Usefulness of the l-type Wako Helicobacter pylori antibody J test.

BACKGROUND AND AIM: Helicobacter pylori antibody levels in the blood are currently measured using an ELISA. In April 2016, FUJIFILM Wako Pure Chemical Corporation launched the "l-type Wako Helicobacter pylori antibody J" test, which is based on the latex agglutination turbidimetric immunoassay. In this study, we investigated the usefulness of the Wako test. METHODS: We measured H. pylori antibody levels using both the ELISA and Wako test in 180 patients who underwent upper gastrointestinal endoscopy at our hospital between September 2017 and February 2019. Ninety patients were infected with H. pylori. We calculated the diagnostic accuracy, sensitivity, and specificity of each test and the concordance rate between the ELISA and Wako test. If lower limits of 90% confidence intervals (CIs) for each diagnostic validity exceeded the 85% threshold, the usefulness of the diagnostic test was confirmed. RESULTS: The diagnostic accuracy, sensitivity, and specificity were 94.4% (90% CI, 90.8-97.0%), 94.4% (90% CI, 88.7-97.8%), and 94.4% (90% CI, 88.7-97.8%), respectively, when the Wako test was used, and 94.4% (90% CI, 90.8-97.0%), 88.9% (90% CI, 81.9-93.8%), and 100% (90% CI, 96.0-100%), respectively, when the ELISA was used. The concordance rate between the two tests was high (κ = 0.8444). CONCLUSIONS: We confirmed the usefulness of the Wako test, especially when screening for H. pylori infection, due to its high sensitivity.

A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori (H. pylori) eradication is usually assessed using the 13C-urea breath test (UBT), anti-H. pylori antibody and the H. pylori stool antigen test. However, a few reports have used pepsinogen (PG), in particular, the percentage change in the PG I/II ratio. Here, we evaluated the usefulness of the percentage changes in serum PG I/II ratios for determining the success of eradication therapy for H. pylori. MATERIALS AND METHODS: In total, 650 patients received eradication therapy from October 2008 to March 2013 in our Cancer Institute Hospital. We evaluated the relationship between H. pylori eradication and percentage changes in serum PG I/II ratios before and 3 months after treatment with CLEIA® (FUJIREBIO Inc, Tokyo, Japan). The gold standard of H. pylori eradication was defined as negative by the UBT performed 3 months after completion of eradication treatment. Cut-off values for percentage changes in serum PG I/II ratios were set as +40, +25 and +10% when the serum PG I/II ratio before treatment was below 3.0, above 3.0 but below 5.0 and 5.0 or above, respectively. RESULTS: Serum PG I and PG II levels were measured in 562 patients with H. pylori infection before and after eradication therapy. Eradication of H. pylori was achieved in 433 patients studied (77.0%). The ratios of first, second, third-line and penicillin allergy eradication treatment were 73.8% (317/429), 88.3% (99/112), 75% (12/16) and 100% (5/5), respectively. An increasing percentage in the serum levels of the PG I/II ratios after treatment compared with the values before treatment clearly distinguished success from failure of eradication (108.2±57.2 vs. 6.8±30.7, p<0.05). Using the above cut-off values, the sensitivity, specificity and validity for determination of H. pylori were 93.1, 93.8 and 93.2%, respectively. CONCLUSION: In conclusion, the percentage changes in serum PG I/II ratios are useful as evaluation criteria for assessing the success of eradication therapy for H. pylori.

Genome-wide gene expression profile of jejunal pouch mucosa as a gastric substitute.

BACKGROUND/AIMS: Gastric cancer is the most common cancer in Japan. Genome-wide gene expression in the jejunal pouch mucosa was examined using a DNA microarray and quantitative real-time PCR (qPCR) to evaluate the safety, especially with regard to carcinogenic changes, of the jejunal pouch in patients who showed long-term survival. METHODOLOGY: Biopsy samples of jejunal pouch and jejunal conduit were collected from four patients who had undergone gastrectomy 9 to 13 years previously. Total RNA was extracted, amplified to give complementary RNA, labeled with Cyanine 3-CTP and hybridized with a whole human genome oligo microarray (44k). Gene expression was confirmed partly by qPCR. RESULTS: Although some changes in the expression of 417 reported cancer genes were observed with the DNA microarray, crucial changes related to small intestinal adenocarcinoma were not observed. Changes in the expression of eight genes related to small intestinal adenocarcinoma were also not detected by qPCR. CONCLUSIONS: Crucial changes in the expression of genes related to small intestinal adenocarcinoma were not observed in the jejunal pouch of these four patients with gastric cancer by either DNA microarray or qPCR. The present results support the safety of the use of a jejunal pouch with a food pooling function in patients who show long-term survival after gastrectomy.

