Role of clinical presentation in diagnosing reflux-related non-cardiac chest pain

INTRODUCTION: Non-cardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health-care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP. Thus the typical symptoms of reflux, such as heartburn and regurgitation, when present as predominant symptoms are quite specific for diagnosing GERD but in patients with NCCP the clinical diagnosis of reflux is difficult, and invasive methods or the omeprazole test are required for its detection. The aim of the present study was to evaluate the role of clinical presentation when diagnosing GERD among patients with NCCP. METHODS: Patients with NCCP underwent upper endoscopy, Bernstein and omeprazole tests. The patients were divided into two groups based on GER- or non-GER-related chest pain, and clinical presentation was compared between these two groups. Gastroesophageal reflux disease was considered positive when at least two methods were positive. RESULTS: From 78 NCCP patients (41 male; mean age 50.4 +/- 2.3 years), the chest pain was related to GERD in 35 patients (44.8%). The two groups were the same based on sex and age. The chest pain severity, site, radiation and relation to food, exercise, and sleep were equal in the two groups, except for two symptoms: pain that was relieved by antacid (P < 0.031) and presence of classical reflux symptoms (P < 0.009), seen in the GERD patients. With regard to recent patient history, heartburn and regurgitation symptoms were seen more frequently in GERD patients (P < 0.036 and P < 0.002, respectively). DISCUSSION: Clinical presentation is important in diagnosing GERD in NCCP. Although the chest pain is the same in reflux- and non-reflux-related NCCP, the symptoms of heartburn or regurgitation in the present or recent patient history are diagnostic for GERD-related chest pain.     

Non-cardiac chest pain: Prevalence of reflux disease and response to acid suppression in an Asian population

Background:  Gastroesophageal reflux disease is thought to be the commonest cause of 'non-cardiac chest pain'. The use of proton-pump inhibitors resulting in improvement in the chest pain symptom would support this causal association.
Objectives:  To determine the prevalence of gastroesophageal reflux disease in non-cardiac chest pain and the response of chest pain to proton-pump inhibitor therapy.
Methods:  Patients with recurrent angina-like chest pain and normal coronary angiogram were recruited. The frequency and severity of chest pain were recorded. All patients underwent esophagogastroduodenoscopy and 48-h Bravo ambulatory pH monitoring before receiving rabeprazole 20 mg bd for 2 weeks.
Results:  The prevalence of gastroesophageal reflux disease was 66.7% (18/27). The improvement in chest pain score was significantly higher in reflux compared to non-reflux patients ( P  = 0.006). The proportion of patients with complete or marked/moderate improvement in chest pain symptoms were significantly higher in patients with reflux (15/18, 83.3%) compared to those without (1/9, 11.1%) ( P  < 0.001).
Conclusion:  The prevalence of gastroesophageal reflux disease in patients with 'non-cardiac chest pain' was high. The response to treatment with proton-pump inhibitors in patients with reflux disease, but not in those without, underlined the critical role of acid reflux in a subset of patients with 'non-cardiac chest pain'.     

Imaging of non-cardiac, non-traumatic causes of acute chest pain

Non-traumatic chest pain is a common symptom in patients who present in the emergency department. From a clinical point of view, it is important to differentiate cardiac chest pain from non-cardiac chest pain (NCCP). Among the plethora of potential causes of NCCP, life-threatening diseases, such as aortic dissection, pulmonary embolism, tension pneumothorax, and esophageal rupture, must be differentiated from non-life threatening causes. The majority of NCCP, however, is reported to be benign in nature. The presentation of pain plays an important role in narrowing the differential diagnosis and initiating further diagnostic management and treatment. As the benign causes tend to recur, and may lead to patient anxiety and great costs, a meticulous evaluation of the patient is necessary to diagnose the underlying disorder or disease.     

