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Shu C, Zhou H, Xu J, Tang J, Zhou S. Up-regulation of thrombospondin-1 inhibits the progression of gallbladder cancer. Med Oncol 2025; 42:170. [PMID: 40259006 PMCID: PMC12011972 DOI: 10.1007/s12032-025-02719-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Accepted: 04/14/2025] [Indexed: 04/23/2025]
Abstract
Gallbladder cancer, the most prevalent malignant neoplasm of the biliary tract, has garnered significant attention due to its dismal prognosis and high degree of malignancy. Identifying key regulatory genes is crucial for the development of effective therapeutic strategies. The differential gene expression in biliary tract malignancies was identified using the Gene Expression Omnibus (GEO) database. Subsequently, the interactions among these differentially expressed genes were analyzed employing the STRING database, and the resultant regulatory network was visualized using Cytoscape software. Utilizing the Cytoscape plugin CytoHubba, the core genes within the network were identified, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Ultimately, the overexpression of THBS1 in the gallbladder cancer cell line (NOZ) was achieved through lentiviral transfection and both in vivo and in vitro experiments were conducted to evaluate its effects. We found that thrombospondin-1 (THBS1) was the core gene of gallbladder cancer and its expression was low in gallbladder cancer. Experimental data, both in vivo and in vitro, indicate that the up-regulation of THBS1 exerts an inhibitory effect on the proliferation, migration, and invasion of gallbladder cancer cells. Furthermore, it facilitates the process of apoptosis and suppresses tumor growth and angiogenesis. The expression of THBS1 is low in gallbladder cancer. Up-regulation of THBS1 can effectively inhibit the occurrence and development of gallbladder cancer and can be used as a biomarker for the diagnosis and treatment of gallbladder cancer.
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Affiliation(s)
- Chang Shu
- The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214100, Jiangsu, China
- Wuxi Medical Center, Nanjing Medical University, Wuxi, 214100, Jiangsu, China
- Wuxi People's Hospital, Wuxi, 214100, Jiangsu, China
| | - Hanxu Zhou
- General Surgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, China
| | - Jinyu Xu
- The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214100, Jiangsu, China.
- Wuxi Medical Center, Nanjing Medical University, Wuxi, 214100, Jiangsu, China.
- Wuxi People's Hospital, Wuxi, 214100, Jiangsu, China.
| | - Jie Tang
- The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214100, Jiangsu, China.
- Wuxi Medical Center, Nanjing Medical University, Wuxi, 214100, Jiangsu, China.
- Wuxi People's Hospital, Wuxi, 214100, Jiangsu, China.
- General Surgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, China.
| | - Shaobo Zhou
- General Surgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, Anhui, China.
- General Surgery, Shenzhen Yantian District People's Hospital, Shenzhen, 518081, Guangdong, China.
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Bojan A, Pricop C, Vladeanu MC, Bararu-Bojan I, Halitchi CO, Giusca SE, Badulescu OV, Ciocoiu M, Iliescu-Halitchi D, Foia LG. The Predictive Roles of Tumour Markers, Hemostasis Assessment, and Inflammation in the Early Detection and Prognosis of Gallbladder Adenocarcinoma and Metaplasia: A Clinical Study. Int J Mol Sci 2025; 26:3665. [PMID: 40332145 PMCID: PMC12027584 DOI: 10.3390/ijms26083665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2025] [Revised: 04/03/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
Gallbladder carcinoma (GBC) is one of the most aggressive malignancies of the biliary tract, often originating from chronic inflammation associated with gallstones and cholecystitis. Persistent inflammation plays a pivotal role in the development of preneoplastic changes, such as metaplasia, which may progress to malignancy. Despite its relatively low incidence, GBC is characterized by a poor prognosis due to late-stage diagnosis, highlighting the urgent need for improved early detection strategies. This study aimed to assess the diagnostic and prognostic significance of CA 19-9 and CEA levels in patients with gallbladder lesions, while also evaluating systemic inflammation and hemostatic dysregulation. A retrospective analysis was conducted on patients diagnosed with gallbladder lesions, with histopathological confirmation of adenocarcinoma and metaplasia. Laboratory assessments included serum levels of tumour markers, inflammatory markers such as CRP, and key hemostatic parameters, including thrombocyte count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen levels. A predictive scoring model was developed using the cutoff values of CA 19-9 and CEA to assess their combined diagnostic potential. Among the patients studied, 48.9% had an initial diagnosis of chronic cholecystitis, while 32.2% presented with acute cholecystitis. Adenocarcinoma was identified in 6.7% of cases after histopathological examination, predominantly in females over 65 years old with acute cholecystitis. Metaplasia was detected in 7.8% of cases, primarily in elderly females with chronic cholecystitis. Laboratory findings revealed significantly elevated levels of CA 19-9, CEA, AFP, and CA-125 in patients with adenocarcinoma. Additionally, abnormalities in hemostatic parameters, including increased fibrinogen levels and alterations in thrombocyte count, were observed in patients with malignancy. A combined predictive score using CA 19-9 and CEA demonstrated strong potential for detecting adenocarcinoma and metaplasia, improving diagnostic accuracy. Our findings emphasize the clinical importance of integrating tumour markers, inflammatory biomarkers, and hemostatic parameters in the evaluation of gallbladder lesions associated with chronic inflammation. The combined assessment of these factors enhances early detection, facilitates malignancy risk stratification, and improves prognostic evaluation, particularly in patients with metabolic and cardiovascular comorbidities.
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Affiliation(s)
- Andrei Bojan
- Department of Surgical Specialties I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania; (A.B.)
| | - Catalin Pricop
- Department of Surgical Specialties I, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania; (A.B.)
| | - Maria-Cristina Vladeanu
- Department of Morpho Functional Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania (M.C.)
| | - Iris Bararu-Bojan
- Department of Morpho Functional Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania (M.C.)
| | - Codruta Olimpiada Halitchi
- Department of Pediatry, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania
| | - Simona Eliza Giusca
- Department of Morpho Functional Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania (M.C.)
| | - Oana Viola Badulescu
- Department of Morpho Functional Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania (M.C.)
| | - Manuela Ciocoiu
- Department of Morpho Functional Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania (M.C.)
| | - Dan Iliescu-Halitchi
- Department of Medical Sciences, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania
| | - Liliana Georgeta Foia
- Discipline of Biochemistry, Faculty of Dental Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania
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Li YC, Gao Q, Tang YC, Shao ZY, Hu JM, Liu ZL, Shi AD, Huang SH, Xu YF, Zhang ZL, Li KS. EEF1AKMT4-eEF1A2 synergistically facilitates the progression of GBC by promoting ribosomal protein output. Genes Dis 2025:101619. [DOI: 10.1016/j.gendis.2025.101619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2025] Open
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Liu Y, Wu Y, He S. Clinical Value of Abnormal Prothrombin and Carbohydrate Antigen 125 in the Diagnosis of Patients With Gallbladder Cancer. Am Surg 2025; 91:608-613. [PMID: 39754532 DOI: 10.1177/00031348241312119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
ObjectiveThis study was aimed at ascertaining the application value of abnormal prothrombin (PIVKA-II) and carbohydrate antigen 125 (CA125) in gallbladder cancer (GBC) diagnosis.MethodsA total of 70 GBC patients, 70 patients with benign gallbladder diseases (gallbladder stones and gallbladder polyps), and 70 normal health examination people were selected as the malignant, benign, and normal groups, respectively. The differences in serum levels and positive rates of PIVKA-II and CA125 were compared. The correlation between serum PIVKA-II and CA125 levels and different clinicopathological characteristics (TNM stage and differentiation degree) of GBC patients was analyzed. The receiver operating characteristic curve was plotted to evaluate the diagnostic value of serum PIVKA-II and CA125 for GBC, and sensitivity, specificity, and Youden's index were calculated.ResultsSerum PIVKA-II and CA125 levels and positive rates of patients in the malignant group were higher vs those in the benign and normal groups. Gallbladder cancer patients at stages III-IV had higher serum PIVKA-II and CA125 levels than those at stages I-II, and poorly differentiated GBC patients had higher serum PIVKA-II and CA125 levels than moderately differentiated and well-differentiated GBC patients. The AUC of serum PIVKA-II and CA125 alone and in combination were 0.771, 0.789, and 0.866, respectively, and the AUC of the two combined was higher vs that of the two alone.ConclusionSerum PIVKA-II and CA125 levels in GBC patients are increased and have significant clinical application value in the diagnosis of GBC.
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Affiliation(s)
- Yanguo Liu
- Department of Hepatobiliary and Pancreatic Surgery, East Hospital of Yantai Mountain Hospital, Yantai, China
| | - Yanfang Wu
- Department of Hepatobiliary and Pancreatic Surgery, East Hospital of Yantai Mountain Hospital, Yantai, China
| | - Shujie He
- Department of Hepatobiliary and Pancreatic Surgery, East Hospital of Yantai Mountain Hospital, Yantai, China
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Chavez M, de Aretxabala X, Losada H, Portillo N, Castillo F, Bustos L, Roa I. T1b gallbladder cancer: is extended resection warranted? HPB (Oxford) 2025; 27:523-529. [PMID: 39824714 DOI: 10.1016/j.hpb.2024.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 12/01/2024] [Accepted: 12/23/2024] [Indexed: 01/20/2025]
Abstract
BACKGROUND Although the prognosis for gallbladder cancer (GBCA) improves with early diagnosis and aggressive surgical treatment, the management of patients with muscle layer invasion (T1b) remains controversial. This study aimed to analyze the optimal surgical approach for these patients. METHODS A database was queried for patients with early T1b GBCA treated at four Chilean hospitals. Patients were prospectively treated and registered by the same surgical team at each hospital. Clinical outcomes, including survival rates according to the type of surgery, were analyzed. RESULTS Between 1988 and 2023, 129 Chilean patients were pathologically diagnosed with T1b GBCA. Simple cholecystectomy (SC) was performed in 86 patients (66.7 %), while extended cholecystectomy (EC) was performed in 43 patients. The overall 5-year survival rate was 83 %, with no significant difference between SC and EC patients. CONCLUSION Simple cholecystectomy demonstrated survival rates comparable to extended cholecystectomy for patients with T1b GBCA. More extensive resections did not improve the prognosis.
