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Xiao YX, Chen J, Li ZY, Zou YX, Zhou XH, Zhang W, Li HL, Bischof EY, Xiang YB. Global trends in gallbladder cancer survival: A 30-year analysis of cancer registry data. Heliyon 2025; 11:e42853. [PMID: 40070950 PMCID: PMC11894304 DOI: 10.1016/j.heliyon.2025.e42853] [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: 07/26/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background Gallbladder cancer has historically been characterized with a poor prognosis. This study aims to describe the global patterns and temporal trends in gallbladder cancer survival using data from cancer registries. Methods We conducted a systematic review by searching six databases-PubMed, Web of Science, EMBASE, SEER, CNKI, and Wanfang-for using of registry-based data published before January 1, 2024. Survival data were carefully extracted and analyzed from the final set of included studies. Results Among the 55 studies included, more than 320,000 people, suggest that survival improvements for gallbladder cancer have stagnated over the past three decades. No significant improvements in 5-year relative survival rates were observed worldwide. After age standardization, the highest 5-year relative survival rate is 30.6 % (Changzhou, China, 2011-2013 and Korea, 2013-2019), while the lowest is 6.0 % (Austria, 1990). The 5-year relative survival rate for gallbladder cancer was generally higher in Asian populations than in other regions. Survival rates were more favorable in younger individuals, with no differences in survival observed between the sexes. Conclusions Over the past 30 years, the prognosis of patients with gallbladder cancer has not improved significantly worldwide. There is an urgent need for new treatments for gallbladder cancer as well as simple and effective screening methods to improve the survival rate of gallbladder cancer.
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Affiliation(s)
- Yu-Xuan Xiao
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Jun Chen
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Zhuo-Ying Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Yi-Xin Zou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Xiao-Hui Zhou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wei Zhang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Hong-Lan Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Evelyne Y. Bischof
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
| | - Yong-Bing Xiang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- School of Public Health, Fudan University, Shanghai, 200025, China
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, 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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Cozma MA, Găman MA, Srichawla BS, Dhali A, Manan MR, Nahian A, Marsool MDM, Suteja RC, Kutikuppala LVS, Kipkorir V, Găman AM, Diaconu CC. Acute cholangitis: a state-of-the-art review. Ann Med Surg (Lond) 2024; 86:4560-4574. [PMID: 39118745 PMCID: PMC11305776 DOI: 10.1097/ms9.0000000000002169] [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: 01/24/2024] [Accepted: 05/05/2024] [Indexed: 08/10/2024] Open
Abstract
Acute cholangitis is a potentially life-threatening bacterial infection of the intra and/or extrahepatic bile ducts. It remains the second and third cause of community-acquired and hospital-acquired bacteremia, respectively, and is associated with mortality rates of up to 15%, despite advances in broad-spectrum antimicrobial therapy and improved access to emergency biliary tract decompression procedures. Even though not much has changed in recent years in terms of diagnosis or treatment, new data have emerged regarding multidrug-resistant bacteria that serve as etiologic agents of cholangitis. Moreover, different approaches in antibiotic regimes depending on severity grading and bile sample cultures as well as novel minimally invasive endoscopic procedures that can help when consecrated treatments such as endoscopic retrograde cholangiopancreatography (ERCP) fail, cannot be performed, or are unavailable have been proposed. This state-of-the-art review aims to offer a complete and updated assessment of the epidemiology, novel diagnostic and therapeutic methods, complications, and prognostic variables of acute cholangitis. The authors will review the prognostic implications of unusual complications, the relevance of regular bile samples and antibiograms, and their new role in guiding antibiotic therapy and limiting antibiotic resistance to present an organized and comprehensive approach to the care of acute cholangitis.
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Affiliation(s)
- Matei-Alexandru Cozma
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest
- Department of Gastroenterology, Colentina Clinical Hospital, Bucharest
| | - Mihnea-Alexandru Găman
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest
- Department of Hematology, Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest
| | - Bahadar S. Srichawla
- Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA
| | - Arkadeep Dhali
- NIHR Academic Clinical Fellow in Gastroenterology, University of Sheffield; Internal Medicine Trainee, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | | | - Ahmed Nahian
- Medical Student, LECOM at Seton Hill, Greensburg, PA, USA
| | | | | | | | - Vincent Kipkorir
- Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
| | - Amelia Maria Găman
- Department of Pathophysiology, University of Medicine and Pharmacy of Craiova
- Clinic of Hematology, Filantropia City Hospital, Craiova, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest
- Internal Medicine Clinic, Clinical Emergency Hospital of Bucharest, Bucharest
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Di Carlo P, Serra N, Fasciana TMA, Giammanco A, D’Arpa F, Rea T, Napolitano MS, Lucchesi A, Cascio A, Sergi CM. Microbial profile in bile from pancreatic and extra-pancreatic biliary tract cancer. PLoS One 2024; 19:e0294049. [PMID: 38381746 PMCID: PMC10880987 DOI: 10.1371/journal.pone.0294049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 09/11/2023] [Indexed: 02/23/2024] Open
Abstract
BACKGROUND Dysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy antibiotics in pancreatic cancer patients colonized by the Escherichia coli and Klebsiella pneumoniae. OBJECTIVE In this study, we investigated the microbial communities that colonize tumours and which bacteria could aid in diagnosing pancreatic and biliary cancer and managing bile-colonized patients. METHODS A retrospective study on positive bile cultures of 145 Italian patients who underwent cholangiopancreatography with PC and EPC cancer hospitalized from January 2006 to December 2020 in a QA-certified academic surgical unit were investigated for aerobic/facultative-anaerobic bacteria and fungal organisms. RESULTS We found that among Gram-negative bacteria, Escherichia coli and Pseudomonas spp were the most frequent in the EPC group, while Escherichia coli, Klebsiella spp, and Pseudomonas spp were the most frequent in the PC group. Enterococcus spp was the most frequent Gram-positive bacteria in both groups. Comparing the EPC and PC, we found a significant presence of patients with greater age in the PC compared to the EPC group. Regarding Candida spp, we found no significant but greater rate in the PC group compared to the EPC group (11.7% vs 1.96%). We found that Alcaligenes faecalis was the most frequent bacteria in EPC than the PC group, among Gram-negative bacterial species. CONCLUSIONS Age differences in gut microbiota composition may affect biliary habitats in our cancer population, especially in patients with pancreatic cancer. Alcaligenes faecalis isolated in the culture of bile samples could represent potential microbial markers for a restricted follow-up to early diagnosis of extra-pancreatic cancer. Finally, the prevalence of Candida spp in pancreatic cancer seems to trigger new aspects about debate about the role of fungal microbiota into their relationship with pancreatic cancer.
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Affiliation(s)
- Paola Di Carlo
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence "G. D’Alessandro”, University of Palermo, Palermo, Italy
| | - Nicola Serra
- Department of Public Health, University Federico II of Naples, Naples, Italy
| | - Teresa Maria Assunta Fasciana
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence "G. D’Alessandro”, University of Palermo, Palermo, Italy
| | - Anna Giammanco
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence "G. D’Alessandro”, University of Palermo, Palermo, Italy
| | - Francesco D’Arpa
- Department of General Surgery and Emergency, University of Palermo, Palermo, Italy
| | - Teresa Rea
- Department of Public Health, University Federico II of Naples, Naples, Italy
| | - Maria Santa Napolitano
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence "G. D’Alessandro”, University of Palermo, Palermo, Italy
| | - Alessandro Lucchesi
- Hematology Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio dei Tumori (IRST) “Dini Amadori”, Meldola, Forl-Cesena, Italy
| | - Antonio Cascio
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence "G. D’Alessandro”, Infectious Disease Unit, University of Palermo, Palermo, Italy
| | - Consolato Maria Sergi
- Lab. Med. and Pathology, Children’s Hospital of Eastern Ontario (CHEO), Ottawa, Canada
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Lv TR, Liu F, Jin YW, Li FY. Comparative analyses between radically re-resected incidental gallbladder carcinoma and primary radically resected gallbladder carcinoma: a single-center experience in China. Langenbecks Arch Surg 2023; 409:2. [PMID: 38087066 DOI: 10.1007/s00423-023-03199-3] [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: 09/11/2023] [Accepted: 12/05/2023] [Indexed: 12/18/2023]
Abstract
PURPOSES The current study was performed to comparatively evaluate the similarities and differences between cases with radically re-resected incidental gallbladder carcinoma (RRIGBC) and those with primary radically resected gallbladder carcinoma (PRGBC). METHODS Comparative analysis between patients with RRIGBC and those with PRGBC were performed in terms of clinic-pathological features and long-terms survival. RESULTS A total of 330 surgically treated GBC patients with 110 patients with IGBC were identified. PRGBCs were generally in a more advanced tumor stage, sharing more aggressive tumor biological features and worse prognosis than those with RRIGBC. Subgroup analyses indicated a comparable prognosis among T1-2 patients between RRIGBC and PRGBC groups. However, among T3-4 patients, patients in the PRGBC group shared a much worse prognosis. Moreover, IGBC itself can be regarded as a prognostic factor but cannot be regarded as an independent prognostic factor. It is the tumor stage which really determined the overall prognosis. CONCLUSION Patients with RRIGBC were generally in a much earlier tumor stage and shared a much better prognosis than those with PRGBC. IGBC itself can be regarded as a prognostic factor but cannot be regarded as the independent prognostic factors. It is the tumor stage which really determine the overall prognosis.
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Affiliation(s)
- Tian-Run Lv
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Fei Liu
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China
| | - Yan-Wen Jin
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
| | - Fu-Yu Li
- Department of Biliary Tract Surgery, General Surgery, West China Hospital, Sichuan University, Sichuan Province, Chengdu, 610041, China.
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Zhang W, Sun Y, Jiang Z, Qu W, Gong C, Zhou A. Nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) as first-line treatment for advanced biliary tract adenocarcinoma: a phase 2 clinical trial. Hepatobiliary Surg Nutr 2023; 12:37-44. [PMID: 36860259 PMCID: PMC9944545 DOI: 10.21037/hbsn-21-172] [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] [Received: 04/30/2021] [Accepted: 09/10/2021] [Indexed: 11/06/2022]
Abstract
Background This study aimed to evaluate the efficacy and safety of a new combination of nab-paclitaxel plus tegafur gimeracil oteracil potassium capsule (S-1) for patients with advanced biliary tract carcinoma (BTC). Methods Patients were treated with nab-paclitaxel at a dose of 125 mg/m2 on day 1 and 8, and S-1, 80 to 120 mg/day on days 1-14 of a 21-day cycle. Treatments were repeated until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR). The secondary endpoints were median progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results The number of patients enrolled were 54, and 51 patients were evaluated for efficacy. A total of 14 patients achieved partial response (PR) with an ORR of 27.5%. The ORR varied by sites, with 53.8% (7/13) for gallbladder carcinoma, 18.4% (7/38) for cholangiocarcinoma. The most common grade 3 or 4 toxicities were neutropenia and stomatitis. The median PFS and OS were 6.0 and 13.2 months, respectively. Conclusions The combination of nab-paclitaxel with S-1 showed explicit antitumor activities and favorable safety profile in advanced BTC and could serve as a potential non-platinum and -gemcitabine-based regimen.
