|
1
|
Qin J, Dong W, Zhao F, Liu T, Chen M, Zhang R, Zhao Y, Zhang C, Wang W. Prediction of metachronous liver metastasis in mid-low rectal cancer using quantitative perirectal fat content from high-resolution MRI. Magn Reson Imaging 2025; 118:110338. [PMID: 39889974 DOI: 10.1016/j.mri.2025.110338] [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: 08/21/2024] [Revised: 01/24/2025] [Accepted: 01/26/2025] [Indexed: 02/03/2025]
Abstract
PURPOSE To investigate the relationship between perirectal fat content and metachronous liver metastasis (MLM) in patients with Mid-low rectal cancer (MLRC). MATERIALS AND METHODS A retrospective analysis was conducted on 254 patients who underwent curative surgery for MLRC between December 2016 and December 2021. Preoperative MRI measurements of the rectal mesenteric fat area (MFA), rectal posterior mesorectal thickness (PMT), and rectal mesenteric fascia envelopment volume (MFEV) were performed, along with collection of relevant clinical, pathological, and imaging data. Patients were categorized into the MLM group (Group A), other recurrence or metastasis group (Group B), and no recurrence and metastasis group (Group C). Analyze the differences between Group A and the other groups, and independent risk factors for MLM were explored. Kaplan-Meier analysis and log-rank test were used to validate independent predictive biomarkers for MLM. RESULTS Patients with MLM from MLRC had later pathological and imaging T stages and lower perirectal fat content (all P < 0.05). Compared to patients with other types of recurrent metastasis, male gender, poorly differentiated tumors, and advanced tumor N stage were more likely to develop MLM (all P < 0.05). In Cox univariate and multivariate regression analysis, smaller rectal PMT (hazard ratio (HR) 0.361 [0.154-0.846], P = 0.019) and MFEV (HR 0.983 [0.968-0.998], P = 0.022) were independently associated with MLM in MLRC (HR 0.361;0.983). Kaplan-Meier analysis showed that patients with rectal PMT <1.43 cm and rectal MFEV <137.46 cm3 had a significantly higher risk of MLM compared to patients with rectal PMT ≥1.43 cm and rectal MFEV ≥137.46 cm3 (all P < 0.05). CONCLUSION Rectal PMT and rectal MFEV can serve as novel parameters for predicting MLM in patients with MLRC.
Collapse
Affiliation(s)
- Jiaming Qin
- The School of Medicine, Nankai University, Tianjin, China
| | - Wenjin Dong
- Tianjin Union Medical Center, Nankai University, Tianjin, China
| | - Fengshu Zhao
- Tianjin Union Medical Center, Nankai University, Tianjin, China
| | - Tianqi Liu
- Graduate School of Tianjin Medical University, Tianjin, China
| | - Mengxin Chen
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Rui Zhang
- The School of Medicine, Nankai University, Tianjin, China
| | - Yumeng Zhao
- The School of Medicine, Nankai University, Tianjin, China
| | - Cheng Zhang
- Graduate School of Tianjin Medical University, Tianjin, China
| | - Wenhong Wang
- Tianjin Union Medical Center, Nankai University, Tianjin, China.
