Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer

BACKGROUND Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer.Neoadjuvant chemoradiotherapy(NCRT)can effectively reduce the postoperative recurrence rate;thus,NCRT with total mesorectal excision(TME)is the most widely accepted standard of care for rectal cancer.The addition of lateral lymph node dissection(LLND)after NCRT remains a controversial topic.AIM To investigate the surgical outcomes of TME plus LLND,and the possible risk factors for lateral lymph node metastasis after NCRT.METHODS This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018.In the NCRT group,TME plus LLND was performed in patients with short axis(SA)of the lateral lymph node greater than 5 mm.In the non-NCRT group,TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm.Data regarding patient demographics,clinical workup,surgical procedure,complications,and outcomes were collected.Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients.RESULTS LLN metastasis was pathologically confirmed in 35 patients(39.3%):26(41.3%)in the NCRT group and 9(34.6%)in the non-NCRT group.The most common site of metastasis was around the obturator nerve(21/35)followed by the internal iliac artery region(12/35).In the NCRT patients,46%of patients with SA of LLN greater than 7 mm were positive.The postoperative 30-d mortality rate was 0%.Two(2.2%)patients suffered from lateral local recurrence in the 2-year follow up.Multivariate analysis showed that cT4 stage(odds ratio[OR]=5.124,95%confidence interval[CI]:1.419-18.508;P=0.013),poor differentiation type(OR=4.014,95%CI:1.038-15.520;P=0.044),and SA≥7 mm(OR=7.539,95%CI:1.487-38.214;P=0.015)were statistically significant risk factors associated with LLN metastasis.CONCLUSION NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter,poorer histological differentiation,or advanced T stage.Selective LLND for NCRT patients can have a favorable oncological outcome.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients

BACKGROUND Epidemiologically,in China,locally advanced rectal cancer is a more common form of rectal cancer.Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival(DFS)and pathologic response after surgery.At present,this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers,but the optimal time for surgery after neoadjuvant therapy is still controversial.AIM To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer.METHODS A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study.The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery:139(60.2%)patients were in group A(≤9 wk),and 92(39.2%)patients were in group B(>9 wk).DFS and pathologic response were analyzed as the primary endpoints.The secondary endpoints were postoperative complications and sphincter preservation.RESULTS For the 231 patients included,surgery was performed at≤9 wk in 139(60.2%)patients and at>9 wk in 92(39.8%).The patients’clinical characteristics,surgical results,and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis.The overall pathologic complete response(pCR)rate was 27.2%(n=25)in the longer time interval group(>9 wk)and 10.8%(n=15)in the shorter time interval group(≤9 wk,P=0.001).The postoperative complications did not differ between the groups(group A,5%vs group B,5.4%;P=0.894).Surgical procedures for sphincter preservation were performed in 113(48.9%)patients,which were not significantly different between the groups(group A,52.5%vs group B,43.5%;P=0.179).The pCR rate was an independent factor affected by time interval(P=0.009;odds ratio[OR]=2.668;95%CI:1.276-5.578).Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval(>9 wk)was a significant independent prognostic factor for DFS(P=0.032;OR=2.295;95%CI:1.074-4.905),but the time interval was not an independent prognostic factor for overall survival(P>0.05).CONCLUSION A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

