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Microbiota in colorectal cancer related to liver metastasis

Chinese Journal of Cancer Research 2024年第1期36卷 17-24页

作者： Peijun Wei Weiming Han Zitong Zhang Xue Tian Chen Yang Qiaoxuan Wang Weihao Xie Ying Liu Yuanhong Gao Hui Chang Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Guangdong Provincial Clinical Research Center for Cancer Guangzhou 510060China Sun Yat-sen University Cancer Center Guangzhou 510060China Department of Pediatric Oncology State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

关键词： Gut microbiota liver metastasis colorectal cancer

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Prognostic value of a nomogram model for postoperative liver metastasis of colon cancer

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1055-1065页

作者： De-Xin Cheng Kang-Di Xu Han-Bo Liu Yi Liu Department of Interventional Medicine Zhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina General Surgery Cancer CenterDepartment of Vascular SurgeryZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina

BACKGROUND Colon cancer is one of the most common malignant tumors of the digestive system.liver metastasis after colon cancer surgery is the primary cause of death in patients with colon cancer.AIM To construct a novel nomogram model including various factors to predict liver metastasis after colon cancer surgery.METHODS We retrospectively analyzed 242 patients with colon cancer who were admitted and underwent radical resection for colon cancer in Zhejiang Provincial People’s Hospital from December 2019 to December 2022.Patients were divided into liver metastasis and non-liver metastasis groups.Sex,age,and other general and clinicopathological data(preoperative blood routine and biochemical test indexes)were compared.The risk factors for liver metastasis were analyzed using singlefactor and multifactorial logistic regression.A predictive model was then constructed and evaluated for efficacy.RESULTS Systemic inflammatory index(SII),C-reactive protein/albumin ratio(CAR),red blood cell distribution width(RDW),alanine aminotransferase,preoperative carcinoembryonic antigen level,and lymphatic metastasis were different between groups(Pliver metastasis after colon cancer surgery(Pliver metastasis occurred postoperatively.The actual curve of the column-line diagram predicting the risk of postoperative liver metastasis was close to the ideal curve,with good agreement.The prediction model curves in the decision curve analysis showed higher net benefits for a larger threshold range than those in extreme cases,indicating that the model is safer.CONCLUSION liver metastases after colorectal cancer surgery could be well predicted by a nomogram based on the SII,CAR,and RDW.

关键词： Systemic immunoinflammatory index C-reactive protein/albumin ratio Erythrocyte distribution width Colon cancer liver metastasis Novel nomogram model

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Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer:A focus on biological mechanisms and therapeutic opportunities

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World Journal of Gastroenterology 2023年第18期29卷 2764-2783页

作者： Federico Selvaggi Teresa Catalano Rossano Lattanzio Roberto Cotellese Gitana Maria Aceto Department of Surgical ASL2 Lanciano-Vasto-ChietiOspedale Clinicizzato SS Annunziata of ChietiChieti 66100Italy Department of Clinical and Experimental Medicine University of MessinaMessina 98125Italy Department of Innovative Technologies in Medicine&Dentistry University“G.d’Annunzio”Chieti-PescaraChieti 66100Italy Department of Medical Oral and Biotechnological SciencesUniversity“G.d’Annunzio”Chieti-PescaraChieti 66100Italy Villa Serena Foundation for Research Villa Serena-Del Dott.L.PetruzziCittàSant’Angelo 65013PescaraItaly Department of Medical Oral and Biotechnological Sciences“G.d’Annunzio”University of Chieti-PescaraChieti 66100Italy

The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.The aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition interactions.In liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and therapies.Treatment of CRLMs is challenging due to its variability and heterogeneity.Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in chemoresistance.At the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie.In this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered.In addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.

