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1.
Gastroenterol Hepatol ; : 502223, 2024 Jun 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38908683

RESUMO

OBJECTIVES: To search for parameters susceptible to optimization when performing capsule endoscopy (CE) in a third level hospital with high volume and experience in this test. PATIENTS AND METHODS: Retrospective observational study, including 1325 CEs performed between 2017 and 2022. Overall diagnostic yield, effective diagnostic yield, by indication, place of request and waiting list, as well as complete examination rate and cleansing degree were analyzed. RESULTS: The overall diagnostic yield was 70.99%, while the effective diagnostic yield was 72.7%. Diagnostic yields varied between 60.2% and 77.9% depending on the indication and between 64.7% and 74.3% depending on the requesting center. The mean waiting list was 101.15 days, with a tendency to worse results when the waiting list was longer. A total of 77.8% of the examinations were complete. Completion rates were lower in patients >70 years of age (p=0.001), as well as in those with gastric transit >60minutes (p=0.000). A total of 77.3% were clean, with debris that did not impede diagnosis being found in 16.9% and debris that did impede diagnosis in 5.8%. There was a relationship, although not significant, between cleansing degree and age. CONCLUSIONS: The diagnostic yields of CE in our center are in line with those previously reported. Differences were found according to the place of request. Waiting list could also influence diagnostic yield. Completion rates are lower in >70 years of age and when gastric transit is >60minutes. Cleansing degree achieved is acceptable.

2.
Gut ; 72(11): 2031-2038, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37468228

RESUMO

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Bismuto/efeitos adversos , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Quimioterapia Combinada , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons , Sistema de Registros , Amoxicilina/uso terapêutico
3.
Int J Colorectal Dis ; 33(6): 827-829, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29532204

RESUMO

INTRODUCTION: The development of novel mechanical endoscopic closure systems allows now the management of some gastrointestinal fistula types in a minimally invasive way. However, the correct location of the fistulous tract is essential to achieve successful endoscopic closure. CASE REPORT: A 69-year-old woman with high risk for surgery presented with recurrent cystitis, pneumaturia, and enteruria 2 months after medical-treated diverticulitis. Computerized tomography demonstrated colovesical fistula but colonoscopy could not locate the fistulous opening. A cystoscopy was performed and the fistulous tract was shown using a guidewire. Then, a novel over-the-scope clip device Padlock® system was released in the sigmoid colon, with successful endoscopic closure through this not previously described collaborative approach between urologists, surgeons, and gastroenterologists.


Assuntos
Colonoscopia , Cistoscopia , Fístula Intestinal/diagnóstico , Fístula Intestinal/cirurgia , Instrumentos Cirúrgicos , Idoso , Feminino , Humanos , Fístula Intestinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/cirurgia
4.
Inflamm Bowel Dis ; 30(2): 167-182, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37536268

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Metabolômica , Intestinos
5.
United European Gastroenterol J ; 12(1): 122-138, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38050339

RESUMO

BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Metronidazol , Claritromicina/uso terapêutico , Levofloxacino/uso terapêutico , Bismuto , Estudos Prospectivos , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/uso terapêutico , Tetraciclina , Sistema de Registros
6.
Dig Liver Dis ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38839456

RESUMO

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

7.
Pediatr Int ; 55(2): 204-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23253156

RESUMO

BACKGROUND: Chronic diarrhea and functional abdominal pain (FAP) in childhood could be an early manifestation of adult irritable bowel syndrome (IBS). The aim of this study was to investigate the presence of chronic functional digestive symptoms in childhood, interviewing adult patients diagnosed with IBS, in an attempt to establish a relationship between them. METHODS: By means of a questionnaire, the history of colic, chronic diarrhea, functional abdominal pain, constipation and migraine in childhood, was analyzed in patients diagnosed with IBS according to the current Rome III criteria, and in control patients without known chronic digestive disorders. Fisher's exact test was used for comparison of frequencies. RESULTS: The IBS study group was made up of 40 patients (24 women; average age, 33.03 years), and the control group by 40 adults (22 women; average age, 29.62 years). IBS-diagnosed adults spoke about a significantly higher prevalence of chronic diarrhea (32.5/7.5%; odds ratio [OR], 7.01; 95% confidence interval [CI]: 26.84-1.80), and FAP (37.5/15%; OR, 4.30; 95%CI: 12.67-1.43) in their childhood, than the control group. There were no differences in the presence of other childhood functional symptoms. Interestingly, the present patients, when asked about the onset of symptoms that led to the diagnosis of IBS, referred to them mostly beginning in adulthood, not linking their current diagnosis of IBS with their background in childhood. CONCLUSIONS: In a proportion of adults with IBS the natural history of their symptoms probably began during their childhood.


