Intraductal papillary neoplasm of the bile duct (IPNB) is a variant of bile duct tumors characterized by papillary growth within the dilated bile duct lumen and secretion with a large amount of mucins.IPNB is an intraductal papillary cancer of the bile duct or a preinvasive lesion classified by the 2010 World Health Organization (WHO) classification.Although the specific etiology and pathogenesis are unclear,IPNB is known to two major risk factors:hepatoliathiasis and clonorchiasis.The clinical manifestations of IPNB include intermittent abdominal pain,acute cholangitis and obstructive jaundice.Results of laboratory test show abnormal liver function resulting from obstruction of bile duct,but it's not specific.The most common imaging findings for IPNB are bile duct dilatation and intraductal masses.Computed tomography,magnetic resonance image and cholangiography are usually performed to access tumor location and extension.According to morphology of the tumor epithelial cells,IPNB are classified into the pancreticbiliary,intestinal,gastric and oncocytic types.The surgical resection is a major treatment of IPNB.In principle,IPNB should be resected in a manner similar to that employed for other types of intrahepatic cholangiocarcinomas and extrabepatic bile duct carcinomas.The type of surgical procedure for IPNB depends upon tumor location and extension.Although several investigations have been conducted for illuminating molecular genetic changes during the development and progression of IPNB,the specific mechanism is still not clear,and further study is needed.

Objective To investigate the expression of interleukin 6 (IL-6) in tumor microenvironment of natural killer/T cell lymphoma (NKTCL) and its relationship with clinical characteristics and prognosis. Methods From January 2005 to December 2012, 93 patients with NKTCL and available paraffin-embedded tissue in Sun Yat-sen University Cancer Center were included. The expression or IL-6 in tumor microenvironment was investigated by immunohistochemistry. The positive IL-6 expression was identified as≥10 cells/HP. The enumeration data and measurement data were compared by t test andχ2 test, respectively. Overall survival (OS) and progression free survival (PFS) were estimated with the Kaplan-Meier method. Survival rates were compared by the Log-rank test. Statistical significance was determined at a level of P<0.05. Results The median count of IL-6 positive cell number was 21 cells/HPF (range, 0-150 cells/HP), and 61.29%(57/93) patients were positive. Positive IL-6 expression was mostly associated with fever and high Korean prognostic index (KPI) score (both P< 0.05). The serum c-reactive protein (CRP) level was (29.28 ± 2.62) mg/L in IL-6 positive patients and (11.14±2.77) mg/L in IL-6 negative patients (t= -2.276, P= 0.025). Patients with negative IL-6 expression had better survival, with 52.7 % of 5-year PFS rate,and 60.0 % of 5-year OS rate; the 5-year PFS and OS rates in those with IL-6 positive were 23.6 % and 27.1 %, respectively (both P= 0.001). Conclusion The high expression of IL-6 in patients with NKTCL might be associated with adverse clinical feature and poor survival.

[Objective]This study was aimed to evaluate treatment outcomes and toxicity of continuous-infusion EPOCH regimen for NK/T-cell lymphoma(NK/TCL).[Methods]From June 2003 to June 2008,34 patients including 30 nasal NK/TCL (88.2%)and 4 nasal type NK/TCL(11.8%)received doxorubicin,vincfistine,etoposide over 96 hours infusion with bolus eyelophosphamide and oral predinisone(EPOCH)chemotherapy as first-line treatment.Median cycles of EPOCH administered were 2.5(1-6 cycles).Additional involved field radiation therapy(IFRT)was administered to patients with localized nasal focus after chemotherapy.[Results]Among 34 patients,33 were eligible for response evaluation.The response rate(RR)was 60.6% (20/33)with complete remission(CR)rate of 45.5%(15/33).The RR of patients with nasal NK/TCL was 66.7%(20/30)with CR rate of 50%(15/30).Only one of the 3 nasal type NK/TCL patients achieved stable disease(SD),the other 2 had progressive disease(PD)during chemotherapy.After a median follow-up of 22(2-68)months,the estimated 3-year overall survival rate(OS)was 52.2%.For patients with nasal NK/TCL,the estimated median survival time was not reached,the 3-year OS was 59.4%.For patients with nasal type NK/TCL,the estimated median survival time was only 7 months.The CR rate was 75.0% for localized nasal NK/TCL who received initial EPOCH chemotherapy followed IFRT with the 3-year OS of 75.0%.Major adverse effect was myelosuppression.The incidence of grade Ⅲ～Ⅳ neutropenia was 30.9%.No treatment-related mortality occurred.[Conclusions]EPOCH regiment was effective and well tolerant for nasal NK/TCL.Combined EPOCH chemotherapy followed by IFRT produced promising outcome for patients with localized disease.However,patients with nasal type NK/TCL responded poorly and more efficacious treatment strategies are urgently needed.

