RESUMO
BACKGROUND: Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy. METHODS: The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan-Meier survival estimates. RESULTS: The trial included 566 patients. Median follow-up was 38 (range 7-67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75). CONCLUSION: After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.
Assuntos
Neoplasias da Mama/cirurgia , Detecção Precoce de Câncer/métodos , Excisão de Linfonodo/métodos , Linfonodo Sentinela/patologia , Adulto , Idoso , Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/secundário , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Mastectomia/métodos , Pessoa de Meia-Idade , Micrometástase de Neoplasia , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/métodos , Taxa de Sobrevida/tendências , Suécia/epidemiologiaRESUMO
PURPOSE: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes. METHODS: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed. RESULTS: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p = 0.037). CONCLUSIONS: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.
Assuntos
Neoplasias da Mama/epidemiologia , Ensaios Clínicos como Assunto/normas , Auditoria Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Excisão de Linfonodo , Metástase Linfática , Auditoria Médica/métodos , Pessoa de Meia-Idade , Micrometástase de Neoplasia , Sistema de Registros , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Suécia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking. METHODS: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy. RESULTS: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer-specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001). CONCLUSION: The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.
Assuntos
Carcinoma de Mama in situ/terapia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Mastectomia Segmentar/métodos , Adulto , Idoso , Carcinoma de Mama in situ/mortalidade , Carcinoma de Mama in situ/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Mastectomia Segmentar/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos Prospectivos , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/mortalidade , Fatores de Risco , Análise de Sobrevida , Suécia/epidemiologia , Carga TumoralRESUMO
BACKGROUND: Sentinel node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles is a novel method in breast cancer. Several studies have verified the non-inferiority of SPIO compared with the standard use of radioisotope 99m Tc with or without blue dye. The aim of the MONOS study presented here was to evaluate the use of SPIO as a sole tracer and the efficacy of tracer injection in the preoperative setting. METHODS: This prospective cohort study was carried out in two hospitals, one using 99m Tc and the other SPIO. 99m Tc was injected in the morning of the day of surgery or the day before. SPIO was either injected before surgery in the outpatient clinic or 1 h before the operation. RESULTS: A total of 338 consecutive patients with breast cancer underwent 343 procedures; SPIO nanoparticles were used in 184 procedures and 99m Tc-labelled tracer in 159. Detection rates for SPIO and 99m Tc were 95·6 and 96·9 per cent respectively (P = 0·537). All nodes with SPIO uptake were coloured brown. Fewer nodes were retrieved with SPIO (mean 1·35 versus 1·89), regardless of whether blue dye was used (P < 0·001). Preoperative SPIO injection (58·7 per cent of procedures), a median of 16 (range 2-27) days before the procedure, was associated with a better tracer-specific detection rate (95·3 versus 86 per cent; P = 0·031) and retrieval of more nodes (mean 1·43 versus 1·03; P < 0·001) than perioperative administration. Skin staining was present in 39·9 per cent of patients, and was related to breast-conserving surgery and periareolar injection. CONCLUSION: The use of SPIO alone is a safe alternative, with results comparable to those of the standard dual technique using 99m Tc and blue dye. The efficacy of injection in the preoperative setting simplifies logistics and improves performance. Skin staining can be prevented by a deeper peritumoral injection.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Compostos Férricos , Linfonodos/patologia , Nanopartículas de Magnetita , Biópsia de Linfonodo Sentinela/métodos , Idoso , Corantes , Custos e Análise de Custo , Feminino , Compostos Férricos/efeitos adversos , Humanos , Metástase Linfática , Nanopartículas de Magnetita/efeitos adversos , Mastectomia Segmentar , Pessoa de Meia-Idade , Satisfação do Paciente , Transtornos da Pigmentação/etiologia , Estudos Prospectivos , Cintilografia , Biópsia de Linfonodo Sentinela/economia , Agregado de Albumina Marcado com Tecnécio Tc 99mRESUMO
BACKGROUND: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced arm morbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late. METHODS: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates. RESULTS: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1·6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence. CONCLUSION: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/cirurgia , Reações Falso-Negativas , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , SuéciaRESUMO
