The role of intestinal flora on tumorigenesis,progression,and the efficacy of PD-1/PD-L1 antibodies in colorectal cancer

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR CRC.In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients.Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC.Herein,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies.In addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

Artificial intelligence-driven radiomics study in cancer:the role of feature engineering and modeling

Modern medicine is reliant on various medical imaging technologies for non-invasively observing patients’anatomy.However,the interpretation of medical images can be highly subjective and dependent on the expertise of clinicians.Moreover,some potentially useful quantitative information in medical images,especially that which is not visible to the naked eye,is often ignored during clinical practice.In contrast,radiomics performs high-throughput feature extraction from medical images,which enables quantitative analysis of medical images and prediction of various clinical endpoints.Studies have reported that radiomics exhibits promising performance in diagnosis and predicting treatment responses and prognosis,demonstrating its potential to be a non-invasive auxiliary tool for personalized medicine.However,radiomics remains in a developmental phase as numerous technical challenges have yet to be solved,especially in feature engineering and statistical modeling.In this review,we introduce the current utility of radiomics by summarizing research on its application in the diagnosis,prognosis,and prediction of treatment responses in patients with cancer.We focus on machine learning approaches,for feature extraction and selection during feature engineering and for imbalanced datasets and multi-modality fusion during statistical modeling.Furthermore,we introduce the stability,reproducibility,and interpretability of features,and the generalizability and interpretability of models.Finally,we offer possible solutions to current challenges in radiomics research.

Microbiome changes in esophageal cancer:implications for pathogenesis and prognosis

Esophageal cancer(EC)is an aggressive malignancy with a poor prognosis.Various factors,including dietary habits,and antacid and antibiotic use,have been shown to influence the esophageal microbiome.Conversely,enrichment and diversity of the esophageal microbiome can also impact its function.Recent studies have revealed prevalent changes in the esophageal microbiome among patients with EC,thus suggesting the potential contribution of the esophageal microbiome to EC development.Additionally,distinct microbiome compositions have been observed in patients with different responses to radiotherapy and chemotherapy,indicating the role of the esophageal microbiome in modulating treatment outcomes.In this review,we have examined previous studies on the esophageal microbiome in healthy individuals and patients with EC or other esophageal diseases,with a focus on identifying microbial communities associated with EC pathogenesis and prognosis.Understanding the role of the microbiome in EC may aid in early detection and optimized treatment strategies,ultimately leading to better outcomes for patients.

First-line immunotherapy for advanced non-small cell lung cancer:current progress and future prospects

Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.

Humanβ-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long noncoding RNA TCONS_00014506

BACKGROUND Colorectal cancer has a low 5-year survival rate and high mortality.Humanβ-defensin-1(hBD-1)may play an integral function in the innate immune system,contributing to the recognition and destruction of cancer cells.Long non-coding RNAs(lncRNAs)are involved in the process of cell differentiation and growth.AIM To investigate the effect of hBD-1 on the mammalian target of rapamycin(mTOR)pathway and autophagy in human colon cancer SW620 cells.METHODS CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration.Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation.Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway.Additionally,p-mTOR(Ser2448),Beclin1,and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.RESULTS hBD-1 inhibited the proliferative ability of SW620 cells,as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1.hBD-1 decreased the expression of p-mTOR(Ser2448)protein and increased the expression of Beclin1 and LC3II/I protein.Furthermore,bioinformatics analysis identified seven lncRNAs(2 upregulated and 5 downregulated)related to the mTOR pathway.The lncRNA TCONS_00014506 was ultimately selected.Following the inhibition of the lncRNA TCONS_00014506,exposure to hBD-1 inhibited p-mTOR(Ser2448)and promoted Beclin1 and LC3II/I protein expression.CONCLUSION hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.

Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice

Gastrointestinal(GI) cancers include esophageal [EC(International Classification of Disease 10^(th) revision: C15)], gastric [GC(C16)], and colorectal [CRC(C18-C21)] cancers. China is a high-incidence country of GI cancers.

Expenditure and financial burden for the diagnosis and treatment of colorectal cancer in China:a hospital.based,multicenter,cross-sectional survey

Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective.

