Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.

Improved in-hospital mortality in women undergoing coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Few studies have examined the changes in in-hospital mortality for women over time. We describe the changing case mix and mortality for women undergoing coronary artery bypass grafting (CABG) from 1987 to 1997 in northern New England. METHODS: Data were collected on 8,029 women and 21,139 men undergoing isolated CABG. The study consisted of three time periods (1987 to 1989, 1990 to 1992, and 1993 to 1997) to account for regional efforts to improve quality of care that occurred during 1990 to 1992. RESULTS: Compared with 1987 to 1989, women undergoing CABG in 1993 to 1997 were older, had poorer ventricular function, and more often required urgent or emergency operations. The crude and adjusted mortality rates for both women and men decreased significantly over time. The absolute magnitude of the change in adjusted rates was greater for women (3.1%) than for men (1.5%). Although women represented only 28% of the study population, the decrease in their mortality accounted for 44% of the total decrease in adjusted mortality during the study period. CONCLUSIONS: Over the last decade there has been a marked decrease in CABG mortality for women, despite a worsening case mix.

Predicting the risk of death from heart failure after coronary artery bypass graft surgery.

UNLABELLED: Heart failure is the most common cause of death among coronary artery bypass graft (CABG) patients. In addition, most variation in observed mortality rates for CABG surgery is explained by fatal heart failure. The purpose of this study was to develop a clinical risk assessment tool so that clinicians can rapidly and easily assess the risk of fatal heart failure while caring for individual patients. Using prospective data for 8,641 CABG patients, we used logistic regression analysis to predict the risk of fatal heart failure. In multivariate analysis, female sex, prior CABG surgery, ejection fraction <40%, urgent or emergency surgery, advanced age (70-79 yr and >80 yr), peripheral vascular disease, diabetes, dialysis-dependent renal failure and three-vessel coronary disease were significant predictors of fatal postoperative heart failure. A clinical risk assessment tool was developed from this logistic regression model, which had good discriminating characteristics (receiver operating characteristic clinical source = 0.75, 95% confidence interval: 0.71, 0.78). IMPLICATIONS: In contrast to previous cardiac surgical scoring systems that predicted total mortality, we developed a clinical risk assessment tool that evaluates risk of fatal heart failure. This distinction is relevant for quality improvement initiatives, because most of the variation in CABG mortality rates is explained by postoperative heart failure.

Use of the internal mammary artery graft and in-hospital mortality and other adverse outcomes associated with coronary artery bypass surgery.

BACKGROUND: There is clear evidence that patients having coronary artery bypass graft surgeries with an internal mammary artery (IMA) have better long-term survival. Some studies have suggested a short-term protective effect as well but, because older and sicker patients are less likely to receive an IMA graft, there has been concern that the apparent protective effect of the IMA on short-term mortality has been confounded by other risk factors. This study was intended to examine the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors. METHODS AND RESULTS: We studied the use of the left IMA (LIMA) in 21 873 consecutive, isolated, first-time coronary artery bypass graft procedures from 1992 through 1999. A total of 87% of the patients received a LIMA graft. LIMA graft use was associated with a significantly decreased risk of mortality. The crude odds ratio for death (LIMA versus no LIMA) was 0.26 (95% confidence intervals, 0.22, 0.31; P:<0.001). LIMA grafts were protective across all major patient and disease subgroups. The odds ratios by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the odds ratio for death was 0.40 (95% confidence intervals, 0.33, 0.48; P:<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so. CONCLUSIONS: These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality.

