Analysis of cancer pain in hospitals in Beijing,China

Objective:This study aimed to survey the characteristics and treatments of cancer pain in Beijing hospitals,China.Methods:At 20:00 on December 22,2009,there conducted a questionnaire survey in 2238 patients with malignant tumors of 26 hospitals in Beijing,and the survey results were statistically analyzed.Results:The 531 cases in 2238 patients had pained and 121 cases (22.79%) had outbreak pain with one week.At 20:00 on December 22,2009,199 cases (38%) in the above-mentioned 531 pain patients suffered the moderate to severe pain (pain scores ≥ 4).The number of pain (pain scores ≥ 4) patients in the consecutive three days from December 20 to December 22 were 150.Conclusion:In the 531 cancer pain patients of the surveyed hospitals,38% of the patients were not satisfied with the pain control.Doctors believed that the main reason for pain not controlled was the non-standard treatment,but patients considered to be afraid of addiction.

Current Status of Diagnosis And Treatment of Primary Breast Cancerin Beijing,2008

Objective：To investigate the status of diagnosis and treatment of primary breast cancer in Beijing,2008.Methods：All the patients who were diagnosed as primary breast cancer in Beijing in 2008 were enrolled in this study.Information of these patients,including the features of tumors,clinical diagnosis and treatment was collected,and filled in the well-designed questionnaire forms by trained surveyors.The missing data were partly complemented through telephone interviews.Results：A total of 3473 Beijing citizens were diagnosed as primary breast cancer（25 patients with synchronal bilateral breast cancer） in Beijing,2008.Of them 82.09% were symptomatic.19.02% and 34.11% were diagnosed using fine needle aspiration biopsy（FNAB） and core needle biopsy（CNB）,respectively.15.92% received sentinel lymph node biopsy（SLNB） and 24.27% received breast conserving surgery（BCS）.Among 476 cases with Her-2 positive,only 96 received anti-Her-2 therapy.We found that the standardization level varied in hospitals of different grades,with higher level in Grade-III hospitals.Of note,some breast cancer patients received non-standard primary tumor therapy：65.63% of the patients with ductal carcinoma in situ（DCIS） received axillary lymph node dissection and 36.88% received chemotherapy;25.89% of the patients underwent breast conserving surgery without margin status;12.10% of the patients received chemotherapy less than 4 cycles.Conclusion：Although most breast cancer patients received basic medical care,the mode of diagnosis and treatment should be improved and should be standardized in the future in Beijing.

Time Trends of Cancer Incidence in Urban Beijing,1998-2007

Objective：To report the time trends of cancer incidence in urban Beijing from 1998 to 2007.Methods：All data were obtained from Beijing Cancer Registry from 1998-2007 in urban Beijing.Time trends of incidence rate of cancer were assessed by annual percentage change（APC） of age-standardized incidence rate（ASR） of world standard population during this 10-year period.Results：For all 156851 cancer cases combined,the incidence rate rose in both males and females,with an APC of 2.23% and 3.74%,respectively.The incidence rate of upper gastrointestinal cancers declined significantly,with an APC of-2.83% in esophageal cancer and-1.37% in male gastric cancer,while lower gastrointestinal cancer,such as colorectal cancer,increased with an APC of 4.08%.The rates of kidney and bladder cancer increased with an APC of 7.93% and 5.57%,respectively.For women,the APC continued to rise in breast cancer（4.98%）,ovary cancer（6.16%）,cervix uteri cancer（11.74%）,corpus uteri cancer（6.96%） and thyroid gland cancer（13.39%）.The rate of prostate cancer among men increased with an APC of 8.58%;the rate of lymphoma and leukemia increased with APC of 5.48% and 5.44%,respectively.Conclusion：Because of population aging and urban modernization,the cancer burden in Beijing has become more and more severe and similar to the western developed countries.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Changing patterns of colorectal cancer in China over a period of 20 years

AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients＇age at diagnosis, sex, the site of the tumor, stage, and the pathology. RESULTS： From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer （induding transverse and ascending colon） increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades. CONCLUSION： These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.

