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  • Recurrence and rejection in liver transplantation for primary sclerosing cholangitis
  • Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease affecting the bile ducts, leading to f ibrosis and eventually cirrhosis in most patients. Its etiology is unknown and so far no effective medical therapy is available. Liver transplantation (LTX) is the only curative treatment and at present PSC is the main indication for LTX in the Scandinavian countries. Close to half of the PSC patients experience one or more episodes of acute cellular rejection (ACR) following transplantation and approximately 1/5 of the transplanted patients develop recurrent disease in the graft. In addition, some reports indicate that ACR early after LTX for PSC can infl uence the risk for recurrent disease. For these important post-transplantation entities affecting PSC patients, we have reviewed the current literature on epidemiology, pathogenesis, treatment and the possible infl uence of rejection on the risk of recurrent disease in the allograft.
  • Multi-modality treatment of colorectal liver metastases
  • Liver metastases synchronously or metachronously occur in approximately 50% of colorectal cancer patients. Multimodality comprehensive treatment is the best therapeutic strategy for these patients. However, the optimal pattern of multimodality therapy is still controversial, and it raises several signif icant concerns. Liver resection is the most important treatment for colorectal liver metastases. The defi nition of resectability has shifted to focus on the completion of R0 resection and normal liver function maintenance. The role of neoadjuvant and adjuvant chemotherapy still needs to be clarified. The management of either progression or complete remission during neoadjuvant chemotherapy is challenging. The optimal sequencing of surgery and chemotherapy in synchronous colorectal liver metastases patients is still unclear. Conversional chemotherapy, portal vein embolization, two-stage resection, and tumor ablation are effective approaches to improve resectability for initially unresectable patients. Several technical issues and concerns related to these methods need to be further explored. For patients with def initely unresectable liver disease, the necessity of resecting the primary tumor is still debatable, and evaluatingand predicting the eff icacy of targeted therapy deserve further investigation. This review discusses different patterns and important concerns of multidisciplinary treatment of colorectal liver metastases.
  • An update on chemotherapy of colorectal liver metastases
  • Surgical resection of liver metastases of colorectal cancer greatly improves the clinical outcome of patients with advanced disease. Developments in chemotherapeutic agents and strategies bring hope of a cure to patients with initially unresectable colorectal liver metastases (CLM). Perioperative chemotherapy signif icantly improves the survival time of patients who receive curative-intent hepatectomy. Even for unresectable CLM, recent studies demonstrated that active preoperative chemotherapy could achieve shrinkage of liver metastasis and thus render some for resection. Furthermore, an increase in tumor resection rate and prolonged survival time among patients with CLM has been observed following the application of monoclonal antibodies in recent years. However, the value of chemotherapy via hepatic arterial infusion is still unclear. More trials should be conducted in patients with CLM in order to improve survival.
  • Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma
  • AIM: To determine the number of regulatory T cells (Tregs) in gastric mucosa of patients with gastritis, peptic ulcers and gastric cancer. METHODS: This study was a retrospective analysis of gastric antrum biopsy specimens from healthy controls (n = 22) and patients with gastritis (n = 30), peptic ulcer (n = 83), or gastric cancer (n = 32). Expression of CD4, CD25 and Foxp3 was determined by immunohistochemistry in three consecutive sections per sample.RESULTS: Compared with healthy controls, there was an increased number of CD25+ and Foxp3+ cells in patients with gastritis (P = 0.004 and P = 0.008), peptic ulcer (P 〈 0.001 and P 〈 0.001), and gastric cancer (P 〈 0.001 and P 〈 0.001). The ratio of CD25+/CD4+ or Foxp3+/CD4+ cells was also significantly higher in all disease groups (P 〈 0.001, respectively). The number of CD4+, CD25+, and Foxp3+ cells, and the ratio of CD25+/CD4+ and Foxp3+/CD4+ cells, were associated with the histological grade of the specimens, including acute inflammation, chronic inflammation, lymphoid follicle number, and Helicobacter pylori infection. The number of CD4+, CD25+ and Foxp3+ cells, and the ratio of CD25+/CD4+ and Foxp3+/CD4+ cells, were negatively associated with intestinal metaplasia among gastritis (P 〈 0.001, P 〈 0.001, P 〈 0.001, P = 0.002 and P = 0.002) and peptic ulcer groups (P = 0.013, P = 0.004, P 〈 0.001, P = 0.040 and P = 0.003).
  • Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test
  • AIM: To investigate the effects of proton pump inhibitor (PPI) treatment on stool antigen test using the TestMate pylori enzyme immunoassay. METHODS: This study assessed 28 patients [16 men and 12 women; mean age (63.1 ± 5.9) years; range, 25-84 years] who underwent stool antigen test and urea breath test (UBT) before and after PPI administration. RESULTS: Using the UBT as the standard, the sensitivity, specif icity and agreement of the stool antigen test in all 28 patients were 95.2%, 71.4%, and 89.3%, respectively, before PPI administration, and 88.9%, 90.9%, and 89.3%, respectively, after PPI treatment. Mean UBT values were 23.98% ± 5.33% before and 16.19% ± 4.75% after PPI treatment and, in 15 patients treated for ≥ 4 wk, were signif icantly lower after than before 4 wk of PPI treatment (12.58% ± 4.49% vs 24.53% ± 8.53%, P = 0.048). The mean optical density (A450/630) ratios on the stool antigen test were 1.16 ± 0.20 before and 1.17 ± 0.24 after PPI treatment (P = 0.989), and were 1.02 ± 0.26 and 0.69 ± 0.28, respectively, in the group treated for 〉 4 wk (P = 0.099).
  • Outcome after gastrectomy in gastric cancer patients with type 2 diabetes
  • AIM: To evaluate the prognosis of type Ⅱ diabetes mellitus (T2DM) after gastrectomy and related factors in gastric cancer patients. METHODS: 403 gastric cancer patients with T2DM were studied, who underwent gastrectomy between May 2003 and September 2009. A review of medica records and telephone interviews was performed in this cross-sectional study. The factors included in the statistical analysis were as follows: gender, age, type of surgery, preoperative body mass index (BMI), current BMI, BMI reduction ratio, preoperative insulin or oral diabetic medicine requirement, follow-up duration, and current state of diabetes. Assessment of diabetes status after surgery was classified into four categories according to the change in hypoglycemic agents after surgery and present status of T2DM: resolution, improvement, same, and worse.(± 20.6 mo), preoperative BMI was 24.7 kg/m2 (± 3.0 kg/m2), and BMI reduction ratio was 9.8% (± 8.6%). After surgery, T2DM was cured in 58 patients (15.1%) and was improved in 117 patients (30.4%). According to the type of surgery, the BMI reduction ratio was signif icantly higher in the total gastrectomy and Roux-en-Y reconstruction group [14.2% ± 9.2% vs 9.2% ± 7.7% (Billroth Ⅱ group), P 〈 0.001] and signif icantly lower in the subtotal gastrectomy and Billroth Ⅰ reconstruction group [7.6% ± 8.0%, 9.2% ± 7.7% (Billroth Ⅱ group), P 〈 0.001]. The BMI reduction ratio, follow-up duration after surgery, type of surgery, extent of gastrectomy, and performance of duodenal bypass were signif icantly correlated to the course of T2DM (P 〈 0.05). The BMI reduction ratio was the most influential factor on T2DM status. In a subgroup analysis of patients with a BMI reduction ratio of 10% or less (n = 206), T2DM was cured in 15 (7.6%) patients and was improved in 57 (28.8%) patients after surgery, and only the duration of surgery was signif icantly correlated to T2DM status (P = 0.022).
  • Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients
  • AIM: To assess the efficacy and safety of combinedpegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients. METHODS: This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patient's complete blood count, liver and kidney prof ile, and cal- culated glomerular f iltration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required. RESULTS: Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patient's kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects. CONCLUSION: The combination of pegylated interferon and ribavirin is effective in...
