Lung cancer is the malignant tumor with the highest incidence and mortality rate in China,and surgical resection is a crucial approach for its treatment.In 2023,significant advancements were made in the field of lung cancer surgery.Firstly,CALGB140503 showed that for peripheral≤2 cm nodular lung cancer,sublobar resection demonstrated no significant difference in survival rates compared to lobectomy,establishing the foundation for its role in early lung cancer treatment.Secondly,JCOG1211 found that segmentectomy could be used to treat 2-3 cm ground-glass opacity-predominant adenocarcinoma,however,patient in this study may undergo overtreatment,which could potentially be mitigated through intraoperative rapid frozen section pathological examination.Furthermore,the ECTOP-1003 study proposed a selective lymph node dissection strategy based on tumor location and intraoperative rapid frozen section pathological examination,achieving a 100%accuracy rate and providing a more precise approach to lymph node dissection.Additionally,the exploration of the cure time window for lung adenocarcinoma was remarkable,emphasizing the importance of timing in surgical intervention to avoid overtreatment in early lung cancer treatment.Finally,the ECTOP-1008 study demonstrated that high-resolution chest computed tomography(CT)scans assisted in determining the pathological invasion degree of lung cancer,aiding in the precise judgment of curative time window.This review summarized the important research progress in the field of lung cancer surgery in 2023,aiming to provide insights for clinical practice and future trials in lung cancer surgery.

Compared with the global situation,it can be found that the cancer incidence in China is close to the world average level,but the mortality rate has difference compared with the global average level.The burden of gynecological cancers in China is increasing,with large differences between urban and rural areas and uneven regional distribution.Therefore,the situation of cancer prevention and control is still challenging.In recent years,new technologies and drugs,such as immune checkpoint inhibitors(ICIs)and antibody-drug conjugate(ADC),have been introduced into clinical practice,bringing new hope for the treatment of gynecological cancers.This article reviewed the major research progress of gynecological cancers in 2023.Among them,in terms of the progress of treatment for cervical cancer,we reviewed the innovation of standard treatment mode and the related progress of post-line treatment for advanced recurrent and metastatic cervical cancer(clinical research such as ENGOT-cx11/GOG-3047/KEYNOTE-A18,KEYNOTE-826).In terms of treatment for ovarian cancer,this review summarized the latest progress of PARP inhibitors,immunotherapy,first-line treatment of newly diagnosed ovarian cancer and treatment of recurrent ovarian cancer(FLAMES,ANITA/ENGOT-Ov41/GEICO 69-O,NRG-GY004,etc.).In terms of treatment for endometrial cancer,this study reviewed the progress in the treatment of locally advanced endometrial cancer(GOG 258,Lunchbox clinical research,etc.)and advanced/recurrent metastatic endometrial cancer(ENGOT-EN6-NSGO/GOG-3031/RUBY research,etc.),and summarized the exploration of back-line targeted immunotherapy(such as KEYNOTE-775,ADAGIO and other clinical studies).This study combed the progress of gynecological tumors in 2023 from the above aspects,aiming at providing reference for clinical practice and clinical research.

Background and purpose:Effective treatment for cervical cancer patients is one of the global strategies to eliminate cervical cancer.By analyzing the metastasis characteristics and survival status of patients with distant metastasis of cervical cancer from a hospital-based cancer registry data,our study provided real-world evidence for better survival of cervical cancer and finally eliminating cervical cancer.Methods:A total of 572 cervical cancer patients who had metastasis cancer at the initial diagnosis or developed distant metastasis during follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study.Medical records review,telephone visits and death registry data linkage were applied in collecting endpoint data.The first follow-up date was the diagnose date of metastasis,and the last follow-up date was November 1,2020.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year overall survival(OS)rates for overall and site-specific patients.Results:The median follow-up time was 38.93 months,and 348 cases died during the follow-up.72.55%were single site metastasis,and 27.45%were multiple metastases.Among all metastatic sites,the proportion of lung metastasis was the highest,41.26%,15.21%to bone,and 11.54%to liver.After metastasis,the 1-year,3-year and 5-year OS rates were 62.29%(95%CI:62.25-62.33),33.13%(95%CI:33.08-33.18)and 23.42%(95%CI:23.37-23.47),respectively.In single site metastasis,1-year OS was the highest after metastasis to the lung(72.52%).Besides,there was no significant difference among different metastatic sites,both in 3-year and 5-year OS.Conclusion:The most frequent distant metastatic sites of cervical cancer are lung,bone and liver.The survival rate after metastasis is poor.Further research with systematic treatment strategy is required for better survival.

