Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Worldwide esophageal cancer collaboration.

The aim of this study is to report assemblage of a large multi-institutional international database of esophageal cancer patients, patient and tumor characteristics, and survival of patients undergoing esophagectomy alone and its correlates. Forty-eight institutions were approached and agreed to participate in a worldwide esophageal cancer collaboration (WECC), and 13 (Asia, 2; Europe, 2; North America, 9) submitted data as of July 1, 2007. These were used to construct a de-identified database of 7884 esophageal cancer patients who underwent esophagectomy. Four thousand six hundred and twenty-seven esophagectomy patients had no induction or adjuvant therapy. Mean age was 62 +/- 11 years, 77% were men, and 33% were Asian. Mean tumor length was 3.3 +/- 2.5 cm, and esophageal location was upper in 4.1%, middle in 27%, and lower in 69%. Histopathologic cell type was adenocarcinoma in 60% and squamous cell in 40%. Histologic grade was G1 in 32%, G2 in 33%, G3 in 35%, and G4 in 0.18%. pT classification was pTis in 7.3%, pT1 in 23%, pT2 in 16%, pT3 in 51%, and pT4 in 3.3%. pN classification was pN0 in 56% and pN1 in 44%. The number of lymph nodes positive for cancer was 1 in 12%, 2 in 8%, 3 in 5%, and >3 in 18%. Resection was R0 in 87%, R1 in 11%, and R2 in 3%. Overall survival was 78, 42, and 31% at 1, 5, and 10 years, respectively. Unlike single-institution studies, in this worldwide collaboration, survival progressively decreases and is distinctively stratified by all variables except region of the world. A worldwide esophageal cancer database has been assembled that overcomes problems of rarity of this cancer. It reveals that survival progressively (monotonically) decreased and was distinctively stratified by all variables except region of the world. Thus, it forms the basis for data-driven esophageal cancer staging. More centers are needed and encouraged to join WECC.

Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS.

OBJECTIVE: To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy. METHODS: Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center. RESULTS: The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers. CONCLUSIONS: This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.

Assessment of a pathophysiology-directed treatment for symptomatic epiphrenic diverticulum.

Epiphrenic diverticulum is a rare disease associated with distal esophageal obstruction and a weakened muscularis propria. We have adhered to an operative strategy of excision (diverticulectomy), repair of esophageal wall, and relief of functional and mechanical obstruction. We sought to assess this pathophysiology-directed treatment strategy. From 1987 to 2005, 44 patients underwent surgery for epiphrenic diverticulum. Diverticulectomy, repair, and relief of distal obstruction was performed in 35 (80%) and esophagectomy in nine (10%). Outcome (symptoms, diet, subsequent therapies and morbidity) was assessed by follow-up. Forty of 44 patients had preoperatively identifiable esophageal obstruction (91%). Distal obstruction was functional in 32 patients and mechanical in 24; these conditions coexisted in 16. After surgery, there were no in-hospital deaths; 15 patients experienced 22 in-hospital complications. Survival was 90% at 5 years and 72% at 10 years. Symptoms improved in most patients (P = 0.0004), except for gastroesophageal reflux; new symptoms of gastroesophageal reflux occurred in 9/27 (33%) without this symptom preoperatively. Diet was less restricted postoperatively (P < 0.0001). Of 35 patients undergoing diverticulectomy, three (8.6%) required dilatation and two (6%) reoperation; 6/9 esophagectomy patients required dilatations. Preoperative assessment must include evaluation for mechanical obstruction. Adherence to a pathophysiology-directed operative strategy is safe and will improve the symptoms of most patients, with little need for reintervention. However, occasional patients will experience new symptoms, particularly reflux. Esophagectomy is the alternative for patients who are not candidates for diverticulectomy, repair of esophageal wall, and relief of distal obstruction.

Clinical experience with 202 adults receiving extracorporeal membrane oxygenation for cardiac failure: survival at five years.

