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Biomedical subjects

Gabriel E Gondolesi

Publications and source records attributed to Gabriel E Gondolesi.

At least 19 recordsLinked to original sources
PubMed2006

End-to-end portocaval shunt for venous drainage of the native foregut in combined liver-intestinal transplantation.

An end-to-side portocaval shunt has been classically described as the standard procedure that needs to be performed to obtain adequate venous drainage of the foregut in combined liver-intestinal transplant. The transplanted organs are placed en bloc in a piggyback fashion on the recipient's vena cava, and graft's porto-mesenteric venous circulation is left intact. Recurrent portal hypertension with hemorrhage has been reported as a complication after such a procedure. In an effort to improve the technical aspects of this complex operation, we began to perform an end-to-end shunt from the recipient portal vein to the infrahepatic donor cava. Here, we describe this new surgical technique and discuss its potential advantages. The new technique is described in detail. Of the 70 intestinal transplants performed in 67 patients at The Mount Sinai Hospital from 1998 to December 2004, three were multivisceral transplants (MVTx) and 28 were combined liver intestine transplants (LITx), post-surgical outcome including recurrent portal hypertension and the presence of splenomegaly and significant thrombocytopenia was retrospectively review between the group that received the classic end-side vs. the new end-end portocaval shunt. Of the 28 LITx, 23 were done with the classic end-side portocaval shunt and in five (one adult, four pediatric) the end-to-end portocaval shunt described in the present study. One patient in this group died on post-operative day 31 (adult); after a mean follow up of 19.5 months there is a 100% patient and graft survival for the pediatric population. Post-operatively there have been no complications related to this technique. Few modifications have been made to the original description of MVTx. This is the first description of this technique that is relatively simple to perform, creating a large vascular conduit with high flow rates and theoretically less turbulence compared with the end-to-side shunt.

Adult↗
PubMed2005

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts.

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.

Adult↗
PubMed2005

Marked Differences in acute cellular rejection rates between living-donor and deceased-donor liver transplant recipients.

BACKGROUND: : Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients. METHODS: : Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling. RESULTS: : Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05). CONCLUSIONS: : Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity.

Acute Disease↗
PubMed2005

Liver-intestine transplant from a pediatric donor with unrecognized mitochondrial succinate cytochrome C reductase deficiency.

The demand for pediatric solid organs for transplantation exceeds the available supply. Transplant surgeons may elect to use organs from a donor whose cause of death is uncertain, especially when the recipient is deteriorating. In such circumstances, it is possible that organs from a patient with a systemic metabolic disorder may be transplanted into the recipient, leading to an adverse outcome. We report the first case in which liver and small bowel were procured from a donor with an unsuspected mitochondrial respiratory transport chain defect (succinate cytochrome C reductase deficiency). We describe the subsequent course of the recipient, who died 10 weeks later of multiorgan failure, and unusual findings at autopsy. In the absence of a clear cause of death in a potential pediatric organ donor, factors such as parental consanguinity should prompt physicians to acknowledge the increased possibility of an inherited metabolic disorder and to take this into consideration before proceeding with the transplant procedure.

Electron Transport Complex III↗
PubMed2005

Characteristics of human calicivirus enteritis in intestinal transplant recipients.

OBJECTIVES: The human caliciviruses, which include Norwalk-like viruses (or Noroviruses) and Sapporo viruses, commonly cause epidemic and endemic viral gastroenteritis of short duration in healthy individuals. However, the impact of human calicivirus in immunosuppressed populations has not been established. The authors report five pediatric patients who developed human calicivirus enteritis after intestinal transplantation. METHODS: Infection was documented with repetitive reverse transcription polymerase chain reaction testing with nucleotide sequencing of tissue and lumen fluid specimens. RESULTS: A single strain, type Miami Beach, affected all patients in the hospital with an apparent index case. A potential mode of transmission was not defined. Severe osmotic or secretory diarrhea necessitated intravenous fluid therapy for 40 days or more in three of the five infants. Concurrent or recent subclinical allograft infection with adenovirus in two patients was associated with more severe symptoms. Virus excretion exceeded 80 days in two patients. Differentiation of human calicivirus enteritis from allograft rejection was difficult, as both disorders were associated with increased enterocyte apoptosis and inflammation. Intensification of immunosuppressive therapy because of suspected rejection appeared to prolong symptoms. CONCLUSION: These findings demonstrate that human calicivirus can be a significant pathogen in intestinal transplant recipients and potentially in other immunocompromised patients.

Age Factors↗
PubMed2004

Biliary complications in 96 consecutive right lobe living donor transplant recipients.