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Affiliation(s)
- Wen Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongkun Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhichao Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wang Qu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Caifeng Gong
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Aiping Zhou
- Department of Medical Oncology, 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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Wang F, Wang FH, Sun K, Jiang C, Peng S, Xu LX, Kuang M, Guo GF, Chen SL. PD-1-mAb Plus Regimen in the First and Second Lines of Advanced and Unresectable Biliary Tract Carcinoma: A Real-World, Multicenter Retrospective Analysis. J Inflamm Res 2022; 15:6031-6046. [PMID: 36339826 PMCID: PMC9635481 DOI: 10.2147/jir.s364303] [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: 03/06/2022] [Accepted: 08/19/2022] [Indexed: 11/05/2022] Open
Abstract
Introduction Advanced biliary tract carcinoma (BTC) has a poor prognosis and few treatment options. We compared the efficacy of the PD-1 monoclonal antibody (PD-1-mAb) combined regimens with the standard chemotherapy in the first-line and second-line treatment of advanced BTC. Methods We retrospectively assessed the patients with advanced BTC, who received treatment at the First Affiliated Hospital of Sun Yat-Sen University and the Sun Yat-Sen University Cancer Center. The patients were treated with PD-1-mAb combined regimens or standard chemotherapy at the first line or treated with PD-1-mAb combined regimens or systematic therapy at the second line. Further subgroup analyses were assessed to identify superior regimens. Results This study included 210 patients. The first-line PD-1-mAb combination group (n = 83) achieved longer median PFS (mPFS) (7.3 vs 5.3 months, p=0.001) and median OS (mOS) (15.6 vs 11.4 months, p=0.002) than the first-line standard chemotherapy group (n=76). Similarly, the second-line PD-1-mAb combination group (n=50) yielded longer mPFS (6.1 vs 2.6 months, p<0.001) and mOS (11.7 vs 7.2 months, p=0.008) than the second-line systematic therapy group (n=51). Subgroup analyses showed that the PD-1-mAb combined with TKI group achieved better mPFS than the chemotherapy group whether in the first-line (HR = 0.468, p=0.005) or the second-line setting (HR = 0.45, p=0.009), but did not achieve superiority in mOS (both p>0.05). Compared with the chemotherapy group, the PD-1-mAb combined with chemotherapy group achieved longer mOS (HR = 0.53, p=0.023) in the first-line setting and longer mPFS in the second-line setting (HR = 0.54, p=0.044). Conclusion The PD-1-mAb combination therapy is superior to the standard chemotherapy in advanced or unresectable BTC, whether as a first-line or second-line treatment. Among the combination therapy, both the PD-1-mAb combined with TKI and combined with standard chemotherapy were promising options for advanced BTC patients.
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Affiliation(s)
- Fang Wang
- Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Feng-Hua Wang
- State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China,Department of Oncology, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Kaiyu Sun
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Chang Jiang
- State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China,Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Sui Peng
- Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Li-Xia Xu
- Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Ming Kuang
- Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China
| | - Gui-Fang Guo
- State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China,Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China,VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
| | - Shu-Ling Chen
- Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China,Correspondence: Shu-Ling Chen; Gui-Fang Guo, Email ;
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Di Carlo P, Serra N, Alduina R, Guarino R, Craxì A, Giammanco A, Fasciana T, Cascio A, Sergi CM. A systematic review on omics data (metagenomics, metatranscriptomics, and metabolomics) in the role of microbiome in gallbladder disease. Front Physiol 2022; 13:888233. [PMID: 36111147 PMCID: PMC9468903 DOI: 10.3389/fphys.2022.888233] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/11/2022] [Indexed: 12/04/2022] Open
Abstract
Microbiotas are the range of microorganisms (mainly bacteria and fungi) colonizing multicellular, macroscopic organisms. They are crucial for several metabolic functions affecting the health of the host. However, difficulties hamper the investigation of microbiota composition in cultivating microorganisms in standard growth media. For this reason, our knowledge of microbiota can benefit from the analysis of microbial macromolecules (DNA, transcripts, proteins, or by-products) present in various samples collected from the host. Various omics technologies are used to obtain different data. Metagenomics provides a taxonomical profile of the sample. It can also be used to obtain potential functional information. At the same time, metatranscriptomics can characterize members of a microbiome responsible for specific functions and elucidate genes that drive the microbiotas relationship with its host. Thus, while microbiota refers to microorganisms living in a determined environment (taxonomy of microorganisms identified), microbiome refers to the microorganisms and their genes living in a determined environment and, of course, metagenomics focuses on the genes and collective functions of identified microorganisms. Metabolomics completes this framework by determining the metabolite fluxes and the products released into the environment. The gallbladder is a sac localized under the liver in the human body and is difficult to access for bile and tissue sampling. It concentrates the bile produced in the hepatocytes, which drains into bile canaliculi. Bile promotes fat digestion and is released from the gallbladder into the upper small intestine in response to food. Considered sterile originally, recent data indicate that bile microbiota is associated with the biliary tract's inflammation and carcinogenesis. The sample size is relevant for omic studies of rare diseases, such as gallbladder carcinoma. Although in its infancy, the study of the biliary microbiota has begun taking advantage of several omics strategies, mainly based on metagenomics, metabolomics, and mouse models. Here, we show that omics analyses from the literature may provide a more comprehensive image of the biliary microbiota. We review studies performed in this environmental niche and focus on network-based approaches for integrative studies.
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Affiliation(s)
- Paola Di Carlo
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Infectious Disease, University of Palermo, Palermo, Italy
| | - Nicola Serra
- Department of Public Health, University “Federico II”, Naples, Italy
| | - Rosa Alduina
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Riccardo Guarino
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy
| | - Antonio Craxì
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Gastroenterology, University of Palermo, Palermo, Italy
| | - Anna Giammanco
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Microbiology, University of Palermo, Palermo, Italy
| | - Teresa Fasciana
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Microbiology, University of Palermo, Palermo, Italy
| | - Antonio Cascio
- Department of Health Promotion, Maternal-Childhood, Internal Medicine of Excellence G. D’Alessandro, Section of Infectious Disease, University of Palermo, Palermo, Italy
| | - Consolato M. Sergi
- Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON, Canada
- Department of Pediatrics, Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
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9
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Tuma F, Abbaszadeh-Kasbi A, Munene G, Shebrain S, Durchholz WC. Trends of the Extra-Hepatic Biliary Cancer and Its Surgical Management: A Cross-Sectional Study From the National Cancer Database. Cureus 2022; 14:e27584. [PMID: 36059334 PMCID: PMC9428418 DOI: 10.7759/cureus.27584] [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] [Accepted: 07/29/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Biliary cancers are rare cancers with poor prognoses. In this study, we aimed to evaluate trends in early detection and surgical treatment and approaches in extra-hepatic biliary tract cancers (EBCs) over 13 years in the US. Methods The most recent data on patients diagnosed with EBC between 2004 and 2016 were extracted from the National Cancer Database (NCDB). The patients’ demographics (sex, age, race), primary tumor sites, tumor grades and stages, staging modalities, diagnostic confirmation, surgical treatment modalities and approaches, and 90-day mortality were analyzed to determine trends. Results Biopsy was the most common staging modality in 63.9% of total 60,291 patients. The bile duct was the primary tumor site (55.0%). Histologic examination was the most common confirmatory diagnostic modality (77.5%). The most common stage was stage II (23%). The most common surgical treatment modality was radical surgery (13.88%). The open surgical approach was used in 27.1% of patients, followed by a laparoscopic approach (4.3%). Conclusion EBC showed no significant change in the trends of the stage at diagnosis, treatment modality, and extent of surgical procedures despite advances in surgical diagnostic and therapeutic modalities; however, the total number of cases slightly increased between 2004 and 2016.
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Yang XG, Sun YY, Li DS, Xu GH, Huang XQ. Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization Combining Immune Checkpoint Inhibitors in Unresectable Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis. Front Immunol 2022; 13:940009. [PMID: 35874708 PMCID: PMC9305385 DOI: 10.3389/fimmu.2022.940009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 06/20/2022] [Indexed: 12/12/2022] Open
Abstract
Purpose To assess the effectiveness and safety of drug-eluting beads transarterial chemoembolization plus immune checkpoint inhibitors (DEB-TACE+ICIs) versus chemotherapy (gemcitabine+cisplatin) for patients with unresectable intrahepatic cholangiocarcinoma (iCCA). Materials and Methods This retrospective study included unresectable iCCA patients treated with DEB-TACE+ICIs or chemotherapy between May, 2019 and August, 2021. The differences in tumor responses, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the 2 groups. Patient baseline characteristics, PFS, and OS were compared among 2 groups before and after propensity score-matching (PSM). Factors affecting PFS and OS were analyzed by Cox’s proportional hazards regression model. Results The study included 49 patients with unresectable iCCA patients, 20 in the DEB-TACE+ICIs group and 29 in the chemotherapy group. PSM analysis created 20 pairs of patients in 2 groups. The patients in the DEB-TACE+ICIs group had a higher objective response rate (55.0% vs. 20.0%, P=0.022), higher PFS (median, 7.2 vs. 5.7 months, P=0.036), and higher OS (median, 13.2 vs. 7.6 months, P=0.015) than those in the chemotherapy group. Multivariate analyses suggested that chemotherapy, tumor size >5cm, and multiple tumors were the independent risk factors for PFS and OS. The incidence of TRAEs was similar between the 2 groups. Conclusion Compared to chemotherapy, DEB-TACE plus ICIs improved survival and was well-tolerated in patients with unresectable iCCA.
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Affiliation(s)
- Xue-Gang Yang
- Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China
| | - Yan-Yuan Sun
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China
| | - De-Shan Li
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China
| | - Guo-Hui Xu
- Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China
| | - Xiao-Qi Huang
- Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xiao-Qi Huang,
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11
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Procopio F, Branciforte B, Nappo G, Di Tommaso L, Lleo A, Torzilli G. Meta-analysis on prognostic value of KRAS mutation in resected mass-forming cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1455-1463. [PMID: 35317947 DOI: 10.1016/j.ejso.2022.03.005] [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: 09/20/2021] [Revised: 02/14/2022] [Accepted: 03/08/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Despite survival improvements for other cancers, the prognosis of resected mass-forming cholangiocellular carcinoma (MFCCC) remains dismal. As a possible background of that, biologic factors could play some role. KRAS mutation has been investigated in the present systematic review and meta-analysis. METHODS MEDLINE, Embase and Cochrane Library databases were searched for studies reporting overall survival (OS) following liver resection for MFCCC with known KRAS status. Secondary outcomes included completeness of resection (R1 vs R0), pathological lymph node (LN) rate, tumor burden (multiple vs single), perineural invasion (PI) rate. RESULTS Eight studies comprising 604 patients resected for MFCCC were eligible for analysis. Of these, 23% of patients were mKRAS. The mKRAS MFCCC showed lower 1-year OS [odd ratio (OR) 3.45, 95% confidence interval (CIs) 1.85-6.42; p < 0.001], 3-years OS (OR 4.82, 95% CI 2.63-8.84; p < 0.001), and 5-years OS (OR 10.60, 95% CI 3.12-36.03; p < 0.001) compared to wtKRAS. Pooled-R1 resection rate was 18% for mKRAS and 23% for those with wtKRAS (OR 1.71, 95%CIs 0.70-4.19; p = 0.239). The pooled-pathological LNs rate was 23% in mKRAS vs 17% (OR 2.36, 95%CIs 0.75-7.48; p = 0.144). The pooled-multifocality rate was 55% in mKRAS vs 19% (OR 5.38, 95%CIs 1.76-16.48; p = 0.003), while the pooled-PI was 77% vs 31% (OR 6.59, 95%CIs 2.13-20.37; p = 0.001). CONCLUSION The KRAS mutation is relatively frequent in MFCCC. The mKRAS is strongly associated with a shortened survival and higher tumoral aggressiveness. Testing for KRAS mutations could be a valuable adjunct in opening a scenario to new treatments and improving prognosis of patients with MFCCC.
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Affiliation(s)
- Fabio Procopio
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy
| | - Bruno Branciforte
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Gennaro Nappo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Pancreatic Surgery Unit, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Division of Pathology, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center - IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy.
