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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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PNPLA3 and nonalcoholic fatty liver disease:towards personalized medicine for fatty liver

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Hepatobiliary Surgery and Nutrition 2020年第3期9卷 353-356页

作者： Liyun Yuan Norah A.Terrrault division of gastrointestinal and liver Diseases University of Southern CaliforniaLos AngelesCAUSA

Nonalcoholic fatty liver disease(NAFLD)affects approximately 25%of the global population and the future clinical and economic consequences are enormous.

关键词： liver NAFLD clinical

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Esophageal liposarcoma:Well-differentiated rhabdomyomatous type

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World Journal of gastrointestinal Oncology 2016年第12期8卷 835-839页

作者： Hisham M Valiuddin Arianna Barbetta Benedetto Mungo Elizabeth A Montgomery Daniela Molena Lake Erie College of Osteopathic Medicine Bradenton Thoracic Surgery Service Department of SurgeryMemorial Sloan Kettering Cancer Center division of Thoracic Surgery Department of SurgeryJohn Hopkins Hospital division of gastrointestinal and liver pathology Department of PathologyJohn Hopkins Hospital

Rhabdomyomatous well-differentiated esophageal liposarcomas are extremely rare. As of August 2016, only one other such case has been reported in the English-language medical literature. Liposarcomas in general are one of the most common soft tissue neoplasms in adults, but the incidence of primary esophageal liposarcomas is exceptionally low. There have been only 42 reported cases of primary liposarcoma of the esophagus worldwide thus far. These malignancies are harbored within giant fibrovascular polyps, which slowly grow within the esophageal lumen causing obstructing symptoms. We hereby present the case of a 68-year-old male patient who came in with a 2-mo history of worsening intermittent dysphagia, persistent cough, and postprandial retrosternal pain. After an esophagogastroduodenoscopy, a computed tomographic scan, and a diagnostic endoscopy, complete endoscopic resection was performed of the 13 cm × 6 cm × 2.6 cm fibrovascular polyp. A literature review was done and results are presented herein.

关键词： Esophageal cancer Esophageal surgery Endoscopy/endoscopic procedures pathology esophagus Liposarcoma Mesenchymal tumor

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Colorectal cancers in ulcerative colitis from a low-prevalence area for colon cancer

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World Journal of Gastroenterology 2015年第12期21卷 3644-3649页

作者： Devendra Desai Sudeep Shah Abhijit Deshmukh Philip Abraham Anand Joshi Tarun Gupta Ramesh Deshpande Varun Khandagale Siji George division of Gastroenterology P.D Hinduja Hospital division of gastrointestinal surgery Department of Surgery P.D Hinduja Hospital division of pathology Department of Pathology P.D Hinduja Hospital

AIM: To determine the incidence and risk factors for colorectal cancer(CRC) in patients with ulcerative colitis from a low prevalence region for ***: Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men(57.7%)] with ulcerative colitis(median disease duration 6, range: 1-39 years) for analysis. Of these, 131(30.5%) had left-sided colitis and 159(37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of ***: Twelve patients(2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease- 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained ***: CRC occurred in 2.8% of patients with ulcerative colitis in our population- an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our *** risk increased with extent and duration of disease.

关键词： Colon cancer Dysplasia Epidemiology Inflammatory b

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Seven-day quintuple regimen as a rescue therapy for Helicobacter pylori eradication

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World Journal of Gastroenterology 2015年第2期21卷 661-666页

作者： Fariborz Mansour-Ghanaei Farahnaz Joukar Mohammad Reza Naghipour Atena Forouhari Seyed Mohammad Seyed Saadat division of Gastroenterology and Hepatology Gastrointestinal and Liver Diseases Research CenterRazi HospitalGuilan University of Medical SciencesRasht 41448-95655Iran gastrointestinal and liver Diseases Research Center Guilan University of Medical SciencesRasht 41448-95655Iran

