RESUMO
OBJECTIVE: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. BACKGROUND: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. METHODS: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. RESULTS: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P =0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P =0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups ( P =0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P =0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. CONCLUSIONS: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. TRIAL REGISTRATION: ISRCTN33682933.
Assuntos
Pancreatite Necrosante Aguda , Qualidade de Vida , Humanos , Resultado do Tratamento , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/cirurgia , Antibacterianos/uso terapêutico , Drenagem/métodosRESUMO
BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).
Assuntos
Antibacterianos/uso terapêutico , Drenagem , Pâncreas/patologia , Pancreatite Necrosante Aguda/terapia , Tempo para o Tratamento , Idoso , Terapia Combinada , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/cirurgiaRESUMO
OBJECTIVE: Despite regular colonoscopy surveillance, colorectal cancers still occur in patients with Lynch syndrome. Thus, detection of all relevant precancerous lesions remains very important. The present study investigates Linked Colour imaging (LCI), an image-enhancing technique, as compared with high-definition white light endoscopy (HD-WLE) for the detection of polyps in this patient group. DESIGN: This prospective, randomised controlled trial was performed by 22 experienced endoscopists from eight centres in six countries. Consecutive Lynch syndrome patients ≥18 years undergoing surveillance colonoscopy were randomised (1:1) and stratified by centre for inspection with either LCI or HD-WLE. Primary outcome was the polyp detection rate (PDR). RESULTS: Between January 2018 and March 2020, 357 patients were randomised and 332 patients analysed (160 LCI, 172 HD-WLE; 6 excluded due to incomplete colonoscopies and 19 due to insufficient bowel cleanliness). No significant difference was observed in PDR with LCI (44.4%; 95% CI 36.5% to 52.4%) compared with HD-WLE (36.0%; 95% CI 28.9% to 43.7%) (p=0.12). Of the secondary outcome parameters, more adenomas were found on a patient (adenoma detection rate 36.3%; vs 25.6%; p=0.04) and a colonoscopy basis (mean adenomas per colonoscopy 0.65 vs 0.42; p=0.04). The median withdrawal time was not statistically different between LCI and HD-WLE (12 vs 11 min; p=0.16). CONCLUSION: LCI did not improve the PDR compared with HD-WLE in patients with Lynch syndrome undergoing surveillance. The relevance of findings more adenomas by LCI has to be examined further. TRIAL REGISTRATION NUMBER: NCT03344289.
Assuntos
Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico por imagem , Aumento da Imagem , Adenoma/patologia , Adulto , Idoso , Cor , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.
Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Proteínas de Ligação a DNA/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Adenoma/diagnóstico , Adenoma/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Feminino , Finlândia/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Países Baixos/epidemiologia , Estudos Prospectivos , beta Catenina/genéticaRESUMO
BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.
Assuntos
Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais/diagnóstico , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
GOALS AND BACKGROUND: Discriminating between patients with nonresponsive but otherwise uncomplicated celiac disease (CD) and patients with refractory celiac disease (RCD) and/or lymphoma is difficult, especially as many abnormalities encountered in complicated CD are not within reach of conventional gastroduodenoscopy. We aimed to describe video capsule endoscopy (VCE) findings in patients with CD and persisting or relapsing symptoms despite a gluten-free diet and to identify VCE findings associated with poor prognosis. METHODS: We retrospectively analyzed 48 VCE studies performed in adult patients with CD because of persisting or relapsing symptoms despite adherence to a gluten-free diet. Patients with either uncomplicated CD or RCD type I were considered to have a good prognosis, whereas patients with either RCD type II or enteropathy-associated T-cell lymphoma were considered to have a poor prognosis. Multivariate analysis was performed to identify VCE findings independently associated with either good or poor prognosis. RESULTS: Proximal focal erythema (odds ratio, 6.7; 95% confidence interval, 1.2-38.7; P=0.033) and absence of progression of the capsule to the distal intestine (odds ratio, 16.5; 95% confidence interval, 1.2-224.9; P=0.035) were independently associated with poor prognosis. Of the 28 patients with none of these 2 features, none died during follow-up, compared with 2 (13.3%) of the 15 patients with one of both features, and 4 (80.0%) of the 5 patients with both the features. CONCLUSIONS: VCE is a minimally invasive endoscopic modality that could be of use in identifying patients with nonresponsive CD who are at risk of poor prognosis.
