Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC). @*Materials and Methods@#An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate. @*Results@#Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC. @*Conclusion@#Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.

Guidelines for Traditional Chinese Medicine Diagnosis and Treatment of Metastatic Colorectal Cancer / 中国实验方剂学杂志

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Clinical characteristics of eight human immunodeficiency virus positive patients with systemic lupus erythematosus / 中华传染病杂志

Objective:To analyze the clinical characteristics, diagnosis and treatment process, and prognosis of human immunodeficiency virus (HIV) positive patients with systemic lupus erythematosus (SLE).Methods:A retrospective study was used to collect and analyze the clinical characteristics, treatment and prognosis of eight HIV-positive patients with SLE treated in Yunnan Provincial Infectious Diseases Hospital from August 2017 to January 2020.Results:All of the eight patients were diagnosed with SLE after HIV infection. All of the patients were female. CD4 + T lymphocyte counts were >500/μL in four cases, 350 to 499/μL in two cases, and 200 to 349/μL in the remaining two cases. Case 6 presented with butterfly erythema on the face. In Case 1, hemoglobin was 40 g/L and urine occult blood was (+ + ). The hemoglobin of Case 2 was 76 g/L, the platelet count was 2×10 9/L, and the granulocyte count was 0.6×10 9/L. The lung computed tomography (CT) examination of Case 3 showed diffuse exudative lesions in both lungs. The 24 h urinary protein levels of Case 4 and 5 were 2 231.6 mg and 2 761.0 mg, respectively, and urine occult blood were (+ + ). The total bilirubin of Case 4 was 70.0 μmol/L and alanine aminotransferase (ALT) was 49 U/L. The total bilirubin of Case 7 was 129.6 μmol/L and ALT was 56 U/L. The lung CT examination of Case 8 showed moderate to massive pericardial effusion in the pericardium. Seven patients received antiviral therapy and immunotherapy, and their conditions were stable without relapse. Case 1 was refractory SLE complicated with autoimmune hemolytic anemia. After treated with rituximab combined with cyclophosphamide the patient achieved clinical remission. Case 7 was injection drug user and died after giving up treatment. Conclusions:The clinical characteristics of HIV-positive patients with SLE are heterogeneous, and the prognosis is generally good after antiviral therapy and immunotherapy. For patients with refractory SLE complicated with autoimmune hemolytic anemia, clinical remission can also be achieved through active treatment.

Investigation of in-patient neonatal death at 18 hospitals in Henan Province / 中华围产医学杂志

