RESUMEN
Everolimus (EVL) has shown a potential to reduce nephrotoxicity associated with cyclosporine (CsA) while providing similar protection against rejection. We analyzed the incidence of acute rejection episodes (ARE) among 20 cadaveric renal transplant recipients treated with the combination of EVL + CsA. Immunosuppression consisted of basiliximab induction given pretransplant and on day 4 posttransplant; EVL at a starting dose of 1.5 mg/day followed by concentration control to trough levels of 3 to 8 ng/mL by day 7; CsA at a starting dose of 4 mg/kg per day and then concentration controlled with C2 monitoring (C2 500-700 ng/mL); and steroids in a tapering regimen to reach 5 mg by day 30. The overall incidence of ARE was 25%. On postoperative day 7, patients with ARE showed significantly lower mean EVL trough concentrations compared with those not experiencing ARE (NO ARE: 2.2 +/- 2.1 ng/mL vs 4.8 +/- 2.4 ng/mL) (P = .05). The CsA C2 values were close to the lower end of the target range on day 3 (583 +/- 334 ng/mL). All rejecting grafts were functioning at 3 months posttransplantations, but mean serum creatinine was higher in the ARE group (ARE 2.2 +/- 0.7 mg/dL vs 1.1 +/- 0.2 NO ARE; P = .04). In conclusion, whenever EVL is used in combination with CsA to protect kidney transplant patients against the risk of acute rejection, a threshold of 3 ng/mL must be reached in the first week posttransplantation. We suggest careful monitoring of EVL exposure and increased EVL starting doses.
Asunto(s)
Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Sirolimus/análogos & derivados , Formación de Anticuerpos , Autoanticuerpos/sangre , Biopsia , Everolimus , Rechazo de Injerto/epidemiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Trasplante de Riñón/patología , Sirolimus/uso terapéuticoRESUMEN
BACKGROUND: Cytomegalovirus (CMV) disease represents a major cause of post-transplantation morbidity and mortality. To estimate the risk of infection and monitor response to antiviral therapy, current guidelines suggest combination of viral load monitoring with direct assessment of CMV-specific immune response. We used enzyme-linked immunospot (ELISpot) for the evaluation of CMV-specific T-cell response in kidney transplant recipients with CMV viremia and investigated how information gained could help manage CMV infection. METHODS: Seventeen patients on pre-emptive antiviral therapy and CMV quantitative polymerase chain reaction (qPCR) ≥500 copies/mL (first episode after transplantation) were assessed using ELISpot and divided into Weak (9 patients with baseline ELISpot <25 spot-forming colonies [SFCs]/200,000 peripheral blood mononuclear cells [PBMCs]) and Strong Responders (8 patients with baseline ELISpot ≥25 SFCs/200,000 PBMCs). CMV-specific T-cell response, infection severity, viral load, and antiviral therapy were prospectively recorded and compared between groups at 1, 2, and 24 months of follow-up. RESULTS: Demographic and transplant characteristics of Weak and Strong Responders were similar. No episodes of CMV disease were observed. Weak Responders were more likely to experience CMV syndrome (56% vs 36.5%) and late virus reactivation (56% vs 25%) than Strong Responders. Weak Responders showed higher baseline median viral loads (19,700 vs 9265 copies/mL) and needed antiviral therapy for longer (179 vs 59.5 days). T-cell response showed 2 main patterns: early and delayed. CONCLUSIONS: ELISpot provides prognostic information about infection severity, risk of late reactivation, and response to therapy. Randomized trials, evaluating the need for antiviral therapy in kidney transplant recipients with asymptomatic infection and effective virus-specific T-cell immune response, are warranted.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/inmunología , Citomegalovirus/inmunología , Ensayo de Immunospot Ligado a Enzimas , Trasplante de Riñón , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Humanos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Linfocitos T/inmunología , Carga Viral , Viremia/tratamiento farmacológicoRESUMEN
Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.
Asunto(s)
Ciclosporina/efectos adversos , Diabetes Mellitus/epidemiología , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Sirolimus/efectos adversos , Adulto , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios RetrospectivosRESUMEN
Lymphocele is a complication of renal transplantation, representing a lymphatic collection around the grafted kidney. The use of the immunosuppressive agent sirolimus (SRL) has been associated with a significant increase in lymphocele formation. This complication has been related to the antiproliferative activity of SRL, which delays surgical wound repair and closure of injured lymphatic vessels. The aim of this study was to relate the incidence of lymphocele with immunosuppression among 158 renal transplant patients operated with routine closure of all the visible lymphatic vessels around the iliac vessels and at the renal hilum. The incidence of lymphocele was not significantly different among the various immunosuppressive regimens.
