Papers by Goran Klintmalm
Perfusion, 2002
We studied the effects of veno-venous bypass (VVBP) circuit surface heparinization on the activat... more We studied the effects of veno-venous bypass (VVBP) circuit surface heparinization on the activation of the plasma defence systems (coagulation, fibrinolysis, kallikrein-kinin and complement) and leukocyte activation in a prospective randomized study in 20 patients during and 1 day after liver transplantation (OLT). To our knowledge, this is the first study of this kind where the possible benefits of surface heparinization of the VVBP circuit in OLT have been investigated. Twenty patients were randomized to either heparin-coated (HC) VVBP equipment or to otherwise identical noncoated (NC) circuits. Five blood samples were drawn during the OLT procedure: one just before VVBP, three during VVBP and one 5 min after portal venous reperfusion (PVR). A further sample was taken 1 day after the operation. Components of the blood coagulation, fibrinolytic and kallikrein-kinin systems were analysed using functional assays (chromogenic peptide substrate assays) or enzyme immunoassays (EIA). Co...
Transplantation, Feb 27, 2009
Liver Transplantation Official Publication of the American Association For the Study of Liver Diseases and the International Liver Transplantation Society, Jun 1, 2007
Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver disease. Once tho... more Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long-term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) Ͼ2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10-yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non-HRS patients undergoing LT over the same study period (P ϭ 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non-HRS population (P Ͻ 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients. Liver Transpl 13: 838-843, 2007.
Cancer Medicine, 2015
Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effect... more Transplant recipients have elevated cancer risk, perhaps partly due to direct carcinogenic effects of immunosuppressive medications. Experimental evidence indicates that calcineurin inhibitors given to transplant recipients increase cellular expression of transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), which could promote cancer. To assess the potential role of these pathways in the transplantation setting, we conducted a case-control study nested in a cohort of liver recipients. Cases had nonmelanoma skin cancer (N = 84), cancer of the lung (N = 29), kidney (N = 20), or colorectum (N = 17), or melanoma (N = 3). We selected N = 463 recipients without cancer as controls. TGF-β1 and VEGF levels were measured in sera obtained, on average, approximately 3 years before case diagnosis/control selection. We also measured platelet factor 4 (PF4), a marker of ex vivo platelet degranulation, because TGF-β1 and VEGF can be released from platelets, and we developed a statistical model to isolate the platelet-derived fraction from the remaining circulating component. Compared with controls, lung cancer cases had higher levels of TGF-β1 (median 22.8 vs. 19.4 ng/mL, P = 0.02) and VEGF (277 vs. 186 pg/mL, P = 0.02). However, lung cancer cases also had higher platelet counts (P = 0.08) and PF4 levels (P = 0.02), while residual serum levels of TGF-β1 and VEGF, after accounting for PF4, were unassociated with lung cancer (P = 0.40 and P = 0.15, respectively). Associations were not seen for other cancers. In conclusion, TGF-β1 and VEGF levels were increased in association with lung cancer among transplant recipients, which may be explained by increased platelet counts and platelet degranulation in lung cancer cases.
Digestive diseases and sciences, 2003
Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United Stat... more Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United States. Previous studies had found a decreased incidence of female gynecological malignancies after liver transplantation. In order to estimate the incidence of ovarian carcinoma after liver transplantation, we evaluated 1708 consecutive liver transplant recipients from 1984 to 2001. Of them, 770 (43%) were female. Routine follow-ups were performed at 1, 2, 5, and 10 years after transplantation. There were two cases of ovarian carcinoma. Both occurred in recipients with a previous history of breast cancer. Based on these data, we conclude that the incidence of ovarian cancer is 1:385 among all female liver transplant recipients, and 1:6.5 among those with a history of pretransplant breast cancer. We recommend that regular check-ups should be undertaken, especially in the population at highest risk.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2000
The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic ... more The time progression of allograft damage in patients with recurrent hepatitis C after orthotopic liver transplantation (OLT) is not precisely determined. The aim of this analysis is to study the progression of disease recurrence and its impact on patient and graft survival. Data for 300 patients who underwent OLT for hepatitis C were analyzed regarding the incidence of histological recurrence, risk factors, immunosuppressive regimen, rejection episodes, and survival. For patients with histological recurrence, the timing and risks for disease progression were analyzed. Data for 30 patients who underwent retransplantation were studied. Histological recurrence occurred in 40.3% of patients, 27.2% of whom progressed to bridging fibrosis or cirrhosis. Eighty-seven percent of the patients experienced recurrence of disease within 24 months of OLT. Patients with histological recurrence within 6 months of OLT had an increased risk for progression to cirrhosis compared with patients with recu...
