Antiproliferative Effects of Short-chain Fatty Acids on Human Colorectal Cancer Cells via Gene Expression Inhibition.

BACKGROUND/AIM: Short-chain fatty acids (SCFAs) inhibit human colorectal cancer cell growth and tumorigenicity. We investigated the mechanism of the anti-proliferative effects of SCFAs on human colorectal cancer cells by examining their effects on gene expression. MATERIALS AND METHODS: The DLD-1 cell line was cultured with different SCFAs. Gene groups whose expression levels decreased to <50% or increased >50% compared to untreated cells and the signalling pathways responsible for DLD-1 cell growth inhibition were identified and analyzed. RESULTS: Genes whose expression levels decreased to ≤50% (791 genes) showed remarkable changes in gene function compared to genes whose expression levels increased ≥50%. These genes encode proteins involved in DNA replication and cell cycle/proliferation that contribute to major pathways responsible for suppression of colorectal carcinogenesis pathways. CONCLUSION: SCFAs inhibited the expression of genes encoding proteins involved in DNA replication and cell cycle/proliferation of human colorectal cancer cells and exerted antiproliferative activity via different pathways.

Identification of the microbial diversity after fecal microbiota transplantation therapy for chronic intractable constipation using 16s rRNA amplicon sequencing.

BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapeutic approach for the treatment of functional gastrointestinal disease by restoring gut microbiota; however, there is a lack of sufficient understanding regarding which microbial populations successfully colonize the recipient gut. This study characterized microbial composition and diversity in patients diagnosed with chronic constipation at 1 month and 1 year after FMT. METHODS: We explored the microbial diversity of pre- and posttransplant stool specimens from patients using 16S rRNA gene sequencing, followed by functional analysis. RESULTS: The results identified 22 species of microorganisms colonized in the recipients from the donors at 1 month after FMT. One-year follow-up of the patient identified the colonization of 18 species of microorganisms, resulting in identification of species in significant abundance, including Bacteroides fragilis and Hungatella hathewayi in the recipient at 1 month after FMT and Dialister succinatiphilus, Coprococcus catus, and Sutterella stercoricanis at 1 year after FMT. The majority of the colonized species belong to the phylum Firmicutes and carry genes related to polysaccharide metabolism and that enhance the energy-harvesting efficiency of the host. CONCLUSION: These results suggest that FMT is effective for the treatment of chronic constipation through the restoration and colonization of donor microbiota in the recipient gut up to 1 year after FMT.

Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.

We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.

Intake of Bifidobacterium longum and Fructo-oligosaccharides prevents Colorectal Carcinogenesis.

INTRODUCTION: We aimed to investigate the effects of intake of yogurt containing Bifidobacterium longum (BB536-y) and fructo-oligosaccharides (FOS) in preventing colorectal carcinogenesis in healthy subjects, and the preventive effects of short-chain fatty acids (SCFA), whose production was enhanced by the intake of BB536-y and FOS, in human colon cancer cell lines. MATERIALS AND METHODS: The subjects were 27 healthy persons who were divided into a group taking yogurt containing BB536 (BB536-y group; n = 14) and a group taking yogurt containing BB536 and FOS (BB536-y with FOS group; n = 13) once a day for 5 weeks. The feces were sampled before and after the intake to analyze the amount of SCFA in the feces and the profile of intestinal flora, such as putrefactive bacteria and Bacteroides fragilis enterotoxin (ETBF). Subsequently, human colon cancer cell lines (DLD-1 cells, WirDr cells) were cultured in the presence of SCFA (butyric acid, isobutyric acid, acetic acid) in order to evaluate the cell growth-inhibitory activity of SCFA (WST-8 assay) by calculating the IC50 value from the dose-response curve. RESULTS: Intake of BB536-y increased the total amount of SCFA in the feces and significantly suppressed the detection rate of ETBF and growth of putrefactive bacteria. Intake of BB536-y with FOS was associated with a higher Bifidobacterium detection rate than that of BB536-y alone. The contents of butyric acid, isobutyric acid, and acetic acid, namely, of SCFA, were also decreased. Analysis of the results of culture of DLD-1 cells and WirDr cells in the presence of butyric acid, isobutyric acid, and acetic acid revealed that each of the substances showed significant cell growth-inhibitory activity, with the activity being the highest for butyric acid, followed by that for isobutyric acid and acetic acid. CONCLUSION: These findings suggest that intake of both BB536-y and BB536-y with FOS prevents colorectal carcinogenesis.How to cite this article: Ohara T, Suzutani T. Intake of Bifidobacterium longum and Fructo-oligosaccharides prevents Colorectal Carcinogenesis. Euroasian J Hepato-Gastroenterol 2018;8(1):11-17.

