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.

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.

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.

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.

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.

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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Short-segment Barrett's esophagus and cardia intestinal metaplasia:A comparative analysis

AIM:To investigate the endoscopy and histology of short-segment Barrett's esophagus (SSBE) and cardia intestinal metaplasia (CIM),and their correlation with Helicobacter pylori (H. pylori) gastritis and gastroesophageal reflux disease (GERD). METHODS:Biopsy specimens were taken from 32 SSBE patients and 41 CIM patients with normal appearance of the esophagogastric junction. Eight biopsy specimens from the lower esophagus,cardia,and gastric antrum were stained with hematoxylin/eosin,Alcian blue/periodic acid-Schiff,Alcian blue/high iron diamine and Gimenez dye. Results were graded independently by one pathologist. RESULTS:The SSBE patients were younger than the CIM patients (P < 0.01). The incidence of dysplasia and incomplete intestinal metaplasia subtype was higher in SSBE patients than in CIM patients (P < 0.01). H. pylori infection was correlated with antral intestinal metaplasia (P < 0.05),but not with reflux symptomatic,endoscopic,or histological markers of GERD in CIM patients. SSBE was correlated with reflux symptomatic and endoscopic esophagitis (P < 0.01),but not with H. pylori infection and antral intestinal metaplasia. CONCLUSION:Dysplasia risk is significantly greater in SSBE patients than in CIM patients. CIM is a manifestation of H. pylori-associated and multifocal atrophic gastritis,whereas SSBE may result from GERD.

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.

The expression of c-src gene in the carcinogenesis process of human cardia adenocarcinoma

AIM To investigate the activation, expression of c src gene and its role in the carcinogenetic process of human cardia adenocarcinoma (CA). METHODS Fifty six cases of CA, 34 cases of normal, 36 cases of protiferative epithelia adjacent to carcinoma, and 20 cases of lymph node metastases of CA were studied for PP60 c src , the expression product of c src gene immunohistochemically by using the specific monoclonal antibody, Mab327. RESULTS The positive rates of PP60 c src in the normal epithelia, protiferative epithelia, CA and lymph node metastases were 29 4% (10/*!34), 94 4% (34/*!36), 71 4% (40/*!56) and 60 0% (12/*!20) , respectively, among them, the differences of the positive rates were statistically significant ( P <0 01) . The expression levels of PP60 c src in CA and proliferative epithelia were significantly higher than that in the normal epithelia ( P <0 01) . The PP60 c src positive rates in the papillary, tubular, poorly differentiated and mucous adenocarcinoma were 75 0% (6/*!8) , 81 8% (18/*!22) , 50 0% (10/*!20) and 100 0% (6/*!6) , respectively, whereas those of tubular and mucous adenocarcinomas were significantly higher than those of papillary and poorly differentiated adenocarcinomas ( P <0 05) , and the PP60 c src expression levels of tubular and mucous adenocarcinomas were also significantly higher than those of papillary and poorly differentiated adenocarcinomas ( P <0 01) . CONCLUSION The activation and expression of c src gene are associated with the initiation and development of human CA; the protein amount of PP60 c src increased during the process of carcinogenesis; and PP60 c src expression is also related to lymph node metastases.

Helicobacter pylori and gastric cardia cancer:What do we know about their relationship?

The incidence of gastric cardia cancer is increasing around the world.Since the discovery of Helicobacter pylori(H.pylori),numerous studies have proved that it is a causative factor for many kinds of digestive system tumors.Although the literature on gastric cardia cancer and H.pylori is not scarce,there are still many controversies on the relationship between gastric cardia cancer and H.pylori.Many Western research results showed that there was a negative or no correlation between H.pylori infection and gastric cardia cancer,but in several studies in Asian countries,such as China,H.pylori was demonstrated to be a risk factor for gastric cardia cancer.Therefore,we intended to analyze the related studies to find out the relationship between H.pylori and gastric cardia cancer and find out the causes of the above controversies.We also conducted a metaanalysis of the relationship between cagA positive expression of H.pylori and gastric cardia cancer,to find out whether there is an effect between those two.The primary purpose of this paper was to explore the relationship between gastric cardia cancer and H.pylori.Through analysis,the study showed the reasons for the controversies mentioned above:(1)Geographical factors could affect the relationship between H.pylori and gastric cardia cancer;(2)The definition of gastric cardia cancer in various studies is inconsistent.The result of a meta-analysis about the relationship between H.pylori virulence factor cagA and gastric cardia cancer showed that there was no relationship between these two.

