Impact of Helicobacter pylori infection on fluid duodenal microbial community structure and microbial metabolic pathways.

BACKGROUND: The bioactivities of commensal duodenal microbiota greatly influence the biofunction of hosts. We investigated the role of Helicobacter pylori infection in extra-gastroduodenal diseases by determining the impact of H. pylori infection on the duodenal microbiota. We sequenced 16 S rRNA genes in samples aspirated from the descending duodenum of 47 (male, 20; female, 27) individuals who were screened for gastric cancer. Samples were analysed using 16 S rRNA gene amplicon sequencing, and the LEFSe and Kyoto Encyclopaedia of Genes and Genomes methods were used to determine whether the duodenal microflora and microbial biofunctions were affected using H. pylori infection. RESULTS: Thirteen and 34 participants tested positive and negative for H. pylori, respectively. We identified 1,404 bacterial operational taxonomic units from 23 phyla and 253 genera. H. pylori infection changed the relative mean abundance of three phyla (Proteobacteria, Actinobacteria, and TM7) and ten genera (Neisseria, Rothia, TM7-3, Leptotrichia, Lachnospiraceae, Megasphaera, F16, Moryella, Filifactor, and Paludibacter). Microbiota features were significantly influenced in H. pylori-positive participants by 12 taxa mostly classified as Gammaproteobacteria. Microbial functional annotation revealed that H. pylori significantly affected 12 microbial metabolic pathways. CONCLUSIONS: H. pylori disrupted normal bacterial communities in the duodenum and changed the biofunctions of commensal microbiota primarily by upregulating specific metabolic pathways. Such upregulation may be involved in the onset of diseases associated with H. pylori infection.

[Efficacy of Antiemetic Therapy with Aprepitant, Palonosetron, and Dexamethasone in Patients Receiving Oxaliplatin-Based Chemotherapy].

Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is recommended for moderately emetogenic chemotherapy in several guidelines to prevent chemotherapy-induced nausea and vomiting. There is a lack of information about the efficacy and safety of antiemetic therapy with aprepitant, palonosetron, and dexamethasone in patients treated with oxaliplatin in Japan. We recruited patients with untreated colorectal cancer who underwent oxaliplatin-based chemotherapy. All patients were treated with aprepitant, palonosetron, and dexamethasone. The complete response and complete protection rates were analyzed. A total of 52 patients were enrolled in this clinical trial. The complete response rate overall, and in the acute and delayed phases was 92.3%, 98.1%, and 92.3%, respectively. The complete protection rate overall and in the acute and delayed phases was 73.1%, 86.5%, and 73.1%, respectively. Grade 3-4 non-hematological toxicity did not occur. Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is effective and safe in patients treated with oxaliplatin.

[The chemotherapy of peritoneal malignant mesothelioma].

Peritoneal malignant mesothelioma is a rare disorder with a poor prognosis, and a standard treatment for it has not yet been established. Therefore, treatment of this disorder tends to be selected according to pleura malignant mesothelioma. We analyzed case reports in Japan. The median survival time(MST)with this disease was 12 months and the 1-year survival rate was 47. 3% in the chemotherapy group. It was found through a case-series study that platinum pharmaceutical plus antimetabolite are effective against peritoneal malignant mesothelioma. A gemcitabine(GEM)plus cisplatin(CDDP)regimen had been selected as a conventional treatment, but subsequently, pemetrexed(MTA)was covered by health insurance for pleural malignant mesothelioma in 2007, and the MTA plus CDDP regimen became the standard treatment. However, a phase III trial of GEM plus CDDP regimen and MTA plus CDDP regimen was not performed. There is a need to perform these phase III trials in the future. In our institution, the MTA plus CDDP regimen was the first-line treatment, and the GEM plus CDDP regimen was the second-line treatment against peritoneal malignant mesothelioma. Palonosetron hydrochloride and aprepitant should be used actively in treatment. Also, carboplatin(CBDCA)is effective as an alternative therapy of the CDDP against renal disorder case, but hematotoxicity requires attention.

[Analysis of the correlation with KRAS gene mutation status and the benefit of cetuximab plus irinotecan as third- line chemotherapy for the Treatment of unresectable metastatic colorectal cancer].

Mutation of the KRAS gene in patients with metastatic colorectal cancer(mCRC)has been established as a predictive marker of poor response to anti-EGFR cetuximab. The Japanese Society of Medical Oncology recommends that the KRAS mutation status at codon 12 and codon 13 should be genotyped by direct-sequencing or allele-specific PCR. In this study, we tested the point mutation of codon 12 and 13 in the KRAS gene by Luminex(xMAP)flow cytometry with sequence-specific oligonucleotide probes for 39 out of 64 unresectable mCRC patients enrolled from Sep 2008 to Oct 2009, who were administered cetuximab in combination with irinotecan(CPT-11)as third-line therapy. We retrospectively analyzed the relationship between KRAS mutation status and responses to combination therapy. Mutations in the KRAS gene were detected in 38. 5% of cases(codon12: 73%, codon 13: 27%), and the median follow-up time was 8. 2 months(range, 1. 4-15. 2 months). The response rates for patients with KRAS wild-type and patients with KRAS mutations were 33. 3%(95%CI 14. 5-52. 2%)and 0%(p=0. 015); the disease control rates were 75%(95%CI 57. 7-92. 3%)and 40%(95%CI, 15. 2-64. 8%; p=0. 044); the median TTF was 7 months(95%CI 4. 6-9. 3)and 2. 3 months(95%CI 1. 3-3. 2; p=0. 0007), and the median OS was 12. 9 months(95%CI 6. 7-19. 1)and 10. 8 months(95%CI 5. 0-16. 7; p=0. 15), respectively. Therefore, we concluded that the KRAS mutation in mCRC is a predictive factor for the lack of response to combination therapy with cetuximab plus CPT- 11, as reported in previous clinical studies.

