Biomedical subjects

Scott L Nyberg

Publications and source records attributed to Scott L Nyberg.

At least 19 recordsLinked to original sources

PubMed2006

Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma.

BACKGROUND: Sixty-five patients with unresectable hilar cholangiocarcinoma (CCA) have undergone orthotopic liver transplantation (OLT) after neoadjuvant chemoradiotherapy per a clinical care protocol developed in 1993. We reviewed our experience with the aim to identify clinicopathological predictors of disease recurrence. METHODS: All patients with CCA that underwent OLT at our institution between 1993 and January 1, 2006 were treated in accord with our published protocol. We analyzed multiple clinical and explant pathologic factors using Cox regression analysis. RESULTS: Sixty-five patients with CCA underwent OLT. Four patients died within six months due to postoperative complications. At last follow-up, 11 patients (17%) had developed recurrence seven to 64 months after OLT. Mean time to recurrence was 29 months, and eight patients had died from recurrent disease. Patient and disease-free survival were 76% and 60% five years after OLT. Predictors of recurrence were older age, pretransplant cancer antigen (CA) 19-9 >100 U/ml, prior cholecystectomy, mass on cross-sectional imaging, residual tumor in explant >2 cm, tumor grade and perineural invasion in explant. Underlying primary sclerosing cholangitis, percutaneous biliary intubation, gender, and other time points for CA 19-9 were not associated with recurrence. Prolonged staging-to-OLT intervals for patients transplanted after implementation of model for end-stage liver disease (MELD) showed a trend toward increased recurrence. CONCLUSIONS: Older patients and those with high CA-19.9 levels, and larger tumors are more likely to develop recurrent disease. Prolonged waiting time may emerge as a significant risk factor with longer follow-up. These findings may guide patient selection, applicability of live donor transplantation and MELD score exceptions for this aggressive protocol.

Adult↗

PubMed2006

Improving utilization of deceased donor kidneys by matching recipient and graft survival.

Younger renal transplant recipients often outlive their allografts, whereas older recipients often die before their allograft fails. Thus, our aim was to assess the utility of matching recipient and graft survival to improve allocation of deceased donor kidneys. We reviewed the records of 49,206 patients (United Network for Organ Sharing, 1995-2002). Donor grafts were stratified by Deceased Donor Score (DDS). We observed a disparity between recipient survival and renal graft survival which contributed to an annual gap between supply and demand of renal transplants. Utilization of DDS and distribution of marginal kidneys to older recipients would improve allocation.

Adolescent↗

PubMed2005

Improving the prediction of donor kidney quality: deceased donor score and resistive indices.

BACKGROUND: The deceased donor score (DDS), expanded criteria donor (ECD) definition, and resistive index (RI) were developed for pretransplant evaluation of donors. DDS and ECD are determined by a calculation of risk from donor variables, while RI is determined from flow characteristics of kidneys during machine preservation (MP). This study was designed to compare DDS, ECD status, and RI as predictors of outcome after deceased donor transplantation. We were also interested to see if DDS or ECD could identify kidneys most likely to benefit from MP. METHODS: We retrospectively reviewed 48,952 deceased donor renal transplants reported to UNOS from 1997-2002. DDS (0-39 pts.), ECD status (+ or -), and preservation technique (MP vs. cold storage [CS]) were determined in all cases. RI during MP was studied in a single-center cohort of 425 transplants. RESULTS: DDS was superior to ECD status and RI in its correlation with early and late renal function after transplantation. DDS identified a subgroup of ECD- kidneys, those with DDS > or = 20 pts, that functioned significantly below expectation and similar to ECD+ kidneys. Benefits of MP, which include improved early graft function and a trend towards longer graft survival, were greatest in the group of kidneys with DDS > or = 20 pts. CONCLUSIONS: DDS was the best predictor of outcome after deceased donor renal transplantation and may be useful in identifying kidneys most likely to benefit from MP.

Cadaver↗

PubMed2005

Living donor liver transplantation using a right lobe graft in an adult with situs inversus.

