To analyze the clinical characteristics of and identify specific risk factors for enterococcal bacteremia following liver transplantation, we performed a study in 405 consecutive liver transplantation recipients prophylaxed with a selective bowel decontamination regimen. Seventy enterococcal bacteremias in 52 patients were identified. Enterococcus faecalis (50) outnumbered Enterococcus faecium isolates (18), and 49% of enterococcal bacteremias were polymicrobial. Biliary tree complications were present in 34% of enterococcal bacteremias. Of the 15 deaths (29%) among the patients with enterococcal bacteremia, 4 were directly associated with enterococcal bacteremia. In a multivariate analysis, Roux-en-Y choledochojejunostomy (P=0.005), a cytomegalovirus-seropositive donor (P=0.013), prolonged transplantation time (P=0.02), and biliary stricturing (P=0.016) were identified as significant risk factors. Other risk factors identified in a univariate analysis included primary sclerosing cholangitis (P=0.009) and symptomatic cytomegalovirus infection (P=0.008). Enterococcal bacteremia is a frequent infectious complication in liver transplantation recipients receiving selective bowel decontamination. Its association with cytomegalovirus and biliary tree abnormalities suggest specific areas for prophylactic intervention.

Fungal infections are associated with a high mortality rate after liver transplantation. To describe risk factors for fungal infections, 405 consecutive liver transplant recipients were analyzed. Forty-five patients (11%) developed invasive fungal infection. Median posttransplantation time to the first episode was 60 days. Pathogens were Candida species (spp) (n=24, 53%), Cryptococcus neoformans (n=10, 22%), Aspergillus spp (n=6, 13%), Rhizopus spp (n=l), and others (n=4). Presentations of infection included disseminated (n=9), intra-abdominal (n=9), esophageal (n=9), lung (n=8), blood (n=6), and central nervous system infections (n=3), and sinusitis with esophagitis (n=1). Eighteen patients (40%) with invasive fungal infection died, and 13 (72%) of these deaths were attributable to fungi. Mortality in the nonfungal infection group was 12%. Univariate analysis identified separate risk factors for Candida (intra-abdominal bleeding), Aspergillus (fulminant hepatitis), and cryptococcal (symptomatic cytomegalovirus infection) infections. In both univariate and multivariate analyses, a high intratransplant transfusion requirement and posttransplant bacterial infection were identified as significant risk factors for all types of fungal infection. The risk factor analysis reported here suggests that different pathogenic processes lead to Candida and non-Candida infection in liver transplant recipients. Their identification should prompt specific prophylactic measures to reduce morbidity and mortality in this population.

Objectives. We studied the rate of thromboembolism in patients undergoing bioprosthetic replacement of the aortic or mitral valve, or bath, at serial intervals after operation and the effects of anticoagulant or antiplatelet treatment and risk factors.Background. Thromboembolism appears to occur early after operation, but the incidence, timing and risk factors for thromboembolism and the role, timing, adequacy, effectiveness, duration and risk of anticoagulation and antiplatelet agents are uncertain.Methods. The rate of thromboembolism was studied at three time intervals after operation (1 to 10, 11 to 90 and >90 days) in 816 patients who underwent bioprosthetic replacement of the aortic or mitral valve, or both, at the Mayo Clinic from January 1975 to December 1982. The effect of antithrombotic therapy (warfarin, aspirin or dipyridamole, alone or in combination) was evaluated.Results. Median follow-up of surviving patients was 8.6 years. The rate of thromboembolism (%/year) decreased significantly (p < 0.01) at each time interval after operation (1 to 10, 11 to 90 and >90 days) for mitral valve replacement (55%, 10% and 2.4%/year, respectively) and over the first time interval for aortic valve replacement (41%, 3.6% and 1.9%/year, respectively). During the first 10 days, 52% to 70% of prothrombin time ratios were low (<1.5 x control). Patients with mitral valve replacement who received anticoagulation had a lower rate of thromboembolism for the entire follow-up period (2.5%/year with vs. 3.9%/year without anticoagulation, p = 0.05). Of 112 patients with a first thrombo embolic episode, permanent disability occurred in 38% and death in 4%. Risk factors for emboli were lack of anticoagulation, mitral valve location, history of thromboembolism and increasing age. Only 10% of aortic, 44% of mitral and 17% of double valve recipients had anticoagulation at the time of an event. Patients with bleeding episodes (2.3%/year) were older and usually underwent anticoagulation. Blood transfusions were required in 60 of 111 patients (1.2%/year), and 13 patients (0.3%/year) died.Conclusions. Thromboembolic risk was especially high for aortic and mitral valve replacement for 90 days after operation, and overall was increased with lack of anticoagulation, mitral valve location, previous thromboembolism and increasing age. Anticoagulation reduced thromboemboli and appears to be indicated in all patients as early as possible for 3 months and thereafter in those with risk factors, but needs prospective testing.

