Gastroparesis versus dyspepsia by intragastric meal distribution: new diagnostics and definitions ahead

Abstract

Gastroparesis often presents a challenge to the practicing gastroenterologist. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also significant disruption of social activities that often center around food. The treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic and idiosyncratic nature of the illness, often with some common psychiatric co-morbidity, parallels other functional disorders of the gastrointestinal tract. These parallels have provided the rationale for studies investigating alternative diagnostic features of the gastric emptying test as employed in the clinical setting. Hence, not only the regular cut-offs of 60% or 10% gastric retention of a meal at 2 and 4?h, but also a new concept, the intragastric meal distribution at time 0 (IMD⁰) is now introduced as a plausible diagnostic feature that should be more aligned with the patients’ symptoms as they appear in close connection with the meal. Impaired gastric accommodation with absence of fundic relaxation followed by dumping of the meal into antrum is suggested to be diagnostic for functional dyspepsia and gastroparesis. The diagnostic cut-off is considered when more than 57% of the meal is distributed to the distal part of the stomach immediately on food intake. This new diagnostic feature of the gastric emptying profile lend support to better understanding of the patients’ symptoms and provides a new basis for pharmacological treatment options in gastroparesis that may provide an improved quality of life in affected individuals.     

Relationships Between Intragastric Food Maldistribution, Disturbances of Antral Contractility, and Symptoms in Functional Dyspepsia

We investigated the relationships between intragastric food maldistribution and antral dysmotility in functional dyspepsia, and whether these abnormalities relate to meal-induced symptoms. Intragastric distribution of food throughout gastric emptying was determined in patients (n = 24) and controls (n = 38) after a liquid nutrient meal labeled with ^99mtechnetium phytate. Antral contractility was also periodically assessed by dynamic scintigraphy and postprandial symptoms were monitored with visual analog scales. Residence of food in the proximal stomach was decreased in 8 (33%) and antral contractility was increased in 9 (37.5%) and decreased in 2 (8%) patients. Proximal and distal stomach motor abnormalities were neither significantly correlated nor associated. Increased antral contractility was significantly correlated (Rs = 0.54; P < .01) with postprandial nausea. We conclude that diminished residence of food in the proximal stomach and disturbed antral contractility occur independently in different subsets of functional dyspepsia patients. Increased antral contractility seems to play a role in postprandial nausea in functional dyspepsia.     

Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping syndrome

Rapid gastric emptying and exaggerated plasma concentrations of the insulinotropic hormone GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients. We suspected that the plasma volume drop associated with rapid gastric emptying (early dumping) would be accompanied by elevated plasma concentrations of norepinephrine. In order to study any relationship between postprandial norepinephrine, the enteroinsular axis, and plasma glucose, twelve patients with dumping syndrome and nine controls were studied. The plasma concentrations of norepinephrine, GLP-1, GIP, glucagon, insulin, and glucose were measured following a 1.5 g/kg lean body mass glucose meal. The early (0–30 min) integrated norepinephrine concentration was significantly higher in dumpers (22.1 ± 3.8 nmol/ml/min) compared to controls (14.7 ± 3.1 nmol/ml/min; P < 0.001) and correlated closely with the postprandial hematocrit increment (r = 0.71; P < 0.05). Early immunoreactivities of GLP-1, GIP, and glucagon peaked 30 min after glucose ingestion and were significantly higher in dumpers. Insulin peaked after 60 min and correlated with early GLP-1. In 11 of the patients glucose fell below baseline after a median interval of 120 min. Glucose at 120 min, when most of the nadirs occurred was lowest in patients with high early GLP-1 concentrations (r = 0.78; P < 0.001). Gel filtration chromatography of the dumpers' plasma revealed that pancreatic glucagon was detectable at time 0 and after 20 min, but not after 120 min. It is concluded that in dumpers pancreatic glucagon is augmented in the early postprandial period, probably through stimulation by catecholamines. At 120 min, when most of the hypoglycemias are encountered, pancreatic glucagon is no longer detectable, probably through inhibition by GLP-1.     

The ultrasound meal accommodation test in 509 patients with functional gastrointestinal disorders

Aim: The Ultrasound Meal Accommodation Test (UMAT) is a clinical test used to assess gastric accommodation, gastric emptying, and visceral sensitivity. It has been used as a clinical tool at Haukeland University Hospital, Bergen for more than 20 years.

