Results of immediate surgical treatment of all acute type A dissections.

BACKGROUND: Surgery for acute type A aortic dissection is associated with a high mortality rate and incidence of postoperative complications. This study was designed to explore perioperative risk factors for death in patients with acute type A aortic dissection. METHODS AND RESULTS: One hundred twenty-four consecutive patients with acute type A aortic dissection between 1984 and 1998 were reviewed. All underwent operation with resection of the intimal tear and open distal anastomosis: 107 patients had surgery within 24 hours and 17 patients had surgery within 72 hours of symptom onset. Median age was 62 years (23 to 89); 89 were men. Forty-three patients had ascending aortic replacement only, 72 had hemiarch repair, in 2 the entire arch was replaced, and in 7 replacement included the proximal descending aorta. The aortic valve was replaced in 54 patients, resuspended in 52, and untouched in 18. Hospital mortality rate was 15.3% (19 of 124): of these, 3 patients died during surgery, 4 had fatal rupture of the distal aorta before discharge, and 2 died of malperfusion-related complications. Multivariate analysis revealed age >60, hemodynamic compromise, and absence of hypertension as preoperative indicators of hospital death (P:<0.05); the presence of new neurological symptoms was a significant preoperative risk factor in univariate analysis. Ominous intraoperative factors included contained hematoma and a comparatively low esophageal temperature but not cerebral ischemic time (mean 32 minutes). The site of the intimal tear did not influence outcome, but mortality rate was higher with more extensive resection: 43% with resection including the descending aorta died versus 14% with only ascending aorta or hemiarch replacement. Overall 5- and 10-year survival was 71% and 54%, respectively; among discharged patients (median follow-up 41 months) survival was 84% and 64% versus expected US survival of 92% and 79%. CONCLUSIONS: Immediate surgical treatment of all acute type A dissections with resection of the intimal tear and use of hypothermic circulatory arrest for distal anastomosis results in acceptable early mortality rates and excellent long-term survival.

Selegiline use to prevent progression of Parkinson's disease. Experience in 22 de novo patients.

To test the hypothesis that selegiline (L-deprenyl), a selective inhibitor of B-type monoamine oxidase, can halt the natural progression of Parkinson's disease, its use in 22 naive patients (mean age, 58 years; mean Parkinson's disease duration, 2.3 years) in the early stages (1 to 2) of the disease was studied. Patients were started and maintained on a daily dose of 10 mg of selegiline, and they underwent neurologic examinations at 3-month intervals using our center's disease staging and total rated disability scores. The criterion set for disease progression was defined as either the appearance of a new objective sign and/or a definite, persistent worsening (greater than 25%) of existing signs after the initiation of the selegiline trial. Patients remained on a regimen of selegiline [corrected] for periods ranging from 7 to 84 months. At the time of their latest neurologic examination, 17 (77%) of the 22 patients had conditions that demonstrably worsened with selegiline alone at an average of 10.8 months from the start of the drug therapy. Six of these 17 patients with worsening conditions (or 27% of the original 22) eventually required the addition of levodopa with carbidopa (Sinemet) on average at 13 months from the start of selegiline therapy; they have continued, to date, taking this combination for an additional mean follow-up period of 20.7 months. Four of the original 22 patients had relatively unchanged, stable neurologic status at the time of their latest examination (average follow-up period, 11.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Selegiline as an adjunct to conventional levodopa therapy in Parkinson's disease. Experience with this type B monoamine oxidase inhibitor in 200 patients.

Two hundred patients at a median age of 63 years, receiving conventional levodopa therapy for 8 years, who had had Parkinson's disease for 10 years, tried a regimen of selegiline (L-deprenyl), a type B monoamine oxidase inhibitor, at a daily dose of 10 mg, for varying periods from less than 6 months to more than 24 months (28% over 24 months). Selegiline does improve parkinsonism during the initial 6 months to 12 to 24 months of combined therapy in one third to almost half of patients with an end-of-dose type of response to long-term levodopa therapy. However, even this particular class of patients is unable to maintain such an improvement by 36 months, much less by 48 months, from the start of the selegiline trial. About one quarter of poor responders to levodopa and those with random deterioration show improvement in their parkinsonian status in the first 6 months of the selegiline trial, but their conditions quickly deteriorate by 1 year. The predominant pattern of response to previous levodopa therapy and the severity of the total disability score at the initiation of the selegiline trial were the two variables that were predictive of risk of failure with the drug. No evidence suggested that selegiline decreases the excess mortality rate of Parkinson's disease above that achieved with the use of levodopa alone. Selegiline as an adjunctive agent to conventional levodopa therapy was not unduly impressive with regard to preventing progression of Parkinson's disease.