Asunto(s)
Enfermedades Renales/cirugía , Trasplante de Riñón/efectos adversos , Linfocele/etiología , Drenaje , Humanos , Inmunosupresores/efectos adversos , Incidencia , Linfocele/epidemiología , Complicaciones Posoperatorias/epidemiología , Terapia de Reemplazo Renal , Sirolimus/efectos adversosRESUMEN
We report two kidney transplant recipients who developed severe limb lymphedema under sirolimus (SRL) immunosuppression. The patients received SRL 10 and 2 mg/d to achieve target levels of 10 to 20 ng/mL with tapering doses of prednisone. Renal function and drug levels were monitored monthly. Patient 1 developed lymphedema of the left upper limb 3 years posttransplantation, after having been exposed to high SRL doses in the preceding 2 years (mean SRL dose-9.5 mg/d, mean trough level-26.3 ng/mL, mean serum creatinine-1.63 mg/dL). In patient 2 lymphedema of both upper and lower right limbs occurred 18 months posttransplantation (mean SRL dose-3.2 mg/d, mean trough level-8.8 ng/mL, mean serum creatinine-2.9 mg/dL). Hypercholesterolemia and hypertriglyceridemia were also observed in both patients before SRL reduction/conversion. No signs of hematopoietic toxicity were observed. In both patients magnetic resonance (MR) angiography of the limb was negative for vascular obstruction, and lymphoscintigraphy revealed lymphatic obstruction. In patient 1 lymphedema improved significantly following SRL reduction and lymphatic drainage massage therapy. Patient 2 was converted to cyclosporine (CsA) improving markedly after conversion. Hypercholesterolemia and hypertriglyceridemia also improved significantly in both patients after reduction/conversion. We conclude that SRL may facilitate the occurrence of lymphatic obstruction by mechanisms that are presently unexplained. Lymphedema of the limbs in renal transplant recipients under SRL treatment, especially if on the same side as the hemodialysis access, should warn the transplant physician to rapidly reduce or withdraw SRL before the occurrence of complete obstruction.
Asunto(s)
Brazo , Trasplante de Riñón/inmunología , Pierna , Linfedema/inducido químicamente , Sirolimus/efectos adversos , Adulto , Femenino , Humanos , Inmunosupresores/efectos adversos , Linfedema/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The hockey-stick surgical incision is becoming more popular than the oblique incision for kidney transplantations. Both incisions are convenient and comfortable. Both have some drawbacks, such as muscle denervation for the former, or section of lateral muscles for the latter. In this retrospective study, we compared these incisions with regard to the incidence of long-term complications, such as postincisional hernia, relaxation of the abdominal wall, and a poor cosmetic result. One hundred patients (50 of each type) were evaluated at an average of 4.5 years after transplantation (3 months-15 years). Occurrence of incisional hernia was 16% in the former (8 cases) versus 4% in the latter (2 cases: X(2) = 4; P < .05). A major relaxation of the abdominal wall was found in 24% of the former (12 cases) versus 8% of the latter (4 cases) (X(2) = 4.76; P < .05). These complications were not correlated with age, sex, weight, side of transplant, or immunosuppressive drugs. In the former patients with hockey-stick incisions, the overall cosmetic results were poor, because in most cases the incision had been prolonged upward, above the transverse umbilical line, even as high as the costal arch. In 20% of the former patients with hockey-stick incisions, the scar had widened, particularly in the upper vertical branch of the J incision. We conclude that the final outcome of the oblique surgical incision was better than the hockey-stick incision because of the lower incidence of hernia and abdominal wall relaxation and the more favorable cosmetic results.
