Publications by authors named "Jui-Ho Wang"

29 Publications

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Shared decision-making and patient decision aids in choosing first-line targeted therapy for metastatic colorectal cancer in Taiwan.

J Oncol Pharm Pract 2021 Jun 1:10781552211020806. Epub 2021 Jun 1.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Introduction: In Taiwan, given the discrepancy between current treatment guidelines and reimbursement options, patients might require a tool to support their decision-making process when selecting a regimen for metastatic colorectal cancer, especially therapeutic strategies, and subsequent costs, along with efficacy and safety outcomes. Therefore, we developed a patient decision aid (PDA) to support patients in choosing between treatment options recommended based on the current evidence and those reimbursed by the Taiwanese National Health Insurance.

Methods: By carefully reviewing the updated data and then interpreting the clinical tool, we conducted a needs assessment using a serial questionnaire to test for a step-by-step adjustment of the PDA.

Results: Patients, their relatives, and medical team members were most concerned about outcomes, such as overall survival, progression-free survival, objective response rate, tumor shrinkage to resectable status, total medical cost, severe gastrointestinal perforation, and severe skin reaction. After a serial alpha test for quality, we performed quantitative evaluation and beta tests, revealing average scores of more than 4 points (on a scale of 1-5) for both perceptibility and utility.

Conclusions: The present findings suggest that PDAs are useful and supplement the shared decision-making practice, helping patients make decisions about preferences and consider the pros and cons of treatment regimens, along with insurance reimbursement options.
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http://dx.doi.org/10.1177/10781552211020806DOI Listing
June 2021

The Long Noncoding RNA LOC441461 (STX17-AS1) Modulates Colorectal Cancer Cell Growth and Motility.

Cancers (Basel) 2020 Oct 28;12(11). Epub 2020 Oct 28.

Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23124, Taiwan.

Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth; cell apoptosis; and metastasis in CRC. This study determined that LOC441461 expression was significantly higher in CRC tissues than in adjacent normal mucosa. Pathway enrichment analysis of LOC441461-coexpressed genes revealed that LOC441461 was involved in biological functions related to cancer cell growth and motility. Knockdown of the LOC441461 expression significantly suppressed colon cancer cell growth by impairing cell cycle progression and inducing cell apoptosis. Furthermore, significantly higher LOC441461 expression was discovered in primary colon tumors and metastatic liver tumors than in the corresponding normal mucosa, and LOC441461 knockdown was noted to suppress colon cancer cell motility. Knockdown of LOC441461 expression suppressed the phosphorylation of MLC and LIMK1 through the inhibition of RhoA/ROCK signaling. Overall, LOC441461 was discovered to play an oncogenic role in CRC cell growth and motility through RhoA/ROCK signaling. Our findings provide new insights into the regulation of lncRNAs and their application in the treatment of colon cancer.
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http://dx.doi.org/10.3390/cancers12113171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692211PMC
October 2020

Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST).

Eur J Cancer 2020 10 20;138:19-29. Epub 2020 Aug 20.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Aim: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.

Methods: The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate.

Results: Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P < 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P < 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively).

Conclusion: The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities.

Clinical Trial Registration: NCT02256800.
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http://dx.doi.org/10.1016/j.ejca.2020.05.031DOI Listing
October 2020

Tumor sidedness and efficacy of first-line therapy in patients with RAS/BRAF wild-type metastatic colorectal cancer: A network meta-analysis.

Crit Rev Oncol Hematol 2020 Jan 15;145:102823. Epub 2019 Nov 15.

Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan. Electronic address:

We conducted a systemic search of several databases for randomized controlled trials (RCTs) that reported efficacy and safety outcomes of drugs for left-sided and right-sided metastatic colorectal cancer (mCRC), to identify the best available treatment. A network meta-analysis with mixed comparisons was created to interpret the best treatment option using the surface under the cumulative ranking curve. In the left-sided rat sarcoma (RAS) wild-type (WT) mCRC patients, bevacizumab, panitumumab, or cetuximab with chemotherapy groups showed a significantly better objective response rate than the chemotherapy alone group. The progression-free survival (PFS) and overall survival were better with panitumumab or cetuximab with chemotherapy than with chemotherapy alone. In the right-sided RAS WT mCRC patients, PFS for bevacizumab with chemotherapy was significantly better than that for cetuximab with chemotherapy. Cetuximab, closely followed by panitumumab, is the most effective treatment in left-sided RAS WT mCRC. Bevacizumab is more effective in right-sided mCRC.
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http://dx.doi.org/10.1016/j.critrevonc.2019.102823DOI Listing
January 2020

Endoscope rotating technique is useful for difficult colorectal endoscopic submucosal dissection.

Surg Endosc 2020 02 3;34(2):1006-1011. Epub 2019 Sep 3.

Division of Colorectal Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD., Kaohsiung, 81346, Taiwan, ROC.

Background: Conventional lesion-up colorectal ESD has the potential risk of iatrogenic perforation due to the knife's direction toward the muscular layer of the bowel wall. If we rotate the endoscope to the proper position, the mucosal flap is easy to be lifted down by tip attachment and the knife is easy to approach the proper dissection plane, which may prevent the perforation and facilitate difficult ESD.

Methods: We aimed to retrospectively assess the safety and efficacy of this rotating technique compared with the conventional lesion-up dissection regardless of shape, location, or size of the tumor, and investigated in short- and long-term outcomes following the ESD procedure.

Results: 41 lesions were enrolled into rotating technique group and 37 lesions in lesion-up group. The dissection speed was significantly faster in the rotating technique group (p = 0.023). R0 resection rate was significantly higher in rotating technique group (p = 0.008). The rate of perioperative complication was significantly higher in lesion-up method group (p = 0.003). Local recurrence was higher in lesion-up group (p = 0.001). Recurrence-free rate was higher in rotating technique group (p = 0.018).