The clinical outcome of capsule endoscopy in patients with obscure gastrointestinal bleeding.

BACKGROUND/AIMS: Capsule endoscopy (CE) represents a significant advance in the investigation of small bowel diseases. Little is known about the clinical outcome of patients with obscure gastrointestinal bleeding (OGIB). METHODOLOGY: Seventy-eight patients underwent CE for OGIB and were followed up for at least 6 months after CE. The diagnostic yield of CE and the rate of re-bleeding during the follow-up period were established. RESULTS: Out of our 78 OGIB patients, 35 (44.9%) had significant lesions. There was a significant difference in the rate of identification of significant lesions between the on-going overt bleeding cases and previous overt bleeding cases (68.8% vs. 37.8%, respectively, p=0.043). Of the 46 patients with significant or insignificant lesions, 12 (26.1%) had one or more re-bleeding episodes during the follow-up period. On the other hand, only one (4%) of the 26 patients with negative findings had a re-bleeding episode (p=0.025). CONCLUSION: In conclusion, our study confirmed the role of CE in the diagnosis of OGIB, especially in the on-going overt bleeding cases. The OGIB patients with negative CE findings showed a low re-bleeding rate in the follow-up period. Further long-term follow-up studies are needed in future to examine the negative CE cases.

Efficacy of double filtration plasmapheresis with pegylated interferon/ribavirin therapy for intractable chronic hepatitis C patients and hepatitis C patients with combined liver cirrhosis by HBV, leading to early viral elimination.

BACKGROUND/AIMS: Therapeutic results for patients with hepatitis C and B complex or patients with genotype lb high viral load treatment-resistant hepatitis C are still not sufficient. The therapeutic effects of concomitant treatment of such intractable patients with double-filtration plasmapheresis (DFPP) and pegylated interferon (PEG-IFN) alpha 2a/ribavirin (RBV) therapy were investigated. METHODOLOGY: The subjects were one patient with genotype 2a hepatitis C combined with liver cirrhosis by HBV and 12 patients with retreated hepatitis C (genotype 2a: two patients, genotype 1b: 10 patients). All subjects were given PEG-IFNalpha2a/RBV therapy (up to 24 weeks for genotype 2a and from 48 to 72 weeks for genotype 1b) and DFPP from the start of treatment for a total of five times. The disappearance of HCV-RNA, hepatic function and peripheral blood were observed with time. RESULTS: In seven of the 13 patients, HCV-RNA became negative by week 4 of treatment and three became negative by week 12. The remaining three patients became HCV-RNA negative by week 20. In the patient with hepatitis C (genotype 2a) combined with liver cirrhosis by HBV, HBV became negative in week 1 of treatment and HCV-RNA was negative by week 2. Sustained viral response (SVR) was detected in this patient with hepatitis C (genotype 2a) and liver cirrhosis by HBV and in two of the genotype 2a hepatitis C patients. Two of the genotype 1b hepatitis C patients are still HCV-RNA negative at 3 months after completion of treatment and eight patients are currently under observation during treatment. CONCLUSIONS: Concomitant treatment with PEG-IFNalpha2a/RBV and DFPP is a new modality of hepatitis treatment that causes HCV-RNA to become negative or markedly reduced at an early stage of treatment and induces SVR.

Acute inflammatory biomarkers in cerebrospinal fluid as indicators of blood cerebrospinal fluid barrier damage in Japanese subjects with infectious meningitis.