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Salehi O, Vega EA, Mellado S, Core MJ, Li M, Kozyreva O, Kutlu OC, Freeman R, Conrad C. High-Quality Surgery for Gallbladder Carcinoma: Rare, Associated with Disparity, and Not Substitutable by Chemotherapy. J Gastrointest Surg 2022; 26:1241-1251. [PMID: 35396641 DOI: 10.1007/s11605-022-05290-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Accepted: 02/26/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Oncologic surgery for T1b-T3 gallbladder carcinoma (GBC) consists of gallbladder fossa resection or bisegmentectomy IVb/V with negative margins and portal/retropancreatic lymphadenectomy. Frequency of high quality oncologic surgery, factors associated with its use, and the ability of chemotherapy to rescue low-quality surgery (LQS) remain unknown. METHODS The NCDB was queried for patients diagnosed with stage I-III (T1b-T3) GBC undergoing curative-intent surgery from 2004 to 2016. These patients were divided into two groups based on receiving high quality surgery (HQS) or not; HQS was defined as cholecystectomy with partial hepatectomy, lymph node harvest ≥ 6, and negative margins. Logistic regression and Kaplan-Meier survival analyses were performed. RESULTS A total of 3796 patients met inclusion criteria; only 364 (9.6%) met HQS criteria, and 3432 (90.4%) did not achieve HQS and were deemed low-quality surgery (LQS). HQS was associated with improved median overall survival (55.1 vs. 25.5 months, P < .001). Adjuvant chemotherapy (AC) was not able to rescue LQS with poorer survival compared to HQS without AC (27.9 vs 55.1 months, P < .001). Factors associated with HQS included private insurance (OR 1.809, P < .001), higher income (OR 1.380, P = .038), urban/rural residence (vs metropolitan) (OR 1.641, P = .001), higher education (OR 1.342, P = .031), Medicaid expansion states (OR 1.405, P = .005), stage 3 GBC (OR 1.642, P = .020), and reresection (OR 2.685, P < .001). Factors associated with LQS included older age (OR 0.974, P < .001), comorbidities (OR 0.701, P = .004), and laparoscopic approach (0.579, P < .001). Facility type incrementally improved HQS rate (integrated cancer network vs. comprehensive community, 9.8% vs. 6.1%, OR 1.694, P = .003; academic/research center vs. integrated cancer network, 14.9% vs. 9.8%, OR 1.599, P = .003). CONCLUSION While HQS for GBC strongly improves survival, it is infrequently practiced. The newly identified factors that improve survival for GBC, such as centralization, open approach, and insurance coverage, are modifiable and, therefore, should be considered to achieve optimal outcomes.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Boston University School of Medicine, 11 Nevins St., Suite 201, Brighton, Boston, MA, 02135, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Boston University School of Medicine, 11 Nevins St., Suite 201, Brighton, Boston, MA, 02135, USA
| | | | - Michael J Core
- Department of Surgery, St. Elizabeth's Medical Center, Boston University School of Medicine, 11 Nevins St., Suite 201, Brighton, Boston, MA, 02135, USA
| | - Mu Li
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Olga Kozyreva
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Onur C Kutlu
- Department of Surgery, University of Miami Health System, Miller School of Medicine, Miami, FL, USA
| | - Richard Freeman
- Department of Surgery, St. Elizabeth's Medical Center, Boston University School of Medicine, 11 Nevins St., Suite 201, Brighton, Boston, MA, 02135, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Boston University School of Medicine, 11 Nevins St., Suite 201, Brighton, Boston, MA, 02135, USA.
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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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Chiow SM, Khoo HW, Low JK, Tan CH, Low HM. Imaging mimickers of cholangiocarcinoma: a pictorial review. Abdom Radiol (NY) 2022; 47:981-997. [PMID: 34978593 DOI: 10.1007/s00261-021-03399-9] [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: 09/17/2021] [Revised: 12/21/2021] [Accepted: 12/22/2021] [Indexed: 12/19/2022]
Abstract
Cholangiocarcinoma (CCA) is the second most common primary hepatobiliary malignancy and presents as three separate morphological subtypes; namely mass-forming, periductal-infiltrating, and intraductal-growing patterns. Each of these subtypes have distinct imaging characteristics, as well as a variety of benign and malignant mimics, making accurate diagnosis of CCA on imaging challenging. Whilst histopathological examination is required to arrive at a definitive diagnosis, it is still important for radiologists to be cognizant of these entities and provide reasonable differential diagnoses, as these potentially have a large impact on patient management. This pictorial essay illustrates the three morphological subtypes of CCA, as well as some important mimics for each subtype, that are encountered in clinical practice.
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Braunwarth E, Schullian P, Kummann M, Reider S, Putzer D, Primavesi F, Stättner S, Öfner D, Bale R. Aggressive local treatment for recurrent intrahepatic cholangiocarcinoma—Stereotactic radiofrequency ablation as a valuable addition to hepatic resection. PLoS One 2022; 17:e0261136. [PMID: 34982804 PMCID: PMC8726471 DOI: 10.1371/journal.pone.0261136] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/24/2021] [Indexed: 11/18/2022] Open
Abstract
Background
To evaluate the efficacy, safety and overall clinical outcome of local treatment for recurrent intrahepatic cholangiocellular carcinoma after hepatic resection.
Methods
Between 2007 and 2019 72 consecutive patients underwent hepatic resection for primary intrahepatic cholangiocellular carcinoma. If amenable, recurrent tumors were aggressively treated by HR or stereotactic radiofrequency ablation with local curative intent. Endpoints consisted of morbidity and mortality, locoregional and de novo recurrence, disease free survival, and overall survival.
Results
After a median follow-up of 28 months, recurrence of intrahepatic cholangiocellular carcinoma was observed in 43 of 72 patients undergoing hepatic resection (60.3%). 16 patients were subsequently treated by hepatic resection (n = 5) and stereotactic radiofrequency ablation (n = 11) with local curative intention. The remaining 27 patients underwent palliative treatment for first recurrence. Overall survival of patients who underwent repeated aggressive liver-directed therapy was comparable to patients without recurrence (p = 0.938) and was better as compared to patients receiving palliative treatment (p = 0.018). The 5-year overall survival rates for patients without recurrence, the repeated liver-directed treatment group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By adding stereotactic radiofrequency ablation as an alternative treatment option, the rate of curative re-treatment increased from 11.9% to 37.2%.
Conclusion
Repeated hepatic resection is often precluded due to patient morbidity or anatomical and functional limitations. Due to the application of stereotactic radiofrequency ablation in case of recurrent intrahepatic cholangiocellular carcinoma, the number of patients treated with curative intent can be increased. This leads to favorable clinical outcome as compared to palliative treatment of intrahepatic cholangiocellular carcinoma recurrence.
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Affiliation(s)
- Eva Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Peter Schullian
- Department of Radiology, Interventional Oncology—Microinvasive Therapy, Medical University of Innsbruck, Innsbruck, Austria
| | - Moritz Kummann
- Department of Radiology, Interventional Oncology—Microinvasive Therapy, Medical University of Innsbruck, Innsbruck, Austria
| | - Simon Reider
- Department of Internal Medicine I, Gastroenterology, Hepatology & Endocrinology, Medical University of Innsbruck, Innsbruck, Austria
| | - Daniel Putzer
- Department of Radiology, Interventional Oncology—Microinvasive Therapy, Medical University of Innsbruck, Innsbruck, Austria
| | - Florian Primavesi
- Department of General, Visceral and Vascular Surgery, Salzkammergut Klinikum, Vöcklabruck, Austria
| | - Stefan Stättner
- Department of General, Visceral and Vascular Surgery, Salzkammergut Klinikum, Vöcklabruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Reto Bale
- Department of Radiology, Interventional Oncology—Microinvasive Therapy, Medical University of Innsbruck, Innsbruck, Austria
- * E-mail:
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Acher AW, Rahnemai-Azar AA, Weber SM, Pawlik TM. Surgical Approach to Pancreas, Liver, Biliary Physiologic Impairment. THE IASGO TEXTBOOK OF MULTI-DISCIPLINARY MANAGEMENT OF HEPATO-PANCREATO-BILIARY DISEASES 2022:31-49. [DOI: 10.1007/978-981-19-0063-1_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wang N, Li J, He J, Jing YG, Zhao WD, Yu WJ, Wang J. Knockdown of lncRNA CCAT1 Inhibits the Progression of Colorectal Cancer via hsa-miR-4679 Mediating the Downregulation of GNG10. J Immunol Res 2021; 2021:8930813. [PMID: 35005034 PMCID: PMC8739552 DOI: 10.1155/2021/8930813] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 08/08/2021] [Accepted: 11/27/2021] [Indexed: 12/24/2022] Open
Abstract
Great concerns have raised crucial roles of long noncoding RNAs (lncRNAs) on colorectal cancer progression due to the increasing number of studies in cancer development. Previous studies reveal that lncRNA CCAT1 plays an important role in the progression of a variety of cancers. However, the role of lncRNA CCAT1 in colorectal cancer is still unclear. In this study, we found that in both colorectal tissues and cell lines the level of lncRNA CCAT1 was increased. Downregulation of lncRNA CCAT1 inhibited the proliferation, migration, and invasion of colorectal cell lines and promoted apoptosis. We then found that hsa-miR-4679 could bind to lncRNA CCAT1 directly, and with further functional analyses, we confirmed that lncRNA CCAT1 sponged hsa-miR-4679 to promote the progression of colorectal cancer. Next, we found that hsa-miR-4679 was directly bound to 3'UTR of GNG10 (guanine nucleotide-binding protein, gamma 10). GNG10 overexpression promoted the progression of colorectal cancer, and this phenotype could be reversed by miR-4679 mimics. At last, we knocked down CCAT1 in vivo and found that sh-CCAT1 reduced the tumor size and the number of proliferating cells. In summary, our findings revealed that lncRNA CCAT1 facilitated colorectal cancer progression via the hsa-miR-4679/GNG10 axis and provided new potential therapeutic targets for colorectal cancer.
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Affiliation(s)
- Ning Wang
- Department of Surgery, School of Clinical Medicine, Dali University, Dali, Yunnan 671000, China
| | - Jun Li
- Department of Surgery, School of Clinical Medicine, Dali University, Dali, Yunnan 671000, China
| | - Ju He
- Department of General Surgery, The First Affiliated Hospital of Dali University, Dali University, Dali, Yunnan 671000, China
| | - Yong-Guang Jing
- Department of Human Anatomy, School of Basic Medical Sciences, Dali University, Dali, Yunnan 671000, China
| | - Wei-dong Zhao
- Laboratory Department, School of Clinical Medicine, Dali University, Dali, Yunnan 671000, China
| | - Wen-jin Yu
- Department of General Surgery, The First Affiliated Hospital of Dali University, Dali University, Dali, Yunnan 671000, China
| | - Jing Wang
- Department of Surgery, School of Clinical Medicine, Dali University, Dali, Yunnan 671000, China
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Fabritius MP, Ben Khaled N, Kunz WG, Ricke J, Seidensticker M. Image-Guided Local Treatment for Unresectable Intrahepatic Cholangiocarcinoma-Role of Interventional Radiology. J Clin Med 2021; 10:jcm10235574. [PMID: 34884275 PMCID: PMC8658286 DOI: 10.3390/jcm10235574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/24/2021] [Accepted: 11/24/2021] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.