BACKGROUND: Biliary reconstruction represents one of the most challenging parts of right lobe (RL) living donor liver transplantations (LDLTs). Different causes, surgical techniques, and treatments have been suggested but are incompletely defined. METHODS: Between June 1999 and January 2002, 96 RL LDLTs were performed in our center. We reviewed the incidence of biliary complications in all the recipients. RESULTS: Roux-en-Y reconstruction was performed in 53 cases (55.2%) and duct-to-duct was performed in 39 cases (40.6%). Both procedures were performed in 4 cases (4.2%). Multiple ducts (> or =2) were found in 58 grafts (60.4%). Thirty-nine recipients (40.6%) had 43 biliary complications: 21 had bile leaks, 22 had biliary strictures, and 4 had both complications. Patients with multiple ducts had a higher incidence of bile leaks than those patients with a single duct (P=0.049). No significant differences in complications were found between Roux-en-Y or duct-to-duct reconstructions. Freedom from biliary complications was 59% at 1 year and 55% at 2 years. The overall 1-year and 2-year survival rates for patients were 86% and 81%, respectively. The overall 1-year and 2-year survival rates for grafts were 80% and 77%, respectively. Occurrence of bile leaks affected patient and graft survival (76% and 65% 2-year patient and graft survival, respectively, vs. 89% and 85% for those without biliary leaks, P=0.07). CONCLUSIONS: Despite technical modifications and application of various surgical techniques, biliary complications remain frequent after RL LDLT. Patients with multiple biliary reconstructions had a higher incidence of bile leaks. Patients who developed leaks had lower patient and graft survival rates.

Bile Duct Diseases↗
PubMed2004

Thrombotic microangiopathy associated with combined sirolimus and tacrolimus immunosuppression after intestinal transplantation.

Calcineurin inhibitor-induced thrombotic microangiopathy (TMA) has been described in up to 14% of solid-organ transplant recipients. Sirolimus has recently been described in two reports in association with TMA. Sirolimus is known to potentiate cyclosporine-induced nephrotoxicity, but such effect has not been shown with tacrolimus. We report two intestinal transplant patients who developed TMA while on a tacrolimus and sirolimus immunosuppressive regimen. This syndrome appeared soon after institution of or increase in sirolimus dosage and improved only after this medication was discontinued.

Adult↗
PubMed2004

Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis.

Very little is known about the natural history, effects of therapy, and survival after recurrence of hepatocellular carcinoma (HCC) after liver transplantation. All adult patients undergoing liver transplant from September 19, 1988, until September 19, 2002, were reviewed. Only patients with histologically proven HCC in the explant who subsequently developed recurrence were included in further analysis. The endpoints analyzed were survival from time of transplant and survival from time of recurrence. Recipient demographics and laboratory values, technique of transplant (whole cadaver, split, or living donor), and tumor characteristics were analyzed. The time to, location of, and any medical or surgical treatment of recurrences also were considered. Of the 311 patients with HCC in the explant, 57 (18.3%) eventually were diagnosed with recurrent tumor after transplant. Median time to recurrence was 12.3. Five-year survival was significantly lower for patients with recurrence (22%) than for patients without recurrence (64%)(P < 0.0001). Multivariate analysis demonstrated that the size and differentiation of the original tumor, as well as the presence of bone recurrence, were independently associated with survival from transplant in patients with recurrence. When survival from the time of recurrence was analyzed, multivariate analysis showed that the absence of bone metastases, recurrence more than 12 months from transplant, and surgical treatment of the recurrence were independently associated with significantly longer survival. In conclusion, recurrence of HCC significantly shortens survival after transplant. Nonetheless, some patients with recurrence can be expected to live for a considerable period of time. Recurrent disease should be treated surgically when possible, because surgery is independently associated with longer survival.

Aged↗
PubMed2004

Anatomic variations in right liver living donors.

BACKGROUND: Anatomic knowledge is crucial in right liver living donor transplantation. STUDY DESIGN: We reviewed radiologic and surgical findings in right liver donors. Arterial and portal anatomy was assessed in 96 donors, biliary anatomy in 77, and hepatic venous anatomy in 65. RESULTS: Portal vein (PV): 86.4% had classic anatomy; 6.3% had a trifurcated PV; 7.3% had a right anterior PV taken off the left PV. Hepatic artery (HA): 70.8% had classic anatomy; 12.5% had a left HA arising from the left gastric artery; 13.5% had a right HA arising from the superior mesenteric artery; 2.1% had a double replaced left HA and right HA; and in 1.0% the common HA arose from the superior mesenteric artery. Biliary tree: 55.8% had normal anatomy; 14.3% had a trifurcated biliary anatomy; in 5.2% the right anterior bile duct and in 15.6% the right posterior bile duct opened into the left bile duct; in 2.6% the right anterior and in 6.5% the right posterior ducts opened into the common bile duct. Hepatic veins: S5 and S8 accessory hepatic veins had incidences of 43% and 49%, respectively. The incidence of S6 or S7 short hepatic vein was 38%. CONCLUSIONS: Anatomic variations are common but do not contraindicate donation; surgeons should be prepared to recognize and manage them.