Use of keratin 35betaE12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type--benign and malignant intraductal proliferations.

A variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK) expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34betaE12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300. The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction (high to very high scores) for CK-34betaE12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34betaE12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH (high to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34betaE12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH (high to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34betaE12) is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We recommend the use of CK-34betaE12 as an adjunct in the diagnosis of a variety of problematic intraductal proliferations of the breast.

Mucoepidermoid carcinoma: a clinicopathologic study of 80 patients with special reference to histological grading.

We sought to review our experience with salivary mucoepidermoid carcinoma (MEC) over two decades to confirm the validity and reproducibility of histologic grading and to investigate MIB-1 index as a prognosticator. Diagnosis was confirmed on 80 cases, and chart review or patient contact was achieved for 48 patients, with follow-up from 5 to 240 months (median 36 months). Immunohistochemistry with citrate antigen retrieval for MIB-1 was performed on a subset of cases. Kaplan-Meier survival curves were generated for each stage, site, and grade according to our proposed grading system. To address the issue of grading reproducibility, 20 slides were circulated among five observers, without prior discussion; slides were categorized as low-, intermediate-, or high-grade according to one's "own" criteria, and then according to the AFIP criteria proposed by Goode et al.10 Weighted kappa (kappa) estimates were obtained to describe the extent of agreement between pairs of rating. The Wilcoxon signed rank test or the Friedman test as appropriate tested variation across ratings. There was no gender predominance and a wide age range (15-86 years, median 49 years). The two most common sites were parotid and palate. All grade 1 MECs presented as Stage I tumors, and no failures were seen for this category. The local disease failure rates at 75 months for grades 2 and 3 MEC were 30% and 70%, respectively. Tumor grade, stage, and negative margin status all correlated with disease-free survival (DFS) (p = 0.0091, 0.0002, and 0.048, respectively). The MIB index was not found to be predictive of grade. Regarding the reproducibility of grading, the interobserver variation for pathologists using their "own" grading, as expressed by the kappa value, ranged from good agreement (kappa = 0.79) to poor (kappa = 0.27) (average kappa = 0.49). A somewhat better interobserver reproducibility was achieved when the pathologists utilized the standardized AFIP criteria (average kappa = 0.61, range 0.38-0.77). This greater agreement was also reflected in the Friedman test (statistical testing of intraobserver equality), which indicated significant differences in using one's own grading systems (p = 0.0001) but not in applying the AFIP "standardized" grading (p = 0.33). When one's own grading was compared with the AFIP grading, there were 100 pairs of grading "events," with 46 disagreements/100 pairs. For 98% of disagreements, the AFIP grading "downgraded" tumors. This led us to reanalyze a subset of 31 patients for DFS versus grade, for our grading schema compared with the AFIP grading. Although statistical significance was not achieved for this subset, the log rank value revealed a trend for our grading (p = 0.0993) compared with the Goode schema (p = 0.2493). This clinicopathologic analysis confirms the predictive value of tumor staging and three-tiered histologic grading. Our grading exercise confirms that there is significant grading disparity for MEC, even among experienced ENT/oral pathologists. The improved reproducibility obtained when the weighted AFIP criteria were used speaks to the need for an accepted and easily reproducible system. However, these proposed criteria have a tendency to downgrade MEC. Therefore, the addition of other criteria (such as vascular invasion, pattern of tumor infiltration [i.e., small islands and individual cells vs cohesive islands]) is necessary. We propose a modified grading schema, which enhances predictability and provides much needed reproducibility.

The influence of acute rejection on long-term renal allograft survival: a comparison of living and cadaveric donor transplantation.

BACKGROUND: We investigated whether recipients of living donor grafts who suffer an acute rejection progress to graft loss because of chronic rejection at a slower rate than recipients of cadaveric grafts. METHODS: A retrospective review was made of 296 renal transplantations performed at Mount Sinai Hospital. Only grafts functioning for at least 3 months were included in this analysis. Demographic variables of donor and recipient age, race, sex, and serum creatinine at 3 months after transplantation were compared between groups. RESULTS: Among the acute rejection-free cohort, the estimated 5-year graft survival was 90% for those receiving transplants from living relatives and 88% for those receiving cadaveric transplants (P=0.76). However, in grafts with early acute rejection, the 5-year survival was 40% for cadaveric recipients compared with 73% for living related graft recipients (P<0.014). Using the proportional hazards model, cadaveric donor source, older donor age, African American recipient race, and elevated 3-month serum creatinine were independent predictors of long-term graft loss caused by chronic rejection. The severity of acute rejection and recipient age had no impact on the risk of graft loss because of chronic rejection. CONCLUSION: These data indicate that the benefit of living related transplantation results from the fact that a living related graft progresses from acute to chronic rejection at a slower rate than a cadaveric graft. Furthermore, a cadaveric graft that is free of acute rejection 3 months after transplantation has an equal likelihood of functioning at 5 years as that of a graft from a living related donor.

