Celiac.com 12/22/2016 - The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors remains controversial. A team of researchers recently set out to better understand the mechanisms by which innate intraepithelial lymphocytes develop in the intestine and become cancerous in celiac disease patients.

The research team included J Ettersperger, N Montcuquet, G Malamut, N Guegan, S Lopez-Lastra, S Gayraud, C Reimann, E Vidal, N Cagnard, P Villarese, I Andre-Schmutz, R Gomes Domingues, C Godinho-Silva, H Veiga-Fernandes, L Lhermitte, V Asnafi, E Macintyre, C Cellier, K Beldjord, JP Di Santo, N Cerf-Bensussan, and B Meresse.

They are variously affiliated with the INSERM UMR1163, Laboratory of Intestinal Immunity, Institut Imagine; Laboratory of Human Lymphohematopoiesis; Institut Necker-Enfants-Malades, INSERM UMR1151 and, Biological Hematology, AP-HP Necker-Enfants-Malades; the Université Paris Descartes-Sorbonne Paris Cité and Institut Imagine in Paris, France; AP-HP, Department of Gastroenterology, Hôpital Européen Georges Pompidou, 75015 Paris, France; Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France; Innate Immunity Unit, Institut Pasteur, 75015 Paris, France; INSERM U 668, Paris, France; Paris-Descartes Bioinformatic Platform, 75015 Paris, France; and with the Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa in Lisbon, Portugal.

The team was able to show, in humans and in mice, innate intestinal IELs expressing intracellular CD3 (iCD3(+)) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin-15 (IL-15), and Granzyme B signals.

In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity. As a result, NOTCH1 target genes necessary for T cell differentiation were silenced, and precursors were reprogrammed into innate cells with T cell marks, including intracellular CD3 and T cell rearrangements.

In the intraepithelial lymphoma complicating celiac disease, iCD3(+) innate IELs acquired gain-of-function mutations in Janus kinase 1 or Signal transducer and activator of transcription 3, which enhanced their response to IL-15.

The research team observed and described gut T cell-like innate IELs, decoded their pathway of change, and showed their malignant transformation in celiac disease.

This study offers an exciting glimpse into the hard work being done in the far corners of celiac disease and cancer research.

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Celiac.com 10/25/2016 - Some potentially big news for people who suffer from enteropathy-associated T-cell lymphoma (EATL), an intestinal tumor that targets intraepithelial T lymphocytes. EATL may be preceded by refractory celiac disease (RCD), which resists treatment with gluten-free diet. In almost all cases, a range of the tumor cells express CD30.

RCD occurs in two types based on the absence (type I) or presence (type II) of abnormal intraepithelial lymphocytes (IEL) showing down-regulation of CD8 and often TCR gamma genes rearrangement. RCD II is now considered as a small cell intraepithelial T-cell lymphoma that could be an intermediate stage between celiac disease and EATL.

A team of researchers recently set out to establish the pattern of CD30 expression in EATL, which help to improve therapies with the use of anti-CD30 monoclonal antibody like brentuximab vedotin (BV). The research team included David Sibon, Georgia Malamut, Virginie Verkarre, Coralie Derrieux, Isabelle Radford, Bertrand Meresse, Elizabeth Macintyre, Christophe Cellier, Nadine Cerf-Bensussan, Nicole Brousse, and Olivier Hermine.

For their study, the team enrolled consecutive adult patients diagnosed with EATL between 2007 and 2013 in Necker University Hospital and Georges Pompidou European Hospital. The team confirmed celiac diagnosis using histopathologic and immunohistochemical review. For the purpose of the present study, two expert hematopathologists reviewed all EATL and extended the phenotypic analysis to reclassify them according to the 2008 WHO classification.

The team used a panel of antibodies directed against CD20, CD3, CD4, CD5, CD8, CD56, granzyme B and ALK1. They also performed CD30 staining with Monoclonal Mouse Anti-Human CD30, Clone Ber-H2 (Dako). As a control group, they used consecutive RCDI and RCDII cases with complete phenotype and clonality analyses diagnosed in the same period. They based celiac disease diagnosis on HLA-DQ2/8 typing, detection of celiac specific antibodies, and of villous atrophy with increased counts of IEL on normal diet. They classified patients RCDI or II, depending on their clinical and histological response to a gluten-free diet, and the presence of abnormal IEL.

