RESUMO
Diabetes is a common metabolic disorder affecting the entire body with high morbidity and mortality worldwide. The major complications related to diabetes are mostly due to the macrovascular and microvascular bed impairment due to metabolic, hemodynamic and inflammatory factors. However, studies over the past decades have added also the lung as a target organ in both type 1 and type 2 diabetes. Diabetes has always been addressed as a major comorbidity conditioning the disease behaviour and the natural history of several respiratory diseases. Increased interest has recently focused on the pathophysiology of the metabolic glycaemic disorder and the respiratory diseases suggesting a similar background shared by the two conditions. The true relationship between pulmonary diseases and diabetes mellitus has not been clarified, this review aims to summarize the link between diabetes and coexisting respiratory diseases such as asthma, chronic obstructive pulmonary disease, respiratory infections, cystic fibrosis, lung cancer and obstructive sleep apnea from a pathogenetic and therapeutic point of view.
Assuntos
Diabetes Mellitus/epidemiologia , Doenças Respiratórias/epidemiologia , Animais , Comorbidade , Diabetes Mellitus/tratamento farmacológico , Humanos , Doenças Respiratórias/tratamento farmacológicoRESUMO
PURPOSE: Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. PATIENTS AND METHODS: Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. RESULTS: Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1-5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. CONCLUSIONS: Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.
Assuntos
DNA Tumoral Circulante , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Seguimentos , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/epidemiologia , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
BACKGROUND: Mammographic density (MD) is a risk factor for breast cancer (BC) development, and recurrence. However, its predictive value has been less studied. Herein, we challenged MD as a biomarker associated with response in patients treated with neoadjuvant therapy (NAT). METHODS: Data on all NAT treated BC patients prospectively collected in the registry of Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy (2009-2019) were identified. Diagnostic mammograms were used to evaluate and score MD as categorized by the Breast Imaging-Reporting and Data System (BI-RADS), which identifies 4 levels of MD in keeping with relative increase of fibro-glandular over fat tissue. Each case was classified according to the following categories a (MD < 25%), b (26-50%), c (51-75%), and d (> 75%). The association between MD and pathological complete response (pCR), i.e., absence of BC cells in surgical specimens, was analyzed in multivariable setting used logistic regression models with adjustment for clinical and pathological variables. RESULTS: A total of 442 patients were analyzed, 120 of which (27.1%) attained a pCR. BI-RADS categories a, b, c, and d accounted for 10.0%, 37.8%, 37.1% and 15.2% of cases. Corresponding pCR were 20.5%, 26.9%, 30.5%, 23.9%, respectively. At multivariable analysis, when compared to cases classified as BI-RADS a, those with denser breast showed an increased likelihood of pCR with odds ratio (OR) of 1.70, 2.79, and 1.47 for b, c and d categories, respectively (p = 0.0996), independently of age, BMI [OR underweight versus (vs) normal = 3.76], clinical nodal and tumor status (OR T1/Tx vs T4 = 3.87), molecular subtype (HER2-positive vs luminal = 10.74; triple-negative vs luminal = 8.19). In subgroup analyses, the association of MD with pCR was remarkable in triple-negative (ORs of b, c and d versus a: 1.85, 2.49 and 1.55, respectively) and HER2-positive BC cases (ORs 2.70, 3.23, and 1.16). CONCLUSION: Patients with dense breast are more likely to attain a pCR at net of other predictive factors. The potential of MD to assist decisions on BC management and as a stratification factor in neoadjuvant clinical trials should be considered.
Assuntos
Densidade da Mama , Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Mamografia , Terapia Neoadjuvante , Razão de Chances , Receptor ErbB-2RESUMO
PURPOSE: To report acute toxicities in breast cancer (BC) patients (pts) recruited in a prospective trial and treated with accelerated partial-breast irradiation (APBI) using Volumetric Modulated Arc Therapy (VMAT) delivered with a hypofractionated schedule. METHODS: From March 2014 to June 2019, pts with early-stage BC (Stage I), who underwent breast conservative surgery (BCS), were recruited in a prospective study started at the National Cancer Institute of Milan. Pts received APBI with a hypofractionated schedule of 30 Gy in five daily fractions. Radiotherapy treatment (RT) was delivered using VMAT. Acute toxicity was assessed according to RTOG/EORTC criteria at the end of RT. RESULTS: Between March 2014 and June 2019, 151 pts were enrolled in this study. 79 Pts had right-side and 72 had left-side breast cancer. Median age was 69 (range 43-92). All pts presented with pathological stage IA BC, molecular classification was Luminal A in 128/151 (85%) and Luminal B in 23/151 (15%) cases. Acute toxicity, assessed at the end of RT, consisted of G1 erythema in 37/151 (24. 5%) pts and skin toxicities higher than G1, did not occur. Fibrosis G1 and G2 were reported in 41/151 (27. 1%) pts and in 2/151 pts (1. 3%), respectively. Edema G1 occurred in 8/151 (5. 3%) pts and asthenia G1 occurred in 1/151 (0. 6%) pts. CONCLUSIONS: APBI with VMAT proved to be feasible and can be a valid alternative treatment option after BCS in selected early breast cancer pts according to ASTRO guidelines. A longer follow-up is needed to assess late toxicity.