Decreasing mortality for aortic and mitral valve surgery in Northern New England. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Although numerous reports have documented declining mortality rates associated with coronary artery bypass surgery in recent years, it is unknown whether similar trends have occurred with valve surgery during this time. METHODS: We conducted a regional, prospective study to assess trends in patient casemix and in-hospital mortality rates over time with aortic valve replacement (AVR), mitral valve replacement (MVR), and mitral valve repair. Data were collected from all patients undergoing AVR (n = 2,596), MVR (n = 759), or mitral valve repair (n = 522) in Northern New England between January 1992 and December 1997. Logistic regression was used to identify significant predictors of in-hospital mortality and to calculate risk-adjusted mortality rates. RESULTS: For AVR, the trend in patient casemix was toward increased risk with increases in patient age and in the proportion of patients with: body surface area less than 1.7, diabetes, coronary artery disease, and prior valve surgery. A decrease was noted in the proportion of patients undergoing additional surgical procedures. For MVR, patient risk improved over the time period with fewer female patients and fewer patients with coronary artery disease. For mitral valve repair patient risk increased over the time period with increases in the proportion of patients with coronary artery disease, diabetes, and whose surgical priority was classified as urgent. In addition, there was a borderline significant increase in the proportion of mitral valve repair patients in New York Heart Association class IV preoperatively. Risk-adjusted mortality decreased 44% from 9.3% in 1992 through 1993 to 5.3% in 1996 through 1997 for patients undergoing AVR (p = 0.01) and decreased 53% from 13.6% in 1992 through 1993 to 8.2% in 1996 through 1997 for patients undergoing MVR (p = 0.01). We observed a statistically insignificant increase in risk-adjusted mortality over the time period for patients undergoing mitral valve repair (from 3.6% in 1992 through 1993 to 5.0% in 1996 through 1997; p = 0.34). CONCLUSIONS: Significant improvement in mortality rates with valve replacement was observed in northern New England during this time period. This improvement persisted following adjustment for changes in patient casemix over this time. These trends mirror improvements in mortality with other cardiac surgical interventions that have been observed in recent years in our region and nationally.

Predictors of 30-day hospital readmission after coronary artery bypass.

BACKGROUND: Risk factors for 30-day hospital readmission following coronary artery bypass grafting (CABG) have not been established. METHODS: We prospectively followed 485 consecutive patients who underwent isolated primary CABG at our institution in 1997. Patients were contacted by telephone at 30 days following operation to determine readmission status. RESULTS: The overall readmission rate was 16% (76 of 485). Female gender (25% versus 11%, p = 0.001) and diabetes (22% versus 12%, p = 0.005) were associated with significantly higher readmission rates. The relationship between female gender and readmission persisted after correcting for age and other comorbidities. Congestive heart failure trended towards a significant relationship with increased readmission rate (22% versus 14%, p = 0.09). There were no significant associations between 30-day readmission rate and age, hypertension, chronic obstructive pulmonary disease, history of myocardial infarction, peripheral vascular disease, creatinine level of > or = 1.4 mg/dL, or decreased left ventricular ejection fraction (< 40%). CONCLUSIONS: These data show that most of the classic risk factors for postoperative mortality are not necessarily associated with increased readmission. However, female gender and diabetes are associated with greater than twice the risk of 30-day readmission following CABG.

Risks of morbidity and mortality in dialysis patients undergoing coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Although dialysis patients are undergoing CABG with increasing frequency, large studies specifically comparing patient characteristics and procedure-related risks in this population have not been performed. METHODS AND RESULTS: We conducted a regional prospective cohort study of 15,500 consecutive patients undergoing CABG in northern New England from 1992 to 1997. We used multiple logistic regression analysis to examine associations between preoperative dialysis-dependent renal failure and postoperative events and to adjust for potentially confounding variables. The 279 dialysis-dependent renal failure patients (1.8%) were 4.4 times more likely to experience in-hospital mortality than were other CABG patients (12.2% versus 3.0%, respectively; P:<0.001). Dialysis-dependent renal failure patients were older and had more comorbidities and more severe cardiac disease than did other CABG patients. After adjusting for these factors in multivariate analysis, however, dialysis-dependent renal failure patients remained 3.1 times more likely to die after CABG (adjusted odds ratio [OR] 3.1, 95% CI 2.1 to 4.7; P:<0.001). Dialysis-dependent renal failure patients compared with other CABG patients also had a substantially increased risk of postoperative mediastinitis (3.6% versus 1.2%, respectively; adjusted OR 2.4, 95% CI 1.2 to 4.7; P:=0.011) and postoperative stroke (4.3% versus 1.7%, respectively; adjusted OR 2. 1, 95% CI 1.1 to 3.9; P:=0.016), even after controlling for potentially confounding variables. Risks of reexploration for bleeding were similar for patients with and without dialysis-dependent renal failure. CONCLUSIONS: Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and mediastinitis after CABG.

Mediastinitis and long-term survival after coronary artery bypass graft surgery.

