Recommendations for articles and reviews in colorectal cancerrelated research at the year-end of 2023

As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)research.We diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly works.Through meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and shortcomings.Undoubtedly,this undertaking demands considerable time and effort.Yet,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC research.Moreover,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.

Prognosis of radiotherapy for esophageal cancer in elderly patients exceeding seventy-five years old

BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.

Current and future research directions in cellular metabolism of colorectal cancer:A bibliometric analysis

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer(CRC).Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric analysis and visualization were conducted using VOSviewer(version 1.6.18)software and CiteSpace 6.1.R6(64-bit)Basic.A comprehensive compilation of 4722 English-language publications,covering the period from January 1,1991 to December 31,2022,was carefully identified and included in the analysis.Among the authors,“Ogino,Shuji”contributed the most publications in this field,while“Giovannucci,E”garnered the highest number of citations.The journal“Cancer Research”ranked first in both publication volume and citations.Institutionally,“Shanghai Jiao Tong University”emerged as the top contributor in terms of published articles,while“Harvard University”led in citation impact.In country-based analysis,the United States held the top position in both publication output and citations,closely followed by China.The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

Phase Ib study of anti-EGFR antibody(SCT200)in combination with anti-PD-1 antibody(SCT-I10A)for patients with RAS/BRAF wild-type metastatic colorectal cancer

Objective:This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor(EGFR)antibody(SCT200)and an anti-programmed cell death 1(PD-1)antibody(SCT-I10A)as third-line or subsequent therapies in patients with rat sarcoma viral oncogene(RAS)/v-raf murine sarcoma viral oncogene homolog B(BRAF)wild-type(wt)metastatic colorectal cancer(mCRC).Methods:We conducted a multicenter,open-label,phase Ib clinical trial.Patients with histologically confirmed RAS/BRAF wt m CRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200.The primary endpoints were the objective response rate(ORR)and safety.The secondary endpoints included disease control rate(DCR),progression-free survival(PFS),and overall survival(OS).Results:Twenty-one patients were enrolled in the study through January 28,2023.The ORR was 28.57%and the DCR was 85.71%(18/21).The median PFS and OS were 4.14 and 12.84 months,respectively.The treatment-related adverse events(TRAEs)were tolerable.Moreover,compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt m CRC in a third-line setting,no significant improvements in PFS and OS were observed in the combination group.Conclusions:SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt m CRC patients with an acceptable safety profile.Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting.(Registration No.NCT04229537).

DNA image cytometry test for primary screening of esophageal cancer: a population-based multi-center study in high-risk areas in China

Objective： To evaluate the feasibility of DNA image cytometry （DNA-ICM） as a primary screening method for esophageal squamous cell cancer （ESCC）. Methods： A total of 5,382 local residents aged 40-69 years from three high-risk areas in China （Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province） from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol＇s iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity （SE）, specificity （SP）, negative predictive values （NPV） and positive predictive values （PPV） as well as their 95% confidence intervals （95% CI） for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic （ROC） curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results： DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions （X2= 18.016, P〈0.001）. The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia （LGIN）, high grade intraepithelial neoplasia （HGIN）, and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test （cutoff point 5,803） combined with liquid-based cytology [threshold atypical squamous cells of undetermined significance （ASCUS）] were separately 72.1% （95% CI： 70.3%-73.9%）, 43.3% （95% CI. 41.3%-45.3%）, 22.8% （95% CI： 21.1%-24.5%） and 87.0% （95% CI： 85.7%-88.3%） for LGIN, 85.7% （95% CI： 84.3%-87.1%）, 41.3% （95% CI： 39.3%-43.3%）, 4.6% （95% CI： 3.8%-5.4%） and 98.9% （95% CI： 98.5%-99.3%） for HGIN, and 96.0% （95% CI： 95.2%-96.8%）, 40.8% （95% CI： 38.8%-42.8%）, 1.7% （95% CI： 1.2%-2.2%） and 99.9% （95% CI： 99.8%-100.0%） for ESCC. Conclusions： It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.

Hemorrhagic cystitis in gastric cancer after nanoparticle albuminbound paclitaxel:A case report

BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

Erratum to Treatment strategies for patients with HER2-positive gastric cancer

For the affiliation information,the affiliation for author Feixue Wang should be Department of GI Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin's Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin Medical University,Tianjin 300060,China.