Conclusion: The endoscope rotating is a useful technique for difficult colorectal ESD due to easy approaching the proper dissection plane. This technique also increases the rate of en bloc resections, R0 resections regardless of size, shape, and location and improves dissection speed without increasing the incidence of adverse events.
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http://dx.doi.org/10.1007/s00464-019-07105-1DOI Listing
February 2020

Incidence and Clinical Outcomes of Gonadal Artery Injury during Colorectal Surgery in Male Patients.

J Gastrointest Surg 2019 10 1;23(10):2075-2080. Epub 2019 Apr 1.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD, Kaohsiung, Taiwan, 81346, Republic of China.

Background: Gonadal artery is susceptible to accidental injury due to their anatomical proximity to the colon and rectum. There are few literature reviews focusing on this injury during colorectal surgery. We conduct a retrospective study to evaluate the incidence and the clinical significance of these injuries in terms of testicular size and testicular enhancement on the contrast CT scan.

Methods: Patients' characteristic data included age, body mass index (BMI), diagnosis, operation type, cause of gonadal artery injury, side of injury, level of injury, method of vessel ligation, and follow-up period. We measured the testicular sizes before and after gonadal artery injury and measured the enhancement level by recording the mean attenuation value on the injury side and non-injury side of the testis on the CT scan.

Results: The incidence of gonadal artery injury was 3.61% and 15 male patients with this injury were enrolled. There were 5 patients with iatrogenic injury and 10 patients with non-iatrogenic injury due to advanced tumor or inflammation. No patients had any complaints of testicular discomforts or atrophy after the surgery. The testicular sizes before and after the surgery showed no significant difference (p = 0.877). The mean attenuation values of the injury side and non-injury side of the testis also showed no significant difference (p = 0.79).

Conclusions: Gonadal artery injury during colorectal surgery is not a rare complication. To prevent this injury, knowledge of the anatomy and staying in the proper plane of dissection are the key points. In patients with gonadal artery injury during colorectal surgery, sacrifice of the gonadal artery is safe without clinical significance in terms of testicular size and testicular enhancement on the contrast CT scan.
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http://dx.doi.org/10.1007/s11605-019-04197-xDOI Listing
October 2019

Placement of SurgiWrap® adhesion barrier film around the protective loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the closure.

Int J Colorectal Dis 2019 Mar 7;34(3):513-518. Epub 2019 Jan 7.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD, Kaohsiung, Taiwan, 81346, Republic of China.

Purpose: A temporary loop stoma is often created after laparoscopic colorectal cancer surgery. Peristomal adhesions may make stoma closure into a complicated operation. We demonstrated how to place the SurgiWrap® adhesion barrier film and evaluated the peristomal adhesion severity and feasibility of stoma closure.

Methods: This is a retrospective case-control study. Patients were divided into a study group (placement of adhesion barrier film) and a control group (no placement). Patient characteristics, operative data, and severity of adhesions were recorded. We used logistic regression to probe the association between the variables and the adhesion severity.

Results: A total of 180 patients were identified with 60 in the study group and 120 in the control group. In the study group, the adhesion severity (p < 0.001), operative time (p = 0.025), and time to flatus (p = 0.042) are significantly reduced. In logistic regression analysis, placement of the film (p < 0.001), neoadjuvant concurrent chemoradiotherapy (p = 0.041), and time interval between stoma creation and closure ≧ 12 weeks (p = 0.038) are three significant factors influencing the peristomal adhesion.

Conclusion: The placement of SurgiWrap® adhesion barrier film around the loop stoma after laparoscopic colorectal cancer surgery may reduce the peristomal adhesion severity and facilitate the stoma closure in terms of operative time and time to flatus.
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http://dx.doi.org/10.1007/s00384-018-03229-3DOI Listing
March 2019

Linc00659, a long noncoding RNA, acts as novel oncogene in regulating cancer cell growth in colorectal cancer.

Mol Cancer 2018 03 10;17(1):72. Epub 2018 Mar 10.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan, Republic of China.

Background: Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death worldwide. In patients with CRC, metastasis is a crucial problem that leads to treatment failure and is the primary cause of the lethality of colon cancer. Long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in the development, cell growth, apoptosis, and metastasis of CRC.

Method: We investigated the transcriptome profiles of human lncRNAs in the primary tumor tissues and in the corresponding normal mucosa of two patients with CRC by using a microarray approach. The expression levels of lncRNAs were verified in colon cancer by real-time PCR. Using bioinformatics approach to illustrate putative biological function of Linc00659 in colon cancer. The effects of Linc00659 on cell growth, proliferation, cell cycle and apoptosis were studies by in vitro assays.

Results: Our data revealed that compared with adjacent normal tissues, 201 lncRNAs were deregulated (fold change ≥ 4 or ≤ 0.25) in CRC tissues. Among them, the expression levels of Linc00659 were significantly increased in colon cancer, and high expression levels were correlated with poor survival in patients with CRC. Bioinformatics analysis results indicated that Linc00659 was significantly coexpressed with cycle-related genes in CRC. Linc00659 expression knockdown could significantly suppress colon cancer cell growth by impairing cell cycle progression. In addition, our results showed that Linc00659 expression knockdown could accelerate cell apoptosis in colon cancer cells treated with chemotherapy drugs. Meanwhile, our results also demonstrated that silencing of Linc00659 expression leads to cell growth inhibition and induced apoptosis, possibly by suppressing PI3K-AKT signaling in colon cancer.

