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The dismal outcome in patients with locally advanced or metastatic gastric cancer (GC) highlights the need for effective systemic neoadjuvant chemotherapy to improve clinical results. This study evaluated the correlation between the expression of three DNA repair genes, namely the excision repair cross-complementing group 1 (ERCC1), excision repair cross-complementing group 2 (ERCC2), and X-ray repair cross-complementing protein 1 (XRCC1) and the clinical outcome of patients with locally advanced or metastatic GC treated with mFOLFOX-4 neoadjuvant chemotherapy. Fifty-eight patients with histologically confirmed locally advanced or metastatic GC following neoadjuvant mFOLFOX-4 chemotherapy were enrolled between January 2009 and January 2018. We analyzed clinicopathological features and ERCC1, ERCC2, and XRCC1 expression to identify potential predictors of clinical response. Among the 58 patients, 16 (27.6%) were categorized into the response group (partial response) and 42 into the nonresponse group (stable disease in 24 patients and progressive disease in 18 patients). A multivariate analysis showed that ERCC1 overexpression (P = 0.003), ERCC2 overexpression (P = 0.049), and either ERCC1 or ERCC2 overexpression (P = 0.002) were independent predictors of response following mFOLFOX-4 neoadjuvant chemotherapy. Additionally, ERCC1 and ERCC2 overexpression did not only predict the response but also progression-free survival (both P < 0.05) and overall survival (both P < 0.05). ERCC1 and ERCC2 overexpression are promising predictive biomarkers for patients with locally advanced or metastatic GC receiving neoadjuvant mFOLFOX-4 chemotherapy and the potential clinical implication is mandatory for further investigation.

BACKGROUND Culture of Helicobacter pylori with previous eradication failure has been emphasized in clinical guidelines. The current unmet need to manage previously treated H pylori is one tool with diagnostic accuracy and ability for antibiotics susceptibility. Gastric juice PCR can provide diagnosis and antibiotics susceptibility; however, whether treatment failure affects its accuracy remains uninvestigated. Our study aimed to investigate diagnostic accuracy and antibiotics susceptibility of juice PCR in previously treated H pylori and to compare with the current standard of culture. METHODS We categorized all 547 patients into treatment-naive, post-1st treatment, post-2nd treatment, and post-3rd treatment. Helicobacter pylori infection was confirmed using gold standards. Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under ROC curve (AUC) of juice PCR and culture were calculated. Intra-gastric H pylori density was evaluated. Lastly, the antibiotics susceptibility results of gastric juice and culture were compared. RESULTS Our findings demonstrated AUC was higher in juice PCR than culture in all patients (96.7% vs 91.3%, P

Background and aim Asian populations have relatively lower prevalence of gastroesophageal reflux disease and tend to exhibit symptoms of prolonged gastric retention. However, it remains unknown if slower gastric emptying influences its features in Asian countries. We prospectively assessed the potential implications of slower gastric emptying in an Asian-Pacific cohort of gastroesophageal reflux disease by a hospital-based survey. Methods One hundred fifty-two patients of gastroesophageal reflux disease complete the scintigraphic measurement of solid phase of gastric emptying. Clinical symptoms and psychological stress are recorded by self-report questionnaire. The status of Helicobacter pylori infection, blood level of pepsinogen I, and I/II ratio are assessed. Results Forty-seven percent and 28% of the patients have slower gastric emptying rate, depending on the incremental defined cut-off values of slower gastric emptying, respectively. Multiple logistic regression analysis indicates that older age and depression score are independently related to slower gastric emptying. Subgroup analysis discloses that patients with slower gastric emptying and higher depression score tend to present with non-erosive esophagitis whereas higher body mass index level and male gender in patients with normal gastric emptying predict the presence of erosive reflux disease. Conclusions Our study cohort of Asian patients indicates distinctive clinical implications of slower gastric emptying in patients with gastroesophageal reflux disease.

The high prevalence of type 2 diabetes mellitus in colorectal cancer patients is a crucial public health issue worldwide. The deregulation of microRNAs has been shown to be associated with the progression of CRC; however, the effects of high blood sugar levels on miR deregulation and, in turn, CRC remain unexplored. In this study, 520 CRC patients were classified into two groups according to their blood sugar levels (≧110 or

Development of robust prognostic/predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of microRNAs might be a simple and reliable biomarker to detect postoperative early relapse in patients with CRC after radical resection. We used microRNA arrays and identified that microRNA-148a (miRNA-148a) had substantially different expression levels in early and nonearly relapsed stage II and III CRC tissues. The validation study, which included 55 early relapsed patients and 55 nonearly relapsed patients, further confirmed overexpression of miRNA-148a in nonearly relapsed samples. Subsequently, we explored whether the serum level of miRNA-148a can be used to predict early CRC recurrence. The in vitro and in vivo effects of miRNA-148a were examined by cell proliferation, migration, and invasion, as well as cell cycles, and xenograft in null mice. Last, miRNA-148a was investigated as a potential biomarker for identifying early relapse. Cellular studies demonstrated that the overexpression of miRNA-148a inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that miRNA-148a caused an accumulation of the G2 population. Moreover, lower levels of miRNA-148a expression were associated with significantly shorter disease-free survival rates and poorer overall survival rates. This study showed that miRNA-148a can inhibit tumorigenesis and reduce the early recurrence of CRC. These findings suggest that miRNA-148a may have potential clinical applications for predicting the early relapse of patients with CRC after radical resection.

Different types of proton pump inhibitor (PPI)-based triple therapies could result in different Helicobacter pylori eradication rates. This study aimed to compare the efficacy and safety of rabeprazole- and lansoprazole-based triple therapies in primary treatment of H. pylori infection. From September 2005 to July 2008, 426 H. pylori -infected patients were randomly assigned to receive a 7-day eradication therapy with either rabeprazole 20mgbid (RAC group, n =222) or lansoprazole 30mgbid (LAC group, n =228) in combination with amoxicillin 1gbid and clarithromycin 500mgbid. The patients received follow-up esophagogastroduodenoscopy (EGD) and/or 13 C-urea breath test 12–16 weeks later to define H. pylori status. Their personal and medical history, compliance and side effects were obtained by using a standardized questionnaire. Intention-to-treat analysis revealed that the eradication rate was 87.84% in the RAC group and 85.96% in the LAC group ( p =0.56). All patients returned for assessment of compliance (100% in the LAC group vs. 99.50% in the RAC group; p =0.32) and adverse events (7.20% in the RAC group vs. 5.70% in the LAC group, p =0.51). Univariate analysis suggested that patients with nonsteroid anti-inflammatory agent (NSAID) use had lower eradication rates than those without (76.71% vs. 88.74%; p =0.006). Our results showed that efficacy and safety were similar in rabeprazole- and lansoprazole-based primary therapies. The influence of NSAID usage on H. pylori eradication needs to be further investigated.

Background To identify factors affecting the harvest of lymph nodes (LNs) and to investigate the association between examining a minimum of 12 LNs and clinical outcomes in stage I-III colorectal cancer (CRC) patients. Methods The clinicopathologic features and the number of examined LNs for 1167 stage I-III CRC patients were analyzed to identify factors affecting the number of LNs harvested and the correlations between clinical outcomes and high harvests (≧12 LNs) and low harvests (

Development of an enteric fistula after surgery is a major therapeutic complication. In this study, we retrospectively examined the potential relationship between preoperative laboratory data and patient mortality by collecting patient data from a tertiary medical center. We included patients who developed enteric fistulas after surgery for gastrointestinal (GI) cancer between January 2005 and December 2010. Patient demographics and data on preoperative and pre-parenteral nutritional statuses were compared between surviving and deceased patients. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to determine the predictors and cut-off values, respectively. Patients with incomplete data and preoperative heart, lung, kidney, and liver diseases were excluded from the study; thus, out of 65 patients, 43 were enrolled. Logistic regression analysis showed that blood urea nitrogen-to-creatinine (BUN/Cr) ratio [p = 0.007; OR = 0.443, 95% confidence interval (CI), 0.245–0.802] was an independent predictor of mortality in patients who developed enteric fistulas after surgery for GI cancer. In conclusion, the results of our study showed that a high preoperative BUN/Cr ratio increases the risk of mortality in patients who develop enteric fistulas after surgery for GI cancer.

