Biomedical subjects
Publications and source records attributed to R E Nakhleh.
Quality in surgical pathology may be defined as accurate, timely, and complete reports. Achieving quality requires substantial investment in the basic structure and in the people who undertake surgical pathology. Quality assurance and improvement works best when it is woven into the systems of surgical pathology with well informed, well trained, and knowledgeable staff.
AIMS: We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS: Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.
Clinical, radiographic, and pathological features of 18 patients with biliary necrosis in their explanted liver allografts were reviewed. Twelve patients were men and ages ranged from 27 to 72 years. Indications for initial liver transplant (LT) were viral hepatitis (n = 7), steatohepatitic cirrhosis (n = 3), cryptogenic cirrhosis (n = 3), secondary sclerosing cholangitis (n = 2), primary sclerosing cholangitis (n = 1), biliary atresia (n = 1), and nodular regenerative hyperplasia (n = 1). Donor age ranged from 16 to 75 years. Duct-to-duct biliary anastomoses were fashioned in 13 cases; warm and cold ischemia times were not significantly different from general LT population. Seventeen allograft biopsies after recirculation had no significant findings. Post-LT, clinical and radiographic evaluation indicated biliary strictures (n = 7), bile leak (n = 7), intrahepatic abscess (n = 1), and duodenal perforation (n = 1). Radiographic vascular studies suggested hepatic arterial thrombosis or stenosis in 11 cases. Biopsies prior to retransplantation were performed on 17 patients and showed acute rejection (n = 10), biliary outflow impairment (n = 4), normal histology (n = 2), and centrilobular necrosis (n = 1). Retransplantation was performed 14 to 334 days after initial LT. Pathological examination of explants revealed perihilar duct necrosis in all cases, with bacterial colonies (n = 10) and fungal organisms (n = 2). Arterial thrombi were seen in 10 cases, and two had prominent arteriosclerosis. Infarction and centrilobular necrosis were seen in 9 and 13 cases, respectively. Four explants showed features of biliary outflow impairment. Twelve patients were alive 6 to 18 months following retransplantation. We conclude that post-LT biliary necrosis is associated with ischemia, and such a complication is rarely evident in allograft biopsies. Biliary and vascular imaging studies are essential in evaluating patients for this complication.
Pericardial metastasis from the oral cavity is a rare event. Squamous cell carcinoma of the buccal mucosa is not known to spread to the pericardium. We present a case of buccal mucosal carcinoma with distant metastases diagnosed by pericardial biopsy.
HYPOTHESIS: We previously showed in a large animal pig model that unmodified donor-specific bone marrow infusion (DSBMI) did not facilitate total bowel engraftment; in contrast, it increased the risks of rejection, infection, and graft-vs-host disease (GVHD) posttransplant. We hypothesize that continuous immunosuppression, in combination with DSBMI, might contribute to-or even trigger-these unwarranted immune responses by both host and graft; therefore, discontinuing immunosuppression might decrease these risks and prolong survival. METHODS: Six groups of outbred, mixed lymphocyte culture-reactive pigs underwent a total (small and large) bowel transplant: group 1, nonimmunosuppressed control pigs (n = 5); group 2, nonimmunosuppressed DSBMI pigs (n = 6); group 3, tacrolimus (indefinite) pigs (n = 7); group 4, tacrolimus (indefinite) plus DSBMI pigs (n = 7); group 5, tacrolimus (10 days only) pigs (n = 5); and group 6, tacrolimus (10 days only) plus DSBMI pigs (n = 6). RESULTS: The combination of short-term immunosuppression and DSBMI (group 6) significantly prolonged survival, compared with short-term immunosuppression only (group 5) or DSBMI only (group 2). Short-term immunosuppression and DSBMI (group 6) did not prolong overall survival, compared with indefinite immunosuppression with (group 4) or without (group 3) DSBMI: survival rates at 7, 14, and 28 days posttransplant were 100%, 100%, and 67% in group 6; 100%, 100%, and 71% in group 3; and 100%, 67%, and 47% in group 4 (P =.14). Short-term immunosuppression and DSBMI (group 6) increased the incidence of rejection, infection, and GVHD, compared with indefinite immunosuppression without (but not with) DSBMI. CONCLUSIONS: Short-term immunosuppression and DSBMI did not prolong survival and did not reduce the incidence of death from rejection, infection, or GVHD, compared with indefinite immunosuppression without DSBMI. But short-term immunosuppression and DSBMI resulted in a lower incidence of death from infection and GVHD, compared with indefinite immunosuppression and DSBMI. When immunosuppression was discontinued 10 days posttransplant, the effect of DSBMI was insufficient to avert death from rejection. CLINICAL RELEVANCE: The clinical results of bowel transplantation trail those of other solid organ transplants. It reduced the rates of infection and GVHD. Our study shows that systemically infused donor-specific bone marrow with short-term or indefinite immunosuppression does not improve outcome after bowel transplantation. It seems necessary to modify the time, dosing, routing, and/or composition of donor-specific bone marrow before it can be successfully used in clinical bowel transplantation.