Material and methods: Five-hundred and nine patients were retrospectively evaluated, 71% females, and 51% were referred from other hospitals or specialists. The aim was to explore the usefulness of UMAT in patients with suspected functional GI disorders (FGID).

Results: One hundred and sixty patients were diagnosed with functional dyspepsia (FD), and 154 patients were diagnosed with irritable bowel syndrome (IBS). The overlap between IBS and FD was 41%. In 36% of FD patients, ultrasound assessment showed impaired gastric accommodation. Of 262 patients filling out all required fields for the FD diagnosis (ROMA II and III), 198 (74%) met the criteria for FD, but only 91 (34%) were later diagnosed with FD by an experienced clinician.

Conclusions: By combining ultrasonography, the symptom response to a standardized meal, and psychological assessment, the UMAT is useful in diagnosis and management of patients with FGID.     

功能性消化不良餐后不适综合征患者52例胃中液体食物分布特点

目的探讨功能性消化不良（FD）餐后不适综合征（PDS）患者液体食物胃中分布情况,了解其胃动力障碍发病机制。方法应用超声诊断仪对52例 PDS 患者和18名健康志愿者进行胃排空检查,在空腹,最大饱腹感,餐后30、60、90和120 min 分别计算近端胃与远端胃面积和容积,近端胃与远端胃面积比率和容积比率,近端胃和远端胃排空率。统计学处理采用 t 检验、卡方检验。结果空腹、餐后120 min时,PDS 组近端胃容积分别为（9．06±7．88）和（24．72±24．02）cm3,健康对照组分别为（5．96±2．13）和（19．48±12．32）cm3,差异均有统计学意义（t＝－1．637、－0．875,P 均＜0．05）。在最大饱腹感时,PDS 组近端胃与远端胃面积比率为1．63±0．42,健康对照组为2．33±0．63,差异有统计学意义（t＝5．044,P ＜0．05）。在空腹时,PDS 组近端胃与远端胃容积比率为0．60±0．38,健康对照组为0．46±0．19,而在最大饱腹感时,PDS 组为0．91±0．27,健康对照组为1．30±0．48,差异有统计意义（t＝－1．505、3．970,P 均＜0．05）。在餐后30、90 min 时,PDS 组近端胃排空率分别为（28．10±25．03）％和（68．80±16．14）％,健康对照组分别为（34．97±14．41）％和（75．86±9．86）％,差异有统计学意义（t ＝1．087、1．718,P ＜0．05）;两组远端胃排空率差异均无统计学意义（P 均＞0．05）。结论PDS 患者液体食物分布在最大饱腹感时远端胃容积大于近端胃容积,这可能是导致其近端胃排空率下降的原因,近端胃对PDS 患者胃动力影响较大。     

Postprandial plasma 5-hydroxytryptamine in diarrhoea predominant irritable bowel syndrome: a pilot study

Background—Increased concentrations of5-hydroxytryptamine (5-HT) can be detected in the systemic circulationafter a meal and may be involved in the physiological control ofgastrointestinal motility. Abnormalities of 5-HT release after a mealmight explain some of the postprandial symptoms associated with theirritable bowel syndrome (IBS).
Aim—To investigate the effect of a standard mealon plasma 5-HT and urinary 5-hydroxyindole acetic acid (5-HIAA)concentrations in patients with diarrhoea predominant IBS and inhealthy volunteers.
Methods—After an overnight fast, six volunteersand five patients with IBS were given a carbohydrate-rich meal. Bloodand urine samples were taken before and for four hours after the meal. Platelet-poor plasma 5-HT and urinary 5-HIAA were analysed by reversedphase high performance liquid chromatography with fluorometric detection. 5-HIAA was expressed as a ratio with urinary creatinine concentration, which was measured by spectrophotometry.
Results—During the four hour postprandial period,5-HT concentrations were significantly higher in patients with IBS than in healthy volunteers at 0.5 hours (p<0.05), 2 hours (p<0.05) and 2.5 hours (p<0.05). 5-HT was not detected in the plasma in the fastingstate in patients or volunteers. Median peak 5-HT in patients with IBS(359 (198-796) nmol/l) was significantly greater than volunteers (83 (7-190)) (p<0.05). "Area under the curve" for 5-HT detection wasgreater for patients with IBS (317(138-771)) than for healthyvolunteers (51 (4-129); p<0.05).The duration of the 5-HT peak wassignificantly longer in patients with IBS (3 (1-3) hours) than in thehealthy volunteers (1 (1-1) hours; p<0.01). Postprandial urinarymedian 5-HIAA values in controls (5.6 (5.5-5.8) µmol/mmolcreatinine) and patients with IBS (3.0(2.5-6.8) µmol/mmolcreatinine) were not significantly different from preprandial values(controls: 5.9 (5.5-6.6) µmol/mmol creatinine; patients with IBS:(6.2 (2.4-9.3) µmol/mmol creatinine).
Conclusion—These findings indicate that there maybe a difference in the way that 5-HT is released in patients withdiarrhoea predominant IBS, and could suggest a possible role for 5-HTin the postprandial symptoms of these patients.