BACKGROUND: Mediastinitis is a dreaded complication of coronary artery bypass surgery (CABG). The long-term effect of mediastinitis on mortality after CABG has not been well studied. METHODS: We examined the survival of 15,406 consecutive patients undergoing isolated CABG surgery from 1992 through 1996. Patient records were linked to the National Death Index. Mediastinitis was defined as occurring during the index admission and requiring reoperation. RESULTS: Mediastinitis occurred in 193 patients (1.25%). Patients with mediastinitis were older and more likely to have had emergency surgery, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, and preoperative dialysis-dependent renal failure. Patients with mediastinitis were also more likely to be severely obese and had somewhat lower preoperative ejection fraction. After multivariate adjustment for these factors, the first year post-CABG survival rate was 78% with mediastinitis and 95% without, and the hazard ratio for mortality during the entire follow-up period was 3.09 (CI 95% 2.28, 4.19; p < 0.0001). CONCLUSIONS: Mediastinitis is associated with a marked increase in mortality during the first year post-CABG and a threefold increase during a 4-year follow-up period.

Trends in rates of reexploration for hemorrhage after coronary artery bypass surgery. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: While mortality rates associated with coronary artery bypass grafting (CABG) have been declining, it is unknown whether similar improvements in the rates of morbidity have been occurring. This study examines trends in reexploration rates for hemorrhage, one of the serious complications of CABG surgery. It also explores changes in patient characteristics and several surgeon practice patterns potentially related to bleeding risks that may explain variations in these rates. METHODS: We performed a regional observational study of all of the 12,555 consecutive patients undergoing isolated CABG surgery in northern New England between 1992 and 1997. The rates of reexploration and patient characteristics were examined between two time intervals: period I (January 1, 1992 to June 1, 1994) and period II (June 1, 1995 to March 31, 1997). All of the region's 23 practicing surgeons responsible for these patients were surveyed to assess changes in practice patterns potentially related to bleeding risks. RESULTS: The adjusted rates of reexploration for bleeding declined 46% between periods I and II (3.6% versus 2.0%, p < 0.001). All of the five cardiac centers in northern New England showed similar trends with adjusted risk reductions ranging from 32% to 48% between the two time periods. This decline occurred despite the patients in period II having higher percentages of risk factors for reexploration for bleeding compared to patients in period I. From the surgeon survey, the number of surgeons using antifibrinolytics markedly increased from period I to period II. More surgeons were also using preoperative aspirin and heparin up until the time of surgery in period II. CONCLUSIONS: Similar to the rates of mortality, the rates of reexploration for bleeding following CABG surgery are substantially declining. This decrease in the reexploration rates occurred despite higher patient risks.

Gender and functional outcome after coronary artery bypass.

BACKGROUND: Female gender is an established risk factor for increased mortality and morbidity after coronary artery bypass graft (CABG) surgery. However, the impact of gender on functional outcome after CABG is not well established. METHODS: Functional status was assessed at baseline and at 6 months with the Duke Activity Status Index (DASI) in 196 consecutive patients undergoing isolated primary CABG. Follow-up data were complete in 158 (81%) patients. The functional status of the 54 (34%) female and the 104 (66%) male patients was compared. RESULTS: The mean DASI score was significantly lower in women at baseline (19.3 +/- 13.8 vs 28.3 +/- 16.8, P = .001) and at 6 months (22.7 +/- 16.3 vs 32.8 +/- 18.2, P = .0007); however, the 6-month change in DASI score (3.3 +/- 16.9 vs 4.5 +/- 20.0, P = .7) was comparable. A similar proportion of women and men (54% vs 53%) had improved above their baseline functional level at 6 months. CONCLUSIONS: These data demonstrate that women undergo CABG at a significantly lower functional level than men; however, the functional improvement after CABG is similar across genders.

Hospital readmission after cardiac surgery. Does "fast track" cardiac surgery result in cost saving or cost shifting?

BACKGROUND: Intense medical and economic pressures have created "fast track" cardiac surgery in which clinical services are streamlined and early discharge is encouraged. Does this strategy promote significant cost saving or merely cost shifting? In a global system of reimbursement, the economic benefit of decreasing patient length of stay may be offset by high rates of patient readmission. This study was undertaken to determine the 30-day readmission rate after cardiac surgery and to analyze trends of readmission diagnoses. METHODS AND RESULTS: From October 1, 1996 to July 31, 1997, 460 consecutive cardiac surgical operations were performed at 1 institution. There were 25 deaths and 8 patients who remained as inpatients at the 30-day postoperative deadline for readmission. Two patients had 2 operations. Therefore, 527 operations were performed on 525 patients. There were 110 readmissions after 527 operations for a readmission rate of 20.9%. A significant number of readmissions (49%) were to outside hospitals. Readmission diagnoses were: atrial fibrillation (23%); angina, congestive heart failure, or ventricular tachycardia (20%); leg wound (15%); sternal wound (5%); pneumonia (5%); gastrointestinal complaints (5%); neurologic event (2%); and miscellaneous (25%). Patients discharged > or = 7 days postoperatively were twice as likely to be readmitted as those discharged on postoperative days 4, 5, or 6. CONCLUSIONS: Readmission after cardiac surgery is common and frequently (49%) to outside institutions. Patients discharged > or = 7 days postoperatively represent the patients at greatest risk of readmission and, therefore, warrant closer scrutiny before discharge.