Background and purpose:Epidermal growth factor receptor exon 20 T790M(EGFR T790M)mutation is one of the acquired resistance mechanisms in non-small cell lung cancer(NSCLC)against first-/second-generation EGFR tyrosine kinase inhibitors(EGFR TKIs).Additionally,EGFR T790M mutation can also be observed in NSCLC patients who have not undergone EGFR TKIs treatment.This study aimed to compare the clinical pathological characteristics and prognostic differences between NSCLC patients with de novo and acquired EGFR T790M mutation,and further explore the immune microenvironment features of acquired T790M mutation in NSCLC.Methods:This study retrospectively included 3 762 cases of NSCLC diagnosed at Fudan University Shanghai Cancer Center from April 2020 to September 2022.Among them,2 070 cases(55.02%)exhibited EGFR mutations,and 556 cases(14.77%)received EGFR TKIs treatment.Specifically,there were 119 cases(3.16%)of NSCLC with EGFR T790M mutation,including 51 cases(1.35%)of de novo T790M mutation and 68 cases(1.81%)of acquired EGFR T790M mutation.Clinical data of the patients were collected for comparative analysis between NSCLC patients with de novo and acquired T790M mutation.Multiple immunofluorescence histochemistry(mIHC)was employed to explore the immune microenvironment characteristics of NSCLC patients with acquired T790M mutation.Results:The proportion of de novo and acquired T790M mutations was higher in female patients compared to males.Patients with de novo T790M mutation tended to be younger.Both de novo and acquired T790M mutations were more commonly found in poorly differentiated carcinomas.Among NSCLC patients with de novo T790M mutation,there was a higher rate of programmed death ligand-1(PD-L1)expression(60.00%).In contrast,among NSCLC patients with acquired T790M mutation,the rate of PD-L1 expression was lower(22.39%).Acquired T790M mutation in NSCLC was often accompanied by TP53 alterations(39.7%).Cox regression analysis results indicated that mesenchymal to epithelial transition(MET)factor alteration was a risk factor for the occurrence of acquired T790M mutation(P=0.000 5).The average overall survival(OS)showed no significant difference between de novo and acquired T790M mutations(35.4 and 37.3 months respectively).However,patients with acquired T790M mutation exhibited a higher proportion of recurrence and metastasis.In acquired T790M mutation,there was a higher presence of immune cell infiltration within the stromal compartment,such as CD20+B cells,CD23+B cells,CD8+T cells,CD8+PD-1-/+cells,CD20+PD-1-/+cells and CD23+PD-1-/+cells.Additionally,the study found that when EGFR was accompanied by tumor suppressor gene(TSG)alterations,the average distance between tumor cells and CD8+T cells,CD20+B cells,CD8+PD-1+cells,CD20+PD-1+cells and CD23+PD-1+cells was closer compared to cases with only EGFR mutations.Conclusion:In comparison to patients with de novo T790M mutation,patients with acquired T790M mutation exhibit a lower rate of PD-L1 positivity.Acquired T790M mutation often accompanies TP53 alterations,and MET alteration is identified as a risk factor triggering acquired T790M mutation.Although patients with acquired T790M mutation face higher risk of recurrence and metastasis,their average OS does not significantly differ from those with de novo T790M mutation.In cases of acquired T790M mutation,the presence of TSG mutations can alter the spatial distribution of immune cells,potentially leading to benefits from immunotherapy.

