Ultrasound transmural healing correlates with higher adalimumab drug concentration in Crohn's disease only in the short-term.

BACKGROUND: Anti-TNF drugs have revolutionized the treatment of Crohn's disease (CD) and have set new therapeutic targets. A direct correlation between anti-TNF trough levels and endoscopic healing in IBD patients has been established, but the association between drug levels and transmural healing assessed by ultrasound is not yet clearly defined. AIMS: To evaluate the correlation between the serum concentration of adalimumab (ADA) and sonographic transmural healing in CD patients at different times during the follow-up of patients. METHODS: In this retrospective, cross-sectional study all patients with CD who were undergoing treatment with ADA in our center were included. Intestinal ultrasound (IUS) was performed before the initiation of the drug and for response monitoring. ADA serum-through levels were compared between patients with and without transmural healing at different periods of time. RESULTS: 92 patients were included, all patients showed signs of inflammatory activity in the baseline IUS. In the IUS monitoring of the response to ADA, 34 (34.8%) patients presented transmural healing. Among patients in the first year of treatment, those with sonographic healing showed higher median levels than patients without transmural healing (12.0 µg/mL vs. 9.3 µg/mL, respectively; p= 0.007). There was no correlation found between adalimumab levels and sonographic healing in patients undergoing treatment for over a year. CONCLUSIONS: Higher adalimumab through levels were corelated with transmural healing with ultrasound during the first year of treatment. This correlation was not found after one year of treatment.

Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease.

AIM: endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). METHODS: cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn's disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. RESULTS: eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn's disease, the diagnostic utility of both tests was lower. CONCLUSIONS: FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn's disease, more studies are needed to determine the role of fecal biomarkers.

Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease

Aim: endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). Methods: cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn’s disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. Results: eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn’s disease, the diagnostic utility of both tests was lower. Conclusions: FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn’s disease, more studies are needed to determine the role of fecal biomarkers. (AU)

Intestinal ultrasonography and fecal calprotectin for monitoring inflammation of ileal Crohn's disease: two complementary tests.

BACKGROUND/AIMS: Tight control of inflammation and adjustment of treatment if activity persists is the current strategy for the management of Crohn's disease (CD). The usefulness of fecal calprotectin (FC) in isolated involvement of the small intestine in CD is controversial. To assess the usefulness of FC to determine the inflammatory activity detected by intestinal ultrasonography (IUS) in ileal CD. METHODS: Patients with exclusively ileal involvement CD who underwent IUS and an FC were prospectively included. Simple ultrasound index was used to determine inflammatory activity. The usual statistical tests for comparison of diagnostic techniques were used. RESULTS: One hundred and five patients were included, IUS showed inflammatory activity in 59% of patients and complications in 18.1%. FC showed a significant correlation with IUS in the weak range (Spearman coefficient r=0.502; P<0.001); the area under the receiver operating characteristic curve was 0.79 (95% confidence interval, 0.70-0.88; P<0.001). The FC value that best reflected the activity in IUS was 100 µg/g with sensitivity, specificity, and positive and negative predictive values of 73.0%, 71.4%, 79.3% and 63.8%, respectively. There were no differences in FC concentration between patients with or without transmural complications. The addition of serum C-reactive protein to FC did not improve the ability to assess IUS activity. CONCLUSIONS: FC has a significant correlation with IUS to monitor ileal CD activity. This correlation is weak and it does not allow assessing the presence of CD complications. Both tests should be used in conjunction for tight control of ileal CD. More studies on noninvasive tests in this location are needed.

Treatment of abdominal fistulas in Crohn's disease and monitoring with abdominal ultrasonography.