Specific immunomodulatory strategies are required to eliminate the need for lifelong dependence on debilitating immunosuppressants. One proposed strategy is to simultaneously transplant the kidney and infuse donor-specific bone marrow cells. We prospectively studied the effect of unmodified donor-specific bone marrow infusion (DSBMI) on rejection, infection, graft-versus-host disease (GvHD), and graft survival. We performed 57 kidney transplants in mixed lymphocyte culture (MLC)-reactive, outbred pigs. The groups of recipient pigs differed according to the use of (1) indefinite versus short-term tacrolimus-based immunosuppression, (2) DSBMI, and (3) recipient preconditioning (RPC: whole body irradiation with 400 rads on day 0 and horse anti-pig thymocyte globulin (ATG) on days -2, -1, and 0). In all, we studied eight groups: group 1, nonimmunosuppressed control pigs (n = 8); group 2, nonimmunosuppressed DSBMI pigs (n = 7); group 3, nonimmunosuppressed RPC + DSBMI pigs (n = 5); group 4, tacrolimus (indefinite) pigs (n = 11); group 5, tacrolimus (10 days only) pigs (n = 5); group 6, DSBMI + tacrolimus (indefinite) pigs (n = 8); group 7, DSBMI + tacrolimus (10 days only) pigs (n = 6); and group 8, RPC + DSBMI + tacrolimus (indefinite) pigs (n = 7). DSBMI alone (group 2) or in combination with RPC (group 3) did not prolong graft survival, as compared with nonimmunosuppressed controls (group 1). In groups 1, 2, and 3, all but one pig died from rejection; in group 3 only, 45% of the pigs died from concurrent infection or GvHD, indicating that RPC in combination with DSBMI aggravated the risk of generalized infection and GvHD. Post-transplant immunosuppression--irrespective of indefinite or short-term administration--was required for prolonged graft survival. With indefinite use of immunosuppression, graft survival rates and death rates from rejection were not different for pigs with (group 6) versus without (group 4) DSBMI; however, the death rate from infection was higher in group 6, suggesting that the bone marrow inoculum increased the risk of systemic infection. With short-term use of immunosuppression, graft survival rates were higher and death rates from rejection lower for pigs with (group 7) versus without (group 5) DSBMI. But DSBMI and short-term immunosuppression (group 7) failed to prolong survival beyond that achieved with indefinite immunosuppression (groups 4 and 6). Although the combination of DSBMI and short-term immunosuppression (group 7) reduced the risk of infection, it did not avert severe rejection. The addition of RPC to DSBMI and indefinite immunosup- pression (group 8) significantly decreased graft survival, as compared with groups 4, 6, and 7. It also increased the incidence of death from rejection, GvHD, and infection, or a combination thereof. Unmodified DSBMI did not prolong graft survival after kidney transplantation, nor did it decrease the incidence of rejection. But it aggravated the risk of GvHD and infection. Short-term immunosuppression with DSBMI reduced the incidence of death from infection or GvHD, but it resulted in a higher incidence of death from rejection (as compared with indefinite use of immunosuppression). RPC, combined with DSBMI and indefinite immunosuppression, increased the death rate from rejection, GvHD, infection, or a combination thereof. In this large animal study, the effect of unmodified DSBMI has been disappointing. The search continues for the optimal way to successfully perform bone marrow augmentation in solid organ transplants.
