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Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis

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World Journal of Gastrointestinal Surgery 2023年第6期15卷 1068-1079页

作者： Fan Ding Run Guo Fang Chen Li-Ping Liu Zheng-Yu Cui Yi-Xing Wang Gang Zhao Hai Hu Center of gallbladder Disease Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Institute of Gallstone Disease School of MedicineTongji UniversityShanghai 200331China Department of Ultrasonography Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Internal Medicine of Traditional Chinese Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China

BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in gallbladder contractility.AIM To investigate the origin of slow wave(SW)in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.METHODS Methylene blue(MB)with light was used to establish selective impaired ICCs gallbladder tissue.gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control(NC),AC12h,AC24h,and AC48h groups of guinea pigs.Hematoxylin and eosin and Massonstained gallbladder tissues were scored for inflammatory changes.ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy.The alterations of c-Kit,α-SMA,cholecystokinin A receptor(CCKAR),and connexin 43(CX43)were assessed using Western blot.RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility.The frequency of SW and gallbladder contractility were significantly lower in the AC12h group.Compared with the NC group,the density and ultrastructure of ICCs were remarkably impaired in the AC groups,especially in the AC12h group.The protein expression levels of c-Kit were significantly decreased in the AC12h group,while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility.The density and ultrastructure of ICCs were clearly impaired in the early stage of AC,while CCKAR and CX43 were significantly reduced at end stage.

关键词： Interstitial cells of Cajal Acute cholecystitis Slow wave gallbladder Contractility

gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

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World Journal of Gastroenterology 2022年第6期28卷 675-682页

作者： Kiyotaka Hosoda Akira Shimizu Koji Kubota Tsuyoshi Notake Hikaru Hayashi Koya Yasukawa Kentaro Umemura Atsushi Kamachi Takamune Goto Hidenori Tomida Shiori Yamazaki Yuri Narusawa Naoko Asano Takeshi Uehara Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of MedicineMatsumoto 390-8621Japan Department of Laboratory Medicine Shinshu University School of MedicineMatsumoto 390-8621Japan

BACKGROUND Malignant lymphoma is a rare form of gallbladder malignancy.Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the literature.Herein,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder adenocarcinoma.CASE SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension screening.His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor.Imaging examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the serosa.Moreover,a periportal lymph node had enlarged to 30 mm.Based on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection.However,the patient was finally diagnosed as having Burkitt’s lymphoma.Although the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge.Thus,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and prednisone.CONCLUSION Burkitt’s lymphoma can occur in the gallbladder.Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

关键词： gallbladder Malignant lymphoma Burkitt’s lymphoma gallbladder cancer Lymphadenopathy Case report

gallbladder carcinoma: prognostic factors and therapeutic options

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World Journal of Gastroenterology 2015年第43期21卷 12211-12217页

作者： Thorsten Oliver Goetze Institut of Clinical Cancer Research UCT-University Cancer Center Frankfurt

The outcome of gallbladder carcinoma is poor,and the overall 5-year survival rate is less than 5%. In early-stage disease,a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma,which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection,primary sclerosing cholangitis,an anomalous junction of the pancreaticobiliary duct,and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However,despite theoretical risk factors,only a third of gallbladder carcinomas are recognized preoperatively. In most patients,the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ‘‘incidental or occult gallbladder carcinoma''(IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore,the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However,the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry(GR),which records the largest number of incidental gallbladder carcinomas in Europe,indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature,a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1 b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a for

关键词： gallbladder carcinoma Stage-adjusted therapy Radic

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中国恶性肿瘤整合诊治指南:胆囊癌

肿瘤 2022年第3期42卷 188-202页

作者：中国抗癌协会李强姜小清彭承宏刘颖斌戴朝六韩风胡冰罗明刘厚宝李斌不详天津医科大学肿瘤医院海军军医大学第三附属医院上海交通大学医学院附属瑞金医院上海交通大学医学院附属仁济医院中国医科大学附属盛京医院河南省肿瘤医院复旦大学附属中山医院上海中医药大学附属上海第七人民医院

