Contrast-enhanced endoscopic ultrasound for swollen lymph nodes.

Endoscopic ultrasound (EUS) is an important tool for the evaluation of lymphadenopathy, especially in intra-thoracic or intra-abdominal regions. EUS also provides tissue diagnosis via EUS fine-needle aspiration or biopsy. To select the target for biopsy or aspiration, conventional B-mode images are used for the evaluation, but this approach still lacks diagnostic accuracy. Contrast-enhanced EUS has been used to evaluate the vascularity of lesions. Most malignant lymphadenopathy shows heterogenous enhancement or defect of enhancement, while quantitative studies using time-intensity curves in contrast-enhanced harmonic EUS show a rapid decline in enhancement pattern. These findings are useful as an auxiliary method for tissue diagnosis or in cases in which tissue diagnosis is contraindicated.

Evaluation of the ex-vivo porcine simulator on EUS-guided cystogastrostomy using lumen-apposing metal stent training.

Bckground and Objectives: EUS-guided cystogastrostomy is a well-established advanced endoscopic technique with a steep-learning curve which necessitates an ex-vivo simulator that would allow for adequate training. The aim of this study is to evaluate the feasibility of the model in allowing training for EUS-guided cystogastrostomy using lumen-apposing metal stent (LAMS). Subjects and Methods: The model was created by ROEYA Training Center, Egypt, using native porcine tissue to create fluid collections simulating both cystic and solid lesions. It was designed and tested in advance while the hydrogel was added on-site. The simulator was evaluated prospectively in five training sessions involving 17 international experts. The task was to successfully deploy the LAMS to drain the created cyst. After using the simulator, the experts were asked to fill a questionnaire to assess their experience. The primary endpoint was overall satisfaction with the model as a training tool. Results: All of the experts were satisfied with the model as a tool to train endoscopists for the technique. 76.5% (n = 11) of the experts thought the model to be moderately realistic. Proper visualization was reported by 94.1% of the experts. All experts believed the lesions to be either slightly like or very similar to real lesions. The model was graded "easy" in difficulty by 11 of the experts. Conclusions: In all parameters assessed, the experts thought the model to be a useful tool for future training. This preliminary study suggests that the aforementioned simulator can be used to train endoscopists on using LAMS in a risk-free environment.

Consensus guidelines on the role of cholangioscopy to diagnose indeterminate biliary stricture.

BACKGROUND: Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. METHODS: The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. RESULTS: Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. CONCLUSION: Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.

Serum Helicobacter pylori antibody reactivity in seven Asian countries using an automated latex aggregation turbidity assay.

BACKGROUND AND AIM: To determine the application range of diagnostic kits utilizing anti-Helicobacter pylori antibody, we tested a newly developed latex aggregation turbidity assay (latex) and a conventional enzyme-linked immunosorbent assay (E-plate), both containing Japanese H. pylori protein lysates as antigens, using sera from seven Asian countries. METHODS: Serum samples (1797) were obtained, and standard H. pylori infection status and atrophy status were determined by culture and histology (immunohistochemistry) using gastric biopsy samples from the same individuals. The two tests (enzyme-linked immunosorbent assay and latex) were applied, and receiver operating characteristics analysis was performed. RESULTS: Area under the curve (AUC) from the receiver operating characteristic of E-plate and latex curves were almost the same and the highest in Vietnam. The latex AUC was slightly lower than the E-plate AUC in other countries, and the difference became statistically significant in Myanmar and then Bangladesh as the lowest. To consider past infection cases, atrophy was additionally evaluated. Most of the AUCs decreased using this atrophy-evaluated status; however, the difference between the two kits was not significant in each country, but the latex AUC was better using all samples. Practical cut-off values were 3.0 U/mL in the E-test and 3.5 U/mL in the latex test, to avoid missing gastric cancer patients to the greatest extent possible. CONCLUSIONS: The kits were applicable in all countries, but new kits using regional H. pylori strains are recommended for Myanmar and Bangladesh. Use of a cut-off value lower than the best cut-off value is essential for screening gastric cancer patients.

Endoscopic ultrasound-guided fine-needle aspiration of the left adrenal mass accessed via the gastrostomy tract: A case report with video.