Conclusion: Linc00659 is a novel oncogenic lncRNA involved in colon cancer cell growth by modulating the cell cycle. Our findings give an insight into lncRNA regulation and provide an application for colon cancer therapy.
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http://dx.doi.org/10.1186/s12943-018-0821-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845323PMC
March 2018

What is the predictor of surgical mortality in adult colorectal perforation? The clinical characteristics and results of a multivariate logistic regression analysis.

Surg Today 2017 Jun 20;47(6):683-689. Epub 2016 Sep 20.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 81346, Taiwan, R.O.C.

Purpose: Colorectal perforations are a serious condition associated with a high mortality. The aim of this study was to describe the clinical characteristics and identify predictors for the surgical mortality in adult patients with colorectal perforation, thereby achieving better outcomes.

Methods: A retrospective study of adult patients diagnosed with colorectal perforation operated was performed. The clinical variables that might influence the surgical mortality were first analyzed, and the significant variables were then analyzed using a logistic regression model.

Results: A total of 423 patients were identified, and the surgical mortality rate was 36.9 %. The most common etiology was diverticulitis (38.2 %). The highest etiology-specific mortality was for colorectal cancer (61.5 %) and ischemic proctocolitis (59.8 %). In a logistic analysis, the significant predictors for the surgical mortality were ≥3 comorbidities (p = 0.034), preoperation American Society of Anesthesiologists score ≥4 (p = 0.025), preoperative sepsis or septic shock (p < 0.001), colorectal cancer or ischemic proctocolitis (p = 0.035), reoperation (p = 0.041), and Hinchey classification grade IV (p = 0.024).

Conclusion: We demonstrated that ≥3 comorbidities, a preoperation American Society of Anesthesiologists score ≥4, preoperative sepsis or septic shock, colorectal cancer or ischemic proctocolitis, reoperation, and Hinchey classification grade IV are predictors for the surgical mortality in the adult cases of colorectal perforation. These predictors should be taken into consideration to prevent surgical mortality and to reduce potentially unnecessary medical expenses.
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http://dx.doi.org/10.1007/s00595-016-1415-4DOI Listing
June 2017

Prospective analysis of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab plus FOLFIRI as the first-line setting: study protocol for a randomized controlled trial.

Trials 2016 Jan 25;17:46. Epub 2016 Jan 25.

Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Background: Irinotecan is approved and widely administered to metastatic colorectal cancer (mCRC) patients; however, it can cause severe toxicities including neutropenia and diarrhea. The polymorphisms of genes encoding drug-metabolizing enzymes can play a crucial role in the increased susceptibility of cancer patients to chemotherapy toxicity. Therefore, we plan to explore the effect of the genetic polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) for irinotecan detoxification in mCRC patients. This trial will compare the clinical outcomes and side effects observed in mCRC patients treated with bevacizumab plus 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) with and without UGT1A1 genotyping and irinotecan dose escalation. A total of 400 mCRC patients were randomized into a study group and a control group.

Methods/design: This trial is a prospective, multicenter, randomized clinical trial comparing UGT1A1 promoter polymorphism for irinotecan dose escalation in mCRC patients administered with bevacizumab plus FOLFIRI as the first-line setting. The enrolled patients were randomly assigned to one of two groups, a study group and a control group, on the basis of receiving UGT1A1 genotyping or not. The study group receive a biweekly FOLFIRI regimen, with irinotecan dose escalation based on UGT1A1 genotyping; whereas the control group receive the conventional biweekly FOLFIRI regimen without UGT1A1 genotyping. The clinicopathological features, response rates, toxicity, and progression-free survival or overall survival will be compared between the two groups.

Discussion: Patients with mCRC undergoing UGT1A1 genotyping may receive escalated doses of irinotecan for a potentially more favorable clinical response and outcome, in addition to comparable toxicities. Such personalized medicine based on genotyping may be feasible for clinical practice.

Trial Registration: NCT02256800 . Date of registration: 3 October 2014. Date of first patient randomized: 16 January 2015.
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http://dx.doi.org/10.1186/s13063-016-1153-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727397PMC
January 2016

Comparison of laparoscopic versus open surgery in a three-stage operation for obstructive left-sided colorectal cancer.

J Chin Med Assoc 2015 Oct 29;78(10):584-90. Epub 2015 Jul 29.

Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address:

Background: Treatment for obstructive left-sided colorectal cancer (OLCC) typically consists of a three-staged procedure. During the first stage, the obstruction is managed with diversion colostomy. Traditionally in the second stage, we perform open resection for the primary tumor. In this study, we evaluated the feasibility of laparoscopic resection of OLCC with diversion colostomy in terms of operative results and short-term outcomes.

Methods: A total of 20 patients underwent laparoscopic resection for OLCC (study group), 48 patients underwent open resection for OLCC (control group 1), and 53 patients underwent laparoscopic resection for non-OLCC (control group 2). Afterwards, results from the procedures were obtained and clinical data were analyzed.

Results: The operative time was significantly longer in the study group than in the control group 1 (153 minutes vs. 126 minutes, p = 0.041), and the length of hospitalization was shorter in the study group than in the control group 1 (5.3 days vs. 7.6 days, p = 0.032). Regarding the operative results and short-term outcomes, there were no significant differences between the study group and control group 2. Colostomy retraction was a specific morbidity which occurred in two patients of the study group.

Conclusion: Laparoscopic resection of OLCC with diversion colostomy is feasible. Abdominal cavity adhesion is only limited. We strongly recommend that laparoscopic resection should be performed at least 2 weeks after diversion colostomy, and the plastic rod should be left in place during the pneumoperitoneum to reduce the risk of colostomy retraction.
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http://dx.doi.org/10.1016/j.jcma.2015.06.003DOI Listing
October 2015

Prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwan.