[Objective]To evaluate the clinical efficacy and side effects of DHAOx±R regimen in the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL).[Methods]Twenty patients with relapsed or refractory NHL were enrolled into this study in Cancer Center of Sun Yat-sen University.These patients were treated with DHAOx±R regimen(Dexamethasone 20 mg/day intravenous(Ⅳ)on day 1 to day 4,cytarabine 2 000 mg/m~2 3 h Ⅳ,every 12 hours on day 2;oxaliplatin 130 mg/m~2 2 h Ⅳ on day 1;with or without rituximab 375 ms/m~2 on day 0).Six patients were followed by high dose chemotherapy with autologous peripheral blood stem cell transplantation.Response to treatment wag assessed according to The International Working Group Criteria,including CR,PR,SD and PD.Side effects were graded according to WHO criteria,including 0-Ⅳ grades.[Results]Twenty patients received 47 cycles chemotherapy,13 patients(65%)received DHAOx chemotherapy and 7(35%)received DHAOx+R.The response rate(RR)for the whole group was 55%(11/20)with comeplete response(CR)rate 35%(7/20).The response can also be obtained in the patients who were already treated by platinum-based regimen before.The major toxicity Wag myelosuppression.The incidence of grade Ⅲ～Ⅳ neutropenia Wag 35%(16/47),and febrile neutropenia was 17%(8/47).The incidence of grade Ⅲ～Ⅳ thrombocytopenia was 20%(9/47).Eight cycles(17%)occurred mild neumtoxicity.With median follow-up of 12 months,1 and 2-year overall survival rate were 70.6%.[Conclusion]DHAOx was an effective regimen for recurrent and relapsed NHL patients with mild side effects and further investigation is needed.

Objective To evaluate the efficacy and toxicity of SMILE regimen for NK/T-cell lymphoma. Methods From November 2006 to February 2008, 5 patients with relapsed and 5 with first treatment NK/T-cell lymphoma were involved in this study. These patients were treated with SMILE regimen including methotrexate, isofosfamide, L-asparaginase and etoposide.1 patient were treated with autolognus hematopoietic stem cell transplantation (AHSCT), and 2 patients received local regional radiation following SMILE. Results Among 10 patients, 8 were eligible to response evaluation. The overall response rate for whole group was 50 %(4/8) without complete remission. The overall response rate for both previously untreated and relapsed patients were 50 %(2/4). Major toxicity were bone marrow supression and transient transaminase elevation, the incidence of grade Ⅲ -Ⅳ neutroponia was 65 %, and febrile neutropenia was 25 %, Grade Ⅲ transaminase elevation was 10 %. Other toxicities were mild, no treatment-related mortality occurred. 26.1% cycles discontinued due to severe side effect. Conclusion SMILE may be an effective regimen for relapsed or refractory NK/T-cell lymphoma while significant toxicities were observed. Further investigation is requried before SMILE become a standard combination for relapsed or refractory NK/T-cell lymphoma.

