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Biomedical subjects

A Tzakis

Publications and source records attributed to A Tzakis.

At least 253 records · Page 14Linked to original sources

Liver transplantation in patients with patent splenorenal shunts.

Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt were eliminated by division of the shunt and splenectomy in three patients and splenectomy alone in the other. All patients recovered; thus the presence of a patent Warren shunt should not be a contraindication for hepatic transplantation.

Adult↗

Liver transplantation across ABO blood groups.

Six hundred seventy-one first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of donor-recipient mismatches or incompatibilities for the ABO blood groups on graft survival. A significant advantage for ABO donor-recipient identity was found, especially in adults and for first grafts. However, a surprisingly large number of ABO incompatible grafts were successful. We recommend that nonidentical or incompatible grafts be limited to patients such as small children for whom the supply of available donors is severely limited or for patients in urgent need of transplantation or retransplantation.

ABO Blood-Group System↗

The antibody crossmatch in liver transplantation.

Six hundred sixty-seven first, second, and third orthotopic liver allografts in 520 patients were reviewed to determine the effect of recipient panel-reactive antibody (PRA) and donor-recipient antibody crossmatch on 2-year patient and liver allograft survival rates. Neither a high panel-reactive antibody nor a positive crossmatch for donor-specific preformed antibody was associated with decreased patient or liver allograft survival for primary grafts or retransplants. Two patients have been given kidney transplants immediately after a liver allograft from a donor with whom each patient had an initial strongly positive donor-specific antibody crossmatch. The liver apparently removed or neutralized circulating anti-donor antibody, since the renal allografts functioned promptly and did not experience hyperacute rejection.

Actuarial Analysis↗

Course of enterovesical fistulas in Crohn's disease.

Enterovesical fistulas occurred in 38 of 683 patients (5.6 percent) with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1977. There were 22 ileovesical fistulas, 8 colovesical fistulas, and 8 fistulas of combined ileal and colonic origin. These cases fell into three different pathophysiologic categories: 16 patients presented with sepsis after a mean duration of 7 years of Crohn's disease, 19 presented without sepsis after a mean of 10 years of disease, and 3 elderly cancer patients presented with an average 25 years disease duration. Sepsis was usually due to deep pelvic or lower quadrant abscess with spontaneous rupture into the bladder. Nonseptic fistulization was a later, more gradual process, reflecting slow penetration into the bladder from a site of chronic cicatrizing bowel disease. Cancer was a very late complication, arising in each patient from an excluded loop. Although medical treatment was successful in delaying surgery in 6 patients and obviated surgery altogether in 2 patients, 36 of 38 patients (95 percent) eventually required operation. Postoperative mortality in this series was limited to two patients (5 percent) with preoperative intraabdominal abscess and sepsis. Five other deaths, unrelated to urinary complications, were caused by intestinal cancer in three patients and by intestinal complications of recurrent Crohn's disease in two patients. The urologic course of patients with enterovesical fistula was completely benign. All operated patients were cured of their enterovesical fistulas, and no urologic sequelae developed. Subsequent reoperations that were required in 45 percent of these patients were all for recurrent bowel disease and not for fistula or other urologic problems.

Adolescent↗

Liver transplantation for hepatocellular carcinoma.

Total hepatectomy plus liver transplantation was performed on 105 patients considered unsuitable for liver resection. Postoperative 5-year actuarial survivals correlated with the pathologic stage of the tumor: stage I 75%, stage II 68%, stage III 52.1%, and stage IVA 11%. The overall 5-year survival for all patients was 36%. Nodal disease, bilobar tumor, and macroscopic venous invasion were significant poor-prognosis features. In addition, 12 patients with pT4N1M0 lesions (also stage IVA) had hepatectomy plus more extensive en bloc regional resection (Whipple procedure or cluster resection) plus transplantation in an effort to prevent local recurrence. Only 2 of these 12 patients (16.7%) are alive and free of disease after 2 years. Seven patients (58%) have died from tumor recurrence usually originating from distant metastases an average of 10.6 months after transplantation. Successful transplantation for hepatoma depends on screening programs to identify early stage disease. Successful outcome of transplantation for late stage disease, which includes most of the patients in our series, awaits the development of neoadjuvant therapy to control distant microscopic metastases, which are almost certainly present though not apparent at the time of transplantation.