A subset of hepatitis C virus (HCV)-positive liver transplant recipients develop cholestatic hepatitis (CH). We investigated the role of pretransplantation disease activity (estimated by Knodell score and HCV RNA quantitation) in the native liver explant on the development of CH and graft and patient outcome. Eight patients with CH were identified among HCV-positive liver transplants and were compared with 20 consecutive patients with recurrent HCV hepatitis of noncholestatic type in liver transplants. We evaluated all 28 explanted native livers histologically using the Knodell scoring system. HCV viral load was measured in the native explant and 5 allograft explants from the CH group using Amplicor HCV RNA Monitor test. Six of 8 patients with CH had HCV RNA levels of 5,000 copies/microg of DNA or greater in the native liver explant, whereas only 1 of the control group had viral loads greater than this level. Greater HCV RNA levels correlated with worse graft and patient survival (P <.001). The 3-year survival rate in the CH group was 18% compared with 77% in the control group (P <.001). There was no difference in the primary immunosuppressive regimens used in the 2 groups. We conclude that (1) CH has a uniformly poor prognosis, (2) type of immunosuppressive therapy appears to have little influence on the development of CH, (3) high pretransplantation HCV RNA levels in the native explant may predict the development of CH, and (4) patients with high HCV RNA levels in the explanted native liver may be appropriate candidates for antiviral therapy to prevent the development of CH.
Persistence of hepatitis C virus (HCV) after orthotopic liver transplantation is almost universal in HCV-infected patients. Histological examination of liver biopsy specimens can be variable in distinguishing between recurrent hepatitis C and acute cellular rejection. The purpose of this study is to determine whether hepatic HCV RNA levels can be used to distinguish rejection from recurrent HCV by determining whether hepatic HCV RNA levels correlate with histological characteristics and clinical course. Seventy-two biopsy specimens were evaluated from 36 liver transplant recipients with HCV and elevated liver-related enzyme levels. Based on histological findings and clinical response to therapy, patients were defined as belonging to 1 of 5 groups: (1) definite rejection, (2) probable rejection, (3) indeterminate findings, (4) probable HCV, and (5) definite HCV. Hepatic HCV RNA was quantified using the Amplicor Monitor assay (Roche Diagnostic Systems Inc, Branchburg, NJ). There was a difference across groups in HCV RNA levels (P =.046). The median HCV RNA level was 10,695 copies/mg of tissue DNA in the definite-HCV group compared with 1,024 copies/mg of tissue DNA in the definite-rejection group. Using pairwise comparisons, significant differences were found between definite HCV and definite rejection, probable HCV and definite rejection, probable HCV and probable rejection, and probable HCV and indeterminate. Our findings support the following conclusions. (1) In liver transplant recipients, hepatic HCV RNA levels are statistically greater in patients with recurrent HCV than rejection, although there is considerable overlap between groups. (2) Patients with low HCV RNA levels were unlikely to have recurrent HCV. (3) Patients with minimal and indeterminate findings on biopsy (group 3) had low HCV RNA levels.
OBJECTIVE: To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection. DESIGN: Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers. SETTING: Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium. PARTICIPANTS: One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program. MAIN OUTCOME MEASURES: Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors < or = 1 cm in diameter, and invasive cancers with lymph nodes negative for metastases. RESULTS: All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size < or = 1 cm (57.8% vs 36.5%), and lymph node-negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P <.001) compared to all other detection methods. CONCLUSIONS: This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.
