Overview
GastroAGI
OverviewIntroduction Tranexamic acid has been widely used across trauma, surgical and hemorrhagic settings because of its antifibrinolytic effects and ability to stabilize clot formation. Earlier small studies suggested potential benefit in gastrointestinal bleeding, leading to interest in its use for acute upper and lower GI hemorrhage.
Problem Statement Despite historical enthusiasm, uncertainty remained regarding the efficacy and safety of tranexamic acid in gastrointestinal bleeding, particularly in the era of modern endoscopic hemostasis, proton-pump inhibitors and contemporary supportive care. Clarification from major societies was required following publication of high-quality randomized evidence.
Summary This position statement from the British Society of Gastroenterology and Association of Coloproctology of Great Britain and Ireland strongly advises against the routine use of tranexamic acid in acute upper or lower gastrointestinal bleeding. The recommendation is primarily based on the landmark HALT-IT trial, a large international randomized placebo-controlled study involving more than 12,000 patients with significant GI bleeding. HALT-IT demonstrated no reduction in bleeding-related mortality with tranexamic acid administration despite earlier smaller studies suggesting possible benefit. Importantly, the trial identified increased risks of venous thromboembolism and seizures among patients receiving tranexamic acid, raising significant safety concerns. The societies emphasize that earlier positive studies were methodologically weak and conducted before widespread use of modern endoscopic therapy and optimized acid suppression. Consequently, the position statement concludes that the overall risk–benefit profile does not support routine TXA use in GI bleeding. The document further states that any exceptionally rare off-guideline use should occur only after exhaustion of standard therapies, require senior consultant-level decision-making and be clearly documented within institutional governance systems. This statement is clinically important because tranexamic acid continues to be intermittently used in GI bleeding despite robust negative evidence. The guidance reinforces evidence-based deimplementation of ineffective interventions and highlights the importance of avoiding therapies associated with potential thrombotic harm in already vulnerable bleeding populations.
Introduction Eosinophilic oesophagitis is an increasingly recognized type 2 inflammatory disorder characterized by oesophageal eosinophilia, dysphagia and food-related symptoms. Although EoE occurs across all age groups, differences in immunologic drivers and clinical phenotype between paediatric-onset and adult-onset disease remain incompletely understood.
Problem Statement Current management strategies for EoE are largely uniform across age groups despite growing evidence suggesting biologic heterogeneity. Clarifying whether paediatric-onset and adult-onset EoE represent distinct atopic endotypes could improve diagnostic evaluation, allergen assessment and personalized therapeutic approaches.
Summary This large population-based cohort study demonstrates that paediatric-onset and adult-onset EoE possess clearly distinct atopic and clinical profiles, supporting the concept of divergent disease endotypes. Paediatric-onset EoE was strongly associated with systemic allergic disease, particularly asthma, atopic dermatitis and food allergy, alongside higher peripheral eosinophil counts. These findings support a predominantly food antigen–driven inflammatory phenotype with broader systemic type 2 immune activation in younger patients. In contrast, adult-onset EoE showed stronger associations with allergic rhinitis and nasal polyposis, suggesting greater involvement of aeroallergen sensitization and upper airway allergic inflammation. The persistence of these findings after matched analysis reinforces that these differences are unlikely to be explained solely by demographic variation. The study highlights that EoE may evolve through distinct immunologic pathways depending on age at onset, potentially explaining differences in symptom presentation, trigger profiles and treatment responsiveness observed in clinical practice. Recognition of these divergent endotypes may have important implications for allergy testing, dietary therapy selection and biologic treatment strategies. The findings also support closer integration between gastroenterology, allergy and airway disease management, particularly in patients with overlapping atopic disorders. Overall, the study advances understanding of EoE heterogeneity and strengthens the rationale for precision medicine approaches tailored to age-specific inflammatory mechanisms.
Introduction Eosinophilic oesophagitis (EoE) is a chronic Th2-mediated inflammatory disease characterized by epithelial barrier dysfunction, basal cell hyperplasia and persistent mucosal remodeling. Even after inflammatory control, epithelial transcriptomic and histologic abnormalities often persist, contributing to ongoing symptoms and disease relapse. Identifying molecular regulators of epithelial dysfunction remains a major therapeutic priority.
Problem Statement Current EoE therapies primarily target inflammation but incompletely restore epithelial homeostasis. The mechanisms linking IL-13-driven inflammation to impaired epithelial differentiation and excessive proliferation are incompletely understood, limiting development of therapies that promote durable mucosal healing.