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Affiliation(s)
- Montserrat Chavez
- Department of Surgery, Padre Hurtado Hospital, Santiago, Chile; Department of Surgery, Universidad del Desarrollo, Santiago, Chile
| | - Xabier de Aretxabala
- Department of Surgery, Padre Hurtado Hospital, Santiago, Chile; Department of Surgery, Universidad del Desarrollo, Santiago, Chile; Surgical Unit, Clinica Alemana, Santiago, Chile.
| | - Hector Losada
- Department of Surgery, Universidad de la Frontera, Temuco, Chile; Surgical Unit, Hospital Hernan Henriquez, Temuco, Chile
| | - Norberto Portillo
- Department of Surgery, Universidad de la Frontera, Temuco, Chile; Surgical Unit, Hospital Hernan Henriquez, Temuco, Chile
| | - Felipe Castillo
- Department of Surgery, Padre Hurtado Hospital, Santiago, Chile; Department of Surgery, Universidad del Desarrollo, Santiago, Chile; Surgical Unit, Clinica Alemana, Santiago, Chile
| | - Luis Bustos
- Department of Epidemiology, Universidad de la Frontera, Temuco, Chile
| | - Ivan Roa
- Pathology Department, Clinica Alemana, Temuco, Chile
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Santucci J, Hua C, Chong L, Lockie E, Lim J, Lim S, Zhou W, Bradshaw L. Operative management and outcomes of gallbladder cancer in Australia: a multi-institutional, retrospective, observational cohort analysis. ANZ J Surg 2025; 95:395-406. [PMID: 39620620 DOI: 10.1111/ans.19300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 10/16/2024] [Accepted: 10/19/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND Data on optimal extent of resection for various stages of gallbladder cancer are lacking. This study aims to evaluate disease-free (DFS) and overall survival (OS) after simple (SC) versus radical cholecystectomy (RC) for gallbladder cancer in the Australian context, and assesses factors associated with post-operative morbidity. METHODS Multi-centre, retrospective cohort analysis including all gallbladder cancer patients who underwent resection across six Australian institutions between January 2010 and January 2020. RESULTS Of 63 patients included, 31 underwent SC and 32 had RC. Liver and other organ resection correlated with prolonged median DFS (41.9 vs. 13.1 months, HR 0.492 [95% CI 0.245-0.987], P = 0.042) and OS on univariate analysis of all patients (55.8% survived five years follow-up at study conclusion vs. median 18.4 months, HR 0.66 [95% CI 0.446-0.972], P = 0.036) but failed to demonstrate effect on multivariable analysis (OS HR 0.31 [95% CI 0.09-1.04], P = 0.057). RC was associated with a higher 30-day complication rate (n = 21 [65.6%] vs. n = 15 [48.4%], P = 0.310) compared to SC, although not statistically significant. There was no significant difference in the major morbidity rate (Clavien-Dindo ≥ Grade III) observed after SC (n = 7 [22.6%]) compared with RC (n = 6 [18.7%], P = 0.754). Neoadjuvant therapy was not utilized and adjuvant treatment used infrequently. CONCLUSION Extended gallbladder cancer resection was associated with prolonged OS and DFS but also considerable post-operative morbidity. Further studies are warranted to determine the optimal extent of surgical resection by stage of gallbladder cancer.
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Affiliation(s)
- Jordan Santucci
- Hepatopancreaticobiliary Unit, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of General Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Cathy Hua
- Hepatopancreaticobiliary Unit, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Lynn Chong
- Hepatopancreaticobiliary Unit, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Elizabeth Lockie
- Department of General Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
| | - Justin Lim
- Department of General Surgery, Eastern Health, Box Hill, Victoria, Australia
| | - Sean Lim
- Department of General Surgery, Monash Health, Clayton, Victoria, Australia
| | - Warren Zhou
- Departent of General Surgery, Epworth Eastern Hospital, Box Hill, Victoria, Australia
| | - Luke Bradshaw
- Hepatopancreaticobiliary Unit, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of General Surgery, Royal Melbourne Hospital, Parkville, Victoria, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
- Departent of General Surgery, Epworth Eastern Hospital, Box Hill, Victoria, Australia
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Ito K, Kawaguchi Y, Nishioka Y, Miyata A, Ichida A, Akamatsu N, Kokudo N, Hasegawa K. Original articles: step-by-step decision-making for achieving oncologically acceptable but avoiding over-invasive surgery for gallbladder cancer. HPB (Oxford) 2025; 27:186-194. [PMID: 39609129 DOI: 10.1016/j.hpb.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/10/2024] [Accepted: 10/29/2024] [Indexed: 11/30/2024]
Abstract
BACKGROUND Gallbladder cancer is a malignancy with a highly dismal prognosis, requiring optimal surgical strategies to achieve effective outcomes. We aimed to evaluate the outcomes of our algorithm-based decision-making approach based on image T-factors and intraoperative pathology of regional lymph node metastases and the bile duct stumps in patients undergoing gallbladder cancer resection. METHODS A prospectively maintained database of patients who underwent gallbladder cancer resection between April 2001 and June 2022 was reviewed. Our approach included the decision on the extent of local lymph node dissection based on image T-factors and intraoperative rapid pathological diagnosis. The need for extra bile duct resection was decided according to the intraoperative rapid pathological diagnosis of the cystic or bile duct stump. RESULTS Overall, 148 patients underwent gallbladder cancer resection and were assessed to evaluate the efficacy of an institutional algorithm-based surgical strategy. Oncologically acceptable surgery rate was 98.6 and 96.9 % in terms of decision-making on the extents of lymph node dissection and bile duct resection, respectively. CONCLUSION Our step-by-step decision-making approach based on image T-factors and intraoperative pathology for gallbladder cancer resection was effective in achieving oncologically acceptable surgeries.
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Affiliation(s)
- Kyoji Ito
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yoshikuni Kawaguchi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yujiro Nishioka
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akinori Miyata
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Gu Y, Yang R, Zhang Y, Guo M, Takehiro K, Zhan M, Yang L, Wang H. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. MOLECULAR BIOMEDICINE 2025; 6:2. [PMID: 39757310 PMCID: PMC11700966 DOI: 10.1186/s43556-024-00239-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/26/2024] [Accepted: 12/02/2024] [Indexed: 01/07/2025] Open
Abstract
Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.
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Affiliation(s)
- Yixiang Gu
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Ruifeng Yang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Yang Zhang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Miaomiao Guo
- The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China
| | | | - Ming Zhan
- The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China
- Department of Systems Biology, Beckman Research Institute, City of Hope, Monrovia, CA, 91016, USA
| | - Linhua Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Hui Wang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
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Lu X, Hu K, Zhang D, Yin X, Nie J, Zhao K. KLF5 silencing restrains proliferation, invasion, migration and angiogenesis of gallbladder carcinoma cells by transcriptional regulation of PDGFA. J Cancer Res Clin Oncol 2024; 151:11. [PMID: 39704786 PMCID: PMC11662046 DOI: 10.1007/s00432-024-06059-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/04/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND Krüppel-like factor 5 (KLF5) is recognized as a tumor mediator in multiple types of tumors. Nevertheless, whether KLF5 plays a role in gallbladder cancer (GBC) remains to be elucidated. This study aims to clarify the role of KLF5 in the proliferation, migration and angiogenesis in GBC cells. METHODS The expressions of KLF5 and platelet-derived growth factor subunit A (PDGFA) in GBC cell lines were analyzed by qRT-PCR and western blot assay. Cell proliferation was assessed utilizing the Cell Counting Kit-8 assay and EDU staining. Cell apoptosis was evaluated using flow cytometry, and apoptosis-related proteins was examined by western blotting. The migratory and invasive capabilities were evaluated utilizing wound healing and Transwell. Angiogenesis was assessed by ELISA, tube formation assay and western blot. The interaction between KLF5 and PDGFA was confirmed by ChIP assay, as well as luciferase reporter assay. RESULTS In this study, we discovered that the levels of KLF5 and PDGFA were upregulated in GBC cells. Silencing of KLF5 reduced the viability and suppressed the proliferation of GBC cells, as well as promoting the apoptosis. In addition, KLF5 silencing restrained the invasion and migration and angiogenesis in NOZ and GBC-SD cells. KLF5 transcription activated PDGFA expression and KLF5 was proved to bind to PDGFA promoter in NOZ cells. Following the silencing of PDGFA, the proliferation, invasion, migration, angiogenesis and apoptosis exhibited similar changes to KLF5 silencing. Additionally, PDGFA overexpression reversed the effects of KLF5 silencing on NOZ cells. CONCLUSION Collectively, our results suggest that KLF5 regulates GBC cell proliferation, invasion, migration, angiogenesis, as well as apoptosis, via mediating PDGFA transcriptionally, which might provide a novel therapeutic strategy for treatment of human GBC.
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Affiliation(s)
- Xiaowei Lu
- Department of General Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China
| | - Kui Hu
- Department of General Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China
| | - Dandan Zhang
- Department of General Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China
| | - Xuefeng Yin
- Department of General Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China
| | - Jifeng Nie
- Department of Emergency Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China
| | - Kai Zhao
- Department of General Surgery, Zhejiang Integrated Traditional and Western Medicine Hospital, Hangzhou, 310009, Zhejiang, China.
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Jang Y, Kim JY, Han SY, Park A, Baek SJ, Lee G, Kang J, Ryu H, Kim SH. Establishment of a chronic biliary disease mouse model with cholecystoduodenal anastomosis for intestinal microbiome preservation. World J Gastroenterol 2024; 30:4937-4946. [PMID: 39679313 PMCID: PMC11612716 DOI: 10.3748/wjg.v30.i46.4937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases. AIM To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases. METHODS We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi. RESULTS In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans. CONCLUSION The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.
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Affiliation(s)
- Yunseon Jang
- Translational Immunology Institute, Chungnam National University School of Medicine, Daejeon 35015, South Korea
| | - Jung Yeon Kim
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea
| | - Song Yeon Han
- Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea
| | - Arum Park
- AtoGen Co., Ltd., Techno 1-ro, Daejeon 35015, South Korea
| | - So Jeong Baek
- AtoGen Co., Ltd., Techno 1-ro, Daejeon 35015, South Korea
| | - Gyurim Lee
- AtoGen Co., Ltd., Techno 1-ro, Daejeon 35015, South Korea
| | - Jihee Kang
- AtoGen Co., Ltd., Techno 1-ro, Daejeon 35015, South Korea
| | - Hyewon Ryu
- Translational Immunology Institute, Chungnam National University School of Medicine, Daejeon 35015, South Korea
- Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea
| | - Seok-Hwan Kim
- Department of Surgery, Chungnam National University Hospital, Daejeon 35015, South Korea
- Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon 35015, South Korea
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11
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Dong J, Zhu Z. Efficacy of neoadjuvant therapy and lymph node dissection in advanced gallbladder cancer without distant metastases: a SEER database analysis. Front Oncol 2024; 14:1511583. [PMID: 39655073 PMCID: PMC11625672 DOI: 10.3389/fonc.2024.1511583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 11/06/2024] [Indexed: 12/12/2024] Open
Abstract
Purpose To investigate the effectiveness of neoadjuvant therapy and lymph node dissection(LND) on overall survival (OS) in patients with stage III/IV gallbladder cancer without distant metastases. Methods Data from 101 patients who received neoadjuvant therapy followed by surgery combined with adjuvant chemotherapy, and 1412 patients who received direct surgical treatment followed by adjuvant chemotherapy, were collected from the SEER database from 2004 to 2020. Patients were divided into group A (neoadjuvant therapy) and group B (direct surgery) based on the treatment modality. A total of 202 cases were obtained after propensity score matching, with 101 cases in each group (A and B). Cox unifactorial and multifactorial analyses were performed to identify independent risk factors for patients with advanced cholecystic carcinoma, and the Kaplan-Meier method was used to analyze overall survival (OS). The Cox proportional hazards model was used to investigate the effect of different subgroups on OS in both patient groups. Further survival analyses were conducted to determine whether lymph node dissection(LND) was beneficial for patients receiving neoadjuvant therapy for gallbladder cancer. Results Cox univariate analysis showed that marital status, AJCC stage, number of LND, tumor size, and treatment modality were associated with OS (P<0.05). Cox multifactorial regression analysis indicated that AJCC stage, LND, tumor size, and treatment modality were independent risk factors for OS in patients with non-metastatic advanced gallbladder cancer (P<0.05). Survival curves demonstrated that the OS in group A was longer than in group B (median OS: 30 months vs. 14 months, P<0.001). Subgroup analysis indicated that neoadjuvant therapy had a consistent effect on the OS of patients with advanced gallbladder cancer, improving both survival time and outcomes. Survival curves indicated that lymph node dissection was not significant in group A patients (p>0.05) but was significant in group B (p<0.05). Conclusion Neoadjuvant therapy can improve the OS of patients with non-metastatic stage III/IV gallbladder cancer and is an independent risk factor affecting prognosis; however, the significance of lymph node dissection in these patients still needs further study.