Gastric cancer screening by combined assay for serum anti-Helicobacter pylori IgG antibody and serum pepsinogen levels - "ABC method".

The current status of screening for gastric cancer-risk (gastritis A, B, C, D) method using combined assay for serum anti-Helicobacter pylori (Hp) IgG antibody and serum pepsinogen (PG) levels, "ABC method", was reviewed and the latest results of our ongoing trial are reported. It was performed using the following strategy: Subjects were classified into 1 of 4 risk groups based on the results of the two serologic tests, anti-Hp IgG antibody titers and the PG I and II levels: Group A [Hp(-)PG(-)], infection-free subjects; Group B [Hp(+)PG(-)], chronic atrophic gastritis (CAG) free or mild; Group C [Hp(+)PG(+)], CAG; Group D [Hp(-)PG(+)]), severe CAG with extensive intestinal metaplasia. Continuous endoscopic follow-up examinations are required to detect early stages of gastric cancer. Asymptomatic Group A, which accounts for 50-80% of all the subjects may be excluded from the secondary endoscopic examination, from the viewpoint of efficiency. Hp-infected subjects should be administered eradication treatment aimed at the prevention of gastric cancer.

Endoscopic diagnosis of intraductal papillary-mucinous neoplasm of the pancreas by means of peroral pancreatoscopy using a small-diameter videoscope and narrow-band imaging.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) is an intraductal tumor in which the mucin-producing epithelium shows proliferated papillary and a wide variety of pathological changes ranging from hyperplasia to adenocarcinoma. Therefore, it is important to determine whether an IPMN is benign or malignant. In the present study of patients with IPMN, the protrusion was observed by a peroral pancreatoscopy (PPS) using a small-diameter videoscope and narrow-band imaging (NBI). We carried out the differential diagnosis of benign lesion to malignant lesion. METHODS: Between April 2003 and May 2009, PPS using a small-diameter videoscope by means of NBI was carried out on 21 hospitalized patients with IPMN (10 cases of adenocarcinoma, 11 cases of adenoma or hyperplasia; 14 males and seven females, with a mean age of 69.4 years). RESULTS: Fifteen focal lesions of the 16 cases in the head of the pancreas (93.7%) and four focal lesions of the five cases in the pancreatic body (80%) were observable, whereas two lesions (adenocarcinoma in the pancreatic body, and adenoma in the uncus of pancreas) were not observable. Endoscopically, seven cases were classified as villous type and two cases as vegetative type, and nine cases were diagnosed as adenocarcinoma. Ten cases with sessile type or semipedunculated type were diagnosed as adenoma or hyperplasia. Vascular patterns and protrusions were detected more clearly in the NBI images than under white light observation. CONCLUSIONS: When combined with a videoscope and NBI, pancreatoscopy provided a clear image and was useful for evaluating whether the IPMN was benign or malignant.

Prescreening of a high-risk group for gastric cancer by serologically determined Helicobacter pylori infection and atrophic gastritis.