| |
Collapse
|
|
2
|
Özşen M, Uğraş N, Yerci Ö, Deligonul A, Taşar P, Işık Ö, Yılmazlar T. Microscopic Growth Pattern of Metastatic Colorectal Carcinomas, Morphological Findings of the Non-Neoplastic Liver, and Their Relationship With Prognosis and Survival. Int J Surg Pathol 2024; 32:1256-1262. [PMID: 38332662 PMCID: PMC11423548 DOI: 10.1177/10668969241226702] [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: 10/23/2023] [Revised: 11/22/2023] [Accepted: 12/24/2023] [Indexed: 02/10/2024]
Abstract
Introduction. Various clinicopathological, radiological, and molecular parameters are predictive of prognosis in patients with colorectal carcinoma and distant organ metastases continue to have a significant place among them. Recent studies reveal that not only the presence of metastases but also the histopathological growth pattern of the metastatic tumor significantly affects prognosis. This study aimed to investigate the prognostic significance of the histopathological growth patterns of metastatic tumors, the morphological findings in the peritumoral non-neoplastic liver, and its relationship with survival in patients who have metastatic colorectal carcinoma. Materials and Method. Hematoxylin and eosin-stained slides of the tumors were re-examined in terms of histopathological diagnosis, growth pattern, presence and degree of peritumoral lymphocytic infiltration, steatosis, cholestasis, and peritumoral ductular reaction in the non-neoplastic liver. Results. In terms of histopathological growth patterns, 24 (47%) tumors showed replacement, 19 (37%) showed desmoplastic and 8 (16%) showed pushing growth pattern. In terms of total survival, there was a significant difference (P = .011) between desmoplastic and replacement growth patterns, and the survival period was shorter in patients with replacement growth patterns. Conclusion. Recent studies show that histopathological growth patterns in metastatic liver tumors may be a promising prognostic and predictive parameter. It is important to include this parameter in the pathology reports as it does not require additional equipment for evaluation in routine pathology practice, does not bring additional costs, or takes a long time to evaluate. This feature can be evaluated standardly by every pathologist.
Collapse
Affiliation(s)
- Mine Özşen
- Department of Pathology, Faculty of Medicine, Uludag University, Bursa, Turkey
| | - Nesrin Uğraş
- Department of Pathology, Faculty of Medicine, Uludag University, Bursa, Turkey
| | - Ömer Yerci
- Department of Pathology, Faculty of Medicine, Uludag University, Bursa, Turkey
| | - Adem Deligonul
- Department of Medical Oncology, Faculty of Medicine, Uludag University, Bursa, Turkey
| | - Pınar Taşar
- Department of General Surgery, Uludag University Faculty of Medicine, Bursa, Turkey
| | - Özgen Işık
- Department of General Surgery, Uludag University Faculty of Medicine, Bursa, Turkey
| | - Tuncay Yılmazlar
- Department of General Surgery, Uludag University Faculty of Medicine, Bursa, Turkey
| |
Collapse
|
|
3
|
Miyata T, Shinden Y, Motoyama S, Sannomiya Y, Tamezawa H, Nagayama T, Nishiki H, Hashimoto A, Kaida D, Fujita H, Ueda N, Takamura H. Non-Alcoholic Fatty Liver Disease May Be a Risk Factor for Liver Metastasis After Radical Surgery for Colorectal Cancer: A Retrospective Study. J Gastrointest Cancer 2024; 55:932-939. [PMID: 38502514 DOI: 10.1007/s12029-024-01042-6] [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] [Accepted: 03/10/2024] [Indexed: 03/21/2024]
Abstract
PURPOSE Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC. METHODS We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD). RESULTS Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1 months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence. CONCLUSION NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery.
Collapse
Affiliation(s)
- Takashi Miyata
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan.
| | - Yuki Shinden
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Shota Motoyama
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Yuta Sannomiya
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Hozumi Tamezawa
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Taigo Nagayama
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Hisashi Nishiki
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Akifumi Hashimoto
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Daisuke Kaida
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Hideto Fujita
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Nobuhiko Ueda
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | - Hiroyuki Takamura
- Department of General and Digestive Surgery, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| |
Collapse
|
|
4
|
Bader H, Yamin S, Alshahwan H, Farraj H, Maghnam J, Omar YA. Association between Metabolic-Dysfunction-Associated Steatotic Liver Disease and Hepatic Cancer: Current Concepts and Future Challenges. J Clin Med 2024; 13:3132. [PMID: 38892843 PMCID: PMC11172711 DOI: 10.3390/jcm13113132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Revised: 05/12/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024] Open
Abstract
Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.