Summary This translational study identifies forkhead box M1 (FOXM1) as a central transcriptional regulator of epithelial remodeling in EoE. FOXM1 expression was markedly increased in active EoE and localized predominantly to the basal epithelial layer. IL-13 stimulation upregulated FOXM1 in oesophageal epithelial cells, organoids and murine EoE models, linking Th2 inflammation directly to epithelial proliferative signaling. Functional inhibition of FOXM1 using the small-molecule inhibitor RCM-1 or siRNA restored epithelial differentiation markers including involucrin and filaggrin, reduced basal cell hyperplasia, suppressed proliferation and improved epithelial barrier integrity. In murine EoE models, FOXM1 inhibition reduced eosinophilic inflammation and reversed histologic remodeling. Mechanistically, FOXM1 directly regulated the cell-cycle gene cyclin B1 (CCNB1), driving epithelial proliferation through altered G2/M transition. The study further demonstrated that IL-13 activates a non-canonical PI3K/AKT–FOXM1 signaling axis, while FOXM1 inhibition reduced STAT6 phosphorylation and suppressed eotaxin-3 (CCL26) expression, indicating simultaneous modulation of epithelial and inflammatory pathways. Importantly, FOXM1 overexpression independently induced epithelial hyperplasia and proliferation even without IL-13 stimulation, reinforcing its pathogenic role. These findings position FOXM1 as a novel therapeutic target capable of simultaneously restoring epithelial differentiation, improving barrier function and attenuating allergic inflammation in EoE. The work also highlights a paradigm shift toward epithelial-directed therapeutic strategies in EoE beyond eosinophil suppression alone.
Introduction Exclusive enteral nutrition (EEN) is a well-established induction therapy in pediatric Crohn’s disease, where it offers anti-inflammatory efficacy while avoiding corticosteroid-related toxicity. In adults, however, EEN has been less widely adopted because of concerns regarding adherence, palatability and uncertain comparative effectiveness relative to standard medical therapy.
Problem Statement The role of EEN in adult Crohn’s disease remains poorly defined due to heterogeneous study designs, variable nutritional formulations and inconsistent remission outcomes across clinical trials. Whether EEN can serve as a practical steroid-sparing strategy in adults—and in which clinical settings it may be most useful—has remained an important unresolved question in inflammatory bowel disease management.
Summary This systematic review and meta-analysis demonstrates that EEN can induce clinical remission in adults with active Crohn’s disease, although its efficacy appears inferior to corticosteroids for remission induction. Across real-world studies, approximately two-thirds of patients achieved remission with EEN, supporting its meaningful anti-inflammatory potential in selected adult populations. Importantly, the analysis found no significant difference in efficacy between elemental and non-elemental formulations, suggesting that therapeutic benefit is independent of formula composition and allowing greater flexibility in nutritional strategy. The review also highlights emerging evidence supporting combination therapy, where EEN used alongside biologics may improve remission outcomes compared with biologic therapy alone. Adverse events were generally mild, with poor palatability remaining the principal limitation affecting tolerability and adherence. These findings reinforce that while EEN is unlikely to replace corticosteroids as first-line induction therapy in most adults, it remains an important steroid-sparing and nutritionally supportive option, particularly in patients where corticosteroid avoidance is desirable or adjunctive nutritional therapy is clinically beneficial. The study supports a more individualized role for EEN within modern adult Crohn’s disease management.
The Rome V Gastroduodenal Disorders chapter introduces several important conceptual, diagnostic, and therapeutic refinements across functional dyspepsia (FD), nausea/vomiting disorders, belching disorders, inability to belch syndrome, and rumination syndrome. The most clinically important changes are the stronger emphasis on symptom-pattern phenotyping, pragmatic clinical diagnosis, and more mechanistically aligned treatment algorithms.
Rome V classifies gastroduodenal disorders into 5 major categories:
Functional dyspepsia (FD) Nausea and vomiting disorders Excessive belching disorders Inability to belch syndrome (new category) *Rumination syndrome
This structure is more clinically intuitive and improves practical differentiation of meal-related symptoms, vomiting syndromes, and behavioral esophagogastric syndromes.
A major conceptual change in Rome V is that although functional dyspepsia (FD) remains the umbrella diagnosis, the committee explicitly recommends that clinicians preferentially classify patients using the symptom phenotype:
Postprandial Distress Syndrome (PDS) Epigastric Pain Syndrome (EPS) or PDS–EPS overlap
This is one of the most important practical refinements in Rome V because it shifts emphasis away from “FD” as a broad label and toward phenotype-driven diagnosis and treatment.
