Fourteen human immunodeficiency virus (HIV)-positive patients with parotid enlargement were reviewed retrospectively in order to elucidate the natural history of this clinical entity. The efficacy of fine-needle aspiration (FNA) in predicting benign nonsurgical disease was evaluated. The most common findings on FNA were proteinaceous fluid and/or epithelial cells consistent with cyst contents in 71% of the patients, followed by reactive lymphadenitis (50%), and chronic or granulomatous inflammation (21%). No evidence of malignancy was seen in any patient. These results correlated well with the histopathologic diagnosis in all operated patients. Surgery did not affect the ultimate clinical outcome. This study suggests that HIV-positive patients with isolated asymptomatic parotid swelling in the absence of other clinical features suggestive of malignancy can be followed conservatively with FNA, avoiding the risks of surgery.

Adult↗

PubMedDate not supplied

The Miami experience with almost 100 multivisceral transplants.

We report our experience with 98 patients who received primary multivisceral transplantations. Three eras can be distinguished based on the evolution of technique, immunosuppression, and monitoring: August 1994 to December 1997 (first era); January 1998 to December 2000 (second era); and January 2001 to present (third era). Sixteen patients were transplanted during the first era, 18 during the second era, and 64 during the third era. Fifty-three patients are alive with a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of mortality was infection (n = 17), followed by rejection (n = 6). Seven patients required retransplantation and five of them subsequently died. The estimated 3-year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7% for era 3. Additionally, 45.3% (29/64) of patients in the third era never developed rejection versus 23.5% (8/34) of patients in the first two eras combined. The percentage of patients who developed a moderate or severe rejection was significantly less in the third era compared with the first two eras combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of developing severe rejection showed a protective effect of the multivisceral graft (P = .0001). In conclusion, multivisceral transplantation is indicated for patients with short bowel syndrome and extended abdominal catastrophies. Evolution in surgical techniques, immunosuppression, and monitoring have improved patient survival, which is now similar to that of other complex solid organ transplants.

Cause of Death↗

PubMedDate not supplied

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Acute Disease↗

PubMedDate not supplied

International grading scheme for acute rejection in small bowel transplantation: implementation and experience at the University of Miami.

In 2003, an international collection of pathologists and clinicians proposed a unified grading system for acute cellular rejection in endoscopically derived small intestine allograft biopsies. This grading system was implemented at the University of Miami over the past 2 years and the results are presented herein. A total of 1136 small bowel allograft biopsies with sufficient tissue for analysis were obtained from 123 hospitalized, clinic, and referral patients. The overall most common diagnosis assessing all time periods was grade IND (40%), and grade 1 rejection or greater was present in 19% percent of biopsies. A suspected vascular component to the acute rejection as identified by specific mucosal vascular changes was present in 6% of cases. Clinical decision making was very consistent with different grades. Our experience has confirmed that this new grading system is reliable and identifies clinical subsets of patients that can receive different therapy. We recommend that this international grading system be implemented for acute cellular rejection in bowel allografts as a means to standardize pathological assessment of alloimmune-induced graft injury, which will allow comparisons between different centers and clinical trials.

Florida↗

PubMedDate not supplied

CD55 and CD59 deficiency in transplant patient populations: possible association with paroxysmal nocturnal hemoglobinuria-like symptoms in Campath-treated patients.

Campath-1H therapy is directed to CD52, a small mw protein that has a glycosylphosphatidylinositol (GPI) anchor, which has a conventional structure similar to other GPI anchors such as CD55 and CD59. Paroxysmal nocturnal hemoglobinuria (PNH) results when cells have a somatic defect in the synthesis of GPI anchors and lack CD55 and CD59, as well as CD52. Several patients treated with Campath developed PNH-like symptoms with hemolysis and thrombosis. These patients were followed after therapy by measurement of peripheral CD55 and CD59 levels and showed an increased number of cells deficient in the expression of these molecules. Thereafter we instituted a screening program for the presence of CD55/59 levels in all pretransplant patients. Our results show that 17.3% of all pretransplant samples contained abnormal (9.7% of samples) or slightly abnormal (7.6% of samples) levels of granulocytes deficient in CD55 or CD59. This high prevalence of CD55/59 deficiency in Campath-treated patients with PNH-like symptoms suggests that a lack of these molecules (including CD52) could predispose to a complication of this immunosuppressive therapy.