In all 25 cases of EATL, large tumor cells strongly expressed CD30. In RCDI and II, CD30 was negative in most cases (∼90%), and was rarely expressed by dispersed atypical lymphocytes, whether in IEL or in lamina propria. TCR gamma genes were clonally rearranged in 11/14 (79%) EATL, 3/25 (12%) RCDI and 18/20 (90%) RCDII.

Based on their findings, the team began a pilot study in 2012. The pilot study combines BV with chemotherapy followed by autologous stem-cell transplantation (ASCT) as frontline treatment for EATL. The team has treated five patients to date. For chemotherapy, the the first two patients received IVE/MTX. After presenting their initial results at ASH 2012 Annual Meeting, the team replaced IVE/MTX with CHP regimen, and treated 3 more patients. Both treatments were well tolerated, and all 5 patients reached clinical remission, and underwent ASCT.

EATL type I strongly expresses CD30. Promising results from combining BV with CHP led the team to plan a phase 2 study of BV and CHP, followed by ASCT, as frontline treatment of EATL.

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Enteropathy-associated T-cell lymphoma is a rare primary intestinal non-Hodgkin lymphoma (NHL) strongly associated with celiac disease. It is an aggressive disease with a median survival of approximately 10 months (Ferreri et al, 2011).

Previous studies suggest that EATL may be more common in Europe and among Whites, among whom celiac disease is prevalent (Delabie et al, 2011; Ferreri et al, 2011). However, a second type of EATL (Type II) not associated with celiac disease is increasingly reported in Asia (Lee et al, 2005; Sun et al, 2011; Tan et al, 2013).

To date, there have been no comparative epidemiological study in a racially diverse large population. A team of researchers recently set out to conduct such a study. The research team included Pawan K. Karanam, Mohammed Al-Hamadani, and Ronald S. Go. They are variously associated with the Departments of Medical Education and Medical Research at the Gundersen Medical Foundation in La Crosse, USA, and with the Division of Hematology at the Mayo Clinic, and the Mayo Clinic's Robert D, and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN, USA.

The team turned to the two largest public cancer databases in the US: the Surveillance, Epidemiology, and End Results (SEER) database (Open Original Shared Link); and the National Cancer Data Base (NCDB; Open Original Shared Link).

Using these databases, the research team was able to find and compare the cases of EATL by race. They were also able to describe the clinical features and overall survival (OS) for these cases. 

The team's study included all patients with an EATL diagnosis according to International Classification of Diseases for Oncology (ICD-O: 9717). The team used SEER-18 registries from 2000 to 2011 to calculate incidence.

To describe clinical outcomes, they used the NCDB NHL-PUF with patients diagnosed between 1998 and 2012 for clinical characteristics and those diagnosed between 1998 and 2006 for OS. Because CoC-accredited programs report survival data only once every 5 years, OS analysis was possible only for patients diagnosed between 1998 and 2006.

From the data, the team calculated the incidence rate (case/1 000 000), age-adjusted to the 2000 standard US population, according to race (White, Black, Asian/Pacific Islander, American Indian/Alaska native) using seer*stat software version 8.1.5 (National Cancer Institute, Bethesda, MD, USA) and performed risk ratio comparisons using Poisson regression.

They analyzed OS using the Kaplan–Meier method and used log-rank tests to compare survival distributions between race cohorts. The prognostic effect of pertinent clinical variables were studied using multivariate Cox proportional hazards models.

They found that, for the years 2000–2010, the overall age-adjusted incidence rate of EATL in the US was 0·111 per 1,000,000. Asians/Pacific Islanders had a higher incidence rate (0·236) compared with other races [White (0·101), Black (0·107), American Indian/Alaska native (0·128)].

The risk ratio of Asians/Pacific Islanders compared with non–Asians/Pacific Islanders was 2·32 [95% confidence interval (CI) 1·39–3·69; P = 0·002].

The incidences for Asians and Pacific Islanders were combined in seer*stat, therefore we could not provide separate incidences for Asians and Pacific Islanders.
All tests of statistical significance were two-sided and P < 0·05 was considered significant.

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Celiac.com 09/22/2014 - The connection between celiac disease and various types of cancer is well supported by scientific evidence. However, to date, there hasn’t been enough data to make accurate predictions of cancer risk in celiac patients. So, we don’t know exactly what the risk levels are for various types of cancer in celiac patients.