OBJECTIVES: We sought to determine 5-year survival after extracorporeal membrane oxygenation for cardiac failure and its predictors, to assess survival and its predictors after bridging to transplantation or weaning from extracorporeal membrane oxygenation, and to identify factors influencing the likelihood of these outcomes. METHODS: Two hundred two adults (mean age, 55 +/- 14 years) were supported with extracorporeal membrane oxygenation between 1992 and July 1999 after cardiac failure. Follow-up extended to 7.5 years (mean, 3.8 +/- 2 years). Multivariable hazard function analysis identified predictors of survival, and logistic regression identified the determinants of bridging or weaning. RESULTS: Survival at 3 days, 30 days, and 5 years was 76%, 38%, and 24%, respectively. Patients surviving 30 days had a 63% 5-year survival. Risk factors (P <.1) included older age, reoperation, and thoracic aorta repair. Forty-eight patients were bridged to transplantation, and 71 were weaned with intent for survival. Survival was similar after either outcome (44% vs 40% 5-year survival, respectively). Failure to bridge or wean included (P <.03) renal and hepatic failure on extracorporeal membrane oxygenator support, occurrence of a neurologic event, and absence of infection. The dominant modes of death were cardiac failure and multisystem organ failure. CONCLUSIONS: Extracorporeal membrane oxygenation is versatile and salvages some patients who would otherwise die. Improvement in intermediate-term outcome will require a multidisciplinary approach to protect organ function and limit organ injury before and during this support.

Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation.

BACKGROUND: The conventional treatment strategy for patients with atrial fibrillation who are to undergo electrical cardioversion is to prescribe warfarin for anticoagulation for three weeks before cardioversion. It has been proposed that if transesophageal echocardiography reveals no atrial thrombus, cardioversion may be performed safely after only a short period of anticoagulant therapy. METHODS: In a multicenter, randomized, prospective clinical trial, we enrolled 1222 patients with atrial fibrillation of more than two days' duration and assigned them to either treatment guided by the findings on transesophageal echocardiography or conventional treatment. The composite primary end point was cerebrovascular accident, transient ischemic attack, and peripheral embolism within eight weeks. Secondary end points were functional status, successful restoration and maintenance of sinus rhythm, hemorrhage, and death. RESULTS: There was no significant difference between the two treatment groups in the rate of embolic events (five embolic events among 619 patients in the transesophageal-echocardiography group [0.8 percent]) vs. three among 603 patients in the conventional-treatment group [0.5 percent], P=0.50). However, the rate of hemorrhagic events was significantly lower in the transesophageal-echocardiography group (18 events [2.9 percent] vs. 33 events [5.5 percent], P=0.03). Patients in the transesophageal-echocardiography group also had a shorter time to cardioversion (mean [+/-SD], 3.0+/-5.6 vs. 30.6+/-10.6 days, P<0.001) and a greater rate of successful restoration of sinus rhythm (440 patients [71.1 percent] vs. 393 patients [65.2 percent], P=0.03). At eight weeks, there were no significant differences between the two groups in the rates of death or maintenance of sinus rhythm or in functional status. CONCLUSIONS: The use of transesophageal echocardiography to guide the management of atrial fibrillation may be considered a clinically effective alternative strategy to conventional therapy for patients in whom elective cardioversion is planned.

AKAP-mediated targeting of protein kinase a regulates contractility in cardiac myocytes.

Compartmentalization of cAMP-dependent protein kinase A (PKA) by A-kinase anchoring proteins (AKAPs) targets PKA to distinct subcellular locations in many cell types. However, the question of whether AKAP-mediated PKA anchoring in the heart regulates cardiac contractile function has not been addressed. We disrupted AKAP-mediated PKA anchoring in cardiac myocytes by introducing, via adenovirus-mediated gene transfer, Ht31, a peptide that binds the PKA regulatory subunit type II (RII) with high affinity. This peptide competes with endogenous AKAPs for RII binding. Ht31P (a proline-substituted derivative), which does not bind RII, was used as a negative control. We then investigated the effects of Ht31 expression on RII distribution, Ca(2+) cycling, cell shortening, and PKA-dependent substrate phosphorylation. By confocal microscopy, we showed redistribution of RII from the perinuclear region and from periodic transverse striations in Ht31P-expressing cells to a diffuse cytosolic localization in Ht31-expressing cells. In the presence of 10 nmol/L isoproterenol, Ht31-expressing myocytes displayed an increased rate and amplitude of cell shortening and relaxation compared with control cells (uninfected and Ht31P-expressing myocytes); with isoproterenol stimulation we observed decreased time to 90% decline in Ca(2+) but no significant difference between Ht31-expressing and control cells in the rate of Ca(2+) cycling or amplitude of the Ca(2+) transient. The increase in PKA-dependent phosphorylation of troponin I and myosin binding protein C on isoproterenol stimulation was significantly reduced in Ht31-expressing cells compared with controls. Our results demonstrate that, in response to beta-adrenergic stimulation, cardiomyocyte function and substrate phosphorylation by PKA is regulated by targeting of PKA by AKAPs.

Comparison of new Doppler echocardiographic methods to differentiate constrictive pericardial heart disease and restrictive cardiomyopathy.