Objective To investigate the situation and the causes of neonatal death in Henan Province.Methods This study retrospectively analyzed the clinical data of 277 neonates who died at 18 hospitals in Henan Province in 2017.Distribution and causes of neonatal deaths,differences between perinatal conditions of premature and term/post-term infants,causes of early (＜ 7 d) and late (7-28 d) neonatal deaths and the differences in neonatal death cases between Maternal and Child Health Care Hospitals and General/Children's Hospitals were analyzed.We used t,rank-sum and Chi-square test (or corrected Chi-square test,or Fisher's exact test) for statistical analysis.Results (1) A total of 50 993 newboms were admitted to the 18 hospitals in 2017,297 of which died with a mortality of 5.82‰.After excluding 20 cases with uncertain birth or maternal pregnancy history or clinical data,277 cases with complete data were analyzed.Among them,168 (60.6％) were preterm neonates and 109 (39.4％) were term/post-term ones.Early and late neonatal deaths accounted for 74.0％ (205 cases) and 26.0％ (72 cases),respectively.(2) The top five causes of neonatal deaths were infection (78 cases,28.2％),asphyxia (54 cases,19.5％),neonatal respiratory distress syndrome (NRDS,33 cases,11.9％),severe congenital malformations (26 cases,9.4％) including cyanotic congenital heart diseases,digestive malformations,airway malformations and neural tube defects and pulmonary hemorrhage (23 cases,8.3％).Among them,the top three causes of early neonatal deaths were asphyxia (48 cases,23.4％),infection (43 cases,21.0％) and NRDS (33 cases,16.1％),while the main causes of late neonatal deaths were infection (35 cases,48.6％),major congenital malformations (9 cases,12.5％) and chromosome abnormities/inherited metabolic diseases (7 cases,9.7％).(3) Maternal complications during pregnancy accounted for 79.1％ (219 cases) and the predominant types were pregnancy-induced hypertension (43 cases,19.6％),followed by infection (36 cases,16.4％),placental-related conditions (32 cases,14.6％),gestational diabetes mellitus (23 cases,10.5％),hypothyroidism (20 cases,9.1％),fetal distress (18,8.2％),twin-twin transfusion syndrome (10 cases,4.6％) and cholestasis syndrome (9 cases,4.1％).(4) Compared with the term/post-term cases,the preterm cases had higher proportions of multiple births [27.4％ (46/168) vs 6.4％ (9/109),x2=14.016,P ＜ 0.05],assisted reproduction [7.1％ (12/168) vs 0.9％ (1/109),x2=4.421,P ＜ 0.05] and maternal hypertensive disorders of pregnancy [21.4％ (36/1 68) vs 6.4％ (7/109),x2=11.353,P ＜ 0.05],infection [16.7％ (28/168) vs 7.3％ (8/109),x2=4.295,P ＜ 0.05] and twin-to-twin transfusion syndrome [6.0％ (10/168) vs 0.0％ (0/109),x2=6.707,P ＜ 0.05].(5) Among all the early neonatal deaths,preterm cases had a higher incidence of NRDS than term/post-term neonates [20.3％ (27/133) vs 8.3％ (6/72),x2=1 1.937,P ＜ 0.05],but lower incidence of meconium aspiration syndrome (MAS),severe congenital malformations and chromosome abnormalities/inherited metabolic diseases [0.8％ (1/133) vs 5.6％ (4/72),x2=4.508;3.8％ (5/133) vs 16.7％ (12/72),x2=10.233;1.5％ (2/133) vs 6.9％ (5/72),~=4.172;all P ＜ 0.05].Among the late neonatal deaths,the incidence of severe intracranial hemorrhage in preterm infants was higher than that in term/post-term neonates [7.1％ (3/42) vs 0.0％ (0/30),x2=2.205,P ＜ 0.05].(6) Compared with the cases in General/Children's Hospitals,those in Maternal and Child Health Care Hospitals showed a higher proportion of preterm neonatal deaths [67.3％ (105/156) vs 52.1％ (63/121),x2=6.010,P ＜ 0.05],younger gestational age [(32.8±5.3) weeks vs (34.6±4.9) weeks,t=3.072,P ＜ 0.05],lower birth weight [(2 132.6± 1 014.5) g vs (2 409.4±987.3) g,t=-2.513,P ＜ 0.05],and higher average age of death [M(P25-P75),3 (1-8) d vs 2 (1-4) d,Z=3.710,P ＜ 0.05].Conclusions Neonatal death occurs mainly within one week after birth in those with maternal complications.Late preterm deaths and term/post-term cases account for nearly half of total neonatal deaths.The causes of death for preterm and term/post-term newborns vary with postnatal age.Infection,asphyxia and severe congenital malformations are important causes of neonatal deaths.

Comparison of efficacy and safety of triple-drug treatment regimens for metastatic colorectal cancer / 中国肿瘤临床

Objective: To evaluate the preliminary efficacy and safety of the 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin (FOLF-OXIRI) and capecitabine, irinotecan, and oxaliplatin (CAPIRINOX) regimens as first-line therapy for unresectable advanced colorectal cancer. Methods: Between January 2013 and November 2018, 73 patients with metastatic colorectal cancer (mCRC) were analyzed. All patients received first-line chemotherapy. Of them, 45 patients were administered FOLFOXIRI, and the remaining 28 patients were ad-ministered CAPIRINOX. The clinical outcomes and safety profiles were evaluated according to the objective response rate (ORR), con-version resection rate, and adverse effects. Results: The ORR, median progression-free survival (mPFS), and R0 resection rate in the FOLFOXIRI group were not statistically different from those in the CAPIRINOX group (60% vs. 57.1%, 7.7 months vs. 9.6 months, 24.4% vs . 17.9% , respectively; P>0.05). No treatment-related deaths occurred. The major adverse events were leukopenia, neutropenia, fa-tigue, nausea, vomiting, diarrhea, alopecia, aspartate aminotransferase/alanine aminotransferase elevation, and neurotoxicity. The to-tal rate of grade 3/4 adverse events in the FOLFOXIRI group was 33.3% (15/45), while the total rate of grade 3/4 adverse events in the CAPIRINOX group was 46.4% (13/28). Toxicities between the two groups were not statistically significant (P=0.263). Conclusions: Both the FOLFOXIRI and CAPIRINOX regimens are effective as first-line treatment for metastatic colorectal cancer. The triple-agent chemo-therapy was associated with good efficacy and tolerable toxicity.