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Affiliation(s)
- Jun Dong
- Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Zhengqiu Zhu
- Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
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12
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Atyah MM, Luo Y, Liu R, Yang Z, Xu L. The application of hepatopancreatoduodenectomy in advanced gallbladder carcinoma: Patients' selection, surgical outcome and influence on survival compared to radical cholecystectomy. Asian J Surg 2024:S1015-9584(24)02415-1. [PMID: 39580293 DOI: 10.1016/j.asjsur.2024.10.139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 10/22/2024] [Indexed: 11/25/2024] Open
Abstract
AIM to investigate hepatopancreatoduodenectomy (HPD) application in gallbladder carcinoma (GBC) and compare it to radical cholecystectomy (RC) regarding patients' characteristics, surgical outcome and survival. METHODS Patients treated in our center were included. Three groups (HPD, RC, no-surgery) were compared. Comparisons included basic characteristics, liver function, tumor biomarkers, surgical complications, outcome, and survival. Differences in severity, surgical risks and survival were investigated. RESULTS In total, 19 patients in HPD, 89 in RC and 20 in no-surgery groups were included. Median follow-up was 42.0 months. Compared to RC, HPD group revealed increased severity represented by significantly higher rates of elevated ALT, AST, TB, DB, preoperative biliary decompression, T3/4, N1/2, stage III/IV, and MVI. Similar severity was observed between HPD and no-surgery groups. Additionally, HPD presented higher risks of perioperative bleeding, transfusion and complications (grade III/IV). Pancreatic fistula and delayed gastric emptying were most encountered in HPD and only one mortality was recorded. Although HPD had shorter survival in general population (HPD: 17 ± 5.804, RC: 49 ± 11.433,P < 0.001); however, in matched (PSM) advanced stages, its benefits matched RC (HPD: 17 ± 4.793, RC: 11 ± 1.169, P = 0.966). Significant survival advantages were observed when comparing HPD to no-surgery group (HPD: 17 ± 5.804, no-surgery: 7 ± 0.836, P = 0.013). CONCLUSION Cases benefiting from HPD are usually severe and comparable to unresectable cases. Although HPD complexity and complication risks are higher than RC, the survival benefits of HPD in advanced GBC stages are not inferior. Thus, HPD is a valuable option in such patients and can be the only approach to achieve R0 resection.
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Affiliation(s)
- Manar Mikhail Atyah
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, 2 East Yinghuayuan Street, Chaoyang District, Beijing, 100029, China.
| | - Yingjixing Luo
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, 2 East Yinghuayuan Street, Chaoyang District, Beijing, 100029, China.
| | - Ruyi Liu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, 2 East Yinghuayuan Street, Chaoyang District, Beijing, 100029, China.
| | - Zhiying Yang
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, 2 East Yinghuayuan Street, Chaoyang District, Beijing, 100029, China.
| | - Li Xu
- Department of Hepatobiliary and Pancreatic Surgery, China-Japan Friendship Hospital, 2 East Yinghuayuan Street, Chaoyang District, Beijing, 100029, China.
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13
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Li R, Chen X, Wang B, Ai B, Min F, Cao D, Zhou J, Yan T. Comparison of treatment models for single primary advanced gallbladder cancer. Front Immunol 2024; 15:1500091. [PMID: 39606221 PMCID: PMC11599203 DOI: 10.3389/fimmu.2024.1500091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024] Open
Abstract
Purpose Treatment for advanced gallbladder cancer (GBC) remains controversial, with various recommendations regarding the choice and combination of surgery and adjuvant therapy. The present article is targeting for the exploration of optimal treatment models for advanced GBC. Methods AJCC (American Joint Committee on Cancer, 8th edition) stage III and stage IV GBC, were defined as advanced GBC. Patients with advanced GBC were identified using the Surveillance, Epidemiology, and End Results (SEER) database and departmental cohort. Because of the most representative, only gallbladder adenocarcinoma (GBAC) patients were selected. Based on their surgical status (No, Non-radical and Radical surgery), chemotherapy status (Chemotherapy, No chemotherapy), and radiotherapy status (Radiotherapy, No radiotherapy), treatment models were categorized. For the purposes of evaluating the treatment outcomes of various treatment models and determining the risk element for cancer-specific survival (CSS), Cox regression analysis was applied. Kaplan-Meier curves were used before and after adjusting for covariates, with log-rank tests used to analyze discrepancies between curves. Immunotherapy was analyzed using clinical data from departmental cohort. Finally, to compensate for the limitations of the database, a review examines the progress in treatment models for advanced GBC. Results 5,154 patients aged over 18 years with solitary primary advanced GBC were identified from the SEER database. In advanced GBC patients, the treatment model has emerged as a significant prognostic factor. "Radical surgery + Chemotherapy + Radiotherapy" models maximally improved the CSS of advanced GBC before and after adjusting for covariates, while "No surgery + No chemotherapy + No radiotherapy" model had the lowest CSS. The present conclusions were supported even after subgroup analysis by AJCC stage. The efficacy of immunotherapy was demonstrated in the departmental cohort analysis. Additionally, this article provides a comprehensive overview of recent advancements in various emerging treatment strategies. Conclusion Even when optimal treatment model cannot be pursued, providing comprehensive combinations of treatments to advanced GBC patients whenever possible is always beneficial for their survival.
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Affiliation(s)
- Rongxuan Li
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bingchen Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bolun Ai
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fangdi Min
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dayong Cao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tao Yan
- Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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14
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Choi SY, Kim JH, Lee JE, Moon JE. Preoperative MRI-based nomogram to predict survival after curative resection in patients with gallbladder cancer: a retrospective multicenter analysis. Abdom Radiol (NY) 2024; 49:3847-3861. [PMID: 38969822 DOI: 10.1007/s00261-024-04444-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/02/2024] [Accepted: 06/07/2024] [Indexed: 07/07/2024]
Abstract
PURPOSE To use preoperative MRI data to construct a nomogram to predict survival in patients who have undergone R0 resection for gallbladder cancer. METHODS The present retrospective study included 143 patients (M:F, 76:67; 67.15 years) with gallbladder cancer who underwent preoperative MRI and subsequent R0 resection between 2013 and 2021 at two tertiary institutions. Clinical and radiological features were analyzed using univariate and multivariate Cox regression analysis to identify independent prognostic factors. Based on the multivariate analysis, we developed an MRI-based nomogram for determining prognoses after curative resections of gallbladder cancer. We also obtained calibration curves for 1-,3-, and 5-year survival probabilities. RESULTS The multivariate model consisted of the following independent predictors of poor overall survival (OS), which were used for constructing the nomogram: age (years; hazard ratio [HR] = 1.04; 95% confidence interval [CI], 1.04-1.07; p = 0.033); tumor size (cm; HR = 1.40; 95% CI, 1.09-1.79; p = 0.008); bile duct invasion (HR = 3.54; 95% CI, 1.66-7.58; p = 0.001); regional lymph node metastasis (HR = 2.47; 95% CI, 1.10-5.57; p = 0.029); and hepatic artery invasion (HR = 2.66; 95% CI, 1.04-6.83; p = 0.042). The nomogram showed good probabilities of survival on the calibration curves, and the concordance index of the model for predicting overall survival (OS) was 0.779. CONCLUSION Preoperative MRI findings could be used to determine the prognosis of gallbladder cancer, and the MRI-based nomogram accurately predicted OS in patients with gallbladder cancer who underwent curative resection.
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Affiliation(s)
- Seo-Youn Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-Ro, Gangnam-gu, Seoul, 06351, Korea
| | - Jung Hoon Kim
- Department of Radiology and Research Institute of Radiological Science, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehang-no, Chongno-gu, Seoul, 110-744, Republic of Korea.
| | - Ji Eun Lee
- Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, 170 Jomaru-ro, Bucheon-Si, Gyeonggi-do, 14584, Republic of Korea
| | - Ji Eun Moon
- Department of Biostatistics, Clinical Trial Center, Soonchunhyang University College of Medicine, Bucheon Hospital, 170 Jomaru-ro, Bucheon, Gyeonggi-do, Republic of Korea
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15
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Li XF, Ma TT, Li T. Risk factors and survival prediction model establishment for prognosis in patients with radical resection of gallbladder cancer. World J Gastrointest Surg 2024; 16:3239-3252. [PMID: 39575289 PMCID: PMC11577418 DOI: 10.4240/wjgs.v16.i10.3239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 08/17/2024] [Accepted: 09/06/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, and is often undetected until advanced stages, making curative surgery unfeasible for many patients. Curative surgery remains the only option for long-term survival. Accurate postsurgical prognosis is crucial for effective treatment planning. tumor-node-metastasis staging, which focuses on tumor infiltration, lymph node metastasis, and distant metastasis, limits the accuracy of prognosis. Nomograms offer a more comprehensive and personalized approach by visually analyzing a broader range of prognostic factors, enhancing the precision of treatment planning for patients with GBC. AIM To identify risk factors and develop a predictive model for GBC prognosis. METHODS A retrospective study analyzed the clinical and pathological data of 93 patients who underwent radical surgery for GBC at Peking University People's Hospital from January 2015 to December 2020. Kaplan-Meier analysis was used to calculate the 1-, 2- and 3-year survival rates. The log-rank test was used to evaluate factors impacting prognosis, with survival curves plotted for significant variables. Single-factor analysis revealed statistically significant differences, and multivariate Cox regression identified independent prognostic factors. A nomogram was developed and validated with receiver operating characteristic curves and calibration curves. RESULTS Among 93 patients who underwent radical surgery for GBC, 30 patients survived, accounting for 32.26% of the sample, with a median survival time of 38 months. The 1-year, 2-year, and 3-year survival rates were 83.87%, 68.82%, and 53.57%, respectively. Univariate analysis revealed that carbohydrate antigen 19-9 expression, T stage, lymph node metastasis, histological differentiation, surgical margins, and invasion of the liver, extrahepatic bile duct, nerves, and vessels (P ≤ 0.001) significantly impacted patient prognosis after curative surgery. Multivariate Cox regression identified lymph node metastasis (P = 0.03), histological differentiation (P < 0.05), nerve invasion (P = 0.036), and extrahepatic bile duct invasion (P = 0.014) as independent risk factors. A nomogram model with a concordance index of 0.838 was developed. Internal validation confirmed the model's consistency in predicting the 1-year, 2-year, and 3-year survival rates. CONCLUSION Lymph node metastasis, tumor differentiation, extrahepatic bile duct invasion, and perineural invasion are independent risk factors. A nomogram based on these factors can be used to personalize and improve treatment strategies.
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Affiliation(s)
- Xing-Fei Li
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Tan-Tu Ma
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Peking University, Beijing 100044, China
| | - Tao Li
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Peking University, Beijing 100044, China
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16
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Dedopoulou P, Rodis N, Lampropoulos C, Kitsou KS, Mpogiatzopoulos N, Kehagias I. Synchronous Primary Gallbladder and Colon Adenocarcinoma: A Case Report and Systematic Literature Review. Cureus 2024; 16:e69092. [PMID: 39391434 PMCID: PMC11466057 DOI: 10.7759/cureus.69092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2024] [Indexed: 10/12/2024] Open
Abstract
Synchronous primary malignancies, defined as two or more primary malignancies diagnosed simultaneously or within six months, are uncommon and present unique diagnostic and therapeutic challenges. Synchronous primary adenocarcinoma of the gallbladder and colon is particularly rare. We report a case of a 48-year-old female presenting with persistent right upper abdominal pain. Laboratory tests and imaging studies initially suggested xanthogranulomatous cholecystitis. However, subsequent laparoscopic cholecystectomy and pathological examination revealed a moderately differentiated adenocarcinoma of the gallbladder (pT2bN1M0). Further staging with CT and PET-CT scans identified a suspicious mass in the transverse colon, confirmed by colonoscopy and surgical resection as well-differentiated adenocarcinoma of the transverse colon (pT3N0M0). Immunohistochemistry and genetic profiling of both tumors indicated distinct primary origins without loss of mismatch repair (MMR) protein expression. The patient underwent additional liver resection, lymph node dissection, and right extended hemicolectomy. She is currently undergoing further staging and awaiting chemotherapy. A review of English-language literature revealed eight reported cases of synchronous primary gallbladder and colorectal cancer and a total of 13 with synchronous primary malignancy of other organs. Such cases are rare and diagnostically complex cases. Common factors contributing to multiple primary malignancies (MPM) include genetic predispositions, previous cancer treatments, and lifestyle factors such as smoking and alcohol consumption. This case underscores the importance of thorough investigation and prompt treatment in patients suspected of having MPM. Advances in diagnostic imaging and molecular profiling are crucial for early detection and tailored therapeutic strategies. Standardized guidelines for managing synchronous cancers are needed to improve patient outcomes.