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OBJECTIVE: To survey the scope of current written institutional policies for types of surgical pathology specimens exempt from submission to the laboratory and those that may be examined by gross inspection only. DESIGN AND SETTING: In the first quarter of 1997, a total of 413 voluntary participant institutions enrolled in the College of American Pathologists Q-Probes quality improvement program completed a checklist of 115 proffered specimens. Also included was a questionnaire defining demographic, practice, and reimbursement variables. MAIN OUTCOME MEASURES: The number and types of specimens exempt from submission and submitted for gross examination only based on written institutional policy rather than on unapproved actual practices. RESULTS: Most institutions had a written policy for types of specimens deemed exempt from submission to pathology (87.1 %) and for types of specimens subject to gross examination only (76.6%). There was a wide range of numbers of specimen types with a median number of 17 (range, 2-40) in the exempt category and 29 (range, 6-57) in the category of gross examination only. Significantly higher absolute counts of specimens exempt from submission to pathology were reported by institutions with a greater surgical pathology volume in 1996 and by nonteaching institutions. No aspect of practice was associated with numbers of specimens for gross examination only. CONCLUSIONS: This Q-Probes study creates a multi-institutional reference database of current practices to assist pathologists and clinical staff in the development of written guidelines pertaining to surgical pathology specimen submission exceptions and gross-only examinations.
OBJECTIVES: To document the level of involvement and communication with nonpathology clinical personnel regarding autopsies and to document the destination of autopsy reports. DESIGN: The College of American Pathologists Q-Probes format was used to collect information on 15 consecutively performed autopsies per institution or for 6 months, whichever occurred first. The following information was recorded for each autopsy: decedent's age, hospital service, length of hospital stay, whether organs were donated, who was present at autopsy, methods of communicating preliminary and final autopsy results, special techniques used to arrive at a preliminary diagnosis, activities for which the autopsy was used, and destination of final report. PARTICIPANTS: Two hundred fifty-six laboratories collected information on 2755 autopsies. RESULTS: The aggregate autopsy rate was 12.4% (median 8.5%). Nonpathology clinical personnel attended 35.8% of all autopsies. A clinical physician was more likely to attend an autopsy if the patient was from a surgical service. Three primary methods were used to communicate preliminary autopsy results, namely, written reports (82.5%), telephone calls (50.6%), and meetings (11.5%). The primary care physician was sent the autopsy report in 91.1% of cases. Approximately half of the autopsy cases were used in both pathology departmental and extradepartmental activities. Aggregate autopsy data were distributed in the majority of cases to various departmental chairpersons and institutional quality assurance committees. CONCLUSIONS: This study provides a comparative multiinstitutional database for the utilization of autopsy results by clinicians and clinical departments. Although autopsy rates are low, autopsy results are routinely being used for hospital quality assurance activities and for educational purposes.