Impacts of microsatellite status, RAS and BRAF mutation on postoperative follow-up strategy in stage II( and III( colorectal cancer / 中华胃肠外科杂志

Colorectal cancer is the third tumor in the world, and nearly half of the stage II( and III( patients undergoing radical resection develop relapse. At present, the survival benefit of follow-up strategy is still unclear, partly due to the neglect of the risk of recurrence and the factors affecting prognosis. Studies found that microsatellite status, BRAF and RAS genotype had certain value for prognosis of colorectal cancer patients after radical resection, but there were differences in prediction among these three factors. Patients with high-frequency microsatellite instability in stage II( have good prognosis, so the follow-up strategy in this set of patients can be appropriately simplified. Locally advanced colorectal cancer patients with BRAF-V600E mutations usually have poor survival after recurrence, and survival benefit appears minimal by intensive follow-up strategy. Besides, standard follow-up strategy, or less intensive follow-up strategy seems an acceptable option for patients with this subtype. In contrast, for patients with wild-type BRAF and RAS in stage II( or III(, the prognosis is usually good after recurrence. Such patients are sensitive to both systemic treatment and local therapy. Therefore, for patients with wild-type BRAF and RAS, early detection of recurrence by intensive follow-up strategy can potentially increase the possibility of second radical resection and prolong survival. It is of clinical significance to explore the feasibility of individualized follow-up strategy for patients with different biological characteristics. In addition, the establishment of individual risk prediction model should take clinical, pathological and molecular features into consideration. Combination of TNM staging and molecular markers for more stratified management and establishment of individualized follow-up system are clinically meaningful in the future.

Appolication of next-generation sequencing for the screening of hereditary gastrointestinal cancer / 中国肿瘤临床

Objective: To explore the significance of next-generation sequencing for the screening of high-risk hereditary gastrointesti-nal cancer patients and the value of high-risk factors in screening. Methods: Twenty-five hereditary high-risk gastrointestinal cancer pa-tients from March 2016 to April 2016 in Peking University Cancer Hospital were enrolled. They received detection of 42 hereditary can-cer syndrome related genes by next-generation sequencing. Results: Out of 25 patients enrolled, 24% (6/25) patients had pathological germline mutations. The expression of mismatch repair protein was absent in 50% (3/6) patients. There were 83% (5/6) patients with family history of malignant tumors and were diagnosed when younger than 50 years. Six patients had hereditary cancer syndrome re-lated gene mutation, 1 patient had MYH gene missense mutation, 1 patient had APC gene deletion mutation, 4 patients had heredi-tary colorectal cancer related gene mutation, including MLH1, MLH3, and TGFBR2 germline missense mutations as well as MSH6 non-sense mutation. Conclusions: Out of 25 patients with high-risk factors of hereditary gastrointestinal cancer, 6 (24%) had pathological germline mutations. Given the high frequency and wide spectrum of mutations, the application of next-generation sequencing for screening of hereditary high-risk gastrointestinal cancer patients has the clinical value for improving the positive rate of diagnosis.

Application value of circulating tumor DNA monitoring effect of epithelial growth factor receptor monoclonal antibody therapy for metastatic colorectal cancer / 中华消化外科杂志