BMC Gastroenterol 2015 Apr 1;15:40. Epub 2015 Apr 1.

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1 st Road, Kaohsiung City, 80424, Taiwan.

Background: To investigate the prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwanese general population.

Methods: From January 2009 to December 2011, consecutive asymptomatic subjects undergoing a health check-up were evaluated by colonoscopy. The colorectal diverticulosis was assessed, and a medical history and demographic data were obtained from each subject. Logistic regression analysis was conducted to search the risk factors of colorectal diverticulosis.

Results: Of the 1899 asymptomatic subjects, the prevalence of colorectal diverticulosis was 13.5%. On univariate logistic regression analysis, age over 60 years old, male, adenomatous polyp, current smoking and heavy alcohol consumption were significantly associated with diverticulosis. Multivariate logistic regression analysis revealed that age over 60 years old (relative risk [RR], 2.57; 95% confidence interval [CI], 1.64-6.47), adenomatous polyps (RR, 2.18; 95% CI, 1.18-4.61) and heavy alcohol consumption (RR, 1.82; 95% CI, 1.04-3.08) were independent predictors for colorectal diverticulosis.

Conclusions: The prevalence of asymptomatic colorectal diverticulosis was 13.5% in Taiwan. Age over 60 years old, adenomatous polyp and heavy alcohol consumption may affect the risk of development of the disease.
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http://dx.doi.org/10.1186/s12876-015-0267-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383068PMC
April 2015

Measurement of peritoneal fluid urea nitrogen and creatinine levels is useful to detect iatrogenic urinary tract leakage in colorectal surgery.

J Chin Med Assoc 2015 May 11;78(5):283-6. Epub 2015 Mar 11.

Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address:

Background: Increased peritoneal drainage after colorectal surgery is a common problem. Measurement of peritoneal fluid urea nitrogen (UN) and creatinine (Cr) is a diagnostic tool to detect the urinary tract leakage (UTL). We evaluated its application in colorectal surgery.

Methods: We conducted a retrospective chart review study. We enrolled patients with iatrogenic UTL, and measured their UN and Cr levels in peritoneal fluid and compared them with those in blood and urine. Meanwhile, we assigned patients without UTL to a control group and compared clinical parameters of both groups.

Results: Twenty-three patients with iatrogenic UTL were recruited. The overall incidence was 0.5%. UN level in peritoneal fluid (322 ± 56 mg/dL) was significantly higher than that in blood (18.7 ± 4.0 mg/dL, p < 0.001); Cr level in peritoneal fluid (69.7 ± 14.3 mg/dL) was also significantly higher than that in blood (1.5 ± 0.5 mg/dL, p < 0.001). UN level in peritoneal fluid was significantly higher in the iatrogenic UTL group than in the control group (322 mL/dL vs. 9.3 mL/dL, p < 0.001); Cr level in peritoneal fluid was also significantly higher (69.7 mg/dL vs. 0.98 mg/dL, p < 0.001).

Conclusion: When increased peritoneal drainage is found postoperatively in colorectal surgery, measurement of UN and Cr levels in peritoneal fluid can be a useful diagnostic tool to determine intraperitoneal iatrogenic UTL.
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http://dx.doi.org/10.1016/j.jcma.2015.01.006DOI Listing
May 2015

Postoperative hypocaloric peripheral parenteral nutrition with branched-chain-enriched amino acids provides no better clinical advantage than fluid management in nonmalnourished colorectal cancer patients.

Nutr Cancer 2014 8;66(8):1269-78. Epub 2014 Oct 8.

a Department of Dietetics and Nutrition, Taipei Veterans General Hospital , Taipei City , Taiwan.

To assess clinical efficacy of using postoperative branched-chain amino acids (BCAAs)-enriched nutritional support in lower gastrointestinal cancer patients, we conducted a retrospective observational study comparing this regimen with traditional fluid management. Sixty-one eligible colorectal cancer patients consecutively admitted in the Colorectal Surgery Ward to receive postoperative hypocaloric peripheral parenteral nutrition (HPPN) were categorized into dextrose-only control group (n = 20), dextrose plus low-dose BCAA fat group (n = 20), and dextrose plus high-dose BCAA fat group (n = 21). Nutritional, clinical, and biochemical outcomes were collected on the day before and 7 days after surgery. Patients were nonmalnourished. Over the 7-day observation period, the control group had a significantly higher reduction in body mass index than the lower dose and the higher dose BCAA groups (P = 0.023 and P = 0.002, respectively). Compared to high-dose BCAA group, the control group also had a lower nitrogen excretion (P < 0.0001) and less reduction in nitrogen balance (P < 0.0001). There were no differences between study groups in biochemical measures, phlebitis, postoperative hospital stay, and in-hospital mortality. We found no better clinical advantage to the postoperative administration of BCAA-enriched HPPN than fluid management in nonmalnourished colorectal cancer patients.
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http://dx.doi.org/10.1080/01635581.2014.956248DOI Listing
August 2015

Prevalence and risk factors of asymptomatic colorectal polyps in taiwan.

Gastroenterol Res Pract 2014 23;2014:985205. Epub 2014 Jun 23.

Department of Radiation Oncology, Chang Gung Memorial Hospital, 123 TA-PEI Road, Kaohsiung City 833, Taiwan.