Why this matters clinically
This improves:
pathophysiologic alignment, treatment selection, and clinical trial stratification. 3. Postprandial Epigastric Pain Is No Longer Automatically EPS
One of the most important Rome V refinements in dyspepsia is the clarification that:
Postprandial epigastric pain in the presence of PDS symptoms should be classified as PDS, not EPS.
This resolves one of the major ambiguities in Rome IV, where meal-related epigastric pain often created diagnostic overlap and therapeutic confusion.
Clinical significance
This is a major advance because patients with:
postprandial fullness, early satiety, and meal-triggered epigastric pain
are now recognized as belonging to the PDS spectrum, which better aligns with impaired accommodation / delayed gastric emptying physiology and favors prokinetic-directed management.
Rome V now explicitly defines postprandial symptoms as those that:
begin or worsen within 2 hours of meal intake
This is a major methodological improvement because it gives a more physiologically meaningful and reproducible definition of meal-related symptom generation.
Symptoms occurring later than 2 hours are considered less likely to reflect classical postprandial dyspeptic physiology and may represent other mechanisms.
Rome V refines symptom thresholds to better reflect real-world disease burden:
PDS
Requires ≥2 days/week of:
bothersome postprandial fullness and/or bothersome early satiation. EPS
Requires ≥1 day/week of:
bothersome epigastric pain and/or bothersome epigastric burning.
These thresholds are more clinically usable and better aligned with symptom burden than prior stricter formulations.
Rome V newly acknowledges that EPS without PDS is not uniform and introduces a provisional subclassification:
Postprandial EPS = pain/burning starts or worsens after meals in ≥50% of episodes Meal-unrelated EPS = pain/burning starts or worsens after meals in <50% of episodes
This is an important conceptual advance because it recognizes probable biological heterogeneity within EPS and sets up future mechanistic stratification.
One of the most clinically relevant Rome V shifts is its more pragmatic diagnostic approach:
In routine clinical practice, patients with typical dyspeptic symptoms and no alarm features can be managed without mandatory upper endoscopy.
Instead, Rome V recommends:
clinical assessment, medication review, H. pylori testing, selective investigations, and endoscopy only when alarm/risk features are present.
For research, however, normal upper endoscopy remains mandatory.
This is a major clinical modernization of Rome criteria.
Rome V makes one recommendation especially explicit:
H. pylori status should be determined in every patient with dyspeptic symptoms.
This is one of the strongest operational recommendations in the chapter.
Further:
if eradication leads to sustained symptom remission, the condition should be classified as H. pylori–associated dyspepsia, not FD.
This is a clinically important distinction and avoids overdiagnosing DGBI in biologically attributable disease.
One of the most important scientific advances in Rome V is the much stronger mechanistic emphasis on duodenal pathobiology in FD.
Rome V moves beyond older motility-centric models and reframes FD as a disorder involving:
impaired gastric accommodation, delayed gastric emptying, visceral hypersensitivity, duodenal barrier dysfunction, mucosal eosinophilia / mast cell activation, neuroimmune signaling, microbiome alteration, bile acid signaling, food-triggered immune activation, and altered central processing.
The pathophysiology diagram on page 4 (Figure 1) is especially important because it visually presents FD as a multifactorial gut–brain disorder centered on duodenal barrier dysfunction, immune activation, neuroimmune dysregulation, and altered brain–gut signaling, rather than simply a gastric motor disorder.
This is one of the biggest conceptual scientific upgrades in Rome V gastroduodenal disease.
A major practical strength of Rome V is the introduction of structured treatment algorithms:
Figure 3 (page 7): PDS treatment algorithm Figure 4 (page 8): EPS treatment algorithm
These are among the most clinically useful additions in the chapter.
PDS algorithm
Progresses through:
diet/lifestyle PPI / first-line prokinetic / herbal therapy endoscopy if needed neuromodulator / brain–gut behavioral therapy gastric emptying testing in refractory disease second-line prokinetics if delayed emptying present EPS algorithm
Progresses through:
diet/lifestyle PPI / herbal therapy endoscopy if needed neuromodulator (especially TCA) / brain–gut behavioral therapy nutritional support / alternate diagnoses in refractory disease
This is one of the most practice-changing parts of Rome V.