Assuntos
Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Estudos Prospectivos , Planejamento da Radioterapia Assistida por ComputadorRESUMO
AIM: To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). METHODS: From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65 years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). RESULTS: ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80 years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80 years discontinued the prescribed therapy earlier and more frequently than younger (65-69 years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. CONCLUSIONS: In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.
Assuntos
Neoplasias da Mama/epidemiologia , Avaliação Geriátrica , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Terapia Combinada , Comorbidade , Feminino , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Cooperação do Paciente , Prognóstico , Hipofracionamento da Dose de Radiação , Radioterapia Adjuvante , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Primary tumor characteristics, which are readily available to all clinicians, may aid in selecting the optimal adjuvant therapy for patients with breast cancer (BC). Herein, we investigated the relationship between tumor size, hormone receptor and HER2 status, Ki67 and age with axillary lymph node metastases (ALNM) in early-BC patients. METHODS: We analyzed data on consecutive 2600 early-BC cases collected in the registry of Fondazione IRCC Istituto Nazionale dei Tumori, Milano, Italy. Correlation between Ki67 and primary tumor size (T-size) was calculated by Spearman's rank correlation coefficient. Association of ALNM with Ki67 and other tumor characteristics was investigated by logistic regression. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in all cases, and separately analyzed according to age, T-size and BC subtype. RESULTS: Large tumor size strongly associated to ALNM, with an adjusted odds ratio (OR) for each 5-mm increase of 1.32 (95% CI 1.24-1.41), except for triple-negative BC (TNBC) cases. In tumors =10 mm, without lymphovascular invasion, representing the strongest predictor of ALNM (OR 6.09, 95% CI 4.93-7.53), Ki67 resulted particularly informative, with a fourfold increased odds of ALNM for values > 30%. CONCLUSIONS: These results raise the question whether axillary node status is redundant in cases with exceptionally good features, i.e., small tumors with low Ki67, or in those candidate to adjuvant systemic treatment/radiotherapy anyway including TNBC, and support the incorporation of primary BC tumor characteristics as stratification factors in ongoing trials aiming at de-escalating axillary surgical procedures.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Idoso , Axila , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Itália/epidemiologia , Antígeno Ki-67/metabolismo , Modelos Logísticos , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Receptor ErbB-2/metabolismo , Receptores de Esteroides/metabolismo , Carga TumoralRESUMO
In order to assess the combined and separate effects of pancreas and kidney transplant on whole-body protein metabolism, 9 insulin-dependent diabetic-uremic patients (IDDUP), 14 patients after combined kidney-pancreas transplantation (KP-Tx), and 6 insulin-dependent diabetic patients with isolated kidney transplant (K-Tx), were studied in the basal postabsorptive state and during euglycemic hyperinsulinemia (study 1). [1-14C]Leucine infusion and indirect calorimetry were utilized to assess leucine metabolism. The subjects were studied again with a combined infusion of insulin and amino acids, given to mimic postprandial amino acid levels (study 2). In the basal state, IDDUP demonstrated with respect to normal subjects (CON): (a) higher