Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study

BACKGROUND Acute esophageal mucosal lesions(AEMLs)are an underrecognized and largely unexplored disease.Endoscopic findings are similar,and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D(RE-D).These diseases could have different pathologies and require different treatments.AIM To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML.METHODS We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury’s shape on the oral side.We examined patient background,blood sampling data,comorbidities at onset,endoscopic characteristics,and outcomes in each group.RESULTS Among the emergency cases,the AEML and RE-D groups had 105(3.1%)and 48(1.4%)cases,respectively.Multiple variables exhibited significantly different results,indicating that these two diseases are distinct.The clinical features of AEML consisted of more comorbidities[risk ratio(RR):3.10;95%confidence interval(CI):1.68–5.71;P<0.001]and less endoscopic hemostasis compared with RE-D(RR:0.25;95%CI:0.10–0.63;P<0.001).Mortality during hospitalization was higher in the AEML group(RR:3.43;95%CI:0.82–14.40;P=0.094),and stenosis developed only in the AEML group.CONCLUSION AEML and RE-D were clearly distinct diseases with different clinical features.AEML may be more common than assumed,and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

Role of the nucleus tractus solitarii in the protection of pre-moxibustion on gastric mucosal lesions

Previous studies have shown that somatic sensation by acupuncture and visceral nociceptive stimulation can converge in the nucleus tractus solitarii where neurons integrate signals impact- ing on the function of organs. To explore the role of the nucleus tractus solitarii in the protective mechanism of pre-moxibustion on gastric mucosa, nucleus tractus solitarii were damaged in rats and pre-moxibustion treatment at the Zusanli （ST36） point followed. The gastric mucosa was then damaged by the anhydrous ethanol lavage method. Morphological observations, enzyme linked immunosorbent assays, and western immunoblot analyses showed that gastric mucosa surface lesion and the infiltration of inflammatory cells were significantly ameliorated after pre-moxibustion treatment. Furthermore, the gastric mucosal damage index and somatostatin level were reduced, and epidermal growth factor content in the gastric mucosa and heat-shock protein-70 expression were increased. These results were reversed by damage to the nucleus tractus solitarii. These findings suggest that moxibustion pretreatment at the Zusanli point is protective against acute gastric mucosa injury, and nucleus tractus solitarii damage inhibits these responses. Therefore, the nucleus tractus solitarii may be an important area for regulating the signal transduction of the protective effect of pre-moxibustion on gastric mucosa.

Effects of pre-moxibustion at Zusanli (ST36) on heat shock protein 70 expression in rats with gastric mucosal lesions after neurotomy

Studies have shown that pre-moxibustion protects the gastric mucosa by up-regulating the expression of heat shock protein 70. However, the signaling pathway underlying this effect remains unclear. Rats were intragastrically administered absolute alcohol, causing obvious lesion of the gastric mucosa. Following pre-moxibustion at Zusanfi （ST36） for 8 days, the ulcer index decreased to different degrees. The results of an enzyme linked immunosorbent assay and western blotting showed significant upregulation of heat shock protein 70 expression in the gastric mucosa and serum. None out of transection of the spinal cord, damage to the nucleus of the solitary tract, neurotomy of the vagal nerve and neurotomy of the common peroneal nerve affected the decrease in ulcer index or the increase in heat shock protein 70 expression in serum after pre-moxibustion at Zusanfi, and heat shock protein 70 expression was obviously decreased in the gastric mucosa. These findings suggest that pre-moxibustion at Zusanfi can protect the gastric mucosa against lesioning, and that the mechanism underlying this effect involves its induction of heat shock protein 70 expression. Neural pathways participate in the regulatory effects of moxibustion on heat shock protein 70 expression in the gastric mucosa.

Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion

Stress-induced gastric mucosal lesion(SGML)is one of the most common visceral complications after trauma.Exploring the nervous mechanisms of SGML has become a research hotspot.Restraint water-immersion stress(RWIS)can induce GML and has been widely used to elucidate the nervous mechanisms of SGML.It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves.Many central nuclei,such as the dorsal motor nucleus of the vagus,nucleus of the solitary tract,supraoptic nucleus and paraventricular nucleus of the hypothalamus,mediodorsal nucleus of the thalamus,central nucleus of the amygdala and medial prefrontal cortex,are involved in the formation of SGML in varying degrees.Neurotransmitters/neuromodulators,such as nitric oxide,hydrogen sulfide,vasoactive intestinal peptide,calcitonin gene-related peptide,substance P,enkephalin,5-hydroxytryptamine,acetylcholine,catecholamine,glutamate,γ-aminobutyric acid,oxytocin and arginine vasopressin,can participate in the regulation of stress.However,inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML,such as the involvement of different nuclei with the time of RWIS,the different levels of involvement of the sub-regions of the same nucleus,and the diverse signalling molecules,remain to be further elucidated.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Effect of moxibustion treatment on cell apoptosis and expressions of heat shock protein and second mitochondrial activator of caspase in acute gastric mucosal lesion of rats

OBJECTIVE:To investigate the effect of moxibustion-acupoint treatment with acupoints of Zusanli(ST 36) and Zhongwan(RN 12) on cell apoptosis and the expressions of heat shock protein(HSP) 60,HSP70 and second mitochondrial activator of caspase(Smac) in rat models of acute gastric mucosal lesion(AGML),and explore the mechanisms underlying protection of gastric mucosal lesion.METHODS:Twenty-four Sprague Dawley rats were divided into 3 groups,blank controlled group(group A),controlled-point group(group B) and acupoint group(group C),8 for each.After 8-day moxibustion treatment in group B and C,gastric lavage of anhydrous ethanol was used to created AGML in all three groups.The Guth method was employed to measure the ulcer index(UI) of gastric mucosal lesion and immunohistochemistry used to measure apoptosis with apoptosis index(AI) and examinetheexpressionsofHSP60,HSP70and Smac.RESULTS:Compared with group A,the expressions of UI,AI,Smac and HSP60 were markedly elevated in group B(P<0.05 or P<0.01).However the expression of HSP70 showed no obvious change(P>0.05);the expressions of UI,HSP60 and HSP70 were markedly elevated in group C(P<0.01) while those of AI and Smac became obviously suppressed(P<0.01).Compared with group B,the expressions of UI,AI and Smac decreased significantly in group C(P< 0.01) while those of HSP60 and HSP70 increased markedly(P<0.01),and the expressions of HSP60 and HSP70 were considerably up-regulated(P< 0.01).CONCLUSION:The moxibustion treatment could alleviate the gastric mucosal lesion caused by anhydrous ethanol,induce the over-expressions of HSP60 and HSP70,and down-regulate the expression of Smac,which could suppress cell apoptosis.

Extrusion process of Acanthopanax senticosus leaves enhances the gastroprotective effect of compound 48/80 on acute gastric mucosal lesion in rats

OBJECTIVE:To investigate the gastroprotective effects of Acanthopanax senticosus leaves(ASLs)extrusion on acute gastric mucosal lesion in rats induced by compound 48/80(C48/80).METHODS:Rats were divided into six groups:normal;C48/80-induced gastric lesion control;gastric lesion positive control(famotidine 4 mg/kg);gastric lesion administered with two levels of extruded ASLs(ASLE,40 and 200 mg/kg);and gastric lesion treated with ASLs(ASL 200 mg/kg).Mucus secretion/damage was determined by immunohistological staining.Immunofluorescence and western blotting were performed to determine gastric mucosal Bax and Bcl-2 expression.Gastric mucosal oxidative-stress-related enzymes and malondialdehyde were determined.RESULTS:C48/80-induced mucus depletion and inflammation in the gastric mucosa were significantly attenuated by ASLs.The increased serum serotonin and histamine concentrations in C48/80-treated rats were also attenuated by ASLs.Gastric mucosal Bax protein expression was increased and Bcl-2 expression was decreased after C48/80 treatment,and ASLs ameliorated Bax and Bcl-2 expression.The extrusion process significantly augmented the effects of ASLs in a dosedependent manner.ASLEs at 200 mg/kg normalized mucus damage/secretion,C48/80-induced increases of mucosal myeloperoxidase activity(index of inflammation),xanthine oxidase,and malondialdehyde content(index of lipid peroxidation).The effects of ASLs on Bax and Bcl-2expression were also enhanced by extrusion.Furthermore,these effects of ASLEs at 200 mg/kg were similar to those of famotidine,a histamine H2-receptor antagonist commonly used to treat gastric ulcers.CONCLUSION:ASLEs prevented acute gastric mucosal lesion progression induced by C48/80,possibly by inducing mucus production,and reduced inflammation and oxidative stress in gastric mucosa through an anti-apoptotic mechanism.