Medical expenditures for colorectal cancer diagnosis and treatment: A 10-year high-level-hospital-based multicenter retrospective survey in China, 2002-2011

Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

BACKGROUND Radical surgery is the most commonly used treatment for hepatocellular carcinoma(HCC).However,the surgical effect remains not ideal,and prognostic evaluation is insufficient.Furthermore,clinical intervention is rife with uncertainty and not conducive to prolonging patient survival.AIM To explore correlations between the systemic immune inflammatory index(SII)and geriatric nutritional risk index(GNRI)and HCC operation prognosis.METHODS This retrospective study included and collected follow up data from 100 HCC.Kaplan–Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival.SII and GNRI were calculated as follows:SII=neutrophil count×platelet count/lymphocyte count;GNRI=[1.489×albumin(g/L)+41.7×actual weight/ideal weight].We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic(ROC)curves,and the relationships between the SII,GNRI,and survival rate using Kaplan–Meier survival curves.Cox regression analysis was utilized to analyze independent risk factors influencing prognosis.RESULTS After 1 year of follow-up,24 patients died and 76 survived.The area under the curve(AUC),sensitivity,specificity,and the optimal cutoff value of SII were 0.728(95%confidence interval:0.600-0.856),79.2%,63.2%,and 309.14,respectively.According to ROC curve analysis results for predicting postoperative death in HCC patients,the AUC of SII and GNRI combination was higher than that of SII or GNRI alone,and SII was higher than that of GNRI(P<0.05).The proportion of advanced differentiated tumors,tumor maximum diameter(5–10 cm,>10 cm),lymph node metastasis,and TNM stage III-IV in patients with SII>309.14 was higher than that in patients with SII≤309.14(P<0.05).The proportion of patients aged>70 years was higher in patients with GNRI≤98 than that in patients with GNRI>98(P<0.05).The 1-year survival rate of the SII>309.14 group(compared with the SII≤309.14 group)and GNRI≤98 group(compared with the GNRI>98 group)was lower(P<0.05).CONCLUSION The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

Nutritional Risk Screening with NRS2002 among Hospitalized Cancer Patients in China

Objective The Nutritional Risk Screening 2002(NRS 2002)was used to assess the nutritional risk of hospitalized oncology patients in China.This study explored the factors affecting the risk of nutrition to provide a scientific basis for the assessment and treatment of malnutrition in oncology patients.Methods We used the NRS 2002 to evaluate the nutritional risk in 48,831 hospitalized cancer patients.Descriptive statistical methods were used to describe the general patient information.A Chi-squared test was applied to analyze the relationship between NRS 2002 scores and different demographic characteristics,and the NRS 2002 scores of cancer patients with different characteristics were compared by one-way ANOVA.Results Among 48,831 patients,43.3%were women and 57.7%were men,and 36.5%(17,802)of patients were at risk of nutrition(score≥3).The NRS 2002 score was the highest in leukemia patients(2.93±1.28).A one-way ANOVA revealed that the differences in NRS 2002 scores among patients of different gender,ages,TNM stages,education levels,occupations and areas of residence were statistically significant(P<0.001).Male patients had slightly higher NRS 2002 scores than females(2.33 vs.2.17).The lowest NRS 2002 scores were in patients aged 45-59(2.00±1.26)years and the highest scores were in patients aged≥70(2.76±1.43)years.The NRS 2002 score of patients receiving surgery was the highest(2.45±1.41),and patients receiving surgery plus radiotherapy/chemotherapy was the lowest(2.00±1.26).The risk of nutrition was highest in patients who were farmers(2.34±1.37 scores)and lowest in office staff(2.15±1.32 scores).Patients living in rural areas had the highest risk of nutrition(2.32±1.37 scores).There were significant differences in the NRS 2002 scores for different cancer sub-types for different ethnic groups(P<0.05),except for Zhuang individuals(P=0.124).The risk of nutrition was highest in Uyghur patients(3.35±1.33 scores)and lowest in Mongolians(2.04±1.37 scores).Conclusion More attention should be paid to people at high risk of nutrition,such as elderly patients,patients with a high TNM stage,patients receiving surgical treatment,and patients living in rural areas.Active nutritional interventions should be carried out to improve the nutritional status of malnourished patients.

