Celiac.com 09/25/2025 - Digestive system cancers are among the most common and deadly forms of cancer worldwide, accounting for a large share of cancer diagnoses and deaths. Because these cancers often develop without clear early symptoms, many are diagnosed late, making them difficult to treat. Researchers have increasingly turned their attention to groups of people who may face higher risks, in order to develop prevention and screening strategies that can improve early detection.

One area of growing interest is the connection between autoimmune diseases and cancer risk. Autoimmune conditions such as celiac disease, type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis involve chronic immune system activity and long-term inflammation. This constant stress on organs and tissues, combined with the effects of lifelong treatment, could contribute to the development of tumors. This systematic review and meta-analysis sought to bring clarity by carefully examining evidence from dozens of studies and accounting for potential bias in past research.

Study Purpose

The central goal of the study was to evaluate whether certain autoimmune diseases are linked to an increased or decreased risk of cancers of the digestive system. The focus was on celiac disease, type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. Researchers wanted to minimize bias in earlier findings and provide reliable estimates that could guide both doctors and patients.

Specifically, the cancers under review included the stomach, esophagus, pancreas, small intestine, liver, gallbladder, colon, and rectum. These cancers represent the majority of digestive system malignancies worldwide.

How the Study Was Conducted

To ensure thoroughness, the team conducted a systematic review of existing scientific publications across multiple databases, without restrictions on publication year. They used strict tools for assessing the quality of the studies and carefully accounted for sources of error. By combining results in a meta-analysis, they were able to analyze data from more than 1.5 million cases across 47 separate studies.

Unlike individual studies that may be limited by small sample sizes or inconsistent definitions, this approach allowed for more reliable estimates. Importantly, the researchers included extensive bias assessment, meaning they adjusted their conclusions to account for potential distortions in the data.

Main Findings

The results revealed a complex picture, with some autoimmune diseases linked to an increased cancer risk and others showing protective associations.

• Celiac Disease: Celiac patients were found to have higher risks of cancer in the pancreas, esophagus, colon, liver, and especially the small intestine. Among all associations, the strongest was between celiac disease and small intestine cancer, with risk more than four times higher than in the general population.
• Systemic Lupus Erythematosus: Patients with lupus showed elevated risks of pancreatic, liver, colon, and esophageal cancers. No increased risk was seen for stomach or rectal cancers.
• Type 1 Diabetes: This condition was linked to greater risks of stomach, pancreatic, liver, colon, esophageal, and gallbladder cancers. It was not strongly connected to small intestine or rectal cancers.
• Multiple Sclerosis: In contrast to the other diseases, multiple sclerosis showed an inverse relationship with several cancers. Patients had lower risks of pancreatic, esophageal, rectal, and colorectal cancers. The reasons for this unexpected finding are not fully understood and require further investigation.

Why Autoimmune Diseases May Influence Cancer Risk

Autoimmune diseases involve the immune system mistakenly attacking the body’s own tissues. This leads to persistent inflammation, which can contribute to cancer development by damaging cells, encouraging abnormal growth, and reducing the body’s ability to control malignant changes. Chronic inflammation is already known to be a major factor in cancer risk in conditions such as inflammatory bowel disease.

In addition, treatments for autoimmune conditions often involve medications that suppress the immune system, potentially altering how the body detects and eliminates cancerous cells. On the other hand, certain immune characteristics of diseases like multiple sclerosis may enhance cancer surveillance, explaining the observed protective effect in some cases.

Implications for Celiac Disease

For individuals with celiac disease, the study’s findings are especially important. While the risk of small intestine cancer is well-documented, this study confirmed associations with other digestive cancers, such as pancreatic and liver cancer, after adjusting for bias. This suggests that people with celiac disease may require closer long-term monitoring, even if they maintain a strict gluten-free diet.

Importantly, the study did not find evidence of increased risk for stomach or colorectal cancers in celiac patients, offering some reassurance. Still, the confirmation of risks in other organs underscores the need for awareness among both doctors and patients.

Why This Matters to Patients

People with autoimmune diseases already face the daily challenges of managing lifelong conditions. Adding the potential for increased cancer risk makes the picture even more complex. For celiac patients and those with other autoimmune disorders, these findings highlight the importance of regular medical checkups, open communication with healthcare providers, and awareness of potential symptoms that should not be ignored.

From a healthcare perspective, the results suggest that screening and preventive strategies may need to be tailored for patients with autoimmune conditions. Identifying individuals at highest risk could enable earlier detection and better outcomes. While the absolute risks for most cancers remain relatively low, the relative increase for certain digestive system cancers is meaningful enough to warrant attention.