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Affiliation(s)
- Matthias P. Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany;
- German Cancer Consortium (DKTK), Partner Site Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Wolfgang G. Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
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Prete MG, Cammarota A, D’Alessio A, Zanuso V, Rimassa L. Current options and future directions of systemic therapy for advanced biliary tract cancer. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2021; 2:416-433. [PMID: 36045701 PMCID: PMC9400707 DOI: 10.37349/etat.2021.00054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 09/09/2021] [Indexed: 11/19/2022] Open
Abstract
Biliary tract cancers (BTCs) are aggressive tumors arising from different portions of the biliary tree and classified according to the anatomical location in intrahepatic (i) cholangiocarcinoma (CCA, iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Due to their silent behavior, BTCs are frequently diagnosed at advanced stages when the prognosis is poor. The available chemotherapeutic options are palliative and unfortunately, most patients will die from their disease between 6 and 18 months from diagnosis. However, over the last decade, amounting interest has been posed on the genomic landscape of BTCs and deep-sequencing studies have identified different potentially actionable driver mutations. Hence, the promising results of the early phase clinical studies with targeted agents against isocitrate dehydrogenase (IDH) 1 mutation or fibroblast growth factor (FGF) receptor (FGFR) 2 aberrations inintrahepatic tumors, and other agents against humanepidermal growth factor receptor (HER) 2 overexpression/mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions or B-type Raf kinase (BRAF) mutations across different subtypes of BTCs, have paved the way for a "precision medicine" strategy for BTCs. Moreover, despite the modest results when used as monotherapy, beyond microsatellite instability-high (MSI-H) tumors, immune checkpoint inhibitors are being evaluated in combination with platinum-based chemotherapy, possibly further expanding the therapeutic landscape of advanced BTCs. This review aims to provide an overview of the approved systemic therapies, the promising results, and the ongoing studies to explore the current and future directions of advanced BTC systemic treatment.
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Affiliation(s)
- Maria Giuseppina Prete
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Antonella Cammarota
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Antonio D’Alessio
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Valentina Zanuso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
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20
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An Integrative Systems Biology Approach Identifies Molecular Signatures Associated with Gallbladder Cancer Pathogenesis. J Clin Med 2021; 10:jcm10163520. [PMID: 34441816 PMCID: PMC8397040 DOI: 10.3390/jcm10163520] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 07/17/2021] [Accepted: 07/30/2021] [Indexed: 12/13/2022] Open
Abstract
Gallbladder cancer (GBC) has a lower incidence rate among the population relative to other cancer types but is a major contributor to the total number of biliary tract system cancer cases. GBC is distinguished from other malignancies by its high mortality, marked geographical variation and poor prognosis. To date no systemic targeted therapy is available for GBC. The main objective of this study is to determine the molecular signatures correlated with GBC development using integrative systems level approaches. We performed analysis of publicly available transcriptomic data to identify differentially regulated genes and pathways. Differential co-expression network analysis and transcriptional regulatory network analysis was performed to identify hub genes and hub transcription factors (TFs) associated with GBC pathogenesis and progression. Subsequently, we assessed the epithelial-mesenchymal transition (EMT) status of the hub genes using a combination of three scoring methods. The identified hub genes including, CDC6, MAPK15, CCNB2, BIRC7, L3MBTL1 were found to be regulators of cell cycle components which suggested their potential role in GBC pathogenesis and progression.
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21
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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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22
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Mimmo A, Tzedakis S, Guéroult P, Belabbas D, Jeddou H, Boudjema K. Kasai-Like Portoenterostomy for Multiple Biliary Duct Reconstruction After Extended Liver Resection of Perihilar Cholangiocarcinoma. Ann Surg Oncol 2021; 28:7741. [PMID: 33993375 DOI: 10.1245/s10434-020-09551-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 12/13/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Surgical resection remains the best therapeutic option for the long-term survival of patients with perihilar cholangiocarcinoma (PCC).1 For patients presenting with Bismuth type 3 or 4 tumors, left or right extended liver resection has been shown to be feasible.2 The Achilles heel of the procedure remains biliary reconstruction due to multiple small-diameter remnant liver bile ducts.3 This study showed how a Kasai-like portoenterostomy allows circumvention of this difficulty. METHODS A 57-year-old woman with a type 3a PCC invading the main portal vein bifurcation underwent a right hepatectomy with en bloc resection of segment 4b, the caudate lobe, and the extrahepatic common bile duct; hepatic pedicle lymphadenectomy; and main portal vein bifurcation reconstruction.4 The cross-section of the left biliary plate was tumor-free at frozen section analysis but involved three small biliary ducts originating from segments 2, 3, and 4a. The biliary plate and the distance between each duct were too large to allow unification. A Roux-en-Y portoenterostomy, inspired by the Kasai procedure,5 was performed between the umbilical plate and the extramucosal wall of an efferent Roux-en-Y jejunal limb. Two temporary external trans-portoenterostomy drains were placed according to the Voelker technique. RESULTS The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The two trans-portoenterostomy drains were removed after 6 weeks, and patient was disease-free at the 2-year follow-up evaluation. CONCLUSIONS In extended PCC, Kasai-like portoenterostomy may facilitate complex biliodigestive reconstructions when multiple biliary ducts are involved.
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Affiliation(s)
- Antonio Mimmo
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, Rennes, France.,Department of Digestive Surgery, Hospital of Le Mans, Le Mans, France
| | - Stylianos Tzedakis
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, Rennes, France.,Department of Digestive, Hepatobiliary, and Endocrine Surgery, Cochin University Hospital AP-HP, Paris, France
| | - Pierre Guéroult
- Department of Visceral Surgery, University Hospital of Angers, Angers, France
| | - Dihia Belabbas
- Department of Radiology, Pontchaillou University Hospital, Rennes, France
| | - Heithem Jeddou
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, Rennes, France
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou University Hospital, Rennes, France.
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23
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Pietge H, Sánchez-Velázquez P, Akhoundova D, Siebenhüner A, Winder T, Bachmann H, Nguyen-Kim TDL, Breitenstein S, Knuth A, Petrowsky H, Pestalozzi B, Clavien PA, Samaras P. Combination of HAI-FUDR and Systemic Gemcitabine and Cisplatin in Unresectable Cholangiocarcinoma: A Dose Finding Single Center Study. Oncology 2021; 99:300-309. [PMID: 33657549 DOI: 10.1159/000512967] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 09/21/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma. METHODS Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1-14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported. RESULTS The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1-49), and median progression-free survival 10.1 months (range 2-40). CONCLUSIONS Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted.
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Affiliation(s)
- Heike Pietge
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | | | - Dilara Akhoundova
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Alexander Siebenhüner
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Thomas Winder
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Helga Bachmann
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | | | | | - Alexander Knuth
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Henrik Petrowsky
- Department of General Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Bernhard Pestalozzi
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Pierre-Alain Clavien
- Department of General Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Panagiotis Samaras
- Department of Medical Oncology and Hematology, Division of Medical Oncology, University Hospital Zurich, Zurich, Switzerland,
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24
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Tovoli F, Guerra P, Iavarone M, Veronese L, Renzulli M, De Lorenzo S, Benevento F, Brandi G, Stefanini F, Piscaglia F. Surveillance for Hepatocellular Carcinoma Also Improves Survival of Incidentally Detected Intrahepatic Cholangiocarcinoma Arisen in Liver Cirrhosis. Liver Cancer 2020; 9:744-755. [PMID: 33442543 PMCID: PMC7768136 DOI: 10.1159/000509059] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 05/29/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Due to its poor survival, intrahepatic cholangiocarcinoma (ICC) is held to be a much more aggressive cancer than hepatocellular carcinoma (HCC). In most published series, patients were diagnosed when symptomatic. However, ICC is now increasingly being discovered during the surveillance for HCC in cirrhosis. Whether this earlier detection of ICC is associated with an equally dismal prognosis or not is unknown. METHODS This is amulticenter retrospective study of consecutive ICC patients. Patients were stratified into subgroups according to the absence/presence of cirrhosis. A propensity score matching was performed to reduce the potential biases. Cirrhotic patients were further stratified according to their surveillance status. The lead-time bias and its potential effects were also estimated. RESULTS We gathered 184 patients. Eighty-five patients (46.2%) were cirrhotic. Liver cirrhosis was not related to a worse overall survival (33.0 vs. 32.0 months, p = 0.800) even after the propensity score analysis (43.0 in vs. 44.0 months in 54 pairs of patients, p = 0.878). Among the cirrhotic population, 47 (55.3%) patients had received a diagnosis of ICC during a surveillance programme. The 2 subgroups differed in maximum tumour dimensions (30 vs. 48 mm in surveyed and non-surveyed patients, respectively). Surveyed patients were more likely to receive surgical treatments (59.8 vs. 28.9%, p = 0.003). Overall survival was higher in surveyed patients (51.0 vs. 21.0 months, p < 0.001). These benefits were confirmed after correcting for the lead-time bias. CONCLUSIONS Cirrhotic patients have different clinical presentation and outcomes of ICC according to their surveillance status. In our series, ICC in cirrhosis was not associated with worse OS. Cirrhosis itself should not discourage either surgical or non-surgical treatments.
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Affiliation(s)
- Francesco Tovoli
- Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Pietro Guerra
- Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Massimo Iavarone
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | - Letizia Veronese
- III Medical Clinic, Department of Internal Medicine, IRCCS − Policlinico San Matteo Foundation, Pavia, Italy
| | - Matteo Renzulli
- Radiology Unit, Azienda Ospedaliero Universitaria S.Orsola-Malpighi di Bologna, Bologna, Italy
| | - Stefania De Lorenzo
- Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesca Benevento
- Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giovanni Brandi
- Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Federico Stefanini
- Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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25
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Personeni N, Lleo A, Pressiani T, Colapietro F, Openshaw MR, Stavraka C, Pouptsis A, Pinato DJ, Rimassa L. Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options. Cancers (Basel) 2020; 12:3370. [PMID: 33202975 PMCID: PMC7696875 DOI: 10.3390/cancers12113370] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/08/2020] [Accepted: 11/11/2020] [Indexed: 12/13/2022] Open
Abstract
Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.
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Affiliation(s)
- Nicola Personeni
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy; (N.P.); (T.P.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (A.L.); (F.C.)
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (A.L.); (F.C.)
- Internal Medicine Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy; (N.P.); (T.P.)
| | - Francesca Colapietro
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (A.L.); (F.C.)
- Internal Medicine Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy
| | - Mark Robert Openshaw
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W120HS, UK; (M.R.O.); (D.J.P.)
| | - Chara Stavraka
- Department of Medical Oncology, Guy’s and St Thomas’ NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK;
| | - Athanasios Pouptsis
- Department of Medical Oncology, “Euromedica” General Clinic, 54645 Thessaloniki, Greece;
| | - David James Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W120HS, UK; (M.R.O.); (D.J.P.)
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano, 20089 Milan, Italy; (N.P.); (T.P.)
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, Italy; (A.L.); (F.C.)
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26
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Shindo Y, Kobayashi S, Wada H, Tokumitsu Y, Matsukuma S, Matsui H, Nakajima M, Yoshida S, Iida M, Suzuki N, Takeda S, Hoshii Y, Eguchi H, Nagano H. Short- and Long-Term Outcomes of Simultaneous Hepatic Artery Resection and Reconstruction for Perihilar Cholangiocarcinoma. Gastrointest Tumors 2020; 8:25-32. [PMID: 33728293 DOI: 10.1159/000511164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 08/24/2020] [Indexed: 12/14/2022] Open
Abstract
Introduction Because surgical resection with simultaneous hepatic artery (HA) resection and reconstruction for perihilar cholangiocarcinoma (PHC) is technically demanding, the surgical indication for this challenging procedure is controversial. Thus, this study aimed to evaluate the efficacy of simultaneous HA resection and reconstruction for PHC. Methods Between January 2002 and January 2018, 13 patients with PHC underwent surgical intervention with simultaneous resection and reconstruction of the HA at Yamaguchi University Hospital (Ube, Japan) and Osaka University Hospital (Suita, Japan). Results There were 2 cases (15.4%) of 90-day postoperative mortality. Nine patients (69.2%) developed major postoperative complications (Clavien-Dindo classification ≥IIIa). Curative resections (R0) were achieved in 8 cases (61.5%). The median survival time (MST) and 1- and 3-year survival rates after resection (including in-hospital deaths) were 20.9 months and 61.5 and 10.3%, respectively. The MST and 1- and 2-year survival rates of 8 patients who underwent R0 resection were significantly better than those of the other 5 patients (24.2 vs. 10.2 months, 75.0 vs. 40.0%, and 50.0 vs. 0.0%, respectively, p = 0.0228). Conclusions Simultaneous HA resection and reconstruction is technically possible and may provide long-term survival in selected patients with locally advanced PHC.