Background and purpose:Gastric-type endocervical adenocarcinoma(G-EAC)is a rare variant of endocervical adenocarcinoma,characterized by atypical clinical manifestations and elusive lesions.Due to these factors,G-EAC is prone to being missed or misdiagnosed,significantly impacting the prognosis.Lobular endocervical glandular hyperplasia(LEGH)and atypical LEGH(aLEGH)are considered to be precancerous lesions of G-EAC.These conditions also present overlapping clinical,pathologic and imaging manifestations,making it challenging to differentiate between them preoperatively.The purpose of this study was to investigate the correlation between magnetic resonance imaging(MRI)findings of cystic-solid lesions in the cervix and their underlying pathology in order to enhance the accuracy of distinguishing between LEGH and G-EAC,ultimately aiding in the early diagnosis and appropriate management of these conditions.Methods:Clinical,imaging and pathological data of 37 LEGH and 53 G-EAC patients who attended the Obstetrics and Gynecology Hospital of Fudan University from July 2016 to August 2023 were collected.Analysis was conducted using Pearson Chi-square χ2,Fisher's exact tests and so on.Multivariate analyses were performed using logistic regression.Receiver operating characteristic(ROC)curves were used for performance evaluation.Results:In this study,differences in age,symptoms,extent,size,composition,degree of enhancement,cervical stromal ring,endometrium invasion,pelvic lymph nodes enlargement,and hydrohystera were statistically significant between the two groups(P＜0.05).In the LEGH and aLEGH groups,lesions were primarily localized to the epithelial layer of the endocervical canal.These lesions were predominantly simple cystic(32/37),and the cystic walls often displayed significant enhancement(31/37).In contrast,the G-EAC group presented with lesions involving the myometrium of the uterine cervix(42/53).These lesions were characterized by a solid component in the majority of cases(52/53),a tendency for the disappearance of the cervical stromal ring(46/53).Logistic regression analysis revealed that among the MRI features,lesion composition(OR=50.064)and incomplete cervical stromal ring(OR=40.180)were significant predictors for G-EAC.ROC analysis,incorporating lesion size,composition,enhancement degree,cervical stromal ring,and endometrial involvement,yielded an area under curve(AUC)of 0.970(95%CI:0.931-1.008).Conclusion:Combining multiple MRI features of cystic-solid lesions in the cervix aids in distinguishing between LEGH and G-EAC.

Background and purpose:Leptomeningeal metastasis is a form of central nervous system metastasis of melanoma.High mobility group A2(HMGA2)has been proven to play an important role in the occurrence and development of various tumors,but its biological functions in leptomeningeal metastatic melanoma cells remain unclear.On the basis of building mouse models of central nervous system metastasis of melanoma,this study investigated the differences in cell migration and cell proliferation among leptomeningeal metastatic melanoma cells,primary site melanoma cells and brain parenchymal metastatic melanoma cells,and further clarified the effects of differentially expressed gene HMGA2 on cell migration and proliferation of leptomeningeal metastatic melanoma cells.Methods:B16 mouse melanoma cells(B16-parental cells,B16-Par)stably expressing tdTomato and luciferase were generated by lentiviral infection.Subsequently,B16 specific brain parenchymal metastatic cells(B16-brain metastatic cells,B16-BrM)and B16 specific leptomeningeal metastatic cells(B16-leptomeningeal metastatic cells,B16-LM)were collected after adaptive screening of metastatic sites in vivo.The differences in migration and proliferation among B16-Par,B16-BrM and B16-LM were assessed by wound healing assay and cell counting kit-8(CCK-8).RNA sequencing(RNA-seq)was used to analyze differential gene expression in B16-Par,B16-BrM and B16-LM,and HMGA2 gene specifically upregulated in B16-LM was screened out.The results were verified by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Gene ontology(GO)analysis was performed for genes which were upregulated in B16-LM specifically.siRNA was used to interfere with the expression of HMGA2 gene in B16-LM,and the knock-down effect was verified by RTFQ-PCR and Western blot.The effects of knocking down HMGA2 on cell migration and proliferation were detected by wound healing assay and CCK-8 assay.Using GSE174401 data in Gene Expression Omnibus(GEO),the specificity of HMGA2 gene expression in leptomeningeal metastatic melanoma cells from patients was verified.Results:Compared with Par cells,tumor cells screened by the brain environment were more likely to colonize the central nervous system.B16-LM had stronger migration and proliferation abilities,and upregulated the expression of HMGA2 gene.GO analysis revealed that HMGA2 was associated with many biological processes such as angiogenesis and cell proliferation.When the expression of HMGA2 gene was knocked down,the migration and proliferation of B16-LM could be inhibited.HMGA2 was upregulated in leptomeningeal metastatic melanoma cells from patients.Conclusion:Leptomeningeal metastatic melanoma cells had relatively unique cellular characteristics,which promoted cell migration and proliferation by upregulating HMGA2 gene expression.