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Affiliation(s)
| | - Nikiforos Rodis
- Department of Surgery, General University Hospital of Patras, Patras, GRC
| | | | | | | | - Ioannis Kehagias
- Department of Surgery, General University Hospital of Patras, Patras, GRC
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17
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Khanal B, Lamichhane P, Bhatta RR, Bastakoti S. Adenosquamous Carcinoma of Gallbladder: A Rare Case Report. Cureus 2024; 16:e68049. [PMID: 39206332 PMCID: PMC11357704 DOI: 10.7759/cureus.68049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2024] [Indexed: 09/04/2024] Open
Abstract
Carcinoma of the gallbladder is an uncommon malignancy with a poor prognosis overall. Histologically, adenocarcinoma is the most common type of gallbladder carcinoma. Adenosquamous carcinoma is a rare histological type of gallbladder carcinoma comprising both the glandular and squamous elements. Adenosquamous carcinoma shows more aggressive behavior than adenocarcinomas and is often detected in a late advanced stage. Treatment is usually extended surgical resection but has a poor prognosis. We present a rare case of adenosquamous carcinoma with lymphovascular invasion in a 72-year-old male who was managed with extended cholecystectomy.
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Affiliation(s)
| | | | - Ranjan R Bhatta
- Pathology, BP Koirala Memorial Cancer Hospital, Bharatpur, NPL
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18
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Marino R, Ratti F, Casadei-Gardini A, Rimini M, Pedica F, Clocchiatti L, Aldrighetti L. The oncologic burden of residual disease in incidental gallbladder cancer: An elastic net regression model to profile high-risk features. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108397. [PMID: 38815335 DOI: 10.1016/j.ejso.2024.108397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 05/04/2024] [Accepted: 05/07/2024] [Indexed: 06/01/2024]
Abstract
INTRODUCTION Incidental Gallbladder Cancer (IGBC) following cholecystectomy constitutes a significant portion of gallbladder cancer diagnoses. Re-exploration is advocated to optimize disease clearance and enhance survival rates. The consistent association of residual disease (RD) with inferior oncologic outcomes prompts a critical examination of re-resection's role as a modifying factor in the natural history of IGBC. METHODS All patients diagnosed with gallbladder cancer between 2012 and 2022 were included. An elastic net regularized regression model was employed to profile high-risk predictors of RD within the IGBC group. Survival outcomes were assessed based on resection margins and RD. RESULTS Among the 181 patients undergoing re-exploration for IGBC, 133 (73.5 %) harbored RD, while 48 (26.5 %) showed no evidence. The elastic net model, utilizing a selected λ = 0.029, identified six coefficients associated with the risk of RD: aspiration from cholecystectomy (0.141), hepatic tumor origin (1.852), time to re-exploration >8 weeks (1.879), positive margin status (2.575), higher T stage (1.473), and poorly differentiated tumors (2.241). Furthermore, the study revealed a median overall survival of 44 months (CI 38-60) for IGBC patients with no evidence of RD, compared to 31 months (23-42) for those with RD (p < 0.001). CONCLUSION Re-resection revealed a high incidence of RD (73.5 %), significantly correlating with poorer survival outcomes. The preoperative identification of high-risk features provides a reliable biological disease profile. This aids in strategic preselection of patients who may benefit from re-resection, underscoring the need to consolidate outcomes with tailored chemotherapy for those with unfavorable characteristics.
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Affiliation(s)
- Rebecca Marino
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Francesca Ratti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy.
| | | | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Hospital, 20132, Milan, Italy
| | - Federica Pedica
- Department of Experimental Oncology, Pathology Unit, San Raffaele Hospital, 20132, Milan, Italy
| | - Lucrezia Clocchiatti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy
| | - Luca Aldrighetti
- IRCCS San Raffaele Hospital, Hepatobiliary Surgery Division, 20132, Milan, Italy; University Vita-Salute San Raffaele, 20132, Milan, Italy
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19
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Naples R, Perlmutter BC, Lu H, Allende D, Tu C, Hitawala A, Chadalavada P, Padbidri V, Haddad A, Simon R, Walsh RM, Augustin T. Intramucosal Extent as a Marker for Advanced Disease and Survival in Gallbladder Adenocarcinoma. Am Surg 2024; 90:1133-1139. [PMID: 38174690 DOI: 10.1177/00031348231220581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
BACKGROUND Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. The clinical significance of focal vs diffuse GBC remains unclear. METHODS A retrospective review was conducted on all patients with non-metastatic GBC at a quaternary care center. Pathology was reviewed, and gallbladder cancer pattern was defined based on the extent of mucosal involvement; "diffuse" if the tumor was multicentric or "focal" if the tumor was only in a single location. Patients undergoing liver resection and portal lymphadenectomy were considered to have definitive surgery. The primary outcome was overall survival and assessed by Kaplan-Meier curves. RESULTS 63 patients met study criteria with 32 (50.7%) having diffuse cancer. No difference was observed in utilization of definitive surgery between the groups (14 [43.8%] with focal and 12 [38.7%] with diffuse, P = .88). Lymphovascular invasion (P = .04) and higher nodal stage (P = .04) were more common with diffuse GBC. Median overall survival was significantly improved in those with focal cancer (5.1 vs 1.2 years, P = .02). Although not statistically significant, this difference in overall survival persisted in patients who underwent definitive surgery (4.3 vs 2.4 years, P = .70). DISCUSSION Patients with diffuse involvement of the gallbladder mucosa likely represent a subset with aggressive biology and worse overall survival compared to focal disease. These findings may aid surgeons in subsequent surgical and medical decision-making for patients with GBC.
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Affiliation(s)
- Robert Naples
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | | | - Haiyan Lu
- Department of Pathology, Cleveland Clinic, Cleveland, OH, USA
| | - Daniela Allende
- Department of Pathology, Cleveland Clinic, Cleveland, OH, USA
| | - Chao Tu
- Department of Quantitative Health Sciences, Cleveland Clinic Learner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Asif Hitawala
- Department of Internal Medicine, Fairview Hospital, Cleveland, OH, USA
| | | | - Vinay Padbidri
- Department of Internal Medicine, Fairview Hospital, Cleveland, OH, USA
| | - Abdo Haddad
- Department of Hematology Oncology, Fairview Hospital, Cleveland, OH, USA
| | - Robert Simon
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Toms Augustin
- Department of General Surgery, Cleveland Clinic, Cleveland, OH, USA
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20
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Zhao ZH, Huang Y, Jiang C, Lv GY, Wang M. Comparative prognosis and risk assessment in gallbladder neuroendocrine neoplasms versus adenocarcinomas. Front Endocrinol (Lausanne) 2024; 15:1326112. [PMID: 38390209 PMCID: PMC10882707 DOI: 10.3389/fendo.2024.1326112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 01/23/2024] [Indexed: 02/24/2024] Open
Abstract
Background Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions. Methods We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores. Results A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively. Conclusion Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.
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Affiliation(s)
| | | | | | | | - Meng Wang
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
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21
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Dronov O, Kozachuk Y, Bakunets Y, Bakunets P, Prytkov F. THE CRYOGENIC TECHNOLOGIES APPLICATION IN THE COMPLEX TREATMENT OF GALLBLADDER ADENOCARCINOMA WITH INVASION INTO THE PORTAL VEIN BRANCHES: CASE REPORT. Exp Oncol 2023; 45:379-385. [PMID: 38186017 DOI: 10.15407/exp-oncology.2023.03.379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Indexed: 01/09/2024]
Abstract
The right trisectionectomy is the main treatment modality for locally advanced gallbladder cancer with invasion of the intraparenchymal portal vein branches because it allows the achievement of negative resection margins (R0). However, only 10%-25% of such patients are eligible for surgery. The cryosurgical method has been successfully used in the complex treatment of hepatopancreatobiliary malignant neoplasms for many years. The possibility of its application close to major blood vessels is one of its advantages. In the presented case, the cryodestruction of the residual tumor with invasion into the anterior wall of the left branch of the portal vein was used as a debulking option during liver resection (R2) due to locally advanced gallbladder cancer. The cryodestruction was performed with application method with a double cryocycle and spontaneous thawing using a Cryo-Pulse device and liquid nitrogen as a cryoagent. No postoperative complications related to cryodestruction were noted. The cryogenic technologies application in the debulking surgery of gallbladder cancer can be a safe treatment modality for residual tumors with invasion into the intraparenchymal branches of the portal vein.
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Affiliation(s)
- O Dronov
- Bogomolets National Medical University, Kyiv, Ukraine
| | - Y Kozachuk
- Bogomolets National Medical University, Kyiv, Ukraine
| | - Y Bakunets
- Bogomolets National Medical University, Kyiv, Ukraine
| | - P Bakunets
- Bogomolets National Medical University, Kyiv, Ukraine
| | - F Prytkov
- Bogomolets National Medical University, Kyiv, Ukraine
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Chen J, Han Y. Development and validation of an online dynamic prognostic nomogram for incidental gallbladder adenocarcinoma patients without distant metastasis after surgery: a population-based study. Front Med (Lausanne) 2023; 10:1175211. [PMID: 38020083 PMCID: PMC10667698 DOI: 10.3389/fmed.2023.1175211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023] Open
Abstract
Background Gallbladder cancer is the most common malignant tumor of the biliary system, most of which is adenocarcinoma. Our study explored developing and validating a nomogram to predict overall and cancer-specific survival probabilities internally and externally for incidental gallbladder adenocarcinoma patients without distant metastasis after surgery. Methods Patients screened and filtered in the Surveillance, Epidemiology, and End Results (SEER) database, whose years of diagnosis between 2010 and 2015 were collected as a derivation cohort, while those between 2016 and 2019 were a temporal validation cohort. Overall survival (OS) and cancer-specific survival (CSS) were chosen as the primary and secondary endpoints of the retrospective study cohort. Potential clinical variables were selected for a Cox regression model analysis by performing both-direction stepwise selection to confirm the final variables. The performance of final nomograms was evaluated by Harrell's C statistic and Brier score, with a graphical receptor operating characteristic (ROC) curve and calibration curve. Results Seven variables of age, race, tumor size, histologic grade, T stage, regional lymph nodes removed, and positive regional lymph nodes were finally determined for the OS nomogram; sex had also been added to the CSS nomogram. Novel dynamic nomograms were established to predict the prognosis of incidental gallbladder adenocarcinoma patients without distant metastasis after surgery. The ROC curve demonstrated good accuracy in predicting 1-, 3-, and 5-year OS and CSS in both derivation and validation cohorts. Correspondingly, the calibration curve presented perfect reliability between the death or cancer-specific death probability and observed death or cancer-specific death proportion in both derivation and validation cohorts. Conclusion Our study established novel dynamic nomograms based on seven and eight clinical variables separately to predict OS and CSS of incidental gallbladder adenocarcinoma patients without distant metastasis after surgery, which might assist doctors in advising and guiding therapeutic strategies for postoperative gallbladder adenocarcinoma patients in the future.