INTRODUCTION AND IMPORTANCE: An adrenal metastasis is uncommon in esophageal cancer. Its diagnosis could be challenging if a percutaneous approach was inaccessible. Moreover, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), a useful adrenal sampling technique, is complicated by the luminal obstruction. CASE PRESENTATION: A patient with esophageal cancer accompanying by adrenal mass and established gastrostomy was described. The EUS-FNA of the adrenal lesion was successfully performed via the dilated gastrostomy tract. Adequate tissue for pathological examination was achieved, and the result indicated metastatic squamous cell carcinoma. Chemotherapy was started accordingly. CLINICAL DISCUSSION: This report described an uncommon event of adrenal metastasis of esophageal primary. Even though it is possible to perform EUS via the gastrostomy tract, performing EUS from an unusual direction might add some difficulty to an endoscopist, considering that EUS involves image pattern recognition in identifying structures. Thus, this technique should be operated by experienced EUS endoscopists. CONCLUSION: Gastrostomy can provide an enteral route for nutrition support in esophageal cancer patients. In addition, it could be an alternative EUS intervention portal when an esophageal stent is not accessible.

ERCP plus endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage for malignant hilar biliary obstruction: a multicenter observational open-label study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may not provide complete biliary drainage in patients with Bismuth III/IV malignant hilar biliary obstruction (MHBO). Complete biliary drainage is accomplished by adding percutaneous transhepatic biliary drainage (PTBD). We prospectively compared recurrent biliary obstruction (RBO) rates between combined ERCP and endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. bilateral PTBD. METHODS: Patients with MHBO undergoing endoscopic procedures (group A) were compared with those undergoing bilateral PTBD (group B). The primary outcome was the 3-month RBO rate. RESULTS: 36 patients were recruited into groups A (n = 19) and B (n = 17). Rates of technical and clinical success, and complications of group A vs. B were 84.2 % (16/19) vs. 100 % (17/17; P = 0.23), 78.9 % (15/19) vs. 76.5 % (13/17; P > 0.99), and 26.3 % (5/19) vs. 35.3 % (6/17; P = 0.56), respectively. Within 3 and 6 months, RBO rates of group A vs. group B were 26.7 % (4/15) vs. 88.2 % (15/17; P  = 0.001) and 22.2 % (2/9) vs. 100 % (9/9; P = 0.002), respectively. At 3 months, median number of biliary reinterventions in group A was significantly lower than in group B (0 [interquartile range] 0-1 vs. 1 [1-2.5]), respectively (P < 0.001). Median time to development of RBO was longer in group A than in group B (92 [56-217] vs. 40 [13.5-57.8] days, respectively; P  =  0.06). CONCLUSIONS: Combined ERCP and EUS procedures provided significantly lower RBO rates at 3 and 6 months vs. bilateral PTBD, with similar complication rates and no significant mortality difference.

Population-based study of Helicobacter pylori infection and antibiotic resistance in Bhutan.

OBJECTIVES: Bhutan suffers from a high prevalence of Helicobacter pylori (H. pylori) infection and gastric cancer-related mortality. In preparation for a countrywide H. pylori eradication program, the antibiotic resistance patterns of H. pylori infection were surveyed in different geographical regions. METHODS: Dyspeptic patients in 6 districts including Thimphu, Punakha, Wangdue, Trongsa, Bumthang, and Haa underwent upper gastrointestinal endoscopy during GASTROCAMP and were enrolled between December 2010 and April 2015. Gastric biopsies were obtained for rapid urease test, histopathology, and H. pylori culture. Antimicrobial susceptibility testing was later performed if the culture was positive. RESULTS: A total of 1178 patients were surveyed. The overall H. pylori infection in Bhutan was 66.2%. Punakha had the highest prevalence of H. pylori infection (85.6%). Thimphu and Punakha (city areas) had higher prevalence of H. pylori infection than rural districts (73.5% vs 63.3%, OR=1.61, 95% CI 1.22-2.13, p=0.0008). There were 357 patients (30.3%) with positive H. pylori culture completed antimicrobial susceptibility testing. The mean age was 40.5 years with female predominance (57.1%). No amoxicillin resistant strains were found. Metronidazole resistance was 81% followed by levofloxacin resistance (8.1%). Clarithromycin (2%) and tetracycline (0.6%) resistance was rare except in Thimphu, the capital city (10%) vs 0% in rural areas, p<0.001. The metronidazole resistance rate remained stable at approximately 80% during the past 5 years of study. Levofloxacin-resistant strains gradually rose from 5.3% in 2010 to 9.9% in 2015. CONCLUSIONS: Bhutan had a high prevalence of H. pylori infection. Metronidazole resistance was extremely high, whereas clarithromycin resistance was quite low in this specific area. Antibiotic resistance pattern could be good evidence for guiding a proper treatment regimen for H. pylori infection in Bhutan.

Prevalence and Antibiotic Resistance Patterns of Helicobacter pylori Infection in Koh Kong, Cambodia.