Rome V makes treatment more phenotype-specific:
PDS → prokinetics, accommodation-targeted therapy, gastric emptying stratification EPS → acid suppression + neuromodulation (especially TCA)
This is one of the most clinically meaningful therapeutic refinements in Rome V.
Examples:
Acotiamide is emphasized for PDS 5-HT1A agonists (e.g., tandospirone/buspirone) for early satiety Mirtazapine for weight loss / early satiety TCA especially for EPS and pain-predominant phenotypes 12. Inability to Belch Syndrome Is a New Rome V Diagnosis
One of the most notable additions in Rome V is the formal inclusion of Inability to Belch Syndrome (retrograde cricopharyngeal dysfunction) as a new diagnostic entity.
This is a major addition because Rome formally recognizes a previously underdiagnosed but clinically distinctive syndrome characterized by:
inability to belch, chest/neck gurgling, bloating, flatulence, chest/epigastric discomfort.
This is one of the most clinically novel additions in the chapter.
Rome V substantially strengthens CHS criteria by requiring:
prolonged cannabis exposure (≥1 year), excessive use (≥4 days/week or ≥15 doses/week), and symptom resolution after sustained abstinence (≥6 months or 3 typical cycles).
This is a major improvement over Rome IV and greatly improves diagnostic specificity.
Clinical Bottom Line
The Rome V Gastroduodenal Disorders chapter is one of the most clinically actionable Rome V updates. Its major advances are:
phenotype-first FD classification (PDS/EPS over generic FD), reclassification of meal-related epigastric pain, explicit 2-hour postprandial definition, pragmatic non-endoscopic clinical diagnosis, mandatory H. pylori testing, stronger duodenal–neuroimmune FD model, structured phenotype-based treatment algorithms, formal recognition of inability to belch syndrome, and stricter CHS criteria.
The single most important Rome V advance in gastroduodenal disease is this: symptom-pattern phenotyping now drives both diagnosis and treatment more explicitly than ever before.
Rome V substantially expands pediatric upper gastrointestinal disorders of gut–brain interaction (DGBI), moving beyond the narrower Rome IV framework to include pediatric esophageal pain disorders, esophageal air-transit disorders, functional pediatric feeding disorders (FPFD), rumination syndrome, cyclic vomiting syndrome (CVS), chronic nausea syndrome (CNS), and functional dyspepsia (FD). The most important conceptual advance is that Rome V aligns pediatric DGBI with contemporary physiology—especially pH-impedance testing, high-resolution impedance manometry (HRIM), and structured multidisciplinary phenotyping—making diagnosis more mechanistically grounded and therapeutically actionable.
The overarching clinical shift is similar to adult Rome V: pediatric upper GI DGBI are no longer framed as vague symptom syndromes diagnosed only after exclusion, but as positive, physiology-supported disorders of gut–brain interaction. This is especially important in pediatrics, where symptom reporting is developmentally constrained and behavioral, sensory, autonomic, and feeding-related phenotypes often overlap. Rome V therefore formalizes a much more multidisciplinary model involving gastroenterology, psychology, nutrition, speech/swallow therapy, and behavioral medicine.
One of the most practice-changing updates in Rome V is the formal separation of pediatric esophageal symptoms previously grouped under presumed GERD into three distinct physiologic phenotypes:
Reflux hypersensitivity (RH) Reflux-negative esophageal pain disorder (RNEPD) (pediatric analog of adult functional heartburn) Disorders of esophageal air-transit (aerophagia syndrome and supragastric belching)
This is a major clinical advance because many children previously labeled as refractory GERD are now more accurately classified into esophageal DGBI phenotypes using endoscopy plus pH-impedance testing, allowing more rational treatment and avoiding unnecessary prolonged acid suppression.
Reflux Hypersensitivity (RH)
Rome V defines pediatric RH as reflux-related pain symptoms with:
normal endoscopy, no eosinophilic esophagitis (EoE), normal acid exposure, but positive symptom association with acid or nonacid reflux on pH-impedance testing.
This is one of the most important pediatric esophageal additions because it formally acknowledges that symptoms may be reflux-triggered despite normal acid burden, shifting the focus from acid quantity to sensory hypersensitivity and reflux perception.
Clinical implications:
PPI response is not diagnostically reliable for RH. Empiric PPI trials may still be used, but should be time-limited (≤8 weeks). Failure to improve should prompt endoscopy + pH-impedance, not indefinite acid escalation. Treatment emphasis shifts toward neuromodulation and CBT, rather than acid suppression alone.
