The Outcomes of Endoanal Ultrasound and Three-Dimensional, High-Resolution Anorectal Manometry do not Predict Fecal Incontinence

Endoanal ultrasound (EUS) is the gold standard for diagnosing anal sphincter defects often seen in patients with fecal incontinence (FI). Threedimensional, high-resolution anorectal manometry (3D-HRARM) is a newer technique that might also be used to diagnose sphincter defects. We aimed to investigate whether FI is associated with anal sphincter defects detected by EUS and 3D-HRARM. Retrospectively, we included all adult patients who had undergone EUS and 3D-HRARM for FI, between January 2012 and February 2015 (N = 37). During 3D-HRARM, the presence of sphincter defects was examined in rest and during maximal anal sphincter contraction. All patients also underwent a balloon retention test to objectively determine whether they suffered from FI for solid stool. Of the 37 patients, 12 patients (32%) suffered from FI. The presence of a sphincter defect detected with EUS, and with 3D-HRARM during contraction, was not associated with the prevalence of FI and no significant correlations were found between these variables. The presence of a sphincter defect, detected by 3D-HRARM in rest, was negatively correlated with the presence of FI (rs -.372, P = .024). Moreover, the prevalence of sphincter defects was lower in patients with FI, detected by 3D-HRARM in rest, than in patients without FI (13% versus 88%, P = .035). FI is not associated with anal sphincter defects detected by EUS and 3D-HRARM. The outcomes of EUS and 3D-HRARM do not thus predict the presence of FI. Instead, extensive anorectal function tests should be performed to form a complete picture of a patient’s anorectal functions and to determine the underlying causes of FI

Prognostic factors and patterns of recurrence in esophageal cancer assert arguments for extended two-field transthoracic esophagectomy

BACKGROUND: High recurrence rates determine the dismal outcome in esophageal cancer. We reviewed our experiences and defined prognostic factors and patterns of recurrences after curatively, intended transthoracic esophagectomy. METHODS: Between January 1991 and December 2005, 212 consecutive patients underwent a radical transthoracic esophagectomy with extended 2-field lymphadenectomy. Recurrence rates, survival, and prognostic factors were analyzed (minimal follow-up period, 2 y). RESULTS: Radicality was obtained in 85.6%. The median follow-up period was 26.6 months. The overall recurrence rate at I, 3, and 5 years was 28%, 44%, and 64%, respectively, and locoregional recurrence rate was 17%, 27%, and 43%, respectively. Overall survival rates, including postoperative deaths, were 45% and 34% at 3 and 5 years, respectively. pT stage and lymph node (LN) ratio greater than .20 were independent prognostic factors for survival and recurrences. Radicality was most prognostic for survival, and for N+ greater than 4 positive LN for recurrences. CONCLUSIONS: Radicality and LN ratio are strong prognostic factors. High radicality and adequate nodal assessment are guaranteed by an extended transthoracic approach. (C) 2010 Elsevier Inc. All rights reserved

Trajectories of Fatigue in Inflammatory Bowel Disease

BACKGROUND: Fatigue is one of the most frequently reported symptoms by patients with inflammatory bowel disease (IBD), both during active disease phases as well as during clinical remission. This study addressed whether different trajectories of fatigue over time can be identified among patients with IBD. Subsequently, we compared the demographic and clinical characteristics between trajectories. METHODS: The current study included 849 patients with IBD diagnosed with either Crohn disease (CD; n = 511) or ulcerative colitis (UC; n = 338) who visited the University Medical Center in Groningen (the Netherlands) at least 3 times during a 9-year follow-up. We conducted latent class growth analyses to identify distinct trajectories. RESULTS: In all patients with IBD (and in the subgroup with CD), we found 5 trajectories for fatigue. In the UC subgroup, we found 4 fatigue trajectories. One trajectory present in both patients with CD (11.45%) and patients with UC (4.75%) was characterized by chronic elevated levels of fatigue across time. Women and parents were more prevalent in trajectories with higher fatigue severity. We also found significant associations among the fatigue trajectories with disease activity and psychological well-being. CONCLUSIONS: The results clearly showed the existence of distinct fatigue paths over time in patients with IBD. Those reporting more chronic elevated levels of fatigue also reported greater disease activity and reduced well-being. Therefore, reducing disease activity may be important for the treatment of fatigue. In addition, given the significant association with well-being, it is possible that reducing fatigue may improve self-reported well-being

A Critical Appraisal of Circumferential Resection Margins in Esophageal Carcinoma