Noncardiac chest pain: diagnostic evaluation

Noncardiac chest pain (NCCP) is a common and challenging clinical problem. It is estimated that more than 70 million Americans (23% of the population) suffer from this condition yearly. Patients with NCCP represent a diagnostic dilemma. Their chest pain is often indistinguishable from cardiac pain leading to extensive and expensive evaluations. Once coronary artery disease and other cardiac and pulmonary sources of chest pain are excluded, patients are frequently referred to gastroenterologists to look primarily for esophageal sources of pain. A variety of diagnostic tests are available to the practicing clinician to identify the origin of pain, including ambulatory pH testing, esophageal motility, upper endoscopy, provocative testing and even therapeutic trials.     

Histopathologic correlates of noncalcific chronic pancreatitis by EUS: a prospective tissue characterization study

BACKGROUND: Studies that correlated EUS features of chronic pancreatitis (CP) with histopathology are retrospective and only include patients with severe disease or calcific pancreatitis. Controversies regarding the significance of EUS features of noncalcific CP (NCCP) remain unresolved. OBJECTIVE: To correlate EUS criteria for NCCP with histology from surgical specimens. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: All patients who underwent EUS for pancreaticobiliary indications and subsequent pancreatic surgery. Patients with calcific pancreatitis were excluded. METHODS: Individual CP features on EUS were carefully documented with relation to different parts of the pancreas. Standard EUS criteria for CP were adopted. All patients underwent surgery within 2 months of EUS. A single pathologist blinded to EUS findings reviewed the specimens and graded fibrosis (total score, 12; >or=6=unequivocal CP). A quantitative receiver operating characteristic (ROC) curve analysis was performed, and Spearman rank correlation coefficients were calculated. MAIN OUTCOME MEASUREMENTS: Correlate EUS criteria for NCCP, with histology from surgical specimens. RESULTS: Of the 42 patients evaluated, NCCP was diagnosed histologically in 21 patients (50%). None of the patients had CP diagnosis by CT. ROC curve analysis revealed that 4 or more EUS criteria provided the best sensitivity (90.5%), specificity (85.7%), and accuracy (88.1%) for diagnosing NCCP. Parenchymal EUS features that were significantly associated with histopathologic NCCP were foci (P<.0001), stranding (P<.001), and lobulations (P=.04); ductal features that were significantly associated with histopathologic NCCP were dilated (P<.0001) or irregular main pancreatic duct (P<.0001), side branches (P<.001), and hyperechoic duct margins (P=.03). There was a significant correlation between the number of EUS criteria and severity of NCCP on histology (r=0.85; P<.0001). LIMITATIONS: Small number of patients. CONCLUSIONS: An excellent correlation exists between EUS and histologic findings of NCCP.     

Neurophysiologic assessment of esophageal sensory processing in noncardiac chest pain

BACKGROUND & AIMS: Esophageal hypersensitivity is thought to be important in the generation and maintenance of symptoms in noncardiac chest pain (NCCP). In this study, we explored the neurophysiologic basis of esophageal hypersensitivity in a cohort of NCCP patients. METHODS: We studied 12 healthy controls (9 women; mean age, 37.1 +/- 8.7 y) and 32 NCCP patients (23 women; mean age, 47.2 +/- 10 y). All had esophageal manometry, esophageal evoked potentials to electrical stimulation, and NCCP patients had 24-hour ambulatory pH testing. RESULTS: The NCCP patients had reduced pain thresholds (PT) (72.1 +/- 19.4 vs 54.2 +/- 23.6, P = .02) and increased P1 latencies (P1 = 105.5 +/- 11.1 vs 118.1 +/- 23.4, P = .02). Subanalysis showed that the NCCP group could be divided into 3 distinct phenotypic classifications. Group 1 had reduced pain thresholds in conjunction with normal/reduced latency P1 latencies (n = 9). Group 2 had reduced pain thresholds in conjunction with increased (>2.5 SD) P1 latencies (n = 7), and group 3 had normal pain thresholds in conjunction with either normal (n = 10) or increased (>2.5 SD, n = 3) P1 latencies. CONCLUSIONS: Normal esophageal evoked potential latencies with reduced PT, as seen in group 1 patients, is indicative of enhanced afferent transmission and therefore increased esophageal afferent pathway sensitivity. Increased esophageal evoked potential latencies with reduced PT in group 2 patients implies normal afferent transmission to the cortex but heightened secondary cortical processing of this information, most likely owing to psychologic factors such as hypervigilance. This study shows that NCCP patients with esophageal hypersensitivity may be subclassified into distinct phenotypic subclasses based on sensory responsiveness and objective neurophysiologic profiles.     