Proton pump inhibitors (PPIs) are the most potent anti-acid agents and are extensively used worldwide. PPI-induced hypergastrinemia is one of the very few side effects associated with these drugs. However, because hypergastrinemia is related to the occurrence of colonic adenomatous polyps, the purpose of this study was to analyze the relationship between the occurrence of gastrointestinal polyps and hypergastrinemia induced by PPIs. This study included 259 patients who underwent colonoscopy and esophagogastroduodenoscopy between January and August 2007. Chart records, including medication history and fasting plasma gastrin level, were reviewed and analyzed. Any subtle polypoid lesions in the stomach and colon were sampled by biopsy for histological examination. Helicobacter pylori infection status was examined by a rapid urea test during esophagogastroduodenoscopy. All patients underwent endoscopy examinations. A total of 122 patients were receiving PPI treatment for either peptic ulcer disease or reflux esophagitis and were included as the study group. The remaining 137 patients were not treated with PPIs and served as the non-PPI group. The mean fasting gastrin level in PPI users versus non-PPI users was 121.8 ng/L versus 56.8 ng/L, respectively (p < 0.001). Although the prevalence of gastric gland polyps was higher in the PPI group (65.6% vs. 37.2%, p < 0.001), there was no difference in the prevalence of colonic adenomatous polyps observed (22.13% vs. 22.62%, p = 0.928). In conclusion, the prevalence of gastric polyps, particularly fundic gland polyps, was higher among PPI users. However, the prevalence of colonic polyps was not affected by PPI use, regardless of past history of colonic adenomatous polyps.

Purpose: Previously we developed membrane-arrays as a promising tool to detect circulating tumor cells (CTC) with KRAS oncogene in patients with malignancies. This study was conducted to determinate the predictive values of CTCs with KARS mutation by membrane-arrays for metastatic colorectal cancer patients treated with cetuximab plus chemotherapy. Experimental Design: Seventy-six metastatic colorectal cancer patients receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy were enrolled. KRAS mutation status in the peripheral blood of these patients was analyzed using membrane-arrays, and KRAS mutation status in tumors was analyzed by DNA sequencing. Results: Among 76 metastatic colorectal cancer patients, KRAS mutations in tumors and in peripheral blood were identified in 33 (43.4%) and 30 (39.5%) patients, respectively. The detection sensitivity, specificity, and accuracy of membrane-arrays for CTCs with KRAS oncogene were 84.4%, 95.3%, and 90.8%, respectively, and indeed a highly significant correlation to KRAS mutations in tumors (P < 0.0001) was observed. Forty-five (59.2%) patients responded to cetuximab plus chemotherapy, and 41 and 40 were wild-type KRAS in tumors and peripheral blood, respectively (both P < 0.0001). Patients with tumors that harbor wild-type KRAS are more likely to have a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Likewise, patients with CTCs of wild-type KRAS in peripheral blood express a better progression-free survival and overall survival when treated with cetuximab plus chemotherapy (P < 0.0001). Conclusions: These findings provide evidence that detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy.

The aim of this retrospective study was to determine which clinicopathological factors influenced the incidence of postoperative relapse and overall survival rates after radical resection of T(2-4)N(0)M(0) colorectal cancer (CRC) patients via harvesting a minimum of 12 lymph nodes.Between January 2001 and June 2006, a total of 342 T(2-4)N(0)M(0) CRC patients who underwent radical resection were retrospectively analyzed in Kaohsiung Medical University Hospital. Of these 342 patients, 155 were observed by harvesting a minimum of 12 lymph nodes. These 155 patients were followed up intensively, and their outcomes were investigated retrospectively.Of 155 patients, 83 were men (53.5%) and 72 (46.5%) were women. The mean age was 65.5 +/- 11.1 years (range, 24-89 years). The median follow-up period was 49 months (range, 19-80 months). The present data showed invasive depth (P = 0.012), vascular invasion (P0.001), and perineural invasion (P = 0.009) as significantly prognostic factors for postoperative 5-year relapse rate by Kaplan-Meier analysis. Likewise, invasive depth (P = 0.013), vascular invasion (P0.001), and perineural invasion (P = 0.008) were significant factors for postoperative 5-year survival rate. Meanwhile, using a Cox proportional hazards analysis, depth of tumor invasion (P = 0.026) and vascular invasion (P = 0.001) were the independent predictors for postoperative relapse. Furthermore, the presence of vascular invasion was considerably correlated to the higher postoperative relapse rate and the poorer overall survival rates by survival analyses (P0.0001).Besides the conventional depth of tumor invasion, this study highlights the potential for using vascular invasion as a means of identifying a subgroup of T(2-4)N(0)M(0) CRC patients with adequate lymph node harvest at higher risk who would potential benefit from adjuvant therapy after surgery.

Postoperative enteric fistula is a serious complication and cause of death following gastrointestinal (GI)-tract surgery. Many reports have demonstrated the effectiveness of parenteral nutrition in the spontaneous closure of enteric fistula. Our study was aimed at analyzing the prognostic factors of parenteral nutritional support in the treatment of enteric fistula for patients with GI-tract cancer following surgery. GI-tract cancer patients receiving surgical interventions, which then unfortunately developed enteric fistula, were included in our study. All of them had to have received parenteral nutrition soon after leakages were recognized, and they were subsequently divided into successful and unsuccessful (classified as "failure") groups according to spontaneous closure of fistula or not, respectively. The studied patients' laboratory data were collected to identify the clinically relevant prognostic factors. Fifty-three primary GI-tract cancer patients with postoperative enteric fistulas were enrolled into our study. Of these, 33 patients were considered as successful parenteral nutritional therapy (successful group) and the other 20 patients (failure group) were not. After a period of parenteral nutritional therapy, serum total bilirubin, creatinine, C-reactive protein (CRP), hemoglobin, and albumin were significantly different between these two groups (all p.05). Using a multivariate logistic regression analysis, it was determined that increased serum albumin level was an independent predictive factor of successful management for enteric fistula (p = .029), in addition to the well-known lower drainage amount (500 mL/day) from the enteric fistula (p = .013). Our observations show that both serum albumin levels and drainage amounts from the enteric fistula can be potentially used as important prognostic predictors of healing enteric fistula under total parenteral nutrition in patients following surgery for GI-tract malignancies.

Metastatic colorectal cancer (mCRC) combined with hyperbilirubinemia is typically considered a contraindication to irinotecan-based therapy, a proven first-line treatment of mCRC. Herein, we present 6 consecutive patients with mCRC combined with hyperbilirubinemia who underwent UGT1A1 genotyping before receiving FOLFIRI plus bevacizumab. Dose escalation of irinotecan was performed according to the results of UGT1A1 genotyping in all patients. Improvement in the serum total bilirubin level to a normal range was noted in all 6 patients. Disease control was 100%. The median progression-free survival was 7.5 months and the median overall survival was 8.5 months. FOLFIRI plus bevacizumab as a first-line chemotherapy may achieve effective disease control and be safe in patients with mCRC and hyperbilirubinemia based on UGT1A1 genotyping. More prospective clinical studies are necessary to evaluate the clinical benefits and safety of this treatment approach.

