Telomerase and hTERT: Can they serve as markers for gastric cancer diagnosis?

AIM: To investigate telomerase activity and human telomerase reverse transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells (nhGMECs) and fibroblasts (nhGMFs).

Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

Expression of Telomerase Subunits in Gastric Cancer

To detect the expression of telomerase subunits （human telomerase reverse transcriptase, human telomerase associated protein 1 and human telomerase RNA） in gastric cancer and to examine the role that different telomerase subunits play in the gastric carcinogenesis, reverse transcription-polymerase chain reaction （RT-PCR） was used to detect telomerase suhunits messenger RNA in 24 samples of gastric cancer and corresponding non-cancerous tissue. The results showed that the positive rate of hTERT mRNA from gastric cancer and corresponding non-cancerous tissues was 100% and 25 %, respectively. The former was significantly higher than the latter （X^2 = 26.4, P〈0.01）. The positive rate of hTEP1 mRNA from gastric cancer and corresponding non-cancerous tissues was 100 % and 91.7%, respectively and no significant difference was found between them （X^2 =2.1, P〉0.05）. The positive rates of hTR for gastric cancer and corresponding non-cancerous tissues were both 100 % and no significant difference existed between them. It is concluded that in contrast to hTEP1 and hTR, the up-regulation of hTERT mRNA expression may play a more important role in the development of gastric cancer.

Comparing upper gastrointestinal X-ray and endoscopy for gastric cancer diagnosis in Korea

AIM:To compare the cost and accuracy of upper gastrointestinal(GI)X-ray and upper endoscopy for diagnosis of gastric cancer using data from the 2002-2004 Korean National Cancer Screening Program(NCSP). METHODS:The study population included 1 503 646 participants in the 2002-2004 stomach cancer screening program who underwent upper GI X-ray or endoscopy.The accuracy of screening was defined as the probability of detecting gastric cancer.We calculated the probability by merging data from the NCSP and the Korea Central Cancer Registry.We estimated the direct costs of the medical examination and the tests for up- per GI X-ray,upper endoscopy,and biopsy. RESULTS:The probability of detecting gastric cancervia upper endoscopy was 2.9-fold higher than via upper GI X-ray.The unit costs of screening using upper GI X-ray and upper endoscopy were$32.67 and$34.89, respectively.In 2008,the estimated cost of identifying one case of gastric cancer was$53094.64 using upper GI X-ray and$16 900.43 using upper endoscopy.The cost to detect one case of gastric cancer was the same for upper GI X-ray and upper endoscopy at a cost ratio of 1:3.7. CONCLUSION:Upper endoscopy is slightly more costly to perform,but the cost to detect one case of gastric cancer is lower.

Controversies in the diagnosis and management of early gastric cancer

Early diagnosis and treatment is the key to improving the prognosis of gastric cancer. The past decades have wimessed the rapid advances in the diagnosis and management of early gastric cancer （EGC）： endoscopy has played an increasingly important role, whereas laparoscopic techniques have also been introduced for EGC treatment. In China, the proportion of EGC is gradually increasing, and this condition will soon become a hot research topic. In this article, we will elucidate some major controversies in the diagnosis and management of EGC.

Expression of Telomerase Activity in Gastric Cancer Cells

Objective To study the relationship between telomerase activity and biological behavior in human gastric cancer cells and appraise the clinical significance of detecting telomerase activity.Methods The telomerase activity in 47 gastric cancer tissue samples , their matched normal tissues, 7 gastric ulcer and 2 gastric cancer cell lines was detected using a PCR-based non-radioisotopic telomeric repeat amplification protocol (TRAP) assay. Results None of the 47 samples from normal gastric tissues expressed telomerase activity. The 41 of 47 cases of gastric cancer presented telomerase activity with an 87.2 % positive rate (P < 0.001). 2/2 gastric cancer cell lines and 0/7 gastric ulcer line were also positive for telomerase activity. The activity of telomerase was associated with the pathological differentiation of gastric cancer. Conclusion Telomerase activity may be related to the biological behavior of gastric cancer and can help in assessing the malignant potential of gastric cancer. Telomerase activity will be a good diagnostic marker for the detection of gastric cancer.

Factors Affecting the Duration between Symptom Onset and Diagnosis in Patients with Gastric Cancer

Background: The prognosis of patients with tumors is partly influenced by the stage when patients are diagnosed. Therefore, the time of confirmed diagnosis after onset can be considered as a prognostic predictor. Although a few of studies work on it, factors that influence the duration remain poorly understood in different areas. Methods: This retrospective study involved patients with gastric cancer. Participants completed questionnaires by either phone or face-to-face interviews. Results: Females are with a longer interval than males. Farms lived in rural area and with New Rural Cooperative Medical Scheme are associated with a longer time interval. Patients whose income is mainly from their spouses also have a longer interval. Abdominal pain seems to be associated with longer interval time, while vomiting leads to a shorter time interval. Taking medicine after symptoms appear is associated with longer time intervals, especially those take medicine nonstandardly and more than 2 weeks. Conclusions: The results demonstrate that the medical resource in rural area should still be enhanced;meanwhile taking medicine without doctor’s advice should be cut down. Additional efforts must be made to devise strategies to properly guide patients’ behavior.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

Recent advances in gastric cancer early diagnosis

Gastric cancer(GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva,stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.

Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer

AIM:To evaluate the diagnostic effectiveness of white light endoscopy,magnifying endoscopy(ME),and magnifying narrow-band imaging endoscopy(ME-NBI) in detecting early gastric cancer(EGC).METHODS:From March 2010 to June 2012,a total of 3616 patients received screening for gastric cancer by magnifying endoscopy. There were 3675 focal gastric lesions detected using conventional high definition white light endoscopy(HD-WLE) in four different referentialhospitals that were recruited for further investigation using ME and ME-NBI. The images obtained from HD-WLE,ME,and ME-NBI were reviewed by four experienced endoscopists to evaluate their diagnostic effectiveness for EGC. The diagnosis of cancerous and non-cancerous lesions was conducted by evaluating the microvascular and microsurface patterns using the VS classification system. The final endoscopic diagnosis of each lesion was determined by consultation when a disagreement occurred. We used histopathological results as the gold standard for the diagnosis of EGC.RESULTS:Among the 3675 lesions found,1508 were validated by pathological findings as chronic gastritis,1279 as chronic gastritis with intestinal metaplasia,631 as low-grade neoplasia,and 257 as EGC. The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of HD-WLE for the diagnosis of EGC were 71.2%,99.1%,85.5%,97.9% and 97.1%,respectively. The results of ME for diagnosing EGC were 81.3%,98.8%,83.3%,98.6% and 97.6%,respectively. The results of ME-NBI for the diagnosis of EGC were 87.2%,98.6%,82.1%,99.0% and 97.8%,respectively. The diagnostic sensitivity and accuracy of paired ME and ME-NBI were significantly better than those of HD-WLE(P < 0.05).CONCLUSION:HD-WLE has a relatively high accuracy for diagnosing EGC and is an effective screening tool. Further investigations of ME and ME-NBI are required to achieve superior accuracy.

Non-invasive diagnosis of gastric mucosal atrophy in an asymptomatic population with high prevalence of gastric cancer

AIM: To validate a non-invasive method to detect gastric mucosal atrophy in a Chilean population with high prevalence of gastric cancer and a poor survival rate. METHODS: We first determined the optimal cut-off level of serum pepsinogen (PG)-1, PG-1/PG-2 ratio and 17-gastrin in 31 voluntary symptomatic patients (mean age: 66.1 years), of them 61% had histologically confirmed gastric atrophy. Then, in a population-based sample of 536 healthy individuals (209 residents in counties with higher relative risk and 327 residents in counties with lower relative risk for gastric cancer), we measured serum anti-H pylori antibodies, PG and 17-gastrin and estimated their risk of gastric cancer. RESULTS: We found that serum PG-1 < 61.5 μg/L, PG-1/PG-2 ratio < 2.2 and 17-gastrin > 13.3 pmol/L had a high specificity (91%-100%) and a fair sensitivity (56%-78%) to detect corpus-predominant atrophy. Based on low serum PG-1 and PG-1/PG-2 ratio together as diagnostic criteria, 12.5% of the asymptomatic subjects had corpus-predominant atrophy (0% of those under 25 years and 20.2% over 65 years old). The frequency of gastric atrophy was similar (12% vs 13%) but H pylori infection rate was slightly higher (77% vs 71%) in the high-risk compared to the low-risk counties. Based on their estimated gastric cancer risk, individuals were classified as: low-risk group (no H pylori infection and no atrophy; n = 115; 21.4%); moderate-risk group(H pylori infection but no atrophy; n = 354, 66.0%); and high-risk group (gastric atrophy, with or without H pylori infection; n = 67, 12.5%). The high-risk group was significantly older (mean age: 61.9 ± 13.3 years), more frequently men and less educated as compared with the low-risk group. CONCLUSION: We propose to concentrate on an upper gastrointestinal endoscopy for detection of early gastric cancer in the high-risk group. This intervention model could improve the poor prognosis of gastric cancer in Chile.

