Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

Recurrent abdominal liposarcoma: Analysis of 19 cases and prognostic factors

AIM: To evaluate the clinical outcome of re-operation for recurrent abdominal liposarcoma following multidis-ciplinary team cooperation. METHODS: Nineteen consecutive patients who had re-current abdominal liposarcoma underwent re-operation by the retroperitoneal sarcoma team at our institution from May 2009 to January 2012. Patient demographic and clinical data were reviewed retrospectively. Multidisciplinary team discussions were held prior to treatment, and re-operation was deemed the best treatment. The categories of the extent of resection were as follows: gross total resection (GTR), palliative resection and partial resection. Surgical techniques were divided into discrete lesion resection and combined contiguous multivisceral resection (CMR). Tumor size was determined as the largest diameter of the specimen. Patients were followed up at approximately 3-monthly intervals. For survival analysis, a univariate analysis was performed using the Kaplan-Meier method, and a multivariate analysis was performed using the Cox pro-portional hazards model. RESULTS: Nineteen patients with recurrent abdominal liposarcoma (RAL) underwent 32 re-operations at our institute. A total of 51 operations were reviewed with a total follow-up time ranging from 4 to 120 (47.4 ± 34.2) mo. The GTR rate in the CMR group was higher than that in the non-CMR group (P = 0.034). CMR was positively correlated with intra-operative bleeding (correlation coefficient = 0.514, P = 0.010). Six cases with severe postoperative complications were recorded. Patients with tumor sizes greater than 20 cm carried a significant risk of profuse intra-operative bleeding (P = 0.009). The ratio of a highly malignant subtype (de-differentiated or pleomorphic) in recurrent cases was higher compared to primary cases (P = 0.027). Both single-factor survival using the Kaplan-Meier model and multivariate analysis using the Cox proportional hazards model showed that overall survival was corre-lated with resection extent and pathological subtype (P < 0.001 and P = 0.02), however, relapse-free interval (RFI) was only correlated with resection extent (P = 0.002). CONCLUSION: Close follow-up should be conducted in patients with RAL. Early re-operation for relapse is preferred and gross resection most likely prolongs the RFI.

Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours

BACKGROUND The prognostic significance of lymph nodes(LNs)metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours(GEP NETs)undergoing curative resection is still debatable.Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy AIM To evaluate the effect of lymph node(LN)status and yield on relapse-free survival(RFS)and overall survival(OS)in patients with resected GEP NETs.METHODS Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively.Grade 3 tumours(Ki67>20%)were excluded.Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS.RESULTS A total of 217 patients were included in the study.The median age was 59 years(21-97 years)and 51%(n=111)were male.Primary tumour sites were small bowel(42%),pancreas(25%),appendix(18%),rectum(7%),colon(3%),gastric(2%),others(2%).Median follow up times for all patients were 41 mo(95%CI:36-51)and 71 mo(95%CI:63–76)for RFS and OS respectively;50 relapses and 35 deaths were reported.LNs were retrieved in 151 patients.Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients.Three or more positive LNs were detected in 62 cases.The result of univariate analysis suggested perineural invasion(P=0.0023),LN positivity(P=0.033),LN retrieval of≥8(P=0.047)and localisation(P=0.0049)have a statistically significant association with shorter RFS,but there was no effect of LN ratio on RFS:P=0.1 or OS:P=0.75.Tumour necrosis(P=0.021)and perineural invasion(P=0.016)were the only two variables significantly associated with worse OS.In the final multivariable analysis,localisation(pancreas HR=27.33,P=0.006,small bowel HR=32.44,P=0.005),and retrieval of≥8 LNs(HR=2.7,P=0.036)were independent prognostic factors for worse RFS.CONCLUSION An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery.Removal of≥8 LNs is associated with increased risk of relapse,which could be due to high rates of LN positivity at the time of surgery.Given that localisation had a significant association with RFS,a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.

Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation:long-term follow-up of a multicenter,randomized controlled trial

Given that randomized studies testing the long-term impact of antithymocyte globulin(ATG)dosing are scarce,we report the results of an extended follow-up from the original trial.In our prospective,multicenter,randomized trial,408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation(haplo-HCT)under our original“Beijing Protocol”were randomly assigned one-to-one to ATG doses of 7.5 mg/kg(n=203,ATG-7.5)or 10 mg/kg(n=205,ATG-10.0)at four sites.Extended follow-up(median 1968 d(range:1300–2710 d)indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease(GVHD)(hazard ratio(HR):1.384,95%confidence interval(CI):0.876–2.189,P=0.164),nonrelapse mortality(HR:0.814,95%CI:0.526–1.261,P=0.357),relapse(HR:1.521,95%CI:0.919–2.518,P=0.103),disease-free survival(HR:1.074,95%CI:0.783–1.473,P=0.658),and GVHD-free/relapse-free survival(HR:1.186,95%CI:0.904–1.555,P=0.219)between groups(ATG-7.5 vs.ATG-10.0).The 5-year rate of late effects did not differ significantly.However,the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort(9.8%vs.1.5%;P=0.003).In summary,patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control.ATG(7.5 mg/kg)is potentially regarded as the standard regimen in the platform.These results support the optimization of ATG use in the“Beijing Protocol”,especially considering the potential economic advantage in developing countries.

Development and validation of a web-based calculator to predict individualized conditional risk of site-specific recurrence in nasopharyngeal carcinoma: Analysis of 10,058 endemic cases

Background:Conditional survival(CS)provides dynamic prognostic estimates by considering the patients existing survival time.Since CS for endemic nasopharyngeal carcinoma(NPC)is lacking,we aimed to assess the CS of endemic NPC and establish a web-based calculator to predict individualized,conditional sitespecific recurrence risk.Methods:Using an NPC-specific database with a big-data intelligence platform,10,058 endemic patients with non-metastatic stage I–IVA NPC receiving intensity-modulated radiotherapy with or without chemotherapy between April 2009 and December 2015 were investigated.Crude CS estimates of conditional overall survival(COS),conditional disease-free survival(CDFS),conditional locoregional relapse-free survival(CLRRFS),conditional distant metastasis-free survival(CDMFS),and conditional NPC-specific survival(CNPC-SS)were calculated.Covariate-adjusted CS estimates were generated using inverse probability weighting.A prediction model was established using competing risk models and was externally validated with an independent,non-metastatic stage I–IVA NPC cohort undergoing intensity-modulated radiotherapy with or without chemotherapy(n=601)at another institution.Results:The median follow-up of the primary cohort was 67.2 months.The 5-year COS,CDFS,CLRRFS,CDMFS,and CNPC-SS increased from 86.2%,78.1%,89.8%,87.3%,and 87.6%at diagnosis to 87.3%,87.7%,94.4%,96.0%,and 90.1%,respectively,for an existing survival time of 3 years since diagnosis.Differences in CS estimates between prognostic factor subgroups of each endpoint were noticeable at diagnosis but diminished with time,whereas an ever-increasing disparity in CS between different age subgroups was observed over time.Notably,the prognoses of patients that were poor at diagnosis improved greatly as patients survived longer.For individualized CS predictions,we developed a web-based model to estimate the conditional risk of local(C-index,0.656),regional(0.667),bone(0.742),lung(0.681),and liver(0.711)recurrence,which significantly outperformed the current staging system(P<0.001).The performance of this webbased model was further validated using an external validation cohort(median follow-up,61.3 months),with C-indices of 0.672,0.736,0.754,0.663,and 0.721,respectively.Conclusions:We characterized the CS of endemic NPC in the largest cohort to date.Moreover,we established a web-based calculator to predict the CS of sitespecific recurrence,which may help to tailor individualized,risk-based,timeadapted follow-up strategies.