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Affiliation(s)
- Jie Chen
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
- Department of General Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
| | - Yehong Han
- Department of General Surgery, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
- Department of General Surgery, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
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23
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Jia W, Wang C. KNTC1 and MCM2 are the molecular targets of gallbladder cancer. Aging (Albany NY) 2023; 15:7008-7022. [PMID: 37480569 PMCID: PMC10415569 DOI: 10.18632/aging.204889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 06/15/2023] [Indexed: 07/24/2023]
Abstract
BACKGROUND Gallbladder carcinoma is a malignant epithelial tumor of gallbladder with a high degree of malignancy. However, relationship between KNTC1 and MCM2 and gallbladder cancer is unclear. METHODS GSE139682 and GSE202479 were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) were screened. Functional enrichment analysis and gene set enrichment analysis (GSEA) were performed. Protein-protein interaction (PPI) Network was constructed and analyzed. Gene expression heat map was drawn. Comparative toxicogenomics database (CTD) analysis was performed to find diseases most related to core genes. TargetScan was performed for screening miRNAs that regulated central DEGs. RESULTS 230 DEGs were identified. According to GObp analysis, they were mainly concentrated in regulation of ossification, regulation of spindle microtubule and centromere attachment, cytoskeleton tissue of cortical actin. According to GOcc analysis, they are mainly concentrated in plasma membrane part, cell junction, plasma membrane region and anterior membrane. According to GOmf analysis, they are mainly enriched in protein homodimerization activity, proximal promoter sequence-specific DNA binding and sulfur compound binding. KEGG showed that target genes were mainly enriched in Hippo signal pathway, p53 signal pathway and cancer pathway. KIFC2, TUBG1, RACGAP1, CHMP4C, SFN and MYH11 were identified as core genes. Gene expression heat map showed that KNTC1, MCM2, CKAP2, RACGAP1, CCNB1 were highly expressed in gallbladder carcinoma samples. CTD analysis showed that KNTC1, MCM2, CKAP2, RACGAP1, CCNB1 were associated with head and neck squamous cell carcinoma, necrosis, inflammation and hepatomegaly. CONCLUSIONS KNTC1 and MCM2 are highly expressed in gallbladder cancer. Higher expression level correlates with worse prognosis.
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Affiliation(s)
- Wei Jia
- Department of Gastrointestinal Surgery, Beijing Rehabilitation Hospital, Capital Medical University, Badachu Xixia, Shijingshan 100144, Beijing, China
| | - Chao Wang
- Department of Hepatobiliary Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
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Kashyap L, Singh A, Tomar S, Gupta A, Sansar B, Chaudhary AK, Mishra BK, Sambasivaiah K, Kapoor A. Pattern of Care and Outcomes of Gallbladder Cancer Patients: Retrospective Study from a High Incidence Region in India. South Asian J Cancer 2023; 12:245-249. [PMID: 38047044 PMCID: PMC10691906 DOI: 10.1055/s-0043-1761440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023] Open
Abstract
Lakhan KasyapIntroduction Gallbladder cancer (GBC) is the 20th most common cancer in India with a crude incidence rate of 2.3 per 100,000 persons. Of note, it is relatively common in states which fall in the Gangetic plains. Patients often present in the advanced stage and have an unfavorable prognosis. Materials and Methods From January to June 2021, 170 treatment-naive GBC (adenocarcinoma) patients who were registered at a tertiary care cancer center in North India, were included. Data were extracted from electronic medical records and was analyzed with SPSS. Results Median age was 56 years (range 32-77 years) and 65.5% ( n = 112) were female. Incidental GBC was found in 20% patient ( n = 34). Majority of patients (79.4%, n = 135) had preserved performance status. Advanced GBC was present in 85.8% ( n = 146) patients (locally advanced = 37.0% and metastatic = 48.8%). Biliary drainage procedure was performed in 24% of patients (68% of patients with obstructive jaundice). More than half of patients (53.5%) were lost to follow-up without any treatment. There were 33 patients (19.4%) who underwent surgery and 20 of them received neoadjuvant chemotherapy. Adjuvant chemotherapy and adjuvant radiotherapy were received by 13 and 2 patients, respectively. Palliative chemotherapy was administered to 46 patients. The most common chemotherapy regimen was gemcitabine-cisplatin. At a median follow-up of 1.7 months (95% confidence interval, 1-2.4 months), 42 patients (24%) progressed and 24 patients (14%) died, with 6 months estimated progression-free survival and overall survival being 60.2 and 79%, respectively. Conclusion GBC is an aggressive and lethal malignancy predominantly affecting females in the fifth decade with dismal outcomes. Improved access to health care, an aggressive approach in operable cases, and optimization of systemic and adjuvant therapy are the need of the hour.
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Affiliation(s)
- Lakhan Kashyap
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Arpita Singh
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Subham Tomar
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Anuj Gupta
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Bipinesh Sansar
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Amit Kumar Chaudhary
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Bal Krishna Mishra
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Kuraparthy Sambasivaiah
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
| | - Akhil Kapoor
- Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
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Ceci L, Han Y, Krutsinger K, Baiocchi L, Wu N, Kundu D, Kyritsi K, Zhou T, Gaudio E, Francis H, Alpini G, Kennedy L. Gallstone and Gallbladder Disease: Biliary Tract and Cholangiopathies. Compr Physiol 2023; 13:4909-4943. [PMID: 37358507 DOI: 10.1002/cphy.c220028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2023]
Abstract
Cholestatic liver diseases are named primarily due to the blockage of bile flow and buildup of bile acids in the liver. Cholestasis can occur in cholangiopathies, fatty liver diseases, and during COVID-19 infection. Most literature evaluates damage occurring to the intrahepatic biliary tree during cholestasis; however, there may be associations between liver damage and gallbladder damage. Gallbladder damage can manifest as acute or chronic inflammation, perforation, polyps, cancer, and most commonly gallstones. Considering the gallbladder is an extension of the intrahepatic biliary network, and both tissues are lined by biliary epithelial cells that share common mechanisms and properties, it is worth further evaluation to understand the association between bile duct and gallbladder damage. In this comprehensive article, we discuss background information of the biliary tree and gallbladder, from function, damage, and therapeutic approaches. We then discuss published findings that identify gallbladder disorders in various liver diseases. Lastly, we provide the clinical aspect of gallbladder disorders in liver diseases and ways to enhance diagnostic and therapeutic approaches for congruent diagnosis. © 2023 American Physiological Society. Compr Physiol 13:4909-4943, 2023.
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Affiliation(s)
- Ludovica Ceci
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Yuyan Han
- School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
| | - Kelsey Krutsinger
- School of Biological Sciences, University of Northern Colorado, Greeley, Colorado, USA
| | | | - Nan Wu
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Debjyoti Kundu
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Konstantina Kyritsi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Tianhao Zhou
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Heather Francis
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
| | - Gianfranco Alpini
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
| | - Lindsey Kennedy
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
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26
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Wang Z, Wang L, Hua Y, Zhuang X, Bai Y, Wang H. Development and validation of a prognostic nomogram for gallbladder papillary adenocarcinoma. Front Oncol 2023; 13:1157057. [PMID: 37260969 PMCID: PMC10228726 DOI: 10.3389/fonc.2023.1157057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 05/03/2023] [Indexed: 06/02/2023] Open
Abstract
Background Gallbladder papillary adenocarcinoma (GBPA) is an uncharacteristically gallbladder cancer subtype. Although some studies have shown that the prognosis of GBPA patients is significantly better than that of gallbladder adenocarcinoma (GBA) and gallbladder mucinous adenocarcinoma (GBMA) due to its rarity, there is a lack of large sample studies necessary to confirm the clinical characteristics and survival rate of GBPA. Therefore, this study aimed to describe the clinicopathological characteristics affecting survival in GBPA. This data was then used to establish a prognostic nomogram for GBPA. Methods The data of patients diagnosed with gallbladder cancer between 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The clinical features and survival of patients with GBPA were compared with those of GBA and GBMA after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for GBPA. Subsequently, the overall survival (OS) and cancer-specific survival (CSS) nomograms were established to predict GBPA prognosis. The performance and discrimination of the nomogram were measured using concordance index (C-index), calibration curves, receptor operating characteristic curves(ROC), and decision curve analysis (DCA) was applied to examine the net benefit of tients with GBPA, 5798 patients with GBA, and 223 patients with GBMA. The mean 1-, 3- and 5-year OS rates for GBPA were 81.3%, 58.8%, and 49.1%, respectively, while the mean 1-, 3- and 5-year CSS rates were 85.0%, 68.1%, and 61.0%, respectively. The median OS rates was 58 months (95% CI: 43-88), while the median CSS was not reached. The PSM analysis showed a differ statistically significantly in the OS between GBPA and GBA. However, there has no statistically difference in CSS. Conversely, the OS and CSS between GBPA and GBMA have statistically significant differences. Age, marital, T stage, and M stage were strongly linked to the prognosis for OS, while T-stage, M-stage, and surgery were significantly associated with the prognosis for CSS in GBPA patients. The AUC for the 1-, 3-, and 5-year OS were 0.722 (95%CI: 0.630-0.813), 0.728 (95%CI: 0.665-0.790), and 0.706 (95%CI: 0.641-0.771), respectively. The AUC for the 1-, 3-, and 5-year CSS were 0.749 (95%CI: 0.659-0.840), 0.698 (95%CI: 0.627-0.770), and 0.665 (95%CI: 0.594-0.735), respectively. The C-indices for the OS and CSS nomograms were 0.701 (95% CI: 0.634-0.744) and 0.651 (95% CI: 0.598-0.703), respectively. The calibration curves showed that the nomograms were well consistency. The DCA showed that compared with the TNM system, the nomogram models had a significant positive net benefit in survival prediction. Conclusion GBPA has distinct clinicopathological characteristics and survival compared to other gallbladder carcinomas. The established nomogram provided a better prediction of survival for GBPA patients than the traditional TNM models.
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Affiliation(s)
- Zhenfeng Wang
- Department of Image, Baotou Cancer Hospital, Baotou, China
| | - Longlong Wang
- Department of Surgical, Baotou Cancer Hospital, Baotou, China
| | - Yunqi Hua
- Department of Internal Medicine, Baotou Cancer Hospital, Baotou, China
| | - Xiang Zhuang
- Department of Image, Baotou Cancer Hospital, Baotou, China
| | - Yu Bai
- Department of Medical, West Angel Health Tech Co. Ltd., Beijing, China
| | - Huming Wang
- Department of Clinical Laboratory, Baotou Cancer Hospital, Baotou, China
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Toyoda J, Sahara K, Takahashi T, Miyake K, Yabushita Y, Sawada Y, Homma Y, Matsuyama R, Endo I, Pawlik TM. Neoadjuvant Therapy for Extrahepatic Biliary Tract Cancer: A Propensity Score-Matched Survival Analysis. J Clin Med 2023; 12:2654. [PMID: 37048737 PMCID: PMC10095506 DOI: 10.3390/jcm12072654] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/19/2023] [Accepted: 03/30/2023] [Indexed: 04/05/2023] Open
Abstract
Background: Although surgery is the mainstay of curative-intent treatment for extrahepatic biliary tract cancer (EBTC), recurrence following surgery can be high and prognosis poor. The impact of neoadjuvant therapy (NAT) relative to upfront surgery (US) among patients with EBTC remains unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) databases was utilized to identify patients who underwent surgery from 2006 to 2017 for EBTC, including gallbladder cancer (GBC) and extrahepatic cholangiocarcinoma (ECC). Trends in NAT utilization were investigated, and the impact of NAT on prognosis was compared with US using a propensity score-matched (PSM) analysis. Results: Among 6582 EBTC patients (GBC, n = 4467, ECC, n = 2215), 1.6% received NAT; the utilization of NAT for EBTC increased over time (Ptrend = 0.03). Among patients with lymph node metastasis, the lymph node ratio was lower among patients with NAT (0.18 vs. 0.40, p < 0.01). After PSM, there was no difference in overall survival (OS) and cancer-specific survival (CSS) among patients treated with NAT versus US (5-year OS: 24.0% vs. 24.6%, p = 0.14, 5-year CSS: 38.0% vs. 36.1%, p = 0.21). A subgroup analysis revealed that NAT was associated with improved OS and CSS among patients with stages III-IVA of the disease (OS: HR 0.65, 95%CI 0.46-0.92, p = 0.02, CSS: HR 0.62, 95%CI 0.41-0.92, p = 0.01). Conclusions: While NAT did not provide an overall benefit to patients undergoing surgery for EBTC, individuals with advanced-stage disease had improved OS and CSS with NAT. An individualized approach to NAT use among patients with EBTC may provide a survival benefit.