Asunto(s)
Trasplante de Riñón/métodos , Desnervación , Femenino , Estudios de Seguimiento , Hernia/epidemiología , Hernia/etiología , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Músculos/inervación , Complicaciones Posoperatorias/clasificación , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Abdominal aortic aneurysms (AAA) requiring surgical management are encountered more frequently in renal transplant recipients, presenting an important technical problem during the repair. The aim of the present study was to analyze the epidemiology and natural evolution of AAA among renal allograft recipients. METHODS: Three hundred ninety-four renal transplant recipients were periodically evaluated with abdominal aortic ultrasound tomography for AAA. The indication for surgery was a maximal diameter >5 cm. Renal function, graft, and patient survival were evaluated after a mean follow-up of 51 months. RESULTS: Four AAA were detected in 394 renal transplant recipients, a prevalence of 1.01%. All of the AAA were found in male recipients of mean age 59.2 +/- 5.5 years and mean time posttransplantation of 82.7 +/- 77.3 months. The mean follow-up period between diagnosis and indication for surgery was 14.2 +/- 10.8 months. Two patients underwent open repair with aneurysmectomy and conventional tube graft positioning, and 2 patients refused surgical repair. To preserve renal graft function during the aortic cross-clamping phase, cold perfusion with 4 degrees C Ringer acetate and local hypothermia with sterile ice were used. Renal function did not change after the operation (preoperative serum creatinine levels were 1.2 and 1.3 mg/dL; postoperative 1.3 and 1.5 mg/dL respectively). The 2 patients who underwent surgery are alive with excellent graft functioning after a follow-up of 1.5 and 7 years, respectively. The 2 patients who refused surgical treatment are dead. CONCLUSIONS: Yearly ultrasound screening for AAA must be recommended in renal transplant recipients as part of the routine posttransplantation follow-up. De novo AAA occurs in younger subject in the transplant population and shows a faster evolution.
Asunto(s)
Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/epidemiología , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/epidemiología , Factores de Edad , Anciano , Aneurisma de la Aorta Abdominal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , UltrasonografíaRESUMEN
OBJECTIVE: To investigate the effects of N-acetylcysteine (NAC) and high-dose atorvastatin (ATOR) in reducing oxidative stress in a rat kidney model of ischemia-reperfusion injury. METHODS: Forty female rats underwent clamping of the left renal artery for 30 minutes, followed by reperfusion. The effects of pre-ischemic administration of NAC and/or ATOR were evaluated within 4 groups: a) control (no NAC, no ATOR); b) NAC (intraperitoneal NAC administration); c) ATOR (oral ATOR administration); and d) NAC+ATOR (both drugs). Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO). Post-ischemia-reperfusion injury was evaluated by means of renal histology. RESULTS: NAC, ATOR, and NAC+ATOR in rats showed lower MPO (P < .05) and higher GPx activity (P < .05) versus control; SOD activity was lower in NAC versus ATOR (P < .05). No difference among groups was found at histology. However, a lower rate of tubular ischemic lesions was evident in NAC+ATOR versus control (P = .07). CONCLUSIONS: Atorvastatin pretreatment provides protection against oxidative stress in a rat kidney model of ischemia-reperfusion injury, reinforcing the evidence of a beneficial effect of statins beyond their cholesterol-lowering properties.
Asunto(s)
Acetilcisteína/farmacología , Atorvastatina/farmacología , Depuradores de Radicales Libres/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Enfermedades Renales/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Animales , Atorvastatina/administración & dosificación , Catalasa/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Riñón/irrigación sanguínea , Riñón/lesiones , Riñón/patología , Enfermedades Renales/metabolismo , Oxidación-Reducción , Peroxidasa/metabolismo , Ratas , Daño por Reperfusión/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: To safely expand our living donor pool, we recently decided to work on 3 areas: analysis of causes of exclusion of potential donors, the results of which we recently published, introduction of laparoscopic donor nephrectomy (LDN), and ABO-incompatible (ABOi) transplantation. We sought to determine the impact of the new strategy on living donor recruitment and transplantation during over a 10-year period at a single institution. METHODS: From January 2005 to September 2014, we evaluated 131 living donors. Of these, 80 (61%) were genetically related, 51 (39%) unrelated, 119 (91%) ABO compatible (ABOc), 12 ABOi (9%). The analysis was divided into 2 eras: era 1, 2005-2010 (n = 53) included the use of open lumbotomy and acceptance of ABOc only; and era 2, 2011-2014 (n = 78), which saw the introduction of LDN and ABOi transplantation. RESULTS: Forty-five (34%) potential candidates successfully donated, 67 (51%) were excluded, and 19 (15%) were actively undergoing evaluation. Overall, 53 potential donors were evaluated in era 1 (8.8 donors/year), 78 in era 2 (19.5 donors/year). There were fewer excluded donors in era 2 vs era 1 (62% era 1 vs 44% era 2), and living donor kidney transplantation (LDKT) significantly increased in era 2 vs era 1 (3.3/year era 1 vs 7.1/year era 2). The establishment of an ABOi LDKT program led to a 15% increase of evaluations in era 2 (12/78 donors). CONCLUSIONS: LDN along with ABOi LDKT allowed for an improvement in recruitment of living donors and corresponding LDKT.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Incompatibilidad de Grupos Sanguíneos , Donadores Vivos/provisión & distribución , Nefrectomía/métodos , Recolección de Tejidos y Órganos/métodos , Adulto , Anciano , Femenino , Humanos , Trasplante de Riñón , Laparoscopía , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We report the case of a 45-year-old man who received a cadaveric renal transplant and subsequently developed a bilateral neoplasm of the native kidneys. Two tumors per each kidney were detected and in the left kidney they were cytologically different, one granular and one clear cell type. Bilateral nephrectomy with radical lymphadenectomy was performed, immunosuppression was withdrawn and medrossiprogesterone was administered. A control CT scan 3 months after surgery demonstrated no evidence of neoplastic recurrence, while ultrasonography detected a liver metastasis. The patient subsequently developed a para-neoplastic syndrome and died 7 months after surgery. We believe that all long-term immunosuppressed transplant patients need close observation. Regular imaging of the native kidneys, by ultrasound or CT, should be carried out yearly. Prophylactic bilateral nephrectomy is not desirable because of the loss of the important mechanism of pressure control. mediated by the renine-angiotensin system.
RESUMEN
Posttransplant diabetes mellitus (PTDM) is a disturbing side effect of immunosuppression. The aim of this study was to evaluate the effect of different immunosuppressive agents on the development of PTDM in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx. Baseline immunosuppression was azathioprine (AZA), cyclosporine (CSA), or tacrolimus (TAC), or sirolimus in combination with calcineurin inhibitors (SIR). All patients received steroids for both induction and maintenance therapy during the first 6 months posttransplantation. Mean follow-up after KTx was 73 +/- 53.5 months (range 6 months to 16 years). PTDM was defined as two consecutive blood glucose determinations above 126 mg/dL. Thirty-six of 538 (6.7%) recipients experienced PTDM, 31 of whom required insulin treatment and five oral antidiabetic medications. PTDM occurred at 25.3 +/- 38 months posttransplantation in 4.8% of KTx treated with AZA, 4.8% of CSA, 6.5% of KTx treated with TAC and 12.5% of KTx treated with SIR. The time of onset of PTDM was significantly shorter (P =.003) among TAC (2.1 +/- 1.7 months posttransplantation) versus CSA (27.8 +/- 34 months). PTDM disappeared in 6 of 36 patients. We conclude that with current levels of immunosuppression, there is no difference in the incidence of PTDM between TAC- and CSA-treated KTx.
Asunto(s)
Diabetes Mellitus/inducido químicamente , Inmunosupresores/efectos adversos , Trasplante de Riñón/inmunología , Administración Oral , Diabetes Mellitus/epidemiología , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Insulina/uso terapéutico , Estudios RetrospectivosRESUMEN
The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 +/- 455 ng/mL; vs Stable, 1236 +/- 347 ng/mL, P = .0001; and adult CRAD, 781 +/- 518 ng/mL; vs Stable, 1088 +/- 452 ng/mL, P = .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients.