Conclusion

This large-scale review and meta-analysis brings new clarity to the relationship between autoimmune diseases and digestive system cancers. For celiac disease, systemic lupus erythematosus, and type 1 diabetes, the study confirms elevated risks for specific cancers, particularly those affecting the pancreas, liver, esophagus, and small intestine. Multiple sclerosis, in contrast, appears to show a protective effect against several digestive cancers, though the mechanisms remain uncertain.

For people with celiac disease, these findings reinforce the importance of careful long-term monitoring and awareness. While a strict gluten-free diet remains the cornerstone of treatment, patients and doctors must also be mindful of broader health risks. Ultimately, this research is a reminder that managing autoimmune diseases is not only about controlling symptoms but also about protecting overall health through vigilance, prevention, and informed care.

Read more at: thelancet.com

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Celiac.com 03/06/2025 - Celiac disease, a chronic autoimmune condition triggered by gluten ingestion, is widely recognized for its impact on the digestive system. Beyond its more common symptoms, the disease has been linked to an elevated risk of certain cancers, particularly those of the digestive tract. This summary reviews a large French cohort study that investigated cancer risks and related inflammatory conditions in patients with celiac disease over a nine-year period.

Study Design and Population

The study analyzed data from the French PMSI (Programme de Médicalisation des Systèmes d’Information) database, covering hospitalizations from 2011 to 2019. Researchers included 27,114 patients diagnosed with celiac disease and matched them with an equal number of individuals without the disease. Participants were monitored over nine years, with demographic and medical information meticulously recorded. This approach allowed for a robust comparison of cancer and comorbidity risks between the two groups.

Key Findings on Cancer Risks

The study confirmed that individuals with celiac disease face a significantly heightened risk for several types of cancers. Below are the most notable findings:

1. Increased Risk of Lymphomas

Enteropathy-associated T-cell lymphoma (EATL): This rare but severe type of lymphoma was exclusively observed in the celiac group, underscoring its strong association with the disease.

Non-Hodgkin lymphoma: The odds ratio (OR) for this cancer was 4.08, indicating more than a fourfold increased risk compared to the control group.

2. Elevated Risks of Digestive Cancers

• Small bowel cancer: This cancer exhibited the highest risk, with an OR of 13.95, making it the most strongly associated digestive cancer in celiac patients.
• Pancreatic cancer: Patients with celiac disease had an OR of 2.41, reflecting a significant increase in risk.
• Esophageal cancer: The risk was elevated with an OR of 1.72.
• Colonic cancer: This cancer showed an OR of 1.69, confirming an increased but moderate risk.
• Gastric cancer: Patients had an OR of 1.52, indicating a slightly higher risk.

3. No Significant Associations

No increased risk was found for rectal cancer, hepatocellular carcinoma, or melanoma.

Interestingly, celiac patients had a lower risk of breast cancer, with an OR of 0.76.

Inflammatory Diseases and Their Role in Cancer Risks

The study also examined the relationship between celiac disease and inflammatory conditions that may predispose patients to cancer. Key findings include:

1. Pernicious Anemia and Gastric Cancer

Celiac patients were over 11 times more likely to develop pernicious anemia (OR: 11.28), a condition strongly linked to gastric cancer. In those with both conditions, the odds of developing gastric cancer increased dramatically (OR: 9.01).

2. Chronic Pancreatitis and Pancreatic Cancer

Nonalcoholic chronic pancreatitis was more common in the celiac group (OR: 1.67) and significantly raised the risk of pancreatic cancer (OR: 5.90) in affected patients.

3. Colonic Cancer and Microscopic Colitis

While Crohn’s disease and ulcerative colitis did not increase colonic cancer risk in celiac patients, microscopic colitis—another inflammatory condition—was associated with a higher risk (OR: 1.84).

Other Comorbidities in Celiac Patients

As expected, the study found higher incidences of autoimmune and metabolic conditions in the celiac group, which serve as internal validation for the results. These include:

• Type 1 diabetes (OR: 2.80)
• Thyroiditis (OR: 5.04)
• Rheumatoid arthritis (OR: 1.41)
• Osteoporosis (OR: 2.16)
• Implications for Clinical Practice

The findings of this study have several important implications:

1. Need for Vigilance and Screening

The high risks of small bowel, pancreatic, and gastric cancers emphasize the importance of regular screening and follow-up in celiac patients. For example, gastric biopsies may be warranted at the time of celiac diagnosis to detect early signs of malignancy.