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Affiliation(s)
- Yoshitaro Shindo
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shogo Kobayashi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Satoshi Matsukuma
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Hiroto Matsui
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Masao Nakajima
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shin Yoshida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Michihisa Iida
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Nobuaki Suzuki
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Shigeru Takeda
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
| | - Yoshinobu Hoshii
- Department of Diagnostic Pathology, Yamaguchi University Hospital, Ube, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan
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27
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Kamada Y, Hori T, Yamamoto H, Harada H, Yamamoto M, Yamada M, Yazawa T, Tani M, Sato A, Tani R, Aoyama R, Sasaki Y, Zaima M. Surgical treatment of gallbladder cancer: An eight-year experience in a single center. World J Hepatol 2020; 12:641-660. [PMID: 33033570 PMCID: PMC7522563 DOI: 10.4254/wjh.v12.i9.641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 07/10/2020] [Accepted: 07/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gallbladder cancer (GBC) is the most common biliary malignancy and has the worst prognosis, but aggressive surgeries [e.g., resection of the extrahepatic bile duct (EHBD), major hepatectomy and lymph node (LN) dissection] may improve long-term survival. GBC may be suspected preoperatively, identified intraoperatively, or discovered incidentally on histopathology. AIM To present our data together with a discussion of the therapeutic strategies for GBC. METHODS We retrospectively investigated nineteen GBC patients who underwent surgical treatment. RESULTS Nearly all symptomatic patients had poor outcomes, while suspicious or incidental GBCs at early stages showed excellent outcomes without the need for two-stage surgery. Lymph nodes around the cystic duct were reliable sentinel nodes in suspicious/incidental GBCs. Intentional LN dissection and EHBD resection prevented metastases or recurrence in early-stage GBCs but not in advanced GBCs with metastatic LNs or invasion of the nerve plexus. All patients with positive surgical margins (e.g., the biliary cut surface) showed poor outcomes. Hepatectomies were performed in sixteen patients, nearly all of which were minor hepatectomies. Metastases were observed in the left-sided liver but not in the caudate lobe. We may need to reconsider the indications for major hepatectomy, minimizing its use except when it is required to accomplish negative bile duct margins. Only a few patients received neoadjuvant or adjuvant chemoradiation. There were significant differences in overall and disease-free survival between patients with stages ≤ IIB and ≥ IIIA disease. The median overall survival and disease-free survival were 1.66 and 0.79 years, respectively. CONCLUSION Outcomes for GBC patients remain unacceptable, and improved therapeutic strategies, including neoadjuvant chemotherapy, optimal surgery and adjuvant chemotherapy, should be considered for patients with advanced GBCs.
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Affiliation(s)
- Yasuyuki Kamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Tomohide Hori
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan.
| | - Hidekazu Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Hideki Harada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Michihiro Yamamoto
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masahiro Yamada
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Takefumi Yazawa
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masaki Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Asahi Sato
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryotaro Tani
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Ryuhei Aoyama
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Yudai Sasaki
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| | - Masazumi Zaima
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
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Guidelines for Management of Urgent Symptoms in Patients with Cholangiocarcinoma and Biliary Stents or Catheters using the Modified RAND/UCLA Delphi Process. Cancers (Basel) 2020; 12:cancers12092375. [PMID: 32825784 PMCID: PMC7565442 DOI: 10.3390/cancers12092375] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/04/2020] [Accepted: 08/17/2020] [Indexed: 12/28/2022] Open
Abstract
Background: Patients with cholangiocarcinoma often have indwelling biliary stents or catheters which are prone to obstructions and/or infections; studies show that 20–40% present with fever and/or jaundice requiring urgent treatment in the outpatient setting for which there are no uniform guidelines. The goal was to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: Thirteen expert physicians from relevant specialties, geography, and practice settings were recruited for the panel. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a scale from 1–9 and classified as appropriate, inappropriate, or uncertain. Scenarios with greater than 2 (>2) ratings of 1–3 (inappropriate) and greater than 2 (>2) ratings of 7–9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions and the UK (8%) and had practiced for a mean 16.5 years (4–33 years). Panelists rated 480 scenarios before the meeting and re-rated 288 of the clinical scenarios after the meeting. The panelists agreed that ongoing treatment with chemotherapy did not influence decision-making and, therefore, 192 scenarios were excluded from the final list. Disagreement decreased from 37.5% before to 10.4% after the meeting. Consensus on stent/tube manipulation and inpatient antibiotic therapy was obtained and summarized in patients as “appropriate” or “maybe appropriate” based on a patient’s bilirubin level at presentation. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in the urgent management of ascending cholangitis in patients with cholangiocarcinoma.
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Use of preoperative controlling nutritional status (CONUT) score as a better prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy. Surg Today 2020; 51:358-365. [PMID: 32761459 DOI: 10.1007/s00595-020-02098-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/16/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE The controlling nutritional status (CONUT) score can be easily calculated from the serum albumin concentration, total cholesterol concentration, and total lymphocyte count. The study aim was to assess the preoperative prognostic factors for the overall survival (OS) of distal cholangiocarcinoma (DCC) following pancreatoduodenectomy (PD) and to demonstrate the utility of the CONUT score. METHODS A total of 149 consecutive patients who underwent PD for DCC between September 2002 and December 2016 were divided into a low-CONUT (LC) group (CONUT scores ≤ 2) and a high-CONUT (HC) group (CONUT scores ≥ 3). The clinicopathological characteristics and OS of the patients were evaluated retrospectively. Prognostic factors of DCC were identified by multivariate analyses. RESULTS The LC and HC groups included 113 and 36 patients, respectively. The OS was better in the LC group than in the HC group (median survival time and 5 year survival rate: 82 months and 56.8% vs. 38 months and 27.6%, P = 0.005). Multivariate analyses for the OS in all patients showed that the tumor differentiation, perineural invasion, residual tumor status, portal vein resection, blood transfusion, and preoperative CONUT score ≥ 3 were independently associated with a poor survival. CONCLUSION The CONUT score may be a useful preoperative factor for predicting the long-term survival in patients with DCC.
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LKB1 inhibits intrahepatic cholangiocarcinoma by repressing the transcriptional activity of the immune checkpoint PD-L1. Life Sci 2020; 257:118068. [PMID: 32653521 DOI: 10.1016/j.lfs.2020.118068] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/28/2020] [Accepted: 07/06/2020] [Indexed: 11/20/2022]
Abstract
AIMS Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumour with increasing incidence and high mortality. Liver kinase B1 (LKB1) regulates cellular energy metabolism and cell division and affects immune microenvironment. This study aimed to uncover the underlying function and mechanism of LKB1 in ICC. MAIN METHODS To determine the correlation between LKB1 levels and clinicopathological features, the expression profile of LKB1 in ICC tissue specimens was examined by qRT-PCR and western blotting. In vitro experiments were conducted to examine the anticancer effect of LKB1 in ICC. Changes in the expression of epithelial-mesenchymal transition (EMT)-associated markers and immune checkpoints were analysed by qRT-PCR, western blotting, immunofluorescence and flow cytometry. The influence of LKB1 on the transcriptional activity of PD-L1 was determined by dual-luciferase reporter assays and IFNγ induction. KEY FINDINGS LKB1 was expressed at low levels in ICC and tightly associated with poor prognosis. LKB1 knockdown promoted the proliferation, migration, matrix adhesion and EMT of ICC cells. Notably, LKB1 silencing upregulated the surface expression of PD-L1 in ICC cells. Suppressed and mutated LKB1 enhanced the transcriptional activity of PD-L1 in ICC cells, leading to high expression of the immune checkpoint PD-L1. Furthermore, inhibiting LKB1 suppressed ICC cell apoptosis induced by IFNγ. SIGNIFICANCE By suppressing malignant transformation and the immune checkpoint PD-L1 of cancer cells, LKB1 plays an important role in inhibiting ICC and is a potential target for clinical diagnosis and treatment. This study may provide new strategies for improving the efficiency of cancer immunotherapy.
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Chung T, Rhee H, Nahm JH, Jeon Y, Yoo JE, Kim YJ, Han DH, Park YN. Clinicopathological characteristics of intrahepatic cholangiocarcinoma according to gross morphologic type: cholangiolocellular differentiation traits and inflammation- and proliferation-phenotypes. HPB (Oxford) 2020; 22:864-873. [PMID: 31735647 DOI: 10.1016/j.hpb.2019.10.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 09/05/2019] [Accepted: 10/01/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is subclassified into mass-forming (MF), periductal-infiltrative (PI), and mixed types grossly; however, their clinicopathological significance remains controversial. METHODS Clinicopathological characteristics of iCCA gross types were analysed according to histopathological type (small-duct, large-duct, indeterminate) or cholangiolocellular differentiation trait (CDT) in 108 iCCAs. The expression levels of inflammation-marker (CRP, FGB) and proliferation-marker (phospho-ERK1/2, Ki-67) were evaluated by immunohistochemistry. RESULTS There were 87 MF, 8 PI, and 13 mixed-gross type. Small-duct-type (39, 44.8%) and CDT (19, 21.8%) were found only in MF-gross type. The inflammation-marker expression was higher in MF-type than in PI- and mixed-gross types (P = 0.023). It was high in small-duct-type, middle in indeterminate-type, and low in large-duct-type (P = 0.015), and iCCAs with CDT showed higher inflammation-marker expression compared to those without (P < 0.001). Proliferation-marker expression did not differ according to gross type; however it was lower in iCCA with CDT compared to those without (P = 0.004). Subgrouping of the gross type according to histopathological type or CDT revealed that MF-type with small-duct-type or CDT had better overall survival compared to the others (P < 0.05). CONCLUSION MF-type iCCA is more heterogeneous than other gross types. High inflammation-marker/low proliferation-marker expression in MF-type with CDT or small-duct-type may be related to a good outcome.
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Affiliation(s)
- Taek Chung
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hyungjin Rhee
- Department of Radiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Ji Hae Nahm
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Youngsic Jeon
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jeong Eun Yoo
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Young-Joo Kim
- Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea
| | - Dai Hoon Han
- Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Young Nyun Park
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
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Torzilli G, Viganò L, Fontana A, Procopio F, Terrone A, Cimino MM, Donadon M, Del Fabbro D. Oncological outcome of R1 vascular margin for mass-forming cholangiocarcinoma. A single center observational cohort analysis. HPB (Oxford) 2020; 22:570-577. [PMID: 31530450 DOI: 10.1016/j.hpb.2019.08.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Recent studies validated the possibility to detach colorectal liver metastases from vessels (R1vasc) featuring R1vasc equivalent to R0 and superior to tumor exposure along the transection plane (R1par). To clarify the outcome of R1 surgery (margin <1 mm) in patients with intrahepatic cholangiocarcinoma (MFCCC), distinguishing R1par and R1vasc resections. METHODS Patients undergoing resection for MFCCC between 2008 and 2016 were considered. Tumor detachment from 1st/2nd-order Glissonean pedicles or hepatic veins was performed in advanced diseases. R0, R1par, and R1vasc were compared. RESULTS The study included 84 resection areas in 59 patients (17 R1vasc). R1vasc group had local recurrence risk similar to R1par group (per-patient analysis 29% vs. 36%; per-resection area analysis 29% vs. 32%), higher than R0 group (3% and 2%, p = 0.003 and p = 0.0003). R1vasc and R1par groups had similar overall and recurrence-free survival (median OS 30 vs. 30 months; RFS 10 vs. 8 months), lower than R0 group (70 and 39 months, p = 0.066 and p = 0.007). CONCLUSION In MFCCC patients, R1vasc resection is not an adequate treatment. Local disease control and survival after R1vasc resection are lower than after R0 resection and similar to R1par resection. R1vasc resection could be exclusively considered to achieve resectability in otherwise unresectable patients.