The role of OKT3 monoclonal antibody administration was studied as a risk factor for symptomatic cytomegalovirus (CMV) infection in 229 consecutive liver transplant recipients not receiving specificCMV prophylaxis. Twenty-six patients (11.4%) receivedOKT3 and 17 ofthem developed CMV infection, 11 (4.8%) being symptomatic. OKT3 use was a significant risk factor for symptomatic CMV infection by both univariate (relative risk [RR], 2.9; 95% confidence interval [CI], 1.5-5.8; P = .002) and multivariate time-dependent (RR, 3.4; 95% CI, 1.7-7.1; P = .001) analyses. A subgroup analysis revealed that OKT3 use was a significant risk factor for symptomatic CMV infection in CMV-seropositive but not seronegative recipients. OKT3 therapy for steroid-resistant rejection is a risk factor for symptomatic CMV infection in liver transplant recipients who are seropositive for CMV before transplantation. This group should be targeted for antiviral prophylaxis when OKT3 antirejection therapy is used.

Fluorescence in situ hybridization is a new methodology which can be used to detect cytogenetic anomalies within interphase tumor cells. We used this technique to identify nonrandom numeric chromosomal alterations in tumor specimens from the poorest prognosis patients with pathological stages T2N0M0 and T3N0M0 prostate carcinomas. Among 1368 patients treated by radical prostatectomy, 25 study patients were ascertained who died most quickly from progressive prostate carcinoma within 3 years of diagnosis and surgery. Tumors from 25 control patients who survival for more than 5 years and who were matched for age, tumor histological grade, and pathological stage also were evaluated. The tumors from all 25 (100%) poor prognosis patients and from 11 of 25 (44%) control patients were found to be aneuploid by fluorescence in situ hybridization (P < 0.0001). Alterations of chromosome 7 were observed in 24 of the tumors (96%) from the poor prognosis patients versus 3 tumors (12%) from the control group (P < 0.0001). Moreover, a characteristic aneuploidy pattern with multiple abnormal chromosomes and a hypertetrasomic population was generally found in tumors from the poor prognosis patients. This preliminary study suggests that fluorescence in situ hybridization studies of prostate cancer specimens may help to identify those patients at highest risk for early cancer death.

BACKGROUND:In epidemiological studies, non-response may raise the question of generalizability to the target population. Most investigations have not been able to access data that could provide information about the potential impact of non-response bias.METHODS:A 55% response rate was realized at baseline for a prospective cohort investigation of the natural history of benign prostatic hyperplasia in Olmsted County, Minnesota, during 1989-1991 (the Olmsted County Study of Urinary Symptoms and Health Status Among Men). This prompted a preliminary study of potential non-response bias among full participants, partial participants and complete non-responders. The medical diagnostic index maintained by the Rochester Epidemiology Project was used to ascertain the prevalence of specific conditions in the 9 years prior to study inception.RESULTS:The age-adjusted period prevalence rate for benign prostatic hyperplasia (%) was 9.6 (95% confidence interval [CI]: 8.1-11.0) for full participants, 8.2 (95% CI: 5.8-10.6) for partial participants and 5.3 (95% CI: 3.6-6.9) for complete non-responders. Other urologic diagnoses followed the same pattern. However, age-adjusted prevalence rates for general medical examination history and major non-urologic morbidities were decidedly similar across response groups.CONCLUSIONS:These data suggest response may have been driven, in part, by concerns about urologic disease. However, the similarity in non-urologic diagnoses and general medical examinations provide some preliminary reassurance that the 55% response rate did not necessarily compromise generalizability.