Objective To determine the relationship between the serum level of β2-microglobin (β2-MG)and international prognostic index (IPI) and investigate the role of IPI in predicting the prognosis and making individualized therapy for peripheral T-cell lymphoma (PTCL).Methods Eighty-one patients with PTCL were treated by standard CHOP regimen.The clinical characteristics,response,long-term surival rates and the relationship between serum level of β2-MG and IPI scores were analyzed retrospectively.Results Eighty-one patients were eligible.All of them were treated by CHOP regimen.The overall response rate (RR) was 82.7 ％ with 53.1％ complete remission (CR) rate.The RR of IPI low risk,low-intermediate risk,high-intermediate risk,and high risk were 95.7 ％,87.5 ％,53.8 ％ and 20.0 ％,with CR rate 74.5 ％,37.5 ％,15.4 ％ and 0,respectively (P ＜0.05).The median survival times (MST) were 31.2 months at a median follow-up of 30 months (2-98 months).The acturial 1-,3-,and 5-year overall survival (OS) rates were 83.5 ％,41.8 ％ and 34.7 ％,respectively.The 5-year OS rates of low risk,low-intermediate risk,high-intermediate risk,high risk were 57.3 ％,55.9 ％,0 and 0,respectively (P ＜0.05).The OS rates of low risk group (IPI 0-2 scores) and high risk group (IPI 3-5 scores) were 54.8 ％ and 0,respectively (P ＜0.05).Serum levels of β2-MG were significantly elevated in the high risk group than those in the low risk group.The proportion of abnormal serum level of [β2-MG were also significantly elevated in the high risk group than those in the low risk group.The results of multivariante analysis showed that serum level of β2-MG and IPI scores were independent prognostic factors for PTCL (P＜0.05).Conclusion The serum level of β2-MG with IPI scores system can be uscd for evaluating the prognosis of PTCL patients.

Objective To investigate the application value of the anatomical location of positive nodes (N staging) from TNM staging systems published by American Joint Committee on Cancer (AJCC) (7th edition),number of metastatic lymph nodes (NMLN),lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) as prognostic predictors in advanced gallbladder carcinoma(GBC).Methods The retrospective crosssectional study was conducted.The clinicopathological data of 176 patients who underwent radical resection of advanced GBC in the First Affiliated Hospital of Xi'an Jiaotong University between January 2008 and December 2014 were collected.According to preoperative assessment,intraoperative exploration and frozen section biopsy,staging and surgical procedure were confirmed.Observation indicators and evaluation criteria:(1) surgical and postoperative situations;(2) follow-up and survival situations;(3) N staging related indicators based on TNM staging systems of AJCC (7th edition):LNR =NMLN / total number of lymph node dissection,LODDS =Log (NMLN+0.5) / (total number of lymph node dissection-NMLN+0.5);(4) lymph node staging based on NMLN,LNR and LODDS:LODDS ＜-1.0 as LODDS 1 staging,-1.0 ≤ LODDS ＜ 0 as LODDS 2 staging,LODDS ≥0 as LODDS 3 staging;(5) prognostic comparisons of patients with different lymph node staging;(6) accuracy of 4 different types of lymph node staging predicting the prognosis of patients.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 31,2017.Measurement data with normal distribution were represented as x-±s.Measurement data with skewed distribution were described as M (range),and comparisons were done using the nonparametric test.The survival rate was calculated by the Kaplan-Meier method,and the Log-rank test was used for survival comparison.Correlation analysis was done using the Spearman correlation analysis,r ≥ 0.800 as a high correlation,0.500 ≤ r ＜ 0.800 as a moderate correlation and 0.300 ≤ r ＜ 0.500 as a low correlation.The receiver operating characteristic (ROC) curve and area under the curve (AUC) were respectively drawn and calculated based on 4 kinds of binary logistic regression