In patients with radically resected colorectal carcinoma, lymph node involvement is particularly important for a good prognosis and adjuvant therapy. The number of such lymph node recoveries is still controversial, with recommendations ranging from 6 to 17 nodes. The aim of this study is to determine if a specified minimum number of lymph nodes examined per surgical specimen can have any effect on the prognosis of patients who have undergone curative resection for T(2-4)N(0)M(0) colorectal carcinoma. Between September 1999 and January 2005, a total of 366 patients who underwent radical resection for T(2-4)N(0)M(0) colorectal carcinoma were retrospectively analyzed in a single institution. All specimen segments were fixed, with node identification performed by sight and palpation. We excluded 186 patients who received postoperative adjuvant chemotherapy via oral or intravenous transmission to prevent possible chemotherapeutic effects on patients' prognosis; therefore, a total of 180 patients with T(2-4)N(0)M(0) colorectal carcinoma were enrolled into this study. After the pathological examination, a mean of 12 lymph nodes (range 0-66) was harvested per tumor specimen. No postoperative relapse was found in this group, where the number of examined lymph nodes was 18 or more. Univariate analysis identified the size of the tumor, depth of invasion, grade of tumor, and number of examined lymph nodes, which were significantly correlated with postoperative relapse (all P0.05). Meanwhile, both the depth of tumor invasion and the number of harvested lymph nodes were independent predictors for postoperative relapse (P0.05). The 5-year overall survival rate of T(2-4)N(0)M(0) colorectal carcinoma patients who had 18 or more lymph nodes examined was significantly higher than those who had less than 18 nodes examined (P = 0.015). Nodal harvest in patients undergoing radical resection for colorectal carcinoma was highly significant in the current investigation. Our results suggest that harvesting and examining a minimum of 18 lymph nodes per surgical specimen might be taken into consideration for more reliable staging of lymph node-negative colorectal carcinoma.

Background A lipid emulsion composed of soybean oil (long-chain triglycerides, LCT), medium-chain triglycerides (MCT) and n-3 poly-unsaturated fatty acids (PUFAs) was evaluated for immune-modulation efficacy, safety, and tolerance in patients undergoing major surgery for gastric and colorectal cancer. Methods In a prospective, randomized, double-blind study, 99 patients with gastric and colorectal cancer receiving elective surgery were recruited and randomly assigned to either the study group, receiving the n-3 PUFAs enriched intravenous fat emulsion (IVFE), or the control group, receiving a lipid emulsion comprised of soybean oil and MCTs (0.8 – 1.5 g · kg-1 · day-1) as part of total parenteral nutrition (TPN) regimen from surgery (day -1) up to post-operative day 7. Safety and efficacy parameters were assessed on day -1 and post-operative visits on day 1, 3, and 7. Adverse events were documented daily and compared between the groups. Results Pro-inflammatory markers, laboratory parameters, and adverse events did not differ prominently between the 2 groups, with the exception of net changes (day 7 minus day -1) of free fatty acids (FFAs), triglyceride, and high-density lipoprotein (HDL). Net decrease of FFAs was remarkably higher in the study group, while the net increase of triglyceride and decrease of HDL was significantly lower. Conclusions The n-3 PUFA-enriched IVFE showed improvements in lipid metabolism. In respect of efficacy, safety and tolerance both IVFE were comparable. In patients with severe stress, there is an inflammation-attenuating effect of n-3 PUFAs. Further, adequately powered clinical trials will be necessary to address this question in postsurgical GI cancer patients. Trial registration US ClinicalTrials.gov NCT00798447.

Objective. This study was designed to compare the effect ofHelicobacter pylori(H. pylori) infection treatment on serum zinc, copper, and selenium levels.Patients and Methods. We measured the serum zinc, copper, and selenium levels inH. pylori-positive andH. pylori-negative patients. We also evaluated the serum levels of these trace elements afterH. pylorieradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry.Results. Sixty-threeH. pylori-positive patients and thirtyH. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference betweenH. pylori-positive andH. pylori-negative groups. There were 49 patients with successfulH. pylorieradication. The serum selenium levels were lower after successfulH. pylorieradication, but not significantly (P=0.06). There were 14 patients with failedH. pylorieradication. In this failed group, the serum selenium level afterH. pylorieradication therapy was significantly lower than that beforeH. pylorieradication therapy (P<0.05). The serum zinc and copper levels had no significant difference between before and afterH. pylorieradication therapies.Conclusion.H pylorieradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).

The aim of this study was to evaluate the efficacy of helical tomotherapy plus capecitabine as a preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Thirty-six LARC patients receiving preoperative CRT were analyzed. Radiotherapy (RT) consisted of 45 Gy to the regional lymph nodes and simultaneous-integrated boost (SIB) 50.4 Gy to the tumor, 5 days/week for 5 weeks. Chemotherapy consisted of capecitabine 850 mg/m2, twice daily, during the RT days. Patients underwent surgery 6–8 weeks after completion of CRT. Information was collected for patient characteristics, treatment response, and acute and late toxicities. Grade 3/4 (G3+) toxicities occurred in 11.1% of patients (4/36). Sphincter preservation rate was 85.2% (23/27). Five patients (14.3%) achieved pathological complete response. Tumor, nodal, and ypT0-2N0 downstaging were noted in 60% (21/35), 69.6% (16/23), and 57.1% (20/35). Tumor regression grade 2~4 was achieved in 28 patients (80%). After a median follow-up time of 35 months, the most common G3+ late morbidity was ileus and fistula (5.7%, 2/35). The study showed that capecitabine plus helical tomotherapy with an SIB is feasible in treatment of LARC. The treatment modality can achieve a very encouraging sphincter preservation rate and a favorable ypT0-2N0 downstaging rate without excessive toxicity.

This study compared the clinical responses of patients with metastatic colorectal cancer (mCRC) with 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) plus bevacizumab therapy either with or without uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping and irinotecan dose escalation. Of 107 total patients with mCRC, 79 were classified as the study group and 28 as the control group. The study group received irinotecan dose escalation based on UGT1A1 genotyping whereas the control group did not. Clinicopathologic features, response rates, and survival were compared for the 2 groups. The clinical response rate of patients with mCRC treated with FOLFIRI plus bevacizumab under UGT1A1 genotyping and irinotecan dose escalation was significantly better than that of those without these prospective tests and dose escalation (P = 0.028). Both progression-free survival (PFS) and overall survival were significantly greater in clinical responders than nonresponders (both, P0.001), and PFS was significantly greater among the study group patients than among the control group patients, with a median PFS of 12.2 months vs 9.4 months (P = 0.025). Grade 3/4 adverse events were not significantly different between the 2 groups (P = 0.189). Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan to obtain a better clinical response/outcome with comparable toxicities.

We aimed to evaluate the performance of fecal occult blood tests (FOBT) for the screening of colorectal cancer (CRC).We selected participants from a medical center in Taiwan, China from November 2009 to June 2011. All participants underwent screening colonoscopy and were asked to provide their stool samples for qualitative immunochemical FOBT (qlFIT), quantitative immunochemical FOBT (qnFIT) and the guaiac-based FOBT(GT). The receiver operating characteristic curve was utilized to determine the optimal cut-off value of qnFIT. We measured the detection ability of the FOBT for colonic polypoid lesions.In all, 699 participants were enrolled in this study. For qnFIT, we found increased levels of fecal hemoglobin in participants with polyps ≥10 mm (251.0 ng/mL), villous-containing adenomas (98.7 ng/mL) and advanced adenomas (187.9 ng/mL). The optimal cut-off value for qnFIT was 25 ng/mL for detecting advanced colorectal neoplasms (ACRN). All three FOBT had a similar but low estimate in detecting small and tubular adenomatous polyps. The qnFIT had a better detection ability for large adenomas (positive likelihood ratio [PLR], 5.6 vs 3.1 vs 0.3) and adenomas with villous-components (PLR 3.7 vs 3.3 vs 0.3) than qlFIT and GT. For the ACRN group, qnFIT also showed the best screening ability with a sensitivity of 56.8%, accuracy of 86.7% and PLR 5.0.Both qnFIT and qlFIT perform better than GT in detecting advanced adenomas and CRC in the Taiwanese population.

Background Few studies have reported the association between lifestyle factors and prognosis of esophageal squamous cell carcinoma (ESCC) and among these, the effects of habitual areca nut chewing have never been examined. Methodology/Principal Findings Data from 718 pathology-proven ESCC patients recruited in a multicenter hospital-based case-control study between 2000 and 2008 in Taiwan were analyzed. Clinical and lifestyle information were obtained by chart review and questionnaire survey. Death was confirmed using the National Death Index. The mean age at diagnosis was 59.8 years and 506 (70.5%) patients presented with stage III or IV diseases. The overall 1- and 5-year survival rates were 41.8% and 9.75% respectively. In addition to clinical stage, habitual alcohol drinking was found to be the strongest predictor for ESCC survival, followed by areca chewing and smoking. Compared with non-users, patients who regularly used all three substances (alcohol, areca nut, and cigarette) had 1.52 times the risk of early death (adjusted hazard ratio = 1.52, 95% CI = 1.02–2.27, p = 0.04). In addition, the more the number of substances used, the worse the prognosis of ESCC (adjusted p for trend = 0.01). Conclusions/Significance Our study found that indulgence in more substances is a significant predictor of ESCC survival. Further mechanistic studies are necessary to elucidate how these substances lead to an adverse outcome.