Adult↗
PubMed2004

Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease.

BACKGROUND: Acute renal failure (ARF) occurs in 5-50% of patients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT. METHODS: We studied all OLT recipients between 9/1/1988 through 12/31/2000. RESULTS: A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post-operatively. One hundred and twenty-three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1-12 yr). Forty-three patients (23%) developed ESRD over median of 3.79 yr (range 1-8 yr). Multivariate logistic regression analysis revealed creatinine levels > 1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre-OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005). CONCLUSIONS: Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre-OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher 10-yr survival rates when compared with patients maintained on dialysis.

Acute Kidney Injury↗
PubMed2004

Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria.

INTRODUCTION: For patients with hepatocellular carcinoma (HCC) in particular, living donor liver transplant (LDLT) improves access to transplant. We report our results in 36 patients with HCC who underwent LDLT with a median follow-up >1 year. METHODS Underlying diagnoses included: hepatitis C (24), hepatitis B (9), cryptogenic cirrhosis (1), hemochromatosis (1), and primary biliary cirrhosis (1). Patients with tumors >or= 5 cm received IV doxorubicin intraoperatively and 6 cycles of doxorubicin at 3-week intervals. Patients were followed with CT scan and alpha-fetoprotein levels every 3 months for 2 years posttransplant. Mean waiting time, pretransplant treatment, tumor variables, and survival were analyzed. Univariate and multivariate analysis were done to analyze tumor variables; Kaplan-Meier and log rank were used to compare survivals. P < 0.05 was considered significant. RESULTS Mean wait for LDLT was 62 days, compared with 459 days in 50 patients with HCC transplanted with cadaveric organs during the same time period (P = 0.0001). At median follow-up of 450 days, there have been 10 deaths due to non-tumor-related causes and 3 deaths from recurrence; recurrence has also been observed in 3 other patients. On univariate and multivariate analysis, bilobar distribution was the only significant tumor variable (P = 0.03, log rank = 0.02). Fifty-three percent of patients exceeded UNOS priority criteria. One- and two-year patient survivals were 75% and 60%, respectively. Freedom from recurrence at 365 and 730 days was 82% and 74%, respectively. Overall and in patients with HCC > 5 cm (n = 12), there were no statistically significant differences in survival or in freedom from recurrence between recipients of living donor and cadaveric grafts. CONCLUSION Although one third of patients had tumors > 5 cm, the incidence of recurrence as well as patient survival and freedom from recurrence are comparable to results after cadaveric transplant. LDLT allows timely transplantation in patients with early or with large HCC.

Adult↗
PubMed2004

Defining normal plasma citrulline in intestinal transplant recipients.

Biopsy is the only means to identify intestinal graft rejection. Plasma citrulline (P-Cit) has been proposed as a marker for rejection after intestinal transplant (IT), but normative data is lacking. We analyzed P-Cit in IT recipients without rejection or other histological abnormalities. In 40 patients, P-Cit was measured with a Beckman amino acid analyzer within 24 h of protocol or clinically indicated endoscopic biopsy procured > 6 and < 360 days post-IT. Measurements included for analysis corresponded to normal (or minimally abnormal) biopsies that remained so for 7 days. These criteria were met by 145 samples from 10 adults and 14 children. Overall mean P-Cit (nmol/mL) was 34.0 +/- 19.9. Mean P-Cit was 22.2 +/- 13.2 between 6 and 30 days post-IT, 34.9 +/- 17.2 (p = 0.001) between 30 and 60 days, 43.6 +/- 15.8 between 60 and 90 days (p = 0.001), then stable until the end of the first year. Plasma citrulline was lower in 13 patients with body surface area (BSA) < or = 1 m2 vs. 11 patients with BSA > or = 1.1 m2 (p = 0.0001). Plasma citrulline increased linearly during the first 120 days in both BSA groups (r = 0.573 and r = 0.512; p = 0.0001). Within 3 months after IT, variations in P-Cit based on body size and postop interval should be considered when evaluating the need for histological confirmation of graft dysfunction.

Biopsy↗
PubMed2004

Medication adherence in pediatric and adolescent liver transplant recipients.