Acute severe hypokalemia caused by treatment of tongue squamous cell carcinoma with docetaxel and cisplatin:A case report

BACKGROUND The tongue squamous cell carcinoma(TSCC)is an oral malignant tumor arising from the squamous epithelium of the tongue mucosa,characterized by a high malignant degree,invasive growth,early lymph node metastasis,and poor prognosis.Paclitaxel,represented by docetaxel,is now the standard first-line treatment for head and neck squamous cell carcinoma.Docetaxel,which belongs to the class of drugs known as paclitaxel,is an antitumor drug that inhibits cell mitosis and proliferation.Its adverse effects include myelosuppression,hair loss,gastrointestinal reactions,fluid retention,and allergic reactions.However,hypokalemia is rare,most cases are mild or moderate,and severe hypokalemia is seldom reported.symptoms of adverse effects early.It is necessary to be considerate regarding individual differences between patients when selecting chemotherapy regimens and adhere to the principle of individualized treatment.Following multiple cycles of chemotherapy,patients should be aware of the accumulation of toxic side effects and receive blood tests reviewed within 24 hours of completion.It is essential to monitor electrolyte levels in patients suffering from severe gastrointestinal reactions to avoid complications that may result in death.

Comparison of clinical features of patients with or without severe gastrointestinal complications in aggressive gastrointestinal lymphomas

BACKGROUND Aggressive primary gastrointestinal non-Hodgkin lymphoma(PGINHL)is an uncommon and heterogeneous group of lymphoid malignancies,that differs from indolent lymphoma and has a high incidence of severe gastrointestinal complications(GICs).AIM To investigate and compare the clinicopathological characteristics,treatments and outcomes in the GICs and No-GICs group with aggressive PGINHL.METHODS This retrospective analysis was performed on aggressive PGINHL patients between January 2013 and December 2021 at our hospital.The independent influence factors of GICs were obtained by univariate and multivariate Logistic regression analysis,the selected variables significantly related to GICs were selected as the final predictors to construct nomogram.Kaplan-Meier curves further analyzed the survival of patients in GICs and No-GICs groups.Survival analysis of GICs group was performed using Cox regression.RESULTS We focused on 124 aggressive PGINHL cases,which had a relatively high incidence 48.4%(60/124 cases)of GICs,the most common histological type in GICs group was diffuse large B-cell lymphoma(DLBCL)(n=49,81.7%).In the GICs group,small intestine was the most common anatomic site of lesion(43.3%),followed by large intestine(31.7%),and then stomach and esophagus(25.0%).Multivariate Logistic regression analysis showed that the independent risk factors for GICs were the small intestine[odd ratio(OR)=3.33;95%confidence interval(CI):1.47-9.41;P=0.009),aggressive B-cell(OR=0.09;95%CI:0.01-0.83;P=0.033),maximum tumor diameter(OR=1.25;95%CI:1.07-1.47;P=0.005),invaded deep serous layer(OR=3.38;95%CI:1.24-9.19;P=0.017).We developed a nomogram to predict risk of GICs in aggressive PGINHL patients based on independent risk factors.The value of area under curve calculated by receiver operating characteristic curve was 0.815,and calibration curve and decision curve analysis further indicated that the prediction effect was superior.The majority of patients with GICs were given combination therapy(chemotherapy combined with surgery or radiation).Event-free survival and overall survival in GICs group were no worse than those in the No-GICs group.CONCLUSION The complication rate of GICs in patients with aggressive PGINHL was relatively high,particularly in PGI-DLBCL.The independent risk factors for GICs were the small intestine,PGI-TNKL,bulky tumor,and depth of invasion.A combination treatment,involving surgery,improved survival in the GICs group.

Systematic treatment in gastric cancer patients with overt bleeding:A propensity score matching analysis

BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.

miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

Ultrasound features of extranodal extension in the metastatic cervical lymph nodes of papillary thyroid cancer:a case-control study

