the early dangerous period and can safely undergo surgery semielectively (rather than emergently); and (2) selected patients who are not considered operative candidates and who survive the initial type A aortic dissection without complication may be treated with aggressive medical therapy and achieve acceptable early and short-term outcomes, which is better than previously expected.

Procedures for estimating growth rates in thoracic aortic aneurysms.

Thoracic aortic aneurysms (TAAs) are potentially lethal medical conditions often requiring surgical intervention. Reliable information on TAA growth rates and associated risk factors is important for managing this challenging patient population. Unfortunately, a number of studies have employed questionable statistical methods, leading to biased and imprecise estimates. The present study describes these statistical problems in existing studies and delineates procedures for obtaining more reliable results. Using data from the Yale Center for Thoracic Aortic Disease, the study compares TAA growth rate estimates using conventional methods versus the recommended approach of instrumental variables (IV) estimation. The IV approach is designed to mitigate problems of measurement errors inherent in existing estimates of TAA growth. The results demonstrate that IV estimation yields more robust and precise estimates of TAA growth rates and risk factors for TAA growth. For example, the conventional approach yields TAA growth rates that fluctuate substantially-from 0.12 cm/yr to 0.90 cm/yr-depending on (1) the minimum serial follow-up period for patient inclusion in the study and (2) how subjects with negative measured growth rates are handled. In contrast, growth rate estimates using the IV approach are much more robust, ranging from 0.12 to 0.13 cm/yr. The 95% confidence intervals of estimated TAA growth are much more compact using the IV approach as well. We conclude that the IV estimation procedure yields more reliable estimates of TAA growth than does the conventional approach.

Penetrating ulcer of the thoracic aorta: what is it? How do we recognize it? How do we manage it?

BACKGROUND: Although classic type A and B aortic dissections have been well described, less is known about the natural history of penetrating atherosclerotic ulcers of the thoracic aorta. This study differentiates penetrating ulcer from aortic dissection, determines the clinical features and natural history of these ulcers, and establishes appropriate correlates regarding optimal treatment. METHODS: A retrospective review of patient records and imaging studies was conducted with 198 patients with initial diagnoses of aortic dissection (86 type A, 112 type B) at our institution from 1985 to 1997. RESULTS: Of the 198 patients, 15 (7.6%) were found to have a penetrating aortic ulcer on re-review of computed tomographic scans, magnetic resonance images, angiograms, echocardiograms, intraoperative findings, or pathology reports. Two ulcers (13.3%) were located in the ascending aorta; the other 13 (86.7%) were in the descending aorta. In comparison with those with type A or B aortic dissection, patients with penetrating ulcer were older (mean age 76.6 years, p = 0.018); had larger aortic diameters (mean diameter 6.5 cm); had ulcers primarily in the descending aorta (13 of 15 patients, 86.7%); and more often had ulcers associated with a prior diagnosed or managed AAA (6 of 15 patients, 40.0%; p = 0.0001). Risk for aortic rupture was higher among patients with penetrating ulcers (40.0%) than patients with type A (7.0%) or type B (3.6%) aortic dissection (p = 0.0001). CONCLUSIONS: Accurate recognition and differentiation of penetrating ulcers from classic aortic dissection at initial presentation is critical for optimal treatment of these patients. For penetrating ulcer, the prognosis may be more serious than with classic type A or B aortic dissection. Surgical management is advocated for penetrating ulcers in the ascending aorta and for penetrating ulcers in the descending aorta that exhibit early clinical or radiologic signs of deterioration.

What is the appropriate size criterion for resection of thoracic aortic aneurysms?

Although many articles have described techniques for resection of thoracic aortic aneurysms, limited information on the natural history of this disorder is available to aid in defining criteria for surgical intervention. Data on 230 patients with thoracic aortic aneurysms treated at Yale University School of Medicine from 1985 to 1996 were analyzed. This computerized database included 714 imaging studies (magnetic resonance imaging, computed tomography, echocardiography). Mean size of the thoracic aorta in these patients at initial presentation was 5.2 cm (range 3.5 to 10 cm). The mean growth rate was 0.12 cm/yr. Overall survivals at 1 and 5 years were 85% and 64%, respectively. Patients having aortic dissection had lower survival (83% 1 year; 46% 5 year) than the cohort without dissection (89% 1 year; 71% 5 year). One hundred thirty-six patients underwent surgery for their thoracic aortic aneurysms. For elective operations, the mortality was 9.0%; for emergency operations, 21.7%. Median size at time of rupture or dissection was 6.0 cm for ascending aneurysms and 7.2 cm for descending aneurysms. The incidence of dissection or rupture increased with aneurysm size. Multivariable regression analysis to isolate risk factors for acute dissection or rupture revealed that size larger than 6.0 cm increased the probability by 32.1 percentage points for ascending aneurysms (p = 0.005). For descending aneurysms, this probability increased by 43.0 percentage points at a size greater than 7.0 cm (p = 0.006). If the median size at the time of dissection or rupture were used as the intervention criterion, half of the patients would suffer a devastating complication before the operation. Accordingly, a criterion lower than the median is appropriate. We recommend 5.5 cm as an acceptable size for elective resection of ascending aortic aneurysms, because resection can be performed with relatively low mortality. For aneurysms of the descending aorta, in which perioperative complications are greater and the median size at the time of complications is larger, we recommend intervention at 6.5 cm.