OBJECTIVES: To examine the frequency and nature of problems caused by inadequate clinical data provided on surgical pathology requisition forms. DESIGN: Participants in the 1996 Q-Probes voluntary quality improvement program of the College of American Pathologists were asked to document prospectively all surgical pathology cases with inadequate information. Inadequate clinical information was defined as the pathologist's need for additional clinical information before a diagnosis could be rendered, regardless of the amount of information already present on the requisition slip. Cases that had no clinical information on a requisition slip were not counted if the lack of history did not hinder diagnosis. The study concluded when 3 months had elapsed or 40 surgical pathology cases were documented. The following data were recorded for each case: anatomic site, type of procedure, nature of disease, method of obtaining additional information, importance of obtained information, and the length of delay in the final diagnosis. PARTICIPANTS: Three hundred forty-one laboratories, 322 of which were from the United States. RESULTS: A total of 5594 cases (0.73%) required additional clinical information for diagnosis (10th through 90th percentile range, 3.01% to 0.08%). Institutions with greater average occupied bedsize, a greater number of cases accessioned per year, and a greater number of pathologists had a lower percentage of cases with inadequate clinical data (P <.05). Sixty-eight percent of these cases had no delay in completion of a case, 16.2% had a delay of 1 day or less, and 15.1% of cases were delayed more than 1 day. In 59.4% of cases, the additional clinical information obtained confirmed the initial diagnostic impression. In 25.1%, the information was not relevant to the pathologic diagnosis. In 6.1% there was a substantial change in the diagnosis or a revised report was issued, and in 2.2% no additional information could be obtained. Specific anatomic sites that correlated with a higher rate of changed diagnoses or revised reports in cases with inadequate information included the small bowel, the bronchus/lung, and the ovary. Resection specimens were also significantly associated with a higher rate of changed diagnoses or revised reports when additional information was obtained, as were malignant neoplasms and therapy-induced changes. CONCLUSIONS: This study establishes an aggregate rate of cases with inadequate clinical information for diagnosis (0.73%) and documents the extent of problems caused by inadequate clinical information. The criticality of appropriate clinical information provided to the pathologist is identified for specific anatomic sites and disease processes and is reflected in changed diagnoses or revised reports.
BACKGROUND: Histologic findings and liver enzymes in liver transplants are often non-diagnostic of recurrent hepatitis C virus (HCV) disease. In addition, the relationship between HCV replication and the presence of recurrent HCV hepatitis after liver transplantation remains unclear. We studied liver transplant recipients to determine if quantitation of HCV RNA in liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) correlates with histopathologic disease and/or liver enzymes. METHODS: Twenty-six patients who received liver transplants for HCV infection were evaluated. Four sequential biopsies were analyzed for each patient. HCV RNA was extracted and quantified using the Amplicor HCV Monitor Test. Histologic examination and RNA quantitation were blinded. All available liver enzymes on the day of liver biopsy were analyzed. RESULTS: HCV RNA quantity in liver tissue was significantly increased at the time of clinically-suspected recurrence (P < .0001). HCV RNA levels were highest in biopsies with lobular hepatitis and nonspecific inflammation, followed by biopsies with cytomegalovirus infection, chronic hepatitis, and acute cellular rejection. HCV RNA quantity had a significant correlation with increasing portal inflammation (P = .0002), decreasing amount of interface hepatitis (P = .0333), and presence of acidophilic bodies (P = .0316). Increasing HCV RNA levels significantly correlated with decreasing number of episodes of treated rejection. HCV RNA quantity did not correlate with other histologic features or liver enzymes. CONCLUSIONS: HCV RNA levels are highest at the time of active hepatocellular destruction. Elevated HCV RNA indicates recurrence. HCV RNA quantitation may be a useful diagnostic test for determining recurrent disease and distinguishing it from other causes of inflammation, such as rejection.