This is a major practical change in pediatrics, where prolonged empiric PPI use has historically been common.
Reflux-Negative Esophageal Pain Disorder (RNEPD)
RNEPD is the pediatric equivalent of adult functional heartburn and refers to reflux-like pain symptoms with:
normal endoscopy, no EoE, normal acid exposure, and no temporal symptom–reflux correlation on pH-impedance testing.
This is highly clinically relevant because it identifies children with esophageal pain not driven by reflux at all, despite symptom similarity to GERD.
The most important therapeutic implication is explicit:
Antireflux surgery is not indicated in RNEPD. Repeated escalation of acid suppression is generally inappropriate. Management should prioritize neuromodulators + CBT, not procedural reflux therapy.
This is one of the most practice-protective statements in Rome V pediatric esophageal care.
Rome V newly formalizes disorders of esophageal air-transit, enabled by advances in impedance and HRIM, which can distinguish directionality of air movement. This is an important pediatric innovation because belching and bloating syndromes have historically been poorly classified and often misdiagnosed as reflux or dyspepsia.
The new subtypes are:
Aerophagia syndrome Supragastric belching (SGB) syndrome Aerophagia Syndrome
Rome V redefines aerophagia as a syndrome only when excessive air swallowing causes clinically significant symptoms such as:
progressive daytime abdominal distention, excessive belching, flatulence, bloating, and quality-of-life impairment.
This is important because Rome V avoids overdiagnosing normal air swallowing as pathology. Testing is often unnecessary unless uncertainty exists; diagnosis is primarily clinical, with abdominal x-ray or impedance used selectively. Treatment is conservative and behavioral (speech therapy/CBT), with decompression reserved for severe cases.
Supragastric Belching (SGB)
SGB is now recognized as a distinct behavioral disorder characterized by repetitive esophageal air intake followed by immediate expulsion. This is a major conceptual advance because many children with repetitive “hiccups,” “belching,” or presumed reflux actually have behavioral air-transit disorders, not acid disease.
Rome V emphasizes:
SGB is usually diagnosable clinically, often does not occur during sleep, and is best treated behaviorally (breathing retraining, speech therapy, CBT), not pharmacologically. 3. Functional Pediatric Feeding Disorders (FPFD): One of the Most Important Rome V Additions
The most novel and clinically transformative pediatric addition in Rome V is the formal introduction of Functional Pediatric Feeding Disorders (FPFD). This is arguably the most important pediatric innovation in the entire Rome V upper GI framework.
Rome V introduces FPFD as a structured, physiology- and behavior-based alternative to the overly broad DSM-5 construct of ARFID, which the committee explicitly argues lacks sufficient granularity for GI practice. Rome V recommends replacing ARFID-like heterogeneity with more precise feeding phenotypes.
This is a major conceptual and practical advance because pediatric feeding problems are common, clinically heterogeneous, and often misclassified.
Rome V introduces four functional feeding phenotypes:
Hypersensitive dysphagia (HD) Anticipatory restrictive feeding (ARF) Hunger dysregulation feeding disorder Medically triggered functional feeding disorder Hypersensitive Dysphagia (HD)
HD is the pediatric analogue of adult functional dysphagia, but adapted for developmental limitations. Children perceive liquids/solids as passing abnormally despite:
normal mucosa, normal structure, no major motor disorder, and normal bolus transit.
This is a clinically valuable distinction because it separates sensory dysphagia from structural and motor disease while accounting for the fact that children often cannot localize symptoms well.
Anticipatory Restrictive Feeding (ARF)
ARF describes children who restrict intake because they anticipate aversive eating-related symptoms such as:
pain, nausea, gagging, choking, bloating, vomiting.
This is one of the most clinically useful new Rome V diagnoses because it identifies fear-based restrictive eating driven by symptom anticipation rather than structural dysfunction.
Hunger Dysregulation Feeding Disorder
Rome V introduces a novel hunger-axis disorder with:
reduced hunger drive, or excessive hunger drive.
This is a uniquely pediatric and clinically important construct, especially for children with severe dysregulated intake patterns not explained by anatomy or classic eating disorders.
Medically Triggered Functional Feeding Disorder
This category recognizes children whose feeding dysfunction began during a medical illness (e.g., GERD, EoE) but persists after the medical condition has resolved, due to retained maladaptive feeding behaviors or sensory conditioning.
This is an especially important practical diagnosis in pediatric GI because it explains why children may remain functionally dysphagic or feeding-avoidant despite complete mucosal healing.