Prognostic prediction and expression validation of NSD3 in pan-cancer analyses

Background:Nuclear receptor binding SET domain protein-3(NSD3)is a histone lysine methyltransferase and a crucial regulator of carcinogenesis in several cancers.We aimed to investigate the prognostic value and potential function of NSD3 in 33 types of human cancer.Methods:The data were obtained from The Cancer Genome Atlas.Kaplan-Meier analysis,CIBERSORT,gene set enrichment analysis,and gene set variation analysis were performed.The expression of NSD3 was measured using quantitative real-time polymerase chain reaction and western blot.Results:The expression of NSD3 was altered in pan-cancer samples.Patients with higher levels of NDS3 generally had shorter overall survival and disease-specific survival.Levels of NSD3 were positively correlated with DNA copy number variation(CNV)in pan-cancer.NSD3 expression was also associated with tumor mutation burden and microsatellite instability.The levels of immune-cell infiltration differed significantly between high and low NSD3 expression.NSD3 negatively correlated with levels of CD8+T cells.Functional enrichment analysis showed that while NSD3 expression was positively associated with several immune cell-related and histone methylation-related pathways,it was negatively correlated with cell metabolism-related,drug transport-related,and drug metabolismrelated pathways.NSD3 levels in the cell lines tested were significantly different.In U251 and NCI-H23 cells,silencing NSD3 inhibited cell proliferation and promoted apoptosis.Conclusions:NSD3 expression was changed in pan-cancer samples that was also verified in cell lines.NSD3 was associated with CNV and immune-cell infiltration.A poor prognosis was predicted in patients with high expression of NSD3.NSD3 might hence be a potential marker for predicting tumor prognosis.

YWHAH activates the HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect the proliferation of gastric cancer cells

Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.

Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Ring finger protein 157 is a prognostic biomarker and is associated with immune infiltrates in human breast cancer

Background: The protein encoded by ring finger protein 157 (RNF157) is known to function as an E3 ubiquitinligase. However, whether the level of RNF157 expression in breast cancer correlates with prognosis and immune cellinfiltration among breast cancer patients remains to be further explored. Methods: In this study, publicly availabledatasets were used for evaluating RNF157 expression in different tumors compared with normal samples. Severalindependent datasets were screened for investigating the relationship between RNF157 and breast cancer survival,different mutation profiles, and tumor immune cell infiltration. We conducted a pathway enrichment analysis toidentify signaling pathways associated with RNF157. Results: Analysis of public and online databases revealed thatRNF157 expression markedly decreased in breast cancer tissue samples compared to non-carcinoma counterparts.Consistently, immunohistochemistry assays also demonstrated this RNF157 down-regulation in breast cancer samples.RNF157 up-regulation could predict the improved survival of breast cancer cases. Further, different RNF157expression level groups exhibited different mutational profiles. Pathway enrichment profiling of RNF157-related genessuggested its possible involvement in regulating breast cancer via the mitogen-activated protein kinase (MAPK)pathway. RNA sequencing (RNA-seq) data and genomic enrichment analysis showed that RNF157 downregulatedseveral genes positively associated with the MAPK signaling pathway. We also explored RNF157 expression andimmune cell infiltration in breast cancer and found that RNF157 mRNA levels were negatively related to non-Timmune cell infiltration. Conclusion: According to our work, RNF157 may be a promising diagnostic biomarker andtherapeutic target for breast cancer.

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.

Sex differences in the scored Patient-Generated Subjective Global Assessment in 19,528 cancer patients