Objective：Extranodal extension in cervical lymph nodes is an important risk factor for the progression and prognosis of papillary thyroid cancer.The purpose of this study was to identify the common and characteristic preoperative ultrasonography features that are associated with the pathologic extranodal extension of metastatic papillary thyroid carcinoma.Methods：We retrospectively assessed and compared clinicopathologic and ultrasound features between 60 papillary thyroid cancer patients with extranodal extension and 120 control patients with papillary thyroid cancer without extranodal extension.Results：With respect to the pathological N stage and clinicopathologic features,N1b stage papillary thyroid carcinomas were more frequently found in patients who were extranodal extension-positive,in comparison with those who were extranodal extension-negative（78.3%vs.63.3%,P=0.043）.Extranodal extension was detected most frequently in level VI cervical lymph nodes（48.7%）.In our univariate analysis of patients with papillary thyroid carcinoma,cervical lymph nodes with extranodal extension showed higher incidences of node matting,microcalcification,cystic area,aspect ratio＆lt;2,and larger diameter than those without extranodal extension（all P〈0.05）.Our multivariate analysis demonstrated that node matting and cystic area were independent risk factors for the presence of extranodal extension[odds ratio（OR）：4.751,95%confidence interval（CI）：1.212~18.626,P=0.025;OR：2.707,95%CI：1.127~6.502,P=0.026].Conclusions：Common ultrasound features may indicate the presence of extranodal extension in patients with metastatic cervical lymph nodes of papillary thyroid carcinoma.

A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.

Associations of the Fat-age-infl ammation Index with Overall Survival in Patients with Metastatic Lung Cancer

Background Metastatic lung cancer(LC)is a threat to human health.We previously proposed a fat age-inflammation(FAIN)index which showed prognostic value in patients with certain cancers.However,whether a similar association exists in patients with metastatic LC remains unknown.Methods We performed a cohort study including 1360 patients with metastatic LC from January 2013 to April 2019.The FAIN index was defined as:(triceps skinfold thickness+albumin)/[age+5×(neutrophil count/lymphocyte count)]×100%.Sex-specific cutoffs of the FAIN were determined using an optimal stratification approach.The associations of the FAIN index with the nutrition related factors,short-term outcomes and overall survival(OS)of patients were comprehensively assessed.Results The study enrolled 865 males and 495 females with a median age of 59.9 years.The continuous FAIN was significantly associated with the OS in both genders(both P<0.05).The optimal stratification-defined FAIN cutoffs were 82 for women and 60 for men.A total of 623 patients(45.8%)were categorized as having a low FAIN.A low FAIN was associated with poorer nutrition-related factors and impaired short-term outcomes including the thirty-day mortality,length of hospital stay,intensive care unit stay and cost(all P<0.05).Multivariate Cox regression analysis revealed that a lower FAIN was also associated with an increased death hazard(HR=1.428,95%CI=1.209-1.686).Conclusion This study assessed the FAIN index,which might act as a feasible tool to monitor nutrition-related factors and help develop management strategies to optimize the clinical outcomes of patients with metastatic LC.

Isolation and characterization of cancer stem-like cells from MHCC97H Cell Lines

Objective：To identify and isolate CD133 positive cancer stem-like cells （CD133^＋ cells） from the highly invasive human hepatocellular carcinoma cell Iine（MHCC97H）, and examine their potential for clonogenicity and tumorigenicity. Methods： CD133^＋ and CD133^- cells were isolated from MHCC97H cell line by magnetic bead cell sorting（MACS）, and the potentials of CD133^＋ cells for colony formation and tumorigenicity were evaluated by soft agar cloning and tumor formation following nude mice inoculation. Results：CD133^＋ cells represent a minority（0.5-2.0%） of the tumor cell population with a greater colony-forming efficiency and greater tumor production ability. The colony-forming efficiency of CD133^＋ cells in soft agar was significantly higher than CD133^- cells（36.8 ± 1.4 vs 12.9 ± 0.8, P 〈 0.05）. After 6 weeks, 3/5 mice inoculated with 1 × 10^3 CD133^＋ cells, 4/5 with 1 × 10^4 CD133^＋ cells and 5/5 with 1× 10^5 CD133^＋ cells developed detectable tumors at the injection site, while only one tumor was found in mice treated with same numbers of CD133 cells. Conclusion： CD133 may be a hallmark of liver cancer stem cells （CSC） in human hepatocellular carcinoma（HCC）, because the CD133^＋ cells identified and isolated with anti-CD133 labeled magnetic beads from MHCC97H cell line exhibit high potentials for clonogenicity and tumorigenicity. These CD 133^＋ cells might contribute to hepatocarcinogenesis, as well as the growth and recurrence of human HCC, and therefore may be a useful target for anti-cancer therapy.