Situs inversus totalis is a rare anatomic variant in which there is a complete mirror image of the thoracic and abdominal viscera. The common association of situs inversus and biliary atresia has led to a variety of modifications of surgical techniques utilizing both living donor and deceased donor liver grafts, with mixed results in the pediatric liver transplant population. The use of a living donor liver graft in an adult with situs inversus has not yet been described. However, living donor liver transplantation (LDLT) has produced excellent results in the adult population, particularly in the cholestatic population, which may be disadvantaged by the model for end-stage liver disease system. This is the first report of a successful living donor right liver graft in an adult with end-stage liver disease secondary to primary sclerosing cholangitis and situs inversus totalis.

Anastomosis, Surgical↗

PubMed2005

Rapid, large-scale formation of porcine hepatocyte spheroids in a novel spheroid reservoir bioartificial liver.

We have developed a novel bioreactor based on the observation that isolated porcine hepatocytes rapidly and spontaneously aggregate into spheroids under oscillation conditions. The purpose of this study was to characterize the influence of oscillation frequency (0.125 Hz, 0.25 Hz), cell density (1-10 x 10(6) cells/mL), and storage condition (fresh, cryopreserved) of porcine hepatocytes on the kinetics of spheroid formation. The viability and metabolic performance of spheroid hepatocytes was also compared to monolayer culture. We observed that both fresh and cryopreserved porcine hepatocytes began formation of spheroids spontaneously at the onset of oscillation culture. Spheroid size was directly related to cell density and time in culture, though inversely related to oscillatory frequency. Spheroid formation by fresh porcine hepatocytes was associated with decreased cell death (lactate dehydrogenase release, 1.3 +/- 1.0 vs. 3.1 +/- 0.7 U/mL, P < 0.05) and increased metabolic performance (albumin production, 14.7 +/- 3.3 vs. 4.6 +/- 1.4 fg/c/h, P < 0.0001; ureagenesis from ammonia, 267 +/- 63 vs. 92 +/- 13 micromol/L/h, P < 0.001) compared with monolayer culture. In conclusion, based on the favorable properties of rapid spheroid formation, increased hepatocellular function, and ease of scale-up, the spheroid reservoir bioreactor warrants further investigation as a bioartificial liver for support of liver failure.

Albumins↗

PubMed2005

United Network for Organ Sharing's expanded criteria donors: is stratification useful?

The United Network for Organ Sharing (UNOS) Expanded Criteria Donor (ECD) system utilizes pre-transplant variables to identify deceased donor kidneys with an increased risk of graft loss. The aim of this study was to compare the ECD system with a quantitative approach, the deceased donor score (DDS), in predicting outcome after kidney transplantation. We retrospectively reviewed 49 111 deceased donor renal transplants from the UNOS database between 1984 and 2002. DDS: 0-39 points; >or=20 points defined as marginal. Recipient outcome variables were analyzed by ANOVA or Kaplan-Meier method. There was a 90% agreement between the DDS and ECD systems as predictors of renal function and graft survival. However, DDS identified ECD- kidneys (10.7%) with a significantly poorer outcome than expected (DDS 20-29 points, n = 5,252). Stratification of ECD+ kidneys identified a group with the poorest outcome (DDS >or=30 points). Predictability of early post-transplant events (i.e. need for hemodialysis, decline of serum creatinine and length of hospital stay) was also improved by DDS. DDS predicted outcome of deceased donor renal transplantation better than the ECD system. Knowledge obtained by stratification of deceased donor kidneys can allow for improved utilization of marginal kidneys which is not achieved by the UNOS ECD definition alone.

Adult↗

PubMed2005

Routine use of livers from deceased donors older than 70: is it justified?

Since 1998, our institution has routinely accepted livers from deceased donors older than 70 years for transplantation. The aim of this study was to determine whether these older donor livers should be used in a routine manner. Twenty-five patients received livers from older donors between 1998 and 2002. Older donor liver recipients' actuarial survival was 95.4% at 1 year and 89.8% at 3 years. Graft survivals were 82.7% at 1 year and 71.7% at 3 years. Five older donor liver recipients with hepatitis C had worse patient survival (80% at 1 year and 40% at 3 years) and graft survival (80% at 1 year and 20% at 3 years). In conclusion, use of livers from deceased older donors affords excellent patient and graft survival, comparable with results achieved with younger donor organs. However, use of older donor livers for patient with hepatitis C may result in worse outcome.