Using a large population register of diagnosed celiac patients in Finland, a team of researchers recently set out to establish a realistic projection of the cancer risk for celiac patients.

The researchers included T. Ilus, K. Kaukinen, L.J. Virta, E. Pukkala, and P. Collin. They are variously associated with the Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital and University of Tampere in Finland; the Department of Medicine at Seinäjoki Central Hospital in Seinäjoki, Finland; the Research Department at The Social Insurance Institution in Turku, Finland; the Finnish Cancer Registry at the Institute for Statistical and Epidemiological Cancer Research in Helsinki, Finland; and the School of Health Sciences at the University of Tampere in Tampere, Finland.

For the period covering 2002-2011, the register contained 32,439 adult celiac patients. The team paired this data with data from the Finnish Cancer Registry, which includes over 98% of diagnosed malignancies. Using incidence figures for the whole population, the team calculated a standardized incidence ratio (SIR) for the malignancies,

They constructed a time-stratified analysis in 11,991 celiac patients diagnosed after 2004. They did not have information on lifestyle factors, such as smoking habits and obesity.

They found that the overall incidence ratio of malignant diseases did not increase until five or more years from the diagnosis of celiac disease (1.31, 1.04-1.63). The results showed higher SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62-2.29), small-intestinal cancer (4.29; 2.83-6.24), colon cancer (1.35; 1.13-1.58), and basal cell carcinoma of the skin (1.13; 1.03-1.22).

However, SIRs for lung cancer (0.60; 0.48-0.74), pancreatic cancer (0.73; 0.53-0.97), bladder cancer (0.53; 0.35-0.77), renal cancer (0.72; 0.51-0.99), and breast cancer (0.70; 0.62-0.79) were lower. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37-4.38).

Overall, there was no increased SIR of cancer in the whole series, but SIR rose after 5 years from the diagnosis of celiac disease. The overall risk of breast and lung cancers in celiac patients was lower, while the risk of small-intestinal cancer and NHL was higher, but not as high as previous data indicated.

So, patients with celiac disease over five years showed higher rates of non-Hodgkin lymphoma, small-intestinal cancer, colon cancer, and basal cell carcinoma of the skin.

Among other benefits, this study will help clinicians and doctors to better focus their attention toward warning signs for these conditions in people with celiac disease.

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Celiac.com 09/15/2014 - Duodenal intraepithelial lymphocytosis (D-IEL) is an early marker for celiac disease, even though a majority of cases are due to non-celiac disease conditions.

Researchers I. Aziz, T. Key, J.G. Goodwin, and D.S. Sanders wanted to identify the predictors of celiac disease in patients presenting with D-IEL. For their study, they reviewed 215 adults with D-IEL who had undergone prospective and systematic evaluation for celiac disease and other recognized associations. They confirmed celiac disease based on presence of HLA-DQ2 and/or DQ8, persistence or progression of D-IEL following a gluten challenge, and an improvement in symptoms with a gluten-free diet.

To compare factors in celiac and non-celiac cases, and to determine their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), the team used binary logistic regression models, adjusted for age and sex. They diagnosed celiac disease in 48 cases (22%) and non-celiac in 167 cases (78%). They found no statistical difference between the celiac and non-celiac group in terms of baseline demographics, anemia, hematinics, or clinical symptoms, such as diarrhea, weight loss, abdominal pain.

Compared with their non-celiac counterparts, celiac patients were significantly more likely to have a positive family history of celiac disease (21% vs. 3.6%, OR 6.73; PPV 62.5%, NPV 81%, specificity 96.4%), positive HLA-DQ status (100% vs. 49.1%; PPV 36.4%, NPV 100%, specificity 50.9%), and presence of endomysial antibody (EMA) (48% vs. 0%; PPV 100%, NPV 87%, specificity 100%); all P≤0.001.

A total of 29.2% celiac and 83.2% non-celiac cases showed normal tissue transglutaminase antibody (TTG) levels (OR 0.084, P<0.001; PPV 9.2%).

