A hybrid coarse-grained model for structure, solvation and assembly of lipid-like peptides.

Reconstituted photosynthetic proteins which are activated upon exposure to solar energy hold enormous potential for powering future solid state devices and solar cells. The functionality and integration of these proteins into such devices has been successfully enabled by lipid-like peptides. Yet, a fundamental understanding of the organization of these peptides with respect to the photosynthetic proteins and themselves remains unknown and is critical for guiding the design of such light-activated devices. This study investigates the relative organization of one such peptide sequence V6K2 (V: valine and K: lysine) within assemblies. Given the expansive spatiotemporal scales associated with this study, a hybrid coarse-grained (CG) model which captures the structure, conformation and aggregation of the peptide is adopted. The CG model uses a combination of iterative Boltzmann inversion and force matching to provide insight into the relative organization of V6K2 in assemblies. The CG model reproduces the structure of a V6K2 peptide sequence along with its all atom (AA) solvation structure. The relative organization of multiple peptides in an assembly, as captured by CG simulations, is in agreement with corresponding results from AA simulations. Also, a backmapping procedure reintroduces the AA details of the peptides within the aggregates captured by the CG model to demonstrate the relative organization of the peptides. Furthermore, a large number of peptides self-assemble into an elongated micelle in the CG simulation, which is consistent with experimental findings. The coarse-graining procedure is tested for transferability to longer peptide sequences, and hence can be extended to other amphiphilic peptide sequences.

Gastric juice-based PCR assay: An alternative testing method to aid in the management of previously treated Helicobacter pylori infection.

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-naïve, 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 < 0.0001). The superiority of juice PCR was statistically significant in previously treated patients (P < 0.0001) but not in treatment-naïve patients (P = 0.13). Antral H pylori density was less marked in previously treated patients (P = 0.014). The comparisons of PCR-RFLP and E-test for Clarithromycin resistance showed reliable AUC = 89.8%. CONCLUSION: Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy. Consequently, gastric juice PCR suits the unmet need to manage previously treated H pylori.

Predictor of slower gastric emptying in gastroesophageal reflux disease: Survey of an Asian-Pacific cohort.

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.

Short- and long-term outcomes of laparoscopic-assisted surgery, mini-laparotomy and conventional laparotomy in patients with Stage I-III colorectal cancer.

BACKGROUND: Three operative techniques have been used for colorectal cancer (CRC) resection: Conventional laparotomy (CL) and the mini-invasive techniques (MITs)- laparoscopic-assisted surgery (LAS) and mini-laparotomy (ML). The aim of the study was to compare the short- and long-term outcomes of patients undergoing the three surgical approaches for Stage I-III CRC resection. PATIENTS AND METHODS: This study enrolled 688 patients with Stage I-III CRC undergoing curative resection. The primary endpoints were perioperative quality and outcomes. The secondary endpoints were oncological outcomes including disease-free survival (DFS), overall survival (OS) and local recurrence (LR). RESULTS: Patients undergoing LAS had significantly less blood loss (P < 0.001), earlier first flatus (P = 0.002) and earlier resumption of normal diet (P = 0.025). Although post-operative complication rates were remarkably higher in patients undergoing CL than in those undergoing MITs (P = 0.002), no difference was observed in the post-operative mortality rate (P = 0.099) or 60-day re-intervention rate (P = 0.062). The quality of operation as assessed by the number of lymph nodes harvested and rates of R0 resection did not differ among the groups (all P > 0.05). During a median follow-up of 5.42 years, no significant difference was observed among the treatment groups in the rates of 3-year late morbidity, 3-year LR, 5-year LR, 5-year OS or 5-year DFS (all P > 0.05). CONCLUSIONS: Patients undergoing CL had higher post-operative morbidities. Moreover, the study findings confirm the favourable short-term and comparable long-term outcomes of LAS and ML for curative CRC resection. Therefore, both MITs may be feasible and safe alternatives to CL for Stage I-III CRC resection.

Patients with Metastatic Colorectal Cancer and Hyperbilirubinemia Treated with FOLFIRI plus Bevacizumab as First-Line Treatment.

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.

Suppression of IL-8-Src signalling axis by 17ß-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.

Factors affecting number of lymph nodes harvested and the impact of examining a minimum of 12 lymph nodes in stage I-III colorectal cancer patients: a retrospective single institution cohort study of 1167 consecutive patients.