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Affiliation(s)
- Junya Toyoda
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Kota Sahara
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA
| | - Tomoaki Takahashi
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Kentaro Miyake
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Yasuhiro Yabushita
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Yuki Homma
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Ryusei Matsuyama
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
| | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA
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Dawuti W, Dou J, Li J, Zhang R, Zhou J, Maimaitiaili M, Zhou R, Lin R, Lü G. Label-free surface-enhanced Raman spectroscopy of serum with machine-learning algorithms for gallbladder cancer diagnosis. Photodiagnosis Photodyn Ther 2023; 42:103544. [PMID: 37004836 DOI: 10.1016/j.pdpdt.2023.103544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 03/24/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023]
Abstract
Gallbladder cancer (GBC) is a rare but frequently fatal biliary tract malignancy that is typically only discovered when it is already advanced. In the search of an efficient diagnosis method. Therefore, in this study, we investigated a novel technique for the quick and non-invasive diagnosis of GBC based on serum surface-enhanced Raman spectroscopy (SERS). SERS spectra of serum from 41 patients with GBC and 72 normal subjects were recorded. Principal component analysis-linear discriminant analysis (PCA-LDA), and PCA-support vector machine (PCA-SVM), Linear SVM and Gaussian radial basis function-SVM (RBF-SVM) algorithms were used to establish the classification models, respectively. When the Linear SVM was used, the overall diagnostic accuracy for classifying the two groups could achieve 97.1%, and when RBF-SVM was used, the diagnostic sensitivity of GBC was 100%. The results demonstrated that SERS in combination with a machine learning algorithm is a promising candidate to be one of the diagnostic tools for GBC in the future.
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Affiliation(s)
- Wubulitalifu Dawuti
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; School of Public Health, Xinjiang Medical University, Urumqi 830054, China
| | - Jingrui Dou
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; School of Public Health, Xinjiang Medical University, Urumqi 830054, China
| | - Jintian Li
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; School of Public Health, Xinjiang Medical University, Urumqi 830054, China
| | - Rui Zhang
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; School of Public Health, Xinjiang Medical University, Urumqi 830054, China
| | - Jing Zhou
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; College of Pharmacy, Xinjiang Medical University, Urumqi 830054, China
| | - Maierhaba Maimaitiaili
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; College of Pharmacy, Xinjiang Medical University, Urumqi 830054, China
| | - Run Zhou
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; College of Pharmacy, Xinjiang Medical University, Urumqi 830054, China
| | - Renyong Lin
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
| | - Guodong Lü
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
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Editorial: Surgical Advances in Pancreaticobiliary Diseases. J Clin Med 2023; 12:jcm12041268. [PMID: 36835803 PMCID: PMC9964516 DOI: 10.3390/jcm12041268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Pancreaticobiliary diseases include malignant tumors arising in organs with a complex anatomy, such as the pancreas and bile ducts, often presenting as locally advanced or metastatic lesions, and they frequently have a poor prognosis [...].
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Zhang Y, Liu Y, Liu J, Liu T, Xiong H, Li W, Fu X, Zhou F, Liao S, Fang L, Liang B. Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review. Front Immunol 2023; 14:1144371. [PMID: 37020545 PMCID: PMC10067585 DOI: 10.3389/fimmu.2023.1144371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 03/06/2023] [Indexed: 04/07/2023] Open
Abstract
Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.
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Affiliation(s)
- Yuzhu Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yuchen Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jing Liu
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Tiande Liu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hu Xiong
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wen Li
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaowei Fu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fan Zhou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shousheng Liao
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Bo Liang, ; Lu Fang, ; Shousheng Liao,
| | - Lu Fang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Bo Liang, ; Lu Fang, ; Shousheng Liao,
| | - Bo Liang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- *Correspondence: Bo Liang, ; Lu Fang, ; Shousheng Liao,
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Uzun MA, Tilki M, Alkan Kayaoğlu S, Çiçek Okuyan G, Kılıçoğlu ZG, Gönültaş A. Long-term results and prognostic factors after surgical treatment for gallbladder cancer. Turk J Surg 2022; 38:334-344. [PMID: 36875276 PMCID: PMC9979551 DOI: 10.47717/turkjsurg.2022.5861] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 11/10/2022] [Indexed: 01/12/2023]
Abstract
Objectives Gallbladder cancer is relatively rare and traditionally regarded as having poor prognosis. There is controversy about the effects of clinicopathological features and different surgical techniques on prognosis. The aim of this study was to investigate the effects of clinicopathological characteristics of the patients with surgically treated gallbladder cancer on long-term survival. Material and Methods We retrospectively analyzed the database of gallbladder cancer patients treated at our clinic between January 2003 and March 2021. Results Of 101 evaluated cases, 37 were inoperable. Twelve patients were determined unresectable based on surgical findings. Resection with curative intent was performed in 52 patients. The one-, three-, five-, and 10-year survival rates were 68.9%, 51.9%, 43.6%, and 43.6%, respectively. Median survival was 36.6 months. On univariate analysis, poor prognostic factors were determined as advanced age; high carbohydrate antigen 19-9 and carcinoembryonic antigen levels; non-incidental diagnosis; intraoperative incidental diagnosis; jaundice; adjacent organ/structure resection; grade 3 tumors; lymphovascular invasion; and high T, N1 or N2, M1, and high AJCC stages. Sex, IVb/V segmentectomy instead of wedge resection, perineural invasion, tumor location, number of resected lymph nodes, and extended lymphadenectomy did not significantly affect overall survival. On multivariate analysis, only high AJCC stages, grade 3 tumors, high carcinoembryonic antigen levels, and advanced age were independent predictors of poor prognosis. Conclusion Treatment planning and clinical decision-making for gallbladder cancer requires individualized prognostic assessment along with standard anatomical staging and other confirmed prognostic factors.
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Affiliation(s)
- Mehmet Ali Uzun
- Clinic of General Surgery, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye.,Clinic of General Surgery, Şişli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
| | - Metin Tilki
- Clinic of General Surgery, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
| | - Sevcan Alkan Kayaoğlu
- Clinic of General Surgery, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
| | - Gülten Çiçek Okuyan
- Clinic of General Surgery, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
| | - Zeynep Gamze Kılıçoğlu
- Clinic of Radiology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
| | - Aylin Gönültaş
- Clinic of Pathology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbul, Türkiye
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Zou L, Yang Y, Zhou B, Li W, Liu K, Li G, Miao H, Song X, Yang J, Geng Y, Li M, Bao R, Liu Y. tRF-3013b inhibits gallbladder cancer proliferation by targeting TPRG1L. Cell Mol Biol Lett 2022; 27:99. [PMID: 36401185 PMCID: PMC9673407 DOI: 10.1186/s11658-022-00398-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 10/25/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND tRNA-derived fragments (tRFs) are newly discovered noncoding RNAs and regulate tumor progression via diverse molecular mechanisms. However, the expression and biofunction of tRFs in gallbladder cancer (GBC) have not been reported yet. METHODS The expression of tRFs in GBC was detected by tRF and tiRNA sequencing in GBC tissues and adjacent tissues. The biological function of tRFs was investigated by cell proliferation assay, clonal formation assay, cell cycle assay, and xenotransplantation model in GBC cell lines. The molecular mechanism was discovered and verified by transcriptome sequencing, fluorescence in situ hybridization (FISH), target gene site prediction, and RNA binding protein immunoprecipitation (RIP). RESULTS tRF-3013b was significantly downregulated in GBC compared with para-cancer tissues. Decreased expression of tRF-3013b in GBC patients was correlated with poor overall survival. Dicer regulated the production of tRF-3013b, and its expression was positively correlated with tRF-3013b in GBC tissues. Functional experiments demonstrated that tRF-3013b inhibited GBC cell proliferation and induced cell-cycle arrest. Mechanically, tRF-3013b exerted RNA silencing effect on TPRG1L by binding to AGO3, and then inhibited NF-κB. TPRG1L overexpression could rescue the effects of tRF-3013b on GBC cell proliferation. CONCLUSIONS This study indicated that Dicer-induced tRF-3013b inhibited GBC proliferation by targeting TPRG1L and repressed NF-κB, pointing to tRF-3013b as a novel potential therapeutic target of GBC.
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Affiliation(s)
- Lu Zou
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Yang Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Biyu Zhou
- Department of Plastic and Reconstructive Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
| | - Weijian Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Ke Liu
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Guoqiang Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Huijie Miao
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Xiaoling Song
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665, Kongjiang Road, Shanghai, 200092, China
| | - Jiahua Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Yajun Geng
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Maolan Li
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China.
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
| | - Runfa Bao
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China.
- Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665, Kongjiang Road, Shanghai, 200092, China.
| | - Yingbin Liu
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
- Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, 200092, China.
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
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Liu J, Qian Y, Yang F, Huang S, Chen G, Yu J, Jiang S, Huang G. Value of prediction model in distinguishing gallbladder adenoma from cholesterol polyp. J Gastroenterol Hepatol 2022; 37:1893-1900. [PMID: 35750491 DOI: 10.1111/jgh.15928] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/25/2022] [Accepted: 06/18/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Gallbladder adenomatous polyp is a pre-cancerous neoplasm, and it is difficult to classify from cholesterol polyps before cholecystectomy. The study aimed to clarify the risk characteristics of gallbladder adenomas and establish a prediction model to differentiate gallbladder adenomas from cholesterol polyp lesions. METHODS From May 2019 to December 2021, the patients underwent cholecystectomy in the Shanghai Eastern Hepatobiliary Surgery Hospital were retrospectively reviewed. According to the permanent pathology test, the patients were divided into adenomas and cholesterol polyps groups. All the included cases received ultrasound equipment examinations before cholecystectomy and their clinical information were completely recorded. Then the patients' baseline characteristics and ultrasound imaging variables were analyzed by logistic regression. Finally, a predictive model for gallbladder adenomas will be established and assessed based on the independent risk factors. RESULTS A total of 423 cases including 296 cholesterol polyps and 127 gallbladder adenomas were analyzed in detail. Multivariate logistic regression analysis revealed that solitary polyp lesion (OR = 2.954, 95% CI 1.759-4.960, P < 0.001), the maximal diameter of lesions (OR = 1.244, 95% CI 1.169-1.324, P < 0.001), and irregular shape of polyp lesions (OR = 5.549, 95% CI 1.979-15.560, P = 0.001) were the independent predictive factors of gallbladder adenomas. According to the results, regression equation of logit(P) = -3.828 + 1.083*number of gallbladder polyps lesions (GPLs) + 0.218*diameter of GPLs + 1.714*shape of GPLs was established. Area under the curve (AUC) was 0.828 (95% CI 0.782-0.874, P < 0.001). When logit P > 0.204, the sensitivity of estimating adenoma was 79.5%, the specificity of recognizing adenoma was 70.6%, and the whole correct ratio was 73.3%. While the AUC of diameter (10 mm) being a predictive factor in this study was only 0.790 (95% CI 0.741-0.839, P < 0.001). And the sensitivity and specificity of 10 mm as the optimal diagnostic cutoff value to diagnose adenomas were 74.8% and 65.9%, respectively. CONCLUSIONS The risk factors of solitary polyp lesion, larger diameter, and irregular morphology feature of polyp lesions were significantly related to gallbladder adenomas. And the predictive model established in the study can effectively identify adenomas from cholesterol polyps and help patients to select the optimal treatment protocol.