AIM: To determine the efficacy of two quintupleregimens for eradication of Helicobacter pylori(H. pylori) in patients who failed previous ***: This prospective, open-label, randomized controlled trial was a phase Ⅱ study conducted from April 2011 to March 2012 at the gastrointestinal and liver Diseases Research Center in Rasht, Iran. A total of 208 patients with dyspepsia who failed previous H. pylori eradication with a ten-day quadruple therapy were enrolled. A random block method was used to assign patients to one of two treatment groups. Patients in the first group were treated with 240 mg bismuth subcitrate, 20 mg omeprazole, 1000 mg amoxicillin, 500 mg clarithromycin and 500 mg tinidazole(BOACT group). Patients in the second group received a regimen containing 240 mg bismuth subcitrate, 20 mg omeprazole, 500 mg tetracycline, 500 mg metronidazole and 200 mg ofloxacin(BOTMO group). Both regimens were given twice daily for a duration of seven days. The eradication was confirmed by a 14 C urea breath test 12 wk after completion of therapy. Patient compliance and drug side effects were evaluated at the end of the treatment period. The success rates were calculated by intention-to-treat and per-protocol ***: A total of 205 patients completed the course of treatment, with three patients excluded due to drug intolerance. The mean age of patients did not differ between the BOACT and BOTMO groups(41.6 ± 12.2 years vs 39.6 ± 11.8 years), and no significant differences were found between the two groups in terms of age, sex, smoking habits or the initial eradication regimen. The intention-to-treat and perprotocol eradication rates were significantly higher in the BOTMO group(86.5%, 95%CI: 0.85-0.87 and 86.7%, 95%CI: 0.80-0.89, respectively) compared with the BOACT group(75.5%, 95%CI: 0.73-0.76 and 76%, 95%CI: 0.69-0.80, respectively)(P < 0.05). Univariate analyses for both groups did not show any association of sex, smoking and initial therapeutic

关键词： Antibiotic resistance Rescue therapy Eradication H

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Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

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World Journal of Gastroenterology 2015年第36期21卷 10468-10474页

作者： Andrea Cacciato Insilla Pinuccia Faviana Luca Emanuele Pollina Paolo De Simone Laura Coletti Franco Filipponi Daniela Campani Department of Surgical MedicalMolecular Pathology and Critical AreaDivision of Surgical PathologyUniversity Hospital of Pisa Department of Surgical MedicalMolecular Pathology and Critical AreaDivision of Liver Surgery and TransplantationUniversity Hospital of Pisa

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here,a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy,the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2,CK8,CK18,CEA(polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3,CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors(GISTs).The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here,we report the clinicopathological features of our case,along with a review of the few cases present in the literature.

关键词： Lymphoepithelioma Lymphoepithelioma-like Hepatocel

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liver stem cells:Plasticity of the liver epithelium

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World Journal of Gastroenterology 2019年第9期25卷 1037-1049页

作者： Atsunori Tsuchiya Wei-Yu Lu division of Gastroenterology and Hepatology Graduate school of medical and dental sciences Niigata University Centre for liver and gastrointestinal Research Institute of Immunology and Immunotherapy the University of Birmingham

The liver has a high regenerative capacity after acute liver injury, but this is often impaired during chronic liver injury. The existence of a dedicated liver stem cell population that acts as a source of regeneration during chronic liver injury has been controversial. Recent advances in transgenic models and cellular reprogramming have provided new insights into the plasticity of the liver epithelium and directions for the development of future therapies. This article will highlight recent findings about the cellular source of regeneration during liver injury and the advances in promoting liver regeneration.

关键词： liver regeneration Stem cells Cellular plasticity

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Incidence and localization of lymphoid follicles in early colorectal neoplasms

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World Journal of Gastroenterology 2005年第43期11卷 6863-6866页

作者： Kuang-I Fu Yasushi Sano Shigeharu Kato Takahiro Fujii Ikura Koba Takayuki Yoshino Atsushi Ochiai Shigeaki Yoshida Takahiro Fujimori division of gastrointestinal Oncology and Digestive Endoscopy division of pathology Department of Surgical and Molecular pathology

AIM： TO investigate the incidence and Iocalizations of lymphoid follicles （LFs） in early colorectal neoplasms in human beings. METHODS： From July 1992 to September 1999, a total of 1 324 early colorectal neoplasms were removed endoscopically or surgically at our hospital; 1 031 （77.9%） were available for analysis in this study. Localization of LFs was defined histologically： as submucosal LFs, if located under the muscularis mucosa; and as intramucosal LFs, if located across or over the muscularis RESULTS： Histologically, the materials included 903 intramucosal neoplasms and 128 submucosal cancers. Overall incidence of LFs was 27.2% （280/1 031）. The incidence of LFs was significantly higher in females （33.6% vs 24.9%, P = 0.0064）, the right-sided colon （32.2% vs 25.6%, P = 0.0403） and in flat or depressed type lesions （34.6% vs 25.2%, P〈O.O001） as compared to males, left-sided colon and protruding type lesions, respectively. The incidences of intramucosal neoplasms and submucosal cancers were 24.3% and 43.8%, respectively （P〈O.O001）. Localizations of LFs （intramucosal LF/submucosal LF） in depressed, flat, and protruding types were 1/24, 14/36, and 131/74, respectively. CONCLUSION： The incidence of LFs in early human colorectal neoplasms significantly differs by gender, location, macroscopic type, and histology. Moreover,localization significantly differs by macroscopic type.