OBJECTIVE: Nonadherence to medications is a leading cause of morbidity in children and adolescents who have had a transplant, yet there are no published data about the use of different methods for detecting whether these children are taking their medications. There are also no published data about the age of transition at which a child assumes responsibility over taking the medications. This information is important if interventions to improve adherence are contemplated. METHODS: We present an analysis of data obtained in the first year of the implementation of an adherence assessment protocol at a pediatric liver transplant clinic in a tertiary medical care center. Data were obtained for children and adolescents who had a liver transplant at least 1 year before the assessments took place. We used 5 adherence detection methods. The 4 subjective methods were self-reported, scaled questionnaires answered by nurses, physicians, caregivers, and patients. For the objective method, a standard deviation (SD) was calculated for tacrolimus blood levels obtained from each patient over time. A higher SD suggests increased variation among patients' blood levels and hence more erratic medication taking. We also asked the patients and caregivers who is responsible for taking the medications and what are the reasons for not taking them. The medical outcome measures were biopsy-proven rejection episodes, number of biopsies regardless of the results, number of hospital admissions, and number of in-patient days. RESULTS: An analysis of 81 cases (258 assessments) revealed that the only method that predicted the medical outcome variables (biopsy-proven rejection and number of biopsies) was the SD of medication blood levels. Patients', clinicians', and caregivers' reports were not predictive. Clinicians' ratings of adherence were not correlated with patients' or caregivers'. The transition of responsibility for medication taking occurred approximately at the age of 12 years. Forgetfulness was cited as the most common reason for nonadherence by patients and caregivers; medication side effects were not frequently cited. CONCLUSIONS: Our results indicate that clinical impression is not sufficient to determine whether children and adolescents are taking their medications after they have had a liver transplant. An objective assessment method should be used. Interventions targeting adherence should address the child's increasing role beginning in early adolescence. A clinical protocol incorporating objective assessments of adherence could potentially be implemented in other settings. It could form the basis for the evaluation of efficacy of interventions seeking to improve adherence to medications.

Adolescent↗
PubMed2003

Isolated intestinal transplantation: proof of clinical efficacy.

BACKGROUND AND AIMS: Isolated intestinal transplantation has been limited by poor patient and graft survival. If high survival could be achieved and if parenteral nutrition-associated liver disease were reversible, this procedure could be more widely applied, with early liver dysfunction indicating the need for transplant evaluation. METHODS: Twenty-six patients who had failed parenteral nutrition received 28 isolated intestinal transplants. We analyzed patient and graft survival, the effect of sirolimus on the severity and frequency of rejection, and the reversibility of liver dysfunction after transplant. RESULTS: Three-year actuarial patient and primary graft survival were 88% and 71%, respectively. Two patients underwent successful retransplants. Twenty-two patients are alive at a mean of 21+/-15 (median 18; range 3-51) months. Actuarial survival with freedom from parenteral support is 81% at 3 years (21 of 26 patients). Actuarial freedom from parenteral support among survivors is 95.5% at 3 years (21 of 22 patients). Early rejection was less frequent with sirolimus (34% vs. 70% without sirolimus) (P=0.007). Moderate and severe rejection was less frequent with sirolimus (1/11 episodes vs. 9/17 episodes without sirolimus) (P=0.05). No grafts were lost after introduction of sirolimus. In all four patients with advanced liver dysfunction, fibrosis and cholestasis regressed within 1 year. CONCLUSIONS: High patient survival and parenteral nutrition-free survival can be achieved after isolated intestinal transplantation. Sirolimus treatment has eliminated graft loss. Parenteral nutrition-associated liver disease is reversible with intestinal transplantation. Refractory liver dysfunction in patients receiving parenteral nutrition should prompt consideration for isolated intestinal transplantation.

Adult↗
PubMed2003

Adenovirus infection in pediatric small bowel transplantation recipients.

BACKGROUND: The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small bowel transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome. METHODS: Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays. RESULTS: All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01). CONCLUSIONS: Adenovirus was commonly isolated from children undergoing intestinal transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.

Adenoviridae Infections↗
PubMed2003

Combined adult-to-adult living donor right lobe liver transplantation and pancreatoduodenectomy for distal bile duct adenocarcinoma in a patient with primary sclerosing cholangitis.

BACKGROUND: Liver transplantation is the best therapeutic option for patients with end-stage liver disease from primary sclerosing cholangitis. Primary sclerosing cholangitis is associated with a markedly increased risk of cholangiocarcinoma, which adversely affects survival. Approximately 20% to 30% of cholangiocarcinomas are localized in the distal bile duct. Pancreatoduodenectomy is the curative therapy for cholangiocarcinomas in this location. STUDY DESIGN: We reviewed our data on a patient with primary sclerosing cholangitis-related end-stage liver disease and a simultaneous distal bile duct tumor, which was treated with a combined right-lobe, living-donor liver transplantation and pancreatoduodenectomy. RESULTS: The patient was discharged 32 days post-transplantation. He is currently alive 1 year after the procedure with no evidence of recurrent cancer. CONCLUSIONS: Combined living-donor liver transplantation and pancreatoduodenectomy is feasible and allows timely and elective surgical control of carefully selected distal bile duct tumors in the setting of end-stage liver disease.

Bile Duct Neoplasms↗