Collapse
Affiliation(s)
- Husam Bader
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; (H.B.); (Y.A.O.)
| | - Saif Yamin
- School of Medicine, University of Jordan, Amman 11942, Jordan;
| | | | - Husam Farraj
- Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87106, USA;
| | - Joud Maghnam
- School of Medicine, Al-Balqa’ Applied University, Al-Salt 19117, Jordan;
| | - Yazan Abu Omar
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; (H.B.); (Y.A.O.)
| |
Collapse
|
|
5
|
Yang Y, Chen Y, Liu Z, Chang Z, Sun Z, Zhao L. Concomitant NAFLD Facilitates Liver Metastases and PD-1-Refractory by Recruiting MDSCs via CXCL5/CXCR2 in Colorectal Cancer. Cell Mol Gastroenterol Hepatol 2024; 18:101351. [PMID: 38724007 PMCID: PMC11227024 DOI: 10.1016/j.jcmgh.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 04/23/2024] [Accepted: 04/24/2024] [Indexed: 05/28/2024]
Abstract
BACKGROUND & AIMS Both nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effects of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated. METHODS We observed the effect of concomitant NAFLD on CRLM in the mouse model and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment and then tested the therapeutic application based on the mechanisms. Finally we validated our findings in the clinical samples. RESULTS Here we prove that in different mouse models, NAFLD induces F4/80+ Kupffer cells to secret chemokine CXCL5 and then recruits CXCR2+ MDSCs to promote the growth of CRLM. CRLM with NAFLD background is refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2+ MDSCs, as well as the hazard of liver metastases in CRC patients. CONCLUSIONS Collectively, our findings highlight the significance of selective CXCR2+/CD11b+/Gr-1+ subset myeloid cells in favoring the development of CRLM with NAFLD background and identify a pharmaceutical medicine that is already available for the clinical trials and potential treatment.
Collapse
Affiliation(s)
- Yue Yang
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China; Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China
| | - Yunsong Chen
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China
| | - Zhaogang Liu
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China
| | - Zhibin Chang
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China; Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China
| | - Zhicheng Sun
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China; Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China
| | - Lei Zhao
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China; Shandong First Medical University and Shandong Academy of Medical Sciences, Huaiyin District, Jinan, China.
| |
Collapse
|
|
6
|
Chen J, Chan TTH, Zhou J. Lipid metabolism in the immune niche of tumor-prone liver microenvironment. J Leukoc Biol 2024; 115:68-84. [PMID: 37474318 DOI: 10.1093/jleuko/qiad081] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 06/23/2023] [Accepted: 07/06/2023] [Indexed: 07/22/2023] Open
Abstract
The liver is a common primary site not only for tumorigenesis, but also for cancer metastasis. Advanced cancer patients with liver metastases also show reduced response rates and survival benefits when treated with immune checkpoint inhibitors. Accumulating evidence has highlighted the importance of the liver immune microenvironment in determining tumorigenesis, metastasis-organotropism, and immunotherapy resistance. Various immune cells such as T cells, natural killer and natural killer T cells, macrophages and dendritic cells, and stromal cells including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes are implicated in contributing to the immune niche of tumor-prone liver microenvironment. In parallel, as the major organ for lipid metabolism, the increased abundance of lipids and their metabolites is linked to processes crucial for nonalcoholic fatty liver disease and related liver cancer development. Furthermore, the proliferation, differentiation, and functions of hepatic immune and stromal cells are also reported to be regulated by lipid metabolism. Therefore, targeting lipid metabolism may hold great potential to reprogram the immunosuppressive liver microenvironment and synergistically enhance the immunotherapy efficacy in the circumstance of liver metastasis. In this review, we describe how the hepatic microenvironment adapts to the lipid metabolic alterations in pathologic conditions like nonalcoholic fatty liver disease. We also illustrate how these immunometabolic alterations promote the development of liver cancers and immunotherapy resistance. Finally, we discuss the current therapeutic options and hypothetic combination immunotherapies for the treatment of advanced liver cancers.