Objective To investigate the application value of circulating tumor DNA (ctDNA) monitoring effect of epithelial growth factor receptor (EGFR) monoclonal antibody therapy for metastatic colorectal cancer (mCRC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 9 mCRC patients who were admitted to the Peking University Cancer Hospital between March 2012 and December 2013 were collected.Patients received single EGFR monoclonal antibody treatment (cetuximab or parni monoclonal antibody).The ctDNA concentration and variations of 22 genes in EGFR pathway of ctDNA were analyzed using high-throughput sequencing and ctDNA.Observation indicators:(1) treatment situations;(2) ctDNA concentration in plasma before and after treatment;(3) related gene mutations of EGFR pathway of ctDNA;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect survival up to August 2015.Results (1) Treatment situations:of 9 patients,6 and 3 underwent respectively single drug treatment using cetuximab monoclonal antibody or parni monoclonal antibody.After EGFR monoclonal antibody treatment,best response was partial remission in 1 patient,stable disease in 6 patients and disease progression in 2 patients.(2) CtDNA concentration in plasma before and after treatment:ctDNA concentration of 9 patients was 1.7-25.0 μg/L before treatment,showing a significantly individual difference.There were some changes in ctDNA concentration of 9 patients during treatment:ctDNA concentration was increased in 1 patient during partial remission;of 6 patients during stable disease,ctDNA concentration was decreased in 5 patients and increased in 1 patient;of 9 patients during disease progression,ctDNA concentration was decreased in 4 patients and increased in 5 patients.(3) Related gene mutations of EGFR pathway of etDNA:① Of 9 patients,2 possessed RAS/RAF genetic mutations after treatment during disease progression,NRAS Q61H and BRAF V600E mutations were found in 1 patient,and mutation abundances were respectively 17.8％ and 5.2％;1 possessed KRAS G13D genetic mutation,a mutation abundance was 5.1％ before treatment and then was increased to 16.7％ during disease progression.② Seven patients possessed TP53 genetic mutation before treatment,5 had partial response or stable disease after treatment,including 4 with a reduced mutation abundance and 1 with an increased mutation abundance.Of 5 patients with partial response or stable disease to disease progression,mutation abundance of TP53 gene was increased in 4 patients and reduced in 1 patient;2 patients had disease progression after treatment and mutation abundances of TP53 gene were reduced.③ Two patients possessed SMAD4 genetic mutation.④ The intron mutations were found in EGFR,PIK3CA,AKT1,ERBB2,PTEN,STK11,MAP2K1,ALK,DDR2,CTNNB1,MET,FBX7,FGFR3,NOTCH1,ERBB4、FGFR1 and FGFR2 genes,without changes of amino acids,these were not included in analysis.(4) Follow-up and survival situations:9 patients were followed up for 1-31 months after treatment,with a median time of 7 months,and died at end of follow-up.Conclusion RAS/RAF gene mutations are detected by monitoring ctDNA when mCRC patients underwent EGFR monoclonal antibody therapy.

Current status of anti-viral treatment in children with acquired immune deficiency syndrome in acquired immune deficiency syndrome care center, Yunnan / 中华传染病杂志

Objective To analyze the effect of long-term anti-viral treatment in children with acquired immune deficiency syndrome (AIDS) and investigate the factors affecting the treatment efficacy and growth and development of the children, so as to provide reference for improving the efficacy of antiviral drugs.Methods Children with AIDS receiving anti-retroviral treatment during 2004 to 2016 were retrospectively enrolled.The height, weight and CD4+ T cell counts were recorded every half year and the measurement of HIV RNA load was recorded on an annual basis.The CD4+ T cell counts and viral inhibition rates for the children who were under the treatment in the first year, 1~0.05);and viral inhibition rates were 92.9% and 97.6%, respectively with no statistical significance (χ2=1.071, P>0.05).The viral inhibition rate for the children receiving the treatment for 1 year was 85.7%, while that for whose treatment lasted for more than 10 years was 100.0%.A total of 5 cases developed drug-resistance (2 cases treated for 1 to 5 years and 3 cases for 5 to 10 years), and the virus replication was completely inhibited after switching to Lopinavir/ritonavir (LPV/r).The drug compliance was more than 95.0%.64.8% of children met the standard height, while 68.5% met the standard body mass.The baseline and last measured CD4+ T cell counts showed no significant differences between family-raised and social organization-raised children (Z=-1.159 and -0.523, respectively, both P>0.05).The children from high-income families had no significant differences compared with those from low-income ones in terms of the baseline and last measured CD4+ T cell counts (Z=-0.019 and -0.776, respectively, both P>0.05).Conclusions The long-term anti-retroviral treatment can effectively elevate the CD4+ T cell counts, inhibit viral replication and ensure drug compliance, which may promote the growth and development of children.However, approximately 30% children are still lower than the normal standards in terms of height and body mass.The drug-taking observer plays a central role on treatment effect.Most of the children′s family suffer from poor economic conditions.