关键词： Wingless/It/β-catenin signaling Colorectal cancer Epithelial-mesenchymal transition/mesenchymal-epithelial transition liver metastasis Markers Surgical and non-surgical therapies

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Clinical characteristics and prognosis of non-small cell lung cancer patients with liver metastasis:A population-based study

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World Journal of Clinical Cases 2022年第30期10卷 10882-10895页

作者： Jun-Feng Wang Hong-Di Lu Ying Wang Rui Zhang Xiang Li Sheng Wang The First Department of Thoracic Oncology Jilin Province Tumor HospitalChangchun 130021Jilin ProvinceChina Big Data Center for Clinical Research Jilin Province Tumor HospitalChangchun 130021Jilin ProvinceChina

BACKGROUND The presence of liver metastasis(LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer(NSCLC) patients.The median overall survival of patients with involvement of the liver is less than 5 mo.At present,identifying prognostic factors and constructing survival prediction nomogram for NSCLC patients with LM(NSCLC-LM) are highly desirable.AIM To build a forecasting model to predict the survival time of NSCLC-LM patients.METHODS Data on NSCLC-LM patients were collected from the Surveillance,Epidemiology,and End Results database between 2010 and 2018.Joinpoint analysis was used to estimate the incidence trend of NSCLC-LM.Kaplan-Meier curves were constructed to assess survival time.Cox regression was applied to select the independent prognostic predictors of cancer-specific survival(CSS).A nomogram was established and its prognostic performance was evaluated.RESULTS The age-adjusted incidence of NSCLC-LM increased from 22.7 per 1000000 in 2010to 25.2 in 2013,and then declined to 22.1 in 2018.According to the multivariable Cox regression analysis of the training set,age,marital status,sex,race,histological type,T stage,metastatic pattern,and whether the patient received chemotherapy or not were identified as independent prognostic factors for CSS(P < 0.05) and were further used to construct a nomogram.The C-indices of the training and validation sets were 0.726 and 0.722,respectively.The results of decision curve analyses(DCAs) and calibration curves showed that the nomogram was well-discriminated and had great clinical utility.CONCLUSION We designed a nomogram model and further constructed a novel risk classification system based on easily accessible clinical factors which demonstrated excellent performance to predict the individual CSS of NSCLC-LM patients.

关键词： Non-small cell lung cancer liver metastasis Nomogram Risk classification system

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Primary testicular neuroendocrine tumor with liver lymph node metastasis: A case report and review of the literature

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World Journal of Clinical Cases 2022年第32期10卷 12028-12035页

作者： Tong Xiao Long-Hua Luo Liang-Fei Guo Li-Qin Wang Liang Feng Department of Urology The First Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina.

BACKGROUND Primary testicular neuroendocrine tumors(TNETs)are sporadic,accounting for only 0.23%of all testicular tumors.Few cases have been reported in the literature,and no uniform treatment protocol exists.We report a case of a primary TNET with liver lymph node metastasis diagnosed at the age of 24 years and discuss its clinicopathological features,diagnosis,differential diagnosis,treatment,and prognosis.CASE SUMMARY We report the case of a 24-year-old patient with a primary TNET with liver lymph node metastasis.The patient was found to have a right testicular swelling of about 3 cm×4 cm in size with unclear borders and no testicular pressure pain seven years ago without any examination or treatment.One month ago,an ultrasound examination was performed for persistent enlargement of the right testis,which showed an occupying lesion of the right testis approximately 110 mm×102 mm×82 mm in size.Magnetic resonance imaging scan of the testis(plain scan)showed that the right testis was an occupying lesion with inhomogeneous density and mixed signal,the boundary was still clear,and the possibility of seminoma was considered;chest X-ray and computed tomography did not show any apparent abnormalities.The patient underwent radical orchiectomy,and the pathological examination suggested a right TNET with a typical carcinoid tumor histological type.One month after the surgery,the patient received nine cycles of lanreotide chemotherapy at a dose of 90 mg/mo without adverse effects.No distant lymph node or other organ metastases were detected at follow-up.He is in good physical condition and attends regular follow-up visits.CONCLUSION Neuroendocrine tumors are rare in clinical practice,and the diagnosis mainly relies on the characteristics of microscopic tumor cells and immunohistochemical features.Treatment involves radical orchiectomy.If it is accompanied by distant lymph node metastasis and the metastatic lesion can be resected,it should be surgically removed;if it cannot be resected,growth inhibitor analog octreotide or

关键词： Testis Neuroendocrine tumor Immunohistochemistry Differential diagnosis Somatostatin analog Lanreotide liver metastasis Treatment Case report

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World Journal of Gastroenterology 2022年第30期28卷 4231-4234页