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Affiliation(s)
- Jiandong Liu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Youwen Qian
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Feng Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Sunhua Huang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Gang Chen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Jian Yu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Shanshan Jiang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Gang Huang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
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Li Y, Song Y, Zhang Y, Liu S. Progress in gallbladder cancer with lymph node metastasis. Front Oncol 2022; 12:966835. [PMID: 36072797 PMCID: PMC9441950 DOI: 10.3389/fonc.2022.966835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/04/2022] [Indexed: 11/13/2022] Open
Abstract
Gallbladder cancer (GBC) is a malignant tumor that originates from the mucosal lining of the gallbladder. It is distinctly regional and is common in certain geographic regions of developing countries. GBC has a high degree of insidiousness as well as a high propensity for metastatic spread, resulting in the majority of patients being diagnosed at an advanced stage. Lymph node metastasis (LNM) is fairly common in GBC patients and is an independent risk factor for a poor prognosis. This article is focused on the lymph node pathways and metastatic directions of GBC. Furthermore, it summarizes the different lymph node groupings, disease stages and treatments. In the future, it is of great significance to develop individualized treatment and predict the outcomes of GBC patients with different lymph node conditions.
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Affiliation(s)
- Yuhang Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yinghui Song
- Central Laboratory of Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China
| | - Yujing Zhang
- Key Laboratory of Molecular Epidemiology of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China
| | - Sulai Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University, Changsha, China
- Central Laboratory of Hunan Provincial People's Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, China
- *Correspondence: Sulai Liu,
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Cai XC, Wu SD. Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review. World J Clin Cases 2022; 10:8212-8223. [PMID: 36159526 PMCID: PMC9403678 DOI: 10.12998/wjcc.v10.i23.8212] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/21/2022] [Accepted: 07/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored.
AIM To review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database.
METHODS Data of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)".
RESULTS The GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006–1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839–5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC.
CONCLUSION The clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.
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Affiliation(s)
- Xing-Chen Cai
- Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China
| | - Sheng-Dong Wu
- Department of Hepato-Pancreato-Billiary Surgery, The affiliated Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, China
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Tidjane A, Boudjenan‐Serradj N, Khalifa S, Ikhlef N, Bengueddach A, Larbi H, Meharzi SEI, Tabeti B. Adenosquamous carcinoma of gallbladder associated with biliopancreatic maljunction and Todani 1c choledochal cyst: A Case Report. ADVANCES IN DIGESTIVE MEDICINE 2022. [DOI: 10.1002/aid2.13327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Anisse Tidjane
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
| | - Nabil Boudjenan‐Serradj
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
| | - Samia Khalifa
- Department of Histopathology, EHU‐1st November 1954 Oran Algeria
| | - Nacim Ikhlef
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
| | | | - Hakim Larbi
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
| | - Sif el Islam Meharzi
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
| | - Benali Tabeti
- Department of Hepatobiliary Surgery and Liver Transplantation, EHU‐1st November 1954 Oran Algeria
- Department of Medicine University of Oran 1 Oran Algeria
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Fangchinoline induces gallbladder cancer cell apoptosis by suppressing PI3K/Akt/XIAP axis. PLoS One 2022; 17:e0266738. [PMID: 35446864 PMCID: PMC9022853 DOI: 10.1371/journal.pone.0266738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/25/2022] [Indexed: 11/19/2022] Open
Abstract
Gallbladder cancer (GBC) is the most common biliary tract malignancy with a dismal prognosis. The development of new drugs may help to improve prognosis. This study found that fangchinoline, a bisbenzylisoquinoline alkaloids, inhibited the proliferation and clone formation of GBC cells in a dose-dependent manner. Moreover, Hoechst staining, TUNEL assays, and flow cytometry demonstrated that fangchinoline effectively induced apoptosis in GBC cells. Further studies found that an anti-apoptotic pathway, the PI3K/Akt/XIAP axis, was significantly inhibited in GBC cells after treating with fangchinoline. Finally, we confirmed that fangchinoline restrained xenograft tumor growth in vivo. Our findings indicate that fangchinoline can be considered a potential drug for GBC treatment.
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Lv TR, Liu F, Hu HJ, Regmi P, Ma WJ, Yang Q, Jin YW, Li FY. The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:482-491. [PMID: 34955314 DOI: 10.1016/j.ejso.2021.11.131] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 10/06/2021] [Accepted: 11/26/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients. METHODS PubMed, EMBASE and the Cochrane Library were searched up to March 1st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. RESULTS EHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01). CONCLUSION EHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Qing Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Yang T, Ma L, Hou H, Gao F, Tao W. FAPI PET/CT in the Diagnosis of Abdominal and Pelvic Tumors. Front Oncol 2022; 11:797960. [PMID: 35059319 PMCID: PMC8763785 DOI: 10.3389/fonc.2021.797960] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Accepted: 11/23/2021] [Indexed: 12/11/2022] Open
Abstract
Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is currently a standard imaging examination used in clinical practice, and plays an essential role in preoperative systemic evaluation and tumor staging in patients with tumors. However, 18F-FDG PET/CT has certain limitations in imaging of some tumors, like gastric mucus adenocarcinoma, highly differentiated hepatocellular carcinoma, renal cell carcinoma, and peritoneal metastasis. Therefore, to search for new tumor diagnosis methods has always been an important topic in radiographic imaging research. Fibroblast activation protein (FAP) is highly expressed in many epithelial carcinomas, and various isotope-labelled fibroblast activation protein inhibitors (FAPI) show lower uptake in the brain and abdominal tissues than in tumor, thus achieving high image contrast and good tumor delineation. In addition to primary tumors, FAPI PET/CT is better than FDG PET/CT for detecting lymph nodes and metastases. Additionally, the highly selective tumor uptake of FAPI may open up new application areas for the non-invasive characterization, staging of tumors, as well as monitoring tumor treatment efficacy. This review focuses on the recent research progress of FAPI PET/CT in the application to abdominal and pelvic tumors, with the aim of providing new insights for diagnostic strategies for tumor patients, especially those with metastases.
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Affiliation(s)
- Tianshuo Yang
- Department of Nuclear Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
| | - Long Ma
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Haodong Hou
- Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Feng Gao
- Key Laboratory for Experimental Teratology of the Ministry of Education and Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Weijing Tao
- Department of Nuclear Medicine, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
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Altiok M, Özdemir HG, Kurt F, Gul MO, Gumus S. Incidental gallbladder cancer: a retrospective clinical study of 40 cases. Ann Surg Treat Res 2022; 102:185-192. [PMID: 35475225 PMCID: PMC9010968 DOI: 10.4174/astr.2022.102.4.185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/23/2022] [Accepted: 02/10/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose Methods Results Conclusion
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Affiliation(s)
- Merih Altiok
- Department of Surgical Oncology, Balcalı Training and Research Hospital, Cukurova University, Adana, Turkey
| | - Hanife Gülnihal Özdemir
- Department of Pathology, Cengiz Gokcek Gynecology, Obstetrics, and Pediatrics Hospital, Gaziantep, Turkey
| | - Feyzi Kurt
- Department of General Surgery, Seyhan Government Hospital, Adana, Turkey
| | - Mehmet Onur Gul
- Department of Surgical Oncology, Balcalı Training and Research Hospital, Cukurova University, Adana, Turkey
| | - Serdar Gumus
- Department of Surgical Oncology, Hatay Training and Research Hospital, Hatay, Turkey
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Lv TR, Yang C, Regmi P, Ma WJ, Hu HJ, Liu F, Yin CH, Jin YW, Li FY. The role of laparoscopic surgery in the surgical management of gallbladder carcinoma: A systematic review and meta-analysis. Asian J Surg 2021; 44:1493-1502. [PMID: 33895048 DOI: 10.1016/j.asjsur.2021.03.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 02/24/2021] [Accepted: 03/19/2021] [Indexed: 02/06/2023] Open
Abstract
Previous studies have explored the role of laparoscopic surgery (LS) in the surgical management of gallbladder carcinoma (GBC) and obtained satisfactory outcomes versus conventional open surgery. However, most of them either included a small number of patients or mainly focused on the early-staged lesions. Therefore, their results were less statistical powerful and a more comprehensive evaluation on the role of LS in GBC is warranted. A thorough database searching was performed in PubMed, EMBASE and Cochrane Library for comparative studies between the laparoscopic and open approach in the surgical management of GBC and 18 comparative studies were finally identified. RevMan 5.3 and Stata 13.0 software were used for statistical analyses. Pooled results revealed that patients in the laparoscopic group recovered faster with less intraoperative hemorrhage and less postoperative morbidity. Comparable operative time, overall recurrence rate, R0 resection rate, lymph node yield, intraoperative gallbladder violation rate and postoperative survival outcomes were also acquired. Regarding the debating issue of port-site recurrence, a significantly higher incidence of port-site recurrence was observed in laparoscopic group. However, having excluded studies on incidental gallbladder carcinoma, the subsequent pooled result showed no significant difference. Considering the inherent inconsistency of the surgical indication between laparoscopic and open surgeries and the deficiency of advanced lesions, we drew a conclusion that laparoscopic surgery seems to be only safe and feasible for early- or middle-staged lesions. Upcoming random controlled trials or comparative studies with equivalent surgical indication focused on advanced lesions are warranted for further evaluation.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Chen Yang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Wen-Jie Ma
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Chang-Hao Yin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Yan-Wen Jin
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
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Kitasaki N, Abe T, Oshita A, Hanada K, Noriyuki T, Nakahara M. Pyloric adenomatous carcinoma of the gallbladder following laparoscopic cholecystectomy: A case report. Int J Surg Case Rep 2021; 85:106278. [PMID: 34388892 PMCID: PMC8361251 DOI: 10.1016/j.ijscr.2021.106278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/01/2021] [Accepted: 08/02/2021] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Adenoma and intra-adenoma carcinoma of the gallbladder are relatively rare diseases, and the World Health Organization classification reports a frequency of 0.3% for gallbladder adenomas. Precise preoperative diagnosis of gallbladder cancer, especially in the early stages, is challenging. Herein, we report a case of pyloric adenomatous carcinoma of the gallbladder, diagnosed by laparoscopic cholecystectomy and pathology, along with a literature review. This case was reported in accordance with the SCARE 2020 Guideline (Ref). PRESENTATION OF CASE A 62-year-old woman was diagnosed with a 4-mm polypoid lesion in the gallbladder during a medical examination. The patient was followed-up by ultrasonography (US) once a year and was referred to our department because of an increase in size. Carcinoembryonic antigen and carbohydrate antigen 19-9 levels were within normal limits. Abdominal ultrasonography revealed a pedunculated polypoid lesion in the body of the gallbladder measuring 8 mm. Computed tomography demonstrated that the whole tumor was enhanced in the early phase without significant lymph node enlargement. Magnetic resonance cholangiopancreatography demonstrated a type Ip polypoid lesion located in the body of the gallbladder without pancreaticobiliary junctional abnormalities. Endoscopic ultrasound detected a superficial nodular-type Ip polypoid lesion in the gallbladder body with a parenchyma-like internal echogenic pattern. DISCUSSION Based on these findings, the patient was diagnosed with gallbladder adenoma, and laparoscopic cholecystectomy was performed. Histopathological examination revealed the tumor was a papillary growth of atypical high columnar epithelial cells. The final diagnosis was pyloric adenoma with high-grade dysplasia and intra-adenoma carcinoma. The patient is currently undergoing outpatient follow-up without recurrence for 1 year. CONCLUSION Early gallbladder carcinoma with adenoma should be considered in patients with small gallbladder polypoid lesions. Considering the surgical stress of cholecystectomy and the malignant potential of gallbladder cancer, preceding surgery would be acceptable.