free-insulin concentration (17.8 +/- 2.8 vs. 6.8 +/- 1.1 microU/ml, P < 0.01) (107 +/- 17 vs. 41 +/- 7 pM); (b) reduced plasma leucine (92 +/- 9 vs. 124 +/- 2 microM, P < 0.05), branched chain amino acids (BCAA) (297 +/- 34 vs. 416 +/- 10 microM, P < 0.05), endogenous leucine flux (ELF) (28.7 +/- 0.8 vs. 39.5 +/- 0.7 mumol.m-2.min-1, P < 0.01) and nonoxidative leucine disposal (NOLD) (20.7 +/- 0.2 vs. 32.0 +/- 0.7 mumol.m-2. min-1, P < 0.01); (c) similar leucine oxidation (LO) (8.0 +/- 0.1 vs. 7.5 +/- 0.1 mumol.m-2.min-1; P = NS). Both KP-Tx and K-Tx patients showed a complete normalization of plasma leucine (116 +/- 5 and 107 +/- 9 microM), ELF (38.1 +/- 0.1 and 38.5 +/- 0.9 mumol.m-2.min-1), and NOLD (28.3 +/- 0.6 and 31.0 +/- 1.3 mumol.m-2.min-1) (P = NS vs, CON). During hyperinsulinemia (study 1), IDDUP showed a defective decrease of leucine (42% vs. 53%; P < 0.05), BCAA (38% vs. 47%, P < 0.05), ELF (28% vs. 33%, P < 0.05), and LO (0% vs. 32%, P < 0.05) with respect to CON. Isolated kidney transplant reverted the defective inhibition of ELF (34%, P = NS vs. CON) of IDDUP, but not the inhibition of LO (18%, P < 0.05 vs. CON) by insulin. Combined kidney and pancreas transplanation normalized all kinetic parameters of insulin-mediated protein turnover. During combined hyperinsulinemia and hyperaminoacidemia (study 2), IDDUP showed a defective stimulation of NOLD (27.9 +/- 0.7 vs. 36.1 +/- 0.8 mumol.m-2.min-1, P < 0.01 compared to CON), which was normalized by transplantation (44.3 +/- 0.8 mumol.m-2.min-1).
Assuntos
Diabetes Mellitus Tipo 1/terapia , Falência Renal Crônica/terapia , Transplante de Rim/fisiologia , Leucina/farmacocinética , Transplante de Pâncreas/fisiologia , Uremia/terapia , Adulto , Glicemia/análise , Feminino , Hemoglobinas/análise , Hormônios/sangue , Humanos , Hiperinsulinismo/metabolismo , Terapia de Imunossupressão , Cetoácidos/análise , Masculino , Nitrogênio/metabolismo , Oxirredução , Proteínas/metabolismo , Uveíte Posterior/metabolismoRESUMO
Between January 1985 and September 1987, we performed a prospective comparative study between segmental-pancreas transplantation with duct obstruction by neoprene (n = 17) and pancreaticoduodenal transplantation with enteric diversion to a Roux-en-Y intestinal loop (n = 14). All recipients had insulin-dependent diabetes. The immunosuppressive protocol consisted of low doses of the steroids cyclosporin A and azathioprine. Mean follow-up was 16.5 mo for the enteric-diversion group and 13.5 mo for duct-obstructed groups. Two-year patient and pancreas- and kidney-graft actuarial survival rates were 92.9, 75.5, and 74.2%, respectively, in the former group and 92.3, 58.4, and 63.7%, respectively, in the latter group (NS). Five whole-organ grafts were lost (3 vascular thromboses, 1 pancreatitis, 1 rejection), and four segmental grafts were lost (2 vascular thromboses, 1 bleeding, 1 patient's death with functional graft). More surgical complications occurred in the recipients of whole-organ grafts and were often related to the intestinal anastomosis. A satisfactory blood glucose control was observed at 3 mo and 1 yr in both groups. Provocative tests showed higher and prompter insulin secretion in patients with whole-organ grafts. In patients with segmental grafts, the response was lower and delayed with a general tendency to impaired glucose tolerance. A marked hyperinsulinemia after meals was observed in whole-organ graft recipients. Slight nocturnal hyperinsulinemia was observed in both groups. At 1 yr, glycosylated hemoglobin was normal in both groups. The absence of a significant difference between the two groups, in terms of survival and graft function, and the lower surgical complication rate seen with segmental grafts have made us return to neoprene-injected segmental grafts.