This study assesses how the newer modalities of tissue Doppler echocardiography and color M-mode flow propagation compare with respiratory variation of Doppler flow in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. We studied 30 patients referred for further evaluation of diastolic function who had a diagnosis of constrictive pericarditis or restrictive cardiomyopathy established by diagnostic tests, including clinical assessment, magnetic resonance imaging, cardiac catheterization, endomyocardial biopsy, and surgical findings. Nineteen patients had constrictive pericarditis and 11 had restrictive cardiomyopathy. We performed 2-dimensional transesophageal echocardiography combined with pulsed-wave Doppler of the pulmonary veins and mitral inflow with respiratory monitoring, tissue Doppler echocardiography of the lateral mitral annulus, and color M-mode flow propagation of left ventricular filling. Respiratory variation of the mitral inflow peak early (peak E) velocity of > or =10% predicted constrictive pericarditis with 84% sensitivity and 91% specificity and variation in the pulmonary venous peak diastolic (peak D) flow velocity of > or =18% distinguished constriction with 79% sensitivity and 91% specificity. Using tissue Doppler echocardiography, a peak early velocity of longitudinal expansion (peak Ea) of > or =8.0 cm/s differentiated patients with constriction from restriction with 89% sensitivity and 100% specificity. A slope of > or =100 cm/s for the first aliasing contour in color M-mode flow propagation predicted patients with constriction with 74% sensitivity and 91% specificity. Thus, the newer methods of tissue Doppler echocardiography and color M-mode flow propagation are equivalent and complimentary with Doppler respiratory variation in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. The additive role of the new methods needs to be established in difficult cases of constrictive pericarditis where respiratory variation may be absent or decreased.

Estradiol and testosterone effects on lipids in black and white boys aged 10 to 15 years.

Previous studies of lipids in adolescent males have shown greater increases in triglycerides and decreases in high-density lipoprotein cholesterol (HDL-C) in white boys compared with black boys, significant correlations between sex hormones and lipids, and complex body mass index (BMI) hormone-lipid associations. Within this frame of reference, we assessed race, BMI, and sex hormones as predictors of lipid parameters in 536 black and white boys recruited from area schools. Black boys were more advanced in puberty than white boys. After adjusting for pubertal stage, estradiol (E2) levels were higher in black boys but free testosterone (T) levels did not differ. Age, pubertal stage, race, BMI, free T, and E2 were entered as explanatory variables for lipids in backward stepwise regression analyses. The BMI and race were retained in every model. Black boys had lower triglycerides and apolipoprotein B (apo B) and higher HDL-C. E2 was inversely associated with total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), apo B, and the LDL-C/HDL-C ratio. Free T was inversely associated with HDL-C and positively associated with apo B. Given the increases in free T and E2 during adolescence and the association of these hormones with both atherogenic and protective lipid parameters, racial differences in E2 could contribute to the more atherogenic lipid profile found in white boys after puberty.

Cardiac rehabilitation participation patterns in a large, tertiary care center: evidence for selection bias.

BACKGROUND: Clinical practice guidelines have been published for cardiac rehabilitation, directing programs to address secondary risk-reduction issues. The role of risk factor profiles in the referral of patients to cardiac rehabilitation programs has not been evaluated. METHODS: Patients from the Cardiovascular Information Registry at the Cleveland Clinic Foundation (CCF) who entered the CCF hospital-based cardiac rehabilitation program (n = 371) were compared with those who did not participate in the CCF program (n = 2960) with respect to gender, demographics, and risk factor profile for CAD. A random subset of those who did not participate in the CCF program (n = 100) was interviewed by phone to determine participation patterns in other rehabilitation programs. RESULTS: Only 11% of patients participated in CCF-based program. Standard risk factors were similar between participants and nonparticipants. Rehabilitation patients were younger (63 +/- 10 versus 66 +/- 10, P < 0.01) and as a group had better left ventricular function (moderate-severe left ventricle: 16% versus 23%, P < 0.01) than nonparticipants. Women were underrepresented in the CCF rehabilitation population (20% versus 30%, P < 0.01). Of the phone survey sample, 21% of patients entered other community-based rehabilitation programs. Similar trends with respect to risk factors, younger age, and better left ventricular function were noted for the community subset. However, women accounted for a greater percentage of the participants in the community programs than the CCF-based program (42.8% versus 19.7%, P < 0.03). CONCLUSIONS: Conclusions based on institution-specific programs likely underestimate overall participation in cardiac rehabilitation. Traditional risk factors apparently are not considered when referring patients to cardiac rehabilitation programs. Younger patients with lower mortality risks preferentially participate in rehabilitation programs. Women are more likely to participate in community-based programs. Overall use of cardiac rehabilitation programs remains low.