作者： Manuel Muro Aurelia Collados-Ros Isabel Legaz Immunology Service Instituto Murciano de investigación biosanitaria(IMIB)Hospital Clínico Universitario Virgen de la Arrixaca(HCUVA)Murcia 30120Spain Department of Legal and Forensic Medicine Biomedical Research Institute(IMIB)Regional Campus of International Excellence“Campus Mare Nostrum”Faculty of MedicineUniversity of MurciaMurcia 30100Spain

Alcohol intake is a risk factor for cancer development and metastatic disease progression.Extracellular vesicle(EV)-mediated interorgan communication is assumed to be significant in boosting tumorigenic pathways and disease progression.Recent research indicates that exosomes have a variety of roles in the development of cancer during pathophysiological conditions.The involvement of EV signaling during cancer progression in the alcohol environment is unknown.Therefore,understanding communication networks and the role of EVs as biomarkers can contribute significantly to developing strategies to address the serious public health problems associated with alcohol consumption and cancer.

关键词： Exosomes liver metastasis Alcohol-associated liver disease Cancer

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Prognostic factors of survival and a new scoring system for liver resection of colorectal liver metastasis

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World Journal of Hepatology 2022年第1期14卷 209-223页

作者： Kai-Chi Cheng Ada Sze-Man Yip Department of Surgery Kwong Wah HospitalHong KongChina

BACKGROUND Hepatic resection has become the preferred treatment of choice for colorectal liver metastasis(CLM)patients.AIM To identify the prognostic factors and to formulate a new scoring system for management of CLM.METHODS Clinicopathologic and long-term survival data were analyzed to identify the significant predictors of survival by univariate and multivariate analyses with the Cox model.A clinical score was constructed based on the analysis results.RESULTS Three factors of worse overall survival were identified in the multivariate analysis.They were number of liver metastases≥5,size of the largest liver lesion≥4 cm,and the presence of nodal metastasis from the primary tumor.These three factors were chosen as criteria for a clinical risk score for overall survival.The clinical score highly correlated with median overall survival and 5-year survival(P=0.002).CONCLUSION Priority over surgical resection should be given to the lowest score groups,and alternative oncological treatment should be considered in patients with the highest score.

关键词： Colorectal cancer liver metastasis liver resection Long-term outcome Overall survival Disease-free survival Prognosis Score

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Curative resection of leiomyosarcoma of the descending colon with metachronous liver metastasis: A case report

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World Journal of Gastrointestinal Surgery 2023年第5期15卷 992-999页

作者： Soo-Hyeon Lee Sang-Ho Bae Sang-Cheol Lee Tae-Sung Ahn Zisun Kim Hae-Il Jung Department of Surgery Soonchunhyang University Cheonan HospitalCheonan 31151ChungnamSouth Korea Department of Internal Medicine Soonchunhyang University Cheonan HospitalCheonan 31151ChungnamSouth Korea Department of Surgery Soonchunhyang University Bucheon HospitalBucheon 14584GyeonggiSouth Korea

BACKGROUND Leiomyosarcoma(LMS)has a poor prognosis and rarely originates from the colon.If resection is possible,surgery is the first treatment most commonly considered.Unfortunately,no standard treatment exists for hepatic metastasis of LMS;although,several treatments,such as chemotherapy,radiotherapy,and surgery,have been used.Subsequently,the management of liver metastases remains controversial.CASE SUMMARY We present a rare case of metachronous liver metastasis in a patient with LMS originating from the descending colon.A 38-year-old man initially reported abdominal pain and diarrhea over the previous two months.Colonoscopy revealed a 4-cm diameter mass in the descending colon,40 cm from the anal verge.Computed tomography revealed intussusception of the descending colon due to the 4-cm mass.The patient underwent a left hemicolectomy.Immunohistochemical analysis of the tumor revealed that it was positive for smooth muscle actin and desmin,and negative for cluster of differentiation 34(CD34),CD117,and discovered on gastrointestinal stromal tumor(GIST)-1,which are characteristic of gastrointestinal LMS.A single liver metastasis developed 11 mo postoperatively;the patient subsequently underwent curative resection thereof.The patient remained disease-free after six cycles of adjuvant chemotherapy(doxorubicin and ifosfamide),and 40 and 52 mo after liver resection and primary surgery,respectively.Similar cases were obtained from a search of Embase,PubMed,MEDLINE,and Google Scholar.CONCLUSION Early diagnosis and surgical resection may be the only potential curative options for liver metastasis of gastrointestinal LMS.