Volumetric-modulated arc therapy vs c-IMRT in esophageal cancer:A treatment planning comparison

AIM： To compare the volumetric-modulated arc ther- apy （VMAT） plans with conventional sliding window intensity-modulated radiotherapy （c-IMRT） plans in esophageal cancer （EC）. METHODS： Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning sys- tem： three using c-IMRT with 5 fields （5F）, 7 fields （7F） and 9 fields （gF）, and two using VMAT with a single arc （1A） and double arcs （2A）. The treatment plans were designed to deliver a dose of 60 Gy to the plan-ning target volume （PTV） with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normal- ized to 95% of the PTV that received 100% of the pre- scribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk （OAR） such as lungs, spinal cord and heart. Monitor units （MU） and normal tissue complication probability （NTCP） of OAR were also reported. RESULTS： Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different Io- cations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions： in cervical and upper thoracic EC, the conformity index （CI） was higher in VMAT （1A 0.78 and 2A 0.8） than in c-IMRT （5F 0.62, 7F 0.66 and 9F 0.73） and homogeneity was slightly better in c-IMRT （7F 1.09 and 9F 1.07） than in VMAT （1A 1,1 and 2A 1.09）, Lung V30 was lower in VMAT （1A 12.52 and 2A 12.29） than in c-IMRT （7F 14.35 and 9F 14.81）. The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT （1A 0.76 and 2A 0.74） was higher than in c-IMRT （5F 0.63 Gy and 7F 0.67 Gy）, and homogeneity was almost similar between VMAT and c-IMRT. V20 （2A 21.49 Gy vs 7F 24.59 Gy and 9F 24.16 Gy） and V30 （2A 9.73 Gy vs 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy） of lungs in VMAT were lower than in c-IMRT, but low doses to lungs （V5 and Vl0） were increased. V30 （1A 48.12 Gy vs 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy）, V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc. CONCLUSION： Compared with c-IMRT, VMAT, especial- ly the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.

Validation And Reliability of Distress Thermometer in Chinese Cancer Patients

Objective：To examine the validation and reliability of the distress thermometer（DT） recommended by National Comprehensive Cancer Network（NCCN） in Chinese cancer patients.Methods：A total of 574 Chinese cancer patients from Beijing Cancer Hospital completed the detection of DT,the Hospital Anxiety and Depression Scale（HADS） and Symptom Checklist 90（SCL-90）,Receiver Operating Characteristic（ROC） curve and Area Under the Curve（AUC） were used to analyze the validation relative to HADS and SCL-90.The patients with DT≥4 and whose distress caused by emotional problems were interviewed with the MiNi International Neuro-psychiatric Interview（MINI）（Chinese Version 5.0）.This version was used to analyze cancer patients＇ psychological and Psychiatric symptoms during the cancer process;3.Another 106 cancer patients in rehabilitation stage and stable condition were asked to fill in DT two times,at the base time and after 7-10 days.Results：Data of ROC indicates that a DT cutoff score of 4 yielded AUC of 0.80 with a optimal sensitivity（0.80） and specificity（0.70） relative to HADS,and AUC of 0.83 with the greatest sensitivity（0.87） and specificity（0.72） against SCL-90.The DT also has acceptable test-retest reliability（r=0.800,P=0.000）;According to the interview results,the most common psychiatric problems cancer patients have adjustment disorder,depression,and anxiety.Conclusion：The data suggest that DT has acceptable overall accuracy and reliability as a screening tool for testing distress severity and specific problems causing distress in Chinese cancer patients.It is worth being used in oncology clinic,the rapid screening and interview could help caregivers to identify psychological and psychiatric problems of cancer patients and provide useful information for further treatment.

Targeting the PI3K-AKT-mTOR signaling network in cancer

The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumour types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.

Expressions of Thymidylate Synthase, Thymidine Phosphorylase, Class Ⅲ β-tubulin, and Excision Repair Cross-complementing Group 1 Predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin

Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27–75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples.

Expression of phosphatase regenerating liver 3 is an independent prognostic indicator for gastric cancer

AIM： To investigate the prognostic significance of phosphatase regenerating liver 3 （PRL-3） protein expression in gastric cancer.METHODS： PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry. Nonoclonal antibody specifically against PRL-3, 3B6, was obtained with hybridoma technique.RESULTS： Positive PRL-3 expression was detected in 43.3% （227 of 293） of gastric cancer cases. High expression of PRL-3 was positively correlated with tumor size, depth of invasion, vascular/lymphatic invasion, lymph node metastasis, high TNM stage and tumor recurrence. Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression （28.3% vs 52.9%, P 〈 0.0001）. Patients who received curative surgery, and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression （hazard ratio of 16.7 and 16.6, respectively; P 〈 0.0001 for both）. Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients, particularly for survival in TNM stage Ⅲ patients. CONCLUSION： PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection,

Global efforts in conquering lung cancer in China

Lung cancer,the most prevalent and deadly malignancy in the world,poses a particularly critical healthcare challenge to China due to the rapidly increasing new cases and the unique cancer genetics in Chinese patient population.Substantial progress has been made in molecular diagnosis and personalized treatment of the disease.The field is now moving towards multiple new directions to include(1) new generation of targeted agents such as epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors to overcome resistance to their early generation counterparts;and(2) deeper understanding of tumor genetics of each individual patient and consequently the application of biomarkers to guide personalized treatment as well as novel drug development including combination therapy.The increasing capacity in innovative cancer drug research and development is supported by extensive collaboration within China and globally,and across academia and industry,to build up expertise and infrastructure in early-phase clinical testing of novel drugs.With these combined efforts,new and better medicines will be available for lung cancer patients in China in the near future.