Collapse
Affiliation(s)
- Jintian Chen
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, SAR, P.R. China
| | - Thomas T H Chan
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, SAR, P.R. China
| | - Jingying Zhou
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong 999077, SAR, P.R. China
| |
Collapse
|
|
7
|
Lee DH, Jo I, Lee HS, Kang J. Combined impact of myosteatosis and liver steatosis on prognosis in stage I-III colorectal cancer patients. J Cachexia Sarcopenia Muscle 2023; 14:2908-2915. [PMID: 37964719 PMCID: PMC10751431 DOI: 10.1002/jcsm.13369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 09/15/2023] [Accepted: 10/06/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND Myosteatosis and liver steatosis (LS) have been recognized as patient-derived image biomarkers that correlate with prognosis in colorectal cancer (CRC) patients. However, the significance of considering fat deposition in multiple body areas simultaneously has been underestimated. This study aimed to investigate the combined effect of myosteatosis and LS in stage I-III CRC patients. METHODS A total of 616 stage I-III CRC patients were included in the study. Myosteatosis was assessed using skeletal muscle radiodensity (SMD), and LS was estimated by calculating the Hounsfield unit of the liver and spleen ratio (LSR). Cox proportional hazard models were utilized to evaluate disease-free survival (DFS). A combination of myosteatosis and LS was proposed, and its discriminatory performance was compared using the C-index. RESULTS Among the 616 participants, the median (interquartile) age was 64 (55-72) years, and 240 (38.9%) were female. The median and interquartile range of LSR were determined as 1.106 (0.967-1.225). The optimal cutoff value for LSR was identified as 1.181, leading to the classification of patients into low (410, 66.5%) and high LSR (206, 33.4%) groups. Among the patients, 200 were categorized into the low SMD group, while 416 were allocated to the high SMD group. Both myosteatosis and LS were identified as independent prognostic factors in the multivariable analysis. The combination of these two variables resulted in a three-group classification: high SMD with low LSR group, high SMD with high LSR group, and low SMD group. When comparing the C-index values, the three-group classification exhibited superior discriminatory performance compared with considering myosteatosis and LS separately. CONCLUSIONS Myosteatosis was associated with poorer survival, while the presence of LS was linked to a better prognosis in non-metastatic CRC patients. Simultaneously considering fat infiltration can serve as a more effective prognosticator in non-metastatic CRC patients.
Collapse
Affiliation(s)
- Dong Hee Lee
- Department of Surgery, Gangnam Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
| | - Il Jo
- Department of Surgery, Gangnam Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
| | - Hye Sun Lee
- Biostatistics Collaboration UnitYonsei University College of MedicineSeoulRepublic of Korea
| | - Jeonghyun Kang
- Department of Surgery, Gangnam Severance HospitalYonsei University College of MedicineSeoulRepublic of Korea
| |
Collapse
|
|
8
|
Haq A, Fraum TJ, Tao Y, Dehdashti F, LeBlanc M, Hoegger MJ, Luo J, Weilbaecher K, Peterson LL. Frequency of Hepatic Metastatic Disease in Patients with Stage IV Breast Cancer Is Similar for Steatotic and Non-Steatotic Livers. Breast Cancer (Auckl) 2023; 17:11782234231166476. [PMID: 37181949 PMCID: PMC10170590 DOI: 10.1177/11782234231166476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 03/13/2023] [Indexed: 05/16/2023] Open
Abstract