World journal of surgery, 1984
Fourteen combined cadaveric renal and segmental pancreatic transplantations with both of the orga... more Fourteen combined cadaveric renal and segmental pancreatic transplantations with both of the organs provided by the same donor were performed, and exocrine diversion was to the recipient's bowel. Nine of the grafts have failed because of technical surgical complications, and 2 grafts failed because of rejection. Three patients are carrying well-functioning grafts 6, 19, and 24 months, respectively, after transplantation. Ten of the kidneys are functioning; thus, the use of combined transplantation has not jeopardized the results of renal grafting. Patients who had functioning pancreatic grafts had normal or near-normal fasting blood glucose levels; studies of intravenous glucose tolerance test revealed k-values around or just over 1.0 and glycosylated hemoglobin levels were normal. When azathioprine was replaced with cyclosporine, 4 of 6 patients showed a significant decline in k-value. This deterioration in blood glucose control was reversible by dosage adjustment.
Lancet, Jan 27, 1984
To investigate whether cyclosporin (CsA) causes chronic renal damage 38 renal allograft biopsies ... more To investigate whether cyclosporin (CsA) causes chronic renal damage 38 renal allograft biopsies were performed 1 to 4 years after transplantation in 28 CsA-treated patients, in the absence of rejection or acute CsA nephrotoxicity. Blind, semi-quantitative light microscopic examination showed that interstitial fibrosis plus tubular atrophy occurred more often in CsA-treated patients than in patients treated with azathioprine. The degree of interstitial fibrosis correlated with high cumulative CsA dose during the first 6 months of treatment, as well as with the number of acute CsA nephrotoxic episodes, which suggests that the findings are an effect of chronic CsA nephrotoxicity. Maintenance doses of CsA (2.3-10.7 mg/kg/day) seemed to contribute little to the renal damage. The pathogenesis of the observed lesions is not known. A high trough CsA level at the time of biopsy correlated with the degree of interstitial mononuclear cell infiltrate in the renal tissue. The results thus demon...
Transplantation, 1992
A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and an... more A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from "marginal" donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donor's weight above 100 kg was the only variable found to be associated with both significantly increased 3-month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (great...
Transplantation, 1992
A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine... more A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was conv...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2002
We prospectively collected data on 1,429 liver transplant recipients between December 1984 and De... more We prospectively collected data on 1,429 liver transplant recipients between December 1984 and December 1998. Fifty-five patients (3.8%; 10 men, 45 women; median age, 44.5 +/- 13 [SD] years) with autoimmune hepatitis (AIH) underwent orthotopic liver transplantation (OLT). Transplant recipients with AIH were younger, more likely to be women, and had a greater likelihood of rejection in the first 3, 6, and 12 months. There was no difference in patient survival or graft survival. There were 11 biopsy-proven recurrences (1 man, 10 women) of AIH after OLT. Almost half the episodes occurred within the first year after OLT. No patient required re-OLT because of recurrent disease. AIH has an incidence of 4% and a recurrence rate of 20% in OLT. Transplant recipients are more likely to be young women and have an increased incidence of acute cellular rejection (ACR) during the first post-OLT year. Recurrence should be suspected in those with abnormal liver function test results in the absence ...
Proceedings (Baylor University. Medical Center), 2014
Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with t... more Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication associated with the transplant recipient. We chronicle a case of PTLD in a failed graft presenting as a small bowel obstruction in a pancreas-only transplant patient. While typical symptoms may be elusive in the complex immunosuppressed patient, graft pain along with persistent graft pancreatitis and a positive Epstein-Barr viremia should raise suspicion for an underlying PTLD.