Extraesophageal and atypical manifestations of GERD

Abstract   Extraesophageal manifestations of gastroesophageal reflux disease (GERD) are essentially complications of GERD that primarily involve organs that are in proximity to the esophagus. Non-cardiac chest pain (NCCP) is an atypical manifestation of GERD, because symptoms originate in essence from the esophagus. In both atypical and extraesophageal manifestation of GERD frequent heartburn is uncommon and lack of GERD symptoms is not unusual. Esophageal mucosal injury is rarely present making upper endoscopy a low-yield procedure in both conditions. While association with GERD has been commonly reported, the extent of causality remains unknown. In NCCP, the usefulness of the proton pump inhibitor (PPI) test in diagnosing GERD-related NCCP has been established. Similar value in extraesophageal manifestations of GERD has been proposed, but rarely studied. While treatment of extraesophageal manifestations of GERD remains a challenge, PPIs in at least double the standard dose, should be considered for the initial therapy. Properly designed therapeutic studies are still lacking as well as the exact role of antireflux surgery in this patient population.     

Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP)

In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS-HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS-HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24-51 years; mean 32 +/- 8 years), and eight NCCP patients (three female, five male; age range 26-58, mean 40.5 +/- 10 years) were studied. Electrical oesophageal stimulation (EOS; 200 microseconds, 0.2 Hz, 25 stimuli) was applied to the oesophageal wall 5 cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS-HRV, before, during, and after oesophageal stimulation. Measured PS-HRV indices included high frequency (HF; 0. 15-0.5 Hz) and low frequency (LF; 0.06-0.15 Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3. 6 +/- 1 vs. 7.8 +/- 2 mA, P < 0.05). EP amplitude was greater (13 +/- 2 vs. 6 +/- 1 microV, P < 0.0001), and latency longer in controls vs. NCCP (191 +/- 7 ms vs. 219 +/- 6 ms, P < 0.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS-HRV) and increased cardiovagal activity (high frequency peak, P < 0.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beats min-1 (P < 0.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.     

大脑感知在GERD相关NCCP发病中作用的初步研究

目的：初步探讨胃食管反流病（GERD）相关非心源性胸痛（NCCP）患者大脑功能区激活的特点，了解内脏高敏感在其发病中的作用。方法：4名正常对照及8名诊断为GRED相关NCCP患者，行食管内酸灌注，灌注前、中、后行功能性磁共振扫描，寻找与食管内刺激相关的脑功能区。结果：（1）静息状态下，正常对照组及GERD相关NCCP组中均观察到部分脑区活跃。（2）在食管内酸刺激时，正常对照组及GERD相关NCCP组患者较静息态时均存在PFC、ACC、IC及丘脑区的明显激活。（3）对两组激活的各脑区进行分析，采用中位数（范围）法，结果发现GERD相关NCCP组丘脑区激活较明显，但两组受试者在上述四个区域激活上无显著统计学差异（P〉0．05）。（4）在GERD相关NCCP亚组中，NERD＋组PFC区BA10激活较明显，NERD-SI-组IC激活较明显。结论：PFC、ACC、IC及丘脑可能是调节GERD相关NCCP患者食管内脏感知的重要脑功能区；GERD相关NCCP患者各亚组可能通过不同的高级皮层调节内脏感觉。