A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America.

To test the safety and efficacy of tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, in improving the outcome of patients with aneurysmal subarachnoid hemorrhage (SAH), 902 patients were enrolled in a prospective randomized, double-blind, vehicle-controlled trial at 54 North American neurosurgical centers. Five patients were excluded prior to receiving any study drug. Of 897 patients who received at least one dose of study medication, 300 received a placebo containing a citrate vehicle, 298 received 2 mg/kg per day tirilazad, and 299 received 6 mg/kg per day tirilazad, all administered intravenously beginning within 48 hours of the SAH and continuing through 10 days posthemorrhage. All patients were also treated with orally administered nimodipine. At 3 months post-SAH, there were no significant differences (p < 0.025) among the groups with regard to mortality rate, favorable outcome on the Glasgow Outcome Scale, or employment status. During the first 14 days after the SAH, there were no significant differences among the groups in the incidence or severity of clinically symptomatic or angiographically identifiable cerebral vasospasm. Mortality data stratified by gender and neurological grade on admission (assessed according to a modified World Federation of Neurological Surgeons scale) demonstrated that the men with Grades IV to V had a 33% mortality rate in the vehicle group, 52% in the 2 mg/kg per day tirilazad group (p = 0.29), and 5% in the 6 mg/kg per day tirilazad group (p = 0.03). Tirilazad was well tolerated at both dose levels. Tirilazad mesylate at dosage levels of up to 6 mg/kg per day for 8 to 10 days following SAH did not improve the overall outcome in patients with aneurysmal SAH in this trial. The differences in the efficacy of tirilazad in this trial and a previously reported trial in Europe, Australia, and New Zealand, in which dosage levels of tirilazad of 6 mg/kg per day reduced mortality rates and increased good recovery, may be a result of differences in admission characteristics of the patients and/or differences in management protocols, including the use of anticonvulsant medications.

Reoperation for failure of mitral valve repair.

BACKGROUND AND OBJECTIVE: Mitral valve repair is the procedure of choice to correct mitral regurgitation of all types. Up to 10% of patients who undergo mitral valvuloplasty require late reoperation for recurrent mitral valve dysfunction. To determine the causes of failed mitral valve repair, we examined the surgical pathology of patients who underwent reoperation for failed mitral valve repair. PATIENTS AND RESULTS: From 1986 to 1994, 81 patients had 86 reoperations for recurrent mitral regurgitation after mitral valve repair. Mean age was 59.2 +/- 1.4 years; 55 were men. Primary valve disease was degenerative in 48 patients (59%), rheumatic in 16 (20%), ischemic in 13 (16%), endocarditic in 3 (4%), and congenital in 1 (1%). Mean time interval between initial mitral valve repair and reoperation was 15.6 +/- 2.5 months. Causes of repair failure were procedure-related (50 cases, 58%), valve-related (33 cases, 38%), or unknown (3 cases, 3%). Procedure-related valve failure was caused by suture dehiscence (21 cases), rupture of previously shortened chordae (19 cases), or incomplete initial correction (10 cases). Valve-related repair failure was caused by progressive primary valve disease (27 cases), endocarditis (5 cases), or extensive leaflet retraction (1 case). Repair failure was procedure-related in 70% of patients with degenerative valvular disease versus only 13% of patients with rheumatic valvular disease (p = 0.0001). At reoperation, mitral valve replacement was performed in 64 patients (79%) and repeat mitral valve repair in 17 (21%). CONCLUSION: We conclude that (1) most mitral valve repair failures are procedure-related in degenerative disease and valve-related in rheumatic disease; (2) rupture of previously shortened chordae is a common cause of late failure in patients with degenerative mitral valve disease; and (3) repeat mitral valve repair results in successful treatment for a minority of patients.

Comparison of stenting and balloon angioplasty for narrowings in aortocoronary saphenous vein conduits in place for more than five years.