Background and purpose:Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis(srICIAM)are poor.Intensified immunosuppressive therapies,including tofacitinib,a novel Janus kinase(JAK)inhibitor,may have some therapeutic benefits.However,due to the lack of sufficient clinical data,the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear.This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM.Methods:This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM.Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group(n=19),while those not treated with tofacitinib were allocated to the control group(n=17).The study compared clinical characteristics,laboratory findings,and imaging results between the two groups.Additionally,follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients.The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University(Approval Number:B2021-275R).This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration.Results:Compared to the control group,and with no significant difference in the cumulative dose and duration of corticosteroids(P＜0.05),the tofacitinib group showed a shorter myocarditis recovery time(median recovery time:86.5 days vs 126.5 days,P=0.021).The myocarditis-related mortality rate was significantly lower in the tofacitinib group than in the control group(5%vs 35%,P=0.025).Conclusion:Tofacitinib may reduce mortality and promote cardiac recovery in srICIAM patients without impeding the anti-tumor effect.It may become one of the potential treatment strategies in the future.

Background and purpose:Deep learning methods can be used for automatic segmentation and detection of lymphocytes on pathological images.This study aimed to assess the performance of using variational autoencoding pre-training method for lymphocyte infiltration detection on pathological images,as well as the impact of removing tumor necrosis regions on model performance.Methods:Using variational autoencoding(VAE)pre-training method,pre-training was performed on a large number of unlabeled pathological images from the Cancer Genome Atlas(TCGA)database(TCGA-COAD and TCGA-READ)to obtain an auto-encoding pre-training model,and then a classifier model of lymphocyte infiltration was trained on the public data samples.To avoid confusion with necrotic regions,a Unet segmentation model for tumor necrotic regions was trained to remove the influence of tumor necrotic regions on lymphocyte identification.Results:The lymphocyte infiltration detection model pre-trained with the VAE model had an area under curve(AUC)of 0.979(95%CI:0.978-0.980),an accuracy of 92.5%(95%CI:92.3%-92.6%),a kappa value of 0.849,sensitivity of 0.908,specificity of 0.941,precision of 0.939,recall of 0.908,and F1 of 0.923 under the receiver operating characteristic(ROC)curve on the training set.The AUC for the validation set was 0.968(95%CI:0.964-0.972),the accuracy was 91.3%(95%CI:90.6%-92.0%),kappa value was 0.826,sensitivity was 0.898,specificity was 0.928,precision was 0.925,recall was 0.898,and F1 was 0.912.The results of Resnet18 model on the labeled dataset were as follows:accuracy of the validation set was 83.2%(95%CI:82.2%-84.1%),kappa value was 0.664,sensitivity was 0.823,specificity was 0.840,precision was 0.838,recall was 0.823 and F1 was 0.830.The Unet model that segmented the necrotic regions of the tumors had a final DICE of 0.78 for the training set,and 0.76 for the validation.After removing the necrotic region,the predictive performance of the pre-trained lymphocyte infiltration detection model using the VAE proposed in this article was improved to some extent,with the AUC on the validation set increasing from 0.968(95%CI:0.964-0.972)to 0.971(95%CI:0.968-0.975).The accuracy was 92.4%(95%CI:91.7%-93.0%),kappa value was 0.849,sensitivity was 0.928,specificity was 0.921,precision was 0.921,recall was 0.928,and F1 was 0.925.Conclusion:Using the variational autoencoding model pre-training method to classify the pathological pictures of lymphocyte infiltration can obtain better model performance compared with direct training,and removing the influence of tumor necrosis areas through Unet can further improve the performance of the model.