Actuarial Analysis↗

PubMed2004

Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus.

BACKGROUND: Sirolimus has been associated with an increased risk of wound-healing complications in several retrospective analyses. The authors compared the rates of wound-healing complications in renal allograft recipients in a prospective, randomized trial of sirolimus-mycophenolate mofetil-prednisone versus tacrolimus-mycophenolate mofetil-prednisone. METHODS: All patients received antithymocyte globulin induction. In the first phase of the study, patients (n = 77) were included regardless of body mass index (BMI). In the second phase (n = 46 patients), the authors excluded patients with a BMI greater than 32 kg/m2, and the target trough sirolimus level was lowered to 10 to 15 ng/mL (previously 15-20 ng/mL). Multivariate logistic regression analyses were performed to identify predictors of wound complications. RESULTS: Fifty-nine patients received tacrolimus and 64 received sirolimus and were included in subsequent analyses. The incidence of complications was 8% (5 of 59) in the tacrolimus group and 47% (30 of 64) in the sirolimus group (P < 0.0001). Rates of perigraft fluid collections, superficial wound infections, and incisional herniae were significantly higher in the sirolimus group. Multivariate logistic regression showed only sirolimus (P = 0.0001) and BMI (P = 0.0021) to independently correlate with complications. In the first phase of the study, the wound complication rate in the sirolimus group was 55% (21 of 38 patients). After excluding obese recipients and decreasing the target sirolimus level, the wound complication rate in the sirolimus group was 35% (9 of 26 patients; P = 0.1040). CONCLUSIONS: The use of sirolimus-based immunosuppressive regimens leads to a higher incidence of wound-healing complications and will require new approaches to patient selection and management to decrease their incidence.

Acute Disease↗

PubMed2004

Decline in native renal function early after bladder-drained pancreas transplantation alone.

BACKGROUND: Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). METHODS: Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. RESULTS: Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. CONCLUSIONS: Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.

Adult↗

PubMed2004

Pancreas-after-kidney transplantation: an increasingly attractive alternative to simultaneous pancreas-kidney transplantation.

BACKGROUND: Historically, the clinical acceptability of pancreas-after-kidney (PAK) transplantation has been hampered by relatively high acute rejection rates and lower pancreas graft survival rates when compared with the more commonly performed simultaneous pancreas-kidney (SPK) transplantation. The purpose of this study was to compare PAK transplantation to SPK transplantation in the Thymoglobulin induction era. METHODS: The authors reviewed all bladder-drained PAK (n=47) transplants receiving rabbit antithymocyte globulin induction from June 1998 to June 2002 and compared them with SPK (n=25) transplants during the same time period at their institution. The authors retrospectively studied data on demographics, patient survival, graft (pancreas and kidney) survival, complications, and biopsy-proven rejection episodes. RESULTS: The actuarial 1-year patient survival was 93% for the PAK group versus 100% for the SPK group (P =not significant [NS]). The actuarial 1-year pancreas graft survival was 87% for the PAK group versus 92% for the SPK group (P =NS). Waiting time for PAK was significantly shorter than for SPK (6.3 +/- 5.2 vs. 16.2 + -13.7 months, P <0.05). Clinical acute rejection rates were similar in the two groups (4.3% for PAK vs. 4.0% for SPK). PAK recipients demonstrated a greater decline in renal function after transplantation compared with SPK. A multivariate analysis failed to elucidate the cause. CONCLUSIONS: Newer immunosuppressive regimens allow PAK transplant patients to achieve immunologic outcomes similar to SPK transplant patients. Although the shorter waiting time and the ability to use living-donor kidneys make PAK an increasingly attractive alternative to SPK transplantation, its effect on renal allograft function deserves further attention.