Asunto(s)
Ciclosporina/sangre , Trasplante de Riñón/inmunología , Adolescente , Adulto , Anciano , Niño , Ciclosporina/uso terapéutico , Monitoreo de Drogas/métodos , Femenino , Humanos , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Trasplante de Riñón/fisiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Experimental and clinical evidence support the role of transforming growth factor beta-1 (TGF-beta(1)), a cytokine with complex immune and nonimmune effects, on the development of chronic renal allograft nephropathy (CAN). We investigated the effects of different immunosuppressive regimens on circulating TGF-beta(1) plasma levels in stable kidney transplant (KTx) recipients. Two hundred ninety-nine TGF-beta(1) plasma levels were measured in 125 kidney transplant (KTX) recipients exhibiting stable renal function, immunosuppressed with cyclosporine (CsA), tacrolimus (TAC), or sirolimus (SIR), and in 18 normal healthy volunteers (C). Activated immunoreactive TGF-beta(1) was detected in platelet-depleted plasma by an enzyme-linked immunoadsorbent assay. Multivariate analyses correlated immunosuppressive regimens with TGF-beta(1) levels. KTX recipients displayed significantly higher TGF-beta(1) levels compared to C (P =.0005). Patients receiving CsA had significantly higher TGF-beta(1) plasma levels compared to those receiving TAC or SIR (P =.0384). Multivariate analyses showed no correlation between TGF-beta(1) levels and immunosuppressive drug trough blood levels or doses, but only correlations with the main immunosuppressive drug. These data show that: (1) TGF-beta(1) production is activated in kidney transplant recipients; (2) CsA patients display significantly higher plasma TGF-beta(1) levels. Follow-up studies seek to assess the possible relationship with clinical events.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Factor de Crecimiento Transformador beta/sangre , Supervivencia de Injerto/efectos de los fármacos , Humanos , Valores de Referencia , Estudios Retrospectivos , Factor de Crecimiento Transformador beta1RESUMEN
The aim of this study was to evaluate the safety of conversion to sirolimus (SRL) immunosuppression among 19 renal transplant recipients (KTX) with progressive chronic renal allograft dysfunction (CRAD). Conversion to SRL was performed with concomitant sharp withdrawal of the calcineurin inhibitor (CI). SRL was added at a starting dose of 3 mg, then adjusted to obtain SRL target trough blood levels of 8 to 10 ng/mL. CI were stopped the evening before starting SRL. All patients enrolled in the study have now completed 6 months of follow-up: all are alive without acute rejection or major infection following rapid conversion to SRL. No significant change in the 6 months postconversion hematologic and hepatic profile was observed compared with the preconversion values, while significant dyslipidemia was induced. After conversion to SRL, significant amelioration of the renal function was found in 36% of patients, stabilization in 21%, and continuous deterioration in 43%. Patients whose renal function improved were found to have been converted at a significantly lower creatinine: (pre 2.6 +/- 0.9 vs post 1.9 +/- 0.2; P =.038) with respect to those patients who had continuous renal deterioration. In KTX with CRAD, sharp withdrawal of CI with concomitant conversion to SRL is safe, avoiding major infections, acute rejections, and significant side effects. Short-term amelioration of the renal function is best obtained when early conversion is performed. Long-term follow-up will be necessary to confirm these preliminary data.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Sirolimus/uso terapéutico , Creatinina/sangre , Ciclosporinas/efectos adversos , Progresión de la Enfermedad , Humanos , Inmunosupresores/efectos adversos , Pruebas de Función Renal , Trasplante de Riñón/patología , Trasplante de Riñón/fisiología , Trasplante HomólogoRESUMEN
The experimental and clinical pharmacology of glycosaminoglycans (GAGs) is discussed, including that of heparin and related compounds, hyaluronic acid and chondroitin sulfates.
Asunto(s)
Glicosaminoglicanos/farmacología , HumanosRESUMEN
In order to investigate the value of ras oncogene expression as a prognostic indicator in colonic adenocarcinoma, we evaluated the level of ras gene protein product (p21) in the available material of 109 surgical specimens resected at our institution between 1978 and 1981. Pathology slides and archived paraffin blocks were retrieved for confirmation of the original diagnosis, determination of stage, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody given definitive staining using the Avidin-Biotin peroxidase method. The analysis indicated that tumors with high (greater than or equal to 1:40,000) p21 titer had a lower five-year survival rate than tumors with low (less than 1:40,000) titers (34.3% vs 60.8%, p less than 0.02). When a logistic regression analysis was used with the dependent variable being five-year survival and the independent variables being age, sex, location of tumor. Dukes' stage, mucin production, p21 titer, differentiation degree and tumor size, the statistically significant relationship of the level of ras gene protein product to long-term survival was negated by the concomitant knowledge of Dukes' stage. On the other hand, when only the variables available in the preoperative period were entered in the multivariate analysis, p21 titers retained a significant relationship with long-term survival (p less than 0.05). We conclude that ras oncogene determination in colonic carcinomas may have clinical importance for the pre-operative identification of a group of colonic tumors with a more aggressive behavior and a poorer prognosis.