  • Risk factors for adverse outcome in low rectal cancer
  • AIM: To demonstrate the oncologic outcomes of low rectal cancer and to clarify the risk factors for survival, focusing particularly on the type of surgery performed. METHODS: Data from patients with low rectal carcinomas who underwent surgery, either sphincter-preserving surgery (SPS) or abdominoperineal resection (APR), at The First Aff iliated Hospital of Sun Yat-sen University in China from August 1994 to December 2005 were retrospectively analyzed. RESULTS: Of 331 patients with low rectal cancer, 159 (48.0%) were treated with SPS. A higher incidence of positive resection margins and a higher 5-year cumulative local recurrence rate (14.7% vs 6.8%, P = 0.041) were observed in patients after APR compared to SPS.The five-year overall survival (OS) was 54.6% after APR and 66.8% after SPS (P = 0.018), and the 5-year disease-free survival (DFS) was 52.9% after APR and 65.5% after SPS (P = 0.013). In multivariate analysis, poor OS and DFS were signif icantly related to positive resection margins, pT3-4, and pTNM Ⅲ-Ⅳ but not to the type of surgery. CONCLUSION: Despite a higher rate of positive resection margins after APR, the type of surgery was not identif ied as an independent risk factor for survival.
  • Germline promoter hypermethylation of tumor suppressor genes in gastric cancer
  • AIM: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16INK4a in suspected cases of hereditary gastric cancer (GC). METHODS: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16INK4a tumor suppressor genes. GenomicDNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfi te DNA sequencing for a specif ic region of the MLH1 promoter. The methylation status of CDH1 or P16INK4a was assayed using methylation-specif ic PCR. Clonal bisulf ite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions. RESULTS: Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16INK4a genes was detected. CONCLUSION: Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16INK4a gene is not a frequent event.
  • Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest
  • AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry.RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a doseand time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.
  • Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation
  • AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.
  • Inflammatory pseudotumor of the liver and spleen diagnosed by percutaneous needle biopsy
  • An inflammatory pseudotumor (IPT) is a relatively rare lesion characterized by chronic inf iltration of inflammatory cells and areas of f ibrosis. IPTs are diff icult to diagnose because of the absence of specif ic symptoms or of characteristic hematological or radiological f indings. In this study, a case of a woman aged over 70 years was reported, who presented with a general malaise lasting more than two months. A computed tomography scan demonstrated a diffusely spread lesion of the liver with a portal vein occlusion and a splenic lesion surrounded by a soft density layer. Since the percutaneous liver biopsy showed f indings that suggested an IPT, although the radiological f indings did not exclude the possibility of a malignancy, we performed a percutaneous spleen biopsy to enable a more defi nitive diagnosis. The microscopic f indings from the spleen specimen lead us to a diagnosis of IPT involving the liver and spleen. Sub-sequent steroid pulse therapy was effective, and rapid resolution of the disease was observed.
  • Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors
  • Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal malignancies. They are rarely seen near the urinary tract. In a literature review, only one case of GIST presenting as a left adrenal tumor was reported. We report two documented cases of gastric GISTs mimicking left adrenal tumors which were successfully treated with pure laparoscopic adrenalectomy and wedge resection of the stomach by excising the tumor from the stomach with serial fi ring of endoscopic gastrointestinal staplers. The surgical margins were clear, and the patients recovered smoothly. No adjuvant therapy with imatinib was prescribed. During the surveillance for 9 mo and 44 mo respectively, no tumor recurrence and metastasis were documented. Laparoscopic tumor excision, when adhering to the principles of surgical oncology, seems feasible and the prognosisis favorable for such tumors.
  • Acknowledgments to reviewers of World Journal of Gastroenterology
  • Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Gastroenterology. The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles (including those published in this issue and those rejected for this issue) during the last editing time period.