Alemtuzumab↗

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Mucosal fibrosis in intestinal transplant biopsies correlates positively with the development of chronic rejection.

Endoscopic biopsies of intestinal allografts are limited to the superficial layers of the bowel. We investigated whether the presence of mucosal fibrosis in graft biopsies was indicative of chronic allograft rejection. We examined graft biopsies of 182 intestinal transplant recipients for the presence of mucosal fibrosis. Kaplan-Meier analysis showed that within 5 years posttransplantation 33% of intestinal transplant patients had graft biopsies positive for mucosal fibrosis. Although the presence of mucosal fibrosis did not affect patient or graft survival, patients with this lesion were at higher risk of developing chronic allograft enteropathy.

Adult↗

PubMedDate not supplied

Etiology and management of alimentary tract ulcers in pediatric intestinal transplantation patients.

Patients who undergo intestinal transplantation encounter several complications in the posttransplant period, one of them being ulcer formation in the alimentary tract. During postoperative endoscopic monitoring of 112 pediatric intestinal transplantation patients at our institution, we identified chronic ulcer formation in 11 patients. There were no common or defining demographic or clinical variables that were found in the patients with ulcers. The ulcers could be located within the allograft or in native tissue. Biopsies were obtained from the ulcer edge and the intervening mucosa as well as an evaluation of possible infectious agents. The most common changes in the ulcers were compatible with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (PTLD; seven cases), acute rejection (six cases), and less commonly, infectious causes (one case). These changes could occur concomitantly and retrospective analysis after therapy showed that the ulcers could have multiple etiologies. Directed biopsies of ulcer edges often displayed morphological changes compatible with acute rejection of the graft, although some biopsies of the intervening mucosa did not show similar changes. Some patients treated based on the changes within the intervening mucosa responded well and led to resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa since pathological changes can vary depending on the underlying cause(s). Infectious agents were rarely present but could be seen superimposed with the underlying cause.

Biopsy↗

PubMedDate not supplied

Analysis of risk factors for the development of posttransplant lymphoprolipherative disorder among 119 children who received primary intestinal transplants at a single center.

UNLABELLED: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication after pediatric transplantation. We analyzed all potential risk factors to assess patient and graft outcomes of 119 children who received intestinal transplantations. MATERIALS AND METHODS: Between August 1994 and March 2005, 119 patients underwent cadaveric intestinal transplantation. Their median age at transplant was 1.4 years (range: 0.6-17), median weight was 9.5 kg (range: 4.7-67), and 57% were boys. The median follow-up among 49 ongoing survivors was 41 months (range: 4-121). All PTLD cases were biopsy proven. In the past 5 years, treatment included antiviral therapy, immunosuppression withdrawal, and use of rituximab. RESULTS: The incidence of PTLD was 11.8% (14/119). No patient experienced graft failure secondary to PTLD, while two patients died from PTLD (14.2%). The PTLD group was divided into an early onset group (<4 months, 6 of 14; 42.8%) and a late onset group (>2 years, 8 of 14; 57.2%). No patient experienced PTLD between 4 months and 2 years after transplantation. The use of OKT3 was the only significant risk factor for the development of PTLD. No factor was specifically associated with the early versus late development of PTLD. CONCLUSIONS: The only factor associated with a significantly higher risk of PTLD was the use of OKT3 to treat a rejection episode. Finally, since the the introduction of anti-CD20 antibodies as part of the treatment protocol for PTLD, the risk of death due to PTLD appears to have become manageably low.

Adolescent↗

PubMedDate not supplied

Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients.

BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody directed against the CD 52 antigen that is present on the surface of T cells, B cells, natural killer cells and monocytes. We studied its application in intestinal transplantation. METHODS: This is a retrospective review of adult patients who underwent intestinal transplantation between December 1994 and May 2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was administered as an induction immunosuppression in four doses (0.3 mg/kg), or in two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10 ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1 and group 2 patients were 57% and 70%, respectively. This difference is not statistically significant. Of 37 patients in group 2, 21 are alive. The incidence of rejection was lower in group 2 (P < .005). Average current tacrolimus level is 6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are maintained solely on tacrolimus. There was no graft versus host disease in group 2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective immunosuppression for intestinal transplantation. Incidence of rejection was less with this regimen using low maintenance tacrolimus and minimal steroids.

Adult↗

PubMedDate not supplied

Association of emergence of HLA antibody and acute rejection in intestinal transplant recipients: a possible evidence of acute humoral sensitization.