National sharing of cadaveric isolated intestinal allografts for human transplantation: a feasibility study.

UNLABELLED: Most isolated intestinal graft losses are immunological. We conducted a pilot study to evaluate the feasibility of national sharing of HLA no-mismatch allografts for cadaveric isolated intestinal transplantation. METHODS: UNOS data were analyzed in a theoretical model. Part I: All solid organ donors between 1/95-8/97 who would have met criteria for bowel donation were considered potential donors for all recipients who actually received isolated intestinal transplants during this period. We then determined how many donor intestines could have been directed to no-mismatch candidates had national sharing been in place. Donor exclusion criteria were CMV+ donors to CMV- recipients, hemodynamic instability, age >50, size mismatch (donor weight greater than recipient), and obesity. Mean and median waits for transplants, as well as theoretical mean and median waits for transplants that would have occurred given national sharing, were calculated. Part II: We estimated, based on registry graft survival data, the number of intestinal transplants necessary to demonstrate a no-mismatch graft survival advantage at 2 years. RESULTS: Part I: Although no actual cadaveric no-mismatch transplant was performed, 12-17% of patients could have received no-mismatch allografts had sharing been in place, using various donor acceptance criteria. The impact on waiting time was variable. Part II: Accepting a 15% rate of no-mismatch cases and a survival advantage of 10% at 2 years, 793 transplants would be required to prove an advantage to HLA matching at P<0.05. If the graft survival advantage were 20% at 2 years, the time to show significance would be approximately 5 years. Using early acute rejection as an endpoint could require fewer transplants (93), and only a few years to complete the study. CONCLUSIONS: National sharing of cadaveric isolated intestinal allografts is feasible. Median waits would not be significantly increased. The time necessary to prove graft survival advantage would be considerable, but a difference in the rate of acute rejection could be seen within 2 years. Additionally, a national sharing arrangement might improve the overall outcome of isolated intestinal transplantation.

Accuracy and significance of computed tomographic scan assessment of hepatic volume in patients undergoing liver transplantation.

BACKGROUND: A small liver volume is considered to be a poor prognostic factor in cirrhosis, often indicative of advanced liver disease. Radiologic assessment of liver volume before liver transplant is routinely performed in many transplant centers. We sought to assess the accuracy and significance of computed tomographic (CT) scanning in hepatic volumetric analysis by correlating CT-derived estimation of liver volume with that of corresponding liver explants. METHODS: A chart review of all patients aged 17 years or older undergoing liver transplant at Mount Sinai Medical Center between 1989 and 1995 was performed. Each patient underwent conventional CT scanning with measurement of liver volume (CTLV). Recipient liver volume (RLV) was defined as weight of liver explant after all attached ligaments, portal structures, and gallbladder were dissected free. Expected liver volume was calculated pretransplant based on age, gender, height, and weight. Patients were categorized into three groups based on etiology of liver disease: (1) hepatocellular (e.g., viral hepatitis, alcohol-related), (2) cholestatic (e.g., primary biliary cirrhosis), and (3) cryptogenic. The ratio of CTLV to RLV was used as a measure of the accuracy of CT volumetric analysis. RESULTS: A total of 579 patients was studied (group 1=376, group 2=139, group 3=64). All three groups were statistically similar with regard to age, prothrombin time and total bilirubin. Median CT liver volume was 1308 ml (range: 338-3847), 1651 ml (range: 641-3861), and 1210 ml (range: 348-2575) in groups 1-3, respectively; median ratio of CTLV to RLV was 1.02 (range: 0.50-2.31), 1.05 (range: 0.52-2.22), and 1.05 (range: 0.50-1.56) for groups 1-3, respectively. When RLV was small, it tended to be overestimated by CTLV. In contrast, when RLV was large, it was often underestimated. Clinical features such as history of esophageal variceal bleed, encephalopathy or ascites, and laboratory data did not influence accuracy of CT volumetric analysis. CONCLUSIONS: CT-derived estimation of liver volume appears to correlate closely with actual weight of liver explant regardless of the etiology of chronic liver disease. With extremes in CT volumetric analysis, actual liver volume tends to be under- or overestimated. For patients with end-stage liver disease, both CT-derived and actual liver volume are greater in cholestatic than in hepatocellular disorders.

Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection.

BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has been shown to play a critical role in the down-regulation of the immune response. We retrospectively examined the association between acute rejection and two polymorphisms in the CTLA4 gene, the dinucleotide (AT)n repeat polymorphism in exon 3 and the single nucleotide polymorphism A/G at position 49 in exon 1, in a cohort of liver and kidney transplant recipients. METHODS AND RESULTS: A total of 207 liver and 167 renal transplant recipients were analyzed. In the case of the (AT)n repeat polymorphism we found an increased incidence of acute rejection in association with allele 3 and 4 in both liver and kidney (P=0.002 and 0.05, respectively). In addition, in liver transplant recipients, allele 7 was associated with acute rejection independent of ethnicity (P<0.05). Allele 1 was less frequently observed in African American as compared with Caucasian liver and kidney transplant recipients, with a frequency of 33.8% and 69%, respectively (P<0.0001). Those patients with allele 1 had a tendency toward a lower rate of rejection at 42% versus 57.8% (P=0.058), suggesting a potential protective effect of allele 1. Analysis of the A/G single nucleotide polymorphism demonstrated no association between either allele and the incidence of acute rejection in the patients studied. CONCLUSION: These initial observations provide the necessary basis to further investigate the risk stratification of transplant recipients based on specific CTLA4 gene polymorphisms.

Long-term medical complications in patients surviving > or = 5 years after liver transplant.

BACKGROUND: Short-term outcomes of liver transplantation are well reported. Little is known, however, about long-term results in liver recipients surviving > or =5 years. We sought to analyze long-term complications in liver recipients surviving > or =5 years after transplant, to assess their medical condition and to compare findings to the general population. METHODS: We analyzed the chart and database records of all patients (n=139) who underwent liver transplantation at a major transplant center before January 1, 1991. Outcome measures included the presence of diabetes, hypertension, heart, renal or neurological disease, osteoporosis, incidence of de novo malignancy or fracture, or other pathology, body mass index, serum cholesterol and glucose, liver function, blood pressure, frequency of laboratory and clinic follow-up, current pharmacological regimen, and late rejection episodes. RESULTS: Ninety-six patients (70%) survived > or =5 years. Compared to numbers expected based on U.S. population rates, transplant recipients had significantly higher overall prevalences of hypertension (standardized prevalence ratio [SPR]=3.07, 95% confidence interval [CI], 2.35-3.93) and diabetes (SPR=5.99, 95% CI, 4.15-8.38), and higher incidences of de novo malignancy (standardized incidence ratio [SIR]=3.94, 95% CI, 2.09-6.73), non-Hodgkin's lymphoma (SIR=28.56, 95% CI, 7.68-73.11), non-melanoma skin cancer (estimated SIR> or =3.16) and fractures in women (SIR=2.05, 95% CI, 1.12-3.43). Forty-one of 87 (47.1%) patients were obese, and 23 patients (27.4%) had elevated serum cholesterol levels (> or =240 mg/dl, 6.22 mmol/L), compared to 33% and 19.5% of U.S. adults, respectively. Prevalences of heart or peptic ulcer disease were not significantly higher. CONCLUSIONS: Liver transplantation is being performed with excellent 5-year survival. Significant comorbidities exist, however, which appear to be related to long-term immunosuppression.

Prevalence and natural history of cryptorchidism.

OBJECTIVE: A prospective hospital-based cohort study was conducted to determine the prevalence rates of cryptorchidism at birth, 3 months, and 1 year of age. DESIGN: A total of 6935 consecutive male neonates delivered at Mount Sinai Hospital in New York City between October 1987 and October 1990 were examined at birth for cryptorchidism. Standardized examination and classification criteria were used. Infants classified as cryptorchid at birth were reexamined at 3 months and 1 year after the expected date of delivery. RESULTS: Of 6935 neonates assessed at birth, 255 (3.7%) were found to be cryptorchid at birth. The rates were significantly elevated for low birth weight, preterm, small-for-gestational age, and twin neonates. The overall rate had declined to 1.0% by the 3-month assessment and 1.1% at the 1-year assessment. Although the rates at the 1-year assessment tended to be higher for low birth weight and preterm infants, no significant group differences were observed. CONCLUSIONS: Since the prevalence rates in this study are similar to those reported several decades ago, these data provide no evidence that the rate of cryptorchidism has increased either at birth or by 1 year of age. Furthermore, most testes that descend spontaneously do so within the first 3 months after the expected date of delivery.