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Affiliation(s)
- Guido Torzilli
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
| | - Luca Viganò
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Andrea Fontana
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Fabio Procopio
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Alfonso Terrone
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Matteo M Cimino
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Matteo Donadon
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Daniele Del Fabbro
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center - IRCCS, Humanitas University, Via Manzoni 56, 20089, Rozzano, Milan, Italy
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Caparica R, Bruzzone M, Hachem GE, Ceppi M, Lambertini M, Glasberg J, de Azambuja E, Van Laethem JL, Hendlisz A. Adjuvant chemotherapy in biliary tract cancer patients: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Oncol Hematol 2020; 149:102940. [PMID: 32252001 DOI: 10.1016/j.critrevonc.2020.102940] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 01/29/2020] [Accepted: 03/16/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The role of adjuvant chemotherapy in biliary tract cancer is controversial. We performed a systematic review and meta-analysis to assess the effect of adjuvant chemotherapy in biliary tract cancer patients. METHODS A literature search was performed to identify randomized controlled trials (RCTs) comparing adjuvant chemotherapy versus observation, and a pooled analysis was conducted using the random-effect model. RESULTS Three RCTs (N = 866) were included. No difference was observed between chemotherapy and observation in terms of OS (HR 0.91; 95 %CI, 0.75-1.09; p = 0.295), whereas a significant improvement in RFS was shown (HR 0.83; 95 %CI, 0.69-0.99; p = 0.040). No subgroup that benefited most from adjuvant chemotherapy was identified, although a trend was observed in N+ patients (HR 0.83; 95 %CI, 0.65-1.08; p = 0.165). DISCUSSION Adjuvant chemotherapy yields a significant RFS benefit in biliary tract cancer patients and should be considered for those who are able to tolerate additional treatment after surgery.
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Affiliation(s)
- Rafael Caparica
- Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium.
| | - Marco Bruzzone
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Georges El Hachem
- Department of Hematology and Medical Oncology, Saint George Hospital University Medical Center, Beirut, Lebanon
| | - Marcello Ceppi
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Matteo Lambertini
- Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy
| | - João Glasberg
- Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, Brazil
| | - Evandro de Azambuja
- Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Jean-Luc Van Laethem
- Department of Gastroenterology, Hepatology and Digestive Oncology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Alain Hendlisz
- Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium
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Köhler M, Harders F, Lohöfer F, Paprottka PM, Schaarschmidt BM, Theysohn J, Herrmann K, Heindel W, Schmidt HH, Pascher A, Stegger L, Rahbar K, Wildgruber M. Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization. J Clin Med 2019; 9:jcm9010056. [PMID: 31881761 PMCID: PMC7020033 DOI: 10.3390/jcm9010056] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/16/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.
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Affiliation(s)
- Michael Köhler
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
| | - Fabian Harders
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
| | - Fabian Lohöfer
- Division of Interventional Radiology, Klinikum rechts der Isar der Technischen Universität München, D-81675 München, Germany; (F.L.); (P.M.P.)
| | - Philipp M. Paprottka
- Division of Interventional Radiology, Klinikum rechts der Isar der Technischen Universität München, D-81675 München, Germany; (F.L.); (P.M.P.)
| | - Benedikt M. Schaarschmidt
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Diagnostic and Interventional Radiology, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Jens Theysohn
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Diagnostic and Interventional Radiology, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Ken Herrmann
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for Nuclear Medicine, Universitätsklinikum Essen, D-41547 Essen, Germany
| | - Walter Heindel
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
| | - Hartmut H. Schmidt
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Gastroenterology and Hepatology, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Andreas Pascher
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department for General, Visceral and Transplantation Surgery, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Lars Stegger
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Nuclear Medicine, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Kambiz Rahbar
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Department of Nuclear Medicine, Universitätsklinikum Münster, D-48149 Münster, Germany
| | - Moritz Wildgruber
- Department of Clinical Radiology, Universitätsklinikum Münster, D-48149 Münster, Germany; (M.K.); (F.H.); (W.H.)
- Network Partner Site Westdeutsches Tumorzentrum, D-45147 Essen, Germany; (B.M.S.); (J.T.); (K.H.); (H.H.S.); (A.P.); (L.S.); (K.R.)
- Correspondence: ; Tel.: +49-251-83-56261
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Bagante F, Ruzzenente A, Conci S, Rusev BC, Simbolo M, Campagnaro T, Pawlik TM, Luchini C, Iacono C, Scarpa A, Guglielmi A. Patterns of gene mutations in bile duct cancers: is it time to overcome the anatomical classification? HPB (Oxford) 2019; 21:1648-1655. [PMID: 31122820 DOI: 10.1016/j.hpb.2019.04.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 03/04/2019] [Accepted: 04/08/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Two recent studies based on multi-omics data analysis identified distinct subtypes of bile-duct cancers (BDC) with important implications in terms of disease classification and patients' treatment. METHODS Patients with mutations in KRAS, NRAS, TP53, and ARID1A genes were classified in KRAS/TP53 group while patients with mutations in IDH1-2, BAP1, and PBRM1 were classified in IDH1-2/BAP1/PBRM1 group. The aim of this study was to define long-term outcomes among patients stratified by patterns of genes mutated. RESULTS Among 105 patients who underwent surgical resection for BDCs, 71 (68%) patients were classified in two groups based on patterns of genes mutated. While in IDH1-2/BAP1/PBRM1 group there were 58%, 22%, and 10% of patients with intrahepatic-cholangiocarcinoma (ICC), perihilar-cholangiocarcinoma (PHCC), and gallbladder cancer (GBC), in KRAS/TP53 group there were 42%, 78%, and 90% of patients with ICC, PHCC, and GBC (p = 0.003), respectively. Patients in IDH1-2/BAP1/PBRM1 group had a 5-year OS of 40% compared with 13% for KRAS/TP53 group (p = 0.032). In a multivariable model adjusted for margins, lymph-node status, microvascular invasion, and tumor grade, patients in KRAS/TP53 group had a 2.1-fold increased risk of death compared with patients in IDH1-2/BAP1/PBRM1 group (p = 0.028). CONCLUSIONS Genetic data were able to overcome the clinical based staging system in predicting patients' prognosis.
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Affiliation(s)
- Fabio Bagante
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy.
| | - Andrea Ruzzenente
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy
| | - Simone Conci
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy
| | - Borislav C Rusev
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Michele Simbolo
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Tommaso Campagnaro
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Claudio Luchini
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Calogero Iacono
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy
| | - Aldo Scarpa
- ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy; Department of Diagnostics and Public Health, Section of Anatomical Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Alfredo Guglielmi
- General and Hepatobiliary Surgery, Department of Surgery, University of Verona, School of Medicine, Verona, Italy
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Maruyama S, Kawaida H, Hosomura N, Amemiya H, Saito R, Shimizu H, Furuya S, Akaike H, Kawaguchi Y, Sudo M, Inoue S, Kono H, Ichikawa D. Indications for extrahepatic bile duct resection due to perineural invasion in patients with gallbladder cancer. World J Surg Oncol 2019; 17:200. [PMID: 31785615 PMCID: PMC6885324 DOI: 10.1186/s12957-019-1735-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 10/29/2019] [Indexed: 02/06/2023] Open
Abstract
Background The indications for extrahepatic bile duct (EHBD) resection remain a major controversy in the surgical management of patients with gallbladder cancer. On the other hand, perineural invasion (PNI) was reported as an important factor in patients with gallbladder cancer because gallbladder cancer cells frequently spread to the tissues surrounding the EHBD via perineural routes. We assessed the correlation of PNI with clinicopathological factors in patients with gallbladder cancer to elucidate EHBD resection indications specifically in patients with PNI. Methods This retrospective study assessed the PNI status of 50 patients with gallbladder cancer who underwent curative resection and examined the correlation between the presence of PNI and clinicopathological factors. Results Thirteen patients (26%) were PNI positive. PNI was significantly correlated with male sex, proximal-type tumor, lymphatic and vascular invasion, and advanced T stage. Multivariate analysis found that PNI positivity (p < 0.001), lymphatic invasion (p = 0.007), and nodal stage (p < 0.001) were independent prognostic factors. PNI was never observed in patients with stage T1 cancer. Conversely, PNI was detected rarely in distal-type tumors, all of whom developed various types of recurrences. Conclusions These results clearly demonstrated the prognostic impact of PNI in patients with gallbladder cancer. We suggest that EHBD resection in combination with cholecystectomy may not be useful for distal-type tumors from a perspective of PNI.
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Affiliation(s)
- Suguru Maruyama
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Naohiro Hosomura
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Hidetake Amemiya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Ryo Saito
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Hiroki Shimizu
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Shinji Furuya
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Hidenori Akaike
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Yoshihiko Kawaguchi
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Makoto Sudo
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Shingo Inoue
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Hiroshi Kono
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan
| | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
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Mehra S, Panwar R, Thakur B, Yadav R, Kumar M, Singh R, Dash NR, Sahni P, Chauhan SS. Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma. Front Oncol 2019; 9:1239. [PMID: 31824841 PMCID: PMC6883407 DOI: 10.3389/fonc.2019.01239] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 10/28/2019] [Indexed: 12/11/2022] Open
Abstract
Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma.
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Affiliation(s)
- Siddharth Mehra
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Rajesh Panwar
- Department of G.I. Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Thakur
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Rajni Yadav
- Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Manish Kumar
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Ratnakar Singh
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
| | - Nihar Ranjan Dash
- Department of G.I. Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Peush Sahni
- Department of G.I. Surgery and Liver Transplantation, All India Institute of Medical Sciences, New Delhi, India
| | - Shyam S Chauhan
- Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
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Vigano L, Soldani C, Franceschini B, Cimino M, Lleo A, Donadon M, Roncalli M, Aghemo A, Di Tommaso L, Torzilli G. Tumor-Infiltrating Lymphocytes and Macrophages in Intrahepatic Cholangiocellular Carcinoma. Impact on Prognosis after Complete Surgery. J Gastrointest Surg 2019; 23:2216-2224. [PMID: 30843133 DOI: 10.1007/s11605-019-04111-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 01/06/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Immune infiltrate impacts prognosis of several tumors. To assess the prognostic impact of tumor-infiltrating lymphocytes and macrophages in patients undergoing resection for intrahepatic cholangiocellular carcinoma (ICC). METHODS All consecutive patients undergoing surgery for ICC between 2008 and 2016 were considered. Inclusion criteria were complete resection and follow-up > 12 months. Tissue sections were immunostained for CD3+, CD4+, CD8+, Foxp3+, and CD68+. The number of positive cells was quantified using a computer-aided image analysis system. Different cut-off values were tested as predictors of overall survival (OS). RESULTS Fifty-three patients were analyzed. ICC were T1 in 28 patients, multifocal in 11, and N+ in 13. After a median follow-up of 42 months, 5-year OS was 52.1%. The following immune infiltrate values were associated with better OS: CD3+ > 0.10% (5-year OS 63.3% vs. 13.6% if ≤ 0.10%, p = 0.001); CD8+ > 0.10% (56.2% vs. 28.6% if ≤ 0.10%, p = 0.051); Foxp3+ absent (59.4% vs. 16.0% if present, p = 0.049). CD4+ and CD68+ infiltrates were not associated with OS. Three-year OS rates in patients with 0, 1, and ≥ 2 negative prognostic factors were 73.6%, 47.3%, and 14.3%, respectively (p < 0.001). CD3+ infiltrate stratified prognosis in T1 tumors (3-year OS 71.7% if CD3+ > 0.10% vs. 14.3% if ≤ 0.10%, p < 0.001). CONCLUSIONS Tumor-infiltrating lymphocytes are associated with prognosis of ICC patients after complete surgery. CD3+ and CD8+ infiltrate is associated with higher survival and lower recurrence risk, while Foxp3+ infiltrate is associated with worse prognosis. CD3+ infiltrate allows refining prediction of prognosis in early tumors.
