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2.
Hernia ; 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172376

RESUMO

AIM: To facilitate midline fascial closure in complex abdominal wall surgery, component separation techniques (CST) are usually required. However, CST is associated with an enlarged morbidity. Prehabilitation could increase the compliance of the abdominal wall and thereby decrease the necessity of myofascial release. This can be accomplished by administration of botulinum toxin type A (BTA) in the lateral abdominal wall musculature. The aim of this study was to determine the effect of BTA on the subsequent necessity to perform CST in patients with complex abdominal wall hernias. METHODS: Patients with a complex abdominal wall hernia, planned to undergo CST between July 2020 and November 2022 were included. Outcome of procedures with 300U of BTA 4 (2-6) weeks prior to surgery, were retrospectively analyzed by comparison with propensity matched subjects of an historical group. Hernia width difference was assessed by CT and operative details were included. RESULTS: A total of 13 patients with a median hernia width of 12 cm (IQR 9-14, range 24) were prehabilitated with BTA between July 2020 and November 2022. A CST was planned for all, however not required in 6/13 patients (46%) to accomplish midline fascial closure. A mean elongation of lateral abdominal wall musculature of 4.01 cm was seen in patients not requiring CST. Compared to the propensity score matched control group, a 27% reduction (p = 0.08) in the need for CST was observed. CONCLUSION: There is a tendency for decrease of necessity for CST by preoperatively administered BTA in patients with complex abdominal wall defects. Although small, as this study used propensity matched comparison, further exploration of BTA should be encouraged.

3.
Hernia ; 27(3): 623-633, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36890358

RESUMO

BACKGROUND: Patients often need admission at an Intensive Care Unit (ICU), immediately after complex abdominal wall reconstruction (CAWR). Lack of ICU resources requires adequate patient selection for a planned postoperative ICU admission. Risk stratification tools like Fischer score and Hernia Patient Wound (HPW) classification may improve patient selection. This study evaluates the decision-making process in a multidisciplinary team (MDT) on justified ICU admissions for patients after CAWR. METHODS: A pre-Covid-19 pandemic cohort of patients, discussed in a MDT and subsequently underwent CAWR between 2016 and 2019, was analyzed. A justified ICU admission was defined by any intervention within the first 24 h postoperatively, considered not suitable for a nursing ward. The Fischer score predicts postoperative respiratory failure by eight parameters and a high score (> 2) warrants ICU admission. The HPW classification ranks complexity of hernia (size), patient (comorbidities) and wound (infected surgical field) in four stages, with increasing risk for postoperative complications. Stages II-IV point to ICU admission. Accuracy of the MDT decision and (modifications of) risk-stratification tools on justified ICU admissions were analyzed by backward stepwise multivariate logistic regression analysis. RESULTS: Pre-operatively, the MDT decided a planned ICU admission in 38% of all 232 CAWR patients. Intra-operative events changed the MDT decision in 15% of all CAWR patients. MDT overestimated ICU need in 45% of ICU planned patients and underestimated in 10% of nursing ward planned patients. Ultimately, 42% went to the ICU and 27% of all 232 CAWR patients were justified ICU patients. MDT accuracy was higher than the Fischer score, HPW classification or any modification of these risk stratification tools. CONCLUSION: A MDT's decision for a planned ICU admission after complex abdominal wall reconstruction was more accurate than any of the other risk-stratifying tools. Fifteen percent of the patients experienced unexpected operative events that changed the MDT decision. This study demonstrated the added value of a MDT in the care pathway of patients with complex abdominal wall hernias.


Assuntos
Parede Abdominal , COVID-19 , Humanos , Parede Abdominal/cirurgia , Pandemias , Estudos Retrospectivos , Herniorrafia/efeitos adversos , Unidades de Terapia Intensiva , Hérnia , Equipe de Assistência ao Paciente
4.
Hernia ; 27(3): 609-616, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36787034