Asunto(s)
Adenocarcinoma/patología , Neoplasias del Colon/patología , Expresión Génica , Genes ras , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Humanos , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Estudios RetrospectivosRESUMEN
We report our experience with the use of the vascular closure staples (VCS) in vascular access for dialysis, as well as in kidney and pancreas transplantation. We used the VCS for 50 endogenous arterio-venous fistulas (AVFs). There were no complications. The use of the VCS contributed in creating an excellent anastomosis and minimising operative time. All AVFs are in use for dialysis (follow up two months to one year). The excellent results from our experience with the use of VCS for vascular access encouraged us to use them in kidney and pancreas transplantation. We performed six cadaveric kidney transplants (the first operation was the first application of the VCS in kidney transplantation in Europe) and two cadaveric pancreas-kidney transplants (the first operation being the first application of the VCS in pancreas transplantation in the world). There were no complications. The use of VCS created an excellent anastomosis and minimised warm ischaemia time. All kidney transplant recipients have normal creatinines (follow up 1-5 months) and the recipients of pancreatic transplants are insulin independent (follow up 1-3 months).
Asunto(s)
Derivación Arteriovenosa Quirúrgica , Trasplante de Riñón , Trasplante de Páncreas , Diálisis Renal , Grapado Quirúrgico , Procedimientos Quirúrgicos Vasculares/métodos , Anastomosis Quirúrgica/instrumentación , Anastomosis Quirúrgica/métodos , Derivación Arteriovenosa Quirúrgica/instrumentación , Derivación Arteriovenosa Quirúrgica/métodos , Humanos , Trasplante de Riñón/instrumentación , Trasplante de Riñón/métodos , Trasplante de Páncreas/instrumentación , Trasplante de Páncreas/métodos , Procedimientos Quirúrgicos Vasculares/instrumentaciónRESUMEN
Annular pancreas (AP) is an uncommon congenital anomaly which often does not become symptomatic until late life. We report a case of successful transplantation of an AP in a type I IDDM woman. The whole pancreas with a duodenal cuff was procured from a 41-year-old previously healthy female. The AP was identified at the time of procurement and did not appear to have caused any significant duodenal obstruction. The graft was transplanted on the external iliac vessels and the exocrine secretions were drained enterically. In order to avoid any possible injury to the ductal system, a side-to-side duodenojejunal anastomosis was fashioned using the first and the second portion of the duodenum, leaving about 2 cm of free duodenal margin proximal to the pancreatic ring. The postoperative course was uneventful and at 1 month graft function is unremarkable. Although challenging from a technical point of view, transplantation of an AP is a safe procedure which allows good results. Given the limited number of organ donors and the difficulty in HLA-matching, every AP should be considered suitable for transplantation.
Asunto(s)
Trasplante de Páncreas/métodos , Páncreas/anomalías , Adulto , Anastomosis Quirúrgica , Diabetes Mellitus Tipo 1/cirugía , Duodeno/cirugía , Femenino , Humanos , Yeyuno/cirugía , Donantes de TejidosRESUMEN
Segmental pancreatic transplantation has been abandoned because of the high incidence of technical complications. We report the first case in the literature of the salvage of a partially ischemic pancreatic allograft. The procedure consisted of resecting the head of the pancreas and draining the residual segment to the ureter with a duct-to-ureter end-to-side anastomosis. The postoperative course was uneventful, and 15 months after surgery graft function is satisfactory with a urinary amylase level of 5000 U/h. The duct-to-ureter drainage technique should be part of every transplant surgeon's repertoire, because in emergency situations like the one described, it can be used to save a pancreatic allograft.
Asunto(s)
Anastomosis Quirúrgica/métodos , Pancreatectomía/métodos , Adulto , Diabetes Mellitus Tipo 1/cirugía , Femenino , Humanos , Trasplante de Páncreas , Conductos Pancreáticos/cirugía , Trasplante HomólogoRESUMEN
We describe a technique for refashioning an aneurysmatic arterio-venous fistula by using the multifire GIA 60 surgical stapler. After obtaining proximal and distal control of the aneurysmatic vein each aneurysmal segment of the anterior wall of the vein is excised by applying the GIA 60 stapler. The layer of the staple-line is re-enforced with one layer of 6/0 prolene continuous suture. After completion of the procedure, the size of the vein is reduced by approximately 50%. The AVFs were successfully re-used for dialysis within four weeks postoperatively.