2. Management of Inflammatory Conditions

Addressing associated inflammatory diseases, such as pernicious anemia and chronic pancreatitis, could mitigate cancer risks. Similarly, identifying and managing microscopic colitis may help reduce the risk of colonic cancer.

3. Role of a Gluten-Free Diet

While a strict gluten-free diet has been shown to reduce the risk of intestinal lymphomas, its effect on other cancers remains less clear. Continued dietary adherence and regular medical evaluations are essential.

Conclusion

This large-scale French cohort study provides compelling evidence of elevated cancer risks in celiac disease patients, particularly for lymphomas and digestive tract cancers. Additionally, it highlights the role of comorbid inflammatory conditions in driving these risks. For individuals with celiac disease, these findings underscore the importance of proactive medical care, including regular screenings and diligent management of associated conditions. By doing so, patients and healthcare providers can work together to reduce long-term health complications and improve overall outcomes.

Read more at: cghjournal.org

Celiac.com 02/19/2024 - A recent study presented at the 2023 annual meeting of the American College of Gastroenterology has raised concerns about the increasing incidence of enteropathy-associated T-cell lymphoma (EATL) – a rare and aggressive form of T-cell, non-Hodgkin lymphoma. This alarming trend has prompted researchers to explore the possible connection between EATL and celiac disease, shedding light on the risks faced by individuals with this autoimmune condition.

Lead investigator Dr. Isabel Hujoel, Clinic Director of the Celiac Disease Center at UW Medical Center, Seattle, highlighted the strong association between EATL and celiac disease. While EATL is rare, most cases are observed in patients with celiac disease, suggesting a potential link between the two conditions. The study, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program database, identified 463 cases of EATL between 2000 and 2020, with an age-adjusted incidence rate of 0.014 per 100,000 people. Alarmingly, the incidence of EATL increased by 2.58% annually over this 20-year period.

Despite advancements in medical treatment, the prognosis for EATL remains poor, with a median survival of approximately six months. Findings from the study revealed that most cases were treated with a combination of surgery and chemotherapy. However, survival outcomes did not improve over the study period, underscoring the urgent need for more effective treatment strategies.

Dr. Sophia Dar, a gastroenterology fellow at Southern Illinois University School of Medicine, emphasized the importance of early detection and treatment. While chemotherapy showed promising results, the overall mortality rate remained high, highlighting the challenges in managing this aggressive cancer.

Researchers emphasized the need for further investigation into the factors contributing to the high mortality rate associated with EATL. Understanding these factors could pave the way for more efficient treatment plans and improved outcomes for patients.

Debra Silberg, MD, PhD, Chief Scientific Officer of the nonprofit Beyond Celiac, emphasized the rarity of EATL and the need for targeted screening. Screening for EATL should be considered in cases of refractory celiac disease or when there is suspicion of complications related to celiac disease.

The rise in cases of EATL serves as a sobering reminder of the potential complications associated with celiac disease. Heightened awareness, early detection, and improved treatment options are crucial in addressing this rare but deadly cancer among individuals with celiac disease.

Read more at gastroendonews.com

Celiac.com 05/01/2023 - Celiac disease is a condition that affects millions of people worldwide. Celiac disease is an immune-mediated enteropathy triggered by gluten, a protein found in wheat and related grains. For people with celiac disease, eating gluten can lead to a range of symptoms and damage to the small intestine. 

The only effective treatment for the disease is a strict gluten-free diet, which allows the intestines to heal and prevents further complications. However, recent research has shed light on the potential dangers of having celiac disease: the danger of malignant complications.

A group of researchers at the Department of Internal Medicine and Gastroenterology, University Hospital Brno, recently conducted a study examining the occurrence of malignancies in patients with celiac disease. They wanted to raise awareness of these potentially life-threatening complications, with the hope of promoting earlier diagnoses and better outcomes.

Occurrence of Malignancies in Patients with Celiac Disease

The study analyzed seven cases of malignancies that occurred among 190 celiac disease patients over a seven-year period. The patients ranged in age from 36 to 82 years old, with a mix of men and women. The malignancies found by the team included small bowel adenocarcinoma, diffuse large B-cell lymphoma, carcinoma of the tongue, and colorectal carcinoma.

The overall findings were alarming, as malignancies were present in nearly 4% of the patients in the study. This highlights the need for better awareness of the potential risks associated with celiac disease. 

Professionals Need to Work Towards Earlier Diagnoses

By understanding the risk factors, recognizing the presentation of malignant complications, and closely monitoring the disease course, healthcare professionals can work towards earlier diagnoses and better outcomes for patients.