BACKGROUND: Though gastric cancer screening by X-ray examination has been confirmed to be effective for reducing gastric cancer mortality, decreases in efficiency have been pointed out. Establishment of an effective screening system, focusing on high-risk status such as Helicobacter pylori infection and atrophic gastritis, is desirable. To date, combined use of serum anti-Helicobacter pylori antibodies and pepsinogen measurement has been assessed prospectively in participants in opportunistic and workplace health check-ups; however, there are no reports of population-based cohort study. AIMS: To clarify the population-based risk of Helicobacter pylori infection and atrophic gastritis for gastric cancer, a cohort study was conducted in rural towns in Kyoto Prefecture. METHODS: Subjects were 1,011 males and 1,848 females recruited in a health check-up in 1987. Their serum was examined for anti-Helicobacter pylori antibodies and pepsinogen I and II. Gastric cancer cases were assessed from the cancer registry of those towns. RESULTS: Up to the end of 1996, 33 males and 28 females developed gastric cancer. A sex- and age-adjusted hazard ratio was calculated by Cox's proportional model. Helicobacter pylori infection increased the risk of gastric cancer even when the subjects had no atrophy (hazard ratio =4.20; 95% confidence interval, 0.96-18.40). The risk increased further when they had both Helicobacter pylori infection and atrophy (hazard ratio =11.23; 95% confidence interval, 2.71-46.51). Subjects with atrophy but negative for anti-Helicobacter pylori antibodies had the highest risk (hazard ratio =14.81; 95% confidence interval, 2.47-88.80). CONCLUSIONS: A high-risk group for gastric cancer can be selected by serological prescreening.

Long-term results of gastric cancer screening using the serum pepsinogen test method among an asymptomatic middle-aged Japanese population.

BACKGROUND AND AIM: In order to reduce gastric cancer death, mass screening for gastric cancer has been established in Japan for several decades. Only photofluorography is considered to be an acceptable screening method so far, but recent evidence may show the usefulness of serum pepsinogen (PG) measurement for gastric cancer screening. The aim of the present study was to elucidate the feasibility of measuring serum PG levels for detection of gastric cancers. METHODS: Serum PG levels (PGI/PGII) were measured in asymptomatic middle-aged Japanese between 1991 and 2005. Those with a PGI

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer.

BACKGROUND AND AIMS: Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry. METHODS: A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[-] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, beta-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(-) groups. RESULTS: Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and beta-catenin was associated with the histopathological type of cancer, but not with LN status. CONCLUSION: Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.

[Case of phlegmonous esophagogastritis associated with hypopharyngeal abscess].

A 62-year-old man was admitted to our hospital complaining of sore throat and epigastralgia. Laboratory tests revealed leukocytosis and an elevated CRP level. CT showed a low density area in the right hypopharynx, wall thickening of the esophageal and gastric wall with an intramural low density area. Phlegmonous esophagogastritis associated with hypopharyngeal abscess was diagnosed. The infection was extension and his condition was serious because of his accompanying poorly controlled diabetes. He was successfully treated by antibiotics and drainage of the hypopharyngeal abscess. CT was useful for early diagnosis, confirmation of the extent of inflammation and follow-up.

Histopathological predictor for regional lymph node metastasis in gastric cancer.

Regional lymph node metastasis in gastric cancer is a definitive indicator of the patient's prognosis. The goal of this study was to identify the predictors for lymph node metastasis among all the possible histopathological parameters, especially by conducting an objective discrimination of the lymphatic and blood vessels. A total of 210 resected primary gastric cancers with or without lymph node metastasis were evaluated based on the conventional histopathological parameters together with immunohistochemistry using antisera-recognizing lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C) antibodies. A multivariate regression analyses of the results indicated that only lymphatic invasion was a significant independent predictor of lymph node metastasis at any stage of cancer invasion. VEGF-C expression was partially related to lymph node metastasis in early gastric cancer. The identification of lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional lymph node metastasis in gastric cancer.

Structural and phylogenetic comparison of three pepsinogens from Pacific bluefin tuna: molecular evolution of fish pepsinogens.

The amino acid sequences of three pepsinogens (PG1, PG2 and PG3) of Pacific bluefin tuna (Thunnus orientalis) were deduced by cloning and nucleotide sequencing of the corresponding cDNAs. The amino acid sequences of the pre-forms of PG1, PG2 and PG3 were composed of a signal peptide (16 residues each), a propeptide (41, 37 and 35 residues, respectively) and a pepsin moiety (321, 323 and 332 residues, respectively). Amino acid sequence comparison and phylogenetic analysis indicated that PG1 and PG2 belong to the pepsinogen A family and PG3 to the pepsinogen C family. Homology modeling of the three-dimensional structure suggested that the remarkably high specific activity of PG2 toward hemoglobin, which had been found previously, was partly due to a characteristic deletion of several residues in the S1'-loop region that widens the space of the active site cleft region so as to accommodate protein and larger polypeptide substrates more efficiently. Including the tuna and all other fish pepsinogen sequences available to date, the molecular phylogenetic comparison was made with reference to evolution of fish pepsinogens. It was suggested that functional divergences of pepsinogens (pepsins) occurring in fishes as well as in mammals, correlated with differences in various aspects of fish physiology.

