Altered expression of imprinted genes in patients with cytogenetically normal­acute myeloid leukemia: Implications for leukemogenesis and survival outcomes.

Genomic imprinting, an epigenetic mechanism that regulates gene expression from parental chromosomes, holds substantial relevance in multiple cancers, including hematopoietic malignancies. In the present study, the expression of a panel of 16 human imprinted genes in bone marrow samples from 64 patients newly diagnosed with cytogenetically normal-acute myeloid leukemia (CN-AML) were examined alongside peripheral blood samples from 85 healthy subjects. The validated findings of the present study revealed significant upregulation of seven genes [COPI coat complex subunit gamma 2 (COPG2), H19 imprinted maternally expressed transcript (H19), insulin like growth factor 2 (IGF2), PEG3 antisense RNA 1 (PEG3-AS1), DNA primase subunit 2 (PRIM2), solute carrier family 22 member 3 SLC22A3 and Zinc finger protein 215 (ZNF215)] in patients with CN-AML (P<0.001). Notably, the expression level of H19 exhibited an inverse association with the survival duration of the patients (P=0.018), establishing it as a predictive marker for two- and five-year survival in patients with CN-AML. Kaplan-Meier analysis demonstrated that patients with lower H19 expression had superior two- and five-year survival rates compared with those with higher H19 expression. The results of the present study highlighted the association between loss of imprinting and leukemogenesis in CN-AML, underscoring the significance of H19 imprinting loss as a prognostic indicator for unfavorable two- and five-year survival in CN-AML patients.

Clinical outcomes of endoscopic submucosal dissection for colorectal neoplasms: A single-center experience in Southern Taiwan.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) as an advanced endoscopic procedure can be considered for the removal of colorectal lesions with high suspicion of limited submucosal invasion or cannot be optimally removed by snare-based techniques. We aimed to analyze the clinical outcomes of ESD for colorectal neoplasms in our hospital. METHODS: We retrospectively enrolled 230 patients with 244 colorectal neoplasms who received ESD procedures from April 2012 to October 2020 at Kaohsiung Chang Gung Memorial Hospital. Clinicopathological data were collected by chart review. We also recorded ESD-related complications and clinical outcomes. RESULTS: The average age was 64 years old, with a mean follow-up time of 22.59 months. There was a loss of follow-up in 34 lesions. Most lesions were lateral spreading tumors of the non-granular type. The average ESD time was 51.9 minutes. Nine cases (3.7%) had procedure-related complications, including two intra-procedure perforations (0.8%) and seven delayed bleeding (2.9%) without procedure-related mortality. 241 lesions (98.8%) achieved en-bloc resection, while 207 lesions (84.8%) achieved R0 resection. Most lesions were tubulo-(villous) adenoma. Malignancy included 35 adenocarcinomas and 5 neuroendocrine tumors. No local recurrence was developed during follow-up. Multivariate analysis for long ESD time revealed significance in size ≥ 10 cm2 and endoscopist's experience < 3 years. Pre-ESD endoscopic ultrasound revealed good prediction in discrimination of mucosal (sensitivity: 0.90) and submucosal lesion (specificity: 0.67). CONCLUSIONS: ESD for colorectal neoplasms is an effective and safe technique. Size ≥ 10 cm2 and endoscopist's experience < 3 years were significantly associated with long procedure time. Pre-ESD EUS provided a good prediction for colorectal neoplasms in invasion depth.

Presume Why Probiotics May Not Provide Protection in Inflammatory Bowel Disease through an Azoxymethane and Dextran Sodium Sulfate Murine Model.