Assuntos
Constipação Intestinal/etiologia , Diarreia/etiologia , Previsões , Síndrome do Intestino Irritável/diagnóstico , Adolescente , Adulto , Criança , Constipação Intestinal/epidemiologia , Diarreia/diagnóstico , Diarreia/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Espanha/epidemiologia , Inquéritos e Questionários , Adulto Jovem
8.
Endosc Int Open ; 11(5): E490-E496, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37206695

RESUMO

Background and study aims Rates of new dysplastic lesions or cancer progression after first dye chromoendoscopy in the era of high-definition endoscopy have yet to be determined. Patients and methods A multicenter, population-based, retrospective cohort study was performed in seven hospitals in Spain. Patients with inflammatory bowel disease and fully resected (R0) dysplastic colon lesions under surveillance with high-definition dye-based chromoendoscopy were sequentially enrolled between February 2011 and June 2017, with a minimum endoscopic follow-up of 36 months. The aim was to assess the incidence of developing more advanced metachronous neoplasia by analyzing possible associated risk factors. Results The study sample included 99 patients and 148 index lesions (145 low-grade dysplasia lesions and three high-grade dysplasia [HGD] lesions with a mean follow-up of 48.76 months [IQR: 36.34-67.15]). The overall incidence of new dysplastic lesions was 0.23 per 100 patient-years, 1.15 per 100 patients at 5 years and 2.29 per 100 patients at 10 years. A history of dysplasia was associated with a higher risk of developing any grade of dysplasia during follow-up ( P  = 0.025), whereas left colon lesions were associated with a lower risk ( P  = 0.043). The incidence of more advanced lesions at 1 year and 10 years was 1 % and 14 % respectively, with lesion size > 1 cm being a risk factor ( P  = 0.041). One of the eight patients (13 %) with HGD lesions developed colorectal cancer during follow-up. Conclusions The risk of dysplasia progressing to advanced neoplasia and, specifically, the risk of new neoplastic lesions after endoscopic resection of colitis-associated dysplasia, are both very low.

9.
Dig Dis Sci ; 57(7): 1880-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22453995

RESUMO

AIMS: The aim of this work is to investigate the accuracy of the urea breath test (UBT) performed immediately after emergency endoscopy in peptic ulcer bleeding (PUB). METHODS: Urea breath test was carried out right after emergency endoscopy in patients with PUB. The accuracy of this early UBT was compared to a delayed one after hospital discharge that was considered the gold standard. Clinical and epidemiological factors were analyzed in order to study their influence on the accuracy of the early UBT. RESULTS: Early UBT was collected without any complication and good acceptance from all the 74 patients included. In 53 of the patients (71.6%), a delayed UBT was obtained. Comparing concordance between the two tests we have calculated an accuracy of 83% for the early UBT. Sensibility and specificity were 86.36 and 66%, respectively, with a positive predictive value of 92.68% and negative predictive value of 50% (Kappa index = 0.468; p = 0.0005; CI: 95%). We found no influence of epidemiological factors, clinical presentation, drugs, times to gastroscopy, Forrest classification, endoscopic therapy, hemoglobin, and urea levels over the accuracy of early UBT. CONCLUSIONS: Urea breath test carried out right after emergency endoscopy in PUB is an effective, safe, and easy-to-perform procedure. The accuracy of the test is not modified by clinical or epidemiological factors, ulcer stage, or by the type of therapy applied. However, we have found a low negative predictive value for early UBT, so a delayed test is mandatory for all negative cases.


Assuntos
Testes Respiratórios/métodos , Serviço Hospitalar de Emergência , Endoscopia Gastrointestinal , Hemorragia Gastrointestinal/cirurgia , Infecções por Helicobacter/diagnóstico , Úlcera Péptica/cirurgia , Ureia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia Gastrointestinal/etiologia , Trato Gastrointestinal/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/metabolismo , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes
10.
Scand J Gastroenterol ; 46(6): 727-31, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21366386

RESUMO

INTRODUCTION: Hepatic fibrosis can be assessed through serum markers or by the implementation of new non-invasive techniques, such as elastography. We must know patients' opinion on percutaneous liver biopsy (PLB) when it comes to comparing it with other procedures. AIMS: To know the point of view of patients undergoing a PLB with regard to information provided to them, as well as the procedures and biopsy consequences. PATIENTS AND METHODS: A questionnaire was sent by mail to 178 patients who underwent PLB from April 2006 to May 2010. Answers were analyzed. Results are expressed in percentages and compared based on gender and age (younger or older than 47 years of age) (Chi-square test). RESULTS: Ninety patients of the group answered, 44 females, mean age 47 ± 12 years. The answers revealed that 93% of patients rated the information concerning the reasons for a PLB as adequate (86% women and 100% men). As for the information concerning the objective of the procedure, 88% of patients regarded it as adequate (81% of women vs. 93% of men, p = 0.08). As for the information concerning the risks of a biopsy, 77.7% see it as sufficient. About 12.20% of patients did not receive any information on the physician who asked for the PLB, or who performed it. PLB was considered very painful by 14% of patients, painful by 21%, bothersome by 41.1% and barely bothersome by 23% of patients. Thirty-five percent of patients required analgesia after the puncture. Even though 92% of patients regard PLB as a useful procedure, 46% of them have not received any treatment or a different nutritional regime (55.8%, among those older than 47 years of age, p = 0.03). Eighty percent of patients think that PLB has more benefits than drawbacks, although 87% would have opted for a less aggressive technique as long as it would have provided the same information. But 21% of patients would have also preferred a less aggressive technique, even though it provided fewer details. CONCLUSIONS: In general, PLB is widely approved by patients and is also regarded as a useful procedure. One out of six patients would rather choose a less-aggressive technique even if it provided less information. PLB does not involve changes in the treatment in around a half of patients.