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Affiliation(s)
| | - Tomoyuki Abe
- Corresponding author at: Department of Surgery, Gastroenterology, Onomichi General Hospital, Onomichi, Hiroshima, Japan.
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Wang S, Su TT, Tong H, Shi W, Ma F, Quan Z. CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression. Cell Death Discov 2021; 7:191. [PMID: 34312371 PMCID: PMC8313687 DOI: 10.1038/s41420-021-00577-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/07/2021] [Accepted: 07/03/2021] [Indexed: 12/29/2022] Open
Abstract
Circular RNAs (circRNAs) have been implicated in modulating biological processes in some tumors. However, the contributions and molecular mechanisms of circRNAs to gallbladder cancer (GBC) remain largely unknown. In the present study, our results showed circPVT1 expression was significantly upregulated in GBC tissues and cells. Higher circPVT1 expression was correlated with lymph node metastasis, advanced TNM stage, and poor overall survival (OS) in patients with GBC. Subsequently, knockdown of circPVT1 significantly impeded GBC cell proliferation, migration, invasion, while induced cell apoptosis in vitro. However, upregulated circPVT1 had the opposite effects. In vivo, we also demonstrated that knockdown of circPVT1 inhibited tumor growth. Furthermore, we confirmed that circPVT1 could regulate Myeloid cell leukemia-1 (MCL-1) expression by sponging to miR-339-3p, which affected tumor progression in GBC cells. In summary, our findings indicated that circPVT1 may serve as a promising prognostic marker and therapeutic target for GBC.
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Affiliation(s)
- Shouhua Wang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Ting Su
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huanjun Tong
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weibin Shi
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Ma
- Department of Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Zhiwei Quan
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Lv TR, Hu HJ, Regmi P, Liu F, Li FY. The effect of preoperative jaundice in the surgical management of gallbladder carcinoma: An updated meta-analysis. ANZ J Surg 2021; 91:E455-E464. [PMID: 34224199 DOI: 10.1111/ans.17000] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 05/27/2021] [Accepted: 05/30/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND An updated meta-analysis was performed on the significance of preoperative jaundice in the surgical management of gallbladder carcinoma (GBC). METHODS A thorough database searching was performed in PubMed, EMBASE, and the Cochrane library for comparative studies between jaundiced and non-jaundiced GBC patients. RevMan5.3 and Stata 13.0 software were used for statistical analysis. A total of nine measured outcomes were identified: resectability, R0 resection rate, concurrent bile duct resection, major hepatectomy, vital vascular reconstruction, combined adjacent organ resections, postoperative morbidities, mortalities, and overall survival (OS). RESULTS A total of eight studies were finally included. Newcastle- Ottawa Quality Assessment Scale was used for evaluating the quality of all included studies and the details were recorded in Table S1. Our pooled results revealed that preoperative jaundice was associated with a significantly lower resectability (p < 0.00001), a significantly lower R0 resection rate (p < 0.00001), a significantly higher concurrent bile duct resection rate (p < 0.00001), major hepatectomy rate (≥3 segments) (p < 0.00001), and vital vascular reconstruction rate (portal vein or hepatic artery) (p < 0.00001). Moreover, jaundiced patients experienced more postoperative morbidities (p < 0.00001), mortalities (p < 0.0001), and worse OS (p < 0.00001). However, jaundice was not related to combined adjacent organ resections (p = 0.58). CONCLUSION Preoperative jaundice in GBC patients seems to be contraindicated to curative resection and the optimal therapeutic strategies should be identified via multidisciplinary team rather than surgery alone. Candidates for curative surgery should be highly selected and experienced centers are preferred. More significant well-designed studies are required for further exploration.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hai-Jie Hu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Parbatraj Regmi
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fei Liu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Fu-Yu Li
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
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Wang S, Wang Y, Wang S, Tong H, Tang Z, Wang J, Zhang Y, Ou J, Quan Z. Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression. Front Genet 2021; 12:674653. [PMID: 34168678 PMCID: PMC8219055 DOI: 10.3389/fgene.2021.674653] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 04/06/2021] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVES The role of lncRNAs in gallbladder cancer (GBC) remains poorly understood. In this study, we explored the function of functional intergenic repeating RNA element (FIRRE) in GBC. MATERIALS AND METHODS Whole transcriptome resequencing was performed in three pairs of GBC tissues and adjacent non-tumor tissues. lncRNA FIRRE expression was verified by real-time PCR. The function of FIRRE in GBC was evaluated by experiments in vitro and in vivo. The mechanism of FIRRE was investigated via fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter assays, and RNA immunoprecipitation. RESULTS FIRRE level was dramatically increased in GBC tissues compared to that in the adjacent non-tumor tissues. High expression of FIRRE was closely related to clinical stage and poor prognosis in GBC patients. Moreover, FIRRE remarkably enhanced proliferation and migration, and inhibited apoptosis of GBC cells. Mechanistically, FIRRE modulated YOD1 expression by sponging miR-520a-3p, thus contributing to the development of GBC. CONCLUSION Our data revealed that FIRRE might act as a novel mediator in GBC progression by sponging miR-520a-3p and regulating YOD1. FIRRE might be regarded as a potential diagnostic marker or target for GBC treatment.
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Affiliation(s)
- Shuqing Wang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Wang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shouhua Wang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huanjun Tong
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhaohui Tang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiandong Wang
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongjie Zhang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jingmin Ou
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiwei Quan
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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García P, Lamarca A, Díaz J, Carrera E, Roa JC, on behalf of the European-Latin American ESCALON Consortium. Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients. Cancers (Basel) 2020; 12:E3670. [PMID: 33297469 PMCID: PMC7762341 DOI: 10.3390/cancers12123670] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 11/06/2020] [Accepted: 11/11/2020] [Indexed: 01/17/2023] Open
Abstract
Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.
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Affiliation(s)
- Patricia García
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester M20 4BX, UK;
| | - Javier Díaz
- Departamento del Aparato Digestivo, Hospital Nacional Edgardo Rebagliati Martins-Essalud, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru;
| | - Enrique Carrera
- Department of Gastroenterology, Hospital Especialidades Eugenio Espejo, Universidad San Francisco de Quito, Quito 170136, Ecuador;
| | - Juan Carlos Roa
- Department of Pathology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile;
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Song X, Hu Y, Li Y, Shao R, Liu F, Liu Y. Overview of current targeted therapy in gallbladder cancer. Signal Transduct Target Ther 2020; 5:230. [PMID: 33028805 PMCID: PMC7542154 DOI: 10.1038/s41392-020-00324-2] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/08/2020] [Accepted: 09/10/2020] [Indexed: 02/08/2023] Open
Abstract
Gallbladder cancer (GBC) is rare, but is the most malignant type of biliary tract tumor. Unfortunately, only a small population of cancer patients is acceptable for the surgical resection, the current effective regimen; thus, the high mortality rate has been static for decades. To substantially circumvent the stagnant scenario, a number of therapeutic approaches owing to the creation of advanced technologic measures (e.g., next-generation sequencing, transcriptomics, proteomics) have been intensively innovated, which include targeted therapy, immunotherapy, and nanoparticle-based delivery systems. In the current review, we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC. Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease, ultimately improving the efficacy of treatment.
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Affiliation(s)
- Xiaoling Song
- Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, 200092, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China
| | - Yunping Hu
- Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, 200092, Shanghai, China
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China
| | - Yongsheng Li
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China
| | - Rong Shao
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
- Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, 200025, Shanghai, China.
| | - Fatao Liu
- Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, 200092, Shanghai, China.
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
| | - Yingbin Liu
- Shanghai Key Laboratory of Biliary Tract Disease Research, 1665 Kongjiang Road, 200092, Shanghai, China.
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
- Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China.
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Fujiwara K, Abe A, Masatsugu T, Hirano T, Sada M. Effect of gallbladder polyp size on the prediction and detection of gallbladder cancer. Surg Endosc 2020; 35:5179-5185. [PMID: 32974780 DOI: 10.1007/s00464-020-08010-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 09/16/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Gallbladder polyps are relatively common. Although most gallbladder polyps are benign, some are malignant. Current guidelines state that malignancy should be suspected for polyps ≥ 10 mm in diameter. We clarified the cancer detection rates in accordance with the size distribution of gallbladder polyps, and evaluated the effectiveness of the reported risk factors in predicting malignancy. METHODS In this retrospective case-control study, our institutional database was searched to identify patients who underwent laparoscopic cholecystectomy for benign or malignant gallbladder polyps at Sada Hospital, Japan. The chi-squared test was used to analyze the risk factors for malignancy. RESULTS There were 227 protruding gallbladder lesions. The 206 benign polyps had a diameter of 2-21 mm, while the 21 malignant polyps were 7-60 mm. The cancer detection rates were 16.4% for lesions ≥ 10 mm, 55.9% for lesions ≥ 15 mm, and 94.1% for lesions ≥ 20 mm. Of the benign lesions, cholesterol polyps were the most frequent (50-100%) in all size ranges, even in large lesions (≥ 15 mm). The sessile lesion morphology was significantly more frequent in malignant (60%) than benign lesions (3.4%, p < 0.00001). Multiple polyps were frequently diagnosed not only as cholesterol polyps (81.1%), but also as adenomas (60%); adenomas were found as a single adenoma within other types of polyps. There were two cases of malignant small gallbladder polyps (< 10 mm); these lesions met the surgical indications of a size increase during observation or a sessile morphology. CONCLUSIONS The cancer detection rate increased significantly with an increase in the lesion size. Risk factors such as a sessile polyp morphology or an increase in lesion size were effective in predicting malignancy for small gallbladder polyps. It might be difficult to accurately predict the pathologic diagnoses of gallbladder polyps preoperatively, as cholesterol polyps were most frequent, even in the large size range.
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Affiliation(s)
- Kenji Fujiwara
- Department of Surgery, Sada Hospital, 2-4-28 Watanabe St, Chuo Ward, Fukuoka, 810-0004, Japan. .,Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka, 812-8582, Japan.
| | - Atsushi Abe
- Department of Surgery, Sada Hospital, 2-4-28 Watanabe St, Chuo Ward, Fukuoka, 810-0004, Japan
| | - Toshihiro Masatsugu
- Department of Surgery, Sada Hospital, 2-4-28 Watanabe St, Chuo Ward, Fukuoka, 810-0004, Japan
| | - Tatsuya Hirano
- Department of Surgery, Sada Hospital, 2-4-28 Watanabe St, Chuo Ward, Fukuoka, 810-0004, Japan
| | - Masayuki Sada
- Department of Surgery, Sada Hospital, 2-4-28 Watanabe St, Chuo Ward, Fukuoka, 810-0004, Japan
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Kumar P, Yadav M, Verma K, Dixit R, Singh J, Tiwary SK, Narayan G, Dixit VK. Expression analysis of aryl hydrocarbon receptor repressor (AHRR) gene in gallbladder cancer. Saudi J Gastroenterol 2020; 27:54-59. [PMID: 32801256 PMCID: PMC8083244 DOI: 10.4103/sjg.sjg_213_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer. METHODS The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters. RESULTS We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) (P = 0.017) and immunohistochemistry analysis (P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls (P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage (P = 0.001), histological differentiation (P = 0.001), and tumors with nodal metastasis (P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients. CONCLUSION In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer.
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Affiliation(s)
- Puneet Kumar
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India,Address for correspondence: Prof. Puneet Kumar, Professor and Head, Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh, India. E-mail:
| | - Manoj Yadav
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Khushi Verma
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Ruhi Dixit
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Juhi Singh
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Satyendra K Tiwary
- Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Gopeshwar Narayan
- Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - V K Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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