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Chronic, Noninfectious Diarrhea: A Review

Author/s: 
Prashant Singh, Allen Lee, Neil M. Sheth

Importance: Chronic diarrhea is defined as loose or watery stools lasting longer than 4 weeks and affects approximately 6% to 7% of adults in the US. More than 90% of patients with chronic diarrhea have a noninfectious etiology.

Observations: The most common causes of chronic, noninfectious diarrhea are irritable bowel syndrome with diarrhea (IBS-D) and functional diarrhea. IBS-D typically presents with recurrent abdominal pain relieved or worsened after defecation. Functional diarrhea is a condition in which more than 25% of bowel movements in the preceding 3 months are loose or watery, but it is not associated with significant abdominal pain. Chronic diarrhea due to a small-bowel source, such as celiac disease or small intestinal bacterial overgrowth, is typically associated with large-volume diarrhea and weight loss, with or without steatorrhea. Celiac disease is an autoimmune condition defined by enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals, and small intestinal bacterial overgrowth is characterized by excessive bacteria in the small bowel. Chronic diarrhea due to colon pathology, such as bile acid diarrhea and microscopic colitis, typically presents with frequent, low-volume stools, with or without urgency and excess mucus. Bile acid diarrhea is characterized by excess bile acids in the colon, and microscopic colitis is characterized by chronic inflammation on colon biopsies despite normal endoscopic appearance. Evaluation of chronic diarrhea includes serological testing for celiac disease (tissue transglutaminase immunoglobulin A, along with total immunoglobulin A) and stool testing for fecal calprotectin to evaluate for inflammatory bowel disease. Patients with gastrointestinal bleeding, unexplained weight loss, 45 years or older, nocturnal diarrhea, steatorrhea, and/or iron deficiency anemia should undergo colonoscopy to evaluate for colorectal cancer as well as upper endoscopy. During colonoscopy, random biopsies are recommended to evaluate for microscopic colitis, which affects 13% of patients with chronic diarrhea. If evaluation does not identify a cause of chronic diarrhea, likely diagnoses are IBS-D or functional diarrhea and the patient should be treated with lifestyle modification, such as regularly scheduled meals, exercise, intake of at least 8 cups of noncaffeinated fluids daily, limiting caffeine to 3 cups or fewer daily, and avoiding alcohol and carbonated beverages. For general treatment of chronic diarrhea, dietary modifications, such as consuming a diet low in fermentable oligosaccharides (legumes, wheat, onions, garlic), disaccharides (lactose), and monosaccharides (fructose), and polyols (sorbitol, mannitol), or medications, such as opiate agonists (loperamide), anticholinergics (hyoscyamine, dicyclomine), or 5-hydroxytryptamine 3 receptor (5-HT3) antagonists (ondansetron), can be prescribed. These therapies typically improve diarrhea in 50% to 80% of patients.

Conclusions and relevance: The most common causes of chronic, noninfectious diarrhea include IBS-D and functional diarrhea. Diagnostic testing should include consideration of celiac disease, inflammatory bowel disease, and microscopic colitis. Empiric therapies for chronic diarrhea include lifestyle and dietary modifications and medications, including opiate agonists, anticholinergics, and 5-HT3 antagonists.

Keywords 
Diarrhea infectious diarrhea Irritable Bowel Syndrome abdominal pain Defecation Steatorrhea

Gastric Cancer: A Review

Author/s: 
Anuj Kishor Patel, Nilay S. Sethi

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.

Keywords 
oncology Gastroenterology Stomach Neoplasms adenocarcinoma Helicobacter Infections abdominal pain

Efficacy of interventions for the treatment of irritable bowel syndrome, functional abdominal pain-not otherwise specified, and abdominal migraine in children: a systematic review and network meta-analysis

Author/s: 
Vasiliki Sinopoulou, Jip Groen, Morris Gordon, Ed Mougey, James P Franciosi, Tim G J de Meij, Merit M Tabbers, Marc A Benninga

Background: Many treatments for abdominal pain-related disorders of gut-brain interaction (AP-DGBI) in children have been studied. We aimed to assess the efficacy and safety of all known treatment options for paediatric AP-DGBI.

Methods: For this systematic review and network meta-analysis, we searched Embase, MEDLINE, and CENTRAL databases from inception to Jan 16, 2025, for published randomised controlled trials. We included trials of any treatment for AP-DGBIs (irritable bowel syndrome, functional abdominal pain-not otherwise specified, and abdominal migraine, excluding functional dyspepsia) in children aged 4-18 years. We excluded randomised controlled trials that solely included children with functional dyspepsia, but we included studies in which children with functional dyspepsia were included alongside children with the other AP-DGBI diagnoses and outcome data could not be separated. Data extraction and quality appraisal were performed in duplicate. The primary outcome for this network meta-analysis was author-defined treatment success. Network meta-analysis methodology was used within a frequentist framework using multivariate meta-analysis and outcomes were assessed using the Grading of Recommendations, Assessment, Development and Evaluation methodology. Clinical relevance of effect sizes was interpreted according to consensus definitions.