Antilymphocyte Serum↗

PubMed2004

Transplantation for hilar cholangiocarcinoma.

1. Patients with primary sclerosing cholangitis (PSC) have a 8 to 12% risk of developing cholangiocarcinoma (CCA). 2. Cytologic techniques for aneuploidy such as digital image analysis and fluorescence in situ hybridization increase the detection rate for CCA. 3. Survival following resection for CCA is 20% to 40% at 5 years. 4. Survival following liver transplantation for unresectable, perihilar CCAs, mass lesion if present <3 cm, is greater than 80% at 5 years. 5. Patients with intrahepatic CCAs are not eligible for liver transplantation.

Bile Duct Neoplasms↗

PubMed2004

Assessment of donor liver steatosis: pathologist or automated software?

Steatosis in donor liver biopsy specimens has been shown to correlate with graft dysfunction after orthotopic liver transplantation. This 2-part (laboratory pilot, clinical retrospective) study compared the traditional interpretation of steatosis by a pathologist with an automated measurement determined by an image analysis system. In our pilot study, Sprague-Dawley rats were studied prospectively by feeding them a choline-deficient diet for up to 7 days. In our clinical group, data from 49 consecutive recipients of cadaveric liver transplantation were reviewed retrospectively. In both studies, the percentages of microvesicular fat, macrovesicular fat, and total fat content within liver biopsy specimens were determined by an automated image analysis software program and a pathologist using the same set of slides. The association between fat content of the donor liver and patient survival and graft survival, along with levels of aspartate aminotransferase, alanine aminotransferase, prothrombin time, and total bilirubin after transplantation, were also examined in the clinical study. A direct correlation was observed between levels of macrovesicular fat determined by a pathologist and the automated software using livers from rats fed a choline-deficient diet and livers from deceased donors. A significant association was observed between macrovesicular fat content in the donor liver biopsy and graft survival by both techniques. We conclude that an image analysis system can be used to automate the determination of fat content in liver biopsy specimens, and that its findings correlate with both the visual interpretation by a pathologist and graft survival. Further study is needed to determine the role of an automated technique in the evaluation of donor livers for transplantation.

Animals↗

PubMed2004

Histologic findings of antibody-mediated rejection in ABO blood-group-incompatible living-donor kidney transplantation.

The purpose of this study was to characterize the histology of antibody-mediated rejection (AMR) in ABO blood-group-incompatible (ABOI) kidney transplants as well as on protocol biopsies performed at the time of stable allograft function. Between 5/99 and 1/02, we performed 32 ABOI kidney transplants (13 A2, 19 non-A2 blood-group living donors). Nineteen biopsies were performed for allograft dysfunction, and 127 protocol biopsies were performed 0, 3, 7, 14, 28 days and 3 and 12 months post transplant. Twenty-five of 32 patients have functioning allografts (mean 585 days post transplant). Nine of 32 (28%) developed clinical AMR. Biopsy revealed glomerular thrombi (78%), mesangiolysis (78%), peritubular capillary C4d staining (56%) and neutrophil infiltration (67%), interstitial hemorrhage and necrosis (56%) and arteriolar thrombi (33%). Subclinical AMR was diagnosed by protocol biopsies in four patients. Findings consisted of glomerular thrombi (100%), mesangiolysis (25%), and C4d staining (100%). In late protocol biopsies performed 214-420 days post transplant, mild mesangiolysis was seen in 2/17 (11.7%), and C4d immunostaining was detected in 3/12 (25%). AMR is characterized by glomerular thrombi, mesangiolysis, peritubular capillary neutrophil infiltration interstitial hemorrhage, necrosis, and C4d deposition. Glomerular thrombi appear early in AMR and may appear prior to graft dysfunction.

ABO Blood-Group System↗

PubMed2004

Liver transplantation for unresectable perihilar cholangiocarcinoma.

