Supply and demand for liver transplant surgery: are we training enough surgeons?

The purpose of our study is to determine whether the current level of transplant fellow training is sufficient to meet the future demand for liver transplantation in the United States. Historical data from the Nationwide Inpatient Samples (NIS) for the years 1998 through 2003 were used to construct an estimate of the annual number of liver transplant procedures currently being performed in the United States, and the number projected for each year through 2020. Estimates for the current and future number of surgeons performing liver transplant procedures were also constructed using the same database. The NIS database was used because current national transplant registries do not include information on the number of surgeons performing liver transplant procedures. Using historical data derived from the NIS database, we project that the estimated number of liver transplant procedures per surgeon will remain relatively stable through 2020, with each surgeon performing an average of 12.9 procedures in 2020 compared to 12.9 currently. We conclude that the relationship between demand for liver transplantation in the United States and the supply of liver transplant surgeons will remain stable over the next 15 years.

Familial hypocalciuric hypercalcemia in the donor and recipient of a living related donor kidney transplant.

Familial hypocalciuric hypercalcemia (FHH) is caused by heterozygous inactivation of the calcium-sensing receptor, which is notably expressed in parathyroid and kidney. FHH is characterized by asymptomatic hypercalcemia and hypophosphatemia and confers minimal, if any, morbidity. Renal transplantation in patients with FHH has not been described previously. This report describes a patient with FHH who developed end-stage renal disease from another cause and subsequently received a living related donor kidney transplant from her FHH-affected daughter. The excellent posttransplant clinical course of both recipient and donor is emphasized.

Obesity predicts increased overall complications following pancreas transplantation.

PURPOSE: We sought to evaluate the role of recipient body mass index (BMI) on postoperative complications in patients receiving pancreas transplants. METHODS: A single-institution retrospective study of 145 consecutive patients undergoing either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK) transplantation from January 1997 through December 2003. Variables analyzed included: age, sex, BMI, number of prior transplants, cytomegalovirus status of donor and recipient, postoperative insulin resistance, complications, and overall patient and graft survival. Differences in continuous variables and dichotomous variables were evaluated using two-tailed t test and Fisher exact test, respectively. Univariate and multivariate logistic regression analyses were employed to identify predictors of overall complications following surgery. RESULTS: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%) had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant difference in age or sex between obese and nonobese patients (P = .98 and P = .56, respectively). The type of transplantation, SPK or PAK, did not affect the complication rate (P = .36). Overall complications (infection, dehiscence, evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis, postoperative bleeding, or death) were significantly higher in the obese group (81% vs 40%, P < .001). Obesity was specifically associated with increased frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression analysis identified age > or = 50 and BMI > or = 30 as independent predictors of overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P < .001, respectively). There was no difference identified between groups with regards to allograft failure, posttransplant insulin resistance, and death. CONCLUSION: Obese patients are at increased risk of overall complications following pancreas transplantation. Specifically, obese patients experience higher frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, and necrotizing fasciitis. This study demonstrates the need for careful postoperative monitoring in the obese patient.

The influence of combined trophic factors on the success of fetal pancreas grafts.

BACKGROUND: Fetal pancreas (FP) has the capacity for abundant proliferation and beta cell differentiation. Insulin-like growth factor-1 (IGF-1) promotes FP engraftment in the i.m. site and reversal of diabetes in a rodent model. However, reversal of diabetes by an FP transplant in rats under the influence of IGF-1 is still an inefficient process requiring multiple FP grafts and a prolonged latent period. Numerous other growth and differentiation factors, which include platelet derived growth factor (PDGF), vascular endothelial growth factor, endothelial cell growth factor-alpha and pancreatic islet neogenesis-associated protein, have been implicated in beta cell neogenesis and proliferation. We have analyzed the in vivo role of these growth factors in FP engraftment and reversal of streptozotocin-induced diabetes in rats. METHODS: IGF-1 alone or in combination with other trophic factors was locally administered to eight FP isografts in the thigh muscle of diabetic rats. RESULTS: Diabetes was reversed in a mean of 60+/-26 days in 11 of 11 animals treated with IGF-1. PDGF alone did not promote reversal of diabetes; however, PDGF + IGF-1 resulted in euglycemia in 6 of 6, with a mean of 36+/-14 days (P<0.05). Islet neogenesis-associated protein +IGF-1 resulted in reversal of diabetes in 6 of 6 rats with a mean interval of 50+/-10 days. Vascular endothelial growth factor or endothelial cell growth factor-alpha + IGF-1 provided no advantage compared with IGF-1 alone. CONCLUSIONS: These results demonstrate that IGF-1 is a potent trophic factor for transplanted FP and that PDGF acts synergistically with IGF-1 to promote reversal of diabetes by transplanting FP.