Why FPFD Matters Clinically
This entire section is one of the most practice-changing contributions of Rome V. It provides a far more clinically useful framework for children previously grouped vaguely under ARFID or “feeding difficulty,” and it strongly emphasizes:
structured multidisciplinary assessment, routine screening for EoE and nutritional deficiencies, behavioral and sensory phenotyping, and targeted psychogastroenterology-based treatment. 4. Rumination Syndrome: Stronger Behavioral Framing
Rome V reframes pediatric rumination syndrome as a behavioral gut–brain disorder, not a reflux disorder. This is highly important clinically because rumination remains commonly mistaken for refractory GERD, gastroparesis, or vomiting disorders.
Rome V reinforces that:
diagnosis is usually clinical, HRIM can confirm in atypical cases, and diaphragmatic breathing is first-line therapy.
This stronger behavioral framing should substantially reduce unnecessary testing and procedural escalation.
Rome V updates pediatric CVS and formally incorporates cannabinoid hyperemesis syndrome (CHS) as a pediatric-relevant subgroup, reflecting increasing adolescent cannabis exposure.
This is clinically important because Rome V now explicitly requires:
chronic cannabis exposure, stereotypical CVS-like vomiting, and symptom resolution with sustained cannabis cessation to diagnose CHS.
This improves diagnostic precision and helps avoid mislabeling adolescents with occasional cannabis exposure as CHS.
Rome V renames and formalizes chronic nausea syndrome, recognizing chronic nausea as a legitimate pediatric DGBI often linked to:
autonomic dysfunction, POTS, anxiety, and functional comorbidity.
This is an important conceptual advance because chronic nausea has historically been under-recognized and often dismissed as nonspecific.
Rome V updates pediatric FD to align more closely with adult criteria, particularly by:
formalizing PDS and EPS subtypes, increasing required symptom frequency for PDS, and refining postprandial symptom timing.
This improves diagnostic consistency across age groups and should improve trial design and phenotype-specific management.
Clinical Bottom Line
Rome V Pediatric Upper GI DGBI is a major advance because it moves pediatric neurogastroenterology from symptom-based empiricism to structured physiologic and behavioral phenotyping. The most important practice-changing advances are:
formal physiologic separation of pediatric esophageal pain syndromes from GERD, introduction of air-transit disorders (aerophagia, SGB), creation of functional pediatric feeding disorders (FPFD) as a major new diagnostic framework, stronger behavioral reframing of rumination syndrome, formal pediatric incorporation of CHS, recognition of chronic nausea syndrome as a distinct disorder, and better harmonization of pediatric FD with adult Rome criteria.
Among these, the single most important innovation is the introduction of FPFD, while the most immediately practice-changing esophageal update is the shift from empiric “refractory GERD” labeling to pH-impedance-based esophageal phenotyping. Collectively, Rome V makes pediatric upper GI DGBI substantially more precise, multidisciplinary, and clinically actionable.
Rome V reframes functional esophageal disorders as esophageal disorders of gut–brain interaction (E-DGBI), emphasizing that these syndromes arise from altered esophageal sensory signaling and central perceptual processing rather than occult structural disease. The defining clinical principle is that patients present with heartburn, chest pain, globus, or dysphagia, but without explanatory structural pathology, major esophageal motor disorders, or pathologic reflux. Rome V’s most important conceptual advance is the formal integration of Lyon Consensus 2.0 for reflux assessment and Chicago Classification v4.0 (CCv4.0) for motility, making the diagnosis of E-DGBI more physiologically rigorous and less exclusionary by approximation.
This update substantially improves clinical precision. Rather than labeling persistent esophageal symptoms as “functional” after a normal endoscopy alone, Rome V now requires systematic exclusion of mucosal disease, GERD, eosinophilic esophagitis (EoE), and major motor disorders using contemporary physiologic testing. This is a major practical shift because it reduces both underdiagnosis of subtle esophageal disease and overdiagnosis of functional syndromes. The central pathophysiologic model is now explicit: symptom generation reflects esophageal hypersensitivity, hypervigilance, altered autonomic regulation, and maladaptive brain–gut processing, often amplified by psychosocial stressors and symptom-specific anxiety.