The study also emphasized the importance of continued research into potential risk factors for malignancies in celiac disease patients. Identifying these factors could help in developing strategies for prevention and early intervention.

For people living with celiac disease, this research underscores the need for regular check-ups and close monitoring of their condition. It's really important for patients to maintain a strict gluten-free diet, as this remains the only real way for celiacs to stay as healthy as possible. By doing so, celiacs can reduce their risk of complications and improve their overall quality of life.

Read more in Journal of Medical Case Reports

Celiac.com 04/10/2023 - The association between celiac disease and the development of small bowel lymphoproliferative disorders and esophageal adenocarcinoma is well-established, but there is limited evidence of an increased risk of colorectal cancer in these patients. 

Cross-sectional Population-based Study

To evaluate the risk of developing colorectal cancer in patients with celiac disease a team of researchers recently conducted a cross-sectional population-based study using a commercial database that contains the electronic health records from 26 major integrated US healthcare systems. 

The team included patients aged 18-65 years of age, and excluded those with inflammatory bowel disease. They used multivariate analysis to calculate the risk of developing colorectal cancer, adjusting for potential confounders.

The Researchers

The research team included Somtochukwu Onwuzo; Antoine Boustany; Mustafa Saleh; Riya Gupta; Chidera Onwuzo; Jessy Mascarenhas Monteiro; Favour Lawrence; Chinenye Emeshiobi; Juliana Odu; and Imad Asaad.

They are variously affiliated with the departments of Internal Medicine and Department of Gastroenterology at the Cleveland Clinic Foundation in Cleveland; the Faculty of Medical Sciences at Lebanese University in Beirut, LBN; the Faculty of Medicine in Kasturba Medical College, Mangalore in Mangalore, IND; the department of Internal Medicine and the General Hospital Lagos Island in Lagos, Nigeria; the department of Internal Medicine at the Ross University School of Medicine in Bridgetown, Barbados; the department of Internal Medicine at Mercy Hospital in Fort Smith, USA; and the department of Public Health at the University of Toledo in Toledo, Ohio, USA. 

Their Findings: Patients with Celiac Disease Face an Increased Risk of Developing Colorectal Cancer

The team's cross-sectional population-based study showed that patients with celiac disease face an increased risk of developing colorectal cancer, even after adjusting for common risk factors. 

Their findings suggest that patients with celiac disease are frequently diagnosed with colorectal cancer, indicating that the disease may involve other parts of the gastrointestinal tract besides the small bowel. 

The results highlight the importance of screening patients with celiac disease for colorectal cancer, even in the absence of traditional risk factors. 

These findings could help to improve the management and follow-up of patients with celiac disease, especially with regard to diagnosis and prevention of colorectal cancer.

Read more at Cureus.com

Celiac.com 03/31/2022 - A number of studies have associated celiac disease with increased mortality rates, partly due to celiac-related cancers. 

However, most studies assessing cancer risk used data from celiac patients diagnosed in an era before celiac disease diagnosis rates and access to gluten-free food become more common. What can we learn from a study of celiac patients diagnosed more recently?

A team of researchers conducted a population-based study to assess cancer risk in celiac disease. The research team included Benjamin Lebwohl; Peter H.R. Green; Louise Emilsson; Karl Mårild;  Jonas Söderling; Bjorn Roelstraete; and Jonas F. Ludvigsson.

Defining celiac disease as duodenal/jejunal villus atrophy, and using the Epidemiology Strengthened by histoPathology Reports in Sweden cohort, the team gathered data on all celiac patients in Sweden. 

The team matched each patient to five or fewer controls by age, sex, and county. They then employed a stratified Cox proportional hazards model, and tracked patients from diagnosis until the first instance of cancer, or to December 31, 2016.

After looking at nearly fifty thousand patients with celiac disease, the team found that nearly sixty-five percent were diagnosed since 2000. After an average follow-up of nearly twelve years, the rate of cancer was 6.5 and 5.7 per 1000 person-years in celiac disease patients and control subjects, respectively. 

The overall risk of cancer rose only in the first year after celiac disease diagnosis and not subsequently, although the risks for hematologic, lymphoproliferative, hepatobiliary, and pancreatic cancers continued. 

People over sixty showed the highest risk, while those diagnosed before age 40 showed no increase in cancer risk. The cancer risk was similar among those diagnosed with celiac disease before or after the year 2000.

Bad news/Good news
The bad news is that the team did find that celiac patients have an elevated risk of developing cancer.

