RESUMO
BACKGROUND: Despite extensive research, the aetiology of atopic dermatitis remains largely unknown, but reduced intestinal microbiota diversity in neonates has been linked to subsequent atopic dermatitis. Consequently, postnatal antibiotics have been proposed as a risk factor, but a potential association between prenatal antibiotics and atopic dermatitis is not well studied. Overall, the current evidence suggests a positive association between exposure to prenatal antibiotics and atopic dermatitis. OBJECTIVE: To investigate the association between prenatal antibiotics and atopic dermatitis among 18-month-old children. METHODS: This study conducted within the Danish National Birth Cohort included 62 560 mother-child pairs. Data on maternal prenatal antibiotics were collected in the 30th gestation week and 6 months post-partum, and offspring atopic dermatitis 18 months post-partum through telephone interviews. Antibiotic use was categorized by the timing of exposure as 1st-2nd trimester (gestation week 0-29), 3rd trimester (gestation week 30-birth), all three trimesters or none. Data were analysed by logistic regression analyses adjusting for potential confounders. RESULTS: Exposure to antibiotics prenatally was associated with increased odds of atopic dermatitis among children born by atopic mothers but only when used in both 1st-2nd and 3rd trimester (ORadj 1.45, 95% CI: 1.19-1.76). The findings were consistent using different definitions of atopic dermatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Prenatal exposure to antibiotics throughout pregnancy was associated with an increased risk of atopic dermatitis but only within the first 18 months of life among children born by atopic mothers. The clinical usefulness of this finding must rest on corroboration in independent data sources.
Assuntos
Antibacterianos/efeitos adversos , Dermatite Atópica/epidemiologia , Dermatite Atópica/etiologia , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Razão de Chances , Vigilância da População , Gravidez , Sistema de Registros , Fatores de Risco , Fatores SocioeconômicosRESUMO
Being intimately intertwined with (C3) photosynthesis, photorespiration is an incredibly high flux-bearing pathway. Traditionally, the photorespiratory cycle was viewed as closed pathway to refill the Calvin-Benson cycle with organic carbon. However, given the network nature of metabolism, it hence follows that photorespiration will interact with many other pathways. In this article, we review current understanding of these interactions and attempt to define key priorities for future research, which will allow us greater fundamental comprehension of general metabolic and developmental consequences of perturbation of this crucial metabolic process.
Assuntos
Plantas/metabolismo , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Respiração Celular , Luz , Fotossíntese , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Plantas/efeitos da radiaçãoRESUMO
Mutations of genes encoding for proteins within the photorespiratory core cycle and associated processes are characterised by lethality under normal air but viability under elevated CO2 conditions. This feature has been described as 'the photorespiratory phenotype' and assumed to be distinctly equal for all of these mutants. In recent years a broad collection of photorespiratory mutants has been isolated, which has allowed a comparative analysis. Distinct phenotypic features were observed when Arabidopsis thaliana mutants defective in photorespiratory enzymes were compared, and during shifts from elevated to ambient CO2 conditions. The exact reasons for the mutant-specific photorespiratory phenotypes are mostly unknown, but they indicate even more plasticity of photorespiratory metabolism. Moreover, a growing body of evidence was obtained that mutant features could be modulated by alterations of several factors, such as CO2 :O2 ratios, photoperiod, light intensity, organic carbon supply and pathogens. Hence, systematic analyses of the responses to these factors appear to be crucial to unravel mechanisms how photorespiration adapts and interacts with the whole cellular metabolism. Here we review current knowledge regarding photorespiratory mutants and propose a new level of phenotypic sub-classification. Finally, we present further questions that should be addressed in the field of photorespiration.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Dióxido de Carbono/metabolismo , Respiração Celular , Luz , Mutação , Oxigênio/metabolismo , Fenótipo , Fotoperíodo , Fotossíntese , Plantas/genética , Plantas/metabolismo , Plantas/efeitos da radiaçãoRESUMO