Low ligation has a lower anastomotic leakage rate after rectal cancer surgery

BACKGROUND For laparoscopic rectal cancer surgery,the inferior mesenteric artery(IMA)can be ligated at its origin from the aorta[high ligation(HL)]or distally to the origin of the left colic artery[low ligation(LL)].Whether different ligation levels are related to different postoperative complications,operation time,and lymph node yield remains controversial.Therefore,we designed this study to determine the effects of different ligation levels in rectal cancer surgery.AIM To investigate the operative results following HL and LL of the IMA in rectal cancer patients.METHODS From January 2017 to July 2019,this retrospective cohort study collected information from 462 consecutive rectal cancer patients.According to the ligation level,235 patients were assigned to the HL group while 227 patients were assigned to the LL group.Data regarding the clinical characteristics,surgical characteristics and complications,pathological outcomes and postoperative recovery were obtained and compared between the two groups.A multivariate logistic regression analysis was performed to evaluate the possible risk factors for anastomotic leakage(AL).RESULTS Compared to the HL group,the LL group had a significantly lower AL rate,with 6(2.8%)cases in the LL group and 24(11.0%)cases in the HL group(P=0.001).The HL group also had a higher diverting stoma rate(16.5%vs 7.5%,P=0.003).A multivariate logistic regression analysis was subsequently performed to adjust for the confounding factors and confirmed that HL(OR=3.599;95%CI:1.374-9.425;P=0.009),tumor located below the peritoneal reflection(OR=2.751;95%CI:0.772-3.985;P=0.031)and age(≥65 years)(OR=2.494;95%CI:1.080-5.760;P=0.032)were risk factors for AL.There were no differences in terms of patient demographics,pathological outcomes,lymph nodes harvested,blood loss,hospital stay and urinary function(P>0.05).CONCLUSION In rectal cancer surgery,LL should be the preferred method,as it has a lower AL and diverting stoma rate.

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy

BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors

BACKGROUND Intraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL. AIM To investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms. METHODS This retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis. RESULTS The univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386;95%CI: 1.808-16.042;P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer. CONCLUSION Intraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals

BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.

Characteristics of neural growth and cryopreservation of the dorsal root ganglion using three-dimensional collagen hydrogel culture versus conventional culture

In vertebrates, most somatosensory pathways begin with the activation of dorsal root ganglion(DRG) neurons. The development of an appropriate DRG culture method is a prerequisite for establishing in vitro peripheral nerve disease models and for screening therapeutic drugs. In this study, we compared the changes in morphology, molecular biology, and transcriptomics of chicken embryo DRG cultured on tissue culture plates(T-DRG) versus three-dimensional collagen hydrogels(C-DRG). Our results showed that after 7 days of culture, the transcriptomics of T-DRG and C-DRG were quite different. The upregulated genes in C-DRG were mainly related to neurogenesis, axon guidance, and synaptic plasticity, whereas the downregulated genes in C-DRG were mainly related to cell proliferation and cell division. In addition, the genes related to cycles/pathways such as the synaptic vesicle cycle, cyclic adenosine monophosphate signaling pathway, and calcium signaling pathway were activated, while those related to cell-cycle pathways were downregulated. Furthermore, neurogenesis-and myelination-related genes were highly expressed in C-DRG, while epithelial–mesenchymal transition-, apoptosis-, and cell division-related genes were suppressed. Morphological results indicated that the numbers of branches, junctions, and end-point voxels per C-DRG were significantly greater than those per T-DRG. Furthermore, cells were scattered in T-DRG and more concentrated in C-DRG, with a higher ratio of 5-ethynyl-2′-deoxyuridine(EdU)-positive cells in T-DRG compared with C-DRG. C-DRG also had higher S100 calcium-binding protein B(S100 B) and lower α-smooth muscle actin(α-SMA) expression than T-DRG, and contained fewer terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)-positive cells after 48 hours of serum starvation. After cryopreservation, C-DRG maintained more intact morphological characteristics, and had higher viability and less TUNEL-positive cells than T-DRG. Furthermore, newly formed nerve bundles were able to grow along the existing Schwann cells in C-DRG. These results suggest that C-DRG may be a promising in vitro culture model, with better nerve growth and anti-apoptotic ability, quiescent Schwann cells, and higher viability. Results from this study provide a reference for the construction, storage, and transportation of tissue-engineered nerves. The study was approved by the Ethics Committee of Aier School of Ophthalmology, Central South University, China(approval No. 2020-IRB16), on March 15, 2020.