A retrospective analysis was performed on 1,035 patients with pathologic Stage C prostate cancer treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. Of these patients, 661 received no immediate adjuvant treatment, 131 adjuvant radiotherapy only, and 103 postoperative adjuvant orchiectomy only. Overall crude survival at five, ten, and fifteen years was 91 percent, 68 percent, and 46 percent, respectively, comparable to the expected survival of 84 percent, 66 percent, and 46 percent, respectively. Cause-specific survival was 96 percent, 81 percent, and 66 percent and overall nonprogression survival was 78 percent, 56 percent, and 48 percent at five, ten, and fifteen years, respectively. Patients with margin-positive and residual disease, high-grade tumors, large tumor bulk, and seminal vesicle involvement were more likely to receive adjuvant treatment. However, both univariately and multivariately, only tumor grade and increasing tumor volume correlated significantly with cause-specific survival and local and systemic progression. Adjuvant treatment significantly decreased local, systemic, and overall progression but did not improve cause-specific or crude survival. Orchiectomy and radiation appeared to demonstrate similar efficacy in controlling local recurrences: five-year local recurrence-free survival in this retrospective analysis was > 95 percent for both treatments compared with 84 percent for those without adjuvant treatment.

Risk factors for cytomegalovirus and severe bacterial infections were studied prospectively by univariate, multivariate and time-dependent Cox model analysis in 79 consecutive liver transplant patients treated with selective bowel decontamination. Cytomegalovirus infection occurred in 39 patients (49%) and was symptomatic in 22 patients. Twenty-six patients (33%) developed at least one of 43 documented severe bacterial infections. In a multivariate analysis of risk factors for all cytomegalovirus infections, the cytomegalovirus seronegative recipient-cytomegalovirus seropositive donor group was the highest risk group (P < 0.001). Using the same analysis for risk factors for symptomatic cytomegalovirvs infections, a prolonged prothrombin time (P < 0.005), a diagnosis of acute fulminant hepatitis as the underlying liver disease (P < 0.01) and a cytomegalovirus seronegative patient receiving a liver from a seropositive donor (P < 0.001) were significant. The treatment with OKT3 therapy (P < 0.008) and hepatic artery thrombosis (P < 0.02) were found to be significant risk factors in a time-dependent univariate analysis but were not independent risk factors when multivariate analysis was utilized. Significant risk factors for major bacterial infections (P < 0.03) using univariate analysis included a prolonged anesthesia, anhepatic and surgical times, as well as the transfusion of large amounts of fresh frozen plasma or autologous blood. In a multivariate analysis, only the transfusion of large amounts of fresh frozen plasma (P < 0.04) was a significant independent risk factor. Cytomegalovirus infection was a risk factor for the development of severe bacterial infections (P < 0.03) in a multivariate time-dependent analysis.

Although the preoperative serum prostate-specific antigen (PSA) concentration has been demonstrated to be directly proportional to pathologic stage, it has been found to be unreliable for predicting final pathologic stage on an individual basis. Statistical analysis was thus performed to determine whether combining various preoperative parameters could enhance the predictive power of PSA. Multivariate logistic regression analysis revealed that, indeed, local clinical stage (determined by digital rectal examination) and tumor grade (determined from the biopsy specimen) significantly enhanced the predictive power of PSA (P < 0.0001 and < 0.0001, respectively). These preoperative parameters were thus all combined into a model from which probability plots were generated. These probability plots allow the practicing urologist to estimate preoperatively for an individual patient the probability of a given pathologic stage and DNA ploidy status. For example, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, when used alone, is 53 percent. However, the predicted probability of organ-confined disease for a patient with a PSA value of 10 ng/mL, clinical Stage B2, and high-tumor grade is only 30 percent. Thus, the findings of this investigation allow the physician maximal use of the preoperative variables to discuss more accurately with the patient what might be expected at the time of operation and to plan more precisely the surgical procedure that will possibly ensure complete removal of the prostate cancer with the least compromise to normal physiologic function (continence and potency).

COCKERILL, F. R. III; MULLER, S. R.; ANHALT, J. P.; MARSH, H. M.; FARNELL, M. B.; MUCHA, P.; GILLESPIE, D. J.; ILSTRUP, D. M.; LARSON-KELLER, J. J.; THOMPSON, R. L. Author Information