Approximately one third of patients with colorectal cancer (CRC) present with metastases confined to the liver only. In 15 % of these patients the metastases are primarily resectable. After resection of colorectal liver metastases the 5-year survival rate is 25 - 40 %. The EORTC trial of Nordlinger et al. has examined the role of perioperative/neoadjuvant chemotherapy of resectable liver metastases and found in the subgroup of resected patients a significant improvement in disease-free survival through chemotherapy. The results were not significant in the intent-to-treat population. Possible arguments pro neoadjuvant therapy of resectable liver metastases are the early eradication of disseminated tumour cells, the identification of a worse prognosis tumour biology in the individual patient and the higher dose density which can be achieved preoperatively versus postoperatively. Arguments against preoperative chemotherapy are the chemotherapy-induced hepatotoxicity and related increase in perioperative morbidity, the risk of achieving a complete remission of lesions which then cannot be detected intraoperatively and the uncertain optimal duration of chemotherapy. Especially surgical oncologists in Germany do not consider the neoadjuvant treatment of resectable liver metastases as a standard of care. In summary, because of the lack of level 1 evidence, patients with resectable liver metastases of colorectal cancer should be discussed within interdisciplinary tumour boards together with surgeons, gastroenterologists and medical oncologists. Potentially, overall survival data of the EORTC trial which is expected for late 2010 could change the level of evidence.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Terapia Neoadjuvante , Antineoplásicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Medicina Baseada em Evidências , Humanos , Neoplasias Hepáticas/mortalidadeRESUMO
Minimally invasive surgery has influenced the treatment of achalasia more than that of any other gastrointestinal disorder. Laparoscopic Heller myotomy has thus evolved to the first-line therapy in patients with achalasia and led to a significant change in the treatment algorithm of this disorder. The aim of this article is to present technical aspects and pitfalls of Heller myotomy with combined antirefluxplasty. After injection of 0.9% NaCl into the muscularis and submucosa of the distal esophagus and proximal fundus, whereby the submucosal layer can be easily separated from the mucosa, myotomy of the longitudinal and circular musculature is performed up to 6-7 cm proximally to the esophagogastric junction and completed distally by 1.5-2 cm onto the fundus. We prefer the 180 degrees anterior semifundoplication according to Dor as antirefluxplasty, which is sutured in a two-rowed manner into the two sites of the myotomy. The pitfalls are incomplete myotomy, especially at its distal, fundic site, with consecutive persistence or recurrence of symptoms, as well as occult mucosal perforations, which can be detected by intraoperative endoscopy.
Assuntos
Acalasia Esofágica/cirurgia , Esôfago/cirurgia , Laparoscopia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Músculo Liso/cirurgia , Algoritmos , Cárdia/cirurgia , Terapia Combinada , Acalasia Esofágica/diagnóstico , Junção Esofagogástrica/cirurgia , Esofagoscopia , Fundoplicatura/métodos , Fundo Gástrico/cirurgia , Refluxo Gastroesofágico/cirurgia , Humanos , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Postoperative venous congestion can lead to graft and remnant liver failure in living donor liver transplantation. This study was designed to delineate 'territorial belonging' of the middle hepatic vein (MHV) and to identify hepatic venous anatomy at high risk of outflow congestion. METHODS: MHV belonging patterns for right (RHL) and left (LHL) hemilivers were evaluated by three-dimensional computed tomographic reconstruction and virtual hepatectomy in 138 consecutive living liver donor candidates. RESULTS: The right hepatic vein (RHV) was dominant in 84.1 per cent and an accessory inferior hepatic vein (IHV) was present in 47.1 per cent of livers. Three MHV belonging types were identified for the RHL. Strong and complex MHV types A and C were associated with large RHL venous congestion. The MHV belonged to the LHL in 65.9 per cent, draining 37 per cent of this hemiliver. In virtual liver resections, left MHV type D was a risk category for small left liver remnants. CONCLUSION: MHV territorial belonging types A and C were identified as high risk for RHL venous congestion. Their presence should prompt consideration of either inclusion of the MHV with the right graft or reconstruction of its tributaries, and preservation of IHV territory.