Central venous catheter use in low-risk coronary artery bypass grafting.

BACKGROUND: To assess the impact of central venous pressure catheter monitoring in low-risk coronary artery bypass grafting (CABG), we compared the hospital course of patients undergoing CABG with central venous pressure catheter monitoring with that of similar patients undergoing CABG with pulmonary artery catheter monitoring. METHODS: All isolated primary CABG procedures (n = 312) performed between April 22 and October 31, 1996, were evaluated, and 194 patients meeting six central venous pressure catheter use criteria were identified. Of these 194 patients, 133 (68%) underwent CABG with central venous pressure catheter monitoring, and 61 (32%) had pulmonary artery catheter monitoring owing to surgeon or anesthesiologist preference. RESULTS: In-hospital mortality was similar. A trend toward increased overall complications was seen in the pulmonary artery catheter group. The total volume infused in the first 12 hours, the 24-hour weight gain, and the intubation time were significantly greater in the pulmonary artery catheter group. Increases in intensive care unit length of stay and in total hospital charges trended toward statistical significance in the pulmonary artery catheter group. CONCLUSIONS: Pulmonary artery catheter use in low-risk patients undergoing CABG was associated with greater weight gain and longer intubation time and may be associated with increased morbidity and utilization of hospital resources.

Clinical and economic impact of diabetes following coronary artery bypass.

BACKGROUND: Diabetes has been shown to have a negative impact on mortality following coronary artery bypass graft (CABG) surgery. This analysis examines the impact of diabetes on additional clinical and economic outcomes. MATERIAL AND METHODS: Between May and October of 1996, 312 consecutive patients undergoing isolated primary CABG were followed through hospital discharge. A total of 114 diabetics (37%) and 198 nondiabetics (63%) was evaluated. Among the diabetics, 62 (54%) were insulin requiring and 52 (46%) were treated with oral hypoglycemic agents or with diet alone. RESULTS: The incidences of major clinical complications including death, renal failure, stroke, reexploration for bleeding, and mediastinitis or sternal dehiscence were not significantly different among insulin-requiring diabetics, noninsulin-requiring diabetics, and nondiabetics. However, insulin-requiring diabetics had a significantly longer (P < 0.01) total length of stay compared to both noninsulin-requiring diabetics and nondiabetics (107 +/- 12.7 days vs. 5.6 +/- 1.5 days vs. 6.8 +/- 5.4 days, respectively), a significantly longer (P < 0.01) intensive care unit length of stay (5.3 +/- 12.4 days vs. 1.4 +/- 0.8 days vs. 2.0 +/- 3.9 days, respectively), and significantly greater (P, 0.01) total hospital charges (48.7 +/- 56.1 thousand dollars vs. 29.3 +/- 4.3 thousand dollar vs. 32.9 +/- 18.9 thousand dollars, respectively). There were no significant differences between the noninsulin-requiring diabetics and the nondiabetics with regard to these clinical and economic outcomes. CONCLUSIONS: Diabetics treated with oral hypoglycemic agents or with diet alone have clinical and economic outcomes similar to nondiabetics following CABG. Insulin-requiring diabetes, however, predicts significantly increased hospital resource utilization. Future outcome assessment and resource utilization analyses must stratify diabetes by treatment to be completely accurate.

Reexploration for hemorrhage following coronary artery bypass grafting: incidence and risk factors. Northern New England Cardiovascular Disease Study Group.