To compare the 1 year outcome of Palmaz-Schatz stent implantation versus balloon angioplasty for treatment of obstructive lesions in saphenous vein grafts, we combined databases from the Palmaz-Schatz vein graft stent registry and the coronary angioplasty arm of the Coronary Angioplasty Versus Excisional Atherectomy Trial II (CAVEAT II) for comparison of baseline characteristics, procedural variables, in-hospital events and 1-year composite end point of death, Q-wave myocardial infarction, and repeat target vessel revascularization. De novo graft lesions not involving the ostia were treated with stent implantation in 377 patients and with coronary angioplasty in 156 patients. The patients were comparable in age, coronary risk profile, interval from bypass surgery (9 +/- 4 years), and reference vessel diameter. The in-hospital composite end point of death, myocardial infarction, and emergency revascularization was lower in the stent group (10%) than in the angioplasty cohort (17%) (p = 0.059). At 1 year, the patients in the stent group had a markedly lower incidence of the composite end point of death, myocardial infarction, or revascularization (23% vs 45%, p <0.001). In this nonrandomized comparison with balloon angioplasty, the treatment of lesions in saphenous vein grafts appears to be favorably influenced by Palmaz-Schatz stent implantation, in terms of in-hospital events and clinical restenosis at 1 year follow-up.

A comparison of debulking versus dilatation of bifurcation coronary arterial narrowings (from the CAVEAT I Trial). Coronary Angioplasty Versus Excisional Atherectomy Trial-I.

We compared the effectiveness of percutaneous transluminal coronary angioplasty and directional coronary atherectomy for the management of bifurcation coronary lesions in 1,012 patients enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial-I. Directional coronary atherectomy was associated with less angiographic residual stenosis, but with a higher rate of side-branch closure and non-Q-wave myocardial infarction.

Repair of anterior leaflet prolapse: chordal transfer is superior to chordal shortening.

UNLABELLED: Several techniques are currently used to repair anterior leaflets with elongated or ruptured chordae. To evaluate the efficacy of these techniques, we analyzed the case histories of 108 patients operated on from 1989 through 1992 with degenerative mitral valve disease and prolapse of the anterior leaflet. The mean age was 59 +/- 15 years (range 18 to 87 years) and 74 (69%) were male. METHODS: Chordal shortening was performed in 31 (29%) and chordal transfer in 77 (71%) of the repairs. Of the transfers, 58 (75%) were from the posterior to the anterior leaflet and 16 (21%) were from the secondary to the primary position of the anterior leaflet. Three patients had both types of transfers. Seventy-one (66%) patients had isolated repairs and the remainder had associated procedures. The degree of preoperative mitral regurgitation was 3+ or greater for 107 (99%) of the patients, mean 3.4 for shortening and 3.7 for transfer. RESULTS: Four (4.0%) hospital deaths occurred, none after isolated repair. Follow-up of hospital survivors was 100% complete at a mean of 4.0 years. A total of 421 patient-years of follow-up were available for analysis. There were seven late deaths, for a 5-year actuarial survival of 93%. Eleven patients underwent reoperation for recurrent mitral regurgitation. Five-year actuarial freedom from reoperation was 90%-96% after chordal transfer and 74% after chordal shortening, p = 0.003. Independent predictors for reoperation include chordal shortening and preoperative New York Heart Association functional class III or IV. The mechanism of valve failure in six of seven patients undergoing reoperation after chordal shortening was rupture of the previously shortened chordae. CONCLUSIONS: We conclude that chordal transfer is superior to chordal shortening, providing a more predictable correction of mitral regurgitation and a lower incidence of reoperation. Reoperations after chordal shortening are a result of rupture of the previously shortened chordae.

Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand.

Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid, has been shown in experimental models to reduce vasospasm following subarachnoid hemorrhage (SAH) and to reduce infarct size from focal cerebral ischemia. To test whether treatment with tirilazad would reduce ischemic symptoms from vasospasm and improve overall outcome in patients with ruptured aneurysms, a prospective randomized, double-blind, vehicle-controlled trial was conducted at 41 neurosurgical centers in Europe, Australia, and New Zealand. One thousand twenty-three patients were randomly assigned to receive 0.6, 2, or 6 mg/kg per day of intravenously administered tirilazad or a placebo containing the citrate vehicle. All patients were also treated with intravenously administered nimodipine. Patients receiving 6 mg/kg per day of tirilazad had reduced mortality (p = 0.01) and a greater frequency of good recovery on the Glasgow Outcome Scale 3 months after SAH (p = 0.01) than similar patients treated with vehicle. There was a reduction in symptomatic vasospasm in the group that received 6 mg/kg per day tirilazad; however, the difference was not statistically significant (p = 0.048). The benefits of treatment with tirilazad were predominantly shown in men rather than in women. There were no material differences between the outcomes in the groups treated with 0.6 and 2 mg/kg tirilazad per day and the group treated with vehicle. Tirilazad was well tolerated at all three dose levels. These observations suggest that tirilazad mesylate, at a dosage of 6 mg/kg per day, is safe and improves overall outcome in patients (especially in men) who have experienced an aneurysmal SAH.