关键词： Leiomyosarcoma Colon liver metastasis Surgical resection Treatment Case report

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Irinotecan-vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients:A retrospective study

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World Journal of Gastrointestinal Surgery 2022年第9期14卷 904-917页

作者： Wei Liu Feng-Lin Chen Kun Wang Quan Bao Hong-Wei Wang Ke-Min Jin Bao-Cai Xing Department of Hepatopancreatobiliary Surgery Peking University School of OncologyBeijing Cancer HospitalBeijing 100142China Department of Hepatopancreatobiliary Surgery Key Laboratory of Carcinogenesis and Translational ResearchMinistry of EducationPeking University School of OncologyBeijing Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Neoadjuvant chemotherapy(NC)improves the survival outcomes of selected patients with colorectal liver metastasis(CRLM).The benefits of irinotecan-based regimens in these patients are still under debate.AIM To compare the benefits of irinotecan-and oxaliplatin-based regimens in patients with resectable CRLM.METHODS From September 2003 to August 2020,554 patients received NC and underwent hepatectomy for CRLM.Based on a 1:1 propensity score matching(PSM)model,175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic,therapeutic,and prognostic characteristics.RESULTS Chemotherapy was based on oxaliplatin in 353(63.7%)patients and irinotecan in 201(36.3%).After PSM,the 5-year progression-free survival(PFS)and overall survival(OS)rates with irinotecan were 18.0%and 49.7%,respectively,while the 5-year PFS and OS rates with oxaliplatin were 26.0%and 46.8%,respectively.Intraoperative blood loss,operating time,and postoperative complications differed significantly between the two groups.In the multivariable analysis,carbohydrate antigen 19-9,RAS mutation,response to NC,tumor size>5 cm,and tumor number>1 were inde-pendently associated with PFS.CONCLUSION In NC in patients with CRLM,irinotecan is similar to oxaliplatin in survival outcomes,but irinotecan is superior regarding operating time,intraoperative blood loss,and postoperative complications.

关键词： Colorectal cancer liver metastasis liver resection Neoadjuvant chemotherapy

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Targeted deep sequencing reveals the genetic heterogeneity in well-differentiated pancreatic neuroendocrine tumors with liver metastasis

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 302-313,I0001-I0005页

作者： Wentao Zhou Xu Han Yuan Ji Dansong Wang Dong Xie Zilong Qiu Wenhui Lou Department of Pancreatic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Pathology Zhongshan HospitalFudan UniversityShanghaiChina CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghaiChina Institute of Neuroscience State Key Laboratory of NeuroscienceChinese Academy of Sciences Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghaiChina Department of General Surgery Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghaiChina

Background:Pancreatic neuroendocrine tumor is a rare and heterogeneous entity,and approximately half of the patients harbored liver metastasis when initially diagnosed,whose prognosis is dismal.High-throughput sequencing has largely uncovered the genomic features of pancreatic neuroendocrine tumor,but the genetic alterations in the metastatic cases remain relatively unclear,which we aimed to study.Methods:Pathologically confirmed well-differentiated pancreatic neuroendocrine tumor samples resected in our hospital from 2000 to 2019 were collected.We performed deep sequencing on the exome of 341 tumor-related genes,and compared the differences of genetic alterations between the metastatic and the non-metastatic cases,as well as between the primary and the paired liver metastatic tumors.Results:Sequencing data of 79 samples from 29 pancreatic neuroendocrine tumor patients were included into analysis.A total of 2,471 somatic variants were identified,75.5%of which were considered as low-abundance.NOTCH1 was the most frequently mutated gene,altered in 26(53.1%)pancreatic neuroendocrine tumor samples from 18(62.1%)patients.Compared with the non-metastatic pancreatic neuroendocrine tumors,the metastatic cases were discovered with more single nucleotide variants and copy number variations,indicating the increased genomic instability.In addition,among the paired metastatic cases,the primary and the metastatic lesions shared limited mutated genes.Conclusions:Through the targeted deep sequencing,we identified the intratumor,intraindividual,and interindividual heterogeneity in the pancreatic neuroendocrine tumor patients,particularly in the metastatic cases,bringing potential challenges for the current biopsy strategies in guiding clinical treatments.

关键词： Pancreatic neuroendocrine tumor(pNET) liver metastasis targeted sequencing genomic alteration heterogeneity

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