Extensive atrophic gastritis linked to increased levels of intraluminal hydrogen gas.

BACKGROUND/AIMS: Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. METHODOLOGY: Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 ml of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. RESULTS: Over all, intragastric and intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%), respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and 13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. CONCLUSIONS: The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.

Extensive atrophic gastritis increases intraduodenal hydrogen gas.

OBJECTIVE: Gastric acid plays an important part in the prevention of bacterial colonization of the gastrointestinal tract. If these bacteria have an ability of hydrogen (H2) fermentation, intraluminal H2 gas might be detected. We attempted to measure the intraluminal H2 concentrations to determine the bacterial overgrowth in the gastrointestinal tract. PATIENTS AND METHODS: Studies were performed in 647 consecutive patients undergoing upper endoscopy. At the time of endoscopic examination, we intubated the stomach and the descending part of the duodenum without inflation by air, and 20 mL of intraluminal gas samples of both sites was collected through the biopsy channel. Intraluminal H2 concentrations were measured by gas chromatography. RESULTS: Intragastric and intraduodenal H2 gas was detected in 566 (87.5%) and 524 (81.0%) patients, respectively. The mean values of intragastric and intraduodenal H2 gas were 8.5 +/- 15.9 and 13.2 +/- 58.0 ppm, respectively. The intraduodenal H2 level was increased with the progression of atrophic gastritis, whereas the intragastric H2 level was the highest in patients without atrophic gastritis. CONCLUSIONS: The intraduodenal hydrogen levels were increased with the progression of atrophic gastritis. It is likely that the influence of hypochlorhydria on bacterial overgrowth in the proximal small intestine is more pronounced, compared to that in the stomach.

Saliva transit from the oral cavity to the esophagus in GERD.

BACKGROUND/AIMS: Normal esophageal acid clearance depends on the neutralization of acid by swallowed saliva, as well as on esophageal peristalsis. This study therefore aimed to investigate the association between saliva production and transport from the oral cavity to the esophagus and developing gastroesophageal reflux disease (GERD) METHODOLOGY: Twenty-eight consecutive patients with GERD symptoms by gastroesophageal reflux self-report questionnaires and 13 healthy volunteers were recruited in the study. After intravenous administration of 99mTc-pertechnetate, anterior sequential imaging was performed every minute for 40 minutes. At 20 minutes after injection of radionuclide, a lemon candy was administered intra-orally to stimulate salivary secretion. Regions of interest (ROI) were selected on the individual oral cavity, the pharynx, and the upper esophagus and time activity curves were drawn for each of these. A time-activity curve in each ROI was subjectively graded, as zero to two-point. The sum of scores in 3 ROIs was considered as a saliva transit total score. RESULTS: The mean transit score of the oral cavity did not differ significantly between GERD patients and healthy volunteers (1.38 vs. 1.61), whereas significantly lower transit scores of pharynx and upper esophagus were found in GERD patients. A 0-point saliva transit score of pharynx and upper esophagus was significantly more frequently detected in GERD patients than in healthy volunteers. CONCLUSIONS: This new modification of saliva scintigraphy is able to evaluate the esophageal motility simply, without a test meal, and to detect impaired saliva transit between pharynx and upper esophagus in GERD patients non-invasively.

Th1/Th2 balance: an important indicator of efficacy for intra-arterial chemotherapy.