Role of symptoms in diagnosis and outcome of gastric cancer

Gastric cancer is one of the most common cancers and the second most common cause of cancer deaths worldwide. Apart from Japan, where screening programmes have resulted in early diagnosis in asymptomatic patients, in most countries the diagnosis of gastric cancers is invariably made on account on dyspeptic and alarm symptoms, which may also be of prognostic significance when reported by the patient at diagnosis. However, their use as selection criteria for endoscopy seems to be inconsistent since alarm symptoms are not sufficiently sensitive to detect malignancies. In fact, the overall prevalence of these symptoms in dyspeptic patients is high, while the prevalence of gastro-intestinal cancer is very low. Moreover, symptoms of early stage cancer may be indistinguishable from those of benign dyspepsia, while the presence of alarm symptoms may imply an advanced and often inoperable disease. The features of dyspeptic and alarm symptoms may reflect the pathology of the tumour and be of prognostic value in suggesting site, stage and aggressiveness of cancer. Alarm symptoms in gastric cancer are independently related to survival and an increased number, as well as specific alarm symptoms, are closely correlated to the risk of death.Dysphagia, weight loss and a palpable abdominal mass appear to be major independent prognostic factors in gastric cancer, while gastro-intestinal bleeding, vomiting and also duration of symptoms, do not seem to have a relevant prognostic impact on survival in gastric cancer.

Endoscopic ultrasound using ultrasound probes for the diagnosis of early esophageal and gastric cancers

Endoscopic ultrasound (EUS) devices were first designed and manufactured more than 30 years ago, and since then investigators have reported EUS is effective for determining both the staging and the depth of invasion of esophageal and gastric cancers. We review the present status, the methods, and the findings of EUS when used to diagnose and stage early esophageal and gastric cancer. EUS using high-frequency ultrasound probes is more accurate than conventional EUS for the evaluation of the depth of invasion of superficial esophageal carcinoma. The rates of accurate evaluation of the depth of invasion by EUS using high-frequency ultrasound probes were 70%-88% for intramucosal cancer, and 83%-94% for submucosal invasive cancer. But the sensitivity of EUS using high-frequency ultrasound probes for the diagnosis of submucosal invasive cancer was relatively low, making it difficult to confirm minute submucosal invasion. The accuracy of EUS using high-frequency ultrasound probes for early gastric tumor classification can be up to 80% compared with 63% for conventional EUS, although the accuracy of EUS using high-frequency ultrasound probes relatively decreases for those patients with depressed-type lesions, undifferentiated cancer, concomitant ulceration, expanded indications, type 0-I?lesions, and lesions located in the upper-third of the stomach. A 92% overall accuracy rate was achieved when both the endoscopic appearance and the findings from EUS using high-frequency ultrasound probes were considered together for tumor classification. Although EUS using high-frequency ultrasound probes has limitations, it has a high depth of invasion accuracy and is a useful procedure to distinguish lesions in the esophagus and stomach that are indicated for endoscopic resection.

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

AIM： To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology （PLC） examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.METHODS： Telomeric repeated amplification protocol （TRAP）-enzyme-linked immunosorbent assay （ELISA） was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen （PCNA） in gastric carcinoma was immunohistochemically examined.RESULTS： The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% （25/60）, and 25.0% （15/60）, respectively. The positive rate of telomerase activity was significantly higher than that Qf PLC in the group of pT, （15/16 vs 9/16, P 〈 0.05）, P1-3 （13/13 vs 9/13, P 〈 0.05） and diffuse type （22/42 vs 13/42, P 〈 0.05）. The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index （PI）, （55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ±10.18 vs 29.15 ±8.31, and 49.82 ± 6.74 vs 24.65 ±7.33, respectively, P 〈 0.05）.CONCLUSION： The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

Chinese guidelines for diagnosis and treatment of gastric cancer 2018(English version)

1.Overview2.Diagnosis2.1 Symptoms2.2 Signs2.3 Imaging 2.3.1 X-ray gas-barium double-contrast imaging 2.3.2 Ultrasonography(US)2.3.3 CT 2.3.4 MRI 2.3.5 Positron emission tomography(PET)-CT 2.3.6 Emission computerized tomography(ECT)2.3.7 Tumor biomarkers 2.3.8 Endoscopy 2.3.9 EUS2.4 Diagnostic criteria and contents of gastric cancer 2.4.1 Qualitative diagnosis 2.4.2 Staging diagnosis 2.4.3 Clinical manifestations.