Assuntos
Duodeno , Transplante de Pâncreas , Ritmo Circadiano , Diabetes Mellitus Tipo 1/cirurgia , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Insulina/sangue , Transplante de Rim , Ductos Pancreáticos/cirurgia , Estudos ProspectivosRESUMO
Since November 1975, 103 pancreas transplantations have been performed in 97 insulin-dependent diabetic patients. Pancreas and kidney were grafted simultaneously in 84 patients (plus 1 double retransplantation). Eighty-nine pancreas grafts were prepared by duct obstruction with neoprene, and 14 were pancreaticoduodenal grafts with enteric diversion in a Roux-en-Y loop. Five immunosuppressive protocols were subsequently used. With the latest protocols, patient and pancreas survival improved to 93 and 72% at 1 yr, respectively. The improvement in graft survival appeared to be particularly related to the reduction of the number of pancreas grafts lost in rejection. The patients treated with the last protocols, including cyclosporin A (CsA) and only low doses of steroids, showed a better glucose tolerance after provocative tests. Pancreas-graft function did not appear to be influenced by CsA treatment.
Assuntos
Terapia de Imunossupressão , Transplante de Pâncreas , Soro Antilinfocitário/uso terapêutico , Azatioprina/uso terapêutico , Ciclosporinas/uso terapêutico , Duodeno/patologia , Teste de Tolerância a Glucose , Sobrevivência de Enxerto , Humanos , Transplante de Rim , NeoprenoRESUMO
In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Denervação , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/cirurgia , Hormônios/sangue , Insulina/metabolismo , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Pâncreas/inervação , Ácido 3-Hidroxibutírico , Adulto , Análise de Variância , Glicemia/metabolismo , Peptídeo C/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/cirurgia , Epinefrina/sangue , Ácidos Graxos não Esterificados/sangue , Retroalimentação , Seguimentos , Glucagon/sangue , Técnica Clamp de Glucose , Hemoglobinas Glicadas/análise , Humanos , Hidroxibutiratos/sangue , Insulina/sangue , Secreção de Insulina , Lactatos/sangue , Polipeptídeo Pancreático/sangue , Somatostatina/sangue , Uremia/etiologia , Uremia/cirurgiaRESUMO
Cardiovascular disease and the development of coronary artery disease play a pivotal role in increasing mortality in patients with type 1 diabetes. The aim of our study was to evaluate the effects of pancreas transplantation on atherosclerotic risk factors, endothelial-dependent dilation (EDD), and progression of intima media thickness (IMT) in patients with uremia and type 1 diabetes after kidney-alone (KA) or kidney-pancreas (KP) transplantation. A cross-sectional study comparing two groups of patients with type 1 diabetes was performed. Sixty patients underwent KP transplantation and 30 patients underwent KA transplantation. Age and cardiovascular risk profile were comparable in patients before transplantation. In all patients, atherosclerotic risks factors (lipid profile, fasting and post-methionine load plasma homocysteine, von Willebrand factor levels, D-dimer fragments, and fibrinogen) were assessed and Doppler echographic evaluation of IMT and endothelial function with flow-mediated and nitrate dilation of the brachial artery was performed. Twenty healthy subjects were chosen as controls (C) for EDD. Compared with patients undergoing KA transplantation, patients undergoing KP transplantation showed lower values for HbA1c (KP = 6.2 +/- 0.1% vs. KA = 8.4 +/- 0.5%; P < 0.01), fasting homocysteine (KP = 14.0 +/- 0.7 mcromol/l vs. KA = 19.0 +/- 2.0 micromol/l; P = 0.02), von Willebrand factor levels (KP = 157.9 +/- 8.6% vs. KA = 212.5 +/- 16.2%; P < 0.01), D-dimer fragments (KP = 0.29 +/- 0.02 microg/ml vs. KA = 0.73 +/- 0.11 microg/ml;P < 0.01), fibrinogen (KP = 363.0 +/- 11.1 mg/dl vs. KA = 397.6 +/- 19.4 mg/dl; NS), triglycerides (KP = 122.7 +/- 8.6 mg/dl vs. KA = 187.0 +/- 30.1 mg/dl; P = 0.01), and urinary albumin excretion rate (KP = 13.5 +/- 1.9 mg/24 h vs. KA = 57.3 +/- 26.3 mg/24 h; P < 0.01). Patients undergoing KP transplantation showed a normal EDD (KP = 6.21 +/- 2.42%, KA = 0.65 +/- 2.74%, C = 8.1 +/- 2.1%; P < 0.01), whereas no differences were observed in nitrate-dependent dilation. Moreover, IMT was lower in patients undergoing KP transplantation than in patients undergoing KA transplantation (KP = 0.74 +/- 0.03 mm vs. KA = 0.86 +/- 0.09 mm; P = 0.04). Our study showed that patients with type 1 diabetes have a lower atherosclerotic risk profile after KP transplantation than after KA transplantation. These differences are tightly correlated with metabolic control, fasting homocysteine levels, lower D-dimer fragments, and lower von Willebrand factor levels. Normal endothelial function and reduction of IMT was observed only in patients undergoing KP transplantation.