Functional Chest Pain: A More Rigorous Diagnosis of Exclusion
Rome V defines functional chest pain as recurrent retrosternal chest pain of presumed esophageal origin, distinct from heartburn and unexplained by GERD, mucosal disease, or major motility disorders. The major practical refinement is that this diagnosis now requires exclusion using Lyon 2.0 reflux thresholds, CCv4.0 motility criteria, and selective mucosal biopsy rather than broad empiricism. Importantly, cardiac disease must still be excluded first, because symptom pattern alone cannot reliably distinguish esophageal from cardiac pain.
A key Rome V change is that esophageal biopsies are no longer required for all patients with chest pain, unlike Rome IV. Biopsies are now recommended only when chest pain is meal-related, where occult EoE may mimic pain-predominant disease. This reduces unnecessary biopsy burden while preserving diagnostic sensitivity in clinically relevant cases. Rome V also clarifies that ineffective esophageal motility (IEM) is not exclusionary, while conclusive EGJOO, achalasia, DES, and hypercontractile esophagus remain exclusionary.
Mechanistically, Rome V strongly anchors functional chest pain in esophageal hypersensitivity and altered central pain processing. Up to 75% of patients demonstrate heightened sensitivity to esophageal distension, and psychiatric comorbidity—particularly anxiety, depression, and somatization—is highly prevalent and clinically relevant. Treatment therefore shifts away from acid suppression and toward neuromodulation and behavioral therapy. TCAs, SNRIs, trazodone, and selected SSRIs remain the pharmacologic backbone, while GI-CBT, gut-directed hypnotherapy, and biofeedback are now explicitly recognized as evidence-based therapeutic options rather than adjunctive alternatives.
Functional Heartburn: More Stringent Separation From GERD
Rome V retains functional heartburn as a distinct diagnosis but makes its boundaries with GERD more rigorous. Functional heartburn is now defined as retrosternal burning that persists despite optimized antisecretory therapy, with no evidence of GERD, EoE, EGJ dysfunction, or major motility disorder. The most important clinical advance is a sharper physiologic distinction between functional heartburn and GERD using Lyon 2.0 criteria, especially prolonged reflux monitoring and adjunctive impedance metrics.
Rome V reinforces that a normal endoscopy is insufficient to exclude GERD. Diagnosis now requires objective reflux exclusion, ideally with 96-hour wireless pH monitoring off therapy. Functional heartburn is favored when acid exposure remains physiologic and symptom association is negative. Mean nocturnal baseline impedance (MNBI) is now clinically useful: MNBI >2500 Ω supports functional heartburn, whereas low impedance favors GERD. This is a major practical step toward physiologic phenotyping of refractory heartburn.
Therapeutically, Rome V strongly discourages repeated invasive testing and explicitly states that antireflux surgery should be avoided in functional heartburn. This is one of the most practice-changing statements in the document. Management should instead focus on reassurance, reduction of hypervigilance, and neuromodulation. GI-CBT, diaphragmatic breathing, hypnotherapy, and low-dose neuromodulators are emphasized as mechanistically aligned and clinically safer than procedural escalation.
Reflux Hypersensitivity: Preserved but Better Defined
Rome V preserves reflux hypersensitivity but refines its boundaries. This disorder now requires heartburn and/or chest pain with physiologic acid exposure but positive reflux–symptom association, distinguishing it from both GERD and functional heartburn. The critical clinical distinction is that symptoms remain temporally linked to reflux events despite physiologic reflux burden.
Rome V now explicitly excludes regurgitation and belching as qualifying symptoms in isolation, which is clinically important because these symptoms often reflect mechanical or behavioral disorders such as rumination or supragastric belching rather than reflux hypersensitivity. This reduces diagnostic contamination and improves phenotypic precision.
Management remains similar to functional heartburn, but Rome V acknowledges that some patients—particularly those with acid-sensitive esophagus or hiatal hernia—may respond to acid suppression or, selectively, antireflux surgery. However, the dominant therapeutic model remains neuromodulation plus psychogastroenterology rather than acid suppression alone.
Globus: Less Procedural, More Conservative
Rome V retains globus largely unchanged but makes one clinically important correction: the role of gastric inlet patch is substantially de-emphasized. Rome IV was more permissive toward inlet patch ablation; Rome V is more conservative and states that while inlet patch may be relevant in selected patients, evidence supporting ablation remains low quality and should not drive routine intervention.
This change matters clinically because globus is common, benign, and often chronic, yet historically over-investigated and overtreated. Rome V favors a structured but conservative approach: exclude local structural disease and laryngeal pathology, consider a short PPI trial, then proceed toward reassurance and behavioral management if unrevealing. Once GERD and structural disease are excluded, CBT-based psychoeducation, speech therapy, pharyngolaryngeal relaxation, and hypnosis are favored over repeated endoscopy, ablation, or procedural escalation.