Background Breast cancer is the most common non-cutaneous malignancy and the second leading cause of cancer mortality in the United States. Breast cancer is a heterogeneous disease; diagnosis at an early stage renders it potentially curable, whereas advanced metastatic disease carries a worse prognosis. Objectives To investigate whether hepatic steatosis (HS) is associated with liver metastases in patients with newly diagnosed stage IV female breast cancer patients (either de novo metastatic breast cancer or recurrent metastatic breast cancer) using non-contrast computed tomography (CT) as a marker of HS. Design Retrospective analysis. Methods We retrospectively identified 168 patients with stage IV breast cancer with suitable imaging from a prospectively maintained oncologic database. Three radiologists manually defined hepatic regions of interest on non-contrast CT images, and attenuation data were extracted. HS was defined as a mean attenuation <48 Hounsfield units. The frequency of hepatic metastatic disease was calculated for patient with and without HS. Relationships between HS and various patient (age, body mass index, race) and tumor (hormone receptor status, HER2 status, tumor grade) characteristics were also analyzed. Results There were 4 patients with liver metastasis in the HS group (41 patients) versus 20 patients with liver metastases in the non-HS group (127 patients). The difference in frequencies of liver metastases among patients with (9.8%) versus without (15.7%) hepatic steatosis (odds ratio = 1.72 [0.53-7.39]) was not statistically significant (P = .45). Body mass index was significantly higher (P = .01) among patients with hepatic steatosis (32.2 ± 7.3 vs 28.8 ± 7.1 kg/m2). Otherwise, there were no significant differences between patients with versus without HS with respect to regarding age, race, hormone receptor status, HER2 status, or tumor grade. Conclusion The frequency of hepatic metastatic disease in patients with stage IV breast cancer is similar for steatotic and non-steatotic livers.
Collapse
Affiliation(s)
- Adeel Haq
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Tyler J Fraum
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
| | - Yu Tao
- Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | - Farrokh Dehdashti
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
| | - Maverick LeBlanc
- Department of Radiology, Ochsner Medical Center, Jefferson, LA, USA
| | - Mark J Hoegger
- Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA
| | - Jingqin Luo
- Department of Surgery, Washington University in St. Louis, St. Louis, MO, USA
| | - Katherine Weilbaecher
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
- Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA
| | - Lindsay L Peterson
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA
- Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA
| |
Collapse
|
|
9
|
Ibrahim MK, Simon TG, Rinella ME. Extrahepatic Outcomes of Nonalcoholic Fatty Liver Disease: Nonhepatocellular Cancers. Clin Liver Dis 2023; 27:251-273. [PMID: 37024206 DOI: 10.1016/j.cld.2023.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, including isolated steatosis, steatohepatitis, and cirrhosis. The overall global prevalence of NAFLD is estimated to be 30%, and the associated clinical and economic burden will continue to increase. NAFLD is a multisystemic disease with established links to cardiovascular disease, type 2 diabetes, metabolic syndrome, chronic kidney disease, polycystic ovarian syndrome, and intra- and extrahepatic malignancies. In this article the authors review the potential mechanisms and current evidence for the association between NAFLD and extrahepatic cancers and the resultant impact on clinical outcomes.
Collapse
Affiliation(s)
- Maryam K Ibrahim
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Tracey G Simon
- Harvard Medical School, Boston, MA, USA; Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, MA, USA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
| | - Mary E Rinella
- University of Chicago Pritzker School of Medicine; University of Chicago Hospitals.