Aim: Dismal clinical results in patients with unresectable advanced or recurrent gastric cancer highlight the need for effective systemic chemotherapy. An increase in adverse events associated with systemic chemotherapy is shown in elderly patients, but it remains controversial whether they should receive the same chemotherapy used for younger patients. We retrospectively studied 73 patients with unresectable advanced or recurrent gastric cancer, including 48 nonelderly patients (Patients and Methods: From January 2006 to June 2011, 73 patients with histologically confirmed unresectable advanced or recurrent gastric cancer were enrolled in this study. All patients were treated with an mFOLFOX-4 regimen of 85 mg/m2 of oxaliplatin and 200 mg/m2 of leucovorin on the first day, followed by a 24-hour continuous infusion of 1,000 mg/m2 of 5-fluorouracil in 2 days with a 2-week interval. Treatment continued until disease progression or intolerable adverse events occurred. Results: Overall response rates show clinical efficacy (41.1%, 30/73 patients), stable cancer (26.0%, 19/73 patients) and progressive cancer (32.9%, 24/73 patients). The response rate was 36.0% in the elderly group and 43.8% in the nonelderly group (p = 0.891). In elderly patients, the overall time to progression was 8.1 months and the median overall survival was 11.9 months. On the other hand, in nonelderly patients, the overall time to progression was 7.9 months (p = 0.483) and the median overall survival was 11.2 months (p = 0.953). The results show no statistical differences in efficacy and adverse events between elderly and nonelderly groups (all p > 0.05). Conclusion: The mFOLFOX-4 therapy is an effective and safe first-line treatment for unresectable advanced or recurrent gastric cancer patients. Moreover, mFOLFOX-4 was well tolerated and effective in both nonelderly and elderly patients.

BACKGROUND/AIMS: Mini laparotomy is technical for the resection of colorectal cancer (CRC) in selected patients. The aim was to compare clinical outcomes of mini laparotomy with conventional laparotomy in CRC patients. METHODOLOGY: Between january 2007 and june 2010, 138 patients and 117 patients underwent elective resection using either mini laparotomy or conventional laparotomy respectively. Mini laparotomy involved a colorectal resection performed through a skin incision ≤8 cm in length. Clinicopathological factors, operative procedure and postoperative course were retrospectively analyzed to compare clinical outcomes between the two groups. RESULTS: Mini laparotomy seems to be an attractive alternative for resection of CRC in selected patients. Clinicopathological and histopathological features were similar between both groups, whereas intraoperative blood loss, operative time and harvested lymph-node numbers in conventional laparotomy were significantly greater (p=0.003, p=0.008 and p=0.024, respectively). Postoperative relapse, complications and hospitalization were significantly better in the mini laparotomy (all p

The objective of this study is to explore the inflammatory modulation effect of glutamine-enriched total parenteral nutrition (TPN) by investigating the alterations of inflammation-related cytokines in gastrointestinal (GI) cancer patients postoperatively. Fifty GI cancer patients received postoperative 7 days of isocaloric and isonitrogenous TPN after operation. They were randomly divided to receive either glutamine-enriched TPN or standard TPN. The inflammation-related cytokines including interleukin-6, interleukin-10, and tumor necrosis factor-α were also determined. Records of nutritional assessments, inflammatory status, and postoperative complications were compared between the two groups. Of 50 enrolled patients, 25 patients were classified as the intervention group, and the control group also comprised 25 patients. The differences of gender, age, primary GI malignancies, and hematological and biochemical data between the two compared groups were not statistically significant (all P0.05). Compared with standard TPN, a higher serum prealbumin level and better nitrogen balance were observed in glutamine-enriched TPN (P = 0.039 and 0.048 respectively). A significantly lower serum interleukin-6 level was found in comparing glutamine-enriched with standard TPN (P = 0.01), but not in interleukin-10 (P = 0.374) and tumor necrosis factor-α levels (P = 0.653). Moreover, a significant lower serum C-reactive protein level was detected in glutamine-enriched TPN compared with standard TPN (P = 0.013). Indeed, four cases of postoperative infectious complications were noted in the control group, but no postoperative infectious complications were observed in the interventional group (P = 0.037). Our present study shows that glutamine-enriched TPN may be beneficial in improving the inflammatory status and decreasing the infectious morbidity in postoperative GI cancer patients.

Metachronous liver metastasis (MLM) occurs in 20-40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection.A total of 1,356 patients who underwent curative intent resection for CRC were retrospectively studied. Of these patients, those who with 30 days postoperative mortality (n=23), incomplete medical record (n=32), synchronous liver metastasis (n=148) and UICC stage IV (n=54) were excluded, and finally 1,099 patients were analyzed, including 977 patients without liver metastasis and 122 patients with MLM-only. Clinical and pathological records for each patient were reviewed from medical charts. The clinicopathologic characteristics of 1,099 patients were investigated.The median timing of developing MLM was 13 months with a range of 4 to 79 months. Univariate analysis identified that preoperative serum carcinoembryonic antigen (CEA) level, depth of invasion, lymph nodes metastasis, vascular invasion, and perineural invasion were significantly correlated with the development of MLM (all P0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level5 ng/ml (Odds Ratio [OR]=1.591; 95% Confidence Interval [CI], 1.065-2.377; P=0.024), tumor depth (OR=2.294; 95% CI, 1.103-4.768; P=0.026), positive lymph node metastasis (OR=2.004; 95% CI, 1.324-3.031; P=0.001) and positive vascular invasion (OR=1.872; 95% CI, 1.225-2.861; P=0.004) were independent prognostic factors contributing to the occurrence of MLM.The present study demonstrates that preoperative serum CEA level, tumor depth, lymph node metastasis, and positive vascular invasion could affect the occurrence of MLM in CRC patients following curative resection, and thus could help to define these high-risk patients who would benefit from enhanced surveillance and therapeutic program(s).

Objectives The objective of the study is to investigate whether multiple chemotherapeutic agent-related genetic polymorphisms are associated with the clinical outcomes of Taiwanese metastatic colorectal cancers (mCRC) patients treated with the first-line FOLFOX-4 chemotherapy. Methods Consecutive mCRC patients were prospectively enrolled into this study. Peripheral blood samples were used for genotyping of polymorphisms in MTHFR, DPD, GSTP1, MDR1, TYMS, ERCC1, XRCC1, and ERCC2 genes by polymerase chain reaction-restriction fragment length polymorphism technique and DNA sequencing. The primary end point of the study was to investigate the association of each genetic polymorphism with progression-free survival and overall survival (OS). Results Favorable genotypes from polymorphisms in ERCC1 codon 118C/C [hazard ratio (HR)=0.061, 95% confidence interval (CI): 0.014-0.274, P< 0.001] and XRCC1 codon 399G/G (HR= 0 . 306 , 95% CI: 0.103-0.905, P=0.032) that are associated with progression-free survival were identified. Furthermore, ERCC1 codon 118C/C (H R = 0.065, 95% CI: 0.011-0.377, P= 0.002) and XRCC1 codon 399G/G (HR=0.152, 95% CI: 0.041-0.568, P=0 . 0 05) were significantly associated with favorable OS. Combining ERCC1 and XRCC1 genetic polymorphisms, patients with both favorable genotypes of ERCC1 codon 118C/C and XRCC1 codon 399G/G were associated with the better OS than those with one or without any favorable genotypes (P