Adolescent↗

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↗

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↗

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↗

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↗

Growth after intestinal transplant in children.

Intestinal transplantation has been more frequent in children with intestinal failure. However, the growth after intestinal transplantation has not been well documented. The demographics, transplant information, postoperative complications, heights, and weights were obtained retrospectively from medical records on 23 children who underwent intestinal transplantation. Z-scores were calculated from the STAT Growth-BP, based on Centers for Disease Control and Prevention growth chart (2000). Transplantations were performed between 1999 and 2004. Patient median age was 1.1 years (range 0.5 to 6.9 years). Twelve were boys and 11 girls. Seventeen children received multivisceral transplantations, one modified multivisceral transplantation, and five isolated intestinal transplantations. Baseline immunosuppression consisted of tacrolimus and corticosteroids. Daclizumab was used as induction agent in 18 patients; alemtuzumab, in five patients. Median pretransplant Z-scores were median -1.67 (n = 23) in weight, and median -3.36 (n = 21) in height. Pretransplant growth was significantly retarded. We analyzed significantly retarded patients with Z-score <-2.0. The change of weight Z-score from pretransplant was: 1.25 at 6 months (n = 11), 1.46 at 12 months (n = 10), and 2.21 at 24 months (n = 7). The change of height Z-score: 1.9 at 6 months (n = 16), 1.42 at 12 months (n = 13), and 1.51 at 24 months (n = 10). Z-score significantly improved (P < .002, ANOVA). Among the analyzed factors sex, age at transplant, length of stay, and rejection within 6 months, were not associated with catch-up growth. Children with retarded growth showed significant catch-up after successful intestinal transplantation.

Body Height↗

Renal function after pediatric intestinal transplant.

Data were analyzed from 44 patients who survived more than 2 years after intestinal transplantation performed between 1994 and 2002. Median age was 1.7 years. Tacrolimus level was defined as average tacrolimus level over 6 months. Kidney function was evaluated using a 6-month average serum creatinine. Glomerular filtration rate (GFR) was calculated with the Schwartz formula. The procedures were: isolated intestinal transplantation (n = 11), liver and intestinal transplantation (n = 9), multivisceral transplantation (n = 22), and modified multivisceral transplantation (n = 2). Forty-four patients were followed for a mean of 3.6 years on tacrolimus. Tacrolimus levels ranged between 3.5 and 19.9 ng/mL (median 14.6 ng/mL) at 0 to 6 months and 6.0 to 18.9 ng/mL (median 13.2 ng/mL) at 0 to 12 months. Pretransplant kidney function as mean GFR was 138 +/- 42 mL/min/1.73 m(2) (n = 44), posttransplant kidney function at 18 to 24 month as mean GFR was 102+/-35 mL/min/1.73 m(2) (n = 44), a value that was 81% of the pretransplant GFR (P < .0001). In an analysis of tacrolimus level versus renal function, a value greater than 13.5 ng/mL during the first 12 months was a significant predictor for impaired renal function at 2 years after transplantation (defined as average GFR less than 90 mL/min/1.73 m(2) at 18 to 24 months; P = .001). Only age among age, sex, diagnosis, transplant type, and rejection episodes showed a correlation with renal function. Renal function dropped significantly at 2 years after pediatric intestinal transplantation to 81% of the pretransplantation value. Tacrolimus level for the first 12 months seemed to predict subsequent development of renal impairment at 2 years.

Adolescent↗

Temporary elevation of serum transaminases after pediatric intestinal transplantation: incidence and clinical correlation in multivisceral transplant vs isolated intestinal transplant.