Assuntos
Endoscopia por Cápsula/métodos , Doença Celíaca/diagnóstico , Intestino Delgado/patologia , Adulto , Doença Celíaca/patologia , Dieta Livre de Glúten , Progressão da Doença , Linfoma de Células T Associado a Enteropatia/complicações , Linfoma de Células T Associado a Enteropatia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the diagnostic accuracy of MR enteroclysis and to compare it to video capsule endoscopy (VCE) in the analysis of suspected small-bowel disease. METHODS: We performed a retrospective analysis of 77 patients who underwent both MR enteroclysis and VCE and compared the findings of these studies with the findings of enteroscopy, surgery, or with the results of clinical follow-up lasting ≥2 years. RESULTS: Findings included malignant neoplasms (n = 13), benign neoplasms (n = 10), refractory celiac disease (n = 4), Crohn's disease (n = 2) and miscellaneous conditions (n = 10). Specificity of MR enteroclysis was higher than that of VCE (0.97 vs. 0.84, P = 0.047), whereas sensitivity was similar (0.79 vs. 0.74, P = 0.591). In 2/32 (6.3%) patients with both negative VCE and negative MR enteroclysis a positive diagnosis was established, compared to 5/11 (45.5%) patients in whom VCE was positive and MR enteroclysis was negative (likelihood ratio 8.1; P = 0.004), 9/11 (81.8%) patients in whom MR enteroclysis was positive and VCE was negative (likelihood ratio 23.5; P < 0.0001), and all 23 patients in whom both VCE and MR enteroclysis showed abnormalities (likelihood ratio 60.8; P < 0.0001). CONCLUSIONS: VCE and MR enteroclysis are complementary modalities. In our study-population, MR enteroclysis was more specific than VCE, while both produced the same sensitivity.
Assuntos
Endoscopia por Cápsula , Enteropatias/diagnóstico , Intestino Delgado , Imageamento por Ressonância Magnética/métodos , Distribuição de Qui-Quadrado , Meios de Contraste , Feminino , Humanos , Enteropatias/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
A dedicated digestive disease endoscopy unit is structurally and functionally differentiating rapidly as a result of increasing diagnostic and therapeutic possibilities in the last 10-20 years. Publications with practical details are scarce, imposing a challenge in the construction of such a unit. The lack of authoritative information about endoscopy unit design means that architects produce their own design with or without consulting endoscopists working in such a unit. A working group of the World Endoscopy Organization discussed and outlined a practical approach fordesign and construction of a modern endoscopy unit. Designing the layout is extremely important, necessitating thoughtful planning to provide comfort to the endoscopy staff and patients, and efficient data archiving and transmission during endoscopic services.
Assuntos
Serviços de Diagnóstico/provisão & distribuição , Endoscopia Gastrointestinal/estatística & dados numéricos , Gastroenteropatias/diagnóstico , Guias como Assunto , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Departamentos Hospitalares/organização & administração , Sociedades Médicas , HumanosRESUMO
Individuals with Lynch syndrome have an increased colorectal cancer risk, hence, biennial colonoscopy surveillance is recommended. We aimed to investigate patients' perception and preferences regarding surveillance, and to further explore compliance behaviour. Individuals with Lynch syndrome received a validated survey evaluating experiences of their three most recent colonoscopies. Individuals were non-compliant to surveillance if the interval between colonoscopies differed ≥ 6 months from the recommended interval. In total, 197 of 291 (68%) invited individuals returned the survey. They mostly underwent colonoscopy biennially (99%), under mild sedation (79%) and with bowel preparation performed by Moviprep® (99%). Surveillance was perceived as impacting quality of life in 21%, and as moderately to extremely burdensome in 57%, particularly in those below age 40. To lower the burden, patients prioritised improvements in volume and taste of bowel preparation, laxation-related bowel movements, waiting times, and a more personal and respectful approach of endoscopic staff. Additionally, many individuals (60%) would favour less-invasive surveillance modalities such as biomarkers. In total, 28% of individuals had delayed colonoscopy surveillance, predominantly for patient-related reasons. An additional 10% considered quitting/postponing surveillance. Upon multivariable analysis, patient-related delay was associated with low and medium education, history of ≤ 4 colonoscopies and having no hospital recall-system. Colonoscopy surveillance in Lynch syndrome is often experienced as burdensome, and frequently delayed. We identified determinants of surveillance behaviour in this population, and present potential interventions to reduce the burden and non-compliance rates.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Humanos , Adulto , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Qualidade de Vida , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controleRESUMO
BACKGROUND AND AIM: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti-thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. METHODS: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti-thrombotic therapy. VCE studies were re-evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti-thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti-thrombotic therapy was resumed before the VCE study. RESULTS: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty-two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti-thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20-60.42, P=0.032). CONCLUSIONS: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti-thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.