Recurrence of Crohn's disease in end ileostomies.

: It appears well established that the recurrence rates following operations for Crohn's disease of ileum and colon are higher after anastomotic operations than after an end ileostomy. To obtain further information regarding the rate of recurrence following end ileostomy we reviewed the charts of 182 patients: 117 with involvement of the ileum as well as the colon, and 65 with Crohn's colitis only, who were operated upon at the Mt. Sinai Hospital during 1952-1984. They were followed until death or the first ileostomy revision or the last contact. Of the ileocolitis group, 50 patients (43%), and of the colitis group, nine patients (14%) required an ileostomy revision. Of the 50 with ileocolitis, 34 (29%) and four of the colitis group (6.2%) had revisions done primarily for recurrent Crohn's disease at or near the stoma. The estimated overall cumulative probability of recurrence was 50% twenty years following ileostomy, and was significantly higher in the ileocolitis group than in the colitis group (64% vs. 15%; p < 0.001), with mean follow-up durations of 6.5 and 7.5 years, respectively. The probability of ileostomy revision for any reason was also significantly higher for patients with ileocolitis (74% vs. 34%; p < 0.001). We conclude that the site of initial Crohn's disease plays a role in the recurrence of disease in an end ileostomy, with a better outlook for patients with colonic involvement alone.

Sialyl-tn antigen expression in Crohn's colitis.

SUMMARY: : Expression of the mucin-associated sialyl-Tn (STn) antigen is correlated with malignant progression in the colon. In patients with longstanding ulcerative colitis (UC) who never exhibited colonic dysplasia, STn was expressed in fewer than 15% of nondysplastic surveillance colonoscopic biopsies, whereas matched patients who developed colon cancer expressed STn in >40% of previous surveillance biopsies, often several years before the first detection of dysplasia. Since no study has systematically examined STn expression in Crohn's colitis, we performed immunohistochemical staining with monoclonal antibody TKH2 on 110 surgical specimens from 59 patients with Crohn's colitis or ileocolitis. Forty percent of specimens expressed STn antigen. STn was preferentially expressed in specimens of the left colon, regardless of whether the patient had segmental left-sided disease or pancolitis. Specimens with active inflammation manifested increased STn expression, regardless of location in the colon or whether the patient had segmental disease or pancolitis. The enhanced expression of STn in Crohn's colitis compared with UC may reflect important differences in local cytokine profiles between the two inflammatory bowel diseases.

Hypothermic circulatory arrest in operations on the thoracic aorta. Determinants of operative mortality and neurologic outcome.

This study was undertaken to determine the factors that influence the final outcome after hypothermic circulatory arrest. Between 1985 and 1992 a uniform method of hypothermic circulatory arrest was used in 200 patients as the primary method of cerebral protection during operations on aneurysms of the thoracic aorta. There were 30 hospital deaths (15%). Age greater than 60 years (relative risk 3.7, p < 0.02), emergency operation and hemodynamic compromise (relative risk 22.2, p < 0.000), concomitant procedures (relative risk 2.7, p < 0.04), presentation with new neurologic symptoms (relative risk 5.2, p < 0.04), and postoperative permanent neurologic deficits (relative risk 9.4, p < 0.000) were found to be significant predictors of operative mortality. A total of 183 patients were available for evaluation of neurologic function and outcome. Multivariate analysis of this cohort of patients by multiple logistic regression showed that temporary neurologic dysfunction occurred in 36 cases (19%). Temporary neurologic dysfunction correlated with the duration of hypothermic circulatory arrest (47 +/- 16 minutes; odds ratio 1.06/minute; p < 0.001) and age (66 +/- 14 years; odds ratio 1.07/year; p < 0.001). Embolic strokes occurred in 22 patients (11%) and were associated with permanent deficits in 13 (7%). Strokes correlated significantly with age (older than 60, 21% versus younger than 60, 1%; p < 0.001) and operations on the arch and descending aortic aneurysms containing clot or atheroma (p < 0.001). This experience shows that the operative mortality is not affected by any parameters related to the use of hypothermic circulatory arrest. The incidence of temporary neurologic dysfunction rises linearly in relation to the age of the patient and the duration of hypothermic circulatory arrest. However, permanent neurologic injury is a result of thromboembolic events and is not related to the method of cerebral protection used. Additional methods to prevent perioperative embolic strokes are needed. Hypothermic circulatory arrest affords adequate cerebral protection if the arrest period is kept less than 60 minutes. We will continue to use this modality until the safety and utility of the alternate methods of cerebral protection are shown to be superior.