Purpose. To investigate the prevalence and risk factors of hyperplastic and adenomatous colorectal polyps in a Taiwanese general population. Methods. From January 2009 to December 2011, consecutive asymptomatic subjects undergoing a routine health check-up were evaluated by colonoscopy. The colorectal polyps were assessed, and medical history and demographic data were obtained from each patient. Logistic regression analysis was conducted to search the independent risk factors for asymptomatic hyperplastic and adenomatous colorectal polyps. Results. Of the 1899 asymptomatic subjects, the prevalences of hyperplastic polyps and adenomatous polyps were 11.1% and 16.1%, respectively. Multivariate analysis revealed that high body mass index (BMI > 25: OR, 1.32, 95% CI, 1.05-1.71) and current smoking (OR, 1.87, 95% CI, 1.42-2.71) were independent predictors for hyperplastic colorectal polyps. Age over 60 years old (OR, 3.49, 95% CI, 1.86-6.51), high body mass index (BMI > 25: OR, 1.75, 95% CI, 1.21-2.71), heavy alcohol consumption (OR, 2.01, 95% CI, 1.02-3.99), and current smoking (OR, 1.31, 95% CI, 1.04-1.58) were independent predictors for adenomatous colorectal polyps. Conclusion. High BMI and smoking are common risk factors for both adenomatous and hyperplastic polyps. Old age and alcohol consumption are additional risk factors for the development of adenomatous polyps.
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http://dx.doi.org/10.1155/2014/985205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094704PMC
July 2014

Drainage placement through the extraperitoneal tunnel can prevent its postoperative dislodgement effectively in laparoscopic rectal surgery.

Surg Laparosc Endosc Percutan Tech 2013 Aug;23(4):410-4

Department of Surgery, Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.

Background: Drainage placement is frequently used in laparoscopic rectal surgery, and dislodgement is common in conventional transperitoneal drainage placement. We proposed that extraperitoneal tunnel for drainage placement is useful to prevent the dislodgement.

Methods: We conducted an observational case-matched control study. In study group, a total of 40 patients undergoing laparoscopic rectal surgery with drainage through the extraperitoneal tunnel were enrolled. In control group, a total of 35 matched patients with drainage through the transperitoneal route were enrolled. Clinical data, tumor features, and intraoperative and postoperative characteristics were analyzed.

Results: Ten patients had drainage dislodgement in the transperitoneal group (28%) and 4 patients in the extraperitoneal group (10%). The P value was 0.039. Postoperative recovery was faster in the extraperitoneal group than in the transperitoneal group, as reflected by a shorter time to diet (P=0.049) and postoperative length of stay (P=0.032). In a multivariate analysis, drain dislodgement had a significant impact on the time to diet (P=0.023) and the postoperative length of stay (P=0.037). Drain placement influenced the time to diet (P=0.055) and the postoperative length of stay (P=0.079).

Conclusions: In laparoscopic rectal surgery, drainage placement through the extraperitoneal tunnel can prevent its postoperative dislodgement effectively and is associated with better postoperative recovery.
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http://dx.doi.org/10.1097/SLE.0b013e31828e3b2bDOI Listing
August 2013

Detection of resectable recurrences in colorectal cancer patients with 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography.

Cancer Biother Radiopharm 2013 Jul-Aug;28(6):479-87. Epub 2013 May 28.

Department of Nuclear Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, Republic of China.

Purpose: To evaluate the usefulness of 2-[(18)F]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the early detection of resectable recurrences of colorectal cancer (CRC) and the impacts on the clinical disease management.

Methods: FDG-PET/CT was performed on patients with elevated serum carcinoembryonic antigen (CEA) levels >5 ng/mL (Group 1) or suspicious recurrences without rise in serum CEA levels (Group 2). The results were analyzed on the basis of histological data, disease progression, and/or clinical follow-up. Recurrence was defined as evidence of recurrent lesions within 6 months of the FDG-PET/CT scan. Resectable recurrences and changes in management were calculated based on medical records.

Results: In our study, 128 consecutive FDG-PET/CT analyses (n=49 in Group 1 and n=79 in Group 2) were performed on 96 recruited patients. Recurrences were proven in 63. The overall sensitivity, specificity, and accuracy of FDG-PET/CT were 98.4%, 89.2%, and 93.8%, respectively, and were 100%, 88.9%, and 95.9% in Group 1 and 96.9% and 89.4% and 92.4% in Group 2, respectively. Surgical resections were performed in 38.7% (12/31) of Group 1 patients and 53.1% (17/32) of Group 2 patients. FDG-PET/CT induced changes in planned management in 48.4% (62/128) of all patients, which included 63.3% (31/49) of Group 1 patients and 39.2% (31/79) of Group 2 patients (p=0.008). After a follow-up, 3.4% (1/29) of patients who underwent surgical resection of recurrent lesions and 34.3% (11/34) patients who did not undergo resection died at the end of study (p=0.004).

Conclusions: The surgical resection of limited recurrent disease, as determined by FDG-PET/CT, improves the survival of CRC patients. FDG-PET/CT should be performed not only in patients with elevated serum CEA levels, but also in those in whom recurrences are suspected to improve the early detection of resectable disease.
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http://dx.doi.org/10.1089/cbr.2012.1382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715809PMC
May 2014

Comparison of the feasibility of laparoscopic resection of the primary tumor in patients with stage IV colon cancer with early and advanced disease: the short- and long-term outcomes at a single institution.

Surg Today 2013 Oct 3;43(10):1116-22. Epub 2012 Nov 3.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st RD., Kaohsiung, 81346, Taiwan, ROC,

Purpose: The role of resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Laparoscopic resection has become an accepted therapeutic option for treating early stage I-III CRC; however, it has not been evaluated for use in patients with advanced stage disease.

Methods: We conducted a retrospective observational study to evaluate the feasibility of laparoscopic resection of the primary tumor exclusively in patients with stage IV colon cancer compared to open resection in patients with stage IV colon cancer and laparoscopic resection in patients with stage I-III colon cancer in terms of operative results and short- and long-term outcomes.