Assuntos
Arteriosclerose/etiologia , Diabetes Mellitus Tipo 1/complicações , Endotélio Vascular/fisiopatologia , Transplante de Rim , Transplante de Pâncreas , Uremia/complicações , Adulto , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose/etiologia , Uremia/fisiopatologiaRESUMO
OBJECTIVE: Diastolic function is frequently impaired in diabetic patients. Our aim was to evaluate the effects of glycometabolic control achieved by pancreas transplantation on left ventricular function in uremic type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Left ventricular systolic and diastolic functions were evaluated using radionuclide ventriculography in 42 kidney-pancreas transplant patients and 26 kidney-alone recipients who had similar clinical characteristics before transplantation. Patients were grouped according to 6, 24, and 48 months of follow-up. Control subjects consisted of 20 type 1 diabetic patients. RESULTS: The left ventricular ejection fraction was normal in all of the patients. However, kidney-pancreas transplant patients with 4 years of graft function had a higher ejection fraction (75.7 +/- 1.8%) than kidney-alone patients with 4 years of graft function (65.3 +/- 2.8%, P = 0.02) and type 1 diabetic patients (61.3 +/- 3.7%, P = 0.004). In patients with 4 years of graft function, normal diastolic parameters were evident in kidney-pancreas but not in kidney-alone or in type 1 diabetic patients (peak filling rate: 4.46 +/- 0.15 end diastolic volume (EDV)/s in kidney-pancreas patients vs. 2.73 +/- 0.24 EDV/s [P < 0.01] and 3.39 +/- 0.30 EDV/s [P < 0.01] in kidney-alone and type 1 diabetic patients, respectively; time-to-peak filling rate: 141.9 +/- 7.8 ms in kidney-alone patients vs. 209.4 +/- 13.5 ms in kidney-alone patients [P < 0.01]; peak filling rate/peak ejection rate ratio: 1.10 +/- 0.04 in kidney-pancreas patients vs. 0.81 +/- 0.08 in kidney-alone patients [P < 0.01]). A significant reduction in diastolic dysfunction rate was observed only in kidney-pancreas patients. CONCLUSIONS: Kidney-pancreas transplantation results in complete insulin independence, a better glycometabolic pattern and blood pressure control, an improvement of left ventricular function, and a reversal of diastolic dysfunction.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Diástole , Transplante de Rim , Transplante de Pâncreas , Disfunção Ventricular Esquerda/terapia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/etiologia , Hipertensão/terapia , Insulina/sangue , Pessoa de Meia-Idade , Cintilografia , Triglicerídeos/sangue , Uremia/cirurgia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologiaRESUMO
There is increasing evidence that metabolic disorders are common in patients with hypertension. To evaluate the relationship between glucose/insulin metabolism and hypertension in diabetes, 61 hypertensive uremic insulin-dependent diabetes mellitus patients who were recipients of kidney or pancreas/kidney transplants were studied through a 1-year follow-up. Twenty of them received a kidney (K) transplant alone, 13 received a kidney and segmental pancreas (KSP), and 28 received a kidney and whole pancreas (KWP) with duodenocystostomy. All subjects received the same immunosuppressive treatment including steroids, azathioprine, and cyclosporine. The three groups of patients were comparable for biochemical parameters, clinical characteristic, cyclosporine levels, and renal function (creatinine < 2 mg/dl). The association between hypertension and type of transplant was evaluated according a global chi-square test, then the results were broken down into two components to test for differences in hypertension between KP versus K and KWP versus KSP groups. The improvement of hypertension rate was statistically associated with KP transplant the first week after surgery, at discharge, and 1 year after transplantation (hypertension% at 1 week: KWP = 75, KSP = 23 vs. K = 70, P = 0.004; at discharge: KWP = 39, KSP = 31 vs. K = 75, P = 0.017; at 1 yr: KWP = 44, KSP = 54 vs. K = 85, P = 0.02). One year after graft fasting, free immunoreactive insulin as well as glycosylated hemoglobin and glucose levels were statistically lower in the KP groups than in the K-alone recipients. The improvement of hypertension observed in KP recipients suggests a key role of glucose and insulin metabolism on pathogenesis of diabetic hypertension.