Keywords:5-hydroxytryptamine; postprandial; diarrhoeapredominant irritable bowel syndrome

     

Recent insights into digestive motility in functional dyspepsia

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.     

经皮穴位电刺激改善功能性消化不良患者症状和胃容受性的相关机制

目的:探索经皮穴位电刺激(TEAS)治疗功能性消化不良(FD)中餐后不适综合征(PDS)的疗效和机制。方法:采用双盲、随机、对照研究,前瞻性选择于浙江大学医学院附属邵逸夫医院就诊、满足罗马Ⅳ诊断标准中的18～70岁的PDS患者40例,患者知情同意后随机分入TEAS组和模拟TEAS组,分别接受经皮电针刺激足三里、内关穴和...     

Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial

INTRODUCTION: Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying. METHODS: Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit. RESULTS: The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms. CONCLUSIONS: The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.     

Correlation between gastric myoelectrical activity recorded by multi-channel electrogastrography and gastric emptying in patients with functional dyspepsia

Objective. To investigate the correlation between the parameters of multi-channel electrogastrography (MEGG) and gastric emptying in patients with functional dyspepsia. Material and methods. The MEGG study included 19 patients with functional dyspepsia and 19 healthy subjects. MEGG was recorded for 30?min in the fasting state and 60?min after a standard test meal (450?kcal). MEGG parameters included the power ratio (PR), the normal percentage of 2–4?cpm gastric slow waves (N%) and the percentage of slow wave coupling (%SWC). Gastric emptying was measured in the 19 patients by SPECT (single photon emission computerized tomography) and the gastric emptying parameters included lag phase (LP), half time of gastric emptying (T1/2), emptying rate of stable phase (ERSP), one hour retention rate (1HRR), and two hour retention rate (2HRR). Results. No significant difference in MEGG parameters was found between normal subjects and patients. There was a significant negative correlation between postprandial N% and LP (r=???0.52, p<0.05) and a significant negative correlation between fasting %SWC and 1HRR (r=???0.48, p<0.04) or 2HRR (r=???0.48, p<0.05). Compared with the patients in the PR?>?1 group, patients in the PR?≤?1 group had significantly higher T1/2 and 2HRR but lower ERSP. Conclusions. Both the temporal regularity and spatial regularity of gastric slow waves have negative correlations with gastric emptying, which suggests that the impaired gastric myoelectrical activity may be responsible for the delayed gastric emptying in patients with functional dyspepsia.     

肺内与肺外源性急性呼吸窘迫综合征

根据急性呼吸窘迫综合征的病因的不同,将ARDS分为肺源性及非肺源性ARDS。不同病因所致的ALI／ARDS治疗效果与预后不同．本综述将肺内外源性ARDS不同的发病机制、呼吸力学、影象学以及对不同通气治疗策略的差异作一简述。     