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Affiliation(s)
- Luca Vigano
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Cristiana Soldani
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy
| | - Barbara Franceschini
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy
| | - Matteo Cimino
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Matteo Donadon
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Massimo Roncalli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Pathology Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Division of Internal Medicine and Hepatology, Department of Internal Medicine, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Luca Di Tommaso
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Pathology Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
| | - Guido Torzilli
- Department of Surgery, Division of Hepatobiliary & General Surgery, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano - Milan, 20089, Italy.
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
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Stereotactic Body Radiation Therapy for Cholangiocarcinoma: Optimizing Locoregional Control With Elective Nodal Irradiation. Adv Radiat Oncol 2019; 5:77-84. [PMID: 32051893 PMCID: PMC7004929 DOI: 10.1016/j.adro.2019.08.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 08/09/2019] [Accepted: 08/12/2019] [Indexed: 12/18/2022] Open
Abstract
Purpose To review our institutional experience of treating cholangiocarcinoma using stereotactic body radiation therapy (SBRT). Methods and Materials A total of 40 patients with intrahepatic (n = 25) or perihilar (n = 15) cholangiocarcinoma treated with SBRT were retrospectively reviewed. SBRT was delivered in 1 to 5 fractions with median dose of 40 Gy. Competing risk analysis was used to estimate cumulative incidence of local in-field, local out-of-field, regional, and distant failure. Kaplan-Meier and log-rank tests were used to calculate overall survival (OS). Toxicity was scored using Common Terminology Criteria for Adverse Events, version 4.0. Results The median follow-up time was 18 months. The 1-year incidence of local in-field, local out-of-field, regional, and distant failure was 8%, 23%, 13%, and 22%, respectively. Median OS was 23 months and 1- and 2-year OS rates were 69% and 39%, respectively. Patients with perihilar tumors had a 1-year incidence of regional failure of 24% and worse OS (P = .013). Patients with regional failure were more likely to develop distant metastases, 32% versus 19% at 1 year (P = .11). Acute grade 3 + hepatobiliary toxicity developed in 15 patients (36%). Conclusions In this series of cholangiocarcinoma patients treated with definitive SBRT, patterns of failure reveal that regional failures are not insignificant, particularly for perihilar tumors. Elective nodal irradiation of regional lymphatics should be considered when using SBRT. A prospective study of elective nodal irradiation in patients with perihilar tumors would further clarify whether this approach improves outcomes without increasing hepatobiliary toxicity.
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Geographical and Temporal Variation in the Incidence and Mortality of Hepato-Pancreato-Biliary Primary Malignancies:1990-2017. J Surg Res 2019; 245:89-98. [PMID: 31404895 DOI: 10.1016/j.jss.2019.07.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/25/2019] [Accepted: 07/12/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatic, pancreas, and biliary (HPB) cancers pose serious challenges to global health care systems. These malignancies demonstrate great geographical variations with shifting trends over time. The aim of the present study was to determine the recent trends in incidence, prevalence, and mortality of primary HPB malignancies to guide the further development of effective strategies for prevention, screening, and treatment. METHODS The Global Burden of Disease (GBD) dataset 1990-2017 was interrogated for end point variables by age, sex, year, and geography. Epidemiologic data were modeled in DisMod-MR 2.1, a Bayesian meta-regression tool that pools data points from different sources and adjusts for known sources of variability. Global Burden of Disease data were extracted from 284 country-year, and 976 subnational-year combinations from 27 countries in North America, Latin America, Europe, India, and New Zealand. RESULTS Although the global incidence of primary HPB malignancies increased by 1.43% from 1990 to 2017 (1,400,739 cases), the incidence of extrahepatic biliary and gallbladder malignancies decreased by -0.32% (210,878 cases) over the same period. There was significant variability in the incidence, prevalence, and mortality of HPB cancers by the sociodemographic index (SDI), as well as by geography. The largest incidence increase of primary liver and pancreas cancers was seen in the high-income Asia-Pacific group, followed by the high-income North America and Western Europe groups. The highest incidences and prevalence of extrahepatic biliary and gallbladder malignancies were observed in Asia-Pacific, Southern Latin American, and Andean Latin American regions. In general, mortality rates of HPB malignancies were larger in the low SDI when compared with the high SDI group in all geographical regions. CONCLUSIONS The global incidence and prevalence of primary liver and pancreatic malignancies continue to increase with great geographical variation. The mortality trends mirror those of the incidence. Although the global incidence and prevalence of extrahepatic biliary and gallbladder malignancies has decreased, the mortality rate has not significantly changed. The results of this article can assist local and regional authorities in policy development to improve health care access for screening, early detection, and treatment of HPB malignancies.
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Long noncoding RNAs as potential biomarkers and therapeutic targets in gallbladder cancer: a systematic review and meta-analysis. Cancer Cell Int 2019; 19:169. [PMID: 31297033 PMCID: PMC6599267 DOI: 10.1186/s12935-019-0891-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 06/23/2019] [Indexed: 02/06/2023] Open
Abstract
Background Mounting evidence has shown that long noncoding RNAs (lncRNAs) can play a substantial role in gallbladder cancer (GBC) development as tumor promotors or suppressors, and their abnormal expression is relevant to GBC patient outcomes. We completed this systematic review and meta-analysis to explore the clinical significance and mechanisms of lncRNAs in GBC. Methods We conducted a comprehensive literature search and selected eligible records according to the inclusion and exclusion criteria. Hazard ratios (HRs) and odds ratios (ORs) were extracted or calculated to estimate the relationships of high lncRNA expression with GBC patient survival and clinical outcomes. Results Eighteen studies were identified as eligible for this systematic review and meta-analysis. Heterogeneity among HRs of overall survival (OS) was notably high (I2 = 86.2%, p < 0.001). Subgroup analysis suggested that overexpression of lncRNAs in a group that is upregulated in GBC showed a significant association with poor OS (HR = 2.454, 95% CI 2.004–3.004, I2 = 0%). Conversely, overexpression of lncRNAs in a downregulated group was markedly related to good OS (HR = 0.371, 95% CI 0.267–0.517, I2 = 0%). High expression levels of lncRNA AFAP1-AS1, MALAT1 and ROR were positively correlated with tumor size. Expression of lncRNA LET, LINC00152 and HEGBC exhibited a positive correlation with high T status. LncRNA LINC00152, HEGBC, MALAT1 and ROR showed a marked correlation with positive lymph node metastasis (LNM), while lncRNA GCASPC, MEG3, LET and UCA1 had the opposite effect. High expression levels of lncRNA HEGBC, PAGBC, PVT1 and UCA1 predicted high tumor node metastasis (TNM) stages, while lncRNA LET, GCASPC and MEG3 indicated low TNM stages. We also summarized the mechanisms of lncRNAs in GBC. Conclusion Aberrant expression of several lncRNAs was indicative of the prognosis of GBC patients, and lncRNAs showed promise as biomarkers and therapeutic targets for GBC.
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Shijo M, Fukase K, Ohtsuka H, Ariake K, Masuda K, Ishida M, Mizuma M, Nakagawa K, Hayashi H, Morikawa T, Motoi F, Naitoh T, Unno M. Metastasis of ovarian cancer to the bile duct: a case report. Surg Case Rep 2019; 5:100. [PMID: 31222668 PMCID: PMC6586734 DOI: 10.1186/s40792-019-0659-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 06/07/2019] [Indexed: 12/29/2022] Open
Abstract
Background Ovarian cancer typically spreads along the peritoneum or metastasizes through the blood or lymphatic stream. The bile duct is an extremely rare site of ovarian cancer-associated metastases. Case presentation A 55-year-old female underwent surgery for advanced left ovarian cancer 2 years ago. She was diagnosed with ovarian serous adenocarcinoma with multiple peritoneal metastases. She received chemotherapy for the residual peritoneal metastases. She achieved a clinical complete response and was followed up with imaging examinations for 1 year. She then complained of dark urine, yellowish discoloration of the eyes, and weight loss. Computed tomography showed an approximately 10-mm solid tumor at the hepatic hilum. Simultaneously, multiple peritoneal metastases were detected in the abdominal and pelvic cavity. Intraductal ultrasonography suggested that the hepatic hilum tumor was located in the bile duct wall. Tumor biopsy and brush cytology of the bile duct indicated atypical cells suspicious for carcinoma. After percutaneous transhepatic portal embolization, she underwent right hepatectomy and extrahepatic bile duct resection for the hepato-hilar tumor. The histopathological features were dysplastic cells with hyperchromatic nuclei and no dysplastic cells in the native biliary epithelium. Immunohistochemical staining revealed that the tumor cells were positive for CK-7 and WT-1 and negative for CK-20 and ER. These results suggested that the tumor was a metastasis of the ovarian serous adenocarcinoma. Conclusion This may be the first case of ovarian cancer metastasis to the bile duct. While it is extremely rare, ovarian cancer may metastasize to the hepatic duct, mimicking hilar cholangiocarcinoma.
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Affiliation(s)
- Masahiro Shijo
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Koji Fukase
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Hideo Ohtsuka
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Kyohei Ariake
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Kunihiro Masuda
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Masaharu Ishida
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Kei Nakagawa
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Hiroki Hayashi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Takanori Morikawa
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Takeshi Naitoh
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
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Di Carlo P, Serra N, D'Arpa F, Agrusa A, Gulotta G, Fasciana T, Rodolico V, Giammanco A, Sergi C. The microbiota of the bilio-pancreatic system: a cohort, STROBE-compliant study. Infect Drug Resist 2019; 12:1513-1527. [PMID: 31354308 PMCID: PMC6578573 DOI: 10.2147/idr.s200378] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 04/13/2019] [Indexed: 12/11/2022] Open
Abstract
Background: The gut microbiota play an essential role in protecting the host against pathogenic microorganisms by modulating immunity and regulating metabolic processes. In response to environmental factors, microbes can hugely alter their metabolism. These factors can substantially impact the host and have potential pathologic implications. Particularly pathogenic microorganisms colonizing pancreas and biliary tract tissues may be involved in chronic inflammation and cancer evolution. Purpose: To evaluate the effect of bile microbiota on survival in patients with pancreas and biliary tract disease (PBD). Patients and Methods: We investigated 152 Italian patients with cholelithiasis (CHL), cholangitis (CHA), cholangiocarcinoma (CCA), gallbladder carcinoma (GBC), pancreas head carcinoma (PHC), ampullary carcinoma (ACA), and chronic pancreatitis (CHP). Demographics, bile cultures, therapy, and survival rates were analyzed in cohorts (T1 death <6 months; T2 death <12 months; T3 death <18 months, T3S alive at 18 months). Results: The most common bacteria in T1 were E. coli , K. pneumoniae, and P. aeruginosa. In T2, the most common bacteria were E. coli and P. aeruginosa. In T3, there were no significant bacteria isolated, while in T3S the most common bacteria were like those found in T1. E. coli and K. pneumoniae were positive predictors of survival for PHC and ACA, respectively. E. coli , K. pneumoniae, and P. aeruginosa showed a high percentage of resistant bacteria to 3CGS, aminoglycosides class, and quinolone group especially at T1 and T2 in cancer patients. Conclusions: An unprecedented increase of E. coli in bile leads to a decrease in survival. We suggest that some strains isolated in bile samples may be considered within the group of risk factors in carcinogenesis and/or progression of hepato-biliary malignancy. A better understanding of bile microbiota in patients with PBD should lead to a multifaceted approach to rapidly detect and treat pathogens before patients enter the surgical setting in tandem with the implementation of the infection control policy.