Transplantation, 1993
The causes of graft loss in liver transplant recipients with a graft functioning for more than 1 ... more The causes of graft loss in liver transplant recipients with a graft functioning for more than 1 year post-transplant were analyzed. Of 500 liver transplants in 434 patients, 362 grafts were functioning for more than 1 year. After 1 year, 42 grafts were later lost (11.6%). Thirty-three grafts were lost by death and 9 retransplants were done with 8 patients. Of the grafts lost by death, 12 had no evidence of dysfunction. The actuarial 2- and 5-year graft survival in liver transplantation recipients with functioning grafts for more than 1 year was 91 and 83%, respectively. The graft loss rate was 3.4 times higher during the 2nd year post-transplant than during 2-5 years post-transplant. The most common causes of graft loss were chronic rejection (26.2%), recurrent hepatitis (23.8%), arterial thrombosis/stenosis (11.9%) and recurrent malignancy (9.5%). No graft was lost from acute rejection. There was no difference in timing of the graft lost between the different causes. The pretransplant diagnosis of hepatitis B, chronic rejection, and malignancy was associated with the highest frequency of late graft lost. In conclusion, long-term graft survival is good after liver transplantation in patients with a functioning graft for more than 1 year. The main causes of graft loss were chronic rejection and recurrent hepatitis. Prevention and treatment for these conditions may further improve the results after liver transplantation.
Transplantation, 2009
Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibod... more Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection. Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets. Patient enrolment was based on acceptance for transplantation determined by donor lymphocyte crossmatch results. Donor-reactive AECA were found in 35 of 147 (24%) patients. A significantly higher proportion of patients with a positive ECXM had rejections (16 of 35, 46%) during the follow-up of at least 3 months compared with those without AECA (13 of 112, 12%; P<0.00005). Both IgG and IgM AECAs were associated with graft rejections. Mean serum creatinine levels were significantly higher in patients with a positive ECXM test at 3 and 6 months posttransplant. XM-ONE is quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte crossmatches.
HPB, 2014
Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This ... more Adequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation. A retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800). Patients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001). A ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.
Transplantation, 2001
The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their us... more The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2002
The aims of this analysis are to characterize the incidence and types of malignancies and tumor-s... more The aims of this analysis are to characterize the incidence and types of malignancies and tumor-specific mortality in our institution. Retransplantation, rejection episodes, and OKT3 use were evaluated. Our single-institution prospective database of 1,570 liver transplantations in 1,421 patients was analyzed. Data were statistically analyzed regarding sex, age at transplantation, time from transplantation to diagnosis of tumor, tumor type, and follow-up time. One hundred twenty-five patients (8.8%) developed de novo tumors; 69 patients were men, 56 patients were women. Seventeen patients received more than one allograft. De novo tumors were as follows: skin, 41; lymphomas, 35; lung, 11; colon, 6; anal, 2; rectal, 1; breast, 7; thyroid, 3; oropharyngeal squamous cell, 3; metastatic without primary tumor identified, 4; renal cell, 3; Kaposi's sarcoma, 1; angiosarcoma, 1; uterine, 1; ovarian, 1; pituitary, 1; pancreatic, 2; cholangiocarcinoma, 1; and esophageal, 1. These tumors dev...
Xenotransplantation, 2007
Clinical xenotransplantation holds great promise by providing one solution to the shortage of hum... more Clinical xenotransplantation holds great promise by providing one solution to the shortage of human organs for transplantation, while also posing a potential public health threat by facilitating transmission of infectious disease from source animals to humans. One potential vector for infectious disease transmission is healthcare workers (HCW) who are involved in administering xenotransplantation procedures. In this study, we studied 49 healthcare workers involved in the care of two subjects who participated in a study of porcine liver perfusion as treatment of fulminant hepatic failure. We looked for serologic and virologic evidence of transmission of porcine endogenous retrovirus, and found that HCW had no evidence of infection. Results of our survey demonstrate that application of standard precautions may be sufficient to prevent transmission of porcine endogenous retrovirus, an agent of concern in ex vivo xenotransplantation products.
World Journal of Surgery, 1982
There has been a high incidence of tumor recurrence after liver transplantation for primary hepat... more There has been a high incidence of tumor recurrence after liver transplantation for primary hepatic malignancy. Nevertheless, a small but significant palliation has been possible with this approach, even in patients who eventually died of recurrence. Two patients with incidental malignancies in their excised livers apparently have been cured. Further gains will be possible only with extremely discriminating selection of prospective recipients.
Transplantation, 2004
Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requirin... more Background. Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. Methods. OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, nϭ637; group II: hemodialysis only post-OLTx, nϭ17; and group III: continuous RRT post-OLTx, nϭ70. Univariate and stepwise logistic multivariate analyses were performed. Results. Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplantϭ(Ϫ2.4586ϩ1.2726 [creatinine Ͼ1.9] ϩ 0.9858 [blood urea nitrogen Ͼ27] ϩ 0.4574 [Model for End-Stage Liver Disease score Ͼ21] ϩ 1.1625 [intensive care unit days Ͼ3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. Conclusions. This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.
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Papers by Goran Klintmalm