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.

Identification of plasma proteomic signatures associated with the progression of cardia gastric cancer and precancerous lesions

Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to identify candidate protein markers.Methods:Plasma samples were obtained from 40 subjects,10 each for CGC,cardia high-grade dysplasia(CHGD),cardia low-grade dysplasia(CLGD),and healthy controls.Proteomic profiles were obtained through liquid chromatography-mass spectrometry(LC-MS/MS-based DIA proteomics.Candidate plasma proteins were identified by weighted gene co-expression network analysis(WGCNA)combined with machine learning and further validated by the Human Protein Atlas(HPA)database.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the biomarker panel.Results:There was a clear distinction in proteomic features among CGC,CHGD,CLGD,and the healthy controls.According to the WGCNA,we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways.Combined with the results from random forests,LASSO regression,and immunohistochemical results from the HPA database,we identified three candidate proteins(GSTP1,CSRP1,and LY6G6F)that could together distinguish CLGD(AUC=0.91),CHGD(AUC=0.99)and CGC(AUC=0.98)from healthy controls with excellent accuracy.Conclusions:The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions.Further validation and a larger-scale study are warranted to assess its potential clinical applications,suggesting a potential avenue for CGC prevention in the future.

"Layer-to-Layer" Esophagogastric Anastomosis Combined with Intrathoracic Esophageal Mucosal Extention in Patients with Esophageal and Cardia Cancer

Objective: To evaluate the clinical value of intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosa extended varied in plane and to study the effective methods to prevent anastomotic leaking or stricture postoperatively. Methods: From May 1985 to December 2002, 2 240 esophageal and stomach cardia cancer patients treated by intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosa extended varied in plane were retrospectively analyzed. Results: There was no anastomotic leaking and severe stricture in all above cases. Conclusion: Intrathoracic esophagogastric "layer-to-layer" anastomosis with esophageal mucosal extended varied in plane is an effective method to prevent anastomotic leaking and stricture postoperatively.

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 &#x0201c;Z&#x0201d; 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.

Prognostic significance of preoperative and postoperative CK19 and CEA m RNA levels in peripheral blood of patients with gastric cardia cancer

AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.

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

AIM To investigate the pathogenesis of gastric cardia and the distal part of stomach cancer and to further characterize the histopathogenesis model for gastric cardia cancer from the high-risk population for esophageal cancer.METHODS Mass survey with endoscopic mucosa biopsy and histopathological examination were carried out on 226 subjects aged above 30 years. Three biopsies were collected one each from the middle part of the esophagus, the gastric cardia and the pyloric antrum. The biopsy tissue was fixed with 85% alcohol and paraffin-embedded.RESULTS The incidence of intestinal metaplasia and dysplasia at gastric cardia epithelium was higher than that at the pyloric antrum from the subjects in the same area. And there were high incidences of both esophageal and gastric cardia cancer, but a low incidence of gastric cancer at the distal part of the stomach.CONCLUSION There might be different etiology and pathogenesis of gastric cardia and pyloric cancer at the distal part of the stomach.

Recurrent inflammatory fibroid polyp of cardia:A case report

Inflammatory fibroid polyp is one of the chronic inflammatory diseases in the digestive tract, which often mimics the submucosal tumor. Precise diagnosis is possible after removal of the detected lesion. Endoscopic removal is recommended as a safe and efficient method of the treatment. In this report the authors present a case of inflammatory fibroid polyp located in the cardia, which has been removed endoscopically. Twelve months later, recurrence of the lesion was noted and the patient was referred to surgical resection.

Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China

AIM： To characterize the histochemical type and pattern of intestinal metaplasia （IM） adjacent to gastric cardia adenocarcinoma （GCA） and distal gastric cancer （GC） in Unzhou, Henan Province, China. METHODS： Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS： The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues （80.64%, P〈0.01）. The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues （31.82% and 63.64%, respectively） were significantly higher than those in GC （5.33% and 21.33%, respectively, P〈0.01）. CONCLUSION： IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.

Relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China

AIM:To study the relationship between ABO blood groups and carcinoma of esophagus and cardia in Chaoshan inhabitants of China, which is a unique Littoral high-risk area of esophageal carcinoma in China. The poor communication and transportation in the past has made Chaoshan a relatively closed area and kept its culture and custure of old China thousand years ago. METHODS: Data on age, sex, ABO blood type and X-ray or pathological diagnose of the patients with carcinoma of esophagus or cardia were collected from the Tumor Hospital. First Affiliated Hospital, Second Affiliated Hospital of Shantou University Medical College; and the Central Hospital of Shantou and the Central Hospital of Jieyang. A total of 6685 patients with esophageal carcinoma (EC) and 2955 patients with cardiac cancer (CC) in Chaoshan district were retrospectively assessed for their association with ABO blood groups. RESULTS: The distribution of ABO blood groups in patients with EC or CC was similar to the normal local population in Chaoshan. However, blood group B in male patients with CC and in the patients with carcinoma in the upper third esophagus was 2.3% and 4.7% higher than the corresponding controls. The relative risk B O was 1.1415 (P【0.05) and 1.2696 (P【0.05), respectively. No relationship was found between ABO blood groups and tumor differentiation. CONCLUSION: ABO blood group B is associated with the incidence of CC in male individuals and carcinoma in the upper third esophagus. The distribution of ABO blood groups varies in the different geographical and ethnic groups. As a result, proper controls are very important for such studies.

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.