BACKGROUND: The blood-cerebrospinal fluid barrier (BCB) has selectivity for protein components with different molecular weights. Protein components in the cerebrospinal fluid (CSF) change when the BCB is damaged. We calculated the alpha2 macroglobulin (alpha2M) index as an indicator of BCB permeability from the point of view of molecular weight and evaluated the relationship between the alpha2M index and CSF concentrations of the inflammatory biomarkers interleukin-6 (IL-6), C-reactive protein (CRP), and serum amyloid A (SAA) in Japanese subjects with infectious meningitis, in order to determine the clinical significance of those inflammatory biomarkers in CSF. METHODS: IL-6, CRP, and SAA levels in CSF and serum were measured using various methods. The alpha2M index was calculated as the ratio of alpha2M (CSF/serum) to albumin (CSF/serum). RESULTS: CSF IL-6 levels were higher than serum IL-6 levels in 16 patients with infectious meningitis. The difference in CSF IL-6 and CRP levels between mycotic or bacterial meningitis cases and healthy controls and in CSF SAA levels between all infectious meningitis cases and healthy controls were significant. There was a significant positive correlation between CSF levels of CRP or SAA and alpha2M indices. CONCLUSIONS: Markedly increased levels of IL-6 in the CSF of patients with infectious meningitis may reflect the degree of intrathecal inflammation. On the other hand, increased CSF levels of CRP in patients with infectious meningitis, particularly mycotic or bacterial meningitis, and SAA in patients with all infectious meningitis may reflect the degree of damage to the BCB.

Laparoscopy-assisted total gastrectomy for advanced gastric cancer with carcinomatous ascites after S1 plus cisplatin chemotherapy: a case report.

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.

CT scan findings of emphysema predict mortality in COPD.

BACKGROUND: Emphysematous change as assessed by CT imaging has been reported to correlate with COPD prognostic factors such as FEV(1) and diffusing capacity of the lung for carbon monoxide (Dlco). However, few studies have assessed the relationship between CT scan assessment and COPD mortality from mild to severe stages of the disease. In this study, we analyzed this relationship in patients with various stages of COPD. METHODS: Two hundred and fifty-one outpatients with stable COPD were included in the study. CT scan and pulmonary function tests were performed at study entry in a single institution. The percentage of low attenuation area was measured to quantitatively evaluate emphysematous change with a custom-made software. Prognostic data also were collected, and the median follow-up time was 8 years. RESULTS: Of the 251 patients, 79 died, with 40 classified as respiratory deaths not involving lung cancer. Univariate Cox analysis revealed that emphysematous change as assessed by CT scan, lung function, age, or BMI were significantly correlated with mortality. Multivariate analysis revealed that emphysematous change as assessed by CT scan had the best association with mortality. CONCLUSIONS: Emphysematous change as assessed by CT scan predicts respiratory mortality in outpatients with various stages of COPD.

Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells.

BACKGROUND AND OBJECTIVE: Connective tissue growth factor (CTGF) is up-regulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke and repeated bacterial infections, both of which are rich sources of LPS, are major causes of COPD. The high levels of LPS in lung epithelial lining fluid also suggest that it may have a considerable impact on the airway epithelium, in terms of cytokine and growth factor production. The aim of this study was to clarify the mechanism of LPS-induced CTGF expression in bronchial epithelial cells. METHODS: The expression and transcriptional regulation of the CTGF gene were assessed using the cultured human bronchial epithelial cell line, BEAS-2B. RESULTS: LPS significantly up-regulated CTGF mRNA expression in a dose-dependent fashion, with 100 microg/mL LPS causing a twofold increase after 2 h. CTGF protein expression was also up-regulated by LPS after 8 h. Transforming growth factor-beta1 mRNA expression was not changed by LPS treatment. A pharmacological inhibitor of nuclear factor (NF)-kappaB, MG132, inhibited LPS-induced CTGF mRNA expression. Furthermore, luciferase assays demonstrated that deletion of base pairs -253 to -53 from the CTGF promoter, where the Smad and proximal NF-kappaB binding sites are located, decreased the induction of CTGF by LPS. After stimulation with LPS, the p65 subunit of NF-kappaB was shown to be bound to the CTGF promoter in vitro and in situ. CONCLUSIONS: LPS directly induced CTGF expression in bronchial epithelial cells, independently of transforming growth factor-beta1, suggesting a possible mechanism for airway remodelling in COPD that is induced by smoking and repeated bacterial infections.

Relationship between peripheral airway function and patient-reported outcomes in COPD: a cross-sectional study.