Pathological diagnosis is maybe non-essential for special gastric cancer: Case reports and review

Histopathological results are critical for the diagnosis and surgical decision regarding gastric cancer. How-ever, opposite opinions from radiology and pathology can sometimes affect clinical decisions. The two cases reported in this article were both highly suspected as gastric cancer by clinical manifestations and radiologic findings, although both showed negative results in the first biopsy examination. One was confirmed as gastric cancer by the time of the 6 th biopsy, while the other was still negative even after 8 biopsies. With a definite pathologic result and the agreement of the patient for the latter case, both of them finally received surgery. Postoperative pathological examination revealed find-ings that were the same as Borrmann type Ⅳ gastric cancer. We believed that duplicate biopsies under ra-diologic guidance were necessary for highly suspected gastric cancer cases in the absence of a definite pathol-ogy result, and patients should be under close follow-up. We propose that, if gastric cancer is highly sus-pected when typical radiology changes of widely diffuse gastric parietal lesions suffice to exclude lymphoma and other similar situations, and even in absence of a posi-tive biopsy result, a diagnostic laparotomy under lapa-roscopy and even radical gastrectomy may be reason-ably performed by an experienced gastric cancer center with the agreement of the patient after being decided by a multidisciplinary discussion team.

Diagnosis of boundary in early gastric cancer

Endoscopic submucosal dissection (ESD) is an advanced therapeutic endoscopic technique,which allowsresection of larger superficial tumors in the esophagus,stomach,and colon.Precise diagnosis of the boundary between tumor and the non-tumorous surrounding portion is especially important before starting ESD,because too much resection can potentially take more time and can induce a higher complication rate,while too little resection can result in a non-curative resection.The boundary diagnosis is often difficult for early gastric cancer,mainly because of the underlying condition of chronic gastritis.Due to recent developments in endoscopy,including magnified endoscopy and narrow band endoscopy,the boundary diagnosis is becoming easy and more accurate.We have also applied magnified endoscopy combined with narrow band imaging to fresh specimens immediately after resection using thetiling method and XY stage.

Chinese quality control indices for standardized diagnosis and treatment of gastric cancer(2022 edition)

Gastric cancer is one of the most common malignancies of the digestive system,and the number of deaths continues to increase.The standardized management of the diagnosis and treatment of gastric cancer is challenging due to the great differences in the diagnosis and treatment of gastric cancer in different regions.The Gastric Cancer Expert Committee of the National Cancer Quality Control Center(NCQCC)identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of gastric cancer.The Gastric Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization,uniformity,and normalization of gastric cancer diagnosis and treatment,which ultimately improved the survival rate and quality of life of gastric cancer patients.A panel of experts with gastrointestinal cancer surgery,gastrointestinal cancer medicine,medical imaging,pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of gastric cancer.The authors then utilized a modified Delphi approach to generate consensus recommendations.

Determination of telomerase activity and its clinical significance in gastric cancer and premalignant lesions

In order to explore the role of telomerase activity (TA) in the development and progression of gastric cancer (GC) and if TA can be used as an indicator for the early diagnosis of GC, TA in 176 specimens of gastric mucosa of 57 cases of chronic atrophic gastritis (CAG), 18 intestinal metaplasia (IM), 8 dysplasia (Dys), 65 GC obtained through operation or endoscopy was determined with PCR-based TRAP assay. Meanwhile, operative specimens of GC were analyzed with serial dilution. It was found that TA was detected in 24. 6% of CGA, 38. 9% of IM, 37.5% of Dys and 92.3% of GC, but not detected in 28 cases of normal tissues. TA detection was not related to patients’ sex, tumor location, size, depth of invasion, differentiation, lymph node metastasis and clinicalstage. Telomerase activity in premalignant lesions indicates that it plays a crucial role in the development and progression of GC. Thus the determination of telomerase activity is helpful to predict the progress of premalignant changes and to diagnose early GC.

Analysis of the diagnosis and treatment of 78 gastric cancer cases in young people

Objective: To summarize the causes of difficulty in gastric cancer diagnosis in young people and explore potential methods of improving diagnostic accuracy. Methods: We retrospectively analyzed 78 cases of gastric cancer in young people (14–35 years). Results: The clinical manifestations of gastric carcinoma in young people show no specificity, and the initial symptoms were diverse, with discomfort in the upper abdomen as the main symptom. There are four causes of difficulty in early detection: (1) The previous physician relied on antacids and did not use or analyze the results of gastroscopic examination and barium meal examination of the upper digestive tract; (2) The physician performing the endoscopic examination did not strictly follow the standards in the biopsy of fine pathological changes in suspected early cancer; (3) The physician lacked a good understanding of the clinical progress of ulcerating-healing-ulcerating in the ulcerating type of early gastric cancer; (4) Lacked a good understanding of precancerous lesions in the gastric mucosa. Conclusion: Early gastroscopy and pathological examina- tion must be conducted for people who above 20 years of age with one or more of the following symptoms: dull pain in the upper abdomen, anorexia, fatigue, tarry stool and vomiting of unknown origin. The results of gastroscopic examination should be taken into consideration for patients with recurrent ulcer, and biopsy should be standardized. Biopsy specimens should be taken from several loci in the suspected lesions, and should be repeated if necessary. Precancerous lesions of gastric mucosa should be closely followed up using gastroscopy.