The good news is that the increased risk is found in people diagnosed with celiac disease after age 40, but it is mainly a factor within the first year of celiac diagnosis, and limited to certain gastrointestinal and hematologic cancers.

However, this study is good news for anyone with celiac disease who might be worried about having an overall higher risk of cancer, as that does no seem to be the case, at least going by this data.

Stay tuned for more on this and related stories.

Read more in Clinical Gastroenterology & Hepatology

The researchers are variously affiliated with the Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York; the Department of Epidemiology, Mailman School of Public Health, Columbia University in New York, USA; School of Medical Science, University of Örebro, Örebro, Sweden; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; the Värmlands Nysäter Health Care Center and Centre for Clinical Research, County Council of Värmland, Sweden; the Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway; the Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; the Department of Pediatric Gastroenterology, Queen Silvia Children’s Hospital, Gothenburg, Sweden; and the Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Celiac.com 02/28/2022 - Immune regulation is important for carcinogenesis; however, the cancer risk profiles associated with immune-mediated diseases, like celiac disease, are not well understood.

A team of researchers recently set out to assess the profiles of cancer risk associated with 48 immune-mediated diseases with the risk of total and individual cancers. They also assessed the prospective association of organ-specific immune-mediated diseases with the risk of local and extra-local cancers.

The research team included Ming-ming He, MD; Chun-Han Lo, MD, MPH; Kai Wang, MD, PhD; Georgios Polychronidis, MD; Liang Wang, MD; Rong Zhong, PhD; Markus D. Knudsen, PhD; Zhe Fang, MD; and Mingyang Song, MD, ScD.

For their prospective cohort study, the team used data from the UK Biobank cohort study on adults aged 37 to 73 years who were recruited at twenty-two assessment centers throughout the UK between January 1, 2006, and December 31, 2010, with follow-up through February 28, 2019.

After adjusting for various potential confounders using time-varying Cox proportional hazards regression, the team assessed the connection between immune-mediated diseases with risk of cancer with multivariable hazard ratios (HRs) and 95% CIs. They used the contrast test method to assess heterogeneity in the associations of organ-specific immune-mediated diseases with local and extra-local cancers.

In this group study of nearly half a million participants, the team found that immune-mediated diseases were associated with an increased total cancer risk. 

Organ-specific immune-mediated diseases showed higher associated risk of local cancers than extra-local cancers, and many immune-mediated diseases were associated with increased risk for cancer in the near and distant organs or other systems. Organ-specific immune-mediated diseases had stronger associations with risk of local cancers than extralocal cancers. 

The associations for individual immune-mediated diseases were largely organ specific, but were also seen for some cancers in the near and distant organs or different systems. 

Their findings suggest that immune-mediated diseases are associated with risk of cancer at the local and systemic levels, which supports the role of local and systemic immunoregulation in the development of cancers.

Read more in JAMA Oncology

The researchers are variously affiliated with the Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; the Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston; the Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston; the Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany; the Study Centre of the German Surgical Society, University of Heidelberg, Heidelberg, Germany; the Center of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; the Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway; the Division of Surgery, Department of Transplantation Medicine, Inflammatory Diseases and Transplantation, Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway; and the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Celiac.com 09/20/2021 - People with celiac disease face an increased risk of death, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in celiac disease diagnosis rates and access to gluten-free food. A team of researchers recently conducted a population-based study to assess the risk of cancer for people with celiac disease.

For their study, the team used the Epidemiology Strengthened by histoPathology Reports in a Swedish cohort to gather data from all celiac disease patients in Sweden, with celiac disease defined as duodenal/jejunal villus atrophy. 

They then matched each patient by age, sex, and county to five or fewer control subjects. Then, following patients from diagnosis until first cancer, or by December 31, 2016, they calculated hazards ratios using the stratified Cox proportional hazards model.

Of nearly 50,000 celiac patients, 64% were diagnosed with celiac disease since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in celiac disease patients and controls, respectively. 

The risk of cancer rose overall, but it was most sharply elevated in the first year after celiac disease diagnosis, and not later on, although the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreatic cancers remained. 

Risk levels were highest for people diagnosed with celiac disease after age 60 years of age, while those diagnosed before age 40 faced no such increase. Lastly, the cancer risk was similar among those diagnosed with celiac disease before or after the year 2000. The team's data showed an overall rise in cancer risk for celiac disease patients, even in recent years. However, the risk increase is only for those diagnosed with celiac disease after age 40, and then mostly within the first year of diagnosis.

This is one of the first studies to give a solid picture of overall cancer risks for people with celiac disease. Stay tuned for more on this and related stories. 