OBJECTIVE: to assess the usefulness of medical treatment to achieve closure of internal fistulas detected on abdominal ultrasound in a series of patients with fistulizing Crohn's disease. MATERIAL AND METHODS: a retrospective analysis was performed of the medical records of patients with Crohn's disease with a fistula detected on abdominal ultrasound from 2010 to 2018. The study included patients who received medical treatment after the diagnosis of this complication and underwent ultrasonographic monitoring of the therapeutic response. The factors associated with the response to medical treatment or the need for surgery were investigated. RESULTS: forty-six patients were included in the study. Enteromesenteric (69.6 %) was the most common type of fistula and associated abscesses were found in 14 (30.4 %) patients. Fistulas were classified as complex in 20 patients. Treatment with immunosuppressants was started in 14 (30.4 %) cases and a biologic drug was added in 18 (39.1 %) patients. Complete closure of the abdominal fistula was observed with ultrasonography in 24 (52.2 %) of the 46 patients. The only factor related to fistula closure was the type of fistula and was more likely to occur in patients with an enteromesenteric fistula. Thirteen (28 %) of the 46 patients needed a surgical resection. The only factor with a significant correlation with a lower need for surgery was fistula closure after treatment (8.3 % vs 50 %, p = 0.002). CONCLUSION: medical treatment achieves internal fistula closure in more than half of cases and almost a third require surgical treatment. Abdominal ultrasound can detect abdominal fistulas at an earlier stage and allow prompt treatment changes.

Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn's Disease.

AIM: To assess the clinical benefits of transmural healing (TH) shown on intestinal ultrasound (IUS) after treatment with tumor necrosis factor-alpha antibodies (anti-TNF) in patients with Crohn's disease. MATERIALS AND METHODS: This prospective study included consecutively 36 patients who underwent IUS in the week prior to start anti-TNF treatment, at 12 weeks, and 1 year after starting treatment. The clinical response to treatment was assessed using the Crohn's disease activity index and C-reactive protein (CRP) values. TH was defined as the normalization of bowel wall thickness on IUS. Treated patients were considered to have a good outcome if none of the following situations presented: need to reintroduce corticosteroids or intensify maintenance therapy and/or need for surgery. RESULTS: After the induction regimen, 29 patients (80.6%) achieved clinical remission, and serum CRP values returned to normal in 20 patients (55.6%). In the IUS at 12 weeks, treatment induced a statistically significant reduction in the wall thickness (p < 0.001) and color Doppler grade (p < 0.001), as well as resolution of complications in 66.7% of patients (p < 0.03). IUS after 1 year of biological therapy showed TH in 14/33 patients (42.4%). During the follow-up (median 48.5 months), 23 of the 33 (69.7%) patients in remission or response after induction therapy presented a good outcome. Sonographic TH was significantly related with better outcomes, with only 1/14 patients having a poor outcome compared to 9/19 without TH (OR 11.7, 95% CI 1.2-108.2 p = 0.01, Chi-squared test). CONCLUSION: Patients who achieve TH on IUS with biological treatment have better clinical outcomes.

Intravenous Contrast-Enhanced Ultrasound for Assessing and Grading Postoperative Recurrence of Crohn's Disease.

PURPOSE: The aim was to investigate the contribution of contrast-enhanced ultrasound (CEUS) to improve the results of US in the evaluation of recurrence in postsurgical Crohn's disease (CD) and establish its role in the assessment of the severity. METHODS: Anastomotic site was assessed in 108 postsurgical CD patients with B-mode, color Doppler and CEUS. Bowel wall thickness (WT), transmural complications or stenosis, color Doppler grade, and bowel wall contrast enhancement (BWCE)-using time-intensity curves-were correlated with endoscopic Rutgeerts score. A receiver operating characteristic (ROC) curve was built to establish the best cutoff to predict recurrence and the severity. A US scoring system was elaborated in order to determine the grade of recurrence. RESULTS: Ileocolonoscopy detected recurrence in 90 (83.3%) subjects and severe recurrence in 62. WT ≥ 3 mm had an accuracy of 90.7% in the detection of endoscopic recurrence. The combination of parameters-WT ≥ 3 mm and BWCE (≥ 46%)-demonstrated similar accuracy (90.7%). A WT ≥ 5 mm showed the best specificity (100%) for the diagnosis of recurrence and a WT ≥ 6 mm the best specificity (95.7%) for the detection of severe recurrence. The combination of sonographic parameters-WT ≥ 6 mm or WT between 5 and 6 mm with BWCE ≥ 70%, or complications-obtained the best results grading the recurrence (sensitivity, specificity, and accuracy of 90.3%, 87%, and 88.9%, respectively). CONCLUSIONS: US shows high sensitivity and specificity for the diagnosis of postsurgical recurrence. When combined with CEUS, it can improve the detection of severe recurrence.