| |
Collapse
|
|
10
|
Yamada S, Morine Y, Ikemoto T, Saito Y, Miyazaki K, Shimizu M, Tsuneyama K, Shimada M. Inhibitory effect of non-alcoholic steatohepatitis on colon cancer liver metastasis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:410-415. [PMID: 36371329 DOI: 10.1016/j.ejso.2022.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 10/29/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND The incidence of non-alcoholic steatohepatitis (NASH) is dramatically increasing, but the effect of NASH on colon cancer liver metastasis (CLM) is controversial. The aim of this study was to investigate the impact and mechanism of action of NASH on CLM using a western diet (WD)-fed mouse model. METHODS Six-week-old male C57BL/6 J mice were used. They were divided into the WD group and control group with normal diet. MC38 colon cancer cells were injected into the spleen at 2, 6, 8 and 16 weeks, and mice were killed at 2 weeks after injection to evaluate hepatic steatosis, fibrosis, metastasis and mRNA/protein expression in the liver. RESULTS Only mice fed a WD for 16 weeks showed hepatic fibrosis. These mice showed significantly higher alanine aminotransferase and total cholesterol levels compared with the control group (p < 0.05). The WD group showed significantly lower tumor number and smaller tumor diameter (p < 0.05). In the WD group, expression of SAA1, IL6, STAT3 and MMP9 mRNA in the liver was significantly lower than in the control group (p < 0.05). Serum amyloid A1 protein expression was also lower in the WD group. CONCLUSIONS The WD-fed NASH mouse model showed an inhibitory effect on CLM. Suppressed interleukin-6/signal transducer and activator of transcription 3 signaling and serum amyloid A/matrix metalloproteinase 9 expression may affect this phenomenon.
Collapse
Affiliation(s)
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Tetsuya Ikemoto
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yu Saito
- Department of Surgery, Tokushima University, Tokushima, Japan
| | | | - Mayuko Shimizu
- Department of Pathology and Laboratory Medicine, Tokushima University, Tokushima, Japan
| | - Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Tokushima University, Tokushima, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| |
Collapse
|
|
11
|
Dong Y, Cheng Y, Guo H, Sun J, Han J, Zhong F, Li Q, Wang D, Chen W, Fan X, Zhao J. Association of obesity and different metabolic status with prognosis in patients with bladder cancer: a retrospective cohort study. Ther Adv Urol 2023; 15:17562872231213720. [PMID: 38033708 PMCID: PMC10685784 DOI: 10.1177/17562872231213720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/25/2023] [Indexed: 12/02/2023] Open
Abstract
Background and objectives Patients with bladder cancer (BC) are at high risk for recurrence rates and readmission costs. However, the evidence about obesity and metabolic abnormalities on the BC prognosis was inconsistent. Our primary aim was to determine the impact of obesity and different metabolic status on the readmission risk in patients with BC. Design and methods We identified 16,649 patients with BC using the 2018 Nationwide Readmissions Database who were hospitalized from January to June 2018 and followed for 180 days. The primary outcome was 180-day readmission. The multivariate Cox regression analysis and ordered logistic regression were performed to analyze data. Results Obesity and metabolic abnormalities were associated with an increased readmission risk in patients with BC [obesity: adjusted hazard ratio (aHR) = 1.08, 95% confidence interval (CI): 1.01-1.16; hyperglycemia: aHR = 1.11, 95% CI: 1.05-1.17; hypertension: aHR = 1.09, 95% CI: 1.03-1.15]. Compared with non-obese and no metabolic abnormalities, the risk of readmission was significantly increased in patients with metabolic abnormalities, irrespective of obesity (non-obese and metabolic abnormalities: aHR = 1.07, 95% CI: 1.02-1.13; obese and metabolic abnormalities: aHR = 1.20, 95% CI: 1.10-1.31), but not in obese and no metabolic abnormalities. These associations were consistent in patients aged 60 years or older and the surgery group. Moreover, hyperglycemia, hypertension, and a graded increment of metabolic risk were associated with an increased readmission risk. We also found increased length of stay for readmission in patients with obesity and metabolic abnormalities (aOR = 1.17, 95% CI: 1.00-1.36). Conclusion Obesity with metabolic abnormalities and metabolic abnormalities alone were associated with higher readmission risks in patients with BC. It is suggested that prevention should focus not only on obesity but also on metabolic abnormalities to decrease the risk of readmission.