S100 calcium-binding proteins such as S100B are elevated in primary malignant melanoma and are used as tumor markers for malignant melanoma and numerous other cancers. The purpose of this study was to identify the novel predictors of early relapse in UICC stages II and III colon cancer patients and thus to identify a subgroup of patients who are at high risk for postoperative early relapse. Clinicopathological factors and S100B expression by immunohistochemical staining were retrospectively analyzed in 357 postoperative UICC stages II and III colon cancer patients to determine the predictors of early relapse. Of 357 patients, 114 patients developed postoperative relapse during the follow-up period. Among 114 relapsed colon cancer patients, postoperative early relapse and non-early relapse were found in 56 patients (49.1%) and 58 patients (50.9%), respectively. Multivariate Cox proportional hazards analysis revealed that the presence of vascular invasion (P = .025; hazard ratio [HR], 5.532; 95% confidence interval [95% CI], 1.985–14.729), high postoperative CEA levels (P = .019; HR, 6.845; 95% CI, 2.393–15.256), and S100B overexpression (P

Objective: Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor (EGFR), has been proven to be efficient in metastatic colorectal cancer (mCRC); however, the therapeutic response is variable and markers predictive of response are urgently required. This study was conducted to determinate the predictive values of KRAS mutation status and EGFR expression in mCRC patients treated with cetuximab plus chemotherapy. Summary Background Data: Clinical benefit with EGFR-targeting antibodies seems to be restricted to a particular subgroup of mCRC patients. Therefore, the identification of reliable predictive factors for mCRC patients is imperative before the introduction of targeted chemotherapy. Methods: Ninety-five mCRC patients receiving cetuximab plus the FOLFIRI or FOLFOX-4 chemotherapy were enrolled into the present study. KRAS mutation status/EGFR expression levels were analyzed using direct sequencing, immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction (RT-PCR) assay, respectively. The association between clinical response, progression-free survival (PFS) and overall survival (OS) as well as KRAS mutation status/EGFR expression levels were evaluated. Results: Of 95 mCRC patients, KRAS mutations were identified in 41 cases, and EGFR overexpression (protein or mRNA levels) were observed in 78 patients. Among 41 tumors with KRAS mutation, 33 were found to be activating mutants at codons 12, 13, 15 or 18, while 8 were nonactivating mutants at codons 20, 30, or 31. Fifty-five patients responded to cetuximab plus chemotherapy, 49 were EGFR overexpression and 46 were wild-type KRAS tumor status. Patients with tumors that express high EGFR levels or harbor wild-type KRAS are more likely to have a better PFS and OS when treated with cetuximab plus chemotherapy (all P 0.05). Furthermore, patients with nonactivating KRAS mutants in tumors had a significantly better PFS and OS than patients with activating KRAS mutants (both P 0.05). However, for patients with wild-type KRAS tumor status, EGFR expression remains a relevant predictor of clinical response. Conclusions: The study suggests that activating KRAS mutants is a particularly important independent predictive marker in mCRC patients treated with cetuximab plus chemotherapy, of which combing activating KRAS mutants and EGFR could help to identify the subgroup of patients who are most likely to respond to cetuximab plus chemotherapy.

Background The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment. Methods Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely. Results Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3–132 months). A multivariate analysis identified that low serum albumin level (P = 0.011), advanced UICC stage (P < 0.001), and high carcinoembryonic antigen (CEA) level (P < 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (P < 0.001), advanced UICC stage (P < 0.001), and high CEA level (P < 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories. Conclusion Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.

The objective of this study was to investigate the potential benefit of branched chain amino acid (BCAA)-enriched total parenteral nutrition (TPN) for malnourished surgical patients with gastrointestinal cancer. Sixty-four malnourished patients with gastrointestinal cancer with elective surgical intervention were equally allocated into two groups to receive isonitrogenous and iso-caloric TPN. All of them must have received TPN soon after surgery and were subsequently randomized and divided into either BCAA-enriched TPN (30% BCAA; intervention group) or standard TPN (24% BCAA; control group). Patient biochemical data, nutritional parameters, and clinical outcome were collected to analyze the significance of BCAA-enriched TPN. After a period of TPN, laboratory data, including white blood cell (WBC), C-reactive protein (CRP), alkaline phosphatase (ALK-P), and gamma-glutamyltransferase (γ-GT) levels, were significantly different between these two groups (all P < 0.05). Decreasing white blood cell and C-reactive protein levels were observed in the intervention group that might partially explain the reduced numbers of infectious complications. Furthermore, elevating alkaline phosphatase and gamma-glutamyltransferase levels being also less prominent might indicate a lesser hepatic burden by using BCAA-enriched TPN. The BCAA-enriched TPN can maintain a patient's serum visceral protein (albumin and prealbumin) and positive nitrogen balance better than standard TPN (all P < 0.05). Furthermore, a prominently decreased frequency of postoperative morbidity was also found in the BCAA-enriched TPN group (P = 0.021) despite no difference regarding surgical mortality. Our observations show that BCAA-enriched TPN may be beneficial in improving the nutritional status and reducing postoperative complications for malnourished patients with gastrointestinal cancer undergoing major surgery.

To detect pre- and postoperative circulating tumor cells (CTCs) in stage I-III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse.Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection.Out of 438 patients, 80 CRC patients were classified to preoperative (-)/postoperative (-), 221 patients were preoperative (+)/postoperative (-), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162-14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793-10.847), and the persistent presence of CTCs (P0.001; HR, 29.486; 95% CI: 10.281-87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P0.001; HR, 7.064; 95% CI: 4.354-11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P0.001).The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.

Adenomatous polyposis coli (APC), K-ras and p53 gene mutations are the most common genetic alterations present in colorectal cancer (CRC). The aim of this study was to analyze tumor mutation frequencies and spectra in a large cohort of Taiwanese patients with CRC.APC, K-ras, and p53 gene mutations in primary tumor tissues and their paired normal tissues of 123 CRC patients were detected by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing.Of these 123 CRC patients, 43.1%, 44.7%, 35% of tumor tissue specimens presented mutations in APC, K-ras, and p53 genes, respectively. Overall, gene mutations in APC, K-ras and/or p53 were present in 78% (96/123) of tumor tissues. Among 96 CRC patients harboring gene mutations, 49 (51%) contained mutations of at least two different genes and 47 (49%) contained mutations of one gene only. The most common combination of gene mutations was APC and K-ras mutations (21.9%), followed by K-ras and p53 mutations (12.5%) and then APC and p53 mutations (10.4%). In addition, there were only 6.3% (6/96) of tumor tissues from CRC patients simultaneously containing mutations of APC, K-ras and p53 genes. The most common mutation spectrum of these genes was missense mutations, at a frequency of 38.8%, 92.7% and 70.5% for APC, K-ras and p53 genes, respectively.These data support that the frequencies and patterns of somatic mutation of the APC, Kras and p53 genes in CRCs are considerably variable and distinct among populations, for which the interaction between exogenous environmental factors and endogenous gene alterations may be important determinants.

Background and Objectives To determine which aspects of tumor histology influenced the postoperative relapse and overall survival rates after radical resection of UICC stage II colorectal cancer (CRC). Methods Data were collected on 259 patients with stage II CRC who underwent radical resection in Kaohsiung Medical University Hospital between January 2002 and December 2005. Results A univariate analysis identified that the depth of invasion, the presence of vascular invasion, the presence of perineural invasion, and the number of examined lymph nodes were significant prognostic factors for postoperative relapse. A combination of depth, vascular invasion, and numbers of lymph node retrieval as predictors of postoperative relapse showed that the more predictors that are involved, the higher chance that postoperative relapse would occur. Furthermore, T4 depth of tumor invasion, the presence of vascular invasion, and the number of examined lymph nodes

Different kinds of proton pump inhibitor-based triple therapies could result in different Helicobacter pylori eradication rates.The aims of this study were to compare the efficacy and safety of rabeprazole- and esomeprazole-based triple therapy in primary treatment of H. pylori infection in Taiwan.From June 2005 to March 2007, 420 H. pylori-infected patients were randomly assigned to receive a 7-day eradication therapy with either esomeprazole 40 mg daily (EAC group, n = 209) or rabeprazole 20 mg b.i.d. (RAC group, n = 211) in combination with amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d.. Follow-up endoscopy with biopsy was done 12-16 weeks after completion of eradication therapy. Those who refused endoscopic exams underwent (13)C-urea breath test to assess the treatment response.Intention-to-treat analysis revealed that the eradication rate was 89.4% in the EAC group and 90.5% in RAC groups (p-value = .72). All of the subjects returned for assessment of compliance (100% in EAC group vs. 99.5% in RAC group, p-value = .32) and adverse events (3.83% in EAC group vs. 6.16% in RAC group, p-value = .27). Sixty (28.7%) and 37 (17.6%) patients in EAC and RAC group, respectively, refused endoscopy and underwent a (13)C-urea breath test to determine the treatment effect.In conclusion, rabeprazole- and esomeprazole-based primary therapies for H. pylori infection are comparable in efficacy and safety.

