To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic p...To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.展开更多
Background: Intussusception is defined as a telescoping of a proximal gastrointestinal segment with its mesentery to a distal one, only 5% occur in adults and in colon the probability that it is caused by a malignant ...Background: Intussusception is defined as a telescoping of a proximal gastrointestinal segment with its mesentery to a distal one, only 5% occur in adults and in colon the probability that it is caused by a malignant disease is up to 65%. Only 1% occurs in a retrograde manner, the rest occur in an anterograde manner. Aim: Describe the clinical presentation of an intussusception in the adult patient as well as its most frequent causes and possible complications that influence decision making for a definitive treatment. Case Presentation: A 66-year-old woman diagnosed with colon adenocarcinoma who underwent elective transverse colectomy and colonic anastomosis with an incidental finding of a transverse colon tumor in a retrograde intussusception was studied. Conclusion: In any adult patient with an intussusception especially in colon a neoplasia should be suspected and the affected segment should be resected without being reduced due to the risk of perforation and tumor dissemination.展开更多
Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This ty...Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.展开更多
The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the c...The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.展开更多
BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.The...BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.展开更多
BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary r...BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.展开更多
Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence...Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.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 Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinom...BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.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 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 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
BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop ...BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.展开更多
BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortali...BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.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 Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocar-cinoma(PDAC),although tumor recurrence,especially l...BACKGROUND Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocar-cinoma(PDAC),although tumor recurrence,especially locally,still inhibits the treatment efficacy.The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC.However,there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC.PDAC.METHODS Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study.All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure.Baseline characteristics,surgical data,and postoperative morbidities were recorded.All of the patients were followed up,and the date and location of tumor recurrence,and death were recorded.The Kaplan-Meier method and log-rank test were used for the survival analysis.RESULTS There were 93 patients included in the study and 37 underwent the TRIANGLE technique.Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group[440(410-480)min vs 320(265-427)min](P=0.001).Intraoperative blood loss[700(500-1200)mL vs 500(300-800)mL](P=0.009)and blood transfusion[975(0-1250)mL vs 400(0-800)mL](P=0.009)were higher in the PDTRIANGLE group.There was a higher incidence of surgical site infection(43.2%vs 12.5%)(P=0.001)and postoperative diarrhea(54.1%vs 12.5%)(P=0.001)in the PDTRIANGLE group.The rates of R0 resection and local recurrence,overall survival,and disease-free survival did not differ significantly between the two groups.CONCLUSION The TRIANGLE technique is safe,with acceptable postoperative morbidities compared with standardized PD,but it does not improve prognosis for patients with resectable PDAC.展开更多
BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the r...BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.展开更多
BACKGROUND Pituitary gland metastasis is an unusual event,and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis.To date,approximately 15 cases have been reported.CASE S...BACKGROUND Pituitary gland metastasis is an unusual event,and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis.To date,approximately 15 cases have been reported.CASE SUMMARY Here,we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma,which was difficult to distinguish from other sellar tumors.The patient presented to the neurosurgery clinic with blurred vision and intermittent headache.During hospitalization,brain computed tomography(CT)and magnetic resonance imaging revealed a pituitary macroadenoma.Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung,which were likely lung cancer.Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region,which was considered malignant.Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma.CONCLUSION Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.展开更多
Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
基金The study was supported by a grant from Zhejiang Provincial Natural Science Foundation(LGF21H190004).
文摘To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.
文摘Background: Intussusception is defined as a telescoping of a proximal gastrointestinal segment with its mesentery to a distal one, only 5% occur in adults and in colon the probability that it is caused by a malignant disease is up to 65%. Only 1% occurs in a retrograde manner, the rest occur in an anterograde manner. Aim: Describe the clinical presentation of an intussusception in the adult patient as well as its most frequent causes and possible complications that influence decision making for a definitive treatment. Case Presentation: A 66-year-old woman diagnosed with colon adenocarcinoma who underwent elective transverse colectomy and colonic anastomosis with an incidental finding of a transverse colon tumor in a retrograde intussusception was studied. Conclusion: In any adult patient with an intussusception especially in colon a neoplasia should be suspected and the affected segment should be resected without being reduced due to the risk of perforation and tumor dissemination.
文摘Dear Editor,Lung adenocarcinoma with choroidal metastasis is a common form of cancer,with breast cancer accounting for 40%-53%and lung cancer accounting for 20%-29%of primary cases with choroidal metastases[1].This type of metastatic cancer typically affects people aged 40-70y,and is more prevalent in women than men[1].Ocular symptoms,including vision loss,can be an early indication of the disease,as many tumors are asymptomatic in their early stages.Studies have shown that 40.3%of cases involve the macular region,which explains why ocular symptoms are often the first manifestation of the disease[2].When choroidal metastasis is suspected in patients without a history of cancer,a combination of diagnostic tools should be used to identify the primary source of the tumor.Choroidal tumors can serve as an indication of future lung cancer diagnosis in some patients with lung cancer[1].In this report,we present a case of bilateral lung adenocarcinoma where ocular symptoms were the first indication of the disease.