Results: Laparoscopic resection was performed in 35 stage IV patients and open resection was performed in 40 stage IV patients. One hundred and eighteen stage I-III patients who underwent laparoscopic resection were evaluated. In the comparison between the laparoscopic group and the open group among patients with stage IV colon cancer, postoperative recovery appeared to be better in the laparoscopic group than in the open group, as reflected by shorter times to resumption of a regular diet (p = 0.049), shorter lengths of hospitalization (p = 0.083), increased feasibility of postoperative chemotherapy (p < 0.001), shorter time intervals from surgery to chemotherapy (p = 0.031) and longer median survival (p = 0.078) at the expense of longer operative times (p = 0.025). In the comparison between the laparoscopic resection in stage IV and stage I-III disease groups, no significant differences were observed in operative results and short- and long-term outcomes, except for the rate of ostomy creation (48.5 vs. 8.5%, p = 0.02).

Conclusion: Laparoscopic resection of the primary tumor in patients with stage IV colon cancer achieves equivalent results to that performed in patients with stage I-III disease and that performed in patients with stage IV disease using open resection. The use of a minimally invasive approach in the laparoscopic procedure is beneficial because it results in shorter times to resumption of a normal diet, shorter lengths of hospitalization, increased feasibility of postoperative chemotherapy and shorter time intervals from surgery to chemotherapy at the expense of longer operative times. We believe that patients undergoing laparoscopic resection can receive targeted chemotherapy earlier and more aggressively, which might provide a survival benefit.
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http://dx.doi.org/10.1007/s00595-012-0398-zDOI Listing
October 2013

Oxaliplatin-induced severe anaphylactic reactions in metastatic colorectal cancer: case series analysis.

World J Gastroenterol 2012 Oct;18(38):5427-33

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, Kaohsiung 81346, Taiwan, China.

Aim: To investigate oxaliplatin-induced severe anaphylactic reactions (SAR) in metastatic colorectal cancer in a retrospective case series analysis and to conduct a systemic literature review.

Methods: During a 6-year period from 2006 to 2011 at Kaohsiung Veterans General Hospital, a total of 412 patients exposed to oxaliplatin-related chemotherapy were retrospectively reviewed. Relevant English-language studies regarding life-threatening SAR following oxaliplatin were also reviewed in MEDLINE® and PubMed® search.

Results: Eight patients (1.9%, 8 of 412 cases) were identified. Seven patients were successful resuscitated without any sequelae and one patient expired. We changed the chemotherapy regimen in five patients and rechallenged oxaliplatin use in patient 3. Twenty-three relevant English-language studies with 66 patients were reported. Patients received a median of 10 cycles of oxaliplatin (range, 2 to 29). Most common symptoms were respiratory distress (60%), fever (55%), and hypotension (54%). Three fatal events were reported (4.5%). Eleven patients (16%) of the 66 cases were rechallenged by oxaliplatin.

Conclusion: SAR must be considered in patients receiving oxaliplatin-related chemotherapy, especially in heavily pretreated patients. Further studies on the mechanism, predictors, preventive methods and management of oxaliplatin-related SAR are recommended.
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http://dx.doi.org/10.3748/wjg.v18.i38.5427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471112PMC
October 2012

Laparoscopic excision of mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor in adults.

Surg Laparosc Endosc Percutan Tech 2012 Oct;22(5):e294-6

Department of Surgery, Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan, ROC.

Mesenteric cysts are rare abdominal tumors with an incidence of 1/105,000 to 250,000 hospitalized adult surgical patients. These cysts may occur in every part of the mesentery, from duodenum to rectum. Most frequently, cysts are localized in small bowel mesentery. They usually present during the first decade of life, mostly occurring in pediatric patients. These lesions characteristically arise from the mesenteric border of the bowel. The majority are asymptomatic and, if found, are discovered incidentally during abdominal exploration or radiologic examination. Traditionally, the treatment of mesenteric cyst is surgical excision by laparotomy. However, in 1993, Mackenzie described the first laparoscopic excision of a mesenteric cyst. Since then, several cases have been reported but mainly in small intestine. Here, we reported an adult patient of a mesenteric duplication enteric cyst embedded in sigmoid mesocolon mimicking retroperitoneal neurogenic tumor, which was completely excised using the laparoscopic approach (Supplemental Digital Content 1, http://links.lww.com/SLE/A73).
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http://dx.doi.org/10.1097/SLE.0b013e3182611d07DOI Listing
October 2012

Factors that influence survival in colorectal cancer with synchronous distant metastasis.

J Chin Med Assoc 2012 Aug 24;75(8):370-5. Epub 2012 Jul 24.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.

Background: Treatments for the purposes of curing or more effectively managing metastatic colorectal cancer (CRC) are evolving. Our study focused on patients with primary CRC with synchronous distant metastasis, and we analyzed the factors influencing patient survival.

Methods: Data review was conducted retrospectively. Clinicopathological parameters included age, sex, site of primary cancer, tumor cell differentiation, number of liver metastasis, presence of extrahepatic metastasis, treatment of liver metastasis, pre-treatment carcinoembryonic antigen (CEA) level, status of treatment response, salvage treatment and survival.