To evaluate the accuracy and clinical utility of two immunochromatographic methods, the STAT-PAK and RAPIRUN tests, in detecting H. pylori antibodies in serum and in urine separately.130 patients undergoing gastroendoscopy (70 men and 60 women; mean age, 50.6 years) were enrolled in this study. Their H. pylori status was determined based on 4 tests: CLO test, culture, histology and UBT test. The H. pylori positive status was confirmed when the culture was positive, or 2 of the other 3 tests were positive. Serum samples and urine samples were collected. We used the STAT-PAK test for detecting H. pylori antibodies in serum, and read the results 24 hours later. Antibodies were also detected in urine by the RAPIRUN test, with a reading time of 25 minutes. 3 doctors read the results of both tests separately, and a positive result was determined when at least 2 of the doctors read a positive result.In the STAT-PAK pretest using serum samples from 21 randomly selected patients (16 patients with H. pylori infection and 5 patients without infection), the sensitivity at 1-hour and 24-hour reading time was 18.7% and 37.5%. Specificity in both reading times was the same at 100%. Of 129 patients, 82 (64%) were H. pylori infected and 47 (36%) were uninfected. The sensitivity, specificity, and positive and negative predictive values were 31.7%, 93.6%, 89.6% and 44.0% in the STAT-PAK test with a 24-hour reading time, and 93.9%, 85.1%, 91.6%, 88.8% in the RAPIRUN test. One female was excluded because of an invalid urine test.The urine RAPIRUN test is a faster and more accurate office-based test than the serum STAT-PAK test for detecting the H. pylori infection in untreated patients in Taiwan. The non-invasive urine RAPIRUN test can be used as a large scale screening test for H. pylori status, particularly in children, uncooperative patients, those who have a family history of gastric cancer, or patients who can not tolerate the suffering of endoscopic examination.

Purpose: In this study, a high-sensitivity colorimetric membrane array method was used to detect circulating tumor cells (CTC) in the peripheral blood of colorectal cancer (CRC) patients with normal perioperative serum carcinoembryonic antigen (CEA) levels. This membrane array method was evaluated as a potential diagnostic and postoperative surveillance tool.Study Design: Membrane arrays consisting of a panel of mRNA markers that include human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and CEA mRNA were used to detect CTCs in the peripheral blood of 157 postoperative CRC patients with normal perioperative serum CEA levels and in 80 healthy individuals. Digoxigenin-labeled cDNA were amplified by reverse transcription-PCR from the peripheral blood samples, which were then hybridized to the membrane array. The sensitivity, specificity, and accuracy of membrane arrays for the detection of CTCs were then calculated.Results: Using the four markers in combination, expression of any three markers or all the four markers in this panel was significantly correlated with the clinicopathologic characteristics, including depth of tumor invasion, lymph node metastasis, tumor-node-metastasis stage, and postoperative relapse (all P < 0.05). The interval between the detection of all four positive molecular markers and subsequent elevated CEA ranged from 3 to 8 months (median 6 months). The expression of all four mRNA markers was an independent predictor for postoperative relapse. CRC patients with all four mRNA markers expression showed a significantly poorer survival rate than those with less than four positive markers.Conclusions: The constructed membrane array method was helpful in the early prediction of postoperative relapse in CRC patients with normal perioperative serum CEA levels.

Background Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and crucial in maintaining genomic stability and expression. Their prognostic impact on colon cancer patients receiving adjuvant chemotherapy has not been well established. We evaluated the association between LINE-1 methylation status and clinicopathologic features and postoperative oncological outcomes in stage III colon cancer patients. Materials and Methods 129 UICC stage III colon cancer patients who had received radical resection and FOLFOX adjuvant chemotherapy were enrolled. Global methylation was estimated by analyzing tumor LINE-1 methylation status using bisulfite-polymerase chain reaction (PCR) and pyrosequencing assay. Demographics, clinicopathological data, and postoperative outcomes were recorded by trained abstractors. Outcome measurements included postoperative recurrence and disease-free survival. Univariate, multivariate, and survival analyses were conducted to identify prognostic factors of oncological outcomes. Results The LINE-1 methylation of all 129 patients was measured on a 0–100 scale (mean 63.3; median 63.7, standard deviation 7.1), LINE-1 hypomethylation was more common in patients aged 65 years and above (61.7%±7.6% vs. 64.6±6.4, p=0.019) and those with post-therapeutic recurrence (61.7±7.4 vs 64.3±6.7, p=0.041). Considering risk adjustment, LINE-1 hypomethylation was found to be an independent risk factor of post-therapeutic recurrence (Adjusted OR=14.1, p=0.012). Kaplan-Meier analysis indicated that patients in the low methylation group had shorter period of disease free survival (p=0.01). In a stratified analysis that included 48 patients with post-therapeutic recurrence, it was found that those who experienced shorter period of disease free survival (≦6 months) appeared to have lower LINE-1 methylation levels than patients who reported of recurrence after 6 months (56.68±15.75 vs. 63.55±7.57, p=0.041) Conclusion There was a significantly greater risk of early postoperative recurrence and a shorter period of disease-free survival in Stage III colon cancer patients exhibiting LINE-1 hypomethylation status after being treated with radical resection and FOLFOX chemotherapy.

The aim of this study was to use glycerol and dextrose in hypocaloric peripheral parenteral nutrition (HPNN) and investigate their effects on postoperative metabolic and nutritional responses. Thirty patients who had undergone major gastrointestinal surgery were examined in a prospective randomized study. The study period extended from the day before operation to postoperative day 7. Fifteen patients (intervention group) received 1.2 g amino acids, 1.2 g glycerol, and 0.5 g fat emulsion/kg/day (approximately 15 kcal/kg/day). The other 15 patients (control group) received 1.2 g amino acids, 1.5 g dextrose, and 0.5 g fat emulsion/kg/day (approximately 15 kcal/kg/day). After 7 days of study, both groups were found to have a decrease in body weight, mid-arm circumference, triceps skin fold, serum albumin, and transferrin and prealbumin levels, but an increase in serum cholesterol and triglyceride levels. However, the differences between them were not significant. Improvements in nitrogen balance were observed in the intervention group (p = .035). These data suggest that advantages favoring the administration of glycerol instead of dextrose in hypocaloric parenteral nutrition could hardly be found in our investigation, except that better nitrogen equilibrium is maintained. Nonetheless, the peripheral intravenously administered ProcalAmine with fat emulsion has been well tolerated and safe for these patients, as well as more convenient for clinical use.

