Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.

Cardioneuroablation for the treatment of symptomatic bradycardia mediated by the cardiac autonomic nervous

Sinus bradycardia is a common clinical problem with a population prevalence of approximately 4/1000.[1]Most patients are asymptomatic,but some patients experience symptoms such as fatigue,dizziness,exercise intolerance,syncope,or pre-syncope,worsening of angina symptoms,worsening of heart failure,or cognitive slowing.Although both European and American guidelines recommend cardiac pacing for patients with severe symptoms of sinus bradycardia,there are problems such as infection,electrode detachment,perforation,and pacemaker replacement.

Pathogenesis,clinical manifestations,diagnosis,and treatment progress of achalasia of cardia

Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter.Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia,and is more likely to occur in the elderly.Histological changes in the esophageal mucosa are considered pathogenic;however,studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia,resulting in dysphagia,reflux,aspiration,retrosternal pain,and weight loss.Currently,the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter,helping to empty the esophagus and relieve symptoms.Treatment measures include botulinum toxin injection,inflatable dilation,stent insertion,and surgical myotomy(open or laparoscopic).Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness,particularly in older patients.Herein,we review clinical epidemiological and experimental data to determine the prevalence,pathogenesis,clinical presentation,diagnostic criteria,and treatment options for achalasia to support its clinical management.

The efficacy of full-thickness endoscopic resection of subepithelial tumors in the gastric cardia

BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is challenging.AIM To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia SETs.METHODS We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at Zhongshan Hospital Fudan University between November 2014 and May 2022.Baseline characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and STER.RESULTS A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common SET.The en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation syndrome.There was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER.In cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.

血管外肺水和肺血管通透性的监测与临床应用

反映肺病理生理的指标较多，有氧合指数、肺泡-动脉分压差、肺内分流、肺顺应性、死腔与潮气容积之比、血管外肺水（extravascu larlung water，EVLW）、肺血管通透性（pulmonary vascularpermeability，PVP）指数等。近年来，基于单一温度稀释技术与脉搏轮廓联合应用的脉搏指示剂连续心排出量监测（pulse indicator continuous cardia coutput，PICCO）法，经过多年的改进，已在临床应用，它可以同时连续监测心排出量、EVLW、PVP指数等指标，对危重病患者的监护达到了刨伤小、简便、连续和精确的优点。近年来EVLW、PVP作为评价肺病理生理的指标在临床上得到更加广泛的认识和应用。

贲门癌淋巴结微转移的临床检测价值

背景与目的贲门癌（Gastric cardia adenocarcinoma,GCA）是发生在胃贲门部的恶性肿瘤,是我国北方常见的恶性肿瘤之一,贲门癌术后长期生存率较低,而淋巴结转移是其主要原因之一。淋巴结微转移是指常规病理学检查难以发现的直径小于2mm的转移灶。而明确淋巴结是否有转移对于临床分期、决定术后综合治疗方案以及判断预后有极其重要意义。本实验采用CK19、CD44v6两种微转移标志物联合检测常规病理学检查无淋巴结转移的贲门癌淋巴结微转移，并探讨贲门癌淋巴结微转移的特点，分析淋巴结微转移与各种临床病理因素的之间关系。

心脏性猝死高危患者家属心肺复苏知识的调查分析

心脏性猝死（sudden cardia death,SCD）指由于心脏原因在急性症状出现之后1h内骤然意识丧失引起的意外自然死亡。冠心病、心肌病、心力衰竭等基础心脏病患者是SCD的高危人群。这些SCD高危患者与其家属朝夕相处,一旦出现呼吸、心跳骤停,现场“第一目击者”常常是患者的家属,

Submucosal tunneling endoscopic resection: An effective and safe therapy for upper gastrointestinal submucosal tumors originating from the muscularis propria layer

AIM To evaluate the effectiveness and safety of submucosal tunneling endoscopic resection(STER) and compare its outcomes in esophageal and cardial submucosal tumors(SMTs) of the muscularis propria(MP) layer.METHODS From May 2012 to November 2017, 173 consecutive patients with upper gastrointestinal(GI) SMTs of the MP layer underwent STER. Overall, 165 patients were included, and 8 were excluded. The baseline characteristics of the patients and SMTs were recorded. The en bloc resection rate, complete resection rate,residual rate, and recurrence rate were calculated to evaluate the effectiveness of STER, and the complication rate was recorded to evaluate its safety. Effectiveness and safety outcomes were compared between esophageal and cardial SMTs.RESULTS One hundred and twelve men and 53 women with a mean age of 46.9 ± 10.8 years were included. The mean tumor size was 22.6 ± 13.6 mm. Eleven SMTs were located in the upper esophagus(6.7%), 49 in the middle esophagus(29.7%), 46 in the lower esophagus(27.9%), and 59 in the cardia(35.7%). Irregular lesions accounted for 48.5% of all lesions. STER achieved an en bloc resection rate of78.7%(128/165) for GI SMTs with an overall complication rate of 21.2%(35/165).All complications resolved without intervention or were treated conservatively without the need for surgery. The en bloc resection rates of esophageal and cardial SMTs were 81.1%(86/106) and 72.1%(42/59), respectively(P = 0.142), and the complication rates were 19.8%(21/106) and 23.7%(14/59), respectively,(P =0.555). The most common complications for esophageal SMTs were gas-related complications and fever, while mucosal injury was the most common for cardial SMTs.CONCLUSION STER is an effective and safe therapy for GI SMTs of the MP layer. Its effectiveness and safety are comparable between SMTs of the esophagus and cardia.

Heterotopic pancreatic tissue in the gastric cardia: A case report and literature review

The heterotopic pancreas, which is usually described as an untypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas, is relatively rare. Clinical manifestations may include bleeding, inflammation, pain and obstruction; however, in most cases it remains silent and is diagnosed during autopsy. Here, we report a case of ectopic pancreatic lesion located in the gastric cardia. The patient was a 73-year-old woman who had a history(over four months) of chronic epigastric pain accompanied by heartburn. Esophagogastroduodenoscopy revealed inflammatory changes throughout the stomach and lower esophagus, as well as a flat polypoid mass with benign features located in the gastric cardia, approx. 10 mm below the "Z" line, measuring approx. 7 mm in diameter. Endoscopic biopsy forceps were used to remove the lesion. Histological examination of the lesion revealed the presence of heterotopic pancreatic tissue in the gastric mucosa. On the basis of the presented case, we suggest that pancreatic ectopia should be a part of differential diagnosis, not only when dealing with submucosal gastric lesions, but also with those that are small, flat and/or untypically located.

Infrequent p53 gene mutation and expression of the cardia adenocarcinomas from a high-incidence area of Southwest China

INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The

Human papillomavirus DNA and P16～(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.

EPIDEMIC STRENGTH OF CARDIA AND DISTANT STOMACH CANCER IN THE HIGH RISK REGION OF ESOPHAGEAL CANCER AND THEIR IMPLICATION TO EDOSCOPIC SCREENING

Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to clarify the tasks for the control of upper gastrointestinal tract cancer as a whole in the region. Methods： Comparisons of incidence and mortality rates of esophageal, cardia and stomach cancers were made between Cixian, Linxian and Shexian Counties with reference to detection rates of cancer in situ and precancerous lesions of the three upper gastrointestinal cancers by endoscopic screening. The screening was performed from 1999 through 2004 in the three adjacent counties including a total of 6233 local residents aged 40 to 69 years old. Results： The incidence rates for cardia cancer for the male and female from 2000 through 2004 were 69.9 and 41.5, and the mortality rates were 54.3 and 33.2 respectively in Shexian County. Esophageal, cardia, and stomach cancers constitute about 70～80 percent of all malignant disease by incidence or mortality rates. Endoscopic survey with iodine staining can effectively detect squamous cell precancerous lesions in the esophagus, but the method is inadequate for the detection of adeno precancerous lesions of the cardia and stomach. Conclusion： The south Taihang mountain region is a high risk area not only for esophagus cancer, but also for cardia and stomach cancers. To control upper gastrointestinal tract cancers as a whole in the region, special attention should be paid to the control of cardia and stomach cancers. Presently, to find effective screening methods for detecting cardia and stomach precancerous lesions is especially important.

Comparative studies on epithelial lesions at gastric cardia and pyloric antrum in subjects from a high incidence area for esophageal cancer in Henan,China

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Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas

Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

Family case of achalasia cardia: Case report and review of literature

Achalasia cardia is an idiopathic disease that occurs as a result of inflammation and degeneration of myenteric plexi leading to the loss of postganglionic inhibitory neurons required for relaxation of the lower esophageal sphincter and peristalsis of the esophagus.The main symptoms of achalasia are dysphagia,regurgitation,chest pain and weight loss.At present,there are three main hypotheses regarding etiology of achalasia cardia which are under consideration,these are genetic,infectious and autoimmune.Genetic theory is one of the most widely discussed.Case report given below represents an inheritable case of achalasia cardia which was not diagnosed for a long time in an 81-year-old woman and her 58-year-old daughter.

Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.