Long-term efficacy evaluation of antiretroviral therapy and genotypic resistance analysis among human immunodeficiency virus 1-infected children in Yunnan / 中华传染病杂志

Objective To evaluate the long-term efficacy of antiretroviral therapy and drug resistance among human immunodeficiency virus-1(HIV-1)-infected children in Yunnan.Methods In this retrospective study,CD4+T cell counts,HIV viral loads and genetic drug resistance results were obtained from HIV-1-infected children who were treated with antiretroviral treatment between January 2004 to July 2015.Results A total of 1 078 HIV/acquired immune deficiency syndrome(AIDS)children were treated with antiviral therapy.Before treatment,the average CD4+cell number was(466.8 ± 397.2)cells/μL. The percentages of children with CD4+cell count >750 cells/μL after 1-year,3-year,5-year and 8-year treatment were 54.31%,62.87%,68.46% and 74.19%,respectively.Virological failure occurred in 150 HIV/AIDS children(13.9%),and the virological failure rate was 4.3/100 child-years.Among those 150 patients with virological failure,104 cases(69.33%)exhibited genetic resistance to antiretroviral drugs.The prevalent mutations associated with drug resistance were M 184V/I(75.0% [78/104]), K103N(43.3%[45/104]),G190A(29.8%[31/104]),Y181C(22.1%[23/104]),T215Y/F(20.2%[21/104]).Conclusions After long-term antiretroviral treatment,most of the HIV-infected children have restored the immunity and suppressed HIV viral replication successfully.HIV resistance is the main cause of virological failure.Drug resistance mutations mainly occur in nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor,and the resistance rate of proteinase inhibitor is low.Early genetic resistance testing and switch to second-line therapy will improve the treatment outcome.

Controversy of primary tumor resection for stage IV colorectal cancer / 中华胃肠外科杂志

Primary tumor resection (PTR) is currently recommended for patients with unresectable stage IV colorectal cancer (CRC) who present symptoms related to their primary tumor (eg, obstruction, perforation, significant bleeding). The role of PTR in asymptomatic patients remains controversial. This article will review the role of PTR in incurable stage IV CRC, including the advantages and risks, with emphasis on identifying patients who may benefit from this palliative intervention.

Using next-generation sequencing technology to evaluate biomarkers associated with anti-EGFR efficacy in metastatic colorectal cancer / 中国肿瘤临床

Objective:To explore genes associated with sensitivity to anti-EGFR therapy. Methods:From March 2012 to August 2013, 31 metastatic colorectal cancer patients in Peking University Cancer Hospital&Institute were treated with anti-EGFR mono-therapy. A total of 21 genes associated with oncogenesis, metastasis, and EGFR signaling pathway were profiled in these 31 patients by using tar-geted next-generation sequencing technology. Results:A total of 31 patients with Kras exon 2 wild-type received anti-EGFR therapy as third-line treatment. Among these patients, the median progression-free survival (PFS) was 89 days, overall survival was 311 days, and objective response rate was 16.1%. Five cases harbored Kras exons 3/4 or Nras exons 2/3 mutations. These five Ras mutation patients showed disease progression during the first evaluation with 31-day PFS. One PIK3CA mutation case exhibited disease progression dur-ing the first evaluation (PFS 35 days), and one case showed mTOR mutation with 91-day PFS. The PFS of two cases with SMAD4 muta-tion were 58 and 59 days, whereas that of the case containing FBXW7 mutation was 93 days. Among the 26 Ras wild-type patients, MLL3, TP53, and APC were the three genes with the highest mutation frequencies of 92.3%(24/26), 53.8%(14/26), and 42.3%(11/26), respectively. Conclusion:Extended Ras analysis (including Kras and Nras exons 2/3/4) is recommended for patients who are candi-dates for anti-EGFR therapy. Mutations in the downstream effectors of the EGFR signaling pathway, such as PI3KCA and mTOR, may al-so have a predictive role in anti-EGFR therapy. Mutations beyond the EGFR pathway such as FBXW7 and SMAD4 may be associated with anti-EGFR efficacy and deserve further attention.