Data were gathered from the records of 51 children of median age 1.5 years who survived more than 6 months after intestinal transplantation. Abnormal liver function tests (LFTs) were defined as serum aspartate aminotransferase (AST) greater than 100 IU/L or total bilirubin greater than 2.0 g/dL lasting more than 3 days. Temporary elevation was defined when LFTs returned to normal without graft loss or death. LFT elevation at the time of transplantation was not included as a temporary LFT elevation. Median follow-up was 36 months. In multivisceral transplant recipients, all patients (n = 34) showed abnormal LFTs at transplantation that normalized within a median period of 2 days. Temporary LFT elevations were seen in 20 of 34 (59%) in multivisceral transplantation and 5 of 17 (29%) in isolated intestinal transplantation. Median length of elevation was 14 days in multivisceral transplantation and 12 days in isolated intestinal transplantation. Peak AST was 353 +/- 190 IU/dL in multivisceral transplantation and 839 +/- 605 IU/dL in isolated intestinal transplantation (P = .0059). Events associated with temporary LFT elevations in multivisceral transplantation were total parental nutrition (TPN) (n = 8), dehydration (n = 2), viral infection (n = 2), others (n = 3), and nonspecific (n = 5). Events in isolated intestinal transplantation were posttransplant lymphoproliferative disorder (n = 2), TPN (n = 1), and nonspecific (n = 2). Temporary LFT elevations were commonly seen among pediatric intestinal recipients, which correlated with events other than rejection. Approximately half of the temporary LFT elevations were associated with no significant clinical events. They resolved spontaneously. Interestingly, the peak AST value was higher in isolated intestinal transplantation compared to multivisceral transplantation.

Adolescent↗

Neurodevelopmental outcomes of infant multivisceral transplant recipients: a longitudinal study.

UNLABELLED: This longitudinal investigation compares cognitive and physical capabilities of transplant recipients, both before and after receiving an intestinal transplant. METHODS: Using the Bayley Scales of Infant Development, we conducted pretransplant and posttransplant assessments on nine children (4 males, 5 females) who received either an isolated intestine, combined intestine and liver, or multivisceral transplants, with a mean age at transplant of 18 months (range 8-29) and a mean time posttransplant of 2 months (range 1-4 months). RESULTS: Scores on the Mental Developmental Index reflected that a majority (55.6%) of patients who scored in the significantly delayed range prior to transplant remained in the significantly delayed classification after receiving a transplant. In addition, 33.3% showed a decrease in their mental classification; either from "mildly delayed" to "significantly delayed" or from "within normal limits" to "mildly delayed". Results on the Motor Developmental Index demonstrated that 78% of recipients had significant delays both before and after receiving a transplant, while 11.1% fell one standard deviation after transplantation. We found that the majority of children who experience developmental delays prior to transplant are still experiencing delays when they are discharged from inpatient care. In addition, those children receiving multivisceral transplantations, as opposed to an isolated bowel, may be at a much greater risk of developing and retaining both cognitive and physical delays. Early neurodevelopmental evaluations of these patients is essential for early parental education and compliance with early intervention services to maximize potential recovery and ability to obtain normal development.

Child Development↗

Neuodevelopmental outcomes for children transplanted under the age of 3 years.

UNLABELLED: Our previous investigations on neurodevelopmental outcomes for intestinal transplanted infants revealed that while some children were able to achieve a normal developmental outcomes, most children suffered from significant motor delays and several experienced severe cognitive delays. In our current investigation, we were especially interested in children who are transplanted before the age of 3 years because the impact of the chronic illness and nutrition impairment on the infant's developing brain may be more severe than those children who receive a liver transplant. METHODS: We evaluated 34 infants using the Bayley Scales of Infant Development. Twenty-seven children received a liver/intestine or multivisceral transplant and seven received a liver transplant. RESULTS: Comparison of the two groups revealed that children receiving an intestine/multivisceral transplant have much poorer outcomes. Seventy-four percent of these children were significantly delayed mentally compared to only 57.14% of the liver transplant infants. Furthermore, 42.86% of the liver-transplanted infants were actually functioning in the normal range posttransplant. The intestinal/multivisceral transplant infants' motor development shows the most striking difference, with 96.3% being severely delayed as compared to liver transplant infants in whom only 71% experienced serious delays. The neurodevelopmental impact of organ failure and transplant before the age of 3 years may depending on the type of organ transplant. Our study found that it may be more likely to expect a good outcome for liver transplant patients than for intestinal and multivisceral transplanted infants. This difference maybe due to the overall severity of the disease and the possible impact of nutritional deficits early in infancy.

Child Development↗

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↗

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↗

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↗

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↗