Assuntos
Veias Hepáticas/anatomia & histologia , Transplante de Fígado/métodos , Fígado/irrigação sanguínea , Doadores Vivos , Tomografia Computadorizada por Raios X/métodos , Adulto , Algoritmos , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Hepatectomia/métodos , Veias Hepáticas/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Fígado/diagnóstico por imagem , Masculino , Tamanho do Órgão , Cuidados Pré-Operatórios , Radiografia IntervencionistaRESUMO
BACKGROUND: The purpose of this study was to provide information concerning the performance of selective transarterial chemoembolization (TACE) as a palliative treatment in patients with hepatocellular carcinoma (HCC), also in the case of multifocal lesions. PATIENTS AND METHODS: We reviewed prospectively collected data on 43 patients with cirrhosis and HCC who underwent selective TACE as a palliative treatment. Patients were assigned to one of two groups: (1) those with one to three HCC lesions, and (2) those with four or more HCC lesions. RESULTS: One hundred and two TACE sessions were applied in 43 patients. There were 39 men and 4 women with a mean age of 65.5 +/- 8.273 years. Alpha fetoprotein levels were elevated to a median value of 73.8 U/mL prior to first TACE (range, 1.5-25615 U/mL). Fourteen patients underwent one session, and 29 patients from two to eight TACE sessions. Bilobar HCC distribution prior to initial TACE was evident in 40% of the patients. Solitary HCC was radiologically diagnosed in 14 patients. Twenty-seven patients were assigned to group 1 and 16 patients to group 2. No significant differences were found between the two groups concerning the number of TACE sessions and the severity of liver cirrhosis. Currently 12 patients are alive after a median follow-up of 25 months (range, 3-84 months). Three- and 5-year survival rates according to patient groups were 45% and 19%, and 42% and 11% for the patients' groups 1 and 2, respectively (P = .87). CONCLUSIONS: HCC patients without a curative therapy option may benefit from palliative TACE, also in the case of multifocal lesions.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Idoso , Angiografia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Transplante de Fígado/fisiologia , Alemanha , Mortalidade Hospitalar , Humanos , Transplante de Fígado/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Sobreviventes , Fatores de TempoRESUMO
One major obstacle for successful clinical transplantation of isolated pancreatic islets (PI) is their limited survival in vivo. The aim of this study was to analyze the functional and morphological regeneration of PI in diabetic rats by Exendin-4 (Ex4) treatment in vivo. Male Wistar rats (n = 3/group) received 20 nmol/kg Ex4 i.p. for 20 days (day 0 to day +20). Diabetes was induced with 50 mg/kg streptozotocin i.v. on day -3 or on day +5. Diabetic and normal control rats received 0.9% NaCl i.p. instead. Body weight (BW), daily blood glucose (BG) and levels, oral glucose tolerance (OGT) were tested on day -5, day +10, day +20, and on day +22, ie, 48 hours after the last Ex4 injection. Histology of the pancreata ended the study on day +24. In vivo application of Ex4 could not prevent the development of diabetes. Injection of Ex4 led to a significant decrease in postprandial BG levels to 35% for 12 hours. Surprisingly, Ex4 increased postprandial BG levels up to 20% in normal rats. Ex4-treated rats showed better OGT than untreated controls. Interestingly, 48 hours after the last Ex4 injection on day +22 OGT was completely impaired. The Ex4-treated rats lost BW much faster than the untreated controls, and showed signs of gastroparesis at autopsy. Immunohistochemistry of the pancreata documented no signs of islet regeneration. Improvement of OGT in diabetic rats after Ex4 treatment may be explained by increased insulin release from the individual PI, which was confirmed by perifusion studies with isolated PI in vitro (data not shown). Yet, Ex4 may also exert an influence on the gastrointestinal tract as it delays the uptake of glucose during gastroparesis.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose , Hipoglicemiantes/uso terapêutico , Ilhotas Pancreáticas/fisiopatologia , Pâncreas/fisiologia , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Exenatida , Ilhotas Pancreáticas/efeitos dos fármacos , Pâncreas/fisiopatologia , Ratos , Ratos Wistar , RegeneraçãoRESUMO