Recent studies have shown dysbiosis is associated with inflammatory bowel disease (IBD). However, trying to restore microbial diversity via fecal microbiota transplantation (FMT) or probiotic intervention fails to achieve clinical benefit in IBD patients. We performed a probiotic intervention on a simulated IBD murine model to clarify their relationship. IBD was simulated by the protocol of azoxymethane and dextran sodium sulfate (AOM/DSS) to set up a colitis and colitis-associated neoplasm model on BALB/c mice. A single probiotic intervention using Clostridium butyricum Miyairi (CBM) on AOM/DSS mice to clarify the role of probiotic in colitis, colitis-associated neoplasm, gut microbiota, and immune cytokines was performed. We found dysbiosis occurred in AOM/DSS mice. The CBM intervention on AOM/DSS mice failed to improve colitis and colitis-associated neoplasms but changed microbial composition and unexpectedly increased expression of proinflammatory IL-17A in rectal tissue. We hypothesized that the probiotic intervention caused dysbiosis. To clarify the result, we performed inverse FMT using feces from AOM/DSS mice to normal recipients to validate the pathogenic effect of dysbiosis from AOM/DSS mice and found mice on inverse FMT did develop colitis and colon neoplasms. We presumed the probiotic intervention to some extent caused dysbiosis as inverse FMT. The role of probiotics in IBD requires further elucidation.

Loss of ZNF215 imprinting is associated with poor five-year survival in patients with cytogenetically abnormal-acute myeloid leukemia.

Genomic imprinting is a form of epigenetic regulation and imprinted genes are silenced in a parental-specific manner. Imprinting is associated with various human diseases and cancers, but its roles in leukemogenesis remains elusive. In this study, the expression of a panel of 16 human imprinted genes was investigated using real-time quantitative polymerase chain reaction and 8 of them were further validated in 114 patients newly diagnosed with cytogenetically abnormal-acute myeloid leukemia (CA-AML) and 85 healthy subjects. Our results demonstrated upregulated expression of 8 imprinted genes (C15orf2, COPG2, H19, IGF2, PEG3-AS1, PRIM2, SLC22A3 and ZNF215) was observed in patients with CA-AML (p < 0.001). Patients' survival days were negatively correlated with the expression levels of H19 (p = 0.024), PGE3-AS1 (p = 0.038), and ZNF215 (p = 0.012). Multivariate logistic regression analysis further revealed the expression level ZNF215 can be used as a predictor for five-year survival for patients with CA-AML (p = 0.009) with a hazard ratio of 0.870 (95.0% confident interval: 0.784-0.965). Our results demonstrated that loss of imprinting of imprinted genes is critical for the leukemogenesis of AML under CA condition, and loss of ZNF215 imprinting is associated with poor five-year survival of patients with CA-AML.

Clinicopathological features and outcome of esophageal neuroendocrine tumor: A retrospective multicenter survey by the digestive endoscopy society of Taiwan.

BACKGROUND & AIMS: Esophageal neuroendocrine tumors (NET) are very rare and mostly carcinomic, carrying poor prognosis. There is still no guideline or consensus on the treatment for esophageal NET. METHODS: Patients with histologically-proven esophageal neuroendocrine tumor were recruited from 9 hospitals in Taiwan between 2002 and 2017. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. RESULTS: In total, 39 esophageal NET were analyzed and 38 were neuroendocrine carcinoma (NEC). Sixteen (41%) patients had mixed components with either adenocarcinoma (N = 9, 23%) or squamous-cell carcinoma (SCC) (N = 7, 18%). 64.1% of the patients experienced dysphagia and ulcerative mass was the most comment endoscopic finding. There was a higher proportion of drinkers (54.1%), betel chewers (21.6%) and smokers (64.9%) among the patients than in the general population in Taiwan. Five patients (12.8%) had been diagnosed with other cancers. Definite chemoradiotherapy (N = 14, 35.9%) and surgery (N = 7, 17.9%) were the major treatment. Patients with Ki-67% above the median level (50%) in the tumors tended to have worse survival (P = 0.06). However, presence of mixed component was not a significant survival predictor in our study (P = 0.56). CONCLUSION: Mixed component of an esophageal NET is commonly observed. Staged workup and the principle of treatment can follow that for the common cancer type of esophagus. The risk factors and behaviors of esophageal NEC in Taiwan seem to be similar to that of esophageal SCC.

Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat model.