RESUMO

PURPOSE: Surgical site occurrences after transversus abdominis release in ventral hernia repair are still reported up to 15%. Evidence is rising that preoperative improvement of risk factors might contribute to optimal patient recovery. A reduction of complication rates up to 40% has been reported. The aim of this study was to determine whether prehabilitation has a favorable effect on the risk on wound and medical complications as well as on length of stay. METHODS: A retrospective cohort study was performed in a tertiary referral center for abdominal wall surgery. All patients undergoing ventral hernia repair discussed at multidisciplinary team (MDT) meetings between 2015 and 2019 were included. Patients referred for a preconditioning program by the MDT were compared to patients who were deemed fit for operative repair by the MDT, without such a program. Endpoints were patients, hernia, and procedure characteristics as well as length of hospital stay, wound and general complications. RESULTS: A total of 259 patients were included of which 126 received a preconditioning program. Baseline characteristics between the two groups were statistically significantly different as the prehabilitated group had higher median BMI (28 vs 30, p < 0.001), higher HbA1c (41 vs 48, p = 0.014), more smokers (4% vs 25%, p < 0.001) and higher HPW classes due to more patient factors (14% vs 48%, p < 0.001). There were no significant differences in intra-operative and postoperative outcome measures. CONCLUSIONS: This study showed prehabilitation facilitates patients with relevant comorbidities achieving the same results as patients without those risk factors. The indication of a preconditioning program might be effective at the discretion of an MDT meeting. Further research could focus on the extent of such program to assess its value.


Assuntos
Parede Abdominal , Hérnia Ventral , Humanos , Estudos Retrospectivos , Exercício Pré-Operatório , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Hérnia Ventral/cirurgia , Hérnia Ventral/etiologia , Músculos Abdominais/cirurgia , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/cirurgia , Parede Abdominal/cirurgia
5.
Tech Coloproctol ; 27(4): 297-307, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36336745

RESUMO

BACKGROUND: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. METHODS: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. RESULTS: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). CONCLUSIONS: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Neoplasias Retais , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Colite Ulcerativa/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Proctocolectomia Restauradora/métodos , Neoplasias Retais/cirurgia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Bolsas Cólicas/efeitos adversos , Resultado do Tratamento
6.
Eur J Nucl Med Mol Imaging ; 49(3): 943-952, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476551

RESUMO

PURPOSE: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. METHODS: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. RESULTS: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8-94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). CONCLUSION: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: HOVON-84: EudraCT: 2006-005,174-42, retrospectively registered 01-08-2008. HOVON-130: EudraCT: 2014-002,654-39, registered 26-01-2015.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Rearranjo Gênico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos
7.
BMJ Open ; 10(5): e035326, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32461297

RESUMO

INTRODUCTION: Adalimumab is effective for maintenance of remission in patients with Crohn's disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW). METHODS AND ANALYSIS: The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBERS: EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).


Assuntos
Doença de Crohn , Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados , Doença de Crohn/tratamento farmacológico , Humanos , Estudos Multicêntricos como Assunto , Países Baixos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa
9.
Ann Hematol ; 97(2): 255-266, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29209924

RESUMO

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Análise Custo-Benefício , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Idoso , Linfoma de Burkitt/complicações , Linfoma de Burkitt/economia , Linfoma de Burkitt/mortalidade , Carmustina/economia , Carmustina/uso terapêutico , Ciclofosfamida/economia , Ciclofosfamida/uso terapêutico , Citarabina/economia , Citarabina/uso terapêutico , Etoposídeo/economia , Etoposídeo/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/economia , Infecções por HIV/mortalidade , Humanos , Ifosfamida/economia , Ifosfamida/uso terapêutico , Masculino , Melfalan/economia , Melfalan/uso terapêutico , Metotrexato/economia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Rituximab/economia , Rituximab/uso terapêutico , Análise de Sobrevida
11.
J Crohns Colitis ; 11(12): 1463-1470, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-28981621

RESUMO

BACKGROUND AND AIMS: The number of patients with inflammatory bowel disease [IBD], of non-Caucasian descent in Western Europe, is increasing. We aimed to explore the impact of ethnicity and country of birth on IBD phenotype. METHODS: IBD patients treated in the eight University Medical Centers in The Netherlands [Dutch IBD Biobank] were divided into two groups according to their ethnicity: 1] Caucasian patients of Western and Central European descent [CEU]; and 2] patients of non-Caucasian descent [non-CEU]. The non-CEU group was subdivided according to country of birth, into: born in The Netherlands or Western Europe [non-CEU European born]; or born outside Western-Europe who migrated to The Netherlands [non-CEU non-European born]. Both comparisons were analysed for phenotype differences [by chi-square test]. RESULTS: The Dutch IBD Biobank included 2921 CEU patients and 233 non-CEU patients. Non-CEU Crohn's disease [CD] patients more often had upper gastro-intestinal disease [16% vs 8%, p = 0.001] and anal stenosis [10% vs 4%, p = 0.002] than CEU CD patients. The use of anti-tumour necrosis factor [TNF] agents and immunomodulators was higher in non-CEU IBD patients than in CEU IBD patients [45% vs 38%, p = 0.042] and [77% vs 66%, p = 0.001], respectively. Non-CEU IBD patients born in Europe [n = 116] were diagnosed at a lower age than non-CEU IBD patients born outside Europe [n = 115] [at 22.7 vs 28.9 years old, p < 0.001]. CONCLUSION: Non-Caucasians had more severe disease behaviour than Caucasians. Non-CEU patients born in Europe were diagnosed at a lower age with IBD than those born outside Europe who migrated to The Netherlands.