A Phase Ⅱ Trial of Gefitinib as Maintenance Therapy after First-Line Chemotherapy for Advanced Non-Small Cell Lung Cancer in China

Objective： To investigate the efficacy and safety of gefitinib as maintenance therapy for advanced non-small cell lung cancer （NSCLC） patients who obtained disease control （DC） after first-line chemotherapy in Chinese population. Methods： Chinese patients with advanced NSCLC treated with standard chemotherapy and obtained DC were assigned to receive gefitinib as maintenance treatment. The primary end point was overall survival time （OS）, the second end point was disease control rate （DCR） and progression-free survival time （PFS）. DCR included complete response （CR） plus partial response （PR） and plus stable disease （SD）. The impact of epidermal growth factor receptor （EGFR） mutation status on the treatment as exploratory point was also evaluated by denaturing high-performance liquid chromatography （DHPLC）. Results： Among 75 enrolled patients, the overall response rate was 37% and the DCR （CR ＋ PR ＋SD） was 66%. The median PFS and OS were 17.13 months and 26.13 months respectively, with 1- and 2-year survival rates 89.3% and 34.7%. Patients harboring somatic EGFR mutations obtained a prolonged median PFS and OS compared with EGFR wide type （25.1 vs. 13.0 months, P=0.019 and 33.37 vs. 25.57 months, P=0.014, respectively）. In COX regression model, only EGFR mutation status was the independently factor influencing both PFS and OS （P=0.029 and 0.017, respectively）, however, rash status was the predictor in terms of PFS （P=0.027）. Conclusion： Gefitinib produced encouraging survival when delivered as maintenance therapy in Chinese patients obtaining DC after first-line chemotherapy, especially for patients carrying somatic EGFR mutations. EGFR mutation is an independently predictive factor of survival.

Reduced serum high-density lipoprotein cholesterol levels and aberrantly expressed cholesterol metabolism genes in colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor of the gastrointestinal tract.Lipid metabolism,as an important part of material and energy circulation,is well known to play a crucial role in CRC.AIM To explore the relationship between serum lipids and CRC development and identify aberrantly expressed cholesterol metabolism genes in CRC.METHODS We retrospectively collected 843 patients who had confirmed CRC and received surgical resection from 2013 to 2015 at the Cancer Hospital of the Chinese Academy of Medical Sciences as our research subjects.The levels of serum total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),highdensity lipoprotein cholesterol(HDL-C),LDL-C/HDL-C and clinical features were collected and statistically analyzed by SPSS.Then,we used the data from Oncomine to screen the differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and used Gene Expression Profiling Interactive Analysis to confirm the candidate DEGs.PrognoScan was used to analyze the prognostic value of the DEGs,and Search Tool for the Retrieval of Interacting Genes was used to construct the protein-protein interaction network of DEGs.RESULTS The serum HDL-C level in CRC patients was significantly correlated with tumor size,and patients whose tumor size was more than 5 cm had a lower serum HDL-C level(1.18±0.41 mmol/L vs 1.25±0.35 mmol/L,P<0.01)than their counterparts.In addition,TC/HDL(4.19±1.33 vs 3.93±1.26,P<0.01)and LDL-C/HDL-C(2.83±1.10 vs 2.61±0.96,P<0.01)were higher in patients with larger tumors.The levels of HDL-C(P<0.05),TC/HDL-C(P<0.01)and LDL-C/HDL-C(P<0.05)varied in different stages of CRC patients,and the differences were significant.We screened 14 differentially expressed genes(DEGs)of the cholesterol metabolism pathway in CRC and confirmed that lipoprotein receptor-related protein 8(LRP8),PCSK9,low-density lipoprotein receptor(LDLR),MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in cancer tissue.Higher expression of LDLR(HR=3.12,95%CI:1.77-5.49,P<0.001),ABCA1(HR=1.66,95%CI:1.11-2.48,P=0.012)and OSBPL1A(HR=1.38,95%CI:1.01-1.89,P=0.041)all yielded significantly poorer DFS outcomes.Higher expression of FDXR(HR=0.7,95%CI:0.47-1.05,P=0.002)was correlated with longer DFS.LDLR,ABCA1,OSBPL1A and FDXR were involved in many important cellular function pathways.CONCLUSION Serum HDL-C levels are associated with tumor size and stage in CRC patients.LRP8,PCSK9,LDLR,MBTPS2 and FDXR are upregulated,while ABCA1 and OSBPL1A are downregulated in CRC.Among them,LDLR,ABCA1,OSBPL1A and FDXR were valuable prognostic factors of DFS and were involved in important cellular function pathways.