Assuntos
Biópsia por Agulha , Hepatopatias/patologia , Fígado/patologia , Satisfação do Paciente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
12.
Mediators Inflamm ; 2009: 580450, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19657406

RESUMO

Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is not well established. Biopsy specimens from patients with ulcerative colitis (UC) and Crohn's disease (CD), from both affected and unaffected areas, and also from a group of colonic biopsies from healthy controls, were included in our study. Cytokines and markers of mucosal damage were analyzed by real-time PCR, and some of the results confirmed by western-blot and ELISA. Levels of IFNgamma, TNFalpha, IL-6, IL-15, IL-18, and IL-23 were increased (above healthy controls) in both affected and unaffected areas from IBD. IL-1beta, IL-6, IL-12, and IL-27 were higher in affected areas compared to unaffected ones in UC but not CD. In general, a correlation was observed between mRNA levels of these cytokines and both iNOS and Granzyme B. SOCS-2 and SOCS-3 were also increased in the affected areas. In conclusion, the unaffected areas from IBD show increased levels of a restricted set of cytokines that may exert immune activating roles in these areas without being able to trigger tissue damage.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Adolescente , Adulto , Western Blotting , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Interferon gama/genética , Interleucina-15/genética , Interleucina-15/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-23/genética , Masculino , Metaloproteinase 3 da Matriz/genética , Óxido Nítrico Sintase Tipo II/genética , Reação em Cadeia da Polimerase , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
14.
Endosc Int Open ; 7(6): E743-E750, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31157291

RESUMO

Background and study aims Chromoendoscopy with targeted biopsy is the technique of choice for colorectal cancer screening in longstanding inflammatory bowel disease. We aimed to analyze results of a chromoendoscopy screening program and to assess the possibility of identifying low-risk dysplastic lesions by their endoscopic appearance in order to avoid histological analysis. Materials and methods We retrospectively reviewed chromoendoscopies performed between February 2011 and June 2017 in seven Spanish hospitals in a standardized fashion. We analyzed the findings and the diagnostic yield of the Kudo pit pattern for predicting dysplasia. Results A total of 709 chromoendoscopies (569 patients) were reviewed. Median duration of disease was 16.7 years (SD 8.1); 80.4 % had ulcerative colitis. A total of 2025 lesions (3.56 lesions per patient) were found; two hundred and thirty-two lesions were neoplastic (11.5 %) (223 were LGD (96.1 %), eight were HGD (3.4 %), and one was colorectal cancer (0.5 %). The correlation between dysplasia and Kudo pit patterns predictors of dysplasia (≥ III) was low, with an area under the curve of 0.649. Kudo I and II lesions were correctly identified with a high negative predictive value (92 %), even by non-experts. Endoscopic activity, Paris 0-Is classification, and right colon localization were risk factors for dysplasia detection, while rectum or sigmoid localization were protective against dysplasia. Conclusions Chromoendoscopy in the real-life setting detected 11 % of dysplastic lesions with a low correlation with Kudo pit pattern. A high negative predictive value would prevent Kudo I and, probably, Kudo II biopsies in the left colon, reducing procedure time and avoiding complications.

18.
Gastroenterol Hepatol ; 30(9): 534-7, 2007 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-17980131

RESUMO

Meckel's diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract. Bleeding from Meckel's diverticulum is the most common clinical presentation, especially in childhood. In adults, manifestations include a broad spectrum of symptoms ranging from an incidental finding in surgery, iron deficiency anemia of unknown etiology, and acute abdomen due to mechanical complications of the diverticulum. Neoplastic transformation has been reported, but gastrointestinal stromal tumors are exceptional in this location. We report a case of gastrointestinal stromal tumor in Meckel's diverticulum, complicated by perforation.


Assuntos
Abdome Agudo/etiologia , Tumores do Estroma Gastrointestinal/complicações , Neoplasias do Íleo/complicações , Divertículo Ileal/complicações , Diagnóstico Diferencial , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Neoplasias do Íleo/diagnóstico , Neoplasias do Íleo/cirurgia , Perfuração Intestinal/etiologia , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico
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