Percutaneous double-valve balloon valvotomy for multivalve stenosis: immediate results and intermediate-term follow-up.

Ten patients each with combined mitral and tricuspid stenosis (group 1) and with combined mitral and aortic stenosis (group 2) underwent double-valve balloon valvotomy as a single staged procedure. The aortic valve was dilated by the Mansfield balloon technique, whereas the mitral and tricuspid valves were dilated with either the Mansfield or Inoue balloon. The mitral valve area increased from 0.78 +/- 0.21 cm2 to 2.05 +/- 0.56 cm2 (p < 0.0005) in group 1 and from 0.75 +/- 0.20 cm2 to 2.1 +/- 0.59 cm2 (p < 0.05) in group 2. The tricuspid valve area increased from 1.11 +/- 0.41 cm2 to 2.52 +/- 0.69 cm2 (p < 0.0005). In group 2, the transaortic gradient decreased from 93.56 +/- 17.7 mm Hg to 28.56 +/- 7.8 mm Hg (p < 0.0005) and the valve area increased from 0.37 +/- 0.05 cm2 to 1.03 +/- 0.25 cm2 (p < 0.005). The excellent symptomatic and hemodynamic results were sustained at 30.3 +/- 9.8 months of follow-up in group 1 and at 23.5 +/- 9.1 months in group 2. Double-valve balloon valvotomy is feasible and safe and provides excellent immediate and intermediate-term follow-up results in selected patients with multivalve disease. A longer follow-up in a larger number of cases is needed to define further the role of this therapy.

Kidney and kidney/pancreas transplantation at Stanford University Medical Center.

The disparity between the supply of cadaveric donors and the demand for renal allografts continues to grow. We have taken a multifaceted approach to increase the allograft pool: 1. Spiral computed tomography to evaluate potential living kidney donors is safer, less invasive, less expensive and more time efficient and thus should encourage living organ donation. 2. Use of selected expanded criteria cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched recipients have short-term function at 3 and 6 months comparable to standard cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59 and with an adjusted creatinine clearance less than 90 ml/min should be used as a dual kidney transplant into an appropriate sized- and aged-matched recipient. 4. Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc grafts, when transplanted into adult recipients. Pediatric renal transplantation poses numerous challenges given the different and problematic etiologies of ESRD, the surgical considerations in small children and infants and the enhanced immune response witnessed in children. Nevertheless, renal transplantation is clearly the therapy of choice for children with ESRD and excellent results can be obtained through strict adherence to surgical detail, tight immunosuppressive management, and aggressive fluid management in infants and small children. We feel it is also critically important that transplantation and follow-up care be carried out by an integrated and experienced surgical and medical team. Managed healthcare has had profound effects on the practice and management of transplantation centers. The one area of greatest impact has been the pressure upon programs to reduce their cost of transplantation. We have initiated a number of new outpatient treatment protocols as part of an effort to contain costs. Most patients with acute rejection are evaluated (including transplant kidney biopsy) and treated in an ambulatory setting. Completion of OKT3 therapy in selected patients is also performed at home through visiting nurses or at our ambulatory care center. Additionally, treatment of CMV disease is now performed almost exclusively on an outpatient basis.

Concurrent balloon dilatation of rheumatic trivalvular stenosis.

A 26-year-old male presented with increasing dyspnoea and exertional palpitations of 2 months duration. The clinical and echo evaluation revealed severe stenosis of the mitral, aortic, and tricuspid valves. Concurrent percutaneous dilatation of all three valves was done as a single stage procedure. The procedure was successful and produced significant clinical and haemodynamic improvement. The mitral and tricuspid valves were dilated using the same Inoue balloon, whereas the aortic stenosis was dilated using the pigtail tipped balloon.