PURPOSE: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cells promotes antitumor immunity. However, the immunological features of liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) treated by intra-arterial chemotherapy are still unclear. The aim of this study was to assess the influence of intra-arterial combination chemotherapy on the Th1/Th2 balance in LC patients with aHCC. METHODS: Twenty-one adult Japanese LC patients with aHCC were treated by intra-arterial combination chemotherapy. The control group was composed of 20 adult Japanese patients with chronic hepatitis C diagnosed from examination of liver biopsy specimens. All control patients were over 55 years old and were stage 1 according to the fibrosis score of Desment. RESULTS: Thirteen of the 21 aHCC patients (group R) showed an objective response, but the other 8 patients (group N) showed no response. There were no significant differences of Th1 cells between group R and group N either before or after chemotherapy. Although there was no significant difference from group R, group N had a significantly higher percentage of Th2 cells than the control group both before and after chemotherapy (p < 0.05 by Tukey's test). CONCLUSIONS: These results indicate that the Th1/Th2 balance might be a useful indicator of the effect of intra-arterial combination chemotherapy in LC patients with aHCC. Inhibition of an increase of Th2 cells might be important for the efficacy of intra-arterial chemotherapy in such patients.

Relationship of peripheral blood CD4-positive T cells to carcinogenesis in patients with HCV-related chronic hepatitis and liver cirrhosis.

INTRODUCTION: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of type 1 T cell responses promotes antitumor immunity. However, detailed information on the immunological background of patients with HCC is still unknown. The objectives of this study were to evaluate the Th1/Th2 balance and to investigate the relation between carcinogenesis and host immunity in patients with chronic hepatitis C, HCV-related liver cirrhosis (LC), or HCC. PATIENTS/METHODS: The study population was 117 patients who had chronic inflammation due to HCV infection diagnosed from pathological examination of liver biopsy specimens, including 32 patients who had HCV-related LC with HCC. Apart from the patients with HCC, they were divided into the four subgroups based on the fibrosis score of Desment (stages 1-4). Blood samples were collected in the early morning before treatment. Flow cytometry was used to assess cytoplasmic IFN-gamma and IL-4 expression by peripheral blood CD4+ T cells, and the percentage of IFN-gamma+ and IL4- T cells (Th1) or IFN-gamma- and IL4+ T cells (Th2) was calculated before the start of each therapy. RESULTS: There were 20 patients in F1, 25 patients in F2, 19 patients in F3, 21 patients in F4, and 32 patients with HCC. In the F4 and HCC groups, Th1 cells tended to increase depending on the extent of fibrosis, although there were no significant differences between these groups and the other groups. In the HCC group, Th2 cells showed a significantly higher percentage than in the F1 or F3 groups. CONCLUSIONS: These results suggest that Th1 dominance is lost due to an increase of Th2 cells in HCC patients and that carcinogenesis might occur in patients with chronic HCV infection and increased level of Th2 cells.

Breath hydrogen and methane levels in a patient with volvulus of the sigmoid colon.

Volvulus of the large bowel is the third most common cause of colonic obstruction. A patient with colonic obstruction or delayed small intestinal transit may frequently have bacterial overgrowth and increased breath hydrogen (H(2)) and/or methane (CH(4)) excretion because the bacterium can contact with food residues for a longer time. A 39 year old woman attended our hospital with complaints of abdominal pain and distension. This patient's abdominal radiograph showed an inverted U-shaped shadow. The fasting breath CH(4) level was 26 ppm. An endoscopic procedure was immediately carried out with suspected sigmoid colon volvulus, and detorsion was achieved. There was resolution of the sigmoid volvulus after colonoscopy, and breath CH(4) concentration in the next morning decreased to 10 ppm. A liquid meal was supplied at noon on the second hospital day. The breath CH(4) concentration increased markedly to 38 ppm at 18:00 although she had no abdominal symptoms. This value peaked at 42 ppm at 18:00 on the third hospital day and was gradually reduced to 20 ppm the next day. The breath H(2) concentration value kept a low level during fasting and increased markedly to 51 ppm the next day after a liquid meal was supplied. The next morning, fasting breath H(2) concentration rapidly decreased to 6 ppm. This suggests that changes in breath H(2) levels may reflect transient malabsorption after a liquid test meal is supplied. In conclusion, breath H(2) and CH(4) analysis may be another tool for evaluating the intestinal circumstances.