基金supported by the National Natural Science Foundation of China(No.81703001)the Natural Science Foundation of Hebei Province(No.H2021406021),Hebei Province Medical Science Research Project(Nos.20210247,20221335)Hebei Province Government-Funded Clinical Medical Outstanding Talents Project,Chengde Medical University Scientific Research Major Projects(No.KY2020005).
文摘The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
文摘BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.
基金Supported by National Natural Science Foundation of China,No.82172737Shanghai Science and Technology Development Funds(Shanghai Sailing Program),No.22YF1427600。
文摘BACKGROUND Lactate,previously considered a metabolic byproduct,is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment.Further investigations confirmed that lactate is a primary regulator,introducing recently described post-translational modifications of histone and non-histone proteins,termed lysine lactylation.Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation.However,our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.AIM To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.METHODS RNA-seq and clinical data of pancreatic adenocarcinoma(PDAC)were obtained from the GTEx(Genotype-Tissue Expression)and TCGA(The Cancer Genome Atlas)databases via Xena Explorer,and GSE62452 datasets from GEO.Data on lactylation-related genes were obtained from publicly available sources.Differential expressed genes(DEGs)were acquired by using R package“DESeq2”in R.Univariate COX regression analysis,LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model.Further analyses,including functional enrichment,ESTIMATE,and CIBERSORT,were performed to analyze immune status and treatment responses in patients with pancreatic cancer.PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention;two PDAC cell lines with the most pronounced lactylation were selected.Subsequently,RT-PCR was employed to assess the expression of LRGs genes;SLC16A1,which showed the highest expression,was selected for further investigation.SLC16A1-mediated lactylation was analyzed by immunofluorescence,lactate production analysis,colony formation,transwell,and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells.In vivo validation was performed using an established tumor model.RESULTS In this study,we successfully identified 10 differentially expressed lactylation-related genes(LRGs)with prognostic value.Subsequently,a lactylation-related signature was developed based on five OS-related lactylationrelated genes(SLC16A1,HLA-DRB1,KCNN4,KIF23,and HPDL)using Lasso Cox hazard regression analysis.Subsequently,we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma.A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups.Furthermore,we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport.Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression,indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.CONCLUSION We constructed a novel lactylation-related prognostic signature to predict OS,immune status,and treatment response of patients with pancreatic adenocarcinoma,providing new strategic directions and antitumor immunotherapies.
文摘Studies reporting the Indian prevalence of Epidermal Growth Factor Receptor (EGFR) mutation are mostly single centers with small sample sizes. This systematic review and meta-analysis summarized the available evidence of EGFR mutation epidemiology in Indian patients with adenocarcinoma (ADC) Non-Small Cell Lung Cancer (NSCLC). We conducted a structured literature search in PubMed, and EMBASE databases from January 2004 through October 2019. The primary outcome of interest was prevalence of EGFR mutation by gender, smoking status, and mutation subtype. The review included 34 studies. EGFR mutation prevalence was 39.5% in patients with ADC, and significantly higher in females, non-smokers, and patients with exon 19 deletions. The EGFR mutation frequency in Indian patients with ADC was higher than reported in Caucasians but at a lower range of that reported in East Asians. These findings support the use of EGFR mutation testing to guide choice of treatment.
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.
基金The study protocol was reviewed and approved by the Institutional Research Committee,Faculty of Medicine,Chulalongkorn University(No.0482/65)registered in the Thai Clinical Trials Registry(TCTR20211109002).
文摘BACKGROUND Volatile organic compounds(VOCs)are a promising potential biomarker that may be able to identify the presence of cancers.AIM To identify exhaled breath VOCs that distinguish pancreatic ductal adenocar-cinoma(PDAC)from intraductal papillary mucinous neoplasm(IPMN)and healthy volunteers.METHODS We collected exhaled breath from histologically proven PDAC patients,radiological diagnosis IPMN,and healthy volunteers using the ReCIVA®device between 10/2021-11/2022.VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups.RESULTS A total of 156 participants(44%male,mean age 62.6±10.6)were enrolled(54 PDAC,42 IPMN,and 60 controls).Among the nine VOCs identified,two VOCs that showed differences between groups were dimethyl sulfide[0.73 vs 0.74 vs 0.94 arbitrary units(AU),respectively;P=0.008]and acetone dimers(3.95 vs 4.49 vs 5.19 AU,respectively;P<0.001).After adjusting for the imbalance parameters,PDAC showed higher dimethyl sulfide levels than the control and IPMN groups,with adjusted odds ratio(aOR)of 6.98(95%CI:1.15-42.17)and 4.56(1.03-20.20),respectively(P<0.05 both).Acetone dimer levels were also higher in PDAC compared to controls and IPMN(aOR:5.12(1.80-14.57)and aOR:3.35(1.47-7.63),respectively(P<0.05 both).Acetone dimer,but not dimethyl sulfide,performed better than CA19-9 in PDAC diagnosis(AUROC 0.910 vs 0.796).The AUROC of acetone dimer increased to 0.936 when combined with CA19-9,which was better than CA19-9 alone(P<0.05).CONCLUSION Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants.Additional prospective studies are required to validate these findings.