BACKGROUND: Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV1) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment. METHODS: We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities. RESULTS: R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores. CONCLUSIONS: IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.

Possibility of preventing colorectal carcinogenesis with probiotics.

BACKGROUND/AIMS: There have been no reports on the relationship between the analyses of the intestinal flora of colorectal cancer patients and colorectal carcinogenesis. In this study we investigated the differences between the intestinal flora of colorectal cancer patients and healthy subjects and assessed the possibility of using probiotics to prevent colorectal carcinogenesis. METHODOLOGY: The subjects were 10 colorectal cancer patients and 20 healthy persons. A stool specimen and peripheral blood specimen were collected from the patients and 10 of the healthy subjects to analyze their intestinal flora and measure natural killer (NK) cell activity and IL-1 beta in their blood. Probiotics (Lactobacillus gasseri OLL2716: LG21) was then administered once daily to 10 of the healthy subjects for 12 weeks. Samples were collected after 4 weeks, 8 weeks, and 12 weeks of administration, and the same examinations were performed. RESULTS: The Lactobacillus detection rate was significantly higher in the healthy group than in the colorectal cancer group, and the total Clostridium perfringens was higher in the colorectal cancer group. The stool pH of the colorectal cancer group indicated alkalosis, and the total amount of short-chain fatty acids in the stools tended to be lower than in the healthy group. After ingestion of the probiotic, the Lactobacillus detection rate increased, a decrease in the total amount of Clostridium perfringens was seen, fecal pH indicated acidosis, synthesis of fecal putrefaction products was inhibited, and an increase in the short-chain fatty acid isobutyric acid was observed. The blood IL-1 beta and NK cell activity values were significantly higher from the 4th week onward than the values before ingestion of probiotics. CONCLUSIONS: A deterioration of the intestinal environment was observed in the colorectal cancer patients in comparison to the healthy controls, and the intestinal environment improved when probiotics was taken. These findings suggest the possibility of preventing colorectal carcinoma with probiotics.

Abnormal swallowing reflex and COPD exacerbations.

BACKGROUND: It is unclear whether an abnormal swallowing reflex affects COPD exacerbations. This study investigated the prevalence of abnormal swallowing reflexes and its relationship with COPD exacerbation prospectively. We also clarified its association with gastroesophageal reflux disease (GERD) and airway bacterial colonization. METHODS: Swallowing reflex and serum C-reactive protein (CRP) levels were examined in subjects with stable COPD and in control subjects. Concurrently, GERD symptoms were assessed using a self-reported questionnaire, and sputum bacterial cultures were investigated in the same subjects. Exacerbations were counted prospectively during the following 12 months. RESULTS: The study group comprised 67 subjects with COPD and 19 controls. The prevalence of abnormal swallowing reflex was significantly higher in subjects with COPD (22/67) than controls (1/19; P = .02). Among subjects with COPD, the serum CRP level, GERD symptoms, isolation of sputum bacteria, and the frequency of exacerbations were significantly increased in those with abnormal swallowing reflexes compared with controls (2.72 vs 1.04 mg/L, P = .04, for serum CRP level; 6.75 vs 4.10 points, P = .04, for GERD symptoms; 5/11 vs 3/22, P = .04, for the isolation of sputum bacteria; and 2.82 vs 1.56/y, P = .007, for the annual frequency of exacerbations). Multivariable analysis confirmed that abnormal swallowing reflex was significantly associated with frequent exacerbations (>or= 3/y; P = 0.01). CONCLUSIONS: Abnormal swallowing reflexes frequently occurred in subjects with COPD and predisposed them to exacerbations. Abnormal swallowing reflexes in COPD might be affected by the comorbidity of GERD, and cause bacterial colonization.

Effects of Lansoprazole on the Lipopolysaccharide-Stimulated Toll-Like Receptor 4 Signal Transduction Systems: A Study Using the 293hTLR4/MD2-CD14 Cells.