Efficacy observation on imatinib reintroduction in gastrointestinal stromal tumor with high recurrence risk after imatinib adjuvant therapy failure / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of imatinib reintroduction in gastrointestinal stromal tumor(GIST) with high recurrence risk after imatinib adjuvant therapy failure.</p><p><b>METHODS</b>Clinical and follow-up data of 24 recurrent GIST patients with high recurrence risk receiving imatinib standard dose reintroduction(400 mg/d or 600 mg/d) after stopping imatinib adjuvant treatment more than 3 months in Department of GI Oncology of Peking University Cancer Hospital from August 2005 to January 2016 were retrospectively analyzed. The objective response rate(ORR), relapse-free survival(RFS) of imatinib reintroduction were evaluated and the difference of efficacy in patients receiving different imatinib adjuvant therapy duration were compared.</p><p><b>RESULTS</b>Of 24 patients, 21 were male and 3 were female. The median age was 53 years(39-72 years). Mutation detection of tumor tissues before imatinib therapy showed 20 patients had c-Kit exon 11 mutation,3 patients exon 9 mutation and 1 patient c-Kit/PDGFRA wild type mutation. The median recurrence time was 14 months in all the patients (95%CI:7.9-20.0) and in those patients receiving imatinib adjuvant therapy for 1 or 2 years (9 patients in each group, 95%CI:11.1-16.9 and 8.2-19.8 respectively). The median recurrence time of 3 patients receiving imatinib adjuvant therapy for 3 years was 24, 41 and 54 months respectively. Of 2 patients receiving imatinib adjuvant therapy for 5 years, the median recurrence time was 4 and 18 months. Only one patient received imatinib adjuvant therapy for 6 years, and the recurrence time was 6 months. Twenty patients with exon 11 mutation and 1 patient with wide type received imatinib treatment at a dose of 400 mg daily, and 3 patients with exon 9 mutation received the dosage of 600 mg per day. Among the patients receiving imatinib reintroduction, 11 patients(45.8%) got partial response(PR), 12 patients(50.0%) had stable disease and 1 patient had progression disease. The response rate in patients receiving imatinib adjuvant therapy for 1 year(6/9, 67%) was significantly higher than that in patients receiving adjuvant therapy for ≥2 years(3/15, 20%)(P=0.036). The median progression-free survival (PFS) of imatinib reintroduction was 31 months in all the patients(95%CI:23.6-38.4). The median PFS in patients receiving imatinib adjuvant therapy for 1 year(9 cases), 2 years (9 cases) and ≥3 years (6 cases) was 50 months(95%CI:27.3-72.7), 26 months(95%CI:10.7-41.3) and fall short of median PFS. No significant difference was observed among three groups(P=0.295).</p><p><b>CONCLUSIONS</b>Imatinib reintroduction is still effective to GIST after imatinib adjuvant therapy failure. The different imatinib adjuvant therapy duration can influence the benefit of imatinib reintroduction.</p>

Difference analysis of chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the relationship between primary tumor location and clinical response of chemotherapy in patients with metastatic colorectal cancer(mCRC).</p><p><b>METHODS</b>Clinical data of 721 mCRC patients who received first-line and second-line chemotherapy in Peking University Cancer Hospital between January 1996 and December 2011 were collected. All the patients were divided into 5 groups according to primary tumor location: ileocecum in 61 patients(8.5%), ascending colon or hepatic flexure in 126 patients (17.5%), transverse colon or splenic flexure in 26 patients (3.6%), descending or sigmoid colon in 172 patients (23.9%), rectum in 336 patients (46.6%). Outcomes of chemotherapy were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1), including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate (ORR) was counted with the total number of patients divided by the number of CR+PR. Differences in first-line and second-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer were compared by using Chi-square test.</p><p><b>RESULTS</b>Of the 571 patients receiving first-line chemotherapy, no one patient was classified as CR, while there were 190 as PR (33.3%), 277 as SD (48.5%) and 104 as PD (18.2%), with ORR 33.3% (190/571). The ORRs of patients with primary tumor located at ileocecum, ascending colon or hepatic flexure, transverse colon or splenic flexure, descending or sigmoid colon, rectum were 21.3% (10/47), 35.3% (36/102), 14.3% (3/21), 41.3% (57/138) and 31.9% (84/263), respectively, with statistically significant difference(P = 0.028). Difference of oxaliplatin-based first-line chemotherapy efficacy among different tumor sites was statistically significant(P = 0.009), while differences in irinotecan-based or single-agent 5-fluorouracil chemotherapy efficacy were not statistically significant (all P>0.05). In patients with primary tumor located at transverse colon or splenic flexure, irinotecan-based first-line chemotherapy had higher ORR than oxaliplatin-based or single-agent 5-fluorouracil chemotherapy, and the difference was statistically significant (P=0.042). There was no significant difference in the efficacy of different first-line chemotherapy regimens in patients with primary tumor located at other sites (all P>0.05). Of the 353 patients receiving second-line chemotherapy, no one patient was classified as CR, while there were 43 as PR (12.2%), 187 as SD (53.0%) and 123 as PD (34.8%), with ORR 12.2%(43/353). The ORRs of patients with primary tumor located at the ileocecum, the ascending colon or the hepatic flexure, the transverse colon or the splenic flexure, the descending or sigmoid colon, the rectum were 4.2%(1/24), 12.1%(8/66), 8.3%(1/12), 15.2%(12/79) and 12.3%(21/171) respectively, without statistically significant difference (P=0.686). Differences in second-line chemotherapy efficacy with the same regimen among different tumor sites were not statistically significant, and there were also no significant differences of efficacy of different second-line chemotherapy regimens in patients with the same tumor site (all P>0.05).</p><p><b>CONCLUSION</b>There are differences in first-line chemotherapy efficacy among different primary tumor sites in metastatic colorectal cancer, while their second-line chemotherapy efficacy is equivalent.</p>