Read more in Clinical Gastroenterology and Hepatology
 

The research team included Benjamin Lebwohl; Peter H.R. Green; Louise Emilsson; Karl Mårild; Jonas Söderling; Bjorn Roelstraete; and Jonas F. Ludvigsson. They are variously affiliated with the Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, New York; the Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York; the Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; the Department of Pediatric Gastroenterology, Queen Silvia Children’s Hospital, Gothenburg, Sweden; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; and the Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

12/06/2021 - A correction was made to the article "64% were diagnosed with celiac disease since 2000."

Celiac.com 08/10/2020 - Small bowel cancers are on the rise. Research has shown some possible connections with celiac disease, but there have not been any detailed large group studies. To better understand the connections between celiac disease and small bowel cancers, a team of researchers recently set out to conduct a large group study.

The UK and Swedish based team turned to the nationwide ESPRESSO cohort study to gather data on everyone diagnosed for celiac disease from 1965 through 2017 at any of the twenty-eight pathology centers in Sweden. 

They defined celiac disease as duodenal or jejunal villous atrophy, with a stage 3 Marsh score, and matched celiac patients with up five control subjects randomly chosen from the general population. They used stratified Cox regression to calculate hazard ratios for small bowel adenocarcinoma, adenomas and carcinoids. Over an average follow up of 11 years, they matched nearly 50,000 celiac patients with about 240,000 controls. 

Overall, for about every 3,000 patients with celiac disease followed for 10 years, they found one extra case of small bowel adenocarcinoma. They observed an inverse relationship between mucosal healing and risk of future small bowel adenocarcinoma, though this was not statistically significant.

Their analysis showed the absolute risk of small bowel adenocarcinoma is low in people with celiac disease. However, even though the absolute risk is low, the team found that risks are still much higher than non-celiacs for small bowel adenocarcinoma and adenomas, but not for carcinoids.

The good news is that the overall risks of developing small bowel adenocarcinoma remain low in people with celiac disease. The bad news is that the risk is still many time greater than it is for people without celiac disease.

Read more in Gastroenterology

The research team included Louise Emilsson, Carol Semrad, Benjamin Lebwohl, Peter Hr Green, and Jonas F Ludvigsson. They are variously affiliated with the Department of General Practice & Department of Health Management and Health Economics, Institute of Health and Society, University of Oslo, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Faculty of Medicine and Health, Örebro University, SE 701 82, Örebro, Sweden; Vårdcentralen Årjäng and Centre for Clinical Research, County Council of Värmland, Värmland, Sweden; the University of Chicago Medicine, Chicago, IL, USA; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA; the Department of Paediatrics at Örebro University Hospital, Örebro, Sweden; and the Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.

Celiac.com 04/28/2020 - People who suffer from small bowel adenocarcinomas (SBAs) usually have poor outcomes, and face limited treatment options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many micro-satellite instability-high (MSI-H) solid tumors. 

A team of researchers recently set out to investigate PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease, Crohn’s disease, or sporadic, recruited through the Small Bowel Cancer Italian Consortium. 

The researchers assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 celiac disease-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. They found that expression of PD-L1 and PD-1 correlated with a number of clinico-pathological factors, such as the origin, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The combined positive score (CPS) showed PD-L1 rates of 26% in the whole cohort of SBAs, with 35% in both celiac disease-SBAs and CrD-SBAs, compared with just 5% in sporadic SBAs. 

Combined positive scores equal to or greater than 1 SBAs were found in 41% of MSI-H cases (41%), compared with just 18% of non-MSI-H cases; however, the team also found 15 CPS equal to or greater than 1 micro-satellite stable SBAs. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more often medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. 

This study shows higher rates of PD-L1+ in both celiac disease-SBAs and CrD-SBAs compared with sporadic SBAs. Moreover, the discovery of a subset of PD-L1+ micro-satellite stable SBAs suggests that it will be beneficial to discover more biomarkers to immune checkpoint inhibitor response, along with MSI-H.