In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM.To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1).A cutoff point of CRM at a parts per thousand currency sign1.0 mm and &gt; 1.0 mm appeared to be an adequate marker for survival and prognosis (both P &lt;0.001). The outcome in patients with CRMs a parts per thousand currency sign1.0 and &gt; 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P &lt;0.001). Survival of patients with positive CRMs (a parts per thousand currency sign1 mm) did not significantly differ from patients with an R1 resection (P = 0.12).Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is a parts per thousand currency sign1 mm and for a free CRM is &gt; 1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.</p

Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease

BACKGROUND: Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn’s disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity. MATERIALS AND METHODS: Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC. RESULTS: Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders. CONCLUSIONS: We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD

Latent cytomegalovirus infection does not influence long-term disease outcomes in inflammatory bowel disease, but is associated with later onset of disease

Objectives: Cytomegalovirus (CMV) infection is common in the general population. CMV infection negatively affects disease course in transplant recipients and HIV patients. Whereas primary CMV infections may occur sporadically in seronegative patients, all seropositive patients with inflammatory bowel syndrome (IBD) are at risk for CMV reactivation due to the inflammatory mucosal and use of immunosuppressive medication. It is unclear whether latent CMV infection, and risk of reactivations, influences long-term disease outcomes. In this study, we aim to explore whether CMV infection affects disease outcomes in IBD patients. Methods: We performed a cross-sectional cohort study with 1404 patients with IBD from a single center. Clinical characteristics and disease outcomes were prospectively collected. We scrutinized CMV serology test results and performed additional CMV serology testing if serum was available. Results: Out of 699 IBD patients with CMV serology, 303 (43.3%) were seropositive, comparable to the general Dutch population. CMV seropositivity was associated with older age, longer IBD disease duration, non-Western origin, birth outside the Netherlands and a lower educational level (p-values ≤.004). CMV seropositivity was not associated with more complicated long-term disease outcomes of IBD (p-values >.05). Seropositive patients presented with symptoms and were diagnosed at an older age compared to seronegative patients (p-values <.01). Conclusions: CMV seropositivity does not influence disease outcomes of IBD patients and seems to be associated with a delay in IBD onset. Guidelines regarding CMV screening in patients with IBD are currently based on a low level of evidence. These data support the recommendation that routine CMV serology measurement is not necessary in the clinical care of IBD

Use of Tumor Necrosis Factor-α Antagonists is Associated with Attenuated IgG Antibody Response against SARS-CoV-2 in Vaccinated Patients with Inflammatory Bowel Disease

Introduction : Patients with Inflammatory Bowel Disease (IBD) frequently receive immunomodulating treatment, which may render them at increased risk of an attenuated immune response upon vaccination. In this study, we assessed the effects of different types of commonly prescribed immunosuppressive medications on the serological response after vaccination against SARS-CoV-2 in patients with IBD. Methods : In this prospective observational cohort study, IgG antibody titers against SARS-CoV-2 were measured 2-10 weeks after completion of standard vaccination regimens in patients with IBD. Clinical characteristics, previous history of SARS-CoV-2 infection, type of vaccine (mRNA- or vector-based) and medication use were recorded at the time of sampling. Subsequently, a chemiluminescent microparticle immunoassay was used for the quantitative determination of IgG antibodies against the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Results : Three hundred and twelve (312) patients with IBD were included (172 Crohn’s disease [CD] and 140 ulcerative colitis [UC]). Seroconversion (defined as titer of >50 AU/ml) was achieved in 98.3% of patients. Antibody concentrations were significantly lower in patients treated with TNF-α-antagonists vs. non-users of TNF-α-antagonists (geometric mean [95% confidence interval]: 2204 [1655-2935] vs. 5002 [4089-6116] AU/ml, P50 years) (P<0.01) and CD (P<0.05) were independently associated with lower anti-SARS-CoV-2 antibody titers. In patients who received mRNA vaccines, users of thiopurines (either prescribed as monotherapy or in combination with biologicals) demonstrated significantly lower antibody titers compared to those who were thiopurine non-users (P<0.05). Conclusion : Despite reassuring findings that most patients with IBD have detectable antibodies after anti-SARS-CoV-2 vaccination, TNF-α-antagonists were found to be strongly associated with an attenuated IgG antibody response after vaccination against SARS-CoV-2, independent of vaccine type, the time elapsed after vaccination and blood sampling, prior SARS-CoV-2 infection and patient age. Patients treated with thiopurines and receiving mRNA-based vaccines demonstrated lower anti-SARS-CoV-2 antibody titers compared with non-users