BACKGROUND AND AIM: Delayed gastric emptying occurs in more than 50% of chronic diabetic patients, and this is associated with significant impairments in quality of life. Traditional therapy for delayed gastric emptying has focused on supportive treatment, and there is no significant effective therapy. The effect of low-energy shock wave on gastric motility is never studied. We investigated low-energy shock wave on gastric motility in a diabetic rat model. METHODS: Twenty-eight male Wistar rats were studied and separated in three groups in randomized order as control, diabetic rats received shock wave, and diabetic rats received the sham procedure. Antral area and motility were recorded using the transabdominal ultrasound. Blood was taken for measurement of gastric motility peptides. Subjects were killed for immunohistochemical stain analysis of enteric plexus of the stomach. RESULTS: We successfully induced 20 diabetic rats and set ultrasound for measuring rat gastric contract and emptying model and demonstrated that 6 weeks of low-energy shock wave could promote gastric contraction and emptying in diabetic rats. Moreover, we demonstrated that shock wave could increase defecation and feces and decrease serum cholesterol and triglycerol. However, no effect on glycohemoglobin and gastric motility peptides was recorded. In the immunohistochemical staining, shock wave increased expression of gastric myenteric neuron plexus. CONCLUSION: Low-energy shock wave can increase gastric contraction and emptying by activating axonal regeneration and increasing myenteric plexus, but not related with motility peptides.

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST).

Gastric neuroendocrine tumors (GNETs) are a heterogeneous group of neoplasm with varying biological characteristics. This study aimed to investigate the clinical features and outcomes of GNET patients after endoscopic diagnosis and treatment in a multicenter registry. Patients with GNETs confirmed histologically were recruited from 17 hospitals between January 2010 and April 2016 in Taiwan. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. Totally 187 (107 female, 80 male) patients were recruited. Mean ( ±â€Šstandard deviation [SD]) age and size of tumors were 63.2-year-old ( ±â€Š14.6) and 2.3-cm ( ±â€Š3.0). World Health Organization (WHO) grading were 93 (49.7%) G1, 26 (13.9%) G2, 40 (21.4%) G3, and 28 (15.0%) unknown. G3 patients were older (mean ±â€ŠSD, 71.6 ±â€Š12.4 vs. 60.9 ±â€Š14.3/56.7 ±â€Š15.4 years), larger (6.1 ±â€Š4.0 vs.1.2 ±â€Š1.3/2.4 ±â€Š2.5 cm), more distally located (35.0% vs. 7.6%/15.4%), lower proportion of superficial lesions (17.5% vs. 61.9%/53.8%) and higher rates of lymphovascular invasion (32.5% vs. 3.2%/7.7%) than G1/G2. There was no nodal or distant organ metastases despite different grading of lesions≦10 mm and those <20 mm limited to mucosa and submucosa layers. GNETs larger than 20 mm with G1, G2, and G3 had lymph node (LN) metastatic rates of 21.4%, 30.0%, and 59.3%, respectively. Survivals were different between grading for those >20 mm (log-rank test P = .02). Male gender (P = .01), deeper invasion (P = .0001), nodal (P < .0001), and distant organ metastases (P = .0001) were associated with worse outcome. In conclusion, treatment strategies for GNET should be decided by grading, size, invasiveness, and LN metastasis risk. Curative endoscopic resection is feasible for G1/2 lesions less than 20 mm and limited to mucosa/submucosa layers without lymphovascular invasion.

The incidence and clinical associated factors of interval colorectal cancers in Southern Taiwan.

BACKGROUND/PURPOSE: Interval colorectal cancer (CRC) is an emerging issue in CRC screening and surveillance. The frequency of interval CRC and its associated factors have not been well studied in Eastern Asia. We aim to clarify the factors associated with interval CRC. METHODS: CRC patients who had negative colonoscopy results 6-36 months prior to cancer diagnosis were defined as cases of interval CRC. Patient characteristics, past history, colon preparation, colonoscopy findings, and pathology were retrospectively evaluated. A total of 670 patients with colorectal adenocarcinoma by pathology who also underwent colonoscopy before diagnosis from January 2005 to November 2014 were recruited. RESULTS: Twenty-two (3.28%) patients (65.7 ± 9.2 years old; 9 male) were diagnosed with interval CRC. The interval CRCs were predominantly located at the rectum and cecum, and presented as earlier stage cancers (Stage I and Stage II: 86.4%, Stage III and Stage IV: 13.6%). Factors associated with interval cancer include end-stage renal disease (ESRD) (hazard ratio: 10.494, 95% confidence interval: 2.131-51.681) and shorter ascending colon withdrawal time (interval cancer: noninterval cancer 2.00±0.82: 4.91±3.74 minutes; hazard ratio: 0.561, 95% confidence interval: 0.345-0.913). Prior polypectomy and tumor size also tended to be related to interval CRC. CONCLUSION: The prevalence of interval CRC in the present study is 3.28%. Comorbidity with ESRD and shorter ascending colon withdrawal time could be factors associated with interval CRC. Good colon preparation for the patients with ESRD and more ascending colon withdrawal time could reduce the interval CRC.