Looking for the artery of Adamkiewicz: a quest to minimize paraplegia after operations for aneurysms of the descending thoracic and thoracoabdominal aorta.

All patients undergoing resection of thoracic or thoracoabdominal aneurysms at Mount Sinai Hospital since November 1993 had spinal cord function monitored with somatosensory-evoked potentials as part of a multimodality approach to reducing spinal cord injury. In the segment to be resected, each pair of intersegmental vessels was sequentially clamped, and they were subsequently sacrificed only if no change in somatosensory evoked potentials occurred within 8 to 10 minutes after occlusion. Adjunctive protective measures included mild hypothermia (31 degrees to 33 degrees C), distal perfusion, corticosteroids, maintenance of high normal blood pressures, avoidance of nitroprusside, and cerebrospinal fluid drainage. Ninety-five consecutive patients operated on since 1993 (group II) were compared with 138 earlier patients (group I). Preoperative characteristics such as age, sex, etiology of aneurysm, emergency operation, and reoperation did not differ between groups, nor did operative variables such as incidence of rupture and extent of resection. Group I had slightly more smokers and slightly fewer hypertensive individuals. Group II patients had a significantly better outcome with respect to in-hospital mortality (10.5% vs 18%, p = 0.045) and paraplegia (2% vs 8%, p = 0.008). By multivariate analysis, rupture and diabetes were associated with significantly higher in-hospital mortality, and smoking greatly increased the incidence of paraplegia. The extent of the aneurysm was a major determinant of mortality and paraplegia. The low paraplegia rate in group II was achieved without reattachment of a single intercostal or lumbar artery. No patient with fewer than 10 intersegmental arteries severed had paraplegia, and spinal cord ischemia was reversible in three patients after adjunctive maneuvers were performed to improve perfusion, suggesting that spinal cord blood supply is unlikely to depend on a single "artery of Adamkiewicz."

Can retrograde perfusion mitigate cerebral injury after particulate embolization? A study in a chronic porcine model.

OBJECTIVE: We assessed the impact on histologic and behavioral outcome of an interval of retrograde cerebral perfusion after arterial embolization, comparing retrograde cerebral perfusion with and without inferior vena caval occlusion with continued antegrade perfusion. METHODS: Sixty Yorkshire pigs (27 to 30 kg) were randomly assigned to the following groups: antegrade cerebral perfusion control; antegrade cerebral perfusion after embolization; retrograde cerebral perfusion control; retrograde cerebral perfusion after embolization; retrograde cerebral perfusion with inferior vena cava occlusion, retrograde cerebral perfusion with inferior vena cava occlusion control, and retrograde cerebral perfusion with inferior vena cava occlusion after embolization. After cooling to 20 degrees C, a bolus of 200 mg of polystyrene microspheres 250 to 750 (microm diameter (or saline solution) was injected into the isolated aortic arch. After 5 minutes of antegrade cerebral perfusion, 25 minutes of antegrade cerebral perfusion, retrograde cerebral perfusion, or retrograde cerebral perfusion with inferior vena cava occlusion was instituted. After the operation, all animals underwent daily assessment of neurologic status until the time of death on day 7. RESULTS: Aortic arch return, cerebral vascular resistance, and oxygen extraction data during retrograde cerebral perfusion showed differences, suggesting that more effective flow occurs during retrograde cerebral perfusion with inferior vena cava occlusion, which also resulted in more pronounced fluid sequestration. Microsphere recovery from the brain revealed significantly fewer emboli after retrograde cerebral perfusion with inferior vena cava occlusion. Behavioral scores showed full recovery in all but one control animal (after retrograde cerebral perfusion with inferior vena cava occlusion) by day 7 but were considerably lower after embolization, with no significant differences between groups. The extent of histopathologic injury was not significantly different among embolized groups. Although no histopathologic lesions were present in either the antegrade cerebral perfusion control group or the retrograde cerebral perfusion control group, mild significant ischemic damage occurred after retrograde cerebral perfusion with inferior vena cava occlusion even in control animals. CONCLUSIONS: Although effective washout of particulate emboli from the brain can be achieved with retrograde cerebral perfusion with inferior vena cava occlusion, no advantage of retrograde cerebral perfusion with inferior vena cava occlusion after embolization is seen from behavioral scores, electroencephalographic recovery, or histopathologic examination; retrograde cerebral perfusion with inferior vena cava occlusion results in greater fluid sequestration and mild histopathologic injury even in control animals. Retrograde cerebral perfusion with inferior vena cava occlusion shows clear promise in the management of embolization, but further refinements must be sought to address its still worrisome potential for harm.