Fascia- vs vessel-oriented lateral lymph node dissection for rectal cancer: Short-term outcomes and prognosis in a single-center experience

BACKGROUND For the management of lateral lymph node(LLN)metastasis in patients with rectal cancer,selective LLN dissection(LLND)is gradually being accepted by Chinese scholars.Theoretically,fascia-oriented LLND allows radical tumor resection and protects of organ function.However,there is a lack of studies comparing the efficacy of fascia-oriented and traditional vessel-oriented LLND.Through a preliminary study with a small sample size,we found that fasciaoriented LLND was associated with a lower incidence of postoperative urinary and male sexual dysfunction and a higher number of examined LLNs.In this study,we increased the sample size and refined the postoperative functional outcomes.AIM To compare the effects of fascia-and vessel-oriented LLND regarding short-term outcomes and prognosis.METHODS We conducted a retrospective cohort study on data from 196 patients with rectal cancer who underwent total mesorectal excision and LLND from July 2014 to August 2021.The short-term outcomes included perioperative outcomes and postoperative functional outcomes.The prognosis was measured based on overall survival(OS)and progression-free survival(PFS).RESULTS A total of 105 patients were included in the final analysis and were divided into fascia-and vesseloriented groups that included 41 and 64 patients,respectively.Regarding the short-term outcomes,the median number of examined LLNs was significantly higher in the fascia-oriented group than in the vessel-oriented group.There were no significant differences in the other short-term outcomes.The incidence of postoperative urinary and male sexual dysfunction was significantly lower in the fascia-oriented group than in the vessel-oriented group.In addition,there was no significant difference in the incidence of postoperative lower limb dysfunction between the two groups.In terms of prognosis,there was no significant difference in PFS or OS between the two groups.CONCLUSION It is safe and feasible to perform fascia-oriented LLND.Compared with vessel-oriented LLND,fascia-oriented LLND allows the examination of more LLNs and may better protect postoperative urinary function and male sexual function.

Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy

BACKGROUND Conventional clinical guidelines recommend that at least 12 lymph nodes shouldbe removed during radical rectal cancer surgery to achieve accurate staging.Thecurrent application of neoadjuvant therapy has changed the number of lymphnode dissection.AIM To investigate factors affecting the number of lymph nodes dissected afterneoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluatethe relationship of the total number of retrieved lymph nodes(TLN)with diseasefreesurvival(DFS)and overall survival(OS).METHODS A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 wereincluded in this study.According to the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor-node-metastasis(TNM)classification system and the NCCN guidelines for rectal cancer,thepatients were divided into two groups:group A(TLN≥12,n=177)and group B(TLN<12,n=54).Factors influencing lymph node retrieval were analyzed byunivariate and binary logistic regression analysis.DFS and OS were evaluated byKaplan-Meier curves and Cox regression models.RESULTS The median number of lymph nodes dissected was 18(range,12-45)in group A and 8(range,2-11)in group B.The lymph node ratio(number of positive lymphnodes/total number of lymph nodes)(P=0.039)and the interval betweenneoadjuvant therapy and radical surgery(P=0.002)were independent factors ofthe TLN.However,TLN was not associated with sex,age,ASA score,clinical T orN stage,pathological T stage,tumor response grade(Dworak),downstaging,pathological complete response,radiotherapy dose,preoperative concurrentchemotherapy regimen,tumor distance from anal verge,multivisceral resection,preoperative carcinoembryonic antigen level,perineural invasion,intravasculartumor embolus or degree of differentiation.The pathological T stage(P<0.001)and TLN(P<0.001)were independent factors of DFS,and pathological T stage(P=0.011)and perineural invasion(P=0.002)were independent factors of OS.Inaddition,the risk of distant recurrence was greater for TLN<12(P=0.009).CONCLUSION A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectalcancer under indications may cause increased number of lymph nodes harvested.Tumor shrinkage and more extensive lymph node retrieval may lead to a morefavorable prognosis.