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Adulto , Causas de Morte , Distribuição de Qui-Quadrado , Estudos de Coortes , Ciclosporina/sangue , Ciclosporina/uso terapêutico , Cistostomia , Duodenostomia , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Masculino , Transplante de Pâncreas/métodos , Transplante de Pâncreas/mortalidade , Estudos RetrospectivosRESUMO
We have investigated the metabolic effects of segmental (neoprene-injected) pancreas transplantation versus whole (enteric-diverted) pancreas transplantation. Seventeen uremic insulin-dependent diabetes mellitus (IDDM) patients received a simultaneous pancreaticorenal transplant: in a prospective, randomized study, 9 patients received a segmental neoprene-injected graft (group A) while 8 patients received a total pancreaticoduodenal graft, with enteric diversion (group B). The immunosuppressive therapy was based on ALG, CsA, azathioprine, and steroids. Three months after surgery, patients were submitted to the following metabolic investigation: i.v. and oral glucose tolerance tests, Hba1, i.v. arginine test, and a 24-hr metabolic profile. The OGTT, HbA1, and metabolic profile were repeated 12 and 24 months after transplantation. At 3 months after transplantation, the OGTT showed delayed insulin secretion and higher blood glucose levels in group A. Serum insulin levels after IVGTT or arginine were higher in group B than in group A. OGTT at 12 and 24 months were unchanged in group B, while in group A a higher incidence of impaired glucose tolerance (IGT) and diabetes mellitus response were observed. HbA1 and blood glucose levels during the 24-hr profile showed good metabolic control in both groups at 3, 12, and 24 months. We can conclude that both the segmental and total pancreas transplantation restore a good metabolic control in IDDM patients, though a higher incidence of IGT and DM responses were observed after OGTT in the patients receiving a segmental graft. These abnormalities do not seem to interfere with metabolic control in everyday life. These results seem to be the consequence of the different B cell masses transplanted with these two techniques.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Insulina/sangue , Transplante de Pâncreas/fisiologia , Adulto , Arginina , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/cirurgia , Seguimentos , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/métodos , Transplante HomólogoRESUMO
Hereditary angioedema (HAE) is a disease related to a complement disorder, namely a deficiency of C1 esterase inhibitor. Complement-split products are implicated in the regulation of the immune response, and we have compared some immunologic parameters between HAE and normal individuals. T-lymphocytes with receptors for IgG were increased in HAE, but no difference in T-cell suppressor activity for B-cells was detected. Furthermore, increased IgG receptor expression was not accompanied by any significant changes in the ratios of OKT4- and OKT8-defined antigens. Numbers of peripheral mononuclear cells (MNC) detected by alpha-naphthyl acetate esterase (ANAE) staining positivity were not significantly modified in HAE patients, although there was a trend toward higher absolute numbers of them showing paranuclear localization of ANAE. HAE patients had significantly reduced numbers of Langerhans cells (LC) showing different morphology and localization patterns. These observations are discussed in terms of differential membrane arrangements related to particular stages of cell activation, possibly attributable to continual complement activation resulting from a lack of control by C1 esterase inhibitor.