Current status of the study on hereditary diffuse gastric cancer / 中华胃肠外科杂志

Hereditary diffuse gastric cancer was discovered 25 years ago. During the last 25 years, the diagnostic standards and molecular mechanism of this type of hereditary gastric cancer have been established. With a better understanding of this disease, germline CDH1 mutation has been linked to hereditary diffuse gastric cancer with autosomal-dominant inheritance pattern. Therefore, strategies on genetic screening and follow-up have been evolved for CDH1 mutation carriers. In China, the studies on hereditary diffuse gastric cancer are sparse. We hope this article will bring more awareness and attention of this peculiar disease to Chinese physicians.

Research on relationships between enterprising and magnanimous psychological characteristics and coping modes in cancer patients / 中华行为医学与脑科学杂志

Objective To explore the relationship between enterprising and magnanimous psychological characteristics and coping modes in cancer patients.Methods Totally 450 cancer patients were randomly chosen to analyze the correlation using enterprising and magnanimous questionnaires and cancer coping modes questionnaires.T-test,Variance analysis and Pearson analysis were employed for statisticals.Results (1) The enterprising and magnanimous psychological characteristics:cancer patients generally got lower scores in the dimensions of enterprising,magnanimous,and total score (59.30±8.09,31.98±6.24,27.32±4.02,respectively) than healthy population (67.44±5.60,34.72±4.57,32.72±3.23,respectively).In demographic level,male and female cancer patients' scores were also lower than the healthy ones'.The higher academic backgrounds they had,the better enterprising and magnanimous psychological attitudes they embraced.In the comparison of occupation,professionals in administrative and companies scored the highest in the dimensions of enterprising,workers in special techniques,commercial and service industries scored higher in the dimensions of magnanimous.All the differences were significant statistically (P＜0.05).(2) Correlation analysis:the correlation index between psychological characteristics of enterprising and magnanimous and the coping modes in cancer patients was 0.463,with a positive correlation(P＜0.01),and the indexes among in the dimensions of enterprising and confrontation were regarded as a positive correlation (r=0.415),and negative correlations (r =-0.139,r =-0.047,respectively) with avoidance and suppression and resignation (P＜0.01).Conclusion The enterprising and magnanimous mental level of cancer patients is lower,which is related to their inappropriate responses of avoidance and suppression and resignation.