Reactivación de hepatitis B en paciente con hepatitis crónica C tratado con antivirales de acción directa / Hepatitis B reactivation in a patient with chronic hepatitis C treated with direct-acting antivirals

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Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case of multiple colorectal adenomas

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Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case of multiple colorectal adenomas.

Chemoprevention is a practical approach to reduce the risk of various cancers including colorectal cancer (CRC). The goal is to reduce the incidence of pre-neoplastic adenomatous polyps and prevent its progression to CRC. Curcumin and silibinin prevent intestinal polyp formation in mice. Curcumin sensitizes silymarin to exert synergistic anticancer activity in colon cancer cells. Patients presenting with multiple colorectal adenomatous polyps (MCRA) have a high lifetime risk for CRC. We present a 57-year-old man with MCRA, without deleterious germline APC or MYH mutations. Our patient had 54 polyps in the first colonoscopy, most of 3 to 8 mm and one of 20 mm with high grade dysplasia / adenocarcinoma. Four subsequent colonoscopies showed continuous development of adenomatous polyps treated by polypectomy for the most part and some with heat. After the treatment with curcumin for 3 months and a half followed by silibinin for 9 months, we find many less polyps than in the previous colonoscopies, going from the finding of 40 adenomas of 3-6 mm in the pre-treatment colonoscopy to 3 polyps after treatment.

Papel del digestólogo en el manejo del paciente obeso / Role of the gastroenterologist in the management of the obese patient

La obesidad es una enfermedad con una elevada prevalencia a nivel mundial en la que el digestólogo puede tener una labor importante. Por una parte, algunas enfermedades digestivas son más frecuentes en este grupo de pacientes y es posible que sea necesario evaluarlos antes de la cirugía. Por otra, la cirugía bariátrica puede presentar complicaciones digestivas a corto y largo plazo en las que sea imprescindible nuestra actuación. Además, no podemos olvidar el papel que el tratamiento endoscópico puede tener en la pérdida de peso. El objetivo de la presente revisión es destacar el papel del digestólogo en el manejo del paciente obeso candidato y/o sometido a tratamiento quirúrgico o endoscópico de la obesidad (AU)

Abstract Obesity is a highly prevalent disease worldwide, and one in which gastroenterologists can play an important role. Some digestive diseases are more common in obese patients, and preoperative evaluation may be required in some cases. Additionally, bariatric surgery can lead to digestive complications in the short and long term that require intervention, and endoscopic treatment can be an important factor in weight loss. The aim of this review is to highlight the role of the gastroenterologist in the management of obese patients who are either scheduled for or have undergone surgical or endoscopic treatment for obesity (AU)

Role of the gastroenterologist in the management of the obese patient. / Papel del digestólogo en el manejo del paciente obeso.

Obesity is a highly prevalent disease worldwide, and one in which gastroenterologists can play an important role. Some digestive diseases are more common in obese patients, and preoperative evaluation may be required in some cases. Additionally, bariatric surgery can lead to digestive complications in the short and long term that require intervention, and endoscopic treatment can be an important factor in weight loss. The aim of this review is to highlight the role of the gastroenterologist in the management of obese patients who are either scheduled for or have undergone surgical or endoscopic treatment for obesity.

Ultrasonographic Changes at 12 Weeks of Anti-TNF Drugs Predict 1-year Sonographic Response and Clinical Outcome in Crohn's Disease: A Multicenter Study.