Development of HLA antibody has been associated with chronic allograft failure in kidney recipients. We tested HLA antibody in posttransplant sera of intestinal recipients: 126 sera from 28 pediatric recipients were tested for HLA antibody by flow PRA (f-PRA). Median age was 1.1 years (0.44-17). Graft types included isolated intestine (n = 6), liver and intestine (n = 3), modified multivisceral (n = 3), and multivisceral grafts (n = 16). Greater than 10% of either class I (CI) or class II (CII) f-PRA was considered positive, and >30% strongly positive. Five of 28 patients had positive f-PRA in multiple samples; the remaining 23 had either no positive or only one positive sample. Three patients had strongly positive f-PRA. Patients with multiple positive samples were recipients of two modified multivisceral and three multivisceral grafts. Only one of these patients had a positive PRA pretransplant. Cytotoxic cross-match at transplant was negative for all. The three with strongly positive f-PRA showed significant episodes of rejection around the time of positive samples. One of them who persistently had f-PRA value >80% (from day 13-113) died of refractory rejection. The other two had f-PRA of 76% and 53% during the early postoperative course with associated episodes of rejection. F-PRA value decreased with rejection therapy. Only one of the 23 patients (4%) with negative f-PRA had an episode of rejection around the time of sample collection. Development of HLA antibody after intestinal transplantation seems to have significant association with acute rejection episodes.

Adolescent↗

PubMedDate not supplied

Inclusion of spleen in pediatric multivisceral transplantation.

Inclusion of the donor spleen may be beneficial for small children who receive multivisceral transplantation (MVT) because asplenia is associated with increased risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together with multivisceral transplantation in 17 children under daclizumab induction (spleen group). The results were compared to 23 children who received multivisceral transplantation without the spleen (control group) with the same immunosuppression regimen. Median age of 17 patients who received a spleen was 0.80 years (range 0.54-1.66). Platelet counts at 30 and 60 days posttransplant were significantly lower in the spleen group (average values: day 30: 399,000 vs 636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and 60 days posttransplant were also decreased in the spleen group but the difference was not statistically significant. Median rejection-free survival was 205 days in the spleen group and 101 days in the control group (P = NS). Median length of hospital stay was 39 days in the spleen group and 61 days in the control group. With a median follow-up of 398 days (spleen group) and 1232 days (control group), 3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD), whereas 1 of 23 (4.5%) in control group did (P = NS). In one patient in each group, GVHD was fatal. No patient developed posttransplant lymphoproliferative disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group developed PTLD. One-year patient survival was 84% in the spleen group and 86% in the control group. Recipients of the spleen as part of a multivisceral graft had significantly lower platelet counts. Rejection-free survival may be prolonged, but the risk of GVHD may be increased.

Antibodies, Monoclonal↗

PubMedDate not supplied

Expanded use of multivisceral transplantation for small children with concurrent liver and intestinal failure.

Fifty-five children with liver and intestinal failure have been transplanted at our center under daclizumab induction therapy since 1998. Of those, 19 received five multiviceral transplantation (MVT), 12 liver-intestine-pancreas transplants, and 2 noncomposite liver and intestine transplants (NCLIT) before 2001 (group 1). During this period, MVT was only used in children with gastric dysmotility. After 2001, we expanded the use of MVT. Therefore, 36 children in this period (group 2) received MVT except for two who received NCLIT. Median age was 1.08 in group 1 and 1.06 in group 2. Median recipient weight was 8.2 kg in group 1 and 7.5 kg in group 2. Six-month, 1-, and 2-year patient survivals were 54%, 37%, and 32% in group 1 and 94%, 91%, and 71% in group 2 (P = .00037). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019) Four died of rejection in group 1 (21%); none died of rejection in group 2. There have been two esophago-gastrostomy strictures (one in each group) and a serious reflux of this anastomosis (group 2). Strictures were treated with balloon dilatation, and the reflux was surgically corrected. In 24 recent cases, gastro-gastric anastomosis was used in MVT with no complications to date. No pancreatic rejection was seen. Small children tolerated MVT with improved survival rates and reduced rates of rejection. Use of MVT may be considered as an alternative to liver-intestine-pancreas transplant.

Antibodies, Monoclonal↗

PubMedDate not supplied

Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

Adolescent↗

PubMedDate not supplied

Nitric oxide donor FK409 attenuates the development of neointimal hyperplasia in a rat aortic allograft model.

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Animals↗