Endosonographic surveillance of 1-3 cm gastric submucosal tumors originating from muscularis propria.

AIM: To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria (SMTMPs). METHODS: By reviewing the computerized medical records over a period of 14 years (2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound (EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in 2016. RESULTS: A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors (GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until 2016. CONCLUSION: Most 1-3 cm gastric SMTMPs (71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size (> 14.0 mm) and irregular border.

A Randomized Control Trial Comparing 2 Levofloxacin-Containing Second-Line Therapies for Helicobacter pylori Eradication.

Summary of Trial Design.Lengthy exposure to quinolone-containing triple therapy in Helicobacter pylori eradication leads to the development of drug resistance. Sequential therapy with a quinolone and metronidazole -containing regimen appears to be an effective treatment option. This randomized controlled trial aimed to compare the efficacy of 5-plus 5 days' levofloxacin and metronidazole-containing sequential therapy (EALM) with that of 10-day levofloxacin-containing triple therapy (EAL) in second-line H pylori eradication treatment.One hundred and sixty-four patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an EALM therapy group (n = 82; esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days) or a 10-day EAL therapy group (n = 82; levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid). One patient was lost to follow-up in each group. Follow-up for H pylori status was performed 4 to 8 weeks later.Eradication rates for the EALM and EAL groups were 90.2% (74/82, 95% confidence interval [CI] = 83.7%-96.8%) and 80.5% (66/82, 95% CI = 71.7%-89.2%, P = 0.077) in the intention-to-treat analysis; and 91.4% (74/81, 95% CI = 85.1%-97.6%) and 81.5% (66/81, 95% CI = 72.8%-90.1%, P = 0.067) in the per-protocol analysis. The adverse events for the EALM and EAL groups were 23.5% versus 11.1%, P = 0.038 but were all very mild and were well tolerated except for 1 patient with poor compliance. The compliances were 98.8% and 100%, respectively, between the 2 groups. An antibiotic resistance to levofloxacin was the clinical factor influencing the efficacy of H. pylori eradication therapy in the EAL group, and dual resistance to levofloxacin and metronidazole in the EALM group.Levofloxacin and metronidazole-containing sequential therapy achieved a >90% eradication rate as a second-line H pylori therapy. Dual antibiotic resistance to levofloxacin and metronidazole was the clinical factor influencing the efficacy of H pylori eradication therapy in the sequential therapy (ClinicalTrials.gov number: NCT02596620).

Associated factors in Streptococcus bovis bacteremia and colorectal cancer.

Reports suggest that between 25% and 80% of patients with Streptococcus bovis/gallolyticus bacteremia have concomitant colorectal tumors. This retrospective study was aimed to identify associations between clinical characteristics and a finding of colorectal neoplasm in patients with S. bovis bacteremia who had colonoscopy examination. We retrospectively reviewed the records of patients with S. bovis bacteremia from Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, between January 2004 and January 2014. Clinical data including age, sex, comorbidities, blood culture, and colonoscopy findings were collected and their relationship to a finding of colorectal cancer was examined. A total of 107 patients with S. bovis bacteremia were identified, of whom 49 (72% male; age 65 ± 12 years) were investigated with colonoscopy; 15 of these patients (30.6%) had colorectal adenocarcinoma. Female sex (p = 0.014) and a history of noncolorectal malignancy (p = 0.004) were associated with a finding of colorectal adenocarcinoma. There were no associations with age, percentage of blood cultures, or the presence of diabetes mellitus, chronic liver disease, heart disease, or end-stage renal disease. Our results show that S. bovis bacteremia is associated with the presence of colorectal adenocarcinoma, especially in female patients, and concomitant existence of other malignancies.