ACUPUNCTURE AT JIANJING FOR TREATMENT OF ACHALASIA OF THE CARDIA

Achalasia of the cardia,also known ascardiospasm or megalo—esophagus,Is char-acterized by the symptom of dysphagia.Diagnosis of the disease and its division intodifferent types are described in the PracticalTextbook of Medicine and Symposium onMedicine.During the recent 10 years,theauthor treated 21 cases of the disease byacupuncture with satisfactory results as re-ported in the following.

Clinical features of cardiac nodularity-like appearance induced by Helicobacter pylori infection

We have previously reported that Helicobacter pylori(H.pylori)-associated nodular gastritis could occur in both the antrum and the cardia.Cardiac nodularity-like appearance(hereafter,called as cardiac nodularity)had a high predictive accuracy for the diagnosis of H.pylori infection.In the previous study,we included only the patients who were evaluated for H.pylori infection for the
rst time,and excluded patients with a history of eradication.Therefore,the prevalence and clinical features of cardiac nodularity remains unknown.AIM To perform this cross-sectional study to explore the characteristics of cardiac nodularity.METHODS Consecutive patients who underwent esophagogastroduodenoscopy betweenMay,2017 and August,2019 in the Toyoshima Endoscopy Clinic were enrolled in this study.We included H.pylori-negative,H.pylori-positive,and H.pylorieradicated patients,and excluded patients with unclear H.pylori status and eradication failure.H.pylori infection was diagnosed according to serum anti-H.pylori antibody and the urea breath test or histology.Cardiac nodularity was defined as a miliary nodular appearance or the presence of scattered whitish circular small colorations within 2 cm of the esophagogastric junction.Nodularity was visualized as whitish in the narrow-band imaging mode.We collected data on the patients’baseline characteristics.RESULTS A total of 1078 patients were finally included.Among H.pylori-negative patients,cardiac nodularity and antral nodularity were recognized in 0.14%each.Among H.pylori-positive patients,cardiac nodularity and antral nodularity were recognized in 54.5%and 29.5%,respectively.Among H.pylori-eradicated patients,cardiac nodularity and antral nodularity were recognized in 4.5%and 0.6%,respectively.The frequency of cardiac nodularity was significantly higher than that of antral nodularity in H.pylori-positive and-eradicated patients.The frequencies of cardiac nodularity and antral nodularity in H.pylori-eradicated patients were significantly lower than those in H.pylori-positive patients(P<0.001).The patients with cardiac nodularity were significantly younger than those without cardiac nodularity(P=0.0013).Intestinal metaplasia score of the patients with cardiac nodularity were significantly lower than those without cardiac nodularity(P=0.0216).Among H.pylori-eradicated patients,the patients with cardiac nodularity underwent eradication significantly more recently compared with those without cardiac nodularity(P<0.0001).CONCLUSION This report outlines the prevalence and clinical features of cardiac nodularity,and confirm its close association with active H.pylori infection.

Oesophagocardiomyotomy for Achalasia Cardia via Thoracotomy in a Teaching Hospital in Ghana: A 5-Year Retrospective Review

Achalasia cardia is a primary oesophageal motility disorder of unknown aetiology characterized manometrically by insufficient relaxation of the lower oesophageal sphincter (LES) and loss of oesophageal peristalsis;radiographically by aperistalsis, oesophageal dilation with minimal LES opening, bird-beak appearance, poor emptying of barium;and endoscopically by dilated oesophagus with retained saliva, liquid and undigested food particles in the absence of mucosal stricturing or tumour. Achalasia cardia patients usually present with difficulty in swallowing both solids and liquids and this may be associated with regurgitation, heartburn and chest pains. Treatment options include medical or pharmacologic therapy, botulinum toxin injection, pneumatic dilation and oesophagocardiomyotomy or the Heller myotomy with or without antireflux procedure and recently the POEM (Perioral oesophageal myotomy). Herein, we present our experience with four cases managed surgically via thoracotomy without antireflux surgery over a 5-year period, from January 2015 to June 2019 at the Komfo Anokye Teaching Hospital, the second largest teaching hospital in Ghana.