BACKGROUND: Gastric cancer, which is the leading cause of cancer mortality in Cambodia, can be prevented by Helicobacter pylori (H. pylori) eradication. There is limited data about H. pylori strains in Cambodia. This study aimed to evaluate H. pylori prevalence and antibiotic resistance in Koh Kong, Cambodia. METHODS: 118 Cambodian dyspeptic patients were scheduled to enter this study and 58 were enrolled between July and September 2019. All patients underwent upper GI endoscopy. 3 gastric biopsies were obtained for rapid urease test, H. pylori culture with E-test and GenoType® HelicoDr (Hain Lifescience factory, Germany). 3-mL blood sample was collected for CYP2C19 genotyping. RESULTS: 58 subjects were enrolled (40 females, 18 males, mean age 43.8 years). Overall H. pylori prevalence was 31.0%. Antibiotic resistance rates were 78.6% for metronidazole, 50.0% for fluoroquinolones, and 27.8% for clarithromycin. There was no amoxicillin and tetracycline resistance. More than half of H. pylori strains (57.1%) were multidrug-resistant. Most (35.7%) were resistant to metronidazole and quinolone. Poor, intermediate and rapid metabolizers were 5.5%, 38.9% and 55.6%, respectively. CONCLUSIONS: H. pylori infection remains common infection in Cambodia. High prevalence of clarithromycin, metronidazole, levofloxacin and multidrug-resistant H. pylori is still major problems in Cambodia. Treatment regimens without clarithromycin and quinolone such as 14-day bismuth-based quadruple therapy might be an appropriate choice for H. pylori eradication in this particular area.

Efficacy of Omeprazole, Tetracycline, and 4 Times Daily Dosing of Amoxicillin in Helicobacter pylori Eradication in Limited Resource Area in Bhutan: A Prospective Randomized Trial (BHUTAN Study).

Backgrourd: H. pylori-associated gastric cancer is the first cancer-related death in Bhutan. Effective regimen for H. pylori eradication is essential to reduce risk of developing gastric cancer. Clarithromycin is not widely used in this limited resource country. Aim of this study was to evaluate proper regimen and prevalence of antibiotic resistance pattern for H. pylori eradication in Bhutan. METHODS: Five hundred and forty-six patients underwent gastroscopy during GASTROCAMP between October 2014 and April 2015 in Bhutan and 77 patients were enrolled. Four gastric biopsies were obtained for rapid urease test, histopathology, H. pylori culture with Epsilometer test. All H. pylori-positive patients were randomized to receive either 7-day or 14-day of 500 mg amoxicillin four times daily, 500 mg tetracycline four times daily, and 20 mg omeprazole twice daily. RESULTS: Seventy-seven subjects were enrolled (54 females, 23 males, mean age = 45.4 years). Of 77 patients, 52 (67.5%) received 7-day regimen while 25 (32.5%) had 14-day regimen. Prevalence of H. pylori was 38.2%. Antibiotic resistance was 80.0% for metronidazole, 11.1% for levofloxacin and no resistance seen in amoxicillin, tetracycline and clarithromycin. Overall eradication rates of 7-day and 14-day regimens were 51.9% and 80.0%, p = 0.02. Female and age ≥40 years had significantly higher eradication rate when receiving 14-day compared to 7-day regimen (94.1% vs. 45.9%, OR = 18.82; 95% CI 2.26-157.02, p = 0.0007 and 86.7% vs. 50.0%, OR = 6.50; 95% CI 1.25-33.91, p = 0.02, respectively). CONCLUSIONS: Fourteen-day regimen might be an acceptable regimen for H. pylori eradication in limited resource area such as Bhutan. Female and age ≥40 years should receive longer duration of treatment. This 14-day regimen could at least reduce the risk of developing H. pylori-associated diseases especially peptic ulcer with complications and gastric cancer which lead to many deaths in Bhutan.
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Serum pepsinogens as a gastric cancer and gastritis biomarker in South and Southeast Asian populations.

Serum pepsinogens have been widely acknowledged as gastric mucosal biomarkers; however, a multicountry report on the benefits of pepsinogens as biomarkers has not yet been published. We analyzed 1,206 sera and gastric mucosal samples collected from Bangladesh, Bhutan, Indonesia, Myanmar, Nepal and Thailand then assessed the association between gastric mucosal changes and Helicobacter pylori infection. The new cutoff values for serum pepsinogen values were evaluated using a receiver operating characteristic analysis. The participants with H. pylori infection had significantly lower pepsinogen I and higher pepsinogen II values, but a lower pepsinogen I/II ratio than participants without the infection (all P < .001). The pepsinogen I and pepsinogen I/II values were significantly higher and lower, respectively, in individuals with atrophic gastritis than in those without (both P < .001). Among uninfected individuals, only the pepsinogen I/II ratio was significantly lower in atrophic individuals. Pepsinogen I/II ratio also were significantly different between disease among H. pylori-positive and H. pylori-negative individuals, suggesting the pepsinogen I/II ratio is a robust biomarker for determining both chronic and atrophic gastritis. The cutoffs for detecting chronic and atrophic gastritis for the pepsinogen I/II ratio were 4.65 and 4.95, respectively. In conclusion, pepsinogen levels are useful biomarker for both chronic gastritis and atrophic gastritis, but they should be used with caution. Population-based validation is necessary to determine the best cutoff values. Among all pepsinogen values, the pepsinogen I/II ratio was the most reliable gastric mucosal-change biomarker.

