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ABSTRACT: Liver transplantation for cholangiocarcinoma has historically been maligned. Because of a high recurrence rate and poor patient survival, the disease has been viewed as an absolute contraindication to transplantation. Based on good results using neoadjuvant and palliative radiation, a protocol for liver transplantation in selected patients with unresectable hilar cholangiocarcinoma was developed in 1993. Neoadjuvant radiation is followed by operative staging to rule out patients with lymph node metastases before liver transplantation. This approach has achieved results superior to standard surgical therapy, with 72% 5-year survival for patients with unresectable disease.
Surgical Oncology Clinics of North America 05/2009; 18(2):325-37, ix. · 1.12 Impact Factor
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American Journal of Hematology 03/2008; 83(2):171. · 4.67 Impact Factor
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ABSTRACT: Resection of certain hepatic metastases of noncolorectal, nonneuroendocrine (NCNNE) origin provides actual long-term (>5 years) survival. We conducted a retrospective outcome study at a single tertiary referral institution. Between January 1988 and October 1998, 64 consecutive patients underwent resection of hepatic metastases from NCNNE primary tumors. Overall and disease-free survival rates were correlated to clinicopathologic factors and operative morbidity and mortality. Thirteen patients underwent a right hepatectomy, 6 underwent a left hepatectomy, 3 had extended right and 2 extended left hepatectomy, 2 patients had segmentectomy, 24 underwent wedge resections, and 14 underwent a combination of these forms of resection. R0 resection was achieved in 56 patients (87.5%). The operative mortality was 1.5% (1 of 64). Actual 1-, 3-, and 5-year survivals were 81%, 43%, and 30%, respectively. The factor adversely associated with overall and disease-free survival was uniformly related to the interval between primary tumor resection and the development of hepatic metastases. A 1.5% operative mortality and an actual 5-year survival of 30% justifies hepatic resection, including major hepatic resection, for certain NCNNE metastases. The factor affecting prognosis in this highly select group of patients was the biological behavior of the tumor, with tumors that metastasize earlier having poorer survival rates.
Journal of Gastrointestinal Surgery 12/2005; 9(9):1361-70. · 2.83 Impact Factor
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ABSTRACT: Compare survival after neoadjuvant therapy and liver transplantation with survival after resection for patients with hilar CCA.
We developed a protocol combining neoadjuvant radiotherapy, chemosensitization, and orthotopic liver transplantation for patients with operatively confirmed stage I and II hilar CCA in 1993. Since then, patients with unresectable CCA or CCA arising in the setting of PSC have been enrolled in the transplant protocol. Patients with tumors amenable to resection have undergone excision of the extrahepatic duct with lymphadenectomy and liver resection.
We reviewed our experience between January 1993 and August 2004 and compared patient survival between the treatment groups.
Seventy-one patients entered the transplant treatment protocol and 38 underwent liver transplantation. Fifty-four patients were explored for resection. Twenty-six (48%) underwent resection, and 28 (52%) had unresectable disease. One-, 3-, and 5-year patient survival were 92%, 82%, and 82% after transplantation and 82%, 48%, and 21% after resection (P = 0.022). There were fewer recurrences in the transplant patients (13% versus 27%).
Liver transplantation with neoadjuvant chemoradiation achieved better survival with less recurrence than conventional resection and should be considered as an alternative to resection for patients with localized, node-negative hilar CCA.
Annals of Surgery 10/2005; 242(3):451-8; discussion 458-61. · 7.49 Impact Factor
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Archives of Surgery 01/2005; 139(12):1383-4. · 4.24 Impact Factor
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ABSTRACT: Renal dysfunction early after kidney transplantation has multiple causes including ischemia-reperfusion (I/R) injury and drug-induced nephrotoxicity. This study assesses the acute nephrotoxicity of tacrolimus (Tac) and sirolimus (Sir) in a rat renal isograft model.
Lewis renal isografts and uninephrectomized rats that did not undergo transplantation were treated with various doses of Tac (0.5-5.0 mg/kg/d) or Sir (0.5-6.5 mg/kg/d). Kidneys were examined on day 14 by routine histology and immunohistochemistry for transforming growth factor (TGF)-beta1 and alpha-smooth muscle actin (SMA).
Both Tac and Sir demonstrated evidence of nephrotoxicity in the early posttransplant period including increased serum creatinine and morphologic changes in the graft including interstitial inflammation, fibrosis, and tubular vacuolization. Nephrotoxicity was most prominent in the high-dose treatment groups for both drugs and was more severe in transplanted kidneys than in uninephrectomized animals that did not undergo transplantation, suggesting an additive effect of I/R injury and drug nephrotoxicity. Both Tac and Sir increased intragraft TGF-beta1 and alpha-SMA, but there were distinct differences in the patterns of TGF-beta1 expression. Both demonstrated TGF-beta1 in tubular epithelial cells, but Sir was associated with proximal tubular TGF-beta1 localization in a bright granular pattern, whereas Tac was associated with diffuse distal tubular staining.
Both Tac and Sir may be nephrotoxic in the early posttransplant period, especially at high doses and when combined with I/R injury. Immunohistochemical localization of TGF-beta1 in the tubular cells was distinctly different with each drug, suggesting possible differences in the mechanism(s) of nephrotoxicity requiring further study.
Transplantation 09/2004; 78(3):338-44. · 4.00 Impact Factor
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ABSTRACT: Major hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma are associated with actual long-term (>5 years) survival.
Retrospective outcome study.
Single tertiary referral institution.
Between 1979 and 1997, 46 consecutive patients had resection of hilar cholangiocarcinoma by major hepatectomy, bile duct resection, and regional lymphadenectomy.
Overall survival and tumor recurrence were correlated to clinicopathological factors, operative morbidity, and mortality.
Twenty-five patients underwent left hepatectomy, 17 underwent right hepatectomy, and 4 had extended right hepatectomy. Eighteen patients underwent resection of segment 1. Negative (R0) resection margins were achieved in 37 patients (80%). The operative mortality rate was 9%, and the surgical morbidity rate was 52%. Actual 1-year, 3-year, and 5-year survival rates were 80%, 39%, and 26%, respectively. Factors adversely associated with patient survival rates included: male sex, lymph node metastases, tumor grade 3 or 4, elevated direct serum bilirubin level at diagnosis, elevated preoperative activated partial thromboplastin time, and more than 4 U of red blood cells transfused perioperatively. Tumor size and R0 resection approached significance for survival. Factors associated with tumor recurrence included: male sex, tumor grade 3 or 4, a low hemoglobin level both at diagnosis and preoperatively, and a low preoperative prothrombin time and low alkaline phosphatase level at diagnosis and preoperatively. Median time to recurrence was 3.6 years. Tumor recurrence was predominantly local and regional.
The actual 5-year survival rate of 26% justifies major partial hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma. The high frequency of local and regional recurrence warrants investigation of adjuvant therapy.
Archives of Surgery 06/2004; 139(5):514-23; discussion 523-5. · 4.24 Impact Factor
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Timothy S Larson,
Humberto Bohorquez, David J Rea,
Scott L Nyberg,
Mikel Prieto,
Sylvester Sterioff,
Stephen C Textor,
Thomas R Schwab,
Matthew D Griffin,
James M Gloor,
Yogish C Kudva,
Walter K Kremers,
Mark D Stegall
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ABSTRACT: 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.
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.
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.
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.
Transplantation 03/2004; 77(6):838-43. · 4.00 Impact Factor
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ABSTRACT: 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).
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.
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.
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.
Transplantation 03/2004; 77(6):844-9. · 4.00 Impact Factor