BACKGROUND: The objective was to assess the long-term effect of biological treatment on transmural lesions of Crohn's disease evaluated with ultrasound, including contrast-enhanced ultrasound. METHODS: Fifty-one patients with active Crohn's disease were included in a prospective multicenter longitudinal study. All patients underwent a clinical assessment and sonographic examination at baseline, 12 weeks after treatment initiation, and after 1-year of treatment. Patients were clinically followed at least 2 years from inclusion until the end of the study. Ultrasonographic evaluation included bowel wall thickness, color Doppler grade, parietal enhancement, and presence of transmural complications or stenosis. Sonographic changes after treatment were classified as normalization, improvement, or lack of response. RESULTS: Improvement at 52 weeks was more frequent in patients with improvement at final of induction (12 weeks) compared with patients who did not improve (85% versus 28%; P < 0.0001). One-year sonographic evolution correlated with clinical response; 28 of the 29 (96.5%) patients with sonographic improvement at 52 weeks showed clinical remission or response. Patients without sonographic improvement at 52 weeks of treatment were more likely to have a change or intensification in medication or surgery (13/20, 65%) during the next year of follow-up than patients with improvement on the sonography (3/28, 11%). Stricturing behavior was the only sonographic feature associated to a negative predictive value of response (P = 0.0001). CONCLUSIONS: Sonographic response after 12 weeks of therapy is more pronounced and predicts 1-year sonographic response. Sonographic response at 1-year examination correlates with 1-year clinical response and is a predictor of further treatment's efficacy, 1-year or longer period of follow-up.

Diagnosis, treatment and long-term outcomes of autoimmune pancreatitis in Spain based on the International Consensus Diagnostic Criteria: A multi-centre study.

OBJECTIVES: Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that has been reported worldwide for the last two decades. The aim of this study is to analyse the clinical profile of patients from Spain with AIP, as well as treatments, relapses and long-term outcomes. METHODS: Data from 59 patients with suspected AIP that had been diagnosed in 15 institutions are retrospectively analysed. Subjects are classified according to the International Consensus Diagnostic Criteria (ICDC). Patients with type 1 AIP (AIP1) and type 2 AIP (AIP2) are compared. Kaplan-Meier methodology is used to estimate the overall survival without relapses. RESULTS: Fifty-two patients met ICDC, 45 patients were AIP1 (86.5%). Common manifestations included abdominal pain (65.4%) and obstructive jaundice (51.9%). Diffuse enlargement of pancreas was present in 51.0%; other organ involvement was present in 61.5%. Serum IgG4 increased in 76.7% of AIP1 patients vs. 20.0% in AIP2 (p = 0.028). Tissue specimens were obtained in 76.9%. Initial successful treatment with steroids or surgery was achieved in 79.8% and 17.3%, respectively. Maintenance treatment was given in 59.6%. Relapses were present in 40.4% of AIP1, with a median of 483 days. Successful long-term remission was achieved in 86.4%. CONCLUSIONS: AIP1 is the most frequent form of AIP in Spain in our dataset. Regularly, ICDC allows AIP diagnosis without the need for surgery. Steroid and chirurgic treatments were effective and safe in most patients with AIP, although maintenance was required many times because of their tendency to relapse. Long-term serious consequences were uncommon.

Association of Streptococcus gallolyticus subspecies gallolyticus with colorectal cancer: Serological evidence.

The colonic opportunist Streptococcus gallolyticus subspecies gallolyticus (SGG) is potentially associated with colorectal cancer (CRC). Large-scale seroepidemiological data for SGG antibodies and their possible association with CRC is currently missing. Associations between CRC and antibody responses to SGG were examined in 576 CRC cases and 576 controls matched by sex, age and province from a population-based multicase-control project (MCC-Spain). MCC-Spain was conducted between 2008 and 2013 in 12 Spanish provinces. Antibody responses to recombinant affinity-purified SGG pilus proteins Gallo1569, 2039, 2178 and 2179 were analysed by multiplex serology. Polyomavirus (PyV) JC VP1 and PyV 6 VP1 proteins served as disease-specificity controls. In the control population, antibody responses to pilus proteins were mostly weak. Antibody responses to individual pilus proteins Gallo2039 (OR: 1.58, 95% CI: 1.09-2.28), Gallo2178 (OR: 1.58, 95% CI: 1.09-2.30) and Gallo2179 (OR: 1.45, 95% CI: 1.00-2.11) were significantly associated with CRC risk. The association was stronger for positivity to two or more pilus proteins of Gallo1569, Gallo2178 and Gallo2179 (OR:1.93, 95% CI: 1.04-3.56) and for double-positivity to Gallo2178 and Gallo2179 (OR: 3.54, 95% CI: 1.49-8.44). The association between SGG infection and CRC risk was stronger among individuals younger than 65 years. For the first time we demonstrated a statistically significant association of exposure to SGG antigens and CRC in a large seroepidemiological study. These results should stimulate further studies on the role of SGG in CRC pathogenesis.

Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies.

OBJECTIVE: The objective of this study was to analyze the accuracy of abdominal ultrasonography (AUS) in the assessment of mucosal healing in patients with Crohn's disease (CD) receiving immunomodulators and/or biological treatment, with ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Thirty patients were included in a prospective longitudinal study. All patients underwent ileocolonoscopy and AUS before and after a minimum of one year of treatment. The Crohn's Disease Endoscopic Inflammatory Index of Severity (CDEIS) was used for endoscopic assessment whereas AUS was analyzed by means of bowel wall thickness, color Doppler grade and percentage of increase of parietal enhancement after contrast injection. RESULTS: In the segmental analysis, endoscopic healing was found in 71.2% of the segments and AUS findings were normalized in 62.8%, with a significant correlation between the two techniques (κ=0.76, p<0.001). In the overall assessment performed after treatment, 18 (60%) patients exhibited endoscopic remission (CDEIS <6 points); of these patients, 15 (83.3%) had normalized sonographic findings, with a good correlation between endoscopic remission and sonographic normalization (κ=0.73, p<0.001). Of the three variables assessed by AUS, parietal thickness was the best variable to predict mucosal healing in both analyses, segmental and global. CONCLUSION: Abdominal ultrasonography is a useful and reliable technique for the assessment of the endoscopic response to treatment with immunomodulators and/or biological drugs in Crohn's disease. AUS is a highly accurate technique for evaluating the healing of the intestinal mucosa.

Contrast-enhanced ultrasonography: usefulness in the assessment of postoperative recurrence of Crohn's disease.

AIM: The aim of this study was to assess whether the contrast-enhanced ultrasonography (CEUS) can increase the value of the ultrasonography in the study of postoperative recurrence of Crohn's disease (CD). MATERIALS AND METHODS: 60 patients with CD who had previously undergone ileocolic resection underwent prospectively both CEUS and colonoscopy within a 3-day period. The sonographic examination included evaluation of bowel wall thickness, transmural complications, colour Doppler grade and contrast-enhanced US. In addition a sonographic score was established. The capacity of CEUS to diagnose endoscopic recurrence, as well as its severity, was assessed by calculating the sensitivity, specificity and positive and negative predictive values, accuracy and odds ratio, with their respective 95% confidence intervals. The areas under the receiver operating characteristic (ROC) curves were also calculated. RESULTS: 49 out of 60 patients showed endoscopic postoperative recurrence. Severe endoscopic recurrence was present in 34 patients (57%). Classic ultrasound parameters (wall thickness >3mm and colour Doppler flow) revealed an accuracy of 88.3% for the diagnosis of recurrence. Sonographic score 2, including thickness >5mm or contrast enhancement >46%, improved the results with a sensitivity, specificity and accuracy of 98%, 100% and 98.3%, respectively, in the diagnosis of endoscopic recurrence. The area under the ROC curve was 0.99, in remarkable agreement with endoscopy (k: 0.946). Sonographic score 3, including thickness >5mm, contrast enhancement >70% or fistula identified 32 out of 34 (94.1%) severe endoscopic recurrences. The area under the ROC curve was 0.836, in good agreement with endoscopy (k: 0.688). CONCLUSION: CEUS shows excellent sensitivity and specificity for the diagnosis of postoperative recurrence in CD and can also detect severe recurrences.