Endoscopic Ultrasound-Guided Vascular Therapy for Portoduodenal Fistula.

Portoenteric fistula is a rare cause of massive upper gastrointestinal bleeding. Most cases can be treated with radiointervention or surgery, but portoenteric fistula is associated with a high mortality. We reported a case of intermittent massive upper gastrointestinal bleeding in a 33-year-old man with cholangiocarcinoma who underwent surgical resection followed by chemoradiation. A portoduodenal fistula due to chronic duodenal ulceration was identified. The bleeding was successfully controlled by endoscopic ultrasound-guided coil placement through the duodenal bulb using the anchoring technique. Follow-up endoscopy and computed tomography scan showed multiple coil placements between a part of the portal vein and the duodenal bulb without any evidence of portal vein thrombosis. There were no complications, and bleeding did not recur during the 8-month follow-up period.

International consensus statements for endoscopic management of distal biliary stricture.

Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico-biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato-biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS.

An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions.

BACKGROUND AND OBJECTIVES: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. METHODS: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. RESULTS: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. CONCLUSION: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Endoscopic ultrasound in diagnosis of solid pancreatic lesions: Elastography or contrast-enhanced harmonic alone versus the combination.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) elastography (EUS-E) and contrast-enhanced harmonic EUS (CH-EUS) are useful methods for the diagnosis of pancreatic lesions. This study aims to compare the accuracy of combined EUS-E and CH-EUS with that of EUS-E or CH-EUS alone in the differential diagnosis of pancreatic solid lesions. PATIENTS AND METHODS: One hundred thirty-six patients with solid pancreatic lesions underwent EUS with both EUS-E and CH-EUS were included. Diagnoses were classified as adenocarcinoma, neuroendocrine tumor (NET), and inflammatory pseudotumor in 95, 22, and 19 patients, respectively. EUS records in each case were rearranged into 3 groups: EUS-E, CH-EUS, and combination. Each modality was randomly reviewed by 3 reviewers with different levels of clinical experience. Sensitivity, specificity, and accuracy of each modality according to each diagnosis group were evaluated. For the combined diagnosis populations, the proportions of correct diagnoses among the 3 modalities were compared by using the multivariate logistic regression analysis. RESULTS: The accuracies of EUS-E, CH-EUS, and the combination of them were 68.4 %, 65.4 %, and 75.7 %, respectively, for adenocarcinoma group; 83.8 %, 82.4 %, and 86.8 % for NET group; 80.1 %, 78.7 %, and 81.6 % for inflammatory pseudotumor group. The multivariate logistic regression analysis for the combined diagnosis populations showed that the proportion of correct diagnoses when EUS-E and CH-EUS were combined was slightly higher than with the other 2 modalities, although the significant differences among them were not observed. CONCLUSION: EUS-E and CH-EUS combined may improve differential diagnosis of solid pancreatic lesions compared with use of the individual modalities.

Prevalence, risk factors, and virulence genes of Helicobacter pylori among dyspeptic patients in two different gastric cancer risk regions of Thailand.

Gastric cancer risk is varied among different regions of Thailand. We examined the characteristics of Helicobacter pylori infection in two regions of Thailand. The H. pylori status of 273 dyspeptic patients (136 from the South and 137 from the North; a low and high incidence of gastric cancer region, respectively) was evaluated, and virulence genotypes (cagA, vacA, hrgA and jhp0562-positive/ß-(1,3)galT) were determined. The overall H. pylori infection rate was 34.1% (93/273). The prevalence was higher in the North than in the South (50.4% vs. 17.6%, P <0.001) and was significantly higher among individuals with the following characteristics: low income, birthplace in the Northeast or North regions, agricultural employment, or consumption of alcohol or unboiling water. Among these socio-demographic determinants, region was an independent risk factor for H. pylori infection (odds ratio = 6.37). Patients including both H. pylori infected and uninfected cases who lived in the North had significantly more severe histological scores than those in the South. In contrast, among H. pylori-positive cases, patients in the South had significantly more severe histological scores than those in the North. Of the 74 strains cultured, 56.8% carried Western-type cagA, with a higher proportion in the South than in the North (76.2% vs. 49.1%, P = 0.05). In disagreement with the current consensus, patients infected with the Western-type cagA strains had more severe inflammation scores in the antrum than those infected with the East Asian-type cagA strains (P = 0.027). Moreover, Western-type cagA strains induced more severe histological scores in patients from the South than those of either genotype from the North. Other virulence genes had no influence on histological scores. The incidence of gastric cancer in Thailand was different among regions and corresponded to differences in the prevalence of H. pylori infection. More careful follow-up for patients in the South will be required, even if they are infected with H. pylori carrying Western-type cagA.