Findings: Of 19 337 records identified through the database search, 155 records representing 91 original randomised controlled trials were included in the network meta-analysis: these 91 trials comprised 7226 participants (4119 females and 2673 males). 12 studies assessed dietary treatments (n=730), 25 assessed pharmacological treatments (n=2140), 23 assessed probiotic treatments (n=1762), and 35 assessed psychosocial treatments (n=2952). Two treatments were probably more effective for treatment success than control treatments (moderate certainty): hypnotherapy (risk ratio [RR] 4·99 [95% CI 2·15 to 11·57]; large effect size) and cognitive behavioural therapy (CBT; RR 1·99 [95% CI 1·33 to 2·98]; moderate effect size). All other treatments evaluated for treatment success were either not effective or the data were of very low certainty and thus no conclusions could be made.

Interpretation: Hypnotherapy and CBT show moderate certainty for treatment efficacy with clinically relevant effect sizes. No conclusions can be made about the other therapies and treatment success due to very low evidence certainty. Future randomised controlled trials should focus on improving the evidence certainty for those other therapies with regard to core AP-DGBI outcomes.

Funding: None.

Keywords 
abdominal pain Irritable Bowel Syndrome Migraine Disorders gut-brain interaction

Acute Abdomen in the Modern Era

Author/s: 
Selwyn O Rogers Jr, Orlando C Kirton

Acute abdominal pain is one of the most common symptoms in patients presenting to the emergency department and accounts for 5 to 10% of all emergency department visits. Pathophysiological conditions that lead to surgical interventions in such patients are mainly gastrointestinal obstruction, hemorrhage, ischemia, and viscus perforation. Acute abdominal pain can be diffuse or localized (i.e., quadrant-based epigastric pain or pain in the right upper quadrant, left upper quadrant, right lower quadrant, or left lower quadrant)2,4,6 and is associated with but not limited to the following disease processes: perforated viscus, peptic ulcer disease, mesenteric ischemia, acute cholecystitis, appendicitis, diverticulitis, pancreatitis, and intraabdominal hemorrhage. The need for emergency general surgery is an independent risk factor for postoperative complications and death, indicating the severity of the condition. Therefore, timely diagnosis of acute abdominal emergencies is essential. From antiquity to modern times, medical students have been taught that the history and the physical examination are the central components in the evaluation of acute abdominal pain.

Keywords 
Abdomen acute abdomen diagnosis abdominal pain

A challenging diagnosis: hereditary angioedema presenting during pregnancy

Author/s: 
Chair, I., Lacuesta, G., Nash, C. M., Cook, V.

• Hereditary angioedema (HAE) is a rare autosomal dominant
disorder characterized by recurrent episodes of painful (and
usually asymmetric) swelling without urticaria that leads to
substantial morbidity and even mortality (in the case of
laryngeal involvement) if left untreated.
• Delayed diagnosis and misdiagnosis of HAE are common,
particularly during pregnancy and the postpartum period.
• Hereditary angioedema should be considered in the differential
diagnosis of any patient presenting with unexplained
abdominal pain and recurrent episodes of angioedema
(particularly if asymmetric in nature) without urticaria.
• Tests to confirm the diagnosis of HAE include measurement of
C4 and C1 inhibitor (INH) antigen and function.
• Successful pregnancy and delivery are possible in HAE with
proper medical management, which includes plasma-derived
C1-INH and collaboration with HAE specialists.

Keywords 
abdominal pain Morbidity diagnosis, differential Hereditary angioedema (HAE) female

Rotavirus

Author/s: 
American Academy of Family Physicians

What is rotavirus?

Rotavirus is a common stomach and intestinal illness. It mostly affects babies and young children. It is one of the most common causes of severe diarrhea. Almost all children will have a rotavirus infection by the time they are 5 years old.

Rotavirus is highly contagious. It spreads through direct or indirect contact with an infected person’s feces (poop). It can happen if you touch a contaminated object, food, water, or the hands or mouth of an infected person. The virus enters your body when your unclean hand touches your nose or mouth.

The risk of catching rotavirus is greatest in the winter and spring (December through June). Adults can get the disease, but their symptoms usually aren’t as severe.

Keywords 
abdominal pain pediatric diaherrea fever
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