Significances of Peripheral Inflammatory Cells and Neutrophil/Platelet-Lymphocyte Ratio in Breast Cancer after Resection

Introduction: Breast cancer had become top leading cause of death in Taiwan and endangered women’s health worldwide. Therefore, we try to invest the peripheral inflammatory cell counts and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) from our routine practice for the predictor of prognosis of breast cancer after resection. Patients and Methods: There were 574 breast cancer patients accepted surgical resection and registered in Cancer Registry Center of our hospital. Patient’s basic profiles, peripheral neutophil, lymphocyte and platelet count were measured for study. The scales of NLR and PLR were derived from the lower and higher normal range in cell count from neutrophil, lymphocyte and platelet respectively. Therefore, the scales for NLR and PLR were ≤1.62, 1.63 - 2.57, ≥2.58 and ≤224, 225 - 253, ≥254 respectively for analysis. Results: Poor 5-yr survival rate was found if higher cell counts of neutrophil and platelet (p ≤ 0.05). Three scales of NLR were ≤1.62, 1.63 - 2.57, ≥2.58, and their 5-year survival rates were 94%, 91% and 84% respectively (p = 0.019). In the subgroup of HER-2 (negative), and 3-Negative breast patients had a higher NLR of poor prognosis. But higher PLR was found less in 3-Negative and non in 3-Positive patients (p = 0.039). The PLR was ≤224, 225 - 253, ≥254 and their 5-year survival rates were 92%, 87%, and 64% respectively (p = 0.001);Multivariate Cox regression model for predictor of breast cancer patients who have 3.39 (PLR ≥ 254) and 2.45 (NLR ≥ 2.58 ) times risk (p = 0.02 and p = 0.002) of poor prognosis respectively. Conclusion: Peripheral inflammatory cell counts are easily to take in our clinical practice and have a potential role as predictors of prognosis. We have to pay attention to the trends of peripheral inflammatory cell count and their ratio in our clinical practice where possible.

Treatment strategies for patients with HER2-positive gastric cancer

Gastric cancer (GC) is a major health concern globally,ranking fifth in frequency and fourth in cancer-associated mortality1.In China,an estimated 396,500 new cases are diagnosed each year,and late-stage disease comprises more than 80%of cases2.Because of late diagnosis and heterogeneous characteristics,the prognosis of GC remains poor.For patients with advanced disease,traditional chemotherapy has been the mainstay of treatment,but its clinical outcomes are far from satisfactory,with a 5-year survival rate below 10%.

Ubiquitin-specific protease 15 contributes to gastric cancer progression by regulating the Wnt/β-catenin signaling pathway

BACKGROUND Ubiquitin-specific protease 15(USP15)is an important member of the ubiquitinspecific protease family,the largest deubiquitinase subfamily,whose expression is dysregulated in many types of cancer.However,the biological function and the underlying mechanisms of USP15 in gastric cancer(GC)progression have not been elucidated.AIM To explore the biological role and underlying mechanisms of USP15 in GC progression.METHODS Bioinformatics databases and western blot analysis were utilized to determine the expression of USP15 in GC.Immunohistochemistry was performed to evaluate the correlation between USP15 expression and clinicopathological characteristics of patients with GC.A loss-and gain-of-function experiment was used to investigate the biological effects of USP15 on GC carcinogenesis.RNA sequencing,immunofluorescence,and western blotting were performed to explore the potential mechanism by which USP15 exerts its oncogenic functions.RESULTS USP15 was up-regulated in GC tissue and cell lines.The expression level of USP15 was positively correlated with clinical characteristics(tumor size,depth of invasion,lymph node involvement,tumor-node-metastasis stage,perineural invasion,and vascular invasion),and was related to poor prognosis.USP15 knockdown significantly inhibited cell proliferation,invasion and epithelialmesenchymal transition(EMT)of GC in vitro,while overexpression of USP15 promoted these processes.Knockdown of USP15 inhibited tumor growth in vivo.Mechanistically,RNA sequencing analysis showed that USP15 regulated the Wnt signaling pathway in GC.Western blotting confirmed that USP15 silencing led to significant down-regulation ofβ-catenin and Wnt/β-catenin downstream genes(c-myc and cyclin D1),while overexpression of USP15 yielded an opposite result and USP15 mutation had no change.Immunofluorescence indicated that USP15 promoted nuclear translocation ofβ-catenin,suggesting activation of the Wnt/β-catenin signaling pathway,which may be the critical mechanism promoting GC progression.Finally,rescue experiments showed that the effect of USP15 on gastric cancer progression was dependent on Wnt/β-catenin pathway.CONCLUSION USP15 promotes cell proliferation,invasion and EMT progression of GC via regulating the Wnt/β-catenin pathway,which suggests that USP15 is a novel potential therapeutic target for GC.