BACKGROUND: Unlike in kidney and heart transplantation, the role of pretransplant donor-specific blood transfusion (DST) has not been studied prospectively in a large animal model of bowel transplantation. We investigated the impact of portal versus systemic DST on overall survival, rejection, graft-versus-host disease (GVHD), and infection after total (small and large) bowel transplantation in pigs. METHODS: Mixed lymphocyte culture-reactive, outbred pigs underwent total enterectomy and orthotopic total bowel transplantation with portal vein graft drainage. One unit of donor blood was transfused via the portal or systemic circulation (according to a randomization protocol) before graft implantation was begun. We studied six groups, all of which underwent at least a total bowel transplant: group 1 (n=5) comprised nonimmunosuppressed control pigs with portal DST; group 2 (n=6), nonimmunosuppressed control pigs with systemic DST; group 3 (n=5), cyclosporine (CsA)-treated pigs with portal DST; group 4 (n=5), CsA-treated pigs with systemic DST; group 5 (n=5), tacrolimus-treated pigs with portal DST; and group 6 (n=5), tacrolimus-treated pigs with systemic DST. All immunosuppressed pigs received prednisone (2 mg/kg/day) and either CsA (to maintain levels between 250 and 350 ng/ml) or tacrolimus (to maintain levels between 10 and 30 ng/ml). Stomal biopsies and autopsies were obtained to study the incidence of rejection, GVHD, and infection. RESULTS: Portal DST and tacrolimus-based immunosuppression resulted in the highest survival rates. At 7, 14, and 28 days after transplantation, survival rates in group 5 were 100%, 100%, and 80%; in group 6, 100%, 60%, and 40%; and in group 3, 100%, 0%, and 0%, respectively. Only the combination of portal DST and tacrolimus prevented the occurrence of, and death from, rejection. Death from rejection at 7, 14, and 28 days in group 5 was 0%, 0%, and 0%; in group 6, 0%, 33%, and 67%; and in group 3, 0%, 100%, and 100%, respectively. Of note, if immunosuppression was used, the groups with portal (versus systemic) DST had a higher risk of death from infection but a lower risk of death from GVHD. Simultaneous immunologic events were noted more frequently in groups with systemic (versus portal) DST. Long-term survival was noted only in groups with tacrolimus-based immunosuppression and was more common for those with portal (versus systemic) DST. CONCLUSIONS: Portal DST at the time of total bowel transplantation and posttransplant immunosuppression with tacrolimus prevent rejection and significantly increase graft survival. The combination of portal antigen presentation and tacrolimus needs to be studied in clinical bowel transplantation.
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Fibrillary glomerulonephritis is an uncommon disease seen in approximately 1% of all native kidney biopsy specimens. We present here a case of a 40-year-old white woman with the rapid loss of graft function secondary to fibrillary glomerulonephritis within 7 days of receiving a living-related renal allograft. This case emphasizes the values of combining urinalysis with prompt allograft kidney biopsy in recipients with an elevated serum creatinine posttransplantation. When one encounters rapidly progressing glomerulonephritis or a pulmonary-renal syndrome in the immediate posttransplantation period, fibrillary glomerulonephritis must be considered in the differential diagnosis. Because of a high recurrence rate and no available treatment to modify a potentially malignant course of this disease, we recommend caution when considering these patients for transplantation.
Endomyocardial biopsy remains the 'gold standard' for the diagnosis of acute rejection after cardiac transplantation, but few guidelines exist to determine the indications for its use in pediatric cardiac transplant recipients. To determine the usefulness of surveillance endomyocardial biopsy, 176 biopsies were reviewed from 12 patients, aged 0.5-16 (average 9.7) yr, maintained on cyclosporine, azathioprine and prednisone immunosuppression, and followed 2.8-45.5 (average 26.3) months after cardiac transplantation. Children old enough to cooperate (n = 6) underwent biopsy on nine occasions in the first 6 months after transplantation and quarterly thereafter. Children too young to cooperate (n = 6) underwent biopsy with general anesthesia on four occasions in the first 6 months after transplantation and every 6 months thereafter. Additional biopsies were performed as warranted by symptoms or noninvasive tests. A new episode of acute rejection was present in 13 biopsies (7%); continuing or resolving rejection in 19 others (11%). Remaining biopsies had no evidence of rejection (82 biopsies, 47%), had lymphocytic infiltrates insufficient for diagnosis (47 biopsies, 27%), were inadequate for diagnosis (14 biopsies, 8%), or were consistent with ischemia (1 biopsy, 0.5%). During the first 6 postoperative months, eight of 101 biopsies were positive for rejection, three occurring on routine surveillance biopsy. After 6 months, five of 75 biopsies showed a new episode of rejection, only one occurring on routine surveillance biopsy. Based on this data, it is concluded that: 1) episodes of rejection are relatively uncommon with triple drug immunosuppression; 2) surveillance biopsies in the first 6 months after cardiac transplantation may show unsuspected rejection; and 3) routine surveillance biopsies more than 6 months after cardiac transplantation are unlikely to show rejection in the absence of symptoms or other tests.