Assuntos
Angioedema/imunologia , Células de Langerhans/patologia , Receptores de Antígenos de Linfócitos T/análise , Linfócitos T/imunologia , Adulto , Angioedema/genética , Angioedema/patologia , Anticorpos Monoclonais , Contagem de Células , Feminino , Imunofluorescência , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Pele/imunologia , Pele/patologia , Linfócitos T Reguladores/imunologiaRESUMO
In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Uremia/cirurgia , Adulto , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 1/mortalidade , Angiopatias Diabéticas/mortalidade , Humanos , Pessoa de Meia-Idade , Análise de Sobrevida , Uremia/mortalidadeRESUMO
PURPOSE: To investigate the influence of diabetes mellitus on patient and graft survival among renal versus renal-pancreatic recipients. METHODS: Among 270 renal transplants performed from 1985 to 2002, a total of 204 (75%) were in diabetic patients and 66 (25%) in nondiabetic patients. Among the 204 diabetic patients 161 (60%) kidneys were transplanted simultaneously with a pancreatic graft (SKPT group). The overall group of patient included 164 (61%) men and 106 (39%) women with mean time on dialysis of 31 +/- 21 months (range 0 to 126 months). The mean duration of diabetes was 24 +/- 7 years (range 5 to 51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% hemodialysis and 20% peritoneal dialysis). RESULTS: The overall rejection rate was similar (NS). Both patient and kidney graft survival rates were worse in diabetics. Patient survival was 82% at 5 years among patients undergoing SKPT, 60% in diabetics receiving only a kidney, and 88% in nondiabetic transplanted patients. Kidney graft survival at 5 years was 77% in diabetics receiving SKPT, 68% in diabetics receiving a kidney alone, and 82% in nondiabetic patients. Overall patient survival was significantly greater among nondiabetics (P =.002) or in diabetics who received SKPT compared with diabetics who only had a kidney transplant (P =.001). CONCLUSIONS: This retrospective clinical evaluation confirms that combined pancreas and kidney transplantation should be the first choice to insulin-dependent diabetes mellitus (IDDM) patients with end-stage diabetic nephropathy.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Transplante de Pâncreas/estatística & dados numéricos , Nefropatias Diabéticas/cirurgia , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Humanos , Transplante de Rim/mortalidade , Transplante de Rim/fisiologia , Pessoa de Meia-Idade , Transplante de Pâncreas/mortalidade , Transplante de Pâncreas/fisiologia , Estudos Retrospectivos , Análise de Sobrevida , Sobreviventes , Fatores de Tempo , Falha de TratamentoRESUMO
Simultaneous kidney and pancreas transplantation (SKPT) is the treatment of choice for a majority of type I diabetic patients with end-stage renal disease. With continual refinements in surgical technique and an evolving immunosuppressive arsenal, graft and patient survival have continually improved. The purpose of this study was to evaluate the short- and long-term results of SKPTs performed in 174 recipients from June 1985 to March 2003 including 37 segmental grafts with duct occlusion, 73 whole pancreas transplants with bladder diversion, and 64 whole pancreas grafts with enteric diversion. The series includes 160 cases with systemic drainage and 14 with portal drainage. In the segmental pancreas group, patient survival was 85%, 76%, and 53% with pancreas survival of 67%, 36%, and 15%, and kidney survival of 82%, 63%, and 15%, respectively, at 1, 5, and 10 years. Among the bladder diversion group, patient survival was 94%, 83%, and 73% pancreas survival 72%, 67%, and 65%, and kidney survival 89%, 78%, and 58%, respectively, 1, 5, and 10 years. Among the enter diversion group patient survival was 90% and 90% at 12 and 108 months, pancreas survival 80% and 65%, and kidney survival 85% and 85%, respectively. There were significant differences between curves of survival distribution according to the surgical technique applied for patients (P =.04), pancreas (P =.007), and kidney (P =.005). Based on the results from our study, the short- and long-term prognosis after SKPT is satisfactory, especially compared to the outcomes of long-term dialysis among patients with end-stage renal disease caused by type I diabetes.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Falência Renal Crônica/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Adulto , Bases de Dados Factuais , Nefropatias Diabéticas/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/métodos , Transplante de Pâncreas/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
The aim of this study was to evaluate the outcome of simultaneous kidney pancreas transplantation (SKPT) by various surgical techniques. The 161 patients submitted to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to 1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50 whole pancreas with enteric diversion (40 with systemic and 10 with portal drainage) (from 1999 to September 2002). A positive effect on patient survival was evident using enteric diversion versus the duct occlusion group (P = .005), and versus the bladder diversion group (.035), and on pancreas graft survival in the enteric diversion versus the duct occlusion group (P < .028). These improvements may be due to refined donor and patient selection criteria, surgical technique, and immunosuppression.
Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Nefropatias Diabéticas/cirurgia , Transplante de Rim/fisiologia , Transplante de Pâncreas/fisiologia , Uremia/cirurgia , Adulto , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/fisiologia , Humanos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Transplante de Pâncreas/métodos , Transplante de Pâncreas/mortalidade , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Terapia de Substituição Renal , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Infecções Urinárias/epidemiologiaRESUMO
Pancreas transplantation has become an accepted therapeutic approach to treat insulin-dependent diabetes mellitus, successfully restoring normoglycemia. In contrast, islet transplantation is still in the experimental phase, only a few operations having being performed world-wide. The aim of this review is to analyze the effects of pancreas transplantation on the late complications of diabetes and to report the endocrino-metabolic effects of pancreas and islet transplantation.