Clinicopathologic and molecular characteristics of 44 patients with pure secretory breast carcinoma

Objective: Secretory breast carcinoma(SBC) is a rare type of breast malignancy, accounting for less than 0.02% of all infiltrating breast malignancies. The pure SBC, a type of SBC without another type of breast malignant neoplasm, is particularly rare. This study aimed to investigate the clinicopathologic and molecular features of pure SBC.Methods: The main pathological parameters such as estrogen receptor(ER), progesterone receptor(PR), and human epithelial growth factor receptor 2(C-erbB-2) were detected by immunohistochemistry(IHC), and the clinicopathologic and prognostic difference were compared with invasive ductal carcinoma(IDC). Fluorescent in situ hybridization(FISH) and reverse transcription polymerase chain reaction(RT-PCR) was performed to identify the ETV6-NTRK3 rearrangement of SBC.Results: We found that the positivity rates of ER, PR, C-erbB-2, p53, and S-100 were 47.7%(21/44), 52.3%(23/44), 36.4%(16/44), 27.3%(12/44), and 95.5%(42/44), respectively, which were higher than those reported in previous studies. Special periodic acid-Schiff analysis was performed in 36 patients, and the value of the Ki-67 index ranged from 1% to 50%(mean value:10%). Interestingly, most patients with pure SBC harbored an ETV6-NTRK3 rearrangement with an 88.6%(39/44) expression rate. Compared with IDC, the tumor size of most patients with SBC was larger than 2 cm(P = 0.024). Ultrasound showed benign lesions, and the total misdiagnosis rate was higher(P = 0.020). Although the pathological classification was mostly triple-negative breast cancers(P = 0.036), there was less metastasis(P = 0.029), and the overall prognosis was better than that of the IDC group.Conclusions: Although axillary lymph node metastasis, local recurrence, or distant metastasis may occur, SBC is also considered an indolent neoplasm with a good prognosis. Once diagnosed, surgical treatment should be performed as soon as possible,followed by appropriate adjuvant chemotherapy, irradiation, and endocrine therapies.

Efficacy of Daily Cone-Beam Computed Tomography as Part of a Rescan Protocol for Large Offset to Reduce the Inter-Fractional Motion of the Prostate

Purpose: To prospectively analyze the inter-fractional motion of the prostate in patients with prostate cancer treated with intensity-modulated radiation therapy (IMRT) using image-guided radiotherapy (IGRT) with daily cone-beam computed tomography (CBCT) as part of a rescan protocol for large offset, and to evaluate the efficacy of our protocol. Materials and Methods: Eligible patients were treated with the following protocol: 1) magnesium oxide and dimethylpolysiloxane were administered to ensure that patients had regular bowel movements;2) the patients were instructed to have an appropriately distended bladder during the planning CT and daily irradiation;3) the daily CBCT image was fused with the planning CT image using the prostate outline;and 4) if large offset was recognized, a rescan CBCT image was obtained after appropriate countermeasures, such as the discharge of gas and defecation, and re-registration was performed. Three shifts for the inter-fractional motion of the prostate were analyzed, in the fractions which needed the CBCT rescan;the displacement data after the final rescan were used. Results: Sixty-one patients were eligible, and a total of 2302 fractions were available for the analysis. Rescans of the CBCT for large offset were performed in 113 (5%) of the 2302 fractions. After the first rescan, the large offset was resolved in 106 (94%) of the 113 fractions. Excessive rectal gas was the reason for the large offset in 94 (83%) of the 113 fractions. The total mean and standard deviation of the inter-fractional motion of the prostate in the AP, LR, and SI directions were 1.1 ± 2.4, -0.1 ± 2.3, and 0.7 ± 3.0 mm, respectively. Conclusion: Large offset was recognized in 5% of all fractions. Daily CBCT with our rescan protocol could resolve the large offset, which was mainly caused by excessive rectal gas, and it may therefore be promising to reduce the inter-fractional motion of the prostate.