BACKGROUND: Klotho is an 'anti-ageing' hormone and transmembrane protein; Klotho deficient mice develop a similar ageing phenotype to smokers including emphysema and muscle wasting. The objective of this study was to evaluate skeletal muscle and circulating Klotho protein in smokers and COPD patients and to relate Klotho levels to relevant skeletal muscle parameters. We sought to validate our findings by undertaking complimentary murine studies. METHODS: Fat free mass, quadriceps strength and spirometry were measured in 87 participants (61 COPD, 13 'healthy smokers' and 13 never smoking controls) in whom serum and quadriceps Klotho protein levels were also measured. Immunohistochemistry was performed to demonstrate the location of Klotho protein in human skeletal muscle and in mouse skeletal muscle in which regeneration was occurring following injury induced by electroporation. In a separate study, gastrocnemius Klotho protein was measured in mice exposed to 77 weeks of smoke or sham air. RESULTS: Quadriceps Klotho levels were lower in those currently smoking (p = 0.01), irrespective of spirometry, but were not lower in patients with COPD. A regression analysis identified current smoking status as the only independent variable associated with human quadriceps Klotho levels, an observation supported by the finding that smoke exposed mice had lower gastrocnemius Klotho levels than sham exposed mice (p = 0.005). Quadriceps Klotho levels related to local oxidative stress but were paradoxically higher in patients with established muscle wasting or weakness; the unexpected relationship with low fat free mass was the only independent association. Within locomotor muscle, Klotho localized to the plasma membrane and to centralized nuclei in humans and in mice with induced muscle damage. Serum Klotho had an independent association with quadriceps strength but did not relate to quadriceps Klotho levels or to spirometric parameters. CONCLUSIONS: Klotho is expressed in skeletal muscle and levels are reduced by smoking. Despite this, quadriceps Klotho protein expression in those with established disease appears complex as levels were paradoxically elevated in COPD patients with established muscle wasting. Whilst serum Klotho levels were not reduced in smokers or COPD patients and were not associated with quadriceps Klotho protein, they did relate to quadriceps strength.
Assuntos
Glucuronidase/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumar/metabolismo , Animais , Feminino , Glucuronidase/sangue , Humanos , Imuno-Histoquímica , Proteínas Klotho , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Músculo Quadríceps/metabolismo , Músculo Quadríceps/fisiopatologia , Análise de Regressão , Fumar/efeitos adversos , Fumar/sangue , EspirometriaRESUMO
BACKGROUND: A phase I trial was performed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics and immunogenicity of the anti-EpCAM immunotoxin (IT) MOC31PE in cancer patients. An important part of the study was to investigate whether the addition of Sandimmune (cyclosporin, CsA) suppressed the development of anti-IT antibodies. METHODS: Patients with EpCAM-positive metastatic disease were eligible for treatment with intravenous MOC31PE using a modified Fibonacci dose escalation sequence. Maximum tolerated dose was first established without, then with intravenously administered CsA. RESULTS: Sixty-three patients were treated with MOC31PE in doses ranging from 0.5 to 8 µg kg(-1). Maximum tolerated dose was 8 µg kg(-1) for MOC31PE alone, and 6.5 µg kg(-1) when combined with CsA. The dose-limiting adverse event was reversible liver toxicity. No radiological complete or partial responses were observed, whereas stable disease was seen in 36% of the patients receiving MOC31PE only. The pharmacokinetic profile of MOC31PE was characterised by linear kinetics and with a half-life of â¼3 h. The addition of CsA delayed the generation of anti-IT antibodies. CONCLUSIONS: Intravenous infusion of MOC31PE can safely be administered to cancer patients. Immune suppression with CsA delays the development of anti-MOC31PE antibodies. The antitumour effect of MOC31PE warrants further evaluation in EpCAM-positive metastatic disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Moléculas de Adesão Celular/antagonistas & inibidores , Imunoconjugados/administração & dosagem , Neoplasias/tratamento farmacológico , Adulto , Idoso , Alanina Transaminase/sangue , Animais , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aspartato Aminotransferases/sangue , Neoplasias da Medula Óssea/tratamento farmacológico , Neoplasias da Medula Óssea/secundário , Carcinoma/química , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Moléculas de Adesão Celular/análise , Moléculas de Adesão Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclosporina/administração & dosagem , Interações Medicamentosas , Molécula de Adesão da Célula Epitelial , Feminino , Meia-Vida , Humanos , Imunoconjugados/efeitos adversos , Infusões Intravenosas , Dose Letal Mediana , Macaca fascicularis , Masculino , Dose Máxima Tolerável , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Micrometástase de Neoplasia , Neoplasias/química , Neoplasias/patologia , Resultado do TratamentoRESUMO
A large outbreak of norovirus (NoV) gastroenteritis caused by contaminated municipal drinking water occurred in Lilla Edet, Sweden, 2008. Epidemiological investigations performed using a questionnaire survey showed an association between consumption of municipal drinking water and illness (odds ratio 4·73, 95% confidence interval 3·53-6·32), and a strong correlation between the risk of being sick and the number of glasses of municipal water consumed. Diverse NoV strains were detected in stool samples from patients, NoV genotype I strains predominating. Although NoVs were not detected in water samples, coliphages were identified as a marker of viral contamination. About 2400 (18·5%) of the 13,000 inhabitants in Lilla Edet became ill. Costs associated with the outbreak were collected via a questionnaire survey given to organizations and municipalities involved in or affected by the outbreak. Total costs including sick leave, were estimated to be â¼8,700,000 Swedish kronor (â¼0·87 million).
Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Gastroenterite/epidemiologia , Microbiologia da Água , Infecções por Caliciviridae/virologia , Fezes/virologia , Gastroenterite/virologia , Humanos , Norovirus/isolamento & purificação , Inquéritos e Questionários/economia , Suécia/epidemiologia , Abastecimento de ÁguaRESUMO
BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection as the routine staging procedure in clinically node-negative breast cancer. False-negative SLN biopsy results in misclassification and may cause undertreatment of the disease. The aim of this study was to investigate whether serial sectioning of SLNs reveals metastases more frequently in patients with false-negative SLNs than in patients with true-negative SLNs. METHODS: This was a case-control study. Tissue blocks from patients with false-negative SLNs, defined as tumour-positive lymph nodes excised at completion axillary dissection or a subsequent axillary tumour recurrence, were reassessed by serial sectioning and immunohistochemical staining. For each false-negative node, two true-negative SLN biopsies were analysed. Tumour and node characteristics in patients with false-negative SLNs were compared with those in patients with a positive SLN by univariable and multivariable regression analysis. RESULTS: Undiagnosed SLN metastases were discovered in nine (18 per cent) of 50 patients in the false-negative group and in 12 (11.2 per cent) of 107 patients in the true-negative group (P = 0.245). The metastases were represented by isolated tumour cells in 14 of these 21 patients. The risk of a false-negative SLN was higher in patients with hormone receptor-negative (odds ratio (OR) 2.50, 95 per cent confidence interval 1.17 to 5.33) or multifocal tumours (OR 3.39, 1.71 to 6.71), or if only one SLN was identified (OR 3.57, 1.98 to 6.45). CONCLUSION: SLN serial sectioning contributes to a higher rate of detection of SLN metastasis. The rate of upstaging of the tumour is similar in false- and true-negative groups of patients.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Pessoa de Meia-Idade , Análise de Regressão , Biópsia de Linfonodo Sentinela/normas , Carga TumoralRESUMO
BACKGROUND: We previously reported that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning reduced the cumulative incidence of eczema. OBJECTIVE: To investigate the impact of feeding LF19 on T-cell maturation. METHODS: One hundred and seventy-nine healthy, term infants with no prior allergic manifestations were randomized to daily intake of cereals with (n = 89) or without (n = 90) the addition of LF19 10(8 ) colony forming units per serving from 4 to 13 months of age. Venous blood was drawn at 5.5 and 13 months of age. We used the cytokine response to polyclonal T-cell stimulation by anti-CD3 plus anti-CD28 monoclonal antibodies, and in vitro stimulation with the vaccine tetanus toxoid (TT) as measures of global adaptive immunity and capacity to raise a specific T-cell response, respectively. Expression levels of IL-2, IFN-γ, IL-4, IL-17A and IL-10 messenger RNAs (mRNAs) were used as proxies for general T-cell stimulation and naive Th0 cells, Th1-, Th2-, Th17- and T regulatory lineages. RESULTS: There was no difference between the two groups at 5.5 months of age. At 13 months, the polyclonal IL-2 response was higher in the placebo group (P < 0.05), whereas the IFN-γ/IL-2 (P < 0.01) and IL-17A/IL-2 (P < 0.05) ratios after polyclonal stimulation were higher in the probiotic group, as was the TT-specific IL17-A response (P < 0.001). In both groups, the IFN-γ and IL-4 responses increased from 5.5 to 13 months upon both polyclonal and specific stimulation (P < 0.01), whereas the IL-10 response remained low (P > 0.05). CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest modest effects by probiotics on T-cell maturation following 9 months of probiotic intake. Future studies should address if specific probiotics may drive immune development with possible preventive effects on the development of allergic disease.