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 (<12 LNs). RESULTS: A multivariate analysis showed that age (P = 0.007), tumor size (P = 0.030), and higher T stage (P = 0.001) were independent factors affecting the examinations of LNs in colon cancer and that tumor size (P = 0.015) was the only independent factor in rectal cancer. Patients with low harvests had poorer overall survival with stage II and stage III CRC (stage II: P < 0.0001; III: P = 0.001) and poorer disease-free survival for stages I-III (stage I: P = 0.023; II: P < 0.0001; III: P = 0.001). CONCLUSIONS: The factors influencing nodal harvest are multifactorial, and an adequate number of examined LNs (≧12) is associated with a survival benefit. Removal of at least 12 LNs will determine the lymph node status reliably.

Prospective double-blind randomized study on the efficacy and safety of an n-3 fatty acid enriched intravenous fat emulsion in postsurgical gastric and colorectal cancer patients.

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.

Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control study.

BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.

17ß-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.

Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17ß-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17ß-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17ß-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.

A case study of lean digital transformation through robotic process automation in healthcare.

Under Taiwan's National Health Insurance (NHI) system, it's crucial for all healthcare providers to accurately submit medical expense claims to the National Health Insurance Administration (NHIA) to avoid incorrect deductions. With changes in healthcare policies and adjustments in hospital management strategies, the complexity of claiming rules has resulted in hospitals expending significant manpower and time on the medical expense claims process. Therefore, this study utilizes the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) management approach to identify wasteful and non-value-added steps in the process. Simultaneously, it introduces Robotic Process Automation (RPA) tools to replace manual operations. After implementation, the study effectively reduces the process time by 380 min and enhances Process Cycle Efficiency (PCE) from 69.07 to 95.54%. This research validates a real-world case of Lean digital transformation in healthcare institutions. It enables human resources to be allocated to more valuable and creative tasks while assisting hospitals in providing more comprehensive and patient-centric services.

The prognostic values of EGFR expression and KRAS mutation in patients with synchronous or metachronous metastatic colorectal cancer.

BACKGROUND: The epidermal growth factor receptor (EGFR)/RAS/RAF/MEK/MAPK pathway is an important pathway in the carcinogenesis, invasion and metastasis of colorectal cancers (CRCs). We conducted a retrospective study to determine the prognostic values of EGFR expression and KRAS mutation in patients with metastatic CRC (mCRC) based on synchronous or metachronous status. METHODS: From October 2002 to March 2012, 205 patients with mCRC were retrospectively analyzed; 98 were found to have metachronous mCRC while 107 were found to have synchronous mCRC. The EGFR expressions were determinate by IHC (immunohistochemistry) analysis and categorized 1+ (weak intensity), 2+ (moderate intensity), and 3+ (strong intensity). Genomic DNA was isolated from frozen primary CRC tissues and direct sequencing of KRAS was performed. The clinicopathological features of these mCRC patients were retrospectively investigated according to EGFR expression and KRAS mutation status. Moreover, we analyzed the prognostic values of EGFR expression and KRAS mutation among these patients. RESULTS: Of the 205 patients with mCRC, EGFR expression was analyzed in 167 patients, and positive EGFR expression was noted in 140 of those patients (83.8%). KRAS mutation was investigated in 205 patients and mutations were noted in 88 of those patients (42.9%). In patients with metachronous mCRC, positive EGFR expression was significantly correlated with well-and moderately-differentiated tumors (P=0.028), poorer disease-free survival (DFS) (P<0.001), and overall survival (OS) (P<0.001). Furthermore, positive EGFR expression was a significant independent prognostic factor of DFS (P=0.006, HR: 4.012, 95% CI: 1.130-8.445) and OS (P=0.028, HR: 3.090, 95% CI: 1.477-10.900) in metachronous mCRC patients. KRAS mutation status was not significantly related to DFS and OS of patients with metachronous mCRC; likewise, KRAS mutation status was not significantly different in the progression-free survival (PFS) and OS of patients with synchronous mCRC (all P>0.05). CONCLUSIONS: The present study demonstrated that EGFR expression has prognostic value only for patients with metachronous mCRC. However, KRAS mutation did not have prognostic value in patients with metachronous or synchronous mCRC.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

A observational study of the efficacy and safety of capecitabine versus bolus infusional 5-fluorouracil in pre-operative chemoradiotherapy for locally advanced rectal cancer.