1前言胆囊癌(gallbladder cancer,GBC)可起源于胆囊底部、体部和颈部或胆囊管等多个部位,是严重威胁人类健康的恶性肿瘤。美国癌症联合会(American Joint Committee on Cancer,AJCC)/国际抗癌联盟(Union for International Cancer Contr... 详细信息

关键词：胆囊癌国际抗癌联盟随访研究 gallbladder 恶性肿瘤胆囊管 GBC AJCC

gallbladder hemorrhage–An uncommon surgical emergency:A case report

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World Journal of Clinical Cases 2022年第27期10卷 9734-9742页

作者： Maria Rosaria Valenti Andrea Cavallaro Maria Di Vita Antonio Zanghi Giovanni Longo Trischitta Alessandro Cappellani Department of Surgery University of Catania Medical SchoolUniversity of CataniaCatania 95123Italy

BACKGROUND gallbladder hemorrhage is a life-threatening disorder.Trauma(accidental or iatrogenic such as a percutaneous biopsy or cholecystectomy surgery),cholelithiasis,biliary tract parasitosis,vasculitis,vascular malformations,autoimmune and neoplastic diseases and coagulopathies have been described as causes of hemorrhage within the lumen of the gallbladder.The use of nonsteroidal anti-inflammatory drugs and anticoagulants may represent a risk factor.CASE SUMMARY We report the case of a 76-year-old male patient.An urgent contrast computed tomography scan demonstrated relevant distension of the gallbladder filled with hyperdense non-homogeneous content.The gallbladder walls were of regular thickness.Near the anterior wall a focus of suspected active bleeding was observed.Due to the progressive decrease in hemoglobin despite three blood transfusions,this was an indication for urgent surgery.CONCLUSION Early diagnosis of this potentially fatal pathology is essential in order to plan a strategy and eventually proceed with urgent surgical treatment.

关键词： gallbladder Hemorrhage Anticoagulants Cholecystectomy Surgery Case report

Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder

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Signal Transduction and Targeted Therapy 2021年第3期6卷 897-908页

作者： Fatao Liu Yongsheng Li Dongjian Ying Shimei Qiu Yong He Maoian Li Yun Liu Yijian Zhang Qin Zhu Yunping Hu Liguo Liu Guoqiang Li Weihua Pan Wei Jin Jiasheng Mu Yang Cao Yingbin Liu Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Shanghai Key Laboratory of Biliary Tract Disease Yangpu DistrictShanghai 200092China State Key Laboratory of Oncogenes and Related Genes ShanghaiChina Shanghai Research Center of Biliary Tract Disease Yangpu DistrictShanghai 200092China Department of Biliary-Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Minimal Invasive Surgery Ningbo Medical Center Lihuili HospitalNingboZhejiang 315040China Department of hepatopancreatobiliary surgery Ganzhou hospital affiliated to Nanchang universityJiangxi 341000China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Information and Big Data Center Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Department of Surgery Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310009China Department of Gastric Surgery Cancer Hospital of the University of Chinese Academy of SciencesHangzhouZhejiang 310022China

Neuroendocrine carcinoma(NEC)of the gallbladder(GB-NEC)is a rare but extremely malignant subtype of gallbladder cancer(GBC).The genetic and molecular signatures of GB-NEC are poorly understood;thus,molecular targeting is currently unavailable.Inthe present study,we applied whole-exome sequencing(WES)technology to detect gene mutations and predicted somatic singlenucleotide variants(SNVs)in 15 cases of GB-NEC and 22 cases of general GBC.in 15 GB-NECs,the C>T mutation was predominantamong the 6 types of SNVs.TP53 showed the highest mutation frequency(73%,11/15).Compared with neuroendocrine carcinomasof other organs,signifcantly mutated genes(SMGs)in GB-NECs were more similar to those in pulmonary large-cell euroendocrinecarcinomas(LCNECs),with drver roles for TP53 and RB1.Iin the COSMIC database of cancer-related genes,211 genes were mutated.Strikingly,RB1(4/15,27%)and NAB2(3/15,20%)mutations were found specifically in GB-NECs;in contrast,mutations in 29 genes,including ERB82 and ERBB3,were identified exclusively in GBC.Mutations in RB1 and NAB2 were significanty related to downregulation of the RB1 and NAB2 proteins,respectively,according to immunohistochemical(IHC)data(p values=0.0453 and0.0303).Clinically actionable genes indicated 23 mutated genes,including ALK,BRCA1,and BRCA2.Iin addition,potential somaticSNVs predicted by ISowN and SomVarlUS constituted 6 primary coSMIC mutation signatures(1,3,30,6,7,and 13)in GB-NEC.Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch,WNT,Hippo,and RTK-RASpathways.In summary,we have systematically identified the mutation landscape of GB-NEC,and these findings may providemechanistic insights into the specifc pathogenesis of this deadly disease.