Five-year sequential changes in secondary antibiotic resistance of Helicobacter pylori in Taiwan.

AIM: To determine changes in the antibiotic resistance of Helicobacter pylori (H. pylori) in southern Taiwan after failure of first-line standard triple therapy. METHODS: We analyzed 137 H. pylori-infected isolates from patients who experienced eradication failure after standard first-line triple therapy from January 2010 to December 2014. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the E-test method. The minimal inhibitory concentration (MIC) was determined by the agar dilution test. MIC values of ≥ 0.5, ≥ 1, ≥ 1, ≥ 4 and ≥ 8 mg/L were considered to be the resistance breakpoints for amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole, respectively. RESULTS: A high resistance rate was found for clarithromycin (65%-75%) and metronidazole (30%-40%) among patients who failed first-line standard therapy. The resistance levels to amoxicillin and tetracycline remained very low; however, levofloxacin resistance was as high as 37.5% in 2010 but did not increase any further during the past 5 years. The rates of resistance to these antibiotics did not show a statistically significant upward or downward trend. CONCLUSION: Antibiotic resistance of H. pylori remains a problem for the effective eradication of this pathogen and its associated diseases in Taiwan. High clarithromycin resistance indicated that this antibiotic should not be prescribed as a second-line H. pylori eradication therapy. Moreover, levofloxacin-based second-line therapy should be used cautiously, and the local resistance rates should be carefully monitored.

Seven-Day Nonbismuth Containing Quadruple Therapy Could Achieve a Grade "A" Success Rate for First-Line Helicobacter pylori Eradication.

This prospective study was to assess the efficacy of nonbismuth containing quadruple therapy as first-line H. pylori treatment and to determine the clinical factors influencing patient outcome. We enrolled 200 H. pylori-infected naïve patients. They were prescribed either a 7-day nonbismuth containing quadruple therapy group (EACM, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarithromycin 500 mg twice daily) or a 7-day standard triple therapy group (EAC, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily). Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by EACM and EAC groups were 95.6% (95% confidence interval [CI] = 89.4%-98.3%) and 79.3% (95% CI = 70%-86.4%) in the per-protocol analysis (P < 0.001) and 88% (95% CI = 80.2%-93.0%) and 73% (95% I = 63.6%-80.3%) in the intention-to-treat analysis (P = 0.007). Clarithromycin resistance, metronidazole resistance, and dual clarithromycin and metronidazole resistances were the clinical factors influencing H. pylori eradication in EACM group. Clarithromycin resistance and dual clarithromycin and metronidazole resistances were the influential factor for EAC treatment. In conclusion, the results suggest that 7-day nonbismuth containing quadruple therapy could achieve a grade "A" report card for first-line H. pylori treatment.

Decreased gastric motility in type II diabetic patients.

BACKGROUND: To differentiate gastric motility and sensation between type II diabetic patients and controls and explore different expressions of gastric motility peptides. METHODS: Eleven type II diabetic patients and health volunteers of similar age and body mass index were invited. All underwent transabdominal ultrasound for gastric motility and visual analogue scales. Blood samples were taken for glucose and plasma peptides (ghrelin, motilin, and glucagon-like peptides-1) by ELISA method. RESULTS: Gastric emptying was significantly slower in diabetic patients than controls (T50: 46.3 (28.0-52.3) min versus 20.8 (9.6-22.8) min, P ≤ 0.05) and less antral contractions in type II diabetic patients were observed (P = 0.02). Fundus dimensions did not differ. There were a trend for less changes in gastrointestinal sensations in type II diabetic patients especially abdomen fullness, hunger, and abdominal discomfort. Although the serum peptides between the two groups were similar a trend for less serum GLP-1 in type II diabetic patients was observed (P = 0.098). CONCLUSION: Type II diabetic patients have delayed gastric emptying and less antral contractions than controls. The observation that there were lower serum GLP-1 in type II diabetic patients could offer a clue to suggest that delayed gastric emptying in diabetic patients is not mainly influenced by GLP-1.

Predicting the progress of caustic injury to complicated gastric outlet obstruction and esophageal stricture, using modified endoscopic mucosal injury grading scale.