Between the groups, there was no difference in the prevalence of TTG levels 1 to 2×upper limit of normal (29.2% celiac vs. 14.4% non-celiac; PPV 33% to 38%). However, TTG levels between 3 and 20×ULN were much more common in the celiac group (33.3% vs. 2.4%, PPV 66.6% to 89%), whereas a TTG>20×ULN was exclusive to celiac disease (8.3%, P<0.001, PPV 100%).

For patients with D-IEL, only a positive EMA or TTG greater than 20×ULN at the outset can yield an immediate celiac diagnosis. On their own, factors such as gastrointestinal symptoms, family history, anemia, or other celiac serology results do not reliably distinguish celiac from non-celiac patients.

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Celiac.com 09/08/2014 - Currently, physicians trying to diagnose celiac disease in patients with lymphocytic enteritis look for subepithelial deposits of anti-tissue transglutaminase IgA. However, it is known that an increase in CD3+TCRγδ+ coupled with a decrease in CD3- intraepithelial lymphocytes (IEL) is a flow cytometric pattern clearly indicating celiac disease with atrophy.

To determine which method yielded better diagnostic results, a research team set out to compare and contrast intestinal intraepithelial lymphocyte cytometric pattern with subepithelial deposits of anti-tissue transglutaminase IgA for diagnosing lymphocytic enteritis due to celiac disease.

The researchers included F. Fernández-Bañares, A. Carrasco, R. García-Puig, M. Rosinach, C. González, M. Alsina, C. Loras, A. Salas, J.M. Viver, M. Esteve.

They are variously affiliated with the Department of Gastroenterology, Hospital Universitari Mutua Terrassa, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), the Department of Pediatrics, Hospital Universitari Mutua Terrassa, University of Barcelona, the Department of Pathology, Hospital Universitari Mutua Terrassa, University of Barcelona, CIBERehd, Terrassa, and the Department of Immunology, CATLAB, Viladecavalls, all in Barcelona, Spain.

For their study, the team evaluated 144 women and 61 men, with positive celiac genetics, who underwent duodenal biopsy for celiac disease. Fifty patients showed villous atrophy, and 70 showed lymphocytic enteritis, while 85 showed normal histology. Eight patients with non-celiac atrophy and 15 with lymphocytic enteritis secondary to Helicobacter pylori served as control group.

The team used duodenal biopsies to assess both celiac disease, IEL flow cytometric (complete or incomplete), and IF patterns. Sensitivity of IF, and complete and incomplete cytometric patterns for celiac disease diagnosis in patients with positive serology (Marsh 1+3) was 92%, 85% and 97% respectively, but only the complete cytometric pattern showed 100% specificity.

Twelve seropositive and 8 seronegative Marsh 1 patients received a celiac disease diagnosis at the beginning of the study or after gluten free-diet, respectively.

For celiac disease diagnosis in lymphocytic enteritis at baseline, cytometric pattern yielded better diagnostic results than both IF pattern and serology (95% vs 60% vs 60%, p = 0.039).

Analysis of the IEL flow cytometric pattern offers fast, accurate reliable way to spot celiac disease in the initial diagnostic biopsy of patients presenting with lymphocytic enteritis, even for patients with negative blood screens, and seems superior to anti-TG2 intestinal deposits.

These results support the analysis of the IEL flow cytometric pattern as the best way to spot celiac disease at the first diagnostic biopsy of patients presenting with lymphocytic enteritis, even for patients with negative blood screens.

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A team of researchers recently tried to find out if overall risk for lymphoproliferative malignancy in people with celiac disease is connected with levels of mucosal healing. The research team included Benjamin Lebwohl, MD, MS; Fredrik Granath, PhD; Anders Ekbom, MD, PhD; Karin E. Smedby, MD, PhD; Joseph A. Murray, MD; Alfred I. Neugut, MD, PhD; Peter H.R. Green, MD; and Jonas F. Ludvigsson, MD, PhD.

The are variously affiliate with the Columbia University College of Physicians and Surgeons, New York, New York; Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Mayo Clinic College of Medicine, Rochester, Minnesota; and Örebro University Hospital, Örebro, Sweden.

For their population-based cohort study, the team looked at data from all 28 pathology departments in Sweden. They evaluated at data for 7625 patients with celiac disease who received follow-up biopsy after initial diagnosis.

Measurements: They used expected rates to assess risk for LPM, compared with that of the general population. They then used Cox regression to compare rates of LPM in patients with persistent villous atrophy against rates for patients with mucosal healing.