The present study was undertaken to evaluate the effects of lansoprazole (LPZ) on lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using the 293hTLR4/MD2-CD14 cells. The cells were incubated and then divided into the following groups: (a) untreated group, (b) non-LPZ treated (1h) group, (c) LPZ-treated (1h) plus non LPS-stimulated (1h) group, (d) LPZ-treated (1h) plus non LPS-stimulated (6h) group, (e) LPZ-treated (1h) plus LPS-stimulated (1h) group, (f) LPZ-treated (1h) plus LPS-stimulated (6h) group, (g) non LPZ-treated (1h) plus LPS-stimulated (1h) group and (h) non LPZ-treated (1h) plus LPS-stimulated (6h) group. Samples from each group were subjected to western blotting for analysis of IkB phosphorylation, intranuclear transfer of NF-kB, phosphorylation of MAP kinase (MAPK), intranuclear transfer of interferon regulatory factor 5 (IRF5), and expression of suppressor of cytokine signaling-1 (SOCS1). In the LPZ-treated groups, neither phosphorylation of MAPK nor intranuclear transfer of IRF5 was suppressed under stimulation with LPS, and enhanced intranuclear transfer of NF-kB and increased expression of SOCS1 were noted by comparison with the group treated with LPS alone. These results suggest that LPZ stimulates the expression of SOCS1 and regulates protein phosphorylation through its activity on TLR4 signal transduction under LPS stimulation.

Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency.

BACKGROUND AND OBJECTIVE: The causes of exacerbations in COPD patients are poorly understood. This study examined the association between cough-reflex sensitivity in patients with stable COPD and the frequency of subsequent exacerbations. METHODS: The sampling frame for cases and controls for this study was patients attending a hospital outpatient clinic. cough-reflex sensitivity was evaluated using the log concentration of capsaicin causing five or more coughs (log C(5)). Subsequent COPD exacerbations were identified prospectively via symptom-based diaries over a 12-month period. RESULTS: The study group comprised 45 COPD subjects and 10 controls. Mean log C(5) was lower in the COPD group than in the control group (0.97 (95% confidence interval (CI): 0.76-1.18) versus 1.26 (95% CI: 0.81-1.71), P = 0.095). In the COPD group, log C(5) was negatively correlated with serum CRP level (r = -0.36, P = 0.02) and significantly associated with the exacerbation frequency (r = -0.38, P = 0.01). Stepwise multiple regression analysis showed that cough-reflex sensitivity was significantly associated with exacerbation frequency (r(2) = 0.15, P = 0.01). CONCLUSIONS: Hypersensitivity of the cough reflex to inhaled capsaicin might reflect airway inflammation in stable COPD patients, which predisposes to frequent exacerbations.

[Pre- and probiotics increase host-cell immunological competence, improve bowel movement, and prevent the onset of colon cancer--an analysis based on movements of intestinal microbiota].

The activation of host immunological competence through improvement of the intestinal environment by pre and probiotics has been reported. NK cell activity, the bactericidal phagocytic activities of neutrophils in peripheral blood, and bowel movements and short chain fatty acids (SCFAs) in intestinal microbiota increase after the administration of pre- and probiotics. SCFAs shift to acidosis of the intestinal environment and advance apoptosis. Furthermore, SCFAs promote intestinal peristaltic movements through SCFA receptors such as GPT 41 and GPR43, located in the intestinal epithelium. It is known that the acceleration of intestinal apoptosis prevents the onset of colon cancer. Improvement of the intestinal environment leads to an increase in host-cell immunological competence, bowel movements, and the prevention of colon cancer.

Is ERCP really necessary in case of suspected spontaneous passage of bile duct stones?

AIM: To investigate the usefulness of magnetic resonance cholangiopancreatography (MRCP) and the need for endoscopic retrograde cholangiopancreatography (ERCP) in cases of suspected spontaneous passage of stones into the common bile duct. METHODS: Thirty-six patients with gallbladder stones were clinically suspected of spontaneous passage of stones into the common bile duct because they presented with clinical symptoms such as abdominal pain and fever, and showed signs of inflammatory reaction and marked rise of hepatobiliary enzymes. These symptoms resolved and they showed normalized values of blood biochemical parameters after conservative treatment without evidence of stones in the common bile duct on MRCP. All these patients were subjected to ERCP within 3 d of MRCP to check for the presence of stones. RESULTS: No stones were detected by ERCP in any patient, confirming the results of MRCP. CONCLUSION: When clinical symptoms improve, blood biochemical parameters have normalized, and MRCP shows there are no stones in the common bile duct, it can be considered the stone has spontaneously passed and thus ERCP is not necessary.