Immediate Versus Delayed Treatment with EGFR Tyrosine Kinase Inhibitors after First-line Therapy in Advanced Non-small-cell Lung Cancer

Objective： To analyze the outcomes of patients who received TKI immediately after the first-line without progression as maintenance treatment （immediate group） vs. those received delayed treatment upon disease progression as second-line therapy （delayed group）. Methods： The study included 159 no-small-cell lung cancer （NSCLC） patients who received gefitinib or erlotinib as maintenance treatment in the immediate group （85 patients） or as second-line therapy in the delayed group （74 patients）. The primary end point was progression-free survival （PFS）. EGFR mutation status was detected using denaturing high-performance liquid chromatography （DHPLC）. Results： PFS was 17.3 and 16.4 months in the immediate and delayed groups, respectively （hazard ratio [HR], 0.99; 95% Confidence Interval [CI]： 0.69-1.42; P=0.947）. In a subgroup analysis that included only patients with EGFR mutation, however, PFS was significantly longer in the immediate group than in the delayed group （HR, 0.48; 95% CI： 0.27-0.85; P=0.012）. In patients with wild type EGFR, the risk for disease progression was comparable between the two groups （HR, 1.23; 95% CI： 0.61-2.51; P=0.564）. No significant difference was demonstrated between the immediate and delayed group in terms of the overall survival （OS） （26.1 months vs. 21.6 months, respectively; HR=0.53; 95% CI： 0.27 to 1.06; P=0.072）. There was also no difference in the incidence of adverse events between the two groups. Conclusions： EGFR TKI maintenance improves PFS in patients with EGFR mutation. Prospectively designed clinical studies that compare TKI immediate vs. delayed treatment after first-line chemotherapy upon disease progression are needed.

内镜逆行胰胆管造影术知情同意研究进展

内镜逆行胰胆管造影术(endoscopic retrograde chola ngiopancreatography,ERCP)是一项有着潜在治疗风险的内镜操作.随着内镜技术的不断发展,现如今ERCP的开展率越来越高,这也意味着出现ERCP相关并发症的概率也在不断上升.但是目前,相当一部分患者对ERCP过程及ERCP相关并发症鲜有了解.本文就ERCP术前知情同意研究进展进行简要综述.

Molecular Ferroelastic Induced by Mono-/Double-Protonation Strategy

Molecular ferroelastics with the natural features of mechanical flexibility and switchable spontaneous strain have attracted widespread attention in the scientific community due to their potential applications in tunable gratings,flexible memorizers,strain sensors,and intelligent actuators.However,most designs of molecular ferroelastics remain in the stage of blind exploration,posing a challenge to achieve a functional ferroelastic more effectively.Herein,we have successfully obtained a molecular ferroelastic,[Me_(2)NH(CH_(2))_(2)NH_(3)](ReO_(4))_(2)(Me_(2)NH(CH_(2))_(2)NH_(3)=N,N-dimethylethylenediammonium),under the guidance of the mono-/double-protonation strategy.The_double-protonated[Me_(2)NH(CH_(2))_(2)NH_(3)](ReO_(4))_(2) undergoes a paraelastic-ferroelastic phase transition with the Aizu notation of 2/mFi at 322 K.Meanwhile,the theoretical calculation and experimental measurement simultaneously show that[Me_(2)NH(CH_(2))_(2)NH_(3)](ReO_(4))_(2) possesses good mechanical flexibility,because its elastic modulus(E)of 8.26 GPa and hardness(H)of 0.45 GPa are smaller than the average values of organic crystals(E of 12.05 GPa and H of 0.5 GPa),which makes it promising to apply in wearable pressure sensors,implantable medical sensors,high-precision tuners,etc.This work further enriches the molecular ferroelastic family and demonstrates that mono-/double-protonation is one of the effective molecular modification strategies for designing ferroelastics.