Assuntos
Endoscopia por Cápsula , Fibrinolíticos/efeitos adversos , Hemorragia Gastrointestinal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiodisplasia/complicações , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Trato Gastrointestinal/irrigação sanguínea , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: Percutaneous endoscopic gastrostomy (PEG) is indicated for prolonged enteral nutrition. This study aimed to analyze the outcome and to identify potential risk factors for complications in PEG procedures. METHODS: A single-center retrospective analysis of the performed PEG procedures during the period January 2010 till January 2020. RESULTS: A PEG placement procedure was performed in 854 patients (64.1% male) and was successful in 833 (97.5%). In total, 513 push (61.6%) and 320 pull (38.6%) PEGs were placed. The mean age was 60.7 years, and the median follow-up was 267 days. The push PEG was associated with peri-procedural bleeding (P = 0.002) and tube dislodgements (P < 0.001), while the pull PEG was significantly associated with buried bumpers (P < 0.001), infected placement sites (P = 0.019), and granulation tissue formation (P = 0.044). The PEG-related mortality rate was 0.2%, but the overall 30-day mortality was 4.0%. CONCLUSION: The current study showed that the push and pull PEG placements are both safe and feasible procedures, with a low PEG-related mortality. Buried bumpers, infected placement sites, and granulation tissue formation are more often seen in the pull PEG, while the push PEG is associated with periprocedural bleeding and tube dislodgements. These complications should be taken into account and there is a need for a prospective trial to identify superiority between the PEG methods.
RESUMO
BACKGROUND & AIMS: Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program. METHODS: The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy. RESULTS: After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without. CONCLUSIONS: With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Mutação , Proteínas Nucleares/genética , Risco , Fatores de TempoRESUMO
PURPOSE: To determine magnetic resonance (MR) enteroclysis findings in patients with uncomplicated celiac disease (CD), refractory CD (RCD) type I, and RCD type II, to develop and validate a scoring system to identify patients with RCD II and to determine the diagnostic accuracy of MR enteroclysis to detect CD-related malignancies. MATERIALS AND METHODS: This study was performed with approval of the institutional review board. One radiologist blinded to clinical details retrospectively evaluated quantitative and qualitative criteria of 28 studies obtained in symptomatic patients with CD (uncomplicated CD, n = 10; RCD I, n = 8; RCD II, n = 10). A scoring system was developed by using parameters identified in multivariate analysis to be associated with RCD II, which two radiologists evaluated in a second group of 40 symptomatic patients with CD. Accuracy to detect malignancy was assessed in the total study group. Cumulative survival was evaluated in the total study group by using the Kaplan-Meier method. RESULTS: MR enteroclysis could not be used to discriminate between uncomplicated CD and RCD I. The presence of less than 10 folds per 5 cm jejunum, mesenteric fat infiltration, and bowel wall thickening were associated with RCD II. A positive MR score was defined as the presence of two or more of these features. In the validation group, the MR score was positive in 13 of 15 patients with RCD II (sensitivity, 0.87) and negative in 24 of 25 patients without RCD II (specificity, 0.96). The 5-year survival rate was 95% in patients with a negative MR score and 56% in patients with a positive MR score (P < .0001). MR enteroclysis helped to identify the presence of seven of eight malignancies and to diagnose absence of malignancy in 58 of 60 studies. CONCLUSION: MR enteroclysis can be used to investigate the presence of RCD II or malignancy in symptomatic patients with CD.
Assuntos
Algoritmos , Doença Celíaca/diagnóstico , Indicadores Básicos de Saúde , Interpretação de Imagem Assistida por Computador/métodos , Intestino Delgado/patologia , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Improvement of radiotherapy efficacy requires better insight in the dynamic responses that occur during irradiation. Here, we aimed to identify the molecular responses that are triggered during clinically applied fractionated irradiation. METHODS: Gene expression analysis was performed by RNAseq or microarray analysis of cancer cells or xenograft tumors, respectively, subjected to 3-5 weeks of 5 × 2 Gy/week. Validation of altered gene expression was performed by qPCR and/or ELISA in multiple cancer cell lines as well as in pre- and on-treatment biopsies from esophageal cancer patients ( NCT02072720 ). Targeted protein inhibition and CRISPR/Cas-induced gene knockout was used to analyze the role of type I interferons and cGAS/STING signaling pathway in the molecular and cellular response to fractionated irradiation. RESULTS: Gene expression analysis identified type I interferon signaling as the most significantly enriched biological process induced during fractionated irradiation. The commonality of this response was confirmed in all irradiated cell lines, the xenograft tumors and in biopsies from esophageal cancer patients. Time-course analyses demonstrated a peak in interferon-stimulated gene (ISG) expression within 2-3 weeks of treatment. The response was accompanied by a variable induction of predominantly interferon-beta and/or -lambda, but blocking these interferons did not affect ISG expression induction. The same was true for targeted inhibition of the upstream regulatory STING protein while knockout of STING expression only delayed the ISG expression induction. CONCLUSIONS: Collectively, the presented data show that clinically applied fractionated low-dose irradiation can induce a delayed type I interferon response that occurs independently of interferon expression or STING signaling. These findings have implications for current efforts that aim to target the type I interferon response for cancer treatment.