Mutations of K-ras gene have been demonstrated in 40-50% of colorectal cancer and large adenoma (>1 cm). This study was intended to clarify the correlation between the existence of K-ras oncogene and the pathological features of colorectal adenomas using our recently developed membrane arrays. Moreover, the downstream genes regulated by K-ras oncogene were explored to serve as potential biomarkers in the early diagnosis and risk assessment of patients with colorectal adenoma. Specimens were collected from 70 patients with colorectal adenoma. The alterations of K-ras oncogene were analyzed by direct sequencing and our constructed membrane arrays, respectively. The results of direct sequencing showed that 21 of 70 samples (30%) had K-ras gene mutations. The most frequently mutated sites included codons 12, 13, 15 and 18. Furthermore, activated K-ras oncogene was identified in 18 of 70 (25.7%) adenoma by membrane arrays. Statistical analyses showed that the membrane array had the accuracy of 90.0%, sensitivity of 88.9%, and specificity of 90.4%. The frequency of the mutational sites of K-ras gene was located as follows: codon 12, 100% (4/4); codon 13, 100% (4/4); codon 15, 75% (6/8); and codon 18, 100% (2/2). The analysis of the correlation between the experimental data and pathological characteristics of adenoma showed that activated K-ras oncogenes were significantly associated with the size, number and histology of adenomas (all P

Approximately 20%-45% of colorectal cancer (CRC) patients ultimately develop local recurrence or metastasis following curative surgical resection. The latter is caused by tumor cells shed from the primary carcinoma prior to or during operation, currently undetected by standard clinical staging. Fortunately, the presence of tumor cells in peripheral blood can be detected by molecular methods and is being regarded increasingly as a clinically relevant prognostic factor.To detect the presence of circulating tumor cells and evaluate their relationship to postoperative metastatic relapse, we simultaneously examined human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic antigen (CEA) mRNA (messenger RNA) in the peripheral blood of 72 CRC patients and 30 healthy individuals. Using a reverse-transcriptase polymerase chain reaction (RT-PCR), these tumor-related mRNAs were amplified; in addition, analyses were carried out for their correlation with patients' clinicopathologic features, as well as the occurrence of postoperative metastasis.In RT-PCR analysis of the peripheral blood, 69.4% (50 out of 72), 66.7% (48 out of 72), 52.8% (38 out of 72), and 72.2% (52 out of 72) of CRC patients were positive for hTERT, CK-19, CK-20, and CEA mRNA respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA expression, while 2 were positive for either CK-19 mRNA or CK-20 mRNA expression. The detection of CEA mRNA was significantly correlated with depth of tumor invasion (P=0.012), vessel invasion (P=0.035), TNM stage (P0.0001), and postoperative metastasis (P0.0001), while positive hTERT mRNA was correlated with TNM stage (P=0.037) and CK-19 was correlated with depth of tumor invasion (P=0.039) and postoperative metastasis (P=0.017). In addition, multivariate logistic regression showed that only CEA mRNA was an independent and significant predictor of postoperative metastasis (P=0.006). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19, and CK-20 for the detection of circulating cancer cells in the peripheral blood of CRC patients.Using RT-PCR for the detection of CEA mRNA is feasible and may be a promising tool for early detection of micrometastatic circulating tumor cells in CRC patients. CRC patients expressing positive CEA mRNA in peripheral blood have a significantly higher risk of postoperative metastasis. Nevertheless, confirmation of CEA mRNA as a prognostic predictive factor requires the continuation of patient follow-up.

The objective of this study is to compare the performance of enzyme immunoassay (Premier Platinum HpSA) and immunochromatographic method (ImmunoCard HpSA STAT) in detecting stool Helicobacter pylori antigen before and after eradication therapy. Two hundred forty dyspeptic patients (143 men and 97 women; mean age, 53.2 years old; range, 19–79 years old) volunteered to participate in this study. Those who delivered improper stool samples, including diarrhea, inadequate amount, or delayed delivery after collection, were excluded. All of the participants received endoscopy, biopsy-based tests, and noninvasive tests, including 13 C-urea breath test ( 13 C-UBT) and 2 stool antigen tests. Fifty-eight patients completed all the above tests before and after eradication therapy, and each contributed to 2 person-times. In total, there were 176 person-times in the preeradication group and 100 in the posteradication group that were analyzed for comparison. Follow-up endoscopic examinations were done 2 to 4 months after completion of eradication therapy, and stool samples were collected within 3 days after endoscopy. Positive H. pylori infection was established when either culture was positive or any 2 of the histology, rapid urease test, and UBT were positive. In the preeradication group ( n = 176), 99 (56.3%) were H. pylori positive and 77 were Hp negative. In the posteradication group ( n = 100), the treatment was successful in 67 (67.0%) of them. In the preeradication group, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were 95.2%, 87.0%, 90.4%, 93.1%, and 91.5%, respectively, for ImmunoCard HpSA STAT, and 83.8%, 90.9%, 92.2%, 81.4%, and 86.9%, respectively, for Premier Platinum HpSA. In the posteradication group, the sensitivity, specificity, PPV, NPV, and accuracy were 100%, 91.0%, 84.6%, 100%, and 94.0%, respectively, for ImmunoCard HpSA STAT, and 84.9%, 92.5%, 84.8%, 92.5%, and 90.0%, respectively, for Premier Platinum HpSA. There were no statistically significant differences between these 2 stool tests. ImmunoCard HpSA STAT is a rapid, simple, and accurate in-clinic test for preeradication diagnosis of H. pylori and posteradication follow-up.

The aim of this study was to compare the outcomes between the LigaSure vessel sealing system and the conventional closed Ferguson hemorrhoidectomy procedure performed by diathermy. A series of 84 patients with grades III and IV hemorrhoids were randomized into two groups: (1) LigaSure hemorrhoidectomy with submucosal dissection (42 patients) and (2) Ferguson hemorrhoidectomy (42 patients). The patient demographics, operative details, parenteral analgesic requirement, postoperative pain score (assessed by an independent assessor), operating time, intraoperative blood loss, hospital stay, early and delayed complications, and time off from work or normal activity were recorded. The patients were regularly followed up at 1, 2, 4, 6, and 8 weeks after surgery. There were no statistically significant differences between the two groups in terms of age, gender, duration of symptoms, grade of the hemorrhoid(s), or number of hemorrhoids resected. The mean operating time for LigaSure hemorrhoidectomy with submucosal dissection was significantly shorter than that for the Ferguson hemorrhoidectomy (11.3 ± 0.4 vs. 34.2 ± 0.7 minutes; P < 0.0001). Patients treated with the LigaSure method had significantly less blood loss (P < 0.0001), a better pain score (P < 0.0001), less parenteral analgesic requirement (P < 0.0001), shorter hospital stay (P < 0.0001), and less time off from work or normal activity (P < 0.0001). There was no difference in the early and delayed postoperative complications between the two groups. LigaSure hemorrhoidectomy with submucosal dissection is a safe, effective procedure for grade III and IV hemorrhoids. Patients derive greater short-term benefits: reduced intraoperative blood loss, operating time, and postoperative pain as well as earlier resumption of work or normal activity. Long-term follow-up with a larger number of patients is required to confirm the long-term results of this procedure.

Results of urea breath test (UBT) are related to the severity of atrophic gastritis and the density of Helicobacter pylori (H. pylori). Recently, it has been reported that low UBT values should be considered to suggest the possibility of gastric cancer. This study compares UBT results in gastric cancer patients with those of peptic ulcer and gastritis patients.Between October 1998 and May 2000, we have consecutively collected 564 H. pylori-positive patients: 128 gastritis patients, 72 gastric cancer patients, 64 gastric ulcer patients and 300 duodenal ulcer patients. Peptic ulcers were classified into active (A), healing (H), and scar (S) stages. Gastric cancer was classified into early stage (EGCA) and advanced stage (AGCA). The dose of 13C-urea was 50mg, and breath samples were analyzed with a mass spectrometer and the data was evaluated by Mann-Whitney test. The cut-off value was 3.5 per thousand.The mean UBT values of gastric cancer, gastric ulcer (GU), duodenal ulcer (DU) and gastritis were 16.95 +/- 12.2 per thousand, 16.3 +/- 9.3 per thousand, 15.13 +/- 9.9 per thousand and 20.07 +/- 13.5 per thousand. There were no significant differences in UBT values between gastric cancer and gastric ulcer (p = 0.745), duodenal ulcer (p = 0.3831), or gastritis (p = 0.2953). There were also no significant differences between subgroups of gastric cancer and gastric ulcer. There were significantly higher UBT values in the DU scar stage (p = 0.001) and healing stage (p = 0.0484) than in the active stage.We conclude that the UBT value is not a good method for the prediction of gastric cancer. In addition, based on the results of our study, the UBT values may explain the relationship between the natural course of duodenal ulcer and H. pylori infection.