OBJECTIVE: To assess mortality and risk factors associated with reexploration for hemorrhage in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Regional cohort study. Patient characteristics, treatment variables, and outcome measures were collected prospectively. SETTING: All 5 centers performing cardiac surgery in Maine, New Hampshire, and Vermont. PATIENTS: A consecutive cohort of 8586 patients undergoing isolated CABG between 1992 and 1995. MAIN OUTCOME MEASURES: Postoperative hemorrhage leading to reexploration, in-hospital mortality, and length of stay. RESULTS: A total of 305 patients (3.6%) underwent reexploration for bleeding. In these patients, in-hospital mortality was nearly 3 times higher (9.5% vs 3.3% for patients not requiring reoperation, P<.001) and average length of stay from surgery to discharge was significantly longer (14.5 days vs 8.6 days, P<.001). High rates of reexploration for hemorrhage were observed in patients with prolonged (> 150 minutes) cardiopulmonary bypass (39 [11.1%] of 351) and in those requiring an intra-aortic balloon pump intraoperatively (12 [8%] of 139). In multivariate analysis, older age, smaller body surface area, prolonged cardiopulmonary bypass, and number of distal anastomoses were associated with increased bleeding risks. The use of thrombolytic therapy within 48 hours of surgery was weakly but not significantly associated with the need for reexploration. Factors not significantly associated with reexploration included patient sex, preoperative ejection fraction, surgical priority, history of liver disease, myocardial infarction, prior CABG, renal failure, and diabetes mellitus. CONCLUSIONS: Hemorrhage requiring reexploration after CABG is associated with markedly increased mortality and length of stay. Patients predicted to have increased risks of bleeding may benefit from prophylactic use of aprotinin, aminocaproic acid, or other agents shown to reduce hemorrhage.

Successful surgical management of an aortic arch aneurysm with acute aorto-pulmonary fistula.

Aortic arch aneurysm with acute aorto-pulmonary fistula is usually a postmortem diagnosis. Few reports of successful surgical management are noted. Despite the many advances in cardiac surgery over the last 30 years, the observed mortality rate for surgical correction has been very high. Early diagnosis and prompt surgical intervention using profound hypothermia and total circulatory arrest are essential to successful outcome.

Preoperative risk factors that predict hospital length of stay in coronary artery bypass patients > 60 years old.

BACKGROUND: The ability to predict prolonged length of stay (LOS) is essential to control escalating hospital costs. Operative mortality is a poor predictor of LOS; morbidity as defined by hospitalization for > 14 days after coronary artery bypass graft surgery (CABG), appears to be responsible for increasing costs. The purpose of this study was to measure preoperative predictive indicators of increased LOS with an eventual plan to offer alternative cost-benefit therapeutic options. METHODS AND RESULTS: Nine hundred twenty-four consecutive patients (age, 60-86 years) undergoing CABG were retrospectively studied by means of the Cox proportional hazards model. Seventeen variables, excluding death, were analyzed and quantified as to importance, and point totals were calculated for each patient. Scores were 12 for congestive heart failure and intra-aortic balloon assist device; 10, creatinine > 2; 6, intra-aortic balloon assist device only; 5, congestive heart failure only; 3, obesity; 6, age > 75 years; 3, age 70-75 years; and 2, 65-69 years. CONCLUSIONS: Increasing index score directly correlated with an exponential increase in LOS. These data substantiate the hypothesis that a mathematical model can predict LOS in CABG patients and may offer rational alternative strategies in delivering cost-effective health care.

Misplaced caval filter and subsequent pericardial tamponade.

Use of the Greenfield filter for partial caval interruption is generally accepted as the most reliable mechanical method of pulmonary embolus prophylaxis. However, there have been reports of a variety of (usually nonfatal) complications. We report here the near-fatal complication of acute pericardial tamponade after misplacement of a Greenfield filter. Because of the filter's unusual location, retrieval required cardiopulmonary bypass, profound hyperthermia, and circulatory arrest.

Review of coronary-subclavian steal following internal mammary artery-coronary artery bypass surgery.

The syndrome of coronary-subclavian steal through an internal mammary artery graft following coronary artery bypass grafting is rare. We are aware of only eight cases reported in the world literature. The cases of these 8 patients are reviewed, and the case of the ninth patient is described. All patients but 1 have been successfully managed by subclavian-carotid artery bypass.

Effects of specific active immunization on tumor recurrence following primary tumor resection in WF rats with 1,2-dimethylhydrazine-induced bowel cancer.