关键词： Lymphoid follicle Early colorectal neoplasm Carcinogenesis

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Intraductal papillary bile duct adenocarcinoma and gastrointestinal stromal tumor in a case of neurofibromatosis type 1

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World Journal of Gastroenterology 2018年第4期24卷 537-542页

作者： Jung Min Lee Jae Min Lee Jong Jin Hyun Hyuk Soon Choi Eun Sun Kim Bora Keum Yoon Tae Jeen Hoon Jai Chun Hong Sik Lee Chang Duck Kim Dong Sik Kim Joo Young Kim division of Gastroenterology and Hepatology Department of Internal Medicine Institute of Gastrointestinal Medical Instrument Research Korea University College of Medicine division of Gastroenterology and Hepatology Department of Internal Medicine Korea University Anam Hospital division of HBP Surgery and liver Trans- plantation Department of Surgery Korea University College of Medicine Department of pathology Korea University College of Medicine

We report our experience with a synchronous case of gastrointestinal stromal tumor(GIST) and intraductal papillary neoplasm of the bile duct(IPNB) in anelderly woman with neurofibromatosis type 1(NF-1). A 72-year-old woman presented with a 2-mo history of right upper abdominal pain unrelated to diet and indigestion. Fourteen years earlier, she had been diagnosed with NF-1, which manifested as café au lait spots and multiple nodules on the skin. Computed tomography(CT) revealed a multilocular low-density mass with septation, and mural nodules in the right hepatic lobe, as well as a 1.7-cm-sized well-demarcated enhancing mass in the third portion of the duodenum. The patient subsequently underwent right hepatectomy and duodenal wedge resection. We present here the first report of a case involving a synchronous IPNB and GIST in a patient with NF-1. Our findings demonstrate the possibility of various tumors in NF-1 patients and the importance of diagnosis at an early

关键词： Neurofibromatosis type 1 Intraductal papillary neoplasm of the bile duct gastrointestinal stromal tumor Synchronous

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Esophagogastric junction outflow obstruction successfully treated with laparoscopic Heller myotomy and Dor fundoplication: First case report in the literature

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World Journal of gastrointestinal Surgery 2019年第2期11卷 112-116页

作者： Pedro F Pereira Andre RP Rosa Leonardo A Mesquita Marcelle J Anzolch Rafael N Branchi Augusto L Giongo Francisco C Paix?o Marcio F Chedid Cleber DP Kruel division of gastrointestinal Surgery and liver Transplantation Hospital de Clinicas de Porto AlegreFederal University of Rio Grande do Sul

BACKGROUND Esophagogastric junction outflow obstruction(EGJOO) is a rare syndrome,characterized by an elevation of the integrated relaxation pressure of the lower esophageal sphincter, not accompanied by alterations in esophageal motility that may lead to the criteria for achalasia. We were unable to find any prior report of the combination of Heller myotomy with anterior partial fundoplication(Dor) as the treatment for EGJOO. We herein report a case of EGJOO treated with laparoscopic Heller myotomy combined with Dor *** SUMMARY A 26-year-old man presented with a 3-year history of solid dysphagia and a 30-kg weight loss. He was treated with oral nifedipine, isosorbide, and omeprazole,without resolution of symptoms. An upper gastrointestinal series(barium swallow) revealed a "bird's beak" sign. Esophagogastroduodenoscopy was positive for Los Angeles grade A peptic esophagitis. High-resolution esophageal manometry was compatible with EGJOO. Esophageal pH monitoring showed pathological acid reflux both in orthostatic and decubitus position. An 8-cm laparoscopic Heller myotomy combined with an anterior 220° Dor fundoplication was performed. Solid diet was introduced on postoperative day 2, and the patient was discharged home the same day. At 17-mo follow-up, he reported no symptoms. Barium swallow was compatible with complete radiologic *** esophageal manometry and upper endoscopy showed normal findings 9 mo after the *** Surgical treatment with Heller myotomy and Dor fundoplication is a potential treatment option for EGJOO refractory to medical treatment.

关键词： Esophagogastric junction outflow obstruction Heller myotomy Partial fundoplication Dor fundoplication Case report

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