Retrograde cerebral perfusion provides negligible flow through brain capillaries in the pig.

OBJECTIVES: Although retrograde cerebral perfusion is being used clinically during aortic arch surgery, whether retrograde flow perfuses the brain effectively is still uncertain. METHODS: Fourteen pigs were cooled to 20 degrees C with cardiopulmonary bypass and perfused retrogradely via the superior vena cava for 30 minutes: 7 underwent standard retrograde cerebral perfusion and 7 underwent retrograde perfusion with occlusion of the inferior vena cava. Antegrade and retrograde cerebral blood flow were calculated by quantitating fluorescent microspheres trapped in brain tissue after the animals were put to death; microspheres returning to the aortic arch, the inferior vena cava, and the descending aorta were also analyzed during retrograde cerebral perfusion. RESULTS: Antegrade cerebral blood flow was 16 +/- 7.7 mL. min(-1). 100 g(-1) before retrograde cerebral perfusion and 22 +/- 6.3 mL. min(-1). 100 g(-1) before perfusion with caval occlusion (P =.14). During retrograde perfusion, calculations based on the number of microspheres trapped in the brain showed negligible flows (0.02 +/- 0.02 mL. min(-1). 100 g(-1) with retrograde cerebral perfusion and 0.04 +/- 0.02 mL. min(-1). 100 g(-1) with perfusion with caval occlusion; P =.09): only 0.01% and 0.02% of superior vena caval inflow, respectively. Less than 13% of retrograde superior vena caval inflow blood returned to the aortic arch with either technique. During retrograde cerebral perfusion, more than 90% of superior vena caval input was shunted to the inferior vena cava and was then recirculated, as indicated by rapid development of an equilibrium in microspheres between the superior and inferior venae cavae. With retrograde perfusion and inferior vena caval occlusion, less than 12% of inflow returned to the descending aorta and only 0.01% of microspheres. CONCLUSIONS: The paucity of microspheres trapped within the brain indicates that retrograde cerebral perfusion, either alone or combined with inferior vena caval occlusion, does not provide sufficient cerebral capillary perfusion to confer any metabolic benefit. The slightly improved outcome previously reported with retrograde cerebral perfusion during prolonged circulatory arrest in this model may be a consequence of enhanced cooling resulting from perfusion of nonbrain capillaries and from venoarterial and venovenous shunting.

Cerebral effects of cold reperfusion after hypothermic circulatory arrest.

OBJECTIVES: This study was undertaken to explore whether an interval of cold reperfusion can improve cerebral outcome after prolonged hypothermic circulatory arrest. METHODS: Sixteen pigs (27-30 kg) underwent 90 minutes of circulatory arrest at a brain temperature of 20 degrees C. Eight animals were rewarmed immediately after hypothermic circulatory arrest (controls), and 8 were reperfused for 20 minutes at 20 degrees C and then rewarmed (cold reperfusion). Electrophysiologic recordings, fluorescent microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, and direct measurements of intracranial pressure (millimeters of mercury) were obtained at baseline (37 degrees C), before hypothermic circulatory arrest, after discontinuing circulatory arrest at 37 degrees C deep brain temperature, and at 2, 4, and 6 hours thereafter. Histopathologic features and percent brain water were determined after the animals were sacrificed. RESULTS: Cerebral blood flow and oxygen consumption decreased during cooling: cerebral oxygen consumption returned to baseline levels after 4 hours, but cerebral blood flow remained depressed until 6 hours in both groups. Cold reperfusion failed to improve electrophysiologic recovery or to reduce brain weight, but median intracranial pressure increased significantly less after cold reperfusion than in controls (P =.02). Although no significant difference in the incidence of histopathologic abnormalities between groups was found, all 3 animals with an intracranial pressure of more than 15 mm Hg after immediate rewarming had histopathologic lesions, and high intracranial pressure was more prevalent among all animals with subsequent histopathologic lesions (P =.03). CONCLUSIONS: Cold reperfusion significantly inhibited the rise in intracranial pressure seen in control pigs after 90 minutes of circulatory arrest at 20 degrees C, suggesting that cold reperfusion may decrease cerebral edema and thereby improve outcome after prolonged hypothermic circulatory arrest.