Read more in Modern Pathology (2020)

The research team included Paolo Giuffrida and Giovanni Arpa, Federica Grillo, Catherine Klersy, Gianluca Sampietro, Sandro Ardizzone, Paolo Fociani, Roberto Fiocca, Giovanni Latella, Fausto Sessa, Antonietta D’Errico, Deborah Malvi, Claudia Mescoli, Massimo Rugge, Gabriella Nesi, Stefano Ferrero, Daniela Furlan, Gilberto Poggioli, Fernando Rizzello, Maria C. Macciomei, Donatella Santini, Umberto Volta, Roberto De Giorgio, Giacomo Caio, Antonio Calabrò, Carolina Ciacci, Maria D’Armiento, Aroldo Rizzo, Gaspare Solina, Michele Martino, Francesco Tonelli, Vincenzo Villanacci, Renato Cannizzaro, Vincenzo Canzonieri, Ada M. Florena, Livia Biancone, Giovanni Monteleone, Roberto Caronna, Antonio Ciardi, Luca Elli, Flavio Caprioli, Maurizio Vecchi, Renata D’Incà, Fabiana Zingone, Anna D’Odorico, Marco Vincenzo Lenti, Barbara Oreggia, Luca Reggiani Bonetti, Marco Astegiano, Elena Biletta, Laura Cantoro, Antonino G. Giannone, Augusto Orlandi, Claudio Papi, Vittorio Perfetti, Erica Quaquarini, Giancarlo Sandri, Marco Silano, Paolo Usai, Valeria Barresi, Rachele Ciccocioppo, Ombretta Luinetti, Paolo Pedrazzoli, Andrea Pietrabissa, Alessandra Viglio, Marco Paulli, Gino R. Corazza, Enrico Solcia, Alessandro Vanoli & Antonio Di Sabatino.

The researchers are variously affiliated with the Anatomic Pathology ASL Biella, Biella, Italy; the Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Department of Biopathology and Image Diagnostics, University of Tor Vergata, Rome, Italy; the Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Institute of Oncology and Transplant Pathology, University of Bologna, St. Orsola-Malpighi Hospital, Bologna, Italy; the Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Department of Gastroenterology, Centro di Riferimento Oncologico (CRO) di Aviano IRCCS, Aviano, Italy; the Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; the Department of Medicine and Surgery, University of Salerno, Salerno, Italy; the Department of Systems Medicine, University of Tor Vergata, Rome, Italy; the Department of Surgical Sciences, La Sapienza University, Rome, Italy; the Department of Surgery, General Surgery II, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Department of Radiological, Oncological, Pathological Sciences, Umberto I Hospital, La Sapienza University, Rome, Italy; the; the Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; the Gastroenterology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; the Gastroenterology Unit, USL Umbria 1, Perugia, Italy; the Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; the General Surgery Unit, Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy; the Section of Pathology, Department of Diagnostic Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy; the General and Specialistic Surgery, Città della Salute e della Scienza-Molinette Hospital, Turin, Italy; the Gastroenterology Unit, Department of Medicine, AOUI Policlinico G.B. Rossi, University of Verona, Verona, Italy; the Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the IBD Unit, San Filippo Neri Hospital, Rome, Italy; the Internal Medicine Unit, S.S. Annunziata Hospital, ASST-Pavia, Varzi, Italy Medical Oncology Unit, IRCCS ICS Maugeri and Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; the Oncology Unit, IRCCS San Matteo Hospital, Pavia, Italy; the Clinical Nutrition Unit, Sant’Eugenio Hospital, Rome, Italy; the Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; the Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy; the Department of Internal Medicine, University of Cagliari, Cagliari, Italy; the Pathology Unit of the Centro di Riferimento Oncologico (CRO) di Aviano IRCCS, Aviano, Italy; the Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; the Pathology Unit of the Department of Surgical and Diagnostic Sciences, University of Genoa and San Martino/IST University Hospital, Genoa, Italy; the Biometry and Statistics Service, Fondazione IRCCS San Matteo Hospital, Pavia, Italy; the Surgery of the Alimentary Tract, Department of Medical and Surgical Sciences, Sant’Orsola—Malpighi Hospital, University of Bologna, Bologna, Italy; the Institute of Pathology, Spedali Civili Hospital, Brescia, Italy; the Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; the Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy; the Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy; the Public Health Department at Federico II University of Naples, Naples, Italy; the Department of Surgery and Translational Medicine, University of Florence, Florence, Italy; the Units of Pathology, Cervello Hospital, Palermo, Italy; the Units of General Surgery, Cervello Hospital, Palermo, Italy; the Unit of IBD Surgery, Luigi Sacco University Hospital, Milan, Italy; the Gastroenterology Unit, Luigi Sacco University Hospital, Milan, Italy; the Pathology Unit, Luigi Sacco University Hospital, Milan, Italy; and the Unit of Human Nutrition and Health, Istituto Superiore di Sanità, Rome, Italy.

Celiac.com 9/26/2019 - Small bowel adenocarcinoma is a rare abnormal tissue growth, that can happen alone, or can also be the result of predisposing conditions, including hereditary syndromes and immune-mediated intestinal disorders, such as celiac disease. 