OBJECTIVES: Adult pig islet isolation has greatly improved in the past few years. Islet grafts may now be tested in large animals. Continuous Glucose Monitoring System (CGMS) was applied to diabetic Goettingen Minipigs (GMP) to improve the management of hyperglycemia and hypoglycemia and their welfare before transplantation. METHODS: GMP (25-35 kg) received a minipig diet once daily. Diabetes was induced by streptozotocin (STZ; 150 mg/kg intravenous [IV]; n = 5) or by surgical pancreatectomy (PGMP; n = 3). Interstitial glucose concentration (IGC) was monitored continuously with an implanted sensor; CGMS was calibrated using conventional blood glucose tests 3-4 times per day; CGMS data were fed into the monitor memory and analyzed using CGMS software. RESULTS: Glucose sensors were handled accurately. Diabetes occurred 2-3 days after STZ or immediately after pancreatectomy with basal C-peptide secretion of <0.4 ng/mL (measured using intravenous glucose tolerance test) and prompt loss of body weight. Insulin substitution was necessary to keep the GMP in good condition for up to 5-6 months, with stable body weight and normal behavior. Some GMP became hypoglycemic, which was only documented by CGMS, but not by conventional glucose assays. Tight glucose control and substitution of exocrine enzymes (Creon 25,000 E/d) reduced morbidity of the PGMP, which was then comparable with that of STZ-GMP. CONCLUSIONS: The CGMS, developed for humans, is equally suitable for the 2 GMP diabetes models. Close-meshed glucose monitoring and insulin treatment improved the general condition of the diabetic GMP, ie, the islet graft recipients, and will thus greatly add to posttransplantation success.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Animais , Técnicas Biossensoriais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Insulina/metabolismo , Insulina/uso terapêutico , Insulina Glargina , Secreção de Insulina , Insulina de Ação Prolongada , Monitorização Fisiológica/métodos , Monitorização Fisiológica/veterinária , Pancreatectomia , Suínos , Porco MiniaturaRESUMO
Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.
Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/métodos , Ducto Hepático Comum , Tumor de Klatskin/cirurgia , Transplante de Fígado , Fígado/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/mortalidade , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Previsões , Ducto Hepático Comum/cirurgia , Humanos , Incidência , Tumor de Klatskin/diagnóstico , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/epidemiologia , Tumor de Klatskin/mortalidade , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Fatores de RiscoRESUMO
BACKGROUND: The appropriate management of the pancreatic remnant following distal pancreatic resection remains a clinically relevant problem. We carried out a retrospective analysis which focused on this issue and compared the two favored techniques of suture and staple closure. PATIENTS AND METHODS: Forty-six patients underwent distal pancreatectomy between October 1999 and January 2006. The patients were retrospectively analysed based on the management of the remaining pancreatic gland. Thirty-seven patients had suture and nine patients had staple closure. The morbidity, mortality, incidence of pancreatic fistula, necessity of secondary surgical intervention, and the duration of hospital stay for the two groups were compared. Pancreatic fistula was considered according to the novel international standard definition (ISGPF). In addition, subgroup analysis of patients receiving octreotide was carried out. RESULTS: Overall, postoperative morbidity due to pancreatic fistula occurred in seven patients (19%) after suture and in one patient (11%) after staple closure (p = 0.54), with no deaths. The number of patients with surgical revision related to pancreatic leakage was two (5%) after suture closure vs no revision after staple closure (p = 0.65). The median number of total hospital days for the suture group was 19 (range 7-78 days) vs 21 (range 12-96 days) for the stapler group (p = 0.21). No significant benefit for the octreotide application could be determined. CONCLUSION: According to the data, no significant difference for either suture or stapler closure was observed, with the tendency for staple closure to be superior.
RESUMO
BACKGROUND: The differential diagnoses of a circumscribed mass of the liver are varied. Especially if a malignant tumor, capable of setting metastases to the liver, is known in a patient's medical history, there might be difficulties in differentiating the tumor's entity. CASUISTRY: We report a case of a 40-year-old male with a history of malignant melanoma in whom follow-up investigations revealed a mass in the liver. RESULTS: The histopathological and microbiological results, however, showed an infestation of liver tissue with nematodes. Malignant tumor cells could not be detected. CONCLUSIONS: Roundworm-infections of the liver can present as lesions suspicious of being malignant. Therefore, along with e.g. microhamartoma, microabscesses and hepatocellular carcinoma, infestation with nematodes should be taken into consideration.