MUC1-positive circulating tumor cells and MUC1 protein predict chemotherapeutic efficacy in the treatment of metastatic breast cancer

Chemotherapy plays an important role in the treatment of metastatic breast cancer. It is important to monitor chemotherapeutic efficacy, to find a simple and efficient tool to guide treatment, and to predict the efficacy of treatment in a timely and accurate manner. This study aimed to detect mucin-1 (MUC1) - positive circulating tumor cells and MUC1 protein in the peripheral blood of patients with metastatic breast cancer and to investigate their relationship to chemotherapeutic efficacy. MUC1 mRNA was detected in the peripheral blood of 34 patients with newly diagnosed metastatic breast cancer by reverse transcription- polymerase chain reaction. The positive rates of MUC1 mRNA were 88.2% before chemotherapy and 70.6% after chemotherapy, without a significant difference (P = 0.564); MUC1 mRNA expression before chemotherapy had no correlation with treatment effectiveness (P = 0.281). The response rate of MUC1 mRNA -negative patients after first-cycle chemotherapy was significantly higher (P = 0.009) and the progression-free survival (PFS) was clearly longer than those of MUC1 mRNA-positive patients (P = 0.095). MUC1 protein in peripheral blood plasma was detected by an ELISA competitive inhibition assay. The patients with decreased MUC1 protein after chemotherapy had a significantly longer PFS than those with elevated MUC1 protein (P = 0.044). These results indicate that the outcomes of MUC1 mRNA - negative patients after chemotherapy are better than those of MUC1 mRNA-positive patients. In addition, patients with decreased expression of MUC1 protein have a better PFS.

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.

Surgical complications after different therapeutic approaches for locally advanced rectal cancer

BACKGROUND Preoperative radiochemotherapy is widely used in locally advanced rectal cancer.It can improve local control of rectal cancer. However, some researchers believe it increases the incidence of surgical complications. They doubt its safety. Patients with locally advanced rectal cancer receive three different treatments in our hospital, including long-course radiochemotherapy, short-course radiotherapy,and surgery directly. We can compare their differences in postoperative complications.AIM To investigate surgical complications caused by different preoperative radiotherapy regimens.METHODS We retrospectively analyzed 1197 patients admitted between 2008 and 2010 with locally advanced rectal cancer. Three hundred and forty-six patients were treated with preoperative long-course radiochemotherapy(25 × 2 Gy) followed by total mesorectal excision(TME) 6–8 wk later, and 259 patients received short-course radiotherapy(10 × 3 Gy) and subsequently TME 7–10 d later. The remaining 592 patients underwent TME alone without neoadjuvant therapy. According to Clavien–Dindo classification, surgical complications were evaluated for up to 30 d after discharge from hospital.RESULTS There were no deaths in 30 d in all groups after treatment. The majorcomplications were anastomotic leakage and perineal wound complications. The results suggested that both long-course [odds ratio(OR) = 3.624, 95% confidence interval(CI): 1.689–7.775, P = 0.001] and short-course(OR = 5.150, 95%CI:1.828–14.515, P = 0.002) radiotherapy were associated with anastomotic leakage.Temporary ileostomy was a protective factor for anastomotic leakage(OR =6.211, 95%CI: 2.525–15.385, P < 0.001). The severity of anastomotic leakage did not increase in patients following preoperative radiotherapy(P = 0.411).Compared with TME alone, short-course radiotherapy was associated with an increase in perineal wound complications(OR = 5.565, 95%CI: 2.203–14.057, P <0.001), but long-course radiotherapy seemed safe regarding this complication(OR= 1.692, 95%CI: 0.651–4.394, P = 0.280). Although the severity of perineal wound complications increased in patients following short-course radiotherapy(P <0.001), additional intervention was not necessary.CONCLUSION Radiotherapy increased the incidence but not severity of anastomotic leakage.Short-course radiotherapy was also accompanied with perineal wound complications, but intervention appeared unnecessary to ameliorate the complications.