How do we apply adjuvant FOLFOX to Japanese patients with curatively resected colorectal cancer?

AIM: In Japan the combination of fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) was approved as adjuvant therapy for stage III or high-risk stage II colon cancer only in September 2009. In this study we evaluated the safety and efficacy of FOLFOX as adjuvant chemotherapy for stage IIIb or IV colorectal cancer (CRC) patients in a Japanese group at a single institute. METHODS: A total of 45 consecutive patients received 12 cycles of adjuvant FOLFOX for stage IIIb (n = 31) or IV (n = 14) CRC. Toxicity and disease-free survival (DFS) were analyzed retrospectively. RESULTS: The median dose intensities of oxaliplatin and 5-FU were 0.7 and 0.74, respectively. Oxaliplatin was discontinued in 10 (22%) patients due to an allergic reaction in five, neurotoxicity in four and gastrointestinal toxicity in one. No severe neurotoxicity occurred. The median duration from completion of treatment until complete recovery from peripheral neuropathy was 582 days (95% CI, 486-678). Two-year DFS for stages IIIb and IV was 56.9% and 56.3%, respectively (log-rank, P = 0.533). Univariate analysis revealed that severe vessel invasion, liver metastasis and higher baseline levels of CA19-9 were associated with shorter DFS in stage IV patients. Multivariate analysis including the selected biomarkers revealed none as a significant prognostic factor. CONCLUSION: Adjuvant FOLFOX was well tolerated in a Japanese cohort of both stage IIIb and IV CRC patients.

Breath Hydrogen Gas Concentration Linked to Intestinal Gas Distribution and Malabsorption in Patients with Small-bowel Pseudo-obstruction.

BACKGROUND: The patient with colonic obstruction may frequently have bacterial overgrowth and increased breath hydrogen (H2) levels because the bacterium can contact with food residues for longer time. We experienced two cases with intestinal obstruction whose breath H2 concentrations were measured continuously. CASE 1: A 70-year-old woman with small bowel obstruction was treated with a gastric tube. When small bowel gas decreased and colonic gas was demonstrated on the plain abdominal radiograph, the breath H2 concentration increased to 6 ppm and reduced again shortly. CASE 2: A 41-year-old man with functional small bowel obstruction after surgical treatment was treated with intravenous administration of erythromycin. Although the plain abdominal radiograph demonstrated a decrease of small-bowel gas, the breath H2 gas kept the low level. After a clear-liquid meal was supplied, fasting breath H2 concentration increased rapidly to 22 ppm and gradually decreased to 9 ppm despite the fact that the intestinal gas was unchanged on X-ray. A rapid increase of breath H2 concentration may reflect the movement of small bowel contents to the colon in patients with small-bowel pseudo-obstruction or malabsorption following diet progression. CONCLUSIONS: Change in breath H2 concentration had a close association with distribution and movement of intestinal gas.

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.

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.

Endoscopic 13C-urea breath test for detection of Helicobacter pylori infection after partial gastrectomy.

BACKGROUND/AIMS: It is difficult to interpret the results of 13C-urea breath test (UBT) in gastrectomy patients because the test urea may pass through the stomach faster. The aim of this study is to evaluate the efficacy of the modified endoscopic UBT for detection of Helicobacter pylori (H. pylori) infection in the residual stomach. METHODOLOGY: An endoscopic UBT was performed in 44 patients who had undergone partial gastrectomy. At endoscopy, 20 mL of water containing 100mg of 13C-urea were sprayed onto the gastric mucosa and an intragastric gas sample was immediately collected through the biopsy channel. Breath samples were collected at 20 min after spraying 13C-urea. RESULTS: The intragastric delta13CO2 value in H. pylori-positive patients was significantly higher than those of 20-minute breath samples. The maximum sensitivity and specificity of intragastric samples were 97% and 100% with cutoff point of 5 per thousand, respectively. The sensitivity and specificity of breath samples at 20 min were 71.4% and 66.7% with cutoff point of 0.6 per thousand, respectively. CONCLUSIONS: An endoscopic UBT was superior to a standard UBT to detect H. pylori infection after partial gastrectomy.

Ten-second endoscopic breath test using a 20-mg dose of 13C-urea to detect Helicobacter pylori infection.

BACKGROUND/AIMS: Attempts to improve the 13C-urea breath test (UBT) have focused on decreasing the amount of substrate used and reducing the duration of the test. To render the test less expensive and more convenient, we designed a more rapid and less expensive endoscopic UBT with a low dose of 20 mg and a shortened measurement time. METHODOLOGY: A total of 178 patients who underwent diagnostic upper endoscopy were enrolled. At endoscopy, 150 mL of intragastric gas sample were collected through a biopsy channel. Following inflation with air, 20 mL of water containing 20 mg of 13C-urea were sprayed onto the gastric mucosa using a spraying instrument. After 10 seconds, a gastric gas sample was collected again. The standard UBT was performed after 3-10 days. RESULTS: The delta13CO2 values of intragastric samples in H. pylori-positive patients and H. pylori-negative patients were 76.7 +/- 132.9 per thousand and 1.6 +/- 1.2 per thousand, respectively. With intragastric samples, the maximum sensitivity and specificity of intragastric samples were 83.7% and 100% with cut-off point of 8 per thousand, respectively. CONCLUSIONS: Ten-second endoscopic UBT using a 20-mg dose of 13C-urea is a rapid, inexpensive, and accurate method for the detection of H. pylori infection in clinical practice.