Results: A total of 420 patients were identified and considered for our study. Of those, 275 patients (65.4%) had liver-only metastasis, 100 patients (23.8%) had concomitant lung metastasis, and 40 patients (9.5%) had other metastases. Additionally, 145 patients (34.5%) had liver-directed treatment including surgical resection (28.5%), radiofrequency ablation (RFA) (10.6%) and transcatheter arterial chemoembolization (TAE) (1.2%). There were 80 patients (19%) with CEA levels < 10, 135 patients (32.1%) with CEA 10-100, and 165 patients (39.2%) with CEA > 100. There were 200 patients (47.6%) who had received chemotherapy, 130 patients (30.9%) with target therapy, and 40 patients (9.5%) who had not undergone any salvage treatment. Three significant factors were identified, including treatment of liver metastasis (p=0.027), pre-treatment CEA (p=0.04), and salvage treatment (p=0.005).

Conclusion: We demonstrated three factors influencing patient survival including treatment of liver metastasis, pre-treatment CEA level, and salvage treatment. Aggressive treatment of liver metastasis including surgical resection or RFA combined with chemotherapeutic agents appear to provide an increased rate of survival to patients.
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http://dx.doi.org/10.1016/j.jcma.2012.03.008DOI Listing
August 2012

Factors that influence survival in unresectable metastatic or locally advanced colorectal cancer.

Int J Colorectal Dis 2011 Dec 15;26(12):1559-66. Epub 2011 May 15.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD, Kaohsiung, Taiwan, 81346, Republic of China.

Purpose: Half of patients with colorectal cancer (CRC) have metastasis during the whole course of the disease. Fewer than 10% of those are still alive at 5 years. Locally advanced CRC accounts for 7% to 33% of CRC relapses. Of these, only a small number of patients are resectable with a curative intent. Management of unresectable metastatic or locally advanced CRC is a significant challenge. In this study, we focus on patients with unresectable locally advanced or metastatic CRC and analyze survival rate and prognostic factors influencing the survival.

Methods: There were 277 patients identified. Several clinicopathologic parameters were evaluated. To determine the prognostic impact of the factors in survival, all parameters were tested from their relationship in Cox-regression model and Cox proportional hazards model. Survival curves were generated according to Kaplan-Meier method and the differences in survival were determined by employing the log-rank test.

Results: Three factors that influence the survival were identified: one or more than two organs involved (p = 0.041), higher carcinoembryonic antigen (CEA) level (p = 0.001), and different salvage treatment (p < 0.001). In Kaplan-Meier survival analysis, there were significant differences between patients with one and more than two organs involved (p = 0.027), different ranges of CEA level (p = 0.004), and different salvage treatment (p < 0.001).

Conclusions: We clearly demonstrated three factors that influence the survival, including more than two organs involved, higher CEA level, and different salvage treatment. The higher the CEA level and the more organs (≥2) involved, the worse the survival. Even in patients with unresectable metastatic or locally advanced, aggressive treatment with target therapy seems to have survival benefit.
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http://dx.doi.org/10.1007/s00384-011-1231-7DOI Listing
December 2011

Acute rectocolitis following endoscopy in health check-up patients--glutaraldehyde colitis or ischemic colitis?

Int J Colorectal Dis 2009 Oct 28;24(10):1193-200. Epub 2009 Jul 28.

Division of Colorectal surgery, Department of Surgery, Kaohsiung Veteran General Hospital, Kaohsiung City, Taiwan, 81346, Republic of China.

Purpose: Acute rectocolitis is a rare complication that follows endoscopy. It could be caused by glutaraldehyde or ischemic injury. The clinical, endoscopic, radiological, and pathological features of glutaraldehyde-induced colitis may mimic those of ischemic colitis. We reported our experiences regarding this problem.

Methods: The medical records of patients with acute rectocolitis following endoscopy treated at Kaohsiung Veterans General Hospital since 2001 were reviewed. The indication of endoscopy was health check-up for all patients. Published English-language studies regarding acute rectocolitis following endoscopy were also reviewed.

Results: An outbreak of six patients occurred in April 2002 and one cirrhotic patient was admitted in July 2008. All patients developed a self-limited syndrome of abdominal pain and bloody diarrhea within 48 h of uncomplicated endoscopy. One severely ill patient required hospitalization to receive intravenous fluid and antibiotics. After the investigation in April 2002, glutaraldehyde-induced colitis was diagnosed due to a defect in the endoscope-cleansing procedure. There were no any deficiencies in the cleansing procedure in July 2008. Considering the patient's concomitant disease, we postulated that ischemic colitis with cirrhosis-related intestinal inflammation and endotoxemia was the possible diagnosis in this sporadic case.

Conclusions: Endoscopists should be aware of this iatrogenic complication in patients presenting with acute rectocolitis, especially in those who have undergone recent endoscopic examination. An outbreak of acute rectocolitis following endoscopy should be considered glutaraldehyde-induced and should lead to an investigation of cleansing and equipment-disinfection procedures. In the absence of strong evidence of an outbreak, an infectious disease, or contamination of glutaraldehyde, a sporadic case should be considered ischemic colitis especially in patients with relevant concomitant diseases or predisposing factors.
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http://dx.doi.org/10.1007/s00384-009-0764-5DOI Listing
October 2009

Shifting to first-line regimen after previous failure of irinotecan and oxaliplatin containing chemotherapies in unresectable metastatic colorectal cancer: a retrospective study of case analysis.

Int J Colorectal Dis 2009 Apr 31;24(4):377-83. Epub 2008 Dec 31.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan, Republic of China.

Purpose: Conventional use of FOLFIRI-FOLFOX or the reverse sequence is the optional regimen in metastatic unresectable colorectal cancer (CRC). We present our experience in chemotherapy (C/T) shifting to first-line regimen after previous failure of irinotecan and oxaliplatin containing regimens.

Materials And Methods: A total of 48 patients with metastatic unresectable CRC were examined retrospectively. All the patients had both failure of a first-line C/T and a second-line C/T. Of these patients, 13 patients received C/T shifting to first-line regimen. Data were collected retrospectively.