Of the 7625 patients with celiac disease and follow-up biopsy, 3308 (43%) showed persistent villous atrophy. Overall risk levels for LPM were higher for celiac patients who had received biopsy (standardized incidence ratio [sIR], 2.81 [95% CI, 2.10 to 3.67]) than for the general population. LPM risk levels were higher for celiac patients with persistent villous atrophy (SIR, 3.78 [CI, 2.71 to 5.12]) than for those with mucosal healing (SIR, 1.50 [CI, 0.77 to 2.62]).

Compared with mucosal healing, persistent villous atrophy was associated with an increased risk for LPM (hazard ratio

One limitation of the study is that it gathered no data about patient adherence to a gluten-free diet.

Higher risk for LPM in celiac disease is connected with follow-up biopsy results, with a higher risk among patients with persistent villous atrophy.

Follow-up biopsy may be an effective way to classify celiac disease patients by risk for subsequent LPM.

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The manner in which clinical presentation, pathological features and therapies influence EATL outcome was the subject of a recent study by a team of researchers.

The research team included: G. Malamut; O. Chandesris; V. Verkarre; B.Meresse, C. Callens, E. Macintyre, Y. Bouhnik, J.M. Gornet; M. Allez; R. Jian; A. Berger; G. Châtellier; N. Brousse, O. Hermine, N. Cerf-Bensussan, and C. Cellier.

They are variously affiliated with the Université Paris Descartes, the Gastroenterology Department of Hôpital Européen Georges Pompidou, APHP, and Inserm U989 in Paris, France.

For their study, the team evaluated the medical files of 37 well-documented patients with celiac disease and T-cell lymphoma. They then analyzed lymphoma and intestinal mucosa by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping.

Using Kaplan-Meier curves with Logrank test and Cox Model they then analyzed patient survival and prognostic factors. They found 15 patients with lymphoma-complicated non-clonal enteropathy, celiac disease, two patients with type I refractory celiac disease, and 20 patients with clonal type II refractory celiac disease. Twenty-five patients underwent surgery with resection of the main tumor mass in 22 cases.

Univariate analysis showed that non-clonal celiac disease, serum albumin levels under 21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p=0.0007, p

Multivariate analysis showed that serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival rates (p

The results reinforce the value of assessing celiac disease type in patients with T-cell lymphoma, and suggest that a combination of nutritional, chemotherapy and reductive surgery may improve survival rates in cases of EATL.

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However, that may be set to change, as the results of a new study suggest that new treatments for T-cell lymphoma my be on the horizon. The study appears in the journal Clinical Lymphoma Myeloma and Leukemia.

The study team included J.R. Bertino, M. Lubin, N. Johnson-Farley, W.C. Chan, L. Goodell, and S. Bhagavathi. They are affiliated with the Departments of Medicine, Pharmacology, and Pathology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ.

The team was attempting to address the fact that doctors treating T-cell lymphomas, especially types of T-cell lymphoma known as peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) have limited treatment options and cannot cure the condition.

Their study noted that a high percentage of PTCL, AITL, and ALCL, along with T-cell leukemia and T-cell lymphoblastic leukemia lack the enzyme methylthioadenosine phosphorylase (MTAP).

Their published results also note that MTAP-deficient cells cannot cleave endogenous methylthioadenosine to adenine and 5-methylthioribose-1-phosphate, a precursor of methionine, and as a result have enhanced sensitivity to inhibitors of de novo purine biosynthesis.

A recently introduced antifolate, pralatrexate, which has been shown to inhibit de novo purine biosynthesis, has been approved for treatment of PTCL and may have an increasing role in therapy. An alternative strategy involving coadministration of methylthioadenosine and high-dose 6-thioguanine has been proposed and may prove to be selectively toxic to MTAP-deficient uncommon lymphomas.

As a result of these MTAP results, the team suggests that new therapies and treatments for T-cell lymphoma may be possible going forward.

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Celiac.com 09/24/2012 - With all the problems that go along with celiac disease, it can be hard to see any benefits to having the disease. However, it would seem that such benefits do exist: a recent study in Sweden shows that women suffering from celiac disease are actually at a decreased risk of developing breast, endometrial and ovarian cancer.