Background. Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy [RRP] for clinically localized prostate cancer [PC]. Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points [progression and survival] and immediate adjuvant hormonal treatment [AHT] rather than to the usual pathologic variables, including the number of positive nodes.Methods. Complete DNA ploidy information was available in 370 patients with Stage D1 disease [age range, 40-77 years; mean, 64 years] undergoing RRP with or without AHT with a follow-up of up to 22 years [mean, 5 years].Results. Overall, 80% of all DNA ploidy classes [diploid, 37%; tetraploid, 46%; and aneuploid, 17%] had AHT that highly significantly delayed progression for diploid [P < 0.0001] more than tetraploid [P < 0.0001] and more than aneuploid [P < 0.0001] tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival [crude and cause-specific] was significantly [P = 0.02] improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid [but not diploid] tumors. Delayed [on progression only] AHT resulted in high progression rates for all DNA ploidy classes [aneuploid > tetraploid > diploid]; e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression [76% at 10 years] and excellent local control, depending on DNA ploidy pattern [diploid > tetraploid > aneuploid] compared with a treatment regimen without AHT [24% overall nonprogression]; only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients [37%] treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed [on progression] hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class [diploid > tetraploid > aneuploid].Conclusion. Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival.

In this long-term study with a median followup of greater than 10 years 62 patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage D1 adenocarcinoma of the prostate were subdivided with respect to nuclear deoxyribonucleic acid ploidy status of the primary cancer and according to whether they received adjuvant early antiandrogen therapy. Patients with diploid cancers who underwent the operation and received adjuvant early endocrine therapy did significantly better than a similar group without early endocrine therapy with respect to disease-free survival (p < 0.001) and survival from prostate cancer death (p = 0.03). Among patients with nondiploid tumors early endocrine therapy was of some benefit for disease-free survival (p = 0.06) but not for prostate cancer death (p = 0.46).

OBJECTIVE:To determine whether selective decontamination of the digestive tract using oral and nonabsorbable antimicrobial agents and parenteral cefotaxime prevents infection in critically ill patients.DESIGN:Randomized, controlled trial without blinding.SETTING:Surgical trauma and medical intensive care units in a tertiary referral hospital.PATIENTS:One hundred fifty patients admitted to surgical trauma and medical intensive care units during a 3-year interval, whose condition suggested a prolonged stay (greater than 3 days).INTERVENTION:Patients were randomly allocated to an experimental group (n = 75) that received cefotaxime, 1 g intravenously every 8 hours for the first 3 days only, and oral, nonabsorbable antibiotics (gentamicin, polymyxin, and nystatin by oral paste and oral liquid) for the entire stay in the intensive care unit. Control patients (n = 75) received usual care.MEASUREMENTS:The number of infections, total hospital days, and deaths, as well as the number of days in intensive care unit, were recorded.RESULTS:Control patients experienced more infections (36 compared with 12, P = 0.04), including bacteremias (14 compared with 4, P = 0.05) and pulmonary infections (14 compared with 4, P = 0.03). Although total hospital days, days in intensive care, and the overall death rate all were lower in the treatment group, these differences were not statistically significant. Clinically important complications of selective decontamination of the digestive tract were not encountered.CONCLUSIONS:Selective decontamination of the digestive tract decreases subsequent infection rates, especially by gram-negative bacilli, in selected patients during long-term stays in the intensive care unit.

We reviewed the records of 83 patients who underwent 100 orthotopic liver transplantations in order to determine the following: (1) the methods to predict blood usage, (2) the consequences of an ABO-incompatible transplant, (3) the benefit of providing cytomegalovirus (CMV)-negative blood products to CMV-negative patients receiving a liver from a CMV-negative donor, (4) the association of donor anti-hepatitis B core antigens and subsequent hepatitis B, and (5) the prognostic consequences of rouleaux observed in pretransplant blood compatibility testing. Patient diagnosis, the presence of ascites, a preoperative prothrombin time greater than 15 seconds, and a multifactorial "risk category" were all predictive of intraoperative blood loss. A history of previous gastrointestinal bleeding or an operation that involved the right upper abdominal quadrant was not predictive of intraoperative blood loss. Although CMV infection is common after liver transplantation, the prophylactic use of CMV antibody-negative blood products in CMV-negative recipients receiving a liver from a CMV-negative donor in our series was not associated with postoperative CMV infection. The transplantation of a liver positive for anti-hepatitis B core antigen was associated with subsequent hepatitis B surface antigen seroconversion in two of four cases. Transplantation of an ABO-incompatible liver and the presence of rouleaux observed in pretransplant blood compatibility testing were both associated with a significantly higher mortality. A careful review of laboratory data and medical records of patients undergoing liver transplantation should enhance the ability to modify the approach to the allocation of limited blood resources and the care and management of these patients.