model.Akaike information criterion (AIC) and Harrell concordance index (Harrell c-index) were respectively calculated based on 4 kinds of COX proportional hazard regression model.The larger values of AUC and Harrell c-index caused a smaller value of AIC,but a lymph node staging standard correlated with greater prognostic accuracy.Harrell c-index ＜ 0.50 was no prediction,and 0.50 ≤ Harrell c-index ≤ 1.00 was an obvious prediction.Results (1) Surgical and postoperative situations:176 patients underwent successful radical resection of GBC,including 161 in R0 resection and 15 in R1 resection,99 with D1 lymph node dissection and 77 with D2 lymph node dissection.Of 176 patients,9 with postoperative complications were improved by symptomatic treatment,including 6 with bile leakage,2 with hepatic dysfunction and 1 with intra-abdominal hemorrhage.Results of postoperative pathological examination:total number of lymph node dissection,NMLN and LNR were respectively 6.7±4.4,0 (range,0-12.0) and 0 (range,0-1.00);high-differentiated,moderate-differentiated and low-differentiated tumors were respectively detected in 16,81 and 79 patients;162 and 14 patients were in T3 and T4 stages;60 patients were combined with infiltration of the liver.(2) Follow-up and survival situations:176 patients were followed up for l-118 months,with a median time of 33 months.The 1-,3-and 5-year overall survival rates were respectively 63.1％,42.0％ and 32.0％.(3) N staging related indicators based on TNM staging systems ofAJCC (7th edition):95,45 and 36 patients were respectively detected in staging N0,N1 and N2.NMLN,LNR and LODDS were respectively 2.0 (range,1.0-7.0),0.40 (range,0.08-1.00),-0.15 (range,-0.99-1.04) in staging N1 and 4.0 (range,1.0-12.0),0.57 (range,0.13-1.00),0.11 (range,-0.70-1.04) in staging N2,with a statistically significant difference in NMLN (Z=-3.888,P＜0.05) and with no statistically significant difference in LNR and LODDS (Z=-1.492,-1.689,P＞0.05).(4) Lymph node staging based on NMLN,LNR and LODDS:NMLN and LNR as a cut-off point were respectively 4.0 and 0.70,NMLN 1 staging (NMLN=0) was detected in 95 patients,NMLN 2 staging (1.0 ≤ NMLN ≤ 4.0) in 61 patients and NMLN 3 staging (NMLN＞4.0) in 20 patients;LNR 1 staging (LNR=0) was detected in 95 patients,LNR 2 staging (0 ＜ LNR ≤ 0.70) in 58 patients and LNR 3 staging (LNR＞0.70) in 23 patients.LODDS 1,2 and 3 stagings was detected in 61,70 and 45 patients,respectively.The lymph node staging based on NMLN and LNR was significantly correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.949,0.922,P＜0.05);the lymph node staging based on LODDS was moderately correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r =0.758,P＜ 0.05).(5) Prognostic comparisons of patients with different lymph node staging:1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in N0 staging patients and 44.4％,22.2％,13.3％ in N1 staging patients and 25.0％,5.6％,2.8％ in N2 staging patients,with a statistically significant difference (x2=88.895,P＜0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in NMLN 1 staging patients and 47.5％,19.7％,11.1％ in NMLN 2 staging patients and 0,0,0 in NMLN 3 staging patients,with a statistically significant difference (x2=121.086,P＜0.05).The 1-,3-and 5-year overall survival rates were respectively 86.3％,65.3％,52.2％ in LNR 1 staging patients and 41.4％,17.2％,11.8％ in LNR 2 staging patients and 17.4％,8.7％,0 in LNR 3 staging patients,with a statistically significant difference (x2 =86.503,P＜ 0.05).The 1-,3-and 5-year overall survival rates were respectively 85.2％,65.5％,51.8％ in LODDS 1 staging patients and 65.7％,40.0％,31.3％ in LODDS 2 staging patients and 28.9％,13.3％,5.9％ in LODDS 3 staging patients,with a statistically significant difference (x2=59.195,P＜0.05).(6) Accuracy of 4 different types of lymph node staging predicting the prognosis of patients:according to N staging of TNM staging systems of AJCC (7th edition),NMLN,LNR and LODDS,AUC,AIC and Harrell c-index of lymph node staging were respectively 0.878,0.881,0.870,0.864 and 1 047.5,1 026.4,1 044.2,1 063.6 and 0.77,0.78,0.77,0.76.AIC value was smaller with increased values of AUC and Harrell c-index based on NMLN,showing a greatest accuracy predicting the prognosis of patients.Conclusion Among N staging of TNM staging system of AJCC (7 edition),NMLN,LNR and LODDS as prognostic predictors,NMLN can more precisely predict radical resection of advanced GBC.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