Data was collected from 28 Swedish pathology departments, identifying 17,852 biopsy-diagnosed women diagnosed with celiac disease between the years of 1969 and 2007. Women in the celiac group were age-matched and compared with a control group of 88,400 women.

Risk of breast, endometrial and ovarian cancer were all estimated using the Cox regression model in both groups. Results showed an inverse relationship between celiac disease and all three forms of cancer. With breast cancer rates, women with celiac disease had a hazard ratio of 0.89 (meaning for every 100 women in the control group, only 89 in the celiac disease group developed breast cancer). Women with celiac disease also had a hazard ratio of 0.89 for ovarian cancer. For endometrial cancer, the decreased risk was even more pronounced with a hazard ratio of 0.6. All calculations carried a confidence interval of 95%.

These numbers became even more pronounced after omitting the first year of followup after diagnosis (presumably the gluten-free diet 'adjustment period'). Breast cancer's hazard ratio fell to 0.82, ovarian cancer's hazard ratio fell to .72 and endometrial cancer's hazard ratio fell to 0.58. 

The study suggests that this negative correlation could be a result of shared risk factors or early menopause associated with celiac disease. Looking at the numbers though, particularly the 'adjustment period' drop off, one has to wonder if the gluten-free diet has some part to play in this as well.

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Celiac.com 07/30/2012 - A number of studies have found higher rates of lymphoma in people with celiac disease. However, few studies make any distinction between lymphoproliferative disorders (LPDs).

A team of researchers recently investigated rates of various lymphoproliferative disorders in patients with celiac disease.

The research team included L.A. Leslie, B. Lebwohl, A.I. Neugut, J. Gregory Mears, G. Bhagat, and P.H. Green. They are affiliated with the Department of Medicine at Columbia University Medical Center in New York, NY.

The team wanted to assess rates of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes.

To do so, they carried out a retrospective cohort study of adults with biopsy-proven celiac disease seen at a US referral center from 1981 to 2010. They also identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype.

They began with a study group of 1,285 patients with celiac disease. The group contained 40 patients with LPD [sIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non-Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28).

Rates of NHL subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI = 1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone (SIR = 37.17, 11.73-76.89), lymphoma were substantially higher
among patients diagnosed with celiac before LPD (n = 24, NHL SIR = 4.47, 95% CI = 2.86-6.44).

Patients who developed LPD were usually older at time of celiac diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028).

EATL patients had a shorter average survival than non-EATL NHL patients (3.2 versus 15.0 years, P = 0.016).

Overall, rates of LPD are higher in celiac disease patients, and those diagnosed at an older age, who present with symptoms of malabsorption, are more likely to be diagnosed with LPD.

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Recently, a clinical team set out to assess GI cancer risks for a larger population. The study team included Peter Elfström, Fredrik Granath, Weimin Ye, and Jonas F. Ludvigsson. They assessed risk GI cancers by using data from large groups of patients with either celiac disease, inflammation, or latent celiac disease.

They assessed data from 28,882 patients with celiac disease, all with villous atrophy, and Marsh scores of 3. They also assessed data for 12,680 patients with inflammation, all with Marsh scores of 1–2. They evaluated biopsy samples at 28 different pathology centers.

They assessed a third group of 3705 patients with latent celiac disease, that is, with normal mucosa, but positive blood tests. The team then compared the results against data from an age- and sex-matched population.

They found that 372 of the patients with celiac disease developed incident GI cancers, while 347 patients with inflammation, and 38 with latent celiac disease developed GI cancers.

That means that the first year after diagnosis and initial biopsy, celiac disease carried a 5.95-times greater risk of incident GI cancer, with a 95% confidence interval [CI], 4.64–7.64). The hazard ratio

After the first year, patients showed no significant increase in GI cancer risk.

The HR for celiac disease was 1.07 (95% CI, 0.93–1.23), for inflammation it was 1.16 (95% CI, 0.98–1.37). HR for latent celiac disease it was 0.96 (95% CI, 0.56–1.66).

The absolute risk for any GI cancer in people with celiac disease was 101/100,000 person-years, with an excess risk of 2/100,000 person-years.

The results carried some relatively good news. That is, even though celiac disease, inflammation, and latent disease all increase a person's risk for GI cancers in the first year after diagnosis, there is no increase in risk beyond the first year.

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