Assuntos
Neoplasias Esofágicas/radioterapia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Interferon Tipo I/genética , Proteínas de Membrana/genética , Animais , Astrocitoma/genética , Astrocitoma/imunologia , Astrocitoma/metabolismo , Astrocitoma/radioterapia , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Feminino , Células HT29 , Humanos , Imunidade/efeitos da radiação , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Aleatória , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Identification of molecular predictive markers of response to neoadjuvant chemoradiation could aid clinical decision-making in patients with localized oesophageal cancer. Therefore, we subjected pretreatment biopsies of 75 adenocarcinoma (OAC) and 16 squamous cell carcinoma (OSCC) patients to targeted next-generation DNA sequencing, as well as biopsies of 85 OAC and 20 OSCC patients to promoter methylation analysis of eight GI-specific genes, and subsequently searched for associations with histopathological response and disease-free (DFS) and overall survival (OS). Thereby, we found that in OAC, CSMD1 deletion (8%) and ETV4 amplification (5%) were associated with a favourable histopathological response, whereas SMURF1 amplification (5%) and SMARCA4 mutation (7%) were associated with an unfavourable histopathological response. KRAS (15%) and GATA4 (7%) amplification were associated with shorter OS. In OSCC, TP63 amplification (25%) and TFPI2 (10%) gene promoter methylation were associated with an unfavourable histopathological response and shorter DFS (TP63) and OS (TFPI2), whereas CDKN2A deletion (38%) was associated with prolonged OS. In conclusion, this study identified candidate genetic biomarkers associated with response to neoadjuvant chemoradiotherapy in patients with localized oesophageal cancer.
Assuntos
Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante , Medicina de Precisão , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Ilhas de CpG , Inibidor p16 de Quinase Dependente de Ciclina/genética , DNA Helicases/genética , Metilação de DNA , Intervalo Livre de Doença , Neoplasias Esofágicas/genética , Feminino , Fator de Transcrição GATA4/genética , Glicoproteínas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
PURPOSE: To evaluate the diagnostic accuracy and interobserver variance of magnetic resonance (MR) enteroclysis in the diagnosis of small-bowel neoplasms, with small-bowel endoscopy, surgery, histopathologic analysis, and follow-up serving as standards of reference, and to identify MR enteroclysis characteristics capable of enabling discrimination between benign and malignant small-bowel neoplasms. MATERIALS AND METHODS: This study was performed in accordance with the guidelines of the institutional review board, and the requirement for informed consent was waived. MR enteroclysis studies of 91 patients (43 women, 48 men; age range, 18-83 years) were retrospectively evaluated by two radiologists blinded to clinical details. Only studies explicitly performed to investigate or exclude the presence of small-bowel neoplasms were included. Radiologic findings were compared with findings of double-balloon endoscopy (n = 45), surgery (n = 18), esophagogastroduodenoscopy (n = 3), ileocolonoscopy (n = 2), autopsy (n = 2), and clinical follow-up for more than 18 months (n = 21). Efficacy parameters were calculated with 95% confidence intervals. Tumor characteristics were compared with the Student t test and the Fisher exact test. RESULTS: Readers 1 and 2 interpreted 31 and 33 studies, respectively, as depicting a small-bowel neoplasm and 19 and 17 studies, respectively, as depicting small-bowel malignancy. In 32 patients, the presence of small-bowel neoplasm was confirmed. In 19 of these patients, the neoplasm was malignant. Sensitivity and specificity in the diagnosis of small-bowel neoplasms was 0.91 and 0.95, respectively, for reader 1 and 0.94 and 0.97, respectively, for reader 2; the kappa value was 0.95. Factors associated with malignancy were the presence of longer solitary nonpedunculated lesions, mesenteric fat infiltration, and enlarged mesenteric lymph nodes. CONCLUSION: Eighty-six of 91 studies were correctly interpreted, resulting in an overall diagnostic accuracy of 0.95 for MR enteroclysis in the detection of small-bowel neoplasms. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090828/-/DC1.