关键词： gallbladder carcinomas organs

gallbladder Metastasis of Non-small Cell Lung Cancer Presenting as Acute Cholecystitis

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Chinese Journal of Cancer Research 2012年第3期24卷 249-252页

作者： Yu-Sook Jeong Hye-Suk Han Sung-Nam Lim Mi-Jin Kim Joung-Ho Han Min-Ho Kang Dong-Hee Ryu Ok-Jun Lee Ki-Hyeong Lee Seung-Taik Kim Department of Internal Medicine College of MedicineChungbuk National University Department of Radiology College of MedicineChungbuk National University Department of Surgery College of MedicineChungbuk National University Department of Pathology College of MedicineChungbuk National University Department of Internal Medicine College of MedicineChungbuk National University

Although non-small cell lung cancer （NSCLC） can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography （CT） scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.

关键词： Cholecystitis gallbladder Non-small cell lung cancer Metastasis

Banxia Xiexin Decoction(半夏泻心汤)Combined with Afatinib in Treatment of Advanced gallbladder Cancer:Case Report and Literature Review

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Chinese Journal of Integrative Medicine 2019年第4期25卷 303-306页

作者： SU Li WANG Miao-miao XU Meng-ran WANG Xiao XIA Hong-zhen ZHANG Mei ZHENG Lei ZHU Yao-dong WANG Ming-qi LI Ping Department of Integrative Medicine Oncology First Affiliated Hospital of Anhui Medical UniversityHefei(230001)China Department of Radiology First Affiliated Hospital of Anhui Medical UniversityHefei(230001)China Department of Pathology Anhui Provincial HospitalHefei(230001)China

gallbladder cancer(GBC)is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developingCurrently,GBC has a low early diagnosis rate and an extremely poor prognosis,leading to major problems for treatment of GBC.Liver invasion and metastasis one of the main causes of its poor prognosis,with its average overall survival of 6 months.

关键词： Banxia Xiexin Decoction 半夏泻心汤 Combined with Afatinib in Treatment of Advanced gallbladder Cancer:Case Report and Literature Review GBC

Flushing as atypical initial presentation of functional gallbladder neuroendocrine carcinoma: A case report

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World Journal of Gastroenterology 2020年第6期26卷 686-695页

作者： Ming Jin Bo Zhou Xiong-Ling Jiang Qi-Yi Zhang Xiang Zheng Yuan-Cong Jiang Sheng Yan Department of General Surgery Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009Zhejiang ProvinceChina Department of Pathology First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Neuroendocrine neoplasms are rarely located in the gallbladder(GB),and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms.CASE SUMMARY We report a case of GB neuroendocrine carcinoma(GB-NEC)in a 65-year-old man,who presented with flushing for 2 mo.Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis.Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space.High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space,but distant metastasis was not seen by positron emission tomography.Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC.Because of the functional characteristics of poorly differentiated NEC,en bloc cholecystectomy,resection of hepatic segments IVb and V,pancreaticoduodenectomy,and regional lymphadenectomy were performed.A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data.Ki-67 index was>80%.The patient refused adjuvant therapy and passed away in the 7th month.CONCLUSION Distinctive manifestation combined with imaging helps make correct preoperative diagnosis.Radical surgery and adjuvant chemotherapy might improve prognosis.

关键词： Malignant carcinoid syndrome Neuroendocrine tumors Carcinoma gallbladder Carcinoid tumor Case report