Effect of temperature on the demography of Galerucella birmanica （Coleoptera： Chrysomelidae）

Studies on the effect of temperature on the development of the water chestnut beetle, Galerucella birmanica Jacoby were carried out in the laboratory at seven different temperatures： 16 ℃, 19 ℃, 22 ℃, 25 ℃, 28 ℃, 31 ℃ and 34 ℃. The developmental time decreased with increase in temperature. The developmental time at 16 ℃, 19℃, 22 ℃, 25 ℃, 28 ℃, 31 ℃ and 34 ℃ was 96.60, 80.68, 58.96, 43.48, 35.03, 30.08 and 28.02 days for the period from egg hatching to adult emergence, respectively. The developmental threshold estimated for a generation by linear regression was 10.36℃. The fecundity per female at 22 ℃, 25 ℃, 28 ℃, 31 ℃ and 34 ℃ was 102.3, 134.5, 141.2, 130.1 and 116.2 eggs, respectively. Oviposition period ranged from 15.6 days at 22 ℃ to 8.6 days at 34 ℃. Hatchability of eggs was highest at 31 ℃ with 76.9% and lowest at 34 ℃ with 57.1%. The highest generation survival rate was 65.3% at 31 ℃, and the intrinsic rate of natural increase （rm） for G. birmanica was the highest at 34 ℃.

CATIRI:An Efficient Method for Content-and-Text Based Image Retrieval

The combination of visual and textual information in image retrieval remarkably alleviates the semantic gap of traditional image retrieval methods,and thus it has attracted much attention recently.Image retrieval based on such a combination is usually called the content-and-text based image retrieval(CTBIR).Nevertheless,existing studies in CTBIR mainly make efforts on improving the retrieval quality.To the best of our knowledge,little attention has been focused on how to enhance the retrieval efficiency.Nowadays,image data is widespread and expanding rapidly in our daily life.Obviously,it is important and interesting to investigate the retrieval efficiency.To this end,this paper presents an efficient image retrieval method named CATIRI(content-and-text based image retrieval using indexing).CATIRI follows a three-phase solution framework that develops a new indexing structure called MHIM-tree.The MHIM-tree seamlessly integrates several elements including Manhattan Hashing,Inverted index,and M-tree.To use our MHIM-tree wisely in the query,we present a set of important metrics and reveal their inherent properties.Based on them,we develop a top-k query algorithm for CTBIR.Experimental results based on benchmark image datasets demonstrate that CATIRI outperforms the competitors by an order of magnitude.

Rechallenge pemetrexed-based chemotherapy provides an option for initially benefited patients with advanced lung adenocarcinoma

To the Editor:Pemetrexed plus platinum(cisplatin or carboplatin)chemotherapy doublets are widely recommended as the standard first-line treatment for non-small cell lung cancer(NSCLC)with no identified genetic mutations.[1]However,their efficiency has been confirmed with a median survival of approximately 10.2 to 13.0 months and a 5-year survival rate of 13%to 15%.Initial chemotherapy with pemetrexed has been confirmed as an effective regimen for advanced lung adenocarcinoma without specific genetic biomarker predicting the benefit of pemetrexed efficacy.[2]Patients treated with pemetrexedbased regimens can also receive a single agent as maintenance treatment after the induction chemotherapy.