功能性消化不良患者胃排空与症状的相关性及影响因素分析

目的了解胃排空异常与消化不良症状的相关性,分析影响功能性消化不良（FD）患者胃排空的因素。方法纳入32例FD患者。量化记录餐后上腹饱胀、上腹痛、上腹烧灼感、早饱、嗳气、恶心、呕吐7组症状及静息心率。以心率的中位数将其转化为二分类变量进行非条件Logistic回归分析统计。运用核素闪烁法检测空腹固体试餐,试餐参考美国胃肠动力学会、神经胃肠学会及核医学联合推荐的标准低脂试餐以及诊断标准。结果 32例FD患者,8例（25%）T1/2延迟,7例（21.88%）Retention%2 h增加,Retention%1 h均在正常范围内。Retention%2 h正常组与Retention%2 h增加组以及T1/2正常组与T1/2延长组之间,心率均存在显著差异（P=0.031,P=0.022）,心率与Retention%2 h、T1/2存在正相关（r=0.448,P=0.01;r=0.423,P=0.016）。在控制了性别、年龄及其他症状因素的影响下,心率〉70 bpm是Retention%2 h增加、T1/2延长的独立因素（OR=12.378,P=0.042;OR=8.180,P=0.072）。在Retention%2 h正常组与Retention%2 h增加组之间恶心症状指数有显著差异（P=0.003）,恶心与Retention%2 h、T1/2存在正相关（r=0.527,P=0.002;r=0.381,P=0.032）。结论心率、恶心症状与功能性消化不良患者的胃排空存在一定相关性,在控制了性别、年龄、BMI及其他症状的因素影响下,静息心率增加、出现恶心症状可能是胃排空延缓的独立因素。     

Targeting postprandial glycaemia in children with diabetes: Opportunities and challenges

Postprandial glycaemia makes a substantial contribution to overall glycaemic control in diabetes, particularly in patients whose preprandial glycaemia is relatively well controlled and glycated haemoglobin (HbA1c) only modestly elevated. Our review addresses the determinants of postprandial glycaemia and how it may be targeted therapeutically in children with diabetes. Postprandial glycaemia is influenced by preprandial glycaemia, macronutrients and their absorption, insulin delivery and sensitivity, the action of the enteroendocrine system, and the rate of gastric emptying. Contemporary continuous glucose monitoring systems reveal patterns of post prandial glycaemia and allow management to be guided more precisely. Delays in blood glucose determination, insulin delivery and its absorption remain challenges in the rapidly evolving closed loop continuous subcutaneous insulin and glucagon delivery systems developed for children with type 1 diabetes. Augmentation of the incretin system through nutritional preloads or incretin mimetics targets postprandial glycaemia by slowing gastric emptying as well as insulinotropic and glucagonostatic effects. These treatments are of particular relevance to children with type 2 diabetes. Following the development of targeted therapies in adults, postprandial blood glucose control will now be increasingly targeted in the treatment of diabetes in children.     

氟哌噻吨美利曲辛片联合常规治疗对功能性消化不良疗效的临床研究

目的 选择常规促胃肠动力剂、PPI治疗效果不佳的患者,给予氟哌噻吨美利曲辛片联合治疗,评价联合治疗的临床疗效.方法 病例选自2011年10月～2012年8月在北京友谊医院消化内科门诊就诊的功能性消化不良(FD)患者,根据FD临床亚型分为餐后不适综合征(PDS)和上腹痛综合征(EPS),分别给予莫沙必利和奥美拉唑治疗4周.对于治疗效果不佳的患者随机分为继续莫沙必利或奥美拉唑常规治疗组和氟哌噻吨美利曲辛片联合莫沙必利或奥美拉唑治疗组,比较常规治疗组和联合治疗组的症状改善情况和治疗有效率.结果 共纳入200名患者,男性89例,女性111例,PDS组92例,EPS组108例.PDS组莫沙必利治疗的总有效率63.0％,EPS组奥美拉唑治疗的有效率为70.3％.PDS组和EPS组中分别有34例和32例患者治疗效果不佳,随机进入治疗的第二阶段.PDS组中氟哌噻吨美利曲辛片联合治疗的总有效率为52.9％.EPS组中氟哌噻吨美利曲辛片联合治疗的总有效率为50.0％.结论 对于常规治疗效果不佳的患者联合应用氟哌噻吨美利曲辛片,可以改善患者的焦虑抑郁情绪,从而改善患者的临床症状.     

Acute respiratory distress syndrome following intrathecal methotrexate administration: a case report and review of literature

 Acute Respiratory distress syndrome (ARDS) is a rare complication following intrathecal (IT) injection of methotrexate (MTX) in adult acute lymphoblastic leukemia (ALL) patients. A 19-year-old man with ALL developed strikingly acute respiratory failure during central nervous system (CNS) prophylaxis with IT MTX administration and cranial irradiation. Histopathologic study of the lungs revealed a pattern of diffuse alveolar damage with interstitial cellular infiltration. His symptoms were relieved soon following treatment with corticosteroids and the pulmonary infiltrates resolved gradually. Pulmonary symptoms did not recur as he was continuously treated with oral corticosteroids. Received: 31 January 2000 / Revised: 16 March 2000 / Accepted: 8 May 2000