Primary gastrointestinal tumors were induced in male WF rats by 16 weekly sc injections of 1,2-dimethylhydrazine [(DMH) CAS: 540-73-8; 20 mg/kg/wk]. Twenty-four to 28 weeks after the start of DMH injections, all rats were surgically explored and gastrointestinal tumors were resected. Rats with no remaining microscopic disease after operation were immunized with one of four tumor isografts. The first isograft, DMH-W163, is a poorly differentiated mucinous adenocarcinoma explanted from a colon cancer in a DMH-treated animal. It has been shown to possess antigens that cross-react with other DMH-induced bowel adenocarcinoma isografts. The second isograft, DMH-W49, is a carcinosarcoma explanted from a DMH-treated primary colon cancer. It has intermediate antigenic cross-reactivity with other colon adenocarcinoma isografts in the WF model. The third isograft, DMH-W15, is a sarcoma explanted from a DMH-induced colon cancer that does not possess antigens cross-reactive with other DMH-induced colon adenocarcinomas. The fourth isograft, SPK, is a spontaneous (non-DMH-induced) renal cell carcinoma that is immunogenic but should not contain tissue-type-specific antigens cross-reacting with the bowel cancers. Immunized rats received three sc weekly injections of 1 X 10(3) irradiated cells. Concomitant control rats received no immunization after resection of the primary tumor. Within 24 weeks of primary tumor resection, 12 of 16 (75%) rats not immunized had tumor recurrence. Only 8 of 24 (34%) rats immunized with DMH-W163 had tumor recurrence (P less than .025 compared to controls). Fifty percent of animals (10/20) immunized with the carcinosarcoma DMH-W49 had a recurrence. Animals immunized with the non-cross-reacting DMH-W15 sarcoma isograft had a recurrence rate similar to that of controls (16/20, 75%). The rats immunized with SPK were not protected from recurrence. Twelve of 19 (63%) had a recurrence at or near the suture line within 24 weeks following primary tumor resection. These results confirm that adjuvant immunotherapy can decrease the rate of recurrence following primary tumor resection in this model. In addition, immunogens that possessed tissue-type-specific antigens were more effective in preventing tumor recurrence than those that did not.

The effect of 1,2-dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the Wistar Furth rat.

1,2-dimethylhydrazine (DMH)-induced colon cancer in Wistar/Furth (W/Fu) rats is analogous in many ways to human colorectal cancer. As part of our attempt to understand the immunobiology of these tumors, we have utilized the recently available monoclonal antibodies W3/25 and OX8 to monitor helper (Th) and suppressor (Ts) lymphocyte subpopulations. Normal untreated male W/Fu rats of less than 1 year of age were phenotyped (n = 43). The mean percentage of Th and Ts was 42 +/- 1 (mean +/- SEM) and 33 +/- 1, respectively. The mean Th/Ts ratio was 1.3 +/- 0.1. A Th/Ts equal to or greater than 1 is considered "normal" in the W/Fu rat. The DMH-treated rats (20 mg/kg/wk) were evaluated in initial experiments at various intervals after treatment. Rats studied 24 hours after a single DMH injection had no alterations in T cell subsets. Rats studied 28, 32, and 65 weeks after the start of 16 weekly DMH injections were found to have a decrease in the percentage of Th and a relative increase in Ts, with Th/Ts ratios of 0.6 +/- 0.2, 0.7 +/- 0.1, and 0.7 +/- 0.1, respectively (each P less than 0.01). In a separate experiment in which rats were studied after 4, 8, and 16 weeks of DMH injections, no alterations in T cell subsets were noted. Rats (n = 5) studied at 20 weeks after the start of DMH were found to have 41 +/- 3% Th and 36 +/- 2% Ts and a Th/Ts ratio of 1.2 +/- 0.1. Three of five rats were found to have adenocarcinomas. Four of five rats had Th/Ts less than 1. One rat with Th/Ts equal to 0.9 had metastatic disease. Rats studied at 25 weeks (n = 8) were found to have more advanced carcinomas (4/8) that were causing obstruction or bleeding in the animal. There was a significant decrease in Th and Ts in this group, with 24 +/- 3% and 26 +/- 3% respectively (P less than 0.001). The Th/Ts ratio for this group was 0.9 +/- 0.1 (P less than 0.01). In other experiments, rats were treated with DMH or placebo over a 16-week period and serially bled during and after treatment. No effect of DMH treatment on T cell subsets was noted. Repeated bleeding alone was noted to cause persistent alterations of T cell subpopulation.(ABSTRACT TRUNCATED AT 400 WORDS)