Assuntos
Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Fístula Intestinal/etnologia , Fenótipo , Características de Residência , Adulto , Idade de Início , Idoso , Canal Anal/patologia , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Constrição Patológica/etnologia , Doença de Crohn/genética , Doença de Crohn/terapia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , População Branca/estatística & dados numéricos
12.
Aliment Pharmacol Ther ; 46(10): 953-963, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28914446

RESUMO

BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni- and multivariate Cox-proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109 /L and infections were classified according to the Common Terminology Criteria for Adverse Events. RESULTS: Sixty hundred and ninety-five patients (90.6%) included in the TOPIC-trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29-112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39-4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71-0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18-3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14-4.07; P = .02]). CONCLUSIONS: Low baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine-induced leucopenia in patients without a TPMT variant.


Assuntos
Azatioprina/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina/efeitos adversos , Metiltransferases/genética , Adulto , Azatioprina/uso terapêutico , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Leucopenia/induzido quimicamente , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco
14.
J Crohns Colitis ; 11(3): 342-352, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27647859

RESUMO

BACKGROUND AND AIMS: Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS: In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS: Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.


Assuntos
Colite Ulcerativa/economia , Colite Ulcerativa/epidemiologia , Efeitos Psicossociais da Doença , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Custos de Cuidados de Saúde , Qualidade de Vida , Fumar/economia , Fumar/epidemiologia , Adulto , Idoso , Colite Ulcerativa/tratamento farmacológico , Comorbidade , Doença de Crohn/tratamento farmacológico , Eficiência , Emprego/estatística & dados numéricos , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Abandono do Hábito de Fumar/economia , Inquéritos e Questionários , Exacerbação dos Sintomas
15.
Eur J Cancer ; 55: 140-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26820684

RESUMO

In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure. In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Rearranjo Gênico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Análise de Sobrevida , Resultado do Tratamento
16.
J Crohns Colitis ; 10(4): 455-61, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26721937

RESUMO

BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.


Assuntos
Doenças Inflamatórias Intestinais/complicações , Fumar/efeitos adversos , Adulto , Artrite/etiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Doença de Crohn/complicações , Doença de Crohn/etiologia , Doença de Crohn/patologia , Estudos Transversais , Feminino , Humanos , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Dermatopatias/etiologia , Abandono do Hábito de Fumar
17.
BMJ Open Gastroenterol ; 2(1): e000026, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26462278

RESUMO

OBJECTIVES: Enteropathy associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma that may complicate coeliac disease and typically occurs in patients with refractoriness to the gluten-free diet. The majority of these patients harbour a clonal expansion of intraepithelial lymphocytes (IELs) with an aberrant phenotype in the small intestine which are thus considered as the 'precursor' lymphoma cells. We describe a 51-year-old female patient with refractory coeliac disease (RCD) who developed an EATL with manifestations in the proximal small intestine and in a mesenteric lymph node that did not evolve from regular type 'aberrant' αß-T-cells but rather from a clonal expansion of γδ-T-cells. METHODS: Duodenal biopsies and lymphoma tissue from a patient with refractory coeliac disease whom developed an EATL were extensively studied by immunophenotypical, T-cell receptor immunogenetic and chromosomal analysis. RESULTS: Flow cytometric analysis of duodenal IELs revealed an unusual large clonal expansion of CD30 negative γδ-T-cells in a patient with RCD. When the patient clinically deteriorated 18 months later, a substantial part (30%) of this cell population did express CD30. In addition, identical immunogenetic aberrancies had developed in a prehepatic lymph node. CONCLUSIONS: We here report on a case of extraintestinal EATL that originated from a clonal γδ-IEL population rather than from aberrant IEL. This EATL displayed a distinctive pattern of immunophenotypical, T-cell receptor immunogenetic and chromosomal aberrancies as compared to classical EATL, defining this lymphoma as a novel variant of EATL.