High levels of serum platelet-derived growth factor-AA and human epidermal growth factor receptor-2 are predictors of colorectal cancer liver metastasis

AIM To develop predictive markers in blood for colorectal cancer liver metastasis.METHODS Twenty colorectal cancer patients were selected and divided into two groups. Group A consisted of 10 patients whose pathological TNM stage was ⅢC(T3-4N2M0), while another 10 patients with synchronous liver metastasis(TNM stage Ⅳ) were recruited for group B. During the surgical procedure, a 10-ml drainage vein(DV) blood sample was obtained from the DV of the tumor-bearing segment prior to the ligation of the DV. At the same time, a 10-ml peripheral vein(PV) blood sample was collected via peripheral venipuncture. The serum levels of 24 molecules that are potentially involved in the mechanism of liver metastasis in both DV blood and PV blood were analyzed by using high-throughput enzyme-linked immunosorbent assay technology.RESULTS Univariate analysis revealed that platelet-derivedgrowth factor AA(PDGFAA) in DV blood(d PDGFAA)(P = 0.001), PDGFAA in PV blood(p PDGFAA)(P = 0.007), and human epidermal growth factor receptor-2 in PV blood(p HER2)(P = 0.001), p MMP7(P = 0.028), pR ANTES(P = 0.013), and pE GF(P = 0.007) were significantly correlated with synchronous liver metastasis. Multivariate analysis identified d PDGFAA(HR = 1.001, P = 0.033) and p HER2(HR = 1.003, P = 0.019) as independent predictive factors for synchronous liver metastasis. Besides, high peripheral HER2 level may also be a risk factor for metachronous liver metastasis, although the difference did not reach statistical significance(P = 0.06). Significant correlations were found between paired DV and PV blood levels for PDGFAA(r = 0.794, P < 0.001), but not for HER2(r = 0.189, P = 0.424).CONCLUSION PDGFAA in tumor drainage and HER2 in PV blood may be useful predictive factors for synchronous liver metastasis of colorectal cancer.

Gastric cancer： current and evolving treatment landscape

Gastric(including gastroesophageal junction) cancer is the third leading cause of cancer-related death in the world.In China,an estimated 420,000 patients were diagnosed with gastric cancer in 2011,ranking this malignancy the second most prevalent cancer type and resulting in near 300,000 deaths.The treatment landscape of gastric cancer has evolved in recent years.Although systemic chemotherapy is still the mainstay treatment of metastatic disease,the introduction of agents targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor/vascular endothelia growth factor receptor has brought this disease into the molecular and personalized medicine era.The preliminary yet encouraging clinical efficacy observed with immune checkpoint inhibitors,e.g.,anti-programmed cell death protein 1/programmed death-ligand 1,will further shape the treatment landscape for gastric cancer.Molecular characterization of patients will play a critical role in developing new agents,as well as in implementing new treatment options for this disease.

Mutations in components of the Wnt signaling pathway in gastric cancer

AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta- catenin) exon3 mutations in 70 GCs. METHODS: The presence of mutations was identified by polymerase chain reaction (PCR)-based denaturing high-performance liquid chromatography and direct DNA sequencing. Beta-catenin expression was detected by immunohistochemical analysis. RESULTS: Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in one case. Four cases, including the case with a mutation in AXIN2, had frameshift mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed nuclear beta- catenin expression. CONCLUSION: These data indicate that the mutationsin AXIN1 and AXIN2 may contribute to gastric carcino- genesis.

Over-expression of Metastasis-associated in Colon Cancer-1 (MACC1) Associates with Better Prognosis of Gastric Cancer Patients

Objective： The aim of this study was to detect metastasis-associated in colon cancer-1 （MACC1） expression in Chinese gastric cancer and analyze the relationship between MACC1 expression and postoperative survival. Methods： The expression of MACC1 and c-MET protein in a sample of 128 gastric cancer tissues was detected by immunohistochemistry. A retrospective cohort study on the prognosis was carried out and data were collected from medical records. Results： The positive rate of MACC1 protein expression in gastric cancer was 47.66%, higher than that in adjacent noncancerous mucosa （P0.001）. MACC1 protein expression was not related to the clinicopathological variables involved. Kaplan-Meier analysis revealed that the survival of MACC1 positive group tended to be better than that of MACC1 negative group, particularly in patients with stage III carcinoma （P=0.032）. Cox regression analysis revealed that MACC1 protein over-expression in gastric cancer tended to be a protective factor with hazard ratio of 0.621 （P=0.057）. Immunohistochemical analysis showed that the positive rate of c-MET protein expression was much higher in cases with positive MACC1 expression in gastric cancer （P=0.002）, but P53 expression was not associated with MACC1 expression. Conclusion： MACC1 over-expression implies better survival and may be an independent prognostic factor for gastric cancer in Chinese patients.

Breast Cancer Subtypes and Survival in Chinese Women with Operable Primary Breast Cancer

Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.