The Protective Effect of a Puerariae flos Extract (Thomsonide) against Ethanol-Induced Gastric Lesions in Rats

Objectives: Puerariae flos has popularly been used to treat alcoholic disorders. However, the effect of Puerariae flos on alcoholic disorders in the gastrointestinal system has not been identified. We investigated the protective effect of an extract of Puerariae flos against the murine gastric mucosa. Methods: Thomsonide, the extracts containing large amounts of isoflavonoid and triterpenoid saponin, was obtained fr om Puerriae flos via Diaion HP-20 column chromatography using water and 99.5% ethanol. It was investigated whether thomsonide, as well as geranylgeranylacetone (teprenone), a popular anti-ulcer agent developed in Japan, had a cytoprotective effect that might be related to endogenous prostaglandins, which played an important role in preventing gastric mucosal lesions. Results: Thomsonide and teprenone inhibited ethanol-induced gastric lesions. Furthermore, thomsonide increased the production of PGE2 and 6-ketoPGF1α, a stable metabolite of PGI2, in the gastric mucosa, and protective effects of thomsonide, as well as teprenone, against ethanol-induced gastric lesions were attenuated by pretreatment with indomethacin. Conclusions: These findings suggest that thomsonide, as well as teprenone, has the gastro protective effect which may be related to the cytoprotective activity of endogenous prostaglandins. The results of this study also suggest that the gastro protective effect of thomsonide may partially mitigate alcoholic disorders in the gastrointestinal tract, and support our pharmacological belief that Puerariae flos is useful for treatment of alcoholic disorders.

High-altitude gastrointestinal bleeding:An observation in Qinghai-Tibetan railroad construction workers on Mountain Tanggula

AIM: To investigate the gastrointestinal bleeding (GIB) in people from lowland to high altitude and in workers on Mountain Tanggula and its causes as well as treatment and prophylaxis.METHODS: From 2001 to October 2003, we studied GIB in 13 502 workers constructing the railroad on Mountain Tanggula which is 4905 m above the sea level. The incidence of GIB in workers at different altitudes was recorded. Endoscopy was performed when the workers evacuated to Golmud (2808 m) and Xining (2261 m). The available data on altitude GIB were analyzed.RESULTS: The overall incidence of GIB was 0.49% in 13 502 workers. The incidence increased with increasing altitude. The onset of symptoms in most patients was within three weeks after arrival at high altitude. Bleeding manifested as hematemesis, melaena or hematochezia, and might be occult. Endoscopic examination showed that the causes of altitude GIB included hemorrhage gastritis, gastric ulcer, duodenal ulcer, and gastric erosion. Experimental studies suggested that acute gastric mucosal lesion (AGML) could be induced by hypoxic and cold stress, which might be the pathogenesis of altitude GIB. Those who consumed large amount of alcohol, aspirin or dexamethasone were at a higher risk of developing GIB. Persons who previously suffered from peptic ulcer or high-altitude polycythemia were also at risk of developing GIB. Early diagnosis, evacuation, and treatment led to early recovery. CONCLUSION: GIB is a potentially life threatening disease, if it is not treated promptly and effectively. Early diagnosis, treatment and evacuation lead to an early recovery. Death due to altitude GIB can be avoided if early symptoms and signs are recognized.