Assuntos
Lactobacillus/imunologia , Ativação Linfocitária/efeitos dos fármacos , Probióticos/uso terapêutico , Linfócitos T/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Citocinas/biossíntese , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Hipersensibilidade/prevenção & controle , Lactente , Ativação Linfocitária/imunologia , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/imunologiaRESUMO
INTRODUCTION: Current guidelines recommend completion axillary lymph node dissection (cALND) in case of a sentinel lymph node (SLN) metastasis larger than 0.2 mm. However, in 50%-65% of these patients, the non-SLNs contain no further metastases and cALND provides no benefit. Several nomograms and scoring systems have been suggested to predict the risk of metastases in non-SLNs. We have evaluated the Tenon score. PATIENTS AND METHODS: In a retrospective review of the Swedish Sentinel Node Multicentre Cohort Study, risk factors for additional metastases were analysed in 869 SLN-positive patients who underwent cALND, using uni- and multivariate logistic regression models. A receiver operating characteristic (ROC) curve was drawn on the basis of the sensitivity and specificity of the Tenon score, and the area under the curve (AUC) was calculated. RESULTS: Non-SLN metastases were identified in 270/869 (31.1%) patients. Tumour size and grade, SLN status and ratio between number of positive SLNs and total number of SLNs were significantly associated with non-SLN status in multivariate analyses. The area under the curve for the Tenon score was 0.65 (95% CI 0.61-0.69). In 102 patients with a primary tumour <2 cm, Elston grade 1-2 and SLN metastases ≤2 mm, the risk of non SLN metastasis was less than 10%. CONCLUSION: The Tenon score performed inadequately in our material and we could, based on tumour and SLN characteristics, only define a very small group of patients in which negative non-sentinel nodes could be predicted.
RESUMO
BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, and few are multicentre studies. METHODS: Between September 2000 and January 2004, patients who were SLN-negative and did not have ALND were included in a prospective cohort. Kaplan-Meier estimates were used to analyse the rates of axillary recurrence and survival. The risk of axillary recurrence was also compared in centres with high and low experience with the SLN biopsy (SLNB) technique. RESULTS: A total of 2195 patients with 2216 breast tumours were followed for a median of 65 months. Isolated axillary recurrence was diagnosed in 1·0 per cent of patients. The event-free 5-year survival rate was 88·8 per cent and the overall 5-year survival rate 93·1 per cent. There was no difference in recurrence rates between centres contributing fewer than 150 SLNB procedures to the cohort and centres contributing 150 or more procedures. CONCLUSION: This study confirmed the low risk of axillary recurrence 5 years after SLNB for breast cancer without ALND.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Mamografia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Exame Físico , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to identify the sources of sporadic domestic Salmonella cases in Sweden and to evaluate the usefulness of a source-attribution model in a country in which food animals are virtually free from Salmonella. The model allocates human sporadic domestic Salmonella cases to different sources according to distribution of Salmonella subtypes in the different sources. Sporadic domestic human Salmonella cases (n=1086) reported between July 2004 and June 2006 were attributed to nine food-animal and wildlife sources. Of all Salmonella cases, 82% were acquired abroad and 2·9% were associated with outbreaks. We estimated that 6·4% were associated with imported food, 0·5% with food-producing animals, and 0·6% with wildlife. Overall, 7·7% could not be attributed to any source. We concluded that domestic food-producing animals are not an important source for Salmonella in humans in Sweden, and that the adapted model is useful also in low-prevalence countries.
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Infecções por Salmonella/epidemiologia , Infecções por Salmonella/transmissão , Animais , Animais Domésticos , Animais Selvagens , Doenças Transmitidas por Alimentos/epidemiologia , Humanos , Salmonelose Animal/epidemiologia , Salmonelose Animal/transmissão , Suécia/epidemiologia , Zoonoses/transmissãoRESUMO
Over 400 office workers from the same unit of a manufacturing company in Stockholm County, Sweden, fell ill with gastroenteritis. A retrospective cohort study of office workers in the affected unit demonstrated that canteen visitors on one day had an increased risk of illness [risk ratio (RR) 27.1, 95% confidence interval (CI) 15.7-46.8] compared to non-visitors. A second study, investigating canteen visitors' consumption of particular food items, showed that both tomatoes from the salad buffet (RR 5.6, 95% CI 3.2-9.6) and hamburgers (RR 4.9, 95% CI 2.4-9.8) were the most likely vehicles of infection. Norovirus GI.3 (Desert Shield) was identified in stool samples from three office workers and from a food handler who prepared the tomatoes for the salad buffet and hamburger ingredients before vomiting at the workplace on 12 November. The outbreak could have been prevented if the food items prepared by the food handler some hours before vomiting had not been served.
Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Doenças Transmitidas por Alimentos/epidemiologia , Gastroenterite/epidemiologia , Norovirus/isolamento & purificação , Adulto , Idoso , Infecções por Caliciviridae/virologia , Fezes/virologia , Feminino , Doenças Transmitidas por Alimentos/virologia , Gastroenterite/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious. METHODS: We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats. RESULTS: The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented. CONCLUSION: The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.
Assuntos
Antineoplásicos/administração & dosagem , Ciclosporina/administração & dosagem , Imunotoxinas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Imunotoxinas/imunologia , Masculino , Metástase Neoplásica , Neoplasias Experimentais/tratamento farmacológico , Ratos , Sirolimo/farmacologia , Tacrolimo/farmacologiaRESUMO
Young children account for a large proportion of reported Yersinia enterocolitica infections in Sweden with a high incidence compared with other gastrointestinal infections, such as salmonellosis and campylobacteriosis. A case-control study was conducted to investigate selected risk factors for domestic sporadic yersiniosis in children aged 0-6 years in Sweden. In total, 117 cases and 339 controls were included in the study. To minimize exclusion of observations due to missing data a multiple non-parametric imputation technique was used. The following risk factors were identified in the multivariate analysis: eating food prepared from raw pork products (OR 3.0, 95% CI 1.8-5.1) or treated sausage (OR 1.9, 95% CI 1.1-3.3), use of a baby's dummy (OR 1.9, 95% CI 1.1-3.2) and contact with domestic animals (OR 2.0, 95% CI 1.2-3.4). We believe that the importance of Y. enterocolitica infection in children has been neglected and that results from this study can be used to develop preventive recommendations.
Assuntos
Yersiniose/epidemiologia , Yersiniose/microbiologia , Yersinia enterocolitica/isolamento & purificação , Animais , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fômites , Microbiologia de Alimentos , Humanos , Lactente , Masculino , Carne/microbiologia , Análise Multivariada , Razão de Chances , Risco , Suécia/epidemiologia , SuínosRESUMO
In 2005 a large outbreak of verotoxin-producing Escherichia coli (VTEC) occurred in Sweden. Cases were interviewed and cohort and case-control studies were conducted. Microbiological investigations were performed using polymerase chain reaction (PCR) to detect the Shiga-like toxin (Stx) genes followed by cultivation and pulsed-field gel electrophoresis. A total of 135 cases were recorded, including 11 cases of hemolytic uremic syndrome. The epidemiological investigations implicated lettuce as the most likely source of the outbreak, with an OR of 13.0 (CI 2.94-57.5) in the case-control study. The lettuce was irrigated by water from a small stream, and water samples were positive for Stx 2 by PCR. The identical VTEC O157 Stx 2 positive strain was isolated from the cases and in cattle at a farm upstream from the irrigation point. An active surveillance and reporting system was crucial and cooperation between all involved parties was essential for quickly identifying the cause of this outbreak. Handling of fresh greens from farm to table must be improved to minimize the risk of contamination.
Assuntos
Infecções por Escherichia coli/epidemiologia , Escherichia coli O157/isolamento & purificação , Contaminação de Alimentos/análise , Síndrome Hemolítico-Urêmica/epidemiologia , Lactuca/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Surtos de Doenças , Escherichia coli O157/patogenicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto JovemRESUMO
Previous outbreaks of Salmonella Enteritidis in Canada and the United States have been associated with the consumption of almonds. From December 2005 to August 2006 a cluster of 15 cases of Salmonella Enteritidis NST 3+ was reported in Sweden. A case-control study was performed to identify the source of transmission. Three controls per case were randomly selected, matched on sex, age and place of residence. Cases and controls were interviewed by telephone and data were analysed with a conditional logistic model. The results showed that eating almonds was a risk factor for infection with Salmonella Enteritidis NST3+ (unmatched odds ratio 45.0, 95% confidence interval: 4.8-421.8). No Salmonella was isolated from almonds tested in the study. In conclusion, almonds could be the source of the outbreak and should be considered when investigating outbreaks as well as sporadic cases of Salmonella Enteritidis.