Patients with unresectable, stage I and II perihilar cholangiocarcinoma were treated with neoadjuvant external beam irradiation, brachytherapy, and 5-fluorouracil and/or oral capecitabine prior to liver transplantation. Fifty-six patients underwent treatment between 1993 and 2003. Four patients died and 4 had disease progression prior to completion of neoadjuvant therapy. Forty-eight patients underwent operative staging and 14 had findings precluding transplantation. Twenty-eight patients underwent transplantation and 6 patients are awaiting transplantation. Three patients died from perioperative complications, and 4 developed recurrent disease 22 to 63 months after transplantation. Actuarial patient survival was 54% at 5 years for all 56 patients, 64% for 48 operatively staged patients, and 84% for 34 patients with negative staging operations. Actuarial survival was 88% at 1 year and 82 % 5 years after transplantation. Neoadjuvant chemoradiotherapy with liver transplantation achieves excellent results for patients with localized, regional lymph node negative, hilar cholangiocarcinoma.

Adult↗

PubMed2004

Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure.

OBJECTIVE: The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. METHODS: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. RESULTS: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n = 147; P = 0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio = 0.56; P = 0.048). CONCLUSIONS: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Adolescent↗

PubMed2004

What's the score?

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Age Factors↗

PubMed2004

Patient and graft outcomes from older living kidney donors are similar to those from younger donors despite lower GFR.

BACKGROUND: Donor age adversely affects deceased-donor kidney transplant outcomes, but its influence on living-donor transplantation is less well characterized. METHODS: Living-donor kidney transplants at a single center between 1998 and 2000 were reviewed. Data were abstracted for 52 transplants from donors aged > or =50 years and for a matched group of 104 transplants from donors aged <50 years. Survival indices were compared during the first three years' post-transplantation. Functional indices, including serial iothalamate clearances, were compared at 1, 12, and 24 months. RESULTS: Predonation glomerular filtration rate (GFR) was lower among older donors (94 +/- 12 vs. 108 +/- 17 mL/min/SA) but post-transplant compensatory hypertrophy was similar (11.7 +/- 26.3% vs. 7.7 +/- 31.4%). Recipients of older-donor grafts were older (52.8 +/- 16.5 vs. 46.1 +/- 15.1 years) and more frequently unrelated to the donor (54% vs. 39%). Trends toward higher frequency of slow graft function, cytomegalovirus (CMV) infection, and polyomavirus nephropathy were observed for older-donor grafts. Three-year recipient, graft, and death-censored graft survivals were > or =90% for both groups. At 1, 12, and 24 months, serum creatinine was higher and GFR was lower among recipients of older- compared with younger-donor grafts. Other functional indices (urine total protein, serum potassium and uric acid, hemoglobin, and number of antihypertensives) were not different. Donor age correlated with graft GFR at 1, 12, and 24 months for the entire study cohort by linear regression. CONCLUSION: Older donor age does not preclude excellent results from living-donor kidney transplantation but should be appreciated as being associated with relatively lower GFR.

Adolescent↗

PubMed2004

MELD and other factors associated with survival after liver transplantation.

Allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the model for end-stage liver disease (MELD) score, a function of bilirubin, creatinine and international normalized ratio (INR). The aim of our study was to determine the association of various pre-transplant risk factors, including the MELD score, on patient survival after orthotopic liver transplantation (OLT). The medical records of 499 consecutive patients (233 female, 266 males, mean age 50.9 +/- 10.6 years) undergoing cadaveric OLT at our institution between June 1990 and February 1998 were reviewed. In the 407 patients alive at the latest contact, follow-up was 4.7 years, with a minimum of 20 months (maximum of 9.4 years). Variables considered for analysis included MELD score, age, pre-transplant renal dysfunction requiring dialysis, Child-Pugh classification, underlying liver disease, diabetes mellitus, and heart disease (ischemic/valvular/other). There were 92 deaths during follow-up. In univariate analysis, the MELD score, renal failure requiring hemodialysis pre-OLT, age > 42 years, and underlying etiology of liver disease were significantly associated with death during long-term follow-up. In multivariate models, age, underlying etiology of liver disease and renal failure requiring hemodialysis were independent predictors of death after OLT.

Female↗