Head and neck squamous cell carcinoma(HNSCC)is the most common head and neck tumor,characterized by high morbidity and high mortality.Since pembrolizumab and nivolumab were approved for the first line and platinum-refractory disease treatment of HNSCC,immunotherapy has become the standard of care for recurrent/metastatic(R/M)HNSCC.With the wide clinical application of immune checkpoint inhibitors,clinical guidance is needed on the use of these agents,including biomarker testing,appropriate patient selection,response assessment and adverse event management.To better guide the clinical treatment of R/M HNSCC patients on immune checkpoint inhibitors,the Chinese Society of Clinical Oncology(CSCO)and the China Anti-Cancer Association(CACA)convened an expert task force charged with developing consensus recommendations on these key aspects.This consensus serves as a guidance to standardize utilization of immunotherapy in HNSCC and to optimize clinical practice.After several rounds of discussion,the expert task force generated the following consensus recommendations.Programmed death-ligand 1(PD-L1)expression is a predictive biomarker of anti-programmed death-1(PD-1)first-line therapy for R/M HNSCC patients.It is recommended to routinely perform PD-L1 combined positive score(CPS)testing in patients before treatment.Pembrolizumab monotherapy or pembrolizumab in combination with platinum and 5-FU is recommended as first-line treatment for R/M HNSCC patients with PD-L1 CPS≥1.There is a need for a comprehensive consideration of PD-L1 CPS score(e.g.,if CPS≥20),tumor burden and clinical symptoms when those patients are treated with pembrolizumab monotherapy or pembrolizumab combination regimen.Pembrolizumab in combination with platinum and 5-FU could be the first-line treatment option for R/M HNSCC patients with PD-L1 unknown or PD-L1 CPS<1.Pembrolizumab in combination with platinum and taxane could be the first-line treatment option for patients who are intolerant of 5-FU.Nivolumab or pembrolizumab is recommended as the late-line treatment for platinum-resistant patients or patients who are platinum-refractory and have not previously received PD-1 inhibitors in R/M setting.For patients who are intolerant of chemotherapy and unsuitable for PD-1 inhibitor monotherapy,pembrolizumab or nivolumab in combination with cetuximab can be the treatment option as first-line or late-line therapy.For patients treated with immune checkpoint inhibitors,it is recommended to closely monitor the signs of adverse events during the whole course of treatment and use the multidisciplinary team(MDT)for treatment strategy if necessary.

Background and purpose:Long noncoding RNA(lncRNA)can regulate gene transcription,mRNA shear,stabilization and translation,and it is an important regulatory factor in a variety of biological processes.This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma(OSCC)and its effect on the malignant biological behavior of OSCC.Methods:The expression of FLJ30679 in head and neck squamous cell carcinoma(HNSCC)tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis.The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays.FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group(SS-FLJ30679),and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group(FLJ30679).The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition(EMT)-related genes in OSCC cells.The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase(AKT)pathway were detected by Western blot.Results:Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues(P＜0.01).HNSCC patients with higher FLJ30679 expression had lower overall survival(P＜0.01).The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells,and was predominantly localized in the nucleus.The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group(P＜0.01).OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group(P＜0.001).RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin(P＜0.01)and downregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.01).FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin(P＜0.01)and upregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.05).Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT)(P＜0.001),and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT(P＜0.01).Conclusion:The expression of FLJ30679 was increased in OSCC tissues and cells.It promoted the proliferation and migration ability of OSCC cells,which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway.