BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyr...BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.展开更多
This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers...This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.展开更多
BACKGROUND Lung cancer is the most prevalent malignant tumor in human body,and is characterized by a high level of malignancy.The most common metastatic sites include the liver,bone,brain,and adrenal gland,while lung ...BACKGROUND Lung cancer is the most prevalent malignant tumor in human body,and is characterized by a high level of malignancy.The most common metastatic sites include the liver,bone,brain,and adrenal gland,while lung cancer resulting in gastrointestinal tract metastasis is uncommon.CASE SUMMARY A 74-years-old man with lung cancer was hospitalized owing to blood in the stool,The cause was identified as metastasis to the small intestine,and the patient subsequently underwent radical resection of the small intestine tumor.Currently,the overall condition of the patient is good,and undergoing combined chemotherapy.CONCLUSION Early intervention in patients with metastatic tumors can significantly improve prognosis.展开更多
BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on lo...BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on long-term survival and the impact of tumor characteristics,surgery,and adjuvant therapy.AIM To bridge this knowledge gap,we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA,along with analyzing the impact of the tumor characteristics,operations and adjuvant therapy on survival outcomes.METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed.This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics,clinical presentation,treatment modalities,and survival outcomes.The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival(OS)and disease-free survival was evaluated using Kaplan-Meier survival curves,the Cox proportional hazards model,and statistical comparisons of survival distributions.RESULTS The median OS time for the cohort was 39 months,with 3-and 5-year OS rates of 51.2%and 43.6%,respectively.Radical resection was performed in 82.6%of cases,and was significantly associated with an improved 5-year OS,with a rate of 57.8%.Adjuvant therapy showed a survival benefit in the specific patient subsets,particularly in tumor stage Ⅱ or Ⅲ tumors,with an improved OS.Adjuvant therapy(hazard ratio=2.71,95%confidence interval:1.30-5.62,P=0.008),pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS.Importantly,postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation,especially in patients with stage III.It highlights the necessity for early diagnosis,tailored surgical approaches,and a nuanced understanding of the role of adjuvant therapy.展开更多
In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients c...In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.展开更多
BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antig...BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.展开更多
Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer...Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.展开更多
BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC...BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.展开更多
Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE ca...BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.展开更多
Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of ...Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.展开更多
BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the dia...BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.展开更多
BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-yea...BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.展开更多
Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)...Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.展开更多
BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metas...BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on ba...BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.展开更多
In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction.Mixed neuroendocrine and non-neuroendocrine neoplasms of the ga...In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction.Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor prognosis.Due to the rarity of these cancers,the standard therapy is poorly defined.The diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell markers.Both endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is required.These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response.Regardless of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine component.Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes.The etiopathogenesis of these mixed tumors remains obscure but poses interesting question.We briefly discuss a few salient points in this editorial.展开更多
BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung can...BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.展开更多
In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two mai...In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two main classifications:Lauren’s and the World Health Organization distinguishing the diverse types of GA depending on clinical,genetic,morphological and epidemiological features.“Crawling-type”adenocarcinoma(CRA)is a subtype characterized by irregularly fused glands with low-grade cellular atypia.Moreover,CRA represents differentiated tumor cells resembling intestinal metaplasia which results in misdiagnosis.The diagnosis is of utmost importance,as well as the subclassification and thorough pathological assessment.With regard to the symptoms of GA,these depend on the stage of the disease.Diagnostic methods play a crucial role in assessing the extent of the tumor and the stage of the disease.Nevertheless,early detection of CRA remains challenging due to its histological features.In summary,CRA is a distinct type of GA with particular clinicopathological and histological characteristics.Despite its significance,it not distinguished as a subtype,resulting in diagnostic challenges.Diagnosis is based on careful observation and thorough biopsy analysis,indicating the importance of comprehensive pathological assessment.展开更多
基金Supported by Guangxi Guilin Science and Technology Fund,No.20190218-7-6.
文摘BACKGROUND Most non-small cell lung cancer patients have epidermal growth factor receptor(EGFR)activating mutations,such as exon 19 deletion and exon 21 replacement mutations.Osimertinib is a third-generation EGFR-tyrosine kinase inhibitors ap-proved for the treatment of lung cancer patients carrying EGFR activating mu-tations.Osimertinib-induced interstitial lung disease(ILD)is a rare and poten-tially fatal pulmonary toxic manifestation of drug therapy.At present,there is no international consensus on the risks and treatment of the osimertinib-induced ILD.CASE SUMMARY We report a case of a 56-year-old woman who was diagnosed with lung adenocar-cinoma with lung hilum,mediastinal lymph nodes and brain metastases(T4N3-M1c stage IVB).The patient received targeted treatment with osimertinib after radiotherapy and chemotherapy.But she developed ILD after osimertinib treat-ment.Following active symptomatic treatment and hormone treatment,the lung injury alleviated.The patient was retreated with furmonertinib combined with prednisone and did not experience ILD again.So far,she has survived for 14 months without disease progression.CONCLUSION Retreatment with furmonertinib under prednisone could be considered as an effective therapeutic option after risk-benefit assessment for EGFR-mutant lung adenocarcinoma patients.
文摘This article discusses the coexistence of prostate adenocarcinoma and prostate urothelial carcinoma.Combining existing literature and research results,the potential mechanisms of the co-occurrence of these two cancers are explored,including the role of androgen receptor,gene mutations,and their complex interactions in cell signaling pathways,etc.Also,the hypothesis of prostate cancer transformation into urothelial carcinoma is explained from some perspectives,including tumor multipotent stem cell differentiation,epithelial-mesenchymal transition,mesenchymal-epithelial transition,and other mechanisms.Ultimately,the goal is to provide more accurate diagnoses and more personalized treatments in clinical practice,as well as to lay the foundation for improving patient prognoses in the future.
文摘BACKGROUND Lung cancer is the most prevalent malignant tumor in human body,and is characterized by a high level of malignancy.The most common metastatic sites include the liver,bone,brain,and adrenal gland,while lung cancer resulting in gastrointestinal tract metastasis is uncommon.CASE SUMMARY A 74-years-old man with lung cancer was hospitalized owing to blood in the stool,The cause was identified as metastasis to the small intestine,and the patient subsequently underwent radical resection of the small intestine tumor.Currently,the overall condition of the patient is good,and undergoing combined chemotherapy.CONCLUSION Early intervention in patients with metastatic tumors can significantly improve prognosis.
基金Supported by Natural Science Foundation of Guangdong Province of China,No.2023A1515010785Key Clinical Technique of Guangzhou,No.2023P-ZD01Clinical Research Program of Nanfang Hospital,Southern Medical University,No.2021CR003.
文摘BACKGROUND Duodenal adenocarcinoma(DA),a rare gastrointestinal malignancy,lacks clear natural history and management strategies.This study aimed to investigate the long-term outcomes of patients with DA,focusing on long-term survival and the impact of tumor characteristics,surgery,and adjuvant therapy.AIM To bridge this knowledge gap,we conducted a hospital-based cohort study in our 15-year experience with DA aimed at investigating the long-term outcomes of the patients with DA,along with analyzing the impact of the tumor characteristics,operations and adjuvant therapy on survival outcomes.METHODS A retrospective analysis of 208 patients diagnosed with non-ampullary DA at a single institution between 2009 and 2023 was performed.This study used SPSS 26.0 software to make a comprehensive statistical analysis of demographic characteristics,clinical presentation,treatment modalities,and survival outcomes.The effectiveness of surgical resection and adjuvant therapy in 5-year oval survival(OS)and disease-free survival was evaluated using Kaplan-Meier survival curves,the Cox proportional hazards model,and statistical comparisons of survival distributions.RESULTS The median OS time for the cohort was 39 months,with 3-and 5-year OS rates of 51.2%and 43.6%,respectively.Radical resection was performed in 82.6%of cases,and was significantly associated with an improved 5-year OS,with a rate of 57.8%.Adjuvant therapy showed a survival benefit in the specific patient subsets,particularly in tumor stage Ⅱ or Ⅲ tumors,with an improved OS.Adjuvant therapy(hazard ratio=2.71,95%confidence interval:1.30-5.62,P=0.008),pancreatic invasion and advanced tumor stage were identified as significant predictors of OS in multivariate analyses.CONCLUSION Radical operation for DA is associated with a remarkable improvement in the 5-year OS.Importantly,postoperative adjuvant therapy can significantly prolong the OS time in patients with radical operation,especially in patients with stage III.It highlights the necessity for early diagnosis,tailored surgical approaches,and a nuanced understanding of the role of adjuvant therapy.
文摘In a recent study by He et al,the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen,thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers,which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer.However,the study’s single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias.Future studies could consider additional confounding factors,such as adjuvant chemotherapy and variations in surgical techniques,to improve the model’s accuracy.Furthermore,it would be valuable to validate the nomogram in broader,prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.
文摘BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.
文摘Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell proliferation.Ki-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine tumors.However,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains uncertain.Methods:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were examined.Grade of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was evaluated.Results:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and RFS.The GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic factors.The tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and RFS.Conclusions:Ki-67 is a valuable prognostic indicator for PDAC.Inclusion of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.
基金Supported by the Songjiang District Tackling Key Science and Technology Research Projects,No.20sjkjgg32Excellent Young Talents Training Program of Songjiang Hospital Affiliated with Shanghai Jiao Tong University School of Medicine,No.QNRC-004Science and Technology project of Songjiang District,No.22SJKJGG81.