Assuntos
Neoplasias Intestinais/diagnóstico , Intestino Delgado , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Padrões de Referência , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Capsule retention in the small bowel is a known complication of small-bowel video capsule endoscopy. Surgery is the most frequently used method of capsule retrieval. OBJECTIVE: To determine the incidence and causes of capsule retention and to describe double-balloon endoscopy (DBE) as the primary technique used for capsule retrieval. DESIGN: Retrospective analysis of all video capsule studies was performed at our center, and evaluation of the outcome of DBE was the first method used to retrieve entrapped video capsules. SETTING: Tertiary referral center. PATIENTS: A total of 904 patients who underwent small-bowel video capsule endoscopy. INTERVENTIONS: Capsule retrieval by DBE. MAIN OUTCOME MEASUREMENTS: The number of patients in whom capsule retention occurred and the number of patients in whom an entrapped capsule could be retrieved by using DBE. RESULTS: Capsule retention occurred in 8 patients (incidence 0.88%; 95% CI, 0.41%-1.80%) and caused acute small-bowel obstruction in 6 patients. All retained capsules were successfully removed during DBE. Five patients underwent elective surgery to treat the underlying cause of capsule retention. One patient required emergency surgery because of multiple small-bowel perforations. LIMITATIONS: Retrospective design. CONCLUSIONS: In our series, the incidence of capsule retention was low. DBE is a reliable method for removing retained capsules and might prevent unnecessary surgery. If surgery is required, preoperative capsule retrieval allows preoperative diagnosis, adequate staging in case of malignancy, and optimal surgical planning.
Assuntos
Cápsulas Endoscópicas , Endoscopia por Cápsula/efeitos adversos , Remoção de Dispositivo/métodos , Endoscopia Gastrointestinal/métodos , Gastroenteropatias/terapia , Feminino , Humanos , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
AIM: To perform a single-center analysis of all double balloon endoscopy (DBE) related cases of pancreatitis identified prospectively from a recorded DBE-complication database. METHODS: From November 2003 until January 2007, 603 DBE procedures were performed on 412 patients, with data on complications recorded in a database. The setting was a tertiary care center offering DBE. DBE was performed from the antegrade or retrograde route. Outcome measurements included age, gender, medication, indication, DBE-endoscope type, insertion depth, procedure duration, findings, interventions, post-procedural abdominal pain, and post-procedural hospitalization. RESULTS: This is the largest single-center study reporting on post-DBE pancreatitis prospectively. Six patients (1.0%) developed post-DBE pancreatitis, all after antegrade DBE. There was no association with gender, duration of the procedure or type of endoscope. The mean age was 51.9 years (range 25-78). Four patients had severe pancreatitis. Of these, two had inflammatory signs in the body-tail region, one had pancreatitis in the tail region, and the total pancreas was involved in one. CONCLUSION: The incidence of post-DBE pancreatitis in our series is higher than previously reported. We found no relation with DBE-endoscope type. The inflammatory changes occurred in the body-tail region of the pancreas, suggesting that post-DBE pancreatitis is caused by repetitive mechanical strain on the pancreas.
Assuntos
Endoscópios , Endoscopia do Sistema Digestório/efeitos adversos , Endoscopia do Sistema Digestório/instrumentação , Pancreatite/etiologia , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Estudos Prospectivos , RadiografiaRESUMO
Capsule endoscopy has revoluzionized the study of the small bowel by providing a reliable method to evaluate, endoscopically, the entire small bowel. In the last six years several papers have been published exploring the possible role of this examination in different clinical conditions. At the present time capsule endoscopy is generally recommended as a third examination, after negative bidirectional endoscopy, in patients with obscure gastrointestinal bleeding. A growing body of evidence suggests also an important role for this examination in other clinical conditions such as Crohn's disease, celiac disease, small bowel polyposis syndromes or small bowel tumors. The main complication of this examination is the retention of the device at the site of a previously unknown small bowel stricture. However there are also some other open issues mainly due to technical limitations of this tool (which is not driven from remote control, is unable to take biopsies, to insufflate air, to suck fluids or debris and sometimes to correctly size and locate lesions). The recently developed double balloon enteroscope, owing to its capability to explore a large part of the small bowel and to take targeted biopsies, although being invasive and time consuming, can overcome some limitations of capsule endoscopy. At the present time, in the majority of clinical conditions (i.e. obscure GI bleeding), the winning strategy seems to be to couple these two techniques to explore the small bowel in a painless, safe and complete way (with capsule endoscopy) and to define and treat the lesions identified (with double balloon enteroscopy).