  • MEETINGS
  • Events Calendar 2012 January 13-15, 2012 Asian Pacif ic Helicobacter pylori Meeting 2012 Kuala Lumpur, Malaysia January 19-21, 2012 American Society of Clinical Oncology 2012 Gastrointestinal Cancers Symposium San Francisco, CA 3000, United States
  • INSTRUCTIONS TO AUTHORS
  • GENERAL INFORMATION World Journal of Gastroenterology (World J Gastroenterol, WJG, print ISSN 1007-9327, online ISSN 2219-2840, DOI: 10.3748) is a weekly, open-access (OA), peer-reviewed journal supported by an editorial board of 1361 experts in gastroenterology and hepatology from 64 countries. The biggest advantage of the OA model is that it provides free, full-text articles in PDF and other formats for experts and the public without regi
  • [EDITORIAL]
    Recurrence and rejection in liver transplantation for primary sclerosing cholangitis(Bjarte Fosby[1,2] Tom H Karlsen[2] Espen Melum[2,3])
    [TOPICHIGHLIGHT]
    Multi-modality treatment of colorectal liver metastases(Guo-Xiang Cai[1,2] San-Jun Cai[1,2])
    An update on chemotherapy of colorectal liver metastases(Chen-ChenWang[1,2] Jin Li[1,2])
    [0RIGINALARTICLE]
    Increased numbers of Foxp3-positive regulatory T cells in gastritis, peptic ulcer and gastric adenocarcinoma
    [BRIEFARTICLE]
    Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test(Masaaki Kodama[1,2] Kazunari Murakami[1] Tadayoshi Okimoto[1] Yoshihiro Fukuda[3] Tadashi Shimoyama[4] Masumi Okuda[3] Chieko Kato[5] Intetsu Kobayashi[6] Toshio Fujioka[1])
    Outcome after gastrectomy in gastric cancer patients with type 2 diabetes(Jong Won Kim[1] Jae-Ho Cheong[2] Woo Jin Hyung[2] Seung-Ho Choi[1] Sung Hoon Noh[2])
    Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients(Abdulrahman A Aljumah[1] Mohamed A Saeed[1] Ahmed I AI Flaiw[2] Ibrahim HAI Traif[1] Abduljaleel M AI AIwan[1] Salem HAI Qurashi[2] Ghormallah A AI Ghamdi[2] Fayez F AI Hejaili[2] Mohammed A AI Balwi[3] Abdulla A AI Sayyari[2])
    Risk factors for adverse outcome in low rectal cancer(Zhi-Hui Chen[1] Xin-Ming Song[1] Shi-Cai Chen[1] Ming-Zhe Li[2] Xin-Xin Li[1] Wen-Hua Zhan[1] Yu-Long He[1])
    Germline promoter hypermethylation of tumor suppressor genes in gastric cancer(Pu-Yuan Wu[1,2] Zheng Zhang[1,2] Jing-Mei Wang[3] Wen-Wen Guo[1,2] Nong Xiao[4] Qiong He[1] Ya-Ping Wang[1,2] Yi-Mei Fan[1,2])
    [Contents]
    Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest(Long-Zhu Li[2] Hong-Xia Deng[1] Wen-Zhu Lou[1] Xue-Yan Sun[1] Meng-Wan Song[1] Jing Tao[1] Bing-Xiu Xiao[1] Jun-Ming Guo[1])
    Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation(Xiao-Bo Chen Jie Yang Ming-Qing Xu Tian-Fu Wen Lu-Nan Yan)
    [CASEREPORT]
    Inflammatory pseudotumor of the liver and spleen diagnosed by percutaneous needle biopsy(Tsukasa Kawaguchi[1] Kiyoshi Mochizuki[1] Takashi Kizu[1] Masanori Miyazaki[1] Takayuki Yakushijin[1] Shusaku Tsutsui[1] Eiichi Morii[2] Tetsuo Takehara[1])
    Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors(Shiu-Dong Chung[1] Jeff Shih-chieh Chueh[2,3,4] Hong-.leng Yu[2])

    Acknowledgments to reviewers of World Journal of Gastroenterology
    MEETINGS
    INSTRUCTIONS TO AUTHORS
    《世界胃肠病学杂志:英文版》封面