BACKGROUND AND OBJECTIVES: This study is to evaluate the safety and efficacy of preoperative radiotherapy (RT) combined with bolus infusional 5-fluorouracil (5-FU) or oral capecitabine in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Seventy-four patients were retrospectively analyzed. Twenty-seven patients were treated with 5-FU (350 mg/m(2) i.v. bolus) and leucovorin (20 mg/m(2) i.v. bolus) for 5 days/week during week 1 and 5 of RT. Forty-seven patients were treated with capecitabine (850 mg/m(2), twice daily for 5 days/week). Both groups received the same RT course (45-50.4 Gy/25 fractions, 5 days/week, for 5 weeks). Patients underwent surgery in 6 weeks after completion of the chemoradiotherapy. Data of the observational study were collected. RESULTS: Grade 3 or 4 toxicities occurred in 40.7% (5-FU) and 19.1% (capecitabine) of the patients (P = 0.044). Six patients in the 5-FU group (22.2%) and six patients in the capecitabine group (14%) achieved complete response. Primary tumor (T) downstaging were achieved in 51.9% (5-FU) and 69.8% (capecitabine) of the patients. The pathological ypT0-2 stage was 40.7% (5-FU) and 67.4% (capecitabine) (P = 0.028). CONCLUSIONS: In consideration of the better ypT0-2 downstaging rate, less severe toxicities, and no need for indwelling intravenous device on oral capecitabine regimen, the administration of oral capecitabine with RT may be a more favorable option in the neoadjuvant treatment for LARC.

A retrospective study of the safety and efficacy of a first-line treatment with modified FOLFOX-4 in unresectable advanced or recurrent gastric cancer patients.

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 (<65 years old) and 25 elderly patients (≥65 years old) who received a combination of oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-4, mFOLFOX-4 regimen). 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/m(2) of oxaliplatin and 200 mg/m(2) of leucovorin on the first day, followed by a 24-hour continuous infusion of 1,000 mg/m(2) 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.

Comparison of mini laparotomy with conventional laparotomy as the surgical approach in stage I-III CRC patients: appealing outcomes.

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<0.001). In comparison of postoperative complications between convention and mini laparotomy, ileus was more frequently encountered in conventional group (p=0.001). Interestingly, the disease-free survival and overall survival in mini laparotomy group were significantly better than control group (p=0.001 and p=0.017, respectively). CONCLUSIONS: Compared to conventional laparotomy, mini laparotomy seems a feasible, minimally invasive and attractive alternative in selected patients.

Multiple genetic polymorphisms in the prediction of clinical outcome of metastatic colorectal cancer patients treated with first-line FOLFOX-4 chemotherapy.

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 (HR=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=0.005) 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<0.001). CONCLUSION: The genetic polymorphisms of ERCC1 and XRCC1 may be useful in predicting clinical outcome in Taiwanese mCRC patients treated with FOLFOX-4. However, further prospective studies will be needed for the potential clinical implication.

S100B protein expressions as an independent predictor of early relapse in UICC stages II and III colon cancer patients after curative resection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < .001; HR, 26.250; 95% CI, 7.463-96.804) were demonstrated to be independent predictors of postoperative early relapse. Furthermore, postoperative relapsed colon cancer patients with S100B overexpression were demonstrated to have significantly lower overall survival rates than those without S100B overexpression (P < .001). CONCLUSIONS: This study suggests that S100B protein expression is a crucial predictor of early relapse in UICC stages II and III postoperative colon cancer patients and thus could help to define patients with this tumor entity who would benefit from enhanced follow-up and therapeutic program(s).

Risk factors for the development of metachronous liver metastasis in colorectal cancer patients after curative resection.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 P<0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level>5 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. CONCLUSIONS: 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).

Influence of Proton Pump Inhibitors and Histamine Receptor 2 Antagonists on Blastocystis ST3 and Selected Microorganisms of Intestinal Microbiota In Vitro.

INTRODUCTION: Proton pump inhibitors (PPIs) and histamine receptor 2 (H2) antagonists are commonly prescribed medications. Association between PPIs and alteration of the gut microbiota has been reported. Blastocystis, the most common intestinal protozoan worldwide, occurs in both healthy and symptomatic people with gastrointestinal or cutaneous disorders, with controversial pathogenicity. The current study was aimed to investigate the influence of PPIs and H2 blockers on the in vitro proliferation of selected intestinal bacteria, fungi, and protozoa. METHODS: Cultures of Lactobacillus rhamnosus, Escherichia coli, Enterococcus faecium, Candida albicans, and Blastocystis subtype 3 were treated with different concentrations of respective medications in vitro, and the numbers of microorganisms were quantified and compared. RESULTS: Pantoprazole and esomeprazole exerted a significant inhibition on Blastocystis and C. albicans, especially at higher concentrations, which were even more effective than metronidazole. On the other hand, treatment with pantoprazole caused an increase in proliferation of L. rhamnosus and E. coli. There was no influence of H2 blockers on the examined microorganisms. DISCUSSION: PPIs, such as pantoprazole, can be a potential treatment in the prophylaxis or eradication of Blastocystis and C. albicans.