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Affiliation(s)
- Paola Di Carlo
- Department of Sciences for Health Promotion, Mother & Child Care, University of Palermo, Palermo, Italy
| | - Nicola Serra
- Statistic Unit, Department of Public Health, University of Naples ‘Federico II’, Naples, Italy
| | - Francesco D'Arpa
- Department of General Surgery and Emergency, University of Palermo, Palermo, Italy
| | - Antonino Agrusa
- Department of General Surgery and Emergency, University of Palermo, Palermo, Italy
| | - Gaspare Gulotta
- Department of General Surgery and Emergency, University of Palermo, Palermo, Italy
| | - Teresa Fasciana
- Department of Sciences for Health Promotion, Mother & Child Care, University of Palermo, Palermo, Italy
| | - Vito Rodolico
- Department of Sciences for Health Promotion, Mother & Child Care, University of Palermo, Palermo, Italy
| | - Anna Giammanco
- Department of Sciences for Health Promotion, Mother & Child Care, University of Palermo, Palermo, Italy
| | - Consolato Sergi
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
- Department of Laboratory Medicine and Pathology, Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
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Rimassa L, Personeni N, Aghemo A, Lleo A. The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. J Autoimmun 2019; 100:17-26. [PMID: 30862450 DOI: 10.1016/j.jaut.2019.03.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 03/05/2019] [Indexed: 12/11/2022]
Abstract
Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown. CCA is characterized by a highly desmoplastic microenvironment containing stromal cells, mainly cancer-associated fibroblasts, infiltrating tumor epithelium. Tumor microenvironment in CCA is a highly dynamic environment that, besides stromal and endothelial cells, encompass also an abundance of immune cells, of both the innate and adaptive immune system (including tumor-associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes) and abundant proliferative factors. It is orchestrated by multiple soluble factors and signals, that eventually define a tumor growth-permissive microenvironment. Through complicate interactions with CCA cells, tumor microenvironment profoundly affects the proliferative and invasive abilities of epithelial cancer cells and plays an important role in accelerating neovascularization and preventing apoptosis of neoplastic cells. In this review, we discuss recent developments regarding the characteristics of the tumor microenvironment, the role of each cellular population, and their multiarticulate interaction with the malignant population. Further we discuss innovative treatment approaches, including immunotherapy, and how identification of CCA secreted factors by both the stromal component and immune cell subsets are leading towards a precision medicine in CCA.
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Affiliation(s)
- Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy
| | - Nicola Personeni
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano (MI), Italy.
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Zhong H, Hao TT, Chen Y, Luo F. Unexpected Gallbladder Cancer during or after Laparoscopic Cholecystectomy: Risk Factors and Experience of Diagnosis and Treatment of 22 Cases. Am Surg 2019. [DOI: 10.1177/000313481908500633] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
This study aims to provide some experience in diagnosis and treatment of unexpected gallbladder cancer (UGBC) and find the major risk factors. Retrospective data were collected and analyzed on 22 patients who were diagnosed with UGBC during or after laparoscopic cholecystectomy from January 2013 to January 2018 at our hospital. Average age of the patients was (60.2 ± 12.8) years (range, 42–83 years). Among them, there were 6 men and 16 women. Gallbladder stones, atrophic gallbladder, uneven thickened wall of the gallbladder, and choledocholithiasis were found to be the major risk factors. Eight patients (36.4%) were diagnosed intraoperatively. Seven cases (31.8%) were at the T1 stage; of these, three were treated with laparoscopic cholecystectomy; two were converted to cholecystectomy; and two underwent cholecystectomy, lymph node dissection, and liver resection. Eight (36.4%) T2 patients, five (22.7%) T3 patients, and one T4 patient had radical cholecystectomy. Partial cholecystectomy and cholecystotomy were carried out in another T4 patient. T1 patients did not receive chemotherapy or radiotherapy. Eleven had chemotherapy and four received chemoradiotherapy. The follow-up period ranged from six months to five years. The one-year survival rate for T1 to T4 patients was 100 per cent, 75 per cent, 40 per cent, and 0 per cent, respectively. A high index of clinical suspicion of UGBC is needed if one patient suffered from both gallbladder stones and choledocholithiasis with atrophic gallbladder or uneven thickened wall of the gallbladder preoperatively. To avoid more UGBC and reoperation, imaging examinations combined with tumor marker tests and intraoperative histopathologic examination are highly recommended.
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Affiliation(s)
- Hua Zhong
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tuan Tuan Hao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yong Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Fang Luo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Liu Z, Chen Q, Hann SS. The functions and oncogenic roles of CCAT1 in human cancer. Biomed Pharmacother 2019; 115:108943. [PMID: 31078038 DOI: 10.1016/j.biopha.2019.108943] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/24/2019] [Accepted: 04/29/2019] [Indexed: 02/07/2023] Open
Abstract
In various human cancers, long non-coding RNAs (lncRNAs), a novel class of RNAs longer than 200 nucleotides without protein-coding potential, are implicated in a variety of biological processes, such as cell proliferation, invasion, metastasis, and apoptosis through regulation of gene expression at various levels including chromatin, splicing, transcriptional and post-transcriptional levels. However, the mechanisms underlying these are still elusive. Colon cancer-associated transcript 1(CCAT1) has received increased attention among those lncRNAs. Studies have shown high expression pattern and oncogenic role of CCAT1 in different types of cancer, and aberrant expression of CCAT1 has been involved in tumor-genesis, progression, metastasis, and patient survival via regulating different target genes and signaling pathways. In this review, we first introduce the concept, identification, and biological function of CCAT1; we then describe the mechanisms by which CCAT1 regulate the cancer proliferation and progression. In the last, we discuss emerging insights into the role of CCAT1 as potential biomarker and therapeutic target for novel treatment paradigms in cancer.
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Affiliation(s)
- Zheng Liu
- Laboratory of Tumor Biology, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510120, China
| | - QianJun Chen
- Department of Mammary Diseases, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510120, China.
| | - Swei Sunny Hann
- Laboratory of Tumor Biology, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510120, China.
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47
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Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70:151-171. [PMID: 30266282 DOI: 10.1016/j.jhep.2018.09.014] [Citation(s) in RCA: 2200] [Impact Index Per Article: 366.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/10/2018] [Accepted: 09/17/2018] [Indexed: 02/06/2023]
Abstract
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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Affiliation(s)
| | | | - John Eaton
- Mayo Clinic College of Medicine, Rochester, MN, USA
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48
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Rhee H, Kim MJ, Park YN, An C. A proposal of imaging classification of intrahepatic mass-forming cholangiocarcinoma into ductal and parenchymal types: clinicopathologic significance. Eur Radiol 2018; 29:3111-3121. [DOI: 10.1007/s00330-018-5898-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 10/23/2018] [Accepted: 11/19/2018] [Indexed: 12/15/2022]
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49
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Siripongsakun S, Vidhyarkorn S, Charuswattanakul S, Mekraksakit P, Sungkasubun P, Yodkhunnathum N, Tangruangkiat S, Ritlumlert N, Sricharunrat T, Jaroenpatarapesaj S, Soonklang K, Kulthanmanusorn A, Auewarakul CU, Mahidol C. Ultrasound surveillance for cholangiocarcinoma in an endemic area: A prove of survival benefits. J Gastroenterol Hepatol 2018; 33:1383-1388. [PMID: 29247982 DOI: 10.1111/jgh.14074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Revised: 12/03/2017] [Accepted: 12/11/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Cholangiocarcinoma (CCA) is an aggressive malignancy with rapid progression and poor prognosis. Abdominal ultrasound surveillance may detect early-stage malignancy and improve surgical outcome. However, little data exist on the benefits of abdominal ultrasound surveillance in populations at high risk for CCA development in an endemic area. This study compared survival outcomes of CCA patients recruited through abdominal ultrasound surveillance program and those presented to the hospital independent of surveillance. METHODS The surveillance population-based cohort was 4225 villagers in Northern Thailand, aged 30-60 years, who consented to a 5-year abdominal ultrasound surveillance program, which included interval ultrasound examinations every 6 months. The non-surveillance cohort was hospital-based CCA patients diagnosed during April 2007 to November 2015. Numbers of operable tumors, percentages of R0 resection, and survival analyses were compared between the two cohorts. RESULTS There were 48 and 192 CCA patients in the surveillance and the non-surveillance cohorts, respectively. Of these, 37/48 (77.1%) and 22/192 (11.5%) were in an operable stage and R0 resections performed in 36/48 (97.3%) and 14/192 (63.6%), respectively. The median survival in each group was 31.8 and 6.7 months, respectively (with correction of lead time bias) (P < 0.0001). By multivariate analysis, abdominal ultrasound surveillance (hazard ratio [HR] = 0.41; P = 0.012), operable stage (HR = 0.11; P < 0.001), and serum albumin ≥ 3.5 g/dL (HR = 0.42; P < 0.001) were significantly associated with decreased mortality, whereas size of CCA (HR = 1.11; P < 0.001), serum alanine aminotransferase > 40 IU/L (HR = 1.71; P = 0.017), and tumor recurrence (HR = 4.86; P = 0.017) were associated with increased mortality. CONCLUSION Abdominal ultrasound surveillance provided survival benefits and should be considered in areas highly endemic for CCA to reduce mortality.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Kamonwan Soonklang
- Data Management Unit, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | | | - Chirayu U Auewarakul
- School of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.,Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Chulabhorn Mahidol
- Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.,HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
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50
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Braunwarth E, Stättner S, Fodor M, Cardini B, Resch T, Oberhuber R, Putzer D, Bale R, Maglione M, Margreiter C, Schneeberger S, Öfner D, Primavesi F. Surgical techniques and strategies for the treatment of primary liver tumours: hepatocellular and cholangiocellular carcinoma. Eur Surg 2018; 50:100-112. [PMID: 29875798 PMCID: PMC5968076 DOI: 10.1007/s10353-018-0537-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 05/02/2018] [Indexed: 12/14/2022]
Abstract
Background Owing to remarkable improvements of surgical techniques and associated specialities, liver surgery has become the standard of care for hepatocellular carcinoma and cholangiocarcinoma. Although applied with much greater safety, hepatic resections for primary liver tumours remain challenging and need to be integrated in a complex multidisciplinary treatment approach. Methods This literature review gives an update on the recent developments regarding basics of open and laparoscopic liver surgery and surgical strategies for primary liver tumours. Results Single-centre reports and multicentre registries mainly from Asia and Europe dominate the surgical literature on primary liver tumours, but the numbers of randomized trials are slowly increasing. Perioperative outcomes of open liver surgery for hepatocellular and cholangiocellular carcinoma have vastly improved over the last decades, accompanied by some progress in terms of oncological outcome. The laparoscopic approach is increasingly being applied in many centres, even for patients with underlying liver disease, and may result in decreased morbidity. Liver transplantation represents a cornerstone in the treatment of early hepatocellular carcinoma and is indispensable to achieve long-term survival. In contrast, resection remains the gold standard for cholangiocarcinoma in most countries, but interventional techniques are on the rise. Conclusion Liver surgery for primary tumours is complex, with a need for high expertise in a multidisciplinary team to achieve acceptable outcomes. Technical developments and clinical stratification tools have optimized individual care, but further improvements in oncological survival will likely require enhanced pre- and postoperative systemic and local treatment options.
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Affiliation(s)
- Eva Braunwarth
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Margot Fodor
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Thomas Resch
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Rupert Oberhuber
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Daniel Putzer
- Department of Radiology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Reto Bale
- Department of Radiology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Manuel Maglione
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Christian Margreiter
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
| | - Florian Primavesi
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria
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