Functional Dysphagia: The Most Important Diagnostic Upgrade
Functional dysphagia undergoes the most meaningful diagnostic modernization in Rome V. While Rome IV relied largely on normal endoscopy and HRM, Rome V now recognizes that subtle EGJ dysfunction and impaired distensibility may be missed by conventional testing. Accordingly, functional lumen imaging probe (FLIP) and supportive timed barium esophagram are now explicitly incorporated into the diagnostic framework. This is arguably the most important technical advance in Rome V functional esophageal disorders.
This change has major practical implications. Rome V acknowledges that many patients previously labeled with functional dysphagia under Rome IV likely had subtle EGJ outflow resistance, impaired distensibility, or borderline achalasia physiology that standard manometry failed to detect. FLIP can identify these hidden physiologic abnormalities and therefore reduce false-positive diagnosis of functional dysphagia. As a result, true functional dysphagia becomes a more specific—and likely less common—diagnosis.
Rome V also clarifies that esophageal biopsies are essential in dysphagia, even when mucosa appears normal, because EoE and other inflammatory disorders may be histologically occult. It further reinforces that IEM does not exclude functional dysphagia, whereas achalasia, conclusive EGJOO, DES, and hypercontractile esophagus do. This improves diagnostic discipline and reduces overcalling minor motility findings as causative.
Management remains conservative and phenotype-directed. Reassurance, swallowing modification, and selective neuromodulation remain foundational. However, Rome V also recognizes that selected patients with unexplained solid-food dysphagia may benefit from empiric bougie dilation, especially where subtle proximal mechanical dysfunction is suspected despite negative routine testing. With FLIP integration, this can now be better targeted and more physiologically justified.
Clinical Bottom Line
Rome V significantly modernizes functional esophageal disorders by replacing broad symptom-based exclusion with physiology-driven phenotyping. The most important practical changes are:
formal integration of Lyon 2.0 and Chicago Classification v4.0, selective rather than routine biopsy in functional chest pain, stronger physiologic separation of functional heartburn vs reflux hypersensitivity vs GERD, de-escalation of procedural management in globus, and incorporation of FLIP as a major diagnostic advance in functional dysphagia.
Collectively, these changes move practice away from empiricism, repeated acid suppression, and procedural overuse, and toward mechanism-based diagnosis, neuromodulation, psychogastroenterology, and precision esophageal physiology. For clinical practice, Rome V is less about renaming functional esophageal disorders and more about redefining them with substantially greater physiologic rigor.
Introduction Achalasia is a chronic oesophagal motility disorder characterised by impaired lower oesophagal sphincter relaxation and food stasis. Long-standing stasis, bacterial overgrowth, and chronic inflammation have raised concerns about an increased risk of oesophagal cancer, particularly squamous cell carcinoma. However, previous studies were small and lacked adjustment for key confounders such as smoking and alcohol. The association with adenocarcinoma has remained even more uncertain. Problem Statement Clinicians often struggle with two key questions: 👉 Does achalasia independently increase the risk of oesophagal cancer? 👉 Should these patients undergo structured cancer surveillance? Existing data have been limited by small sample sizes and inadequate adjustment for major risk factors. In particular, whether achalasia contributes to adenocarcinoma risk beyond associated gastroesophageal reflux remains unclear. Summary This large multinational population-based study from Nordic countries provides robust evidence addressing these gaps. Achalasia was found to be strongly associated with oesophagal squamous cell carcinoma, with nearly a 9-fold increased risk, even after adjusting for smoking and alcohol. This confirms that achalasia itself is an independent risk factor for squamous malignancy. In contrast, achalasia showed only a modest association with oesophagal adenocarcinoma, which became non-significant after adjusting for GERD. This suggests that the observed risk of adenocarcinoma is largely driven by reflux rather than achalasia per se. Interestingly, patients who had undergone treatment such as myotomy or dilation had an even higher risk of squamous cell carcinoma, likely reflecting longer disease duration and persistent mucosal exposure to stasis-related injury. Overall, the study clearly differentiates cancer risk patterns in achalasia: high and independent risk for squamous cell carcinoma Limited and GERD-mediated risk for adenocarcinoma These findings reinforce the need for heightened awareness of squamous cancer risk in long-standing achalasia while suggesting a more nuanced approach toward adenocarcinoma surveillance.
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