Helicobacter pylori virulence genes of minor ethnic groups in North Thailand.

BACKGROUND: There are few studies analyzed concurrently the prevalence and genotypes of Helicobacter pylori infection with the ancestor origins from different ethnics, especially with including minority groups. We recruited a total of 289 patients in MaeSot, Thailand (154 Thai, 14 Thai-Chinese, 29 Karen and 92 Hmong ethnics). The virulence genes and genealogy of the strains were determined by PCR-based sequencing. RESULTS: Based on culture and histology/immunohistochemistry, the prevalence of H. pylori infection was 54.5% (158/289). Among 152 isolates cultured, the East-Asian-type cagA was predominant genotype among strains from Hmong, Thai-Chinese and Thai (96.0% [48/50], 85.7% [6/7] and 62.7% [47/75], respectively), whilst majority of strains from Karen had Western-type cagA (73.3% [11/15]). Patients infected with the East-Asian-type cagA strains had significantly higher activity and intestinal metaplasia in the antrum and activity in the corpus than those with Western-type cagA (P = 0.024, 0.006 and 0.005, respectively). The multilocus sequencing typing analysis discriminated that most strains from Hmong and Thai-Chinese belonged to hspEAsia (92.0 and 85.7%, respectively), whereas strains from Karen predominantly possessed hpAsia2 (86.7%) and strains from Thai were classified into hspEAsia (45.2%) and hpAsia2 (31.1%). CONCLUSIONS: Helicobacter pylori genotypes were relatively different among ethnic groups in Thailand and were associated with the source of ancestor even living in a small rural town. Caution and careful check-up are required especially on Hmong ethnic associated with high prevalence of virulence genotypes of H. pylori.

Impact of Fecal Hb Levels on Advanced Neoplasia Detection and the Diagnostic Miss Rate For Colorectal Cancer Screening in High-Risk vs. Average-Risk Subjects: a Multi-Center Study.

OBJECTIVES: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to identify high-risk subjects for advanced neoplasia. However, the appropriate fecal immunochemical test (FIT) cutoff for high-risk population may be different from that of average-risk population. We aimed to evaluate the FIT performance at different cutoffs in high-risk subjects undergoing colorectal cancer (CRC) screening. METHODS: We prospectively enrolled asymptomatic subjects aged 50-75 years. Using the APCS score, subjects were stratified into either the average-risk or high-risk groups. All subjects were tested with one-time quantitative FIT and underwent colonoscopy. We compared the FIT performance for advanced neoplasia between two groups using different cutoffs (5 (FIT5), 10 (FIT10), 20 (FIT20), 30 (FIT30), and 40 (FIT40) µg Hb/g feces). RESULTS: Overall, 1,713 subjects were recruited, and 1,222 (71.3%) and 491 (28.7%) were classified as average-risk and high-risk, respectively. Advanced neoplasia was detected in 90 (7.4%) of the average-risk subjects and 65 (13.2%) of the high-risk subjects. In the high-risk group, by decreasing the cutoff from FIT40 to FIT5, the sensitivity increased by 33.8 percentage points with decreased specificity by 11 percentage points. In the average-risk group, the sensitivity increased by 20 percentage points with decreased specificity by 9.6 percentage points. At the lowest cutoff (FIT5), the number of needed colonoscopies to find one advanced neoplasia was 2.8 and 6.1 for the high-risk and average-risk groups, respectively. CONCLUSIONS: Using an appropriate FIT cutoff for CRC screening in high-risk subjects could improve CRC screening performance and reduce the unnecessary colonoscopies. To maintain high sensitivity and specificity for advanced neoplasia, the optimal cutoff FIT in the high-risk subjects should be lower than that in the average-risk subjects.

Interleukin-17C in Human Helicobacter pylori Gastritis.

The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases remains to be determined.