文摘BACKGROUND Gastric cancer(GC)is a significant health problem worldwide,and early detection and accurate diagnosis are crucial for improving patient outcomes.Crawling-type gastric adenocarcinoma is a rare subtype of GC that has unique histopathological and clinical characteristics,and its diagnosis and management can be challenging.This pathological type of GC is also rare.CASE SUMMARY Here,we report the case of a patient who underwent ordinary endoscopy,na-rrow-band imaging,and endoscopic ultrasonography intending to determine the extent of tumor invasion and upper abdominal enhanced computed tomography and whether there was tumor metastasis.Then,endoscopic submucosal dissection was performed.After pathological and immunohistochemical examination,the pathological diagnosis was crawling-type gastric adenocarcinoma.This is a very rare and special pathological type of tumor.This case highlights the importance of using advanced endoscopic techniques and pathological examination in diagnosing and managing gastric crawling-type adenocarcinoma.Moreover,the findings underscore the need for continued research and clinical experience in this rare subtype of GC to improve patient outcomes.CONCLUSION The“crawling-type”GC is a rare and specific tumor pathology.It is difficult to identify and diagnose gliomas via endoscopy.The tumor is ill-defined,with a flat appearance and indistinct borders due to the lack of contrast against the background mucosa.Pathology revealed that the tumor cells were hand-like,so the patient has diagnosed with“crawling-type”gastric adenocarcinoma.
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
基金The Health Science and Technology Foundation of Inner Mongolia,No.202201436Science and Technology Innovation Foundation of Inner Mongolia,No.CXYD2022BT01.
文摘BACKGROUND In recent years,confocal laser endomicroscopy(CLE)has become a new endoscopic imaging technology at the microscopic level,which is extensively performed for real-time in vivo histological examination.CLE can be performed to distinguish benign from malignant lesions.In this study,we diagnosed using CLE an asymptomatic patient with poorly differentiated gastric adenocarcinoma.CASE SUMMARY A 63-year-old woman was diagnosed with gastric mucosal lesions,which may be gastric cancer,in the small curvature of the stomach by gastroscopy.She consented to undergo CLE for morphological observation of the gastric mucosa.Through the combination of CLE diagnosis and postoperative pathology,the intraoperative CLE diagnosis was considered to be reliable.According to our experience,CLE can be performed as the first choice for the diagnosis of gastric cancer.CONCLUSION CLE has several advantages over pathological diagnosis.We believe that CLE has great potential in the diagnosis of benign and malignant gastric lesions.
文摘Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.
文摘BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.
基金Changzhou High-level Medical Talents Training Project of the Health Commission of the Changzhou City,No.2022CZBJ079Changzhou Sci&Tech Program,No.CE20235064.
文摘BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.
文摘Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.
文摘BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
文摘BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.
文摘In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal junction.Mixed neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor prognosis.Due to the rarity of these cancers,the standard therapy is poorly defined.The diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell markers.Both endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is required.These cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and response.Regardless of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine component.Multidisciplinary services and strategies are required for the management of these mixed malignancies to provide the best oncological outcomes.The etiopathogenesis of these mixed tumors remains obscure but poses interesting question.We briefly discuss a few salient points in this editorial.
文摘BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)significantly improve the survival of patients with Epidermal growth factor receptor(EGFR)sensitive mutations in non-small cell lung cancer(NSCLC).CASE SUMMARY A 67-year-old female patient in advanced lung adenocarcinoma suffered from drug resistance after EGFR-TKIs treatment.Secondary pathological tissue biopsy confirmed squamous cell carcinoma(SCC)transformation.Patients inevitably encountered drug resistance issues after receiving EGFR-TKIs treatment for a certain period of time,while EGFR-TKIs can significantly improve the survival of patients with EGFR-sensitive mutations in NSCLC.Notably,EGFR-TKIs resistance includes primary and acquired.Pathological transformation is one of the mechanisms of acquired resistance in EGFR-TKIs,with SCC transformation being relatively rare.Our results provide more detailed results of the patient’s diagnosis and treatment process on SCC transformation after EGFR-TKIs treatment for lung adenocarcinoma.CONCLUSION Squamous cell carcinoma transformation is one of the acquired resistance mechanisms of EGFR-TKIs in advanced lung adenocarcinoma with EGFR mutations.
文摘In this editorial we comment on the article by Xu et al.Gastric adenocarcinoma(GA)is a malignancy which arises from the gastric mucosa and encompasses heterogenous tumors with varying characteristics.There are two main classifications:Lauren’s and the World Health Organization distinguishing the diverse types of GA depending on clinical,genetic,morphological and epidemiological features.“Crawling-type”adenocarcinoma(CRA)is a subtype characterized by irregularly fused glands with low-grade cellular atypia.Moreover,CRA represents differentiated tumor cells resembling intestinal metaplasia which results in misdiagnosis.The diagnosis is of utmost importance,as well as the subclassification and thorough pathological assessment.With regard to the symptoms of GA,these depend on the stage of the disease.Diagnostic methods play a crucial role in assessing the extent of the tumor and the stage of the disease.Nevertheless,early detection of CRA remains challenging due to its histological features.In summary,CRA is a distinct type of GA with particular clinicopathological and histological characteristics.Despite its significance,it not distinguished as a subtype,resulting in diagnostic challenges.Diagnosis is based on careful observation and thorough biopsy analysis,indicating the importance of comprehensive pathological assessment.