Human epidermal growth factor receptor 2 expression in rectal cancer and its clinical implication / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the consistence of human epidermal growth factor receptor 2 (HER-2) expression in resection samples and biopsy samples from rectal cancer and its clinical implication.</p><p><b>METHODS</b>Clinical data and tissue samples of 544 rectal cancer patients who received surgical resection at Peking University Cancer Hospital from September 2009 to March 2012 were collected and analyzed retrospectively. Immunohistochemical method was used to test HER-2 expression in both surgical resection samples and preoperative biopsy samples. Suspect positive samples with HER-2 (++) were further examined by FISH. Consistence of HER-2 expression between resection samples and biopsy samples, and between resection samples from those patients undergoing neoadjuvant radiotherapy or radiochemotherapy and biopsy samples was analyzed. Association between HER-2 expression and clinicopathological characteristics was examined as well.</p><p><b>RESULTS</b>Among 544 surgical resection samples, positive HER-2 samples of 20 cases (3.7%) were identified either by immunohistochemistry (HER-2, +++) or by FISH amplification. Among 235 paired biopsy samples, positive HER-2 samples of 5 cases (2.1%) were identified. Consistence of HER-2 expression between these two samples was 99.6% (234/235). The kappa value of consistence test was 0.907 (P<0.01). Consistence between resection samples from patients receiving neoadjuvant therapy and biopsy samples was 98.6% (73/74). There was no association of HER-2 over-expression or amplification with gender, age, tumor differentiation grade, lymph-node metastasis, distant metastasis, TNM stage and overall survival.</p><p><b>CONCLUSIONS</b>Positive rate of HER-2 expression is quite low in rectal cancer and has no relation to clinicopathological characteristics and prognosis. HER-2 status in biopsy samples of rectal cancer is highly consistent with paired surgical resection samples, which is not affected by neoadjuvant radiochemotherapy.</p>

Correlation of ABCG2 expression with the efficacy of irinotecan chemotherapy in colorectal cancer patients / 中国肿瘤临床

Objective:To identify the ABCG2 expression levels in colorectal cancer patients and its relationship with clinicopath-ological features and the efficacy of irinotecan-based chemotherapy and to provide further theoretical basis for individualized treatment. Methods:Clinical data and tumor samples from patients with metastatic CRC who have received irinotecan-based chemotherapy at the Department of Gastroenterological Oncology, Peking University Cancer Hospital from January 1996 to December 2011 were collected. The immunohistochemical method was used to detect ABCG2 expression levels both in colorectal carcinoma and tumor-adjacent nor-mal tissues. The correlations of the expression of ABCG2 with clinicopathological features and the efficacy of irinotecan-based chemo-therapy were statistically analyzed. Results:1) Immunohistochemical staining shows that the positive rate of ABCG2 expression in the colorectal cancer samples is 93.2%, which is significantly higher than that in normal colon mucosa at 43.6%(P0.05). Conclusion:ABCG2 expression has no significant correlation with the efficacy of irinotecan chemotherapy in patients with colorectal cancer.

Trastuzumab combined with chemotherapy in patients with HER2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.</p><p><b>METHODS</b>Twenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.</p><p><b>RESULTS</b>The twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.</p><p><b>CONCLUSIONS</b>Combination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.</p>

Clinical observation of highly active antiretroviral therapy in 70 pediatric patients with acquired immunodeficiency syndrome / 中华传染病杂志

Objective To observe the treatment response and potential issues related to antiretroviral therapy (ART) in pediatric patients with acquired immunodeficiency syndrome (AIDS) and to provide a basis for revising the treatment guideline and improving the clinical practice. Methods Children eligible for ART according to the current treatment guideline were recruited from Dehong area. Enrolled patients were provided with ART and followed up for regular clinical check and laboratory tests. Results By the end of March 2009, a total of 70 children had received ART. Among them, 60 patients were treated with regimen including zidovudine (AZT)+ lamivudine (3TC)+nevirapine (NVP). Twelve, eighteen, twenty-three and nineteen patients have tested for HIV viral load after 3 month, 6 month, 12 month and 18 month treatment, respectively. Among them, 7, 12,14 and 14 patients respectively achieved HIV viral load lower than 1000 copy/mL. Average CD4+ Tlymphocyte count increased from (317.8±288.8) × 106/L at baseline to (1037.2±1086. 1) × 106/Lafter 18 month treatment. Side effects mainly occurred within the first 3 months of treatment. Nearly 50% of children had gastrointestinal symptoms. Resistance to 3TC, NVP and efavirenz (EFV) were found in five patients who have completed 12 months of treatment. Conclusions Pediatric AIDS patients show good compliance and treatment response to ART. Most side effects happen in the first 3months of treatment and the most common side effects are gastrointestinal symptoms.