Results: Rate of disease control of 38.4% was achieved (five in 13 patients). In the positive disease control group, metastatic sites were all extra-hepatic (five patients). In the negative disease control group, hepatic metastatic rate was 62.5% (five in eight patients, P=0.044).

Conclusions: Even after previous failure of irinotecan and oxaliplatin containing C/T, we observe positive disease control response and survival benefit in selected patients with C/T shifting to the first-line regimen especially in extra-hepatic metastasis. The preliminary results are proposed to gain insight into the need for further investigations and large-scale studies.
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http://dx.doi.org/10.1007/s00384-008-0621-yDOI Listing
April 2009

Factors that influence 12 or more harvested lymph nodes in early-stage colorectal cancer.

World J Surg 2009 Feb;33(2):333-9

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD., Kaohsiung, 81346, Taiwan, ROC.

Background: The number of lymph nodes required for accurate staging is a critical component in early-stage (stage A and B) colorectal cancer (CRC). Current guidelines demand at least 12 lymph nodes to be retrieved. Results of previous studies were contradictory in factors, which influenced the number of harvested lymph nodes. This study was designed to determine the factors that influence the number of harvested lymph nodes (> or =12) in early-stage CRC in a single institution.

Methods: Between 2003 and 2007, data on patients who underwent surgery for early-stage CRC were analyzed retrospectively. Data for a total of 470 patients were collected and all the tumor-bearing specimens were fixed with node identification performed. Several possible factors that influence 12 or more harvested lymph nodes were investigated and classified into four aspects: (1) operating surgeon, (2) examining pathologist, (3) patient (age, sex, and body mass index), and (4) disease (maximal length of tumor, length of specimen, tumor localization, tumor cell differentiation, Dukes stage, type of resection, and type of tumor).

Results: A total of 289 patients (61.5%) with 12 or more harvested lymph nodes and 181 patients (38.5%) with < 12 lymph nodes were analyzed. The results demonstrate that within a single institution the maximal length of tumor, tumor localization, and depth of tumor invasion according to Dukes stage were independent influencing factors of 12 or more harvested lymph nodes. Maximal length of tumor was associated with more harvested lymph nodes (P < 0.001). Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes.

Conclusions: The number of harvested lymph nodes was highly variable in patients who underwent resection of early-stage CRC. Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. Therefore, from the viewpoint of the surgeons, disease itself is the most important factor influencing the number of harvested lymph nodes.
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http://dx.doi.org/10.1007/s00268-008-9850-zDOI Listing
February 2009

Epigenetic inactivation of the metastasis suppressor RECK enhances invasion of human colon cancer cells.

J Cell Physiol 2007 Oct;213(1):65-9

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.

Down-regulation of RECK, an important metastasis suppressor gene, has been found in human colon cancer. However, the molecular mechanism for this down- regulation and its biological significance are still unclear. In the present study, we investigated whether down-regulation of RECK is caused by epigenetic inactivation via promoter methylation and tested the effect of DNA methyltransferase (DNMT) inhibitor on RECK expression and cell invasion. The mRNA and protein levels of RECK in colon tumor tissues and their normal counterparts were compared. We found that down-regulation of RECK was found in 48% of the twenty five tumors analyzed. MSP analysis demonstrated that methylation of RECK promoter was detected in 44% (11/25) of the tumor tissues and a strong correlation between down-regulation and promoter methylation was found (P = 0.028). Promoter methylation was also found in SW480 and SW620 human colon cancer cell lines. DNA methyltransferase (DNMT) inhibitor 5'-azacytidine reversed promoter methylation, restored RECK expression and suppressed invasion by these two cell lines. Restoration of RECK is critical for 5'-azacytidine-mediated suppression of cell invasion because inhibition of RECK by a specific antibody significantly attenuated the anti-invasive ability of 5'-azacytidine. Taken together, our results suggest that down-regulation of the metastasis suppressor RECK in colon cancer is associated with promoter methylation and that a DNMT inhibitor may restore RECK expression to inhibit cell invasion.
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http://dx.doi.org/10.1002/jcp.21089DOI Listing
October 2007

Recombinant E. coli efficiently delivers antigen and maturation signals to human dendritic cells: presentation of MART1 to CD8+ T cells.

Int J Cancer 2003 Jul;105(6):811-9

Cancer Research UK Molecular Oncology Unit, Imperial College London, Hammersmith Hospital, London, United Kingdom.

The generation of tumour-specific cytotoxic T-lymphocyte (CTL) responses is the primary focus in the design of immunotherapeutic cancer vaccines. We have recently demonstrated generation of ovalbumin (OVA)-specific CTLs and tumour-protection in a murine tumour model using vaccination with dendritic cells (DCs) pulsed with E. coli expressing listeriolysin O (LLO) and OVA as a model antigen. In this system paraformaldehyde fixation of E. coli/LLO provided an additional safety feature without compromising vaccine efficacy. We therefore reasoned that paraformaldehyde-fixed recombinant E. coli expressing LLO would be an efficient vehicle for the delivery of human tumour antigens to human DCs. In the present study, we demonstrate that fixed E. coli expressing LLO are taken up efficiently by human monocyte-derived DCs (MoDCs) with minimal toxicity. As a consequence of the interaction with bacteria, human DCs undergo marked phenotypic and functional maturation. Furthermore, we show that fixed E. coli/LLO expressing the well-characterised human melanoma antigen, MART1, efficiently deliver the HLA-A2-restricted MART1(27-35) epitope for processing and presentation on human MoDCs, suggesting the potential of this system as a novel strategy for human tumour immunotherapy.
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http://dx.doi.org/10.1002/ijc.11149DOI Listing
July 2003
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