Assuntos
Hepatopatias Parasitárias/diagnóstico , Neoplasias Hepáticas/diagnóstico , Melanoma/diagnóstico , Melanoma/secundário , Infecções por Nematoides/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/patologia , Masculino , Infecções por Nematoides/parasitologia , Infecções por Nematoides/patologiaRESUMO
Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, genetic variation in the ApoD is associated with long-term clinical outcome to antipsychotic treatment. We genotyped two single-nucleotide polymorphisms in the ApoD gene in 343 chronic patients with schizophrenia spectrum disorders (ICD-10) and 346 control subjects of Danish origin. We did not find ApoD alleles, genotypes or haplotypes to be associated with disease. However, we did find that long-term clinical outcome was associated with the ApoD polymorphism rs7659 (P = 0.041) following adjustment for lifetime clinical global impression, age at first admission and gender.
Assuntos
Apolipoproteínas/genética , Polimorfismo de Nucleotídeo Único , Esquizofrenia/genética , Adulto , Antipsicóticos/uso terapêutico , Apolipoproteínas D , Estudos de Casos e Controles , DNA/análise , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
Therapeutically options for the treatment of patients with primary hepatic malignancies have grown in recent years. Apart from liver resection and organ transplantation, representing the only curative strategies for primary hepatic malignancies, a variety of palliative procedures have been introduced. Some of these result in extended patient survival. However, the combination of a malignant disease and an irreversible organ damage remains to be the main problem in the majority of patients with primary liver Cancer. Liver resection is the only curative therapy for patients with isolated hepatic colorectal metastases and can be performed with low morbidity and mortality if a correct indication and a standardized procedure is applied. In case of intrahepatic tumour recurrence re-resection is indicated as long as extrahepatic metastases can be excluded. In patients with primary unresectable metastases a downstaging-chemotherapy, two-stage hepatectomy or portal vene embolization might result in a secondary respectability. Locally ablative procedures are being evaluated at present, in the palliative Situation survival can be prolonged. In the future multimodal therapeutic approaches will dominate the treatment of primary and secondary hepatic malignancies.
Assuntos
Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Cuidados PaliativosRESUMO
BACKGROUND AND AIMS: The passenger leukocytes harboured within an allograft induce a massive allo-immune response that leads to allograft rejection if not countered by immunosuppression. We compared the response to short-term immunosuppression of parathyroid gland transplants possessing few passenger leukocytes with that of passenger leukocyte-rich small bowel transplants. METHODS: Heterotopic parathyroid and orthotopic small bowel transplantation was performed in a Wistar Furth-to-Lewis rat strain combination. Immunosuppression with cyclosporine A (CsA) was administered in different dosages for 14 days. Dysfunctional allografts were examined immunohistologically. RESULTS: CsA more effectively suppressed the immune response provoked by immunogenic small bowel grafts than that induced by less-immunogenic parathyroid grafts. Immunosuppression with 20 mg/kg per day induced long-term survival in the small bowel (165+/-21 days) but not in the parathyroid (28+/-3 days). All rejected grafts featured massive cellular infiltration by activated T cells as a sign of immune rejection. CONCLUSION: Immunosuppressive dosages effective in passenger leukocyte-rich small bowel transplants were not as effective in parathyroid gland transplants harbouring few passenger leukocytes. In spite of the paucity of passenger leukocytes in parathyroid grafts it is more difficult to control by immunosuppression the immune response to them than that to the passenger leukocyte-rich small bowel.
Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/imunologia , Imunossupressores/uso terapêutico , Leucócitos/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Glândulas Paratireoides/transplante , Animais , Cálcio/sangue , Ciclosporina/administração & dosagem , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Masculino , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos WF , Transplante HomólogoRESUMO
This survey was established to evaluate everyday use of interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) in metastatic renal-cell carcinoma (mRCC). Of 186 centers (with 2200 patients per year) that responded, 182 support immunotherapy by using it themselves (147 centers) or by referring patients (35 centers). Effectiveness and tolerance are the main reasons for use. 133 centers use IL-2 subcutaneously, 64 by inhalation, 24 use it locally or intratumorally. Continuous intravenous IL-2 is used in 13 centers only. Most centers use subcutaneous combinations of IL-2 and IFN-alpha, either alone or with 5-fluorouracil and/or isotretinoin; IFN-alpha/Vinblastin combinations, IFN-alpha-monotherapy, and IL-2 s.c.-monotherapy are used with similar frequency. Average treatment duration is 3-6 months. Maintenance therapy is used in responding patients in 118 centers. Subcutaneous and local application of IL-2 is standard treatment for mRCC in Germany and subcutaneous IL-2 and IFN-alpha represents the most frequently used combination.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Metástase Neoplásica/terapia , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/imunologia , Quimioterapia Combinada , Alemanha , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Interferon-alfa/efeitos adversos , Interleucina-2/efeitos adversos , Neoplasias Renais/imunologia , Taxa de SobrevidaRESUMO
Two different aspects of the influence of neuromonitoring on the possible reduction of post-operative recurrent laryngeal nerve palsies require critical examination: the nerve identification and the monitoring of it's functions. Due to the additional information from the EMG signals, neuromonitoring is the best method for identifying the nerves as compared to visual identification alone. There are still no randomized studies available that compare the visual and electrophysiological recurrent laryngeal nerve detection in thyroid operations with respect to the postoperative nerve palsies. Nevertheless, comparisons with historical collectives show that a constant low nerve-palsy-rate was achieved with electrophysiological detection in comparison to visual detection. The rate of nerve identification is normally very high and amounts to 99 % in our own patients. The data obtained during the "Quality assurance of benign and malignant Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve-palsy-rates are achieved with neuromonitoring as compared to solely visual detection. Following subtotal resection, this discrepancy becomes even statistically significant. While monitoring the nerve functions with the presently used neuromonitoring technique, it is possible to observe the EMG-signal remaining constant or decreasing in volume. Assuming that a constant neuromonitoring signal represents a normal vocal cord, our evaluation shows that there is a small percentage of false negative and positive results. Looking at the permanent recurrent nerve palsy rates, this method has a specificity of 98 %, a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative prognostic value of 100 %. Although an altered neuromonitoring signal can be taken as a clear indication of eventual nerve damage, an absolutely reliable statement about the postoperative vocal cord function is presently not possible with intraoperative neuromonitoring.
Assuntos
Complicações Intraoperatórias/prevenção & controle , Monitorização Intraoperatória , Tireoidectomia , Paralisia das Pregas Vocais/prevenção & controle , Eletromiografia , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Valor Preditivo dos Testes , Garantia da Qualidade dos Cuidados de Saúde , Paralisia das Pregas Vocais/diagnósticoRESUMO
We investigated 238 patients with 431 nerves at risk (NAR) undergoing thyroid surgery. Positive identification of the recurrent laryngeal nerve was obtained in 99.3 % of NAR with intraoperative neuromonitoring. 19 patients (4.4 % NAR) suffered from unilateral vocal cord dysfunction in the early postoperative phase. A complete restitution of vocal cord function could be demonstrated in 18 of these patients, leaving one patient (0.23 % NAR) with a permanent vocal cord dysfunction. Our data show that reliable predictions concerning the postoperative outcome of nerve function cannot always be made on the basis of the intraoperative findings. Thus, our own data show a specifity of 98.5 % and a negative predictive value of 96.8 %. On the other hand, sensitivity was 23.5 % and positive predictive value was 40 %. Misinterpretation of the intraoperative signal can lead to risky operative manoeuvres. Possible reasons for the misinterpretation of the intraoperative signal and a critical reflection on the possibilities and predictive values of neuromonitoring will be discussed.
Assuntos
Monitorização Intraoperatória , Complicações Pós-Operatórias/prevenção & controle , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia , Paralisia das Pregas Vocais/prevenção & controle , Erros de Diagnóstico , Alemanha , Hospitais Universitários , Humanos , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , Paralisia das Pregas Vocais/diagnósticoRESUMO
Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroid surgery can cause serious consequences for patients who depend on control of pitch and a clear and forceful voice, like singers or professional speakers. We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of cases. The recording electrode could be placed either into the cricothyroid muscle or the vocal cord. The latter position proved superior if the recurrent laryngeal nerve had to be identified as well. 16 percent of the nerves crossed the branches of the superior thyroid artery at or below the upper pole of the gland, posing a "high risk" for intraoperative lesions. Our data confirm the results of smaller studies reporting this type of nerve course in 12 % to 14 % of patients. The present findings show a significant number of EBSLN to be in danger of injury when the superior thyroid artery is ligated during thyroid surgery. Neuromonitoring proofed to be a reliable method to identify the nerve, which is an important element in concepts to prevent its injury.