The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation.

Cell surface expression of CD45, a receptor-like protein tyrosine phosphatase (PTPase), is required for T cell antigen receptor (TCR)-mediated signal transduction. Like the majority of transmembrane PTPases, CD45 contains two cytoplasmic phosphatase domains, whose relative in vivo function is not known. Site-directed mutagenesis of the individual catalytic residues of the two CD45 phosphatase domains indicates that the catalytic activity of the membrane-proximal domain is both necessary and sufficient for restoration of TCR signal transduction in a CD45-deficient cell. The putative catalytic activity of the distal phosphatase domain is not required for proximal TCR-mediated signaling events. Moreover, in the context of a chimeric PTPase receptor, the putative catalytic activity of the distal phosphatase domain is not required for ligand-induced negative regulation of PTPase function. We also demonstrate that the phosphorylation of the C-terminal tyrosine of Lck, a site of negative regulation, is reduced only when CD45 mutants with demonstrable in vitro phosphatase activity are introduced into the CD45-deficient cells. These results demonstrate that the phosphatase activity of CD45 is critical for TCR signaling, and for regulating the levels of C-terminal phosphorylated Lck molecules.

The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction.

Engagement of the T cell antigen receptor (TCR) by peptide antigen bound to the major histocompatibility complex (MHC) molecules initiates a biochemical cascade involving protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). Recent biochemical and genetic evidence has implicated at least three cytoplasmic protein tyrosine kinases (PTKs), Lck, Fyn, and ZAP-70, that are involved in the initiation of TCR signal transduction. In addition, genetic evidence has demonstrated the requirement of the transmembrane PTPase, CD45, for TCR function. Activation of T cells through the TCR represents an alteration in the dynamic equilibrium between PTKs and PTPases. The TCR is a multi-subunit complex composed of at least six different gene products. Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the zeta chain subunits. These two modules have in common peptide sequences within their cytoplasmic domains termed antigen recognition activation motifs (ARAMs) that are responsible for transducing signaling events. Moreover, the ARAM sequence is also found in subunits associated with a variety of other hematopoietic cell antigen receptors and is likely to form the basis for interactions with effector molecules within the signaling cascades of these receptors. Here we review the mechanism by which the ARAM sequences interact with PTKs and the cascades of PTKs and PTPases that are involved in mediating TCR function.

Catheter atherectomy of intimal fibroplasia of the common iliac artery.

An 18-year-old woman presented with renovascular hypertension and left lower extremity claudication. Aorto-iliac angiography showed stenotic lesions in the left renal artery and the left common iliac artery. For uncontrolled hypertension, nephrectomy was performed and histopathology of the renal artery showed intimal fibroplasia, an uncommon type of fibromuscular dysplasia. The left common iliac artery lesions were treated with directional atherectomy, which produced excellent immediate angiographic and symptomatic improvement.

Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase.

CD45, a transmembrane protein tyrosine phosphatase (PTPase), is required for TCR signaling. Multiple CD45 isoforms, differing in the extracellular domain, are expressed in a tissue- and activation-specific manner, suggesting an important function for this domain. We report that a chimeric protein in which the extracellular and transmembrane domains of CD45 are replaced with those of the EGF receptor (EGFR) is able to restore TCR signaling in a CD45-deficient cell. Thus, the cytoplasmic domain of CD45 is necessary and sufficient for TCR signal transduction. Moreover, EGFR ligands functionally inactivate the EGFR-CD45 chimera in a manner that is dependent on dimerization of the chimeric protein. Inactivation of EGFR-CD45 chimera function results in the loss of TCR signaling, indicating that CD45 function is continuously required for TCR-mediated proximal signaling events. These results suggest that ligand-mediated regulation of receptor-PTPases may have mechanistic similarities with receptor tyrosine kinases.

Percutaneous mitral valvotomy using Inoue and double balloon technique: comparison of clinical and hemodynamic short term results in 350 cases.