Severe caustic injury to the gastrointestinal tract carries a high risk of luminal strictures. The aim of this retrospective study was to identify predicting factors for progress of caustic injury to gastric outlet obstruction (GOO) and esophageal strictures (ES), using modified endoscopic mucosal injury grading scale. We retrospectively reviewed medical records of patients with caustic injuries to the gastrointestinal tract in our hospital in the past 7 years. We enrolled 108 patients (49 male, 59 female, mean age 50.1 years, range 18-86) after applying strict exclusion criteria. All patients received early upper gastrointestinal endoscopy within 24 hours of ingestion. Grade III stomach injuries were found in 58 patients (53.7%); 43 (39.8%) esophageal, and 13 (12%) duodenal. Of the 108 patients, 10 (9.3%) died during the acute stage. Age over 60 years (OR 4.725, P = 0.029) was an independent risk factor of mortality for patients after corrosive injury. Among the 98 survivors, 36 developed luminal strictures (37.1%): ES in 18 patients (18.6%), GOO in 7 (7.2%), and both ES and GOO in 11 (11.3%). Grade III esophageal (OR 3.079, P = 0.039) or stomach (OR 18.972, P = 0.007) injuries were independent risk factors for obstructions. Age ≥ 60 years was the independent risk factor for mortality after corrosive injury of GI tract. Grade III injury of esophagus was the independent risk factor for development of ES. Grade III injury of stomach was the independent risk factor for development of GOO.

Deregulated expression of circadian clock genes in gastric cancer.

BACKGROUND: Gastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death. Circadian rhythm exhibits a 24-hour variation in physiological processes and behavior, such as hormone levels, metabolism, gene expression, sleep and wakefulness, and appetite. Disruption of circadian rhythm has been associated with various cancers, including chronic myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However, the expression of circadian clock genes in GC remains unexplored. METHODS: In this study, the expression profiles of eight circadian clock genes (PER1, PER2, PER3, CRY1, CRY2, CKIϵ, CLOCK, and BMAL1) of cancerous and noncancerous tissues from 29 GC patients were investigated using real-time quantitative reverse-transcriptase polymerase chain reaction and validated through immunohistochemical analysis. RESULTS: We found that PER2 was significantly up-regulated in cancer tissues (p < 0.005). Up-regulated CRY1 expression was significantly correlated with more advanced stages (stage III and IV) (p < 0.05). CONCLUSIONS: Our results suggest deregulated expressions of circadian clock genes exist in GC and circadian rhythm disturbance may be associated with the development of GC.

Ten-Day versus 14-Day Levofloxacin-Containing Triple Therapy for Second-Line Anti-Helicobacter pylori Eradication in Taiwan.

Second-line Helicobacter pylori (H. pylori) eradication with fluoroquinolone-containing triple therapy is one of the recommended treatment options, but neither 7-day nor 10-day regimens provide >90% success rates. The current retrospective study aimed to clarify the effects of 10-day and 14-day levofloxacin-containing triple therapies for second-line H. pylori eradication in a Taiwanese cohort and to evaluate the potential clinical factors influencing eradication. A total of 200 patients who failed H. pylori eradication using the standard triple therapy were prescribed with either a 10-day (EAL-10) or a 14-day (EAL-14) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily). Follow-up studies to assess treatment response were carried out 8 weeks later. Eradication rates attained by EAL-10 and EAL-14 were 75.6%; 95% CI = 63.9-85.3% and 92.5%; 95% CI = 84.5-98.1%, P = 0.002 in the per protocol analysis and 68%; 95% CI = 56.6-78.5% and 86%; 95% CI = 76.8-93.4%, P = 0.002 in the intention-to-treat analysis. The duration of H. pylori therapy is the independent risk factor of H. pylori eradication (P = 0.003). In conclusion, 14-day levofloxacin-containing triple therapy can provide a >90% H. pylori eradication rate, but 10-day treatment duration may be suboptimal. The longer duration of H. pylori therapy (14 days) is the independent risk factor.

The effects of endoscopic-guided balloon dilations in esophageal and gastric strictures caused by corrosive injuries.