This study assesses the role of endoscopic ultrasonography (EUS) and portography in selection of mode of devascularization surgery for esophagogastric varices (EGV) in patients with portal hypertension and reports our experience in the treatment of EGV with modified devascularization surgery. Forty-two cirrhotic patients with EGV were treated with devascularization surgery for variceal hemorrhage. Preoperatively, percutaneous transhepatic portography (PTP) and EUS were used as the guiding mode for therapy of EGV. In addition to devascularization and splenectomy, esophageal transection (ET) was performed in 26 patients with upward-flow varices (UFV), whereas 16 patients with downward-flow varices (DFV) underwent proximal gastrectomy instead of ET. In both UFV and DFV groups, grade II of intramural varices and extramural collaterals were most commonly observed on EUS imaging. There was no significant difference of EUS grading between these two groups ( P > 0.05). The incidence of postoperative complications, mortality, and recurrent varices were not significantly different between these two groups. The overall 5-year survival rate for UFV group was 69.2 per cent, whereas that for the DFV group was 68.7 per cent ( P > 0.05). Our study shows that devascularization surgery is highly effective for the prevention of recurrent bleeding from EGV, and it provides an alternative treatment modality. Combined PTP and EUS are very helpful in determining adequate modalities of devascularization surgery.

Current researches have proposed a genetic model for colorectal cancer (CRC), in which the sequential accumulation of mutations in specific cancer-related genes, including adenomatous polyposis coli (APC), K- ras, and p53, drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal cancer. To identify patients with an increased risk of tumor recurrence or metastasis and evaluate the prognostic values of APC, K- ras, and p53 gene mutations, we investigated the frequency of these three mutated genes in tumors and sera of CRC patients. APC, K- ras, and p53 gene mutations in primary tumor tissues and their paired preoperative serum samples of 118 CRC patients were detected by using polymerase chain reaction– single strand conformation polymorphism (PCR-SSCP) analysis, followed by direct DNA sequencing of the PCR-amplified genomic DNA. Subsequently, serum molecular markers were analyzed for their correlation with patients’ clinicopathologic features and presence of postoperative recurrence/metastasis. We did not observe any significant difference in the association of APC or K- ras or p53 gene mutations in primary tumors with patients’ demographic data (all were P > 0.05). In contrast, both serum APC and p53 molecular markers were closely correlated with lymph node metastasis and TNM stage (both P < 0.05). Moreover, the serum overall molecular markers (at least one of the three markers) were prominently associated with depth of tumor invasion ( P = 0.033), lymph node metastasis ( P < 0.001), and TNM stage ( P < 0.001). In addition, a significantly higher postoperative metastasis/recurrence rate in patients positive for overall molecular markers compared to those negative for these molecular markers were also demonstrated ( P < 0.001). APC and K- ras molecular markers were more frequently observed in patients with locoregional metastasis (both P < 0.05), while p53 molecular marker was usually detected in the cases of peritoneal metastasis ( P = 0.004). Our findings suggest that serum molecular markers are potentially useful in the determination of colorectal cancer patients harboring gene mutations at high risk of metastasis. Serial analysis is warranted in order to assess their long-term prognostic significance and the therapeutic implications.

Helicobacter pylori infection has a close relationship with many upper digestive tract diseases, but a gold standard for identifying this infection has not yet been well established, especially in clinical application. There is an increasing interest in non-invasive diagnostic tests. In this study, we will compare two non-invasive tests (ELISA method of urine and serum) in clinical use.170 patients (82 women, 88 men; mean age 52.4 yr) were included in this study and all underwent gastroendoscopy. None of the patients had received any H. pylori eradication therapy. The H. pylori infection status was evaluated by histology, culture, CLO test, and 13C-UBT. We also collected urine and serum for the ELISA method. H. pylori infection was defined as positive if the culture was positive or if two of the other three tests (histology, CLO test and 13C-UBT) were positive. If all four tests were negative or only one of the other three tests was positive, the result would be interpreted as negative.Of these 170 patients, 107 (62.94%) were H. pylori infected and 63 (37.06%) were uninfected. The sensitivity, specificity, positive predictive value and negative predictive value of serum ELISA were 96.26%, 74.60%, 86.55%, and 92.16% respectively; while those of urine ELISA were 93.46%, 92.06%, 95.24% and 89.23% respectively. There was no significant difference between these two tests in sensitivity, but urine ELISA has better specificity than serum ELISA significantly.Urine ELISA is a better non-invasive test for H. pylori infection than serum ELISA in clinical practice, because no blood need be drawn, it is safer, easier, and more convenient for sampling and has better specificity. Therefore it would be suitable in epidemiological screening of H. pylori infection, especially in young children, older patients and those who cannot cooperate.

Free cancer cells exfoliated from the serosal surfaces of primary cancers are considered to be responsible for peritoneal dissemination, which are both the most frequent pattern of treatment failure and the most important cause of death in gastric cancer patients. Detection of free cancer cells in the peritoneal cavity at the time of surgery, therefore, is thought to be of great value in predicting peritoneal recurrence and accordingly the prognosis of gastric cancer patients. This study was designed to determine whether free cancer cells in peritoneal lavage fluid from gastric cancer patients could be identified by a reverse-transcriptase polymerase chain reaction (RT-PCR) method specific to carcinoembryonic antigen (CEA) mRNA. Simultaneously, the results from conventional cytological examination were evaluated and the levels of CEA in peritoneal lavage were determined. Of the 40 gastric cancer patients enrolling in this investigation, 11 (27.5%) were positive for CEA mRNA in their peritoneal lavage, whereas only 6 (15%) and 8 (20%) were shown to be positive by cytological examination and peritoneal CEA (pCEA) assay, respectively. Furthermore, RT-PCR positive for CEA mRNA was correlated with the depth of tumor invasion (P

In Taiwan, CagA and VacA cannot be used as markers to evaluate the risk of developing serious gastroduodenal pathogenesis in the hosts. Recent research suggests that the low molecular weight proteins, 35kDa and 19kDa, in Helicobacter pylori may be related to duodenal ulcers and gastric MALToma (mucosa-associated lymphoid tissue lymphoma) respectively. The aims of this study were to examine the sero-prevalence of antibodies against specific Helicobacter pylori antigen in patients with different gastroduodenal diseases and further to find possible virulence factor(s) associated with the development of clinically relevant disease in Helicobacter pylori-infected subjects in Taiwan.Sera were obtained from 108 patients, of which 22 had gastric adenocarcinoma, 31 had non-ulcer dyspepsia and 65 had peptic ulcer disease. The sera were analyzed for specific Helicobacter pylori antigen by using one commercial kit (HelicoBlot 2.0, Genelabs Diagnostic, Singapore, HB2.0). Helicobacter pylori infection was confirmed when the culture was positive or when any two of the other three tests (biopsy CLO test, histology and 13C-urea breath test) were positive.The data showed a high prevalence of CagA and VacA proteins [CagA(+): gastric adenocarcinoma--88.1%, non-ulcer dyspepsia--87.1%, peptic ulcer disease--91%; VacA(+): gastric adenocarcinoma--78.6%, non-ulcer dyspepsia--58.1%, peptic ulcer disease--71.4%] in Taiwan. This is similar to the findings in other Chinese and Taiwanese studies. No significant difference was found among the three groups (P0.05) for any Helicobacter pylori protein. We found that antibody responses to the 26.5-kDa and 116-kDa (CagA) antigens were most prevalent in the peptic ulcer disease group. Consequently, we analyzed two special phenotypes, which have simultaneous presence in bands at 116 and 26.5kDa. The phenotype [116-kDa (+) and 26.5kDa(+)] predicted the risk of peptic ulcer disease with 76.7% sensitivity and 62% specificity.We confirm the universal prevalence of CagA and VacA-positive Helicobacter pylori infection in Taiwan independent of disease. Although we did not find any single specific Helicobacter pylori protein which could act as an indicator of clinical outcome, we found a possible marker of peptic ulcer disease which may be acceptable. This is the phenotype with simultaneous presence in bands at 116kDa and 26.5kDa protein. Our report differs from some previous reports from other regions. This may reflect differences of race and geography.