The effect of retrograde cerebral perfusion after particulate embolization to the brain.

Neurologic injury as a consequence of cerebral embolism of either air or atherosclerotic debris during cardiac or aortic surgery is still a major cause of postoperative morbidity and mortality. While exploring various means of improving cerebral protection during complex cardiothoracic procedures, we have developed a chronic porcine model to study retrograde cerebral perfusion. We have previously demonstrated that retrograde perfusion results in a small amount of nutritive flow and provides cerebral protection that appears to be superior to simple prolonged hypothermic circulatory arrest. The current study was designed to evaluate the efficacy of retrograde cerebral perfusion in mitigating the effects of particulate cerebral embolism occurring during cardiac surgery. Four groups of pigs (19 to 28 kg) underwent cardiopulmonary bypass with deep hypothermia at an esophageal temperature of 20 degrees C: an antegrade control group (AC, n = 5), an antegrade embolism group (AE, n = 10), a retrograde control group (RC, n = 5), and a retrograde embolism group (RE, n = 10). In addition, because of extreme heterogeneity in outcome in the initial RE group, an additional group of 10 animals underwent embolism and retrograde perfusion at a later time. Embolization was accomplished by injection of 200 mg of polystyrene microspheres (250 to 750 micrograms in diameter) via the aortic cannula into an isolated aortic arch preparation in the AE and RE groups; the control groups received injections of 10 ml of saline solution. After infusion of the microspheres or saline solution, conventional perfusion, with the aortic arch pressure maintained at 50 mm Hg, was continued for a total of 30 minutes in the antegrade groups; in the retrograde groups, retrograde flow was initiated via a cannula positioned in the superior vena cava, and was continued for 25 minutes. Superior vena caval flow was regulated to maintain a sagittal sinus pressure of approximately 30 mm Hg in the retrograde groups, and blood returning to the isolated aortic arch was collected and measured. All animals were allowed to recover and were evaluated daily according to a quantitative behavioral score in which 9 indicates apparently complete normalcy, with lower numbers indicating various degrees of cerebral injury. At the time of planned death on day 6, half of the brain was used for recovery of embolized microspheres after digestion with 10N sodium hydroxide. The other half was submitted for histologic study. Neurologic recovery in both the antegrade and retrograde control groups appeared to be complete, although mild evidence of histologic damage was present in some animals in the retrograde control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurologic outcome after ascending aorta-aortic arch operations: effect of brain protection technique in high-risk patients.

OBJECTIVE: We sought to assess the optimal strategy for avoiding neurologic injury after aortic operations requiring hypothermic circulatory arrest. METHODS: All 717 patients who survived ascending aorta-aortic arch operations through a median sternotomy since 1986 were examined for factors influencing stroke. Temporary neurologic dysfunction was assessed in all patients who survived the operation without stroke since 1993. Multivariate analyses were carried out to determine independent risk factors for neurologic injury. RESULTS: Independent risk factors for stroke were as follows: age greater than 60 years (P <.001; odds ratio, 4.5); emergency operation (P =.02; odds ratio, 2.2); new preoperative neurologic symptoms (P =.05; odds ratio, 2.9); presence of clot or atheroma (P <.001; odds ratio, 4.4); mitral valve replacement or other concomitant procedures (P =.055; odds ratio, = 3.7); and total cerebral protection time, defined as the sum of hypothermic circulatory arrest and any retrograde or antegrade cerebral perfusion (P =.001; odds ratio, 1.02/min). In 453 patients surviving operations without stroke after 1993, independent risk factors for temporary neurologic dysfunction included age (P <.001; odds ratio, 1.06/y), dissection (P =.001; odds ratio, 2.2), need for coronary artery bypass grafting (P =.006; odds ratio, 2.1) or other procedures (P =.023; odds ratio, 3.4), and total cerebral protection time (P <.001; odds ratio, 1.02/min). When all patients with total cerebral protection times between 40 and 80 minutes were examined, the method of cerebral protection did not influence the occurrence of stroke, but antegrade cerebral perfusion resulted in a significant reduction in incidence on temporary neurologic dysfunction (P =.05; odds ratio, 0.3). CONCLUSIONS: The occurrence of stroke is principally determined by patient- and disease-related factors, but use of antegrade cerebral perfusion can significantly reduce the occurrence of temporary neurologic dysfunction.