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.
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.
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.
文摘BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.
文摘BACKGROUND Gastric cancer is the third most common cause of cancer related death worldwide.Surgery with or without chemotherapy is the most common approach with curative intent;however,the prognosis is poor as mortality rates remain high.Several indexes have been proposed in the past few years in order to estimate the survival of patients undergoing gastrectomy.The preoperative nutritional status of gastric cancer patients has recently gained attention as a factor that could affect the postoperative course and various indexes have been developed.The aim of this systematic review was to assess the role of the prognostic nutritional index(PNI)in predicting the survival of patients with gastric or gastroesophageal adenocarcinoma who underwent gastrectomy with curative intent.AIM To investigate the role of PNI in predicting the survival of patients with gastric or gastroesophageal junction adenocarcinoma.METHODS A thorough literature search of PubMed and the Cochrane library was performed for studies comparing the overall survival(OS)of patients with gastric or gastroesophageal cancer after surgical resection depending on the preoperative PNI value.The PRISMA algorithm was used in the screening process and finally 16 studies were included in this systematic review.The review protocol was registered in the International Prospective Register of Systematic Reviews(PRO) RESULTS Sixteen studies involving 14551 patients with gastric or esophagogastric junction adenocarcinoma undergoing open or laparoscopic or robotic gastrectomy with or without adjuvant chemotherapy were included in this systematic review.The patients were divided into high-and low-PNI groups according to cut-off values that were set according to previous reports or by using receiver operating characteristic curve analysis in each individual study.The 5-year OS of patients in the low-PNI groups ranged between 39%and 70.6%,while in the high-PNI groups,it ranged between 54.9%and 95.8%.In most of the included studies,patients with high preoperative PNI showed statistically significant better OS than the low PNI groups.In multivariate analyses,low PNI was repeatedly recognised as an independent prognostic factor for poor survival.CONCLUSION According to the present study,low preoperative PNI seems to be an indicator of poor OS of patients undergoing gastrectomy for gastric or gastroesophageal cancer.
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.
基金Supported by the National Natural Science Foundation of China,No.31971518.
文摘BACKGROUND Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocar-cinoma(PDAC),although tumor recurrence,especially locally,still inhibits the treatment efficacy.The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC.However,there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC.PDAC.METHODS Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study.All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure.Baseline characteristics,surgical data,and postoperative morbidities were recorded.All of the patients were followed up,and the date and location of tumor recurrence,and death were recorded.The Kaplan-Meier method and log-rank test were used for the survival analysis.RESULTS There were 93 patients included in the study and 37 underwent the TRIANGLE technique.Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group[440(410-480)min vs 320(265-427)min](P=0.001).Intraoperative blood loss[700(500-1200)mL vs 500(300-800)mL](P=0.009)and blood transfusion[975(0-1250)mL vs 400(0-800)mL](P=0.009)were higher in the PDTRIANGLE group.There was a higher incidence of surgical site infection(43.2%vs 12.5%)(P=0.001)and postoperative diarrhea(54.1%vs 12.5%)(P=0.001)in the PDTRIANGLE group.The rates of R0 resection and local recurrence,overall survival,and disease-free survival did not differ significantly between the two groups.CONCLUSION The TRIANGLE technique is safe,with acceptable postoperative morbidities compared with standardized PD,but it does not improve prognosis for patients with resectable PDAC.
文摘BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.
文摘BACKGROUND Pituitary gland metastasis is an unusual event,and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis.To date,approximately 15 cases have been reported.CASE SUMMARY Here,we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma,which was difficult to distinguish from other sellar tumors.The patient presented to the neurosurgery clinic with blurred vision and intermittent headache.During hospitalization,brain computed tomography(CT)and magnetic resonance imaging revealed a pituitary macroadenoma.Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung,which were likely lung cancer.Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region,which was considered malignant.Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma.CONCLUSION Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.