Background:The scored Patient-Generated Subjective Global Assessment(PG-SGA)has been widely used to assess the nutritional status of cancer patients.The purpose of this study is to compare the differences in PG-SGA scores and the 7 domain scores of the PG-SGA in male and female cancer patients.Methods:This study was conducted at 72 hospitals from July 2013 to December 2018,a part of the Investigation on Nutritional Status and its Clinical Outcomes of Common Cancers.The PG-SGA was recorded to evaluate the nutritional status of patients.A total of 19,528 patients with 13 common malignancies were included in this study.Student t test and the χ^(2) test were applied to analyze the sex diferences in the 7 domain scores.The Cancer Genome Atlas(TCGA)database was used to analyze the expression levels of symptom-related genes.Results:There were significant sex dfferences in the PG-SGA(P=0.032),notably in patients with gastric cancer(male vs female:9.09±4.86 vs 9.58±5.07,P=0.005)and esophageal cancer(9.64±4.90 vs 10.46±4.96,P=0.011)and the average total PG-SGA of female patients was slightly higher than that of male patients(7.64±4.98 vs 7.77±5.14).The differences were mainly related to the weight,eating,symptom,as well as activity and physical function scores in the stratified analysis.Possible causes of the sex differences were the rates of nausea,vomiting,dry mouth,and other symptoms,in both gastric and esophageal cancer patients.Analysis of the TCGA database suggested that most of the related genes were sex neutral,except for genes related to dysphagia in gastric cancer(VEGFC was higher in female patients,VEGFA and VEGFB higher in male patients).Conclusions:There are sex differences in the PG-SGA scores in patients with various tumor types(female patients generally had higher scores than male patients),with differences mainly in the weight,eating,symptom,as well as activity and physical function scores.The sex differences in PG-SGA scores might be due to the differences in the clinical manifestations of the disease,and further studies should be carried out to investigate other factors influencing the PG-SGA scores in cancer patients.This study provides basic data supporting the individualized nutritional treatment of cancer patients in clinical practice.

基于卡诺模型的社区乳腺癌患者健康服务需求分析

目的为乳腺癌患者提供满意的医疗服务,可有效减轻患者的负担和医疗资源压力。本研究的目的是利用卡诺模型探讨社区乳腺癌患者的健康服务需求。方法2023年1月—3月对某三级肿瘤医院出院的乳腺癌患者进行横断面调查。患者填写了基于卡诺模型自行设计的健康服务需求调查问卷,同时也提供了社会人口学信息。调查问卷中包括30项健康服务内容,基于卡诺模型对这些项目的属性进行分类和优先级排序。结果共回收有效问卷296份。对30项医疗服务的需求属性进行评价的结果显示,30项服务中有1项被归类为“必备型属性”(身体形象管理),13项被归类为“期望型属性”(侧重于医疗保障支持、健康管理和健康咨询),3项被归类为“魅力型属性”(侧重于沟通需求和远程保健服务),11项被归类为“无差异型属性”(主要集中在社会心理服务领域)。结论社区乳腺癌患者对不同健康服务项目的需求程度不同。医务工作者应根据患者需求确定有效的健康服务策略,优先提供必备型和期望型属性的服务,努力提供魅力型属性服务,以提高社区乳腺癌患者的生活质量。

Left lower lobe sleeve resection for the clear cell variant of pulmonary mucoepidermoid carcinoma:A case report

BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.

Primary pancreatic peripheral T-cell lymphoma:A case report

BACKGROUND Primary pancreatic lymphoma(PPL)is an exceedingly rare tumor with limited mention in scientific literature.The clinical manifestations of PPL are often nonspecific,making it challenging to distinguish this disease from other panc-reatic-related diseases.Chemotherapy remains the primary treatment for these individuals.CASE SUMMARY In this case study,we present the clinical details of a 62-year-old woman who initially presented with vomiting,abdominal pain,and dorsal pain.On further evaluation through positron emission tomography-computed tomography,the patient was considered to have a pancreatic head mass.However,subsequent endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA)revealed that the patient had pancreatic peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS).There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin,decitabine,and oxaliplatin(brentuximab vedotin and Gemox).The patient had significant improvement in radiological findings at the end of the first cycle.CONCLUSION Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma,in which the clinical manifestations are often nonspecific.It is difficult to diagnose,and the prognosis is poor.Imaging can only be used for auxiliary diagnosis of other diseases.With the help of immunostaining,EUS-FNA could be used to aid in the diagnosis of PPL.After a clear diagnosis,chemotherapy is still the first-line treatment for such patients,and surgical resection is not recommended.A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma.However,identifying new CD30-targeted therapies for different types of lymphoma is urgently needed.In the future,further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum:Two case reports

BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.