New double-stapling technique for esophagojejunostomy and esophagogastrostomy in gastric cancer surgery, using a peroral intraluminal approach with a digital stapling system.

In the abdominal-transhiatal approach for resection of adenocarcinoma of the cardia or subcardia, and in laparoscopy-assisted total gastrectomy (LATG), the use of a circular stapling device has potential problems with the placement of the purse-string suture and insertion of the anvil of the instrument. We describe a new double-stapling technique for esophagojejunostomy and esophagogastrostomy, using a peroral intraluminal approach with a digital stapling system, a flexible shaft remote-control stapler - the Surg-ASSIST and Power Circular Stapler 21 mm (PCS). The overtube of the flexible shaft of the PCS is prepared with a nylon tie and secured to a nasogastric (NG) tube. The flexible shaft is manually advanced down the esophagus with guidance by pulling the NG tube from the abdominal cavity side. The trocar of the flexible shaft is removed from the stump of the abdominal esophagus and connected to the anvil and they are approximated; the stapler device is then fired to form a double-stapled esophagojejunostomy and esophagogastrostomy. Our peroral intraluminal approach does not require a suturing technique, and it can make anastomosis after resection for carcinoma of the esophagogastric junction and after LATG safe and simple.

Confirmation of the antispasmodic effect of shakuyaku-kanzo-to (TJ-68), a Chinese herbal medicine, on the duodenal wall by direct spraying during endoscopic retrograde cholangiopancreatography.

The purpose of the study was to evaluate the suppressive effect of TJ-68 on duodenal spasms during endoscopic retrograde cholangiopancreatography (ERCP). At the point when the duodenal papilla was confirmed after insertion of the endoscope during ERCP, 5.0 g TJ-68 (Tsumura Co., Tokyo, Japan) was dissolved in 50 ml of saline at 36 degrees C, and the whole volume was sprayed slowly using a spray tube from the orifice of the forceps to the duodenal papilla of the 50 patients who demonstrated peristalsis of the digestive tract ("duodenal spasm"). The endoscopic procedure was not performed during that time, and the time until the spasm was suppressed was determined. After the arrest of the spasm, the intended tests and treatment were conducted, and the time until the duodenal spasm started again was determined. The suppressive effect on duodenal spasm was observed in 38 (76%) of 50 patients. The duration from the spraying of TJ-68 of the patients who observed the suppressive effect on duodenal spasm was 50-182 s (mean 122 +/- 21 s). The spasm arrest duration was 7.2-21 min (mean 9.6 +/- 1.2 min). Direct spraying of TJ-68 on the duodenal mucosa suppressed duodenal spasm, and it may be useful during ERCP when anticholinergic agents are contraindicated.

Single nucleotide polymorphism typing of the human toll-like receptor 4 gene at the 2-kb upstream region of the 5' untranslated region: New enclosure strategy for the risk grouping of poorly-differentiated gastric adenocarcinoma patients.

To date, no enclosure method for risk grouping patients with poorly-differentiated gastric adenocarcinoma has been identified. We examined the relationship between mutations in toll-like receptor 4 (TLR4) and patients with poorly-differentiated gastric adenocarcinoma. Genomic DNA was extracted from the peripheral blood of 38 patients, 20 with well-differentiated and 18 with poorly-differentiated gastric cancer, from 25 patients with colorectal cancer and from 10 healthy volunteers. The polymorphism of TLR4 up to the 2-kb upstream region of the 5' untranslated region (UTR) was analyzed. The results revealed the presence of single nucleotide polymorphisms (SNPs) only among patients with poorly-differentiated gastric adenocarcinoma. SNPs were found at 3 sites: -2081, -2026 and -1601 in 12, 15 and 15 of the 18 cases of poorly-differentiated gastric adenocarcinoma, respectively. The results of the determination of a consensus among the base sequences of the core promoter, basal promoter and upstream promoter elements reveal that the variant sites were present in the TLR4 mRNA promoter region, suggesting that they were biologically significant variations. Polymorphism analysis of the upstream region of the 5' UTR of TLR4 may be a useful new enclosure strategy for the risk grouping of poorly-differentiated gastric adenocarcinoma patients.