Objective:To explore the incidence and factors of the influence of preoperative related factors on postoperative orthopedic evaluation, through the evaluation of thoracic shape orthopedic evaluation of children pectus excavatum, during plate implantation after Nuss procedure.Methods:From April 2012 to April 2019, the clinical data were analyzed retrospectively for 159 hospitalized cases of Nuss procedure for pectus excavatum in Xi’an Children’s Hospital.The mean age was(6.8±3.4) years old(3.2-17.0 years old); males 124, females 35; Haller index 4.0±1.0(2.7-7.5); 6 cases(4%) were poor orthopedic evaluation with the thoracic shape, males 5, femal 1; 23 cases (14%) were average satisfied with the thoracic shape, males 16, femals 7; 130 cases (82%)were good orthopedic evaluation with the thoracic, males 103, femals 27. Follow-ups were conducted for at least 2 years, Retrospective analysis of the relationship between postoperative thoracic satisfaction and age, gender, Haller index, how the plates were placed during surgery and symmetry of funnel chest, t test and χ2 test were used for statistical analysis. Results:There were statistically significant differences between thoracic orthopedic evaluation after postoperative and classification of pectus excavatum ( P=0.001), and poor orthopedic evaluation after asymmetric pectus excavatum operationand ; There were no significant differences in gender, Haller index, surgical method and how the plates were placed during surgery( P>0.05). However, it can be seen from the mean and percentage that with the decrease of age, and the increase of Haller index, the orthopedic evaluation gradually becomes worse. Conclusion:According to our single-center study, asymmetric pectus excavatum is a factor for poor orthopedic evaluation during plate implantation after Nuss, especially for young children and children with larger Haller index.

Acetaminophen, also known as N-acetyl-p-aminophenol (APAP), is commonly used as an antipyretic and analgesic agent. APAP overdose can induce hepatic toxicity, known as acetaminophen-induced liver injury (AILI). However, therapeutic doses of APAP can also induce AILI in patients with excessive alcohol intake or who are fasting. Hence, there is a need to understand the potential pathological mechanisms underlying AILI. In this review, we summarize three main mechanisms involved in the pathogenesis of AILI: hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. The relevant factors are elucidated and discussed. For instance, N-acetyl-p-benzoquinone imine (NAPQI) protein adducts trigger mitochondrial oxidative/nitrosative stress during hepatocyte necrosis, danger-associated molecular patterns (DAMPs) are released to elicit sterile inflammation, and certain growth factors contribute to liver regeneration. Finally, we describe the current potential treatment options for AILI patients and promising novel strategies available to researchers and pharmacists. This review provides a clearer understanding of AILI-related mechanisms to guide drug screening and selection for the clinical treatment of AILI patients in the future.
Acetaminophen/toxicity* ; Analgesics, Non-Narcotic/toxicity* ; Animals ; Chemical and Drug Induced Liver Injury/pathology* ; Chemical and Drug Induced Liver Injury, Chronic/pathology* ; Humans ; Inflammation/metabolism* ; Liver/pathology* ; Mice ; Mice, Inbred C57BL ; Necrosis/pathology*