18.
Neth J Med ; 72(4): 218-23, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24829178

RESUMO

Reports on the outcome of patients with primary central nervous system lymphoma (PCNSL) are mainly based on results obtained in the context of clinical trials. However, due to poor performance status and cognitive impairment, most patients are actually treated outside clinical studies. The aim of this retrospective study was to get more insight into the outcome of HIV-negative PCNSL patients, treated between 2000-2010 in two hospitals (one academic centre and one categorical cancer centre). Fifty-two patients were identified. Eight patients were treated with corticosteroids only. Sixteen patients received high-dose methotrexate (MTX)-based chemotherapy, ten received radiotherapy and 18 patients were treated with a combination of MTX-based chemotherapy and radiotherapy. At a median follow-up of 63.1 months, the median overall survival for all patients was 24.4 months (95% CI: 11.5-39.8 months), with an event-free survival of 14 months (95% CI: 7.3-24.4 months). Causes of death were progressive PCNSL in 29 patients, MTX toxicity in four patients and epileptic seizures in one patient. These results are comparable with the outcome of prospective clinical trials in this disease, which still has a relatively poor prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos como Assunto , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
Colorectal Dis ; 15(6): e323-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23406347

RESUMO

AIM: Restorative surgery after (procto)colectomy with ileo-neorectal anastomosis (INRA) or restorative proctocolectomy with ileal pouch anal anastomosis (RPC) combines cure of ulcerative colitis (UC) with restoration of intestinal continuity. This study aimed to evaluate these two operations. METHOD: Patients having INRA and RPC were matched according to sex, age at onset of UC, age at restorative surgery and duration of follow-up. Patients were included if they were over 18 years of age, had UC confirmed histopathologically and had undergone either operation. Long-term function, anal and neorectal physiology, complications, quality of life (QoL) and health status (HS) were determined. RESULTS: Seventy-one consecutive patients underwent surgery with the intention of having an INRA procedure. This was successfully carried out in 50, and 21 underwent intra-operative conversion to RPC. Median defaecation frequency was 6/24 h. In 11/71 patients reservoir failure occurred and 13/71 developed pouchitis. QoL and HS were comparable to the healthy population. Median follow-up was 6.2 years. These patients were matched with 71 patients who underwent RPC. RPC was successful in all patients. Median defaecation frequency was 8/24 h. Failure occurred in 7/71 patients and 13/71 developed pouchitis. QoL and HS were comparable with the healthy population. Median follow-up was 6.9 years. CONCLUSION: Comparison of INRA and RPC on an intention to treat basis was not considered to be realistic due to the high intra-operative conversion rate and the failures in the INRA group. RPC remains the procedure of choice for restoring intestinal continuity after proctocolectomy for UC.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas , Proctocolectomia Restauradora , Adulto , Estudos de Coortes , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Complicações Pós-Operatórias , Pouchite , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
20.
Clin Oncol (R Coll Radiol) ; 25(3): 197-204, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23183305

RESUMO

AIM: To investigate changes in health-related quality of life and sexual function in men after high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT), with or without androgen deprivation therapy, for localised prostate cancer. MATERIALS AND METHODS: Eligible men who had undergone HDR brachytherapy/EBRT for their prostate cancer completed questionnaires before any treatment (baseline) and at 3 monthly intervals. The European Organization for Research and Treatment of Cancer (EORTC) C30 quality of life measure (QLQ-C30), the PR25 prostate-specific supplement and the International Index of Erectile Function-Short Form (IIEF-SF) were completed. An analysis of changes from baseline to 2 years, for the 87 men who completed surveys, was carried out. RESULTS: The mean EORTC QLQ-C30 quality of life scores, urinary, bowel and sexual symptoms had all improved. However, improvements did not return men to baseline levels at 2 years. Sexual function as measured by both scales was least likely to recover. There were no differences due to androgen deprivation therapy. Minimally important differences were still reported by men at 2 years as follows: urinary (36%), bowel (24%), hormone treatment side-effects (40%), IIEF-SF (55%). Discrepancies between mean and minimally important differences changes are explained by some men remaining more affected by their therapy than others. CONCLUSION: The findings do not support our first hypothesis that urinary, bowel and sexual problems in these men will return to baseline levels once therapy is completed and 2 years have elapsed. Our findings indicate the changes men experience are significant, do occur early, and many do not resolve in the longer term.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Braquiterapia/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Disfunções Sexuais Fisiológicas/etiologia , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/fisiopatologia , Qualidade de Vida , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Comportamento Sexual/efeitos da radiação , Inquéritos e Questionários
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