However, researchers still don't know very much about small bowel adenocarcinoma in the context of celiac disease. To get some answers, a research team recently set out to show the main clinical features, diagnostic procedures and management options of small bowel adenocarcinoma cases detected in a large cohort of celiac patients diagnosed in a single tertiary care center.

The research team included Giacomo Caio, Umberto Volta, Francesco Ursini, Roberto Manfredini, and Roberto De Giorgio.

They are variously affiliated with the Department of Medical Sciences, University of Ferrara, St. Anna Hospital in Ferrara, Italy; the Mucosal Immunology and Biology Research Center and Celiac Center, Massachusetts General Hospital- Harvard Medical School, Boston, MA, USA; the Department of Medical and Surgical Sciences, University of Bologna in Bologna, Italy; and the Department of Medical Sciences, University of Ferrara, St. Anna Hospital, Ferrara, Italy.

The team retrospectively reviewed all small bowel adenocarcinoma cases from a group of 770 celiac disease patients of the Celiac Disease Referral Center at the University Hospital in Bologna, Italy from January 1995 to December 2014. The group included nearly 600 females, spanned 18 to 80 years of age, and averaged 36 years old at diagnosis.

A total of five of the 770 celiac disease patients developed small bowel adenocarcinoma. All were female, and about 53 years old on average, though the individuals ranged from 38 to 72 years old. 

The small bowel adenocarcinoma was diagnosed along with the celiac disease in three cases. It was localized to the jejunum in four cases, and to the duodenum in one case. 

The clinical presentation of small bowel adenocarcinoma was characterized by intestinal sub-occlusion in two cases, while the main presentation in the other three cases were iron deficiency anaemia, abdominal pain and acute intestinal obstruction, respectively. 

All the patients underwent surgery, while three patients with advanced stage neoplasia also received chemotherapy. The overall survival rate at 5 years was 80% for the group.

The observed celiac disease-related small bowel adenocarcinoma cases were marked by a younger age of onset, were mainly female, and faced better odds of survival, compared with sporadic, Crohn- and hereditary syndrome-related small bowel adenocarcinoma.

Read more in BMC Gastroenterology volume 19, Article number: 45 (2019)

Celiac.com 05/22/2019 - What are the risks for lymphoma and gastrointestinal cancer in patients 55 years and older with newly diagnosed adult-onset celiac disease?

Researchers and clinicians have reported connections between celiac disease and the development of certain lymphoid and gastrointestinal (GI) cancers, but there just isn't much good data. Without good data, it's impossible to develop effective evidence-based follow-up protocols.

In an effort to develop better information on the subject, a team of researchers recently set out to determine relative (RR) and absolute risks of lymphoma and GI carcinoma for newly diagnosed adult celiac patients.

The research team included Tom van Gils, Petula Nijeboer, Lucy IH Overbeek, Michael Hauptmann, Daan AR Castelijn, Gerd Bouma, Chris JJ Mulder, Flora E van Leeuwen, and Daphne de Jong. They are variously affiliated with the Celiac Center Amsterdam, Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands; the Foundation PALGA (The Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands), Houten, the Netherlands; the Department of Epidemiology and Biostatistics, the Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, the Netherlands; and the Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.

To assess RR with cases (lymphoma or GI carcinoma) and controls--melanoma or basal cell carcinoma diagnosed from 1994–2014, the team conducted a case-control design using the Dutch nationwide population-based pathology database (PALGA). 

Among this group, the team identified patients with prior histologically proven or simultaneously diagnosed with the malignancy. The team found celiac disease in a total of 349 of 301,425 cases (0.1%) and 282 of 576,971 (0.05%) control subjects. 

Adults diagnosed with celiac disease had a substantially higher risk of T-cell lymphoma, mainly enteropathy-associated T-cell lymphoma (EATL). Clinicians should look out for EATL (both intestinal and extra-intestinal) and small bowel adenocarcinoma in patients with celiac disease diagnosed at 50 years of age or later.

Although most often synchronously diagnosed, risk of T-cell lymphoma 1 year or more after celiac disease diagnosis was still elevated at 12.7 (95% CI 7.6–21.3). 

Other celiac disease-associated malignancies were small bowel adenocarcinoma, with RR of 11.9 (95% CI 8.2–17.2), and esophageal squamous cell carcinoma (RR = 3.5 (95% CI 2.1–5.8)). 

Absolute risks of developing these cancers were relatively low. Celiac disease did not show any higher risk of developing other types of lymphomas and GI carcinomas.

Read more in the United European Gastroenterology Journal