BACKGROUND: Esophageal stricture (ES) and gastric outlet obstruction (GOO) can occurred in patients injured by the ingestion of corrosive agents. These complications may occur concurrently but has not been reported in the literature. The aims of this study are to assess the effects and complications of endoscopic-guided balloon dilations (EBD) in patients with corrosive-induced upper gastrointestinal strictures, either ES or GOO alone and simultaneous occurrences of both (ES + GOO). METHODS: From July 2002 to December 2009, 36 patients with corrosive-induced upper gastrointestinal strictures in a tertiary hospital were recruited into this study. The patients were divided into three groups, ES group (n = 18), GOO (n = 7), and ES + GOO group (n = 11). All strictures were dilated under direct visualization by using through-the-scope balloon catheters to the end point of 15 mm. The end-point of treatment was successful ingestion of a solid or semisolid diet without additional dilation for more than 12 months. RESULTS: These 36 patients included 15 males and 21 females with average age of 47 years ranging from 25 to 79 years. The success rates for ES group is significantly better than GOO and ES + GOO group (83.3% vs. 57.1% vs. 36.4% p = 0.035). Less complications were observed in ES group than in GOO and ES + GOO group (16.7% vs. 42.9% vs. 36.4%, p = 0.041). GOO group needed more sessions of dilations in order to achieve success dilations than ES and GOO groups (13.7 ± 4.9 vs. 6.1 ± 4.7 vs. 5.5 ± 2.1, p = 0.011). CONCLUSIONS: Corrosive injuries complicated with ES can be effectively and safely treated by EBD. However, the success rates declined significantly in patients with GOO with or without ES and amore complications occurred.

Altered expression of SIRT gene family in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) include a group of malignant neoplasms that arise from the upper aerodigestive tract and represent the seventh most common cause of cancer-related death. The overall 5-year survival rates have not significantly improved for decades in spite of the advances in the field of oncology and surgery, encouraging further research on factors that might modify disease prognosis. The silent information regulator (SIR) genes (Sirtuins) play key roles in cellular stress and are associated with aging-related diseases including cancer. Currently, seven human sirtuin (SIRT1-7) genes have been identified, but the roles of SIRT genes in HNSCC are still uncertain. Therefore, in this study, we used real-time quantitative reverse transcription-polymerase chain reaction to investigate the expressions of the seven SIRT genes in human HNSCC tissues to assess the changes in cancerous and noncancerous parts and the correlation with different tumor behaviors. Our results demonstrated that the expression levels of SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly downregulated in cancerous tissues compared with noncancerous tissues (all p<0.01). The expression levels of SIRT1, SIRT2, SIRT3, SIRT5, and SIRT7 showed downregulation in advanced stages in respect to early stages (p<0.05). These results indicate that the downregulation of SIRT genes expression may contribute to the development of cancer and trigger the neoplastic disease to more advanced stages. Our study indicates that SIRT genes expression could help in the diagnosis and represent a prognostic biomarker in HNSCC.

Impact factors for difficult cecal intubation during colonoscopy.

BACKGROUND: There are no accepted means of identifying patients in whom colonoscopy is likely to be more difficult and allocate time accordingly. AIMS: To identify patient-related, endoscopist-related, and procedure-related factors associated with difficult cecal intubation. METHODS: This was a prospective study performed at the Kaohsiung Chang Gung Memorial Hospital, Kaohsiung Medical Center, from January to December 2009. Data pertaining to patient information (age, sex, weight, waist circumference and buttock girth, bowel habit, and abdomen surgery history) were recorded prospectively. Procedure-specific information including the need to alter patient position, application of external compression, and cecal intubation time (CIT) was documented. RESULTS: A total of 859 consecutive patients were enrolled. The mean age of the patients was 50.5 ± 11.4 years. CIT was longer in women compared with men (410 ± 195 vs. 376 ± 224 s; P = 0.021). Older patients had longer CITs--an additional 2.1 seconds for each incremental year (P = 0.001), and poor bowel preparation increased CIT (P = 0.019). Patients who required a position change or abdominal compression took longer to reach the cecum (P<0.001). CONCLUSIONS: Our findings emphasize the importance of colon preparation and the need for abdominal compression and a change of position when performing a difficult colonoscopy.