The results of percutaneous mitral valvotomy (PMV) by double balloon (N = 230, Group I) and Inoue single balloon (N = 120, Group II) technique were compared. The groups were similar with respect to baseline characteristics. Following PMV there were marked symptomatic and haemodynamic benefits in both the groups. There was significant increase in mitral valve area (MVA) estimated by Gorlin's equation (Group I: from 0.83 +/- 0.18 cm2 to 2.10 +/- 0.45 cm2, p < 0.001; Group II: from 0.83 +/- 0.17 cm2 to 2.16 +/- 0.39 cm2, p < 0.001) and by echoplanimetry (Group I: from 0.84 +/- 0.18 cm2 to 1.91 +/- 0.35 cm2, p < 0.001; Group II: from 0.88 +/- 0.17 cm2 to 1.96 +/- 0.30 cm2, p < 0.001). However, the percentage increase in MVA in the two groups by echoplanimetry (Group I: 136 +/- 59; Group II: 130 +/- 51; p = NS) and by Gorlin's equation (Group I: 164 +/- 69; Group II: 168 +/- 61; p = NS) were not statistically significant. Results were considered optimal when increase in MVA was > or = 1.5 cm2, percentage increase was > or = 50, and mitral regurgitation was < 2/4. Out of 216 patients in Group I where PMV could be performed, optimal results were achieved in 184 (85.2%) by Gorlin's equation and 178 (82.4%) by echoplanimetry. In Group II, out of 116 patients, optimal results were achieved in 107 (92.2%) by Gorlin's equation and 103 (89%) by echoplanimetry. Incidence of mitral regurgitation although higher in Group II (24.1% vs. 18.9%) was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon valvotomy for mitral restenosis after open or closed surgical commissurotomy.

Balloon mitral valvotomy was performed in 48 patients (Group I) with mitral restenosis following prior surgical commissurotomy 3-21 years previously. Their results were compared with those of balloon valvotomy in 302 patients without prior commissurotomy (Group II). The procedure was successful in 91.7% of Group I. The mitral valve area, cardiac output, mitral valve gradient, mean left atrial and pulmonary arterial pressures significantly improved following valvotomy (all P < 0.001) in Group I and similar results were obtained in Group II. A comparison of the absolute and percentage change in the mitral valve area following valvotomy amongst the two groups revealed no significant difference (P = N.S.). The baseline clinical characteristics in both the groups were similar except for a higher echocardiographic score (8.64 +/- 1.5 vs. 7 +/- 1.7; P < 0.005) in Group I. Despite the high echo score, achievement of an 'optimal' result and occurrence of postprocedural mitral regurgitation were similar in both groups. The complications included systemic embolus in one patient and increase in mitral regurgitation to > or = 2+ in 2. There were no deaths. Balloon valvotomy for mitral restenosis following surgical commissurotomy is safe, effective and produces clinical and hemodynamic results comparable to those in unoperated cases.

Percutaneous mitral valvotomy in 200 patients using Inoue balloon-immediate and early haemodynamic results.

We report our experience with percutaneous balloon valvotomy using the Inoue technique in 200 cases with rheumatic mitral stenosis. The procedure was successful in 195 (97.5%) cases with a fluoroscopy time of 9 +/- 2.7 and procedure time of 60 +/- 19 minutes. Mitral valve area as estimated by Gorlin's equation and pressure half time increased from 0.86 +/- 0.17 to 2.21 +/- 0.41 and from 0.94 +/- 0.14 to 1.90 +/- 0.26 (p < 0.001) respectively. Other hemodynamic variables including mitral valve gradient, cardiac output, left atrial mean and pulmonary artery pressure improved significantly. There were no deaths and the incidence of major complications was small. Increase in mitral regurgitation was observed in 35 (17.9%) with grade 2+ increase in 7 (3.6%). Inoue balloon technique is safe, easy to perform and provides excellent clinical and hemodynamic benefits in majority of cases.

Selective coronary angiography via antegrade venous route in congenital cyanotic heart disease.

An antegrade venous technique was utilised to perform selective coronary angiography in cyanotic infants and children. The procedure was successful in 88% (37/42) cases and excellent quality angiograms were recorded. The importance of proper catheter selection and details of the technique are discussed.