Collapse
Affiliation(s)
- Yingchun Dong
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Yiping Cheng
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Honglin Guo
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Jiaxing Sun
- Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Junming Han
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Fang Zhong
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Qihang Li
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Dawei Wang
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China
- Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China
- Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Wenbin Chen
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Xiude Fan
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| | - Jiajun Zhao
- Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China
| |
Collapse
|
|
12
|
Allegrini S, Garcia-Gil M, Pesi R, Camici M, Tozzi MG. The Good, the Bad and the New about Uric Acid in Cancer. Cancers (Basel) 2022; 14:cancers14194959. [PMID: 36230882 PMCID: PMC9561999 DOI: 10.3390/cancers14194959] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/30/2022] [Accepted: 10/06/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary The concentration of uric acid in blood is sex-, age- and diet-dependent and is maintained close to its maximal solubility, indicating that it plays some important role. Indeed, it has been demonstrated that, at physiological concentrations, uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. At high intracellular concentration, uric acid has been demonstrated to act as a pro-oxidant molecule. Recently, uric acid has been reported to affect the properties of several proteins involved in metabolic regulation and signaling, and the relationship between uric acid and cancer has been extensively investigated. In this review, we present the most recent results on the positive and negative effects played by uric acid in cancer and some new findings and hypotheses about the implication of this metabolite in the pathogenesis of several diseases such as metabolic syndrome, diabetes, and inflammation, thus favoring the development of cancer. Abstract Uric acid is the final product of purine catabolism in man and apes. The serum concentration of uric acid is sex-, age- and diet-dependent and is maintained close to its maximal solubility, indicating that it plays some important role. Indeed, it has been demonstrated that, at physiological concentrations, uric acid is a powerful antioxidant, while at high intracellular concentrations, it is a pro-oxidant molecule. In this review, we describe the possible causes of uric acid accumulation or depletion and some of the metabolic and regulatory pathways it may impact. Particular attention has been given to fructose, which, because of the complex correlation between carbohydrate and nucleotide metabolism, causes uric acid accumulation. We also present recent results on the positive and negative effects played by uric acid in cancer and some new findings and hypotheses about the implication of this metabolite in a variety of signaling pathways, which can play a role in the pathogenesis of diseases such as metabolic syndrome, diabetes, and inflammation, thus favoring the development of cancer. The loss of uricase in Homo sapiens and great apes, although exposing these species to the potentially adverse effects of uric acid, appears to be associated with evolutionary advantages.
Collapse
Affiliation(s)
- Simone Allegrini
- Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
- Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, Università di Pisa, 56126 Pisa, Italy
- CISUP, Centro per L’Integrazione della Strumentazione dell’Università di Pisa, 56127 Pisa, Italy
- Correspondence:
| | - Mercedes Garcia-Gil
- Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”, Università di Pisa, 56126 Pisa, Italy
- CISUP, Centro per L’Integrazione della Strumentazione dell’Università di Pisa, 56127 Pisa, Italy
- Unità di Fisiologia Generale, Dipartimento di Biologia, Università di Pisa, Via San Zeno 31, 56127 Pisa, Italy
| | - Rossana Pesi
- Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
| | - Marcella Camici
- Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
| | - Maria Grazia Tozzi
- Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
| |
Collapse
|
|
13
|
Simillis C, Taylor B, Ahmad A, Lal N, Afxentiou T, Powar MP, Smyth EC, Fearnhead NS, Wheeler J, Davies RJ. A systematic review and meta-analysis assessing the impact of body mass index on long-term survival outcomes after surgery for colorectal cancer. Eur J Cancer 2022; 172:237-251. [DOI: 10.1016/j.ejca.2022.05.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 05/02/2022] [Accepted: 05/15/2022] [Indexed: 01/27/2023]
|
|
14
|
Bai L, Yan XL, Lu YX, Meng Q, Rong YM, Ye LF, Pan ZZ, Xing BC, Wang DS. Circulating Lipid- and Inflammation-Based Risk (CLIR) Score: A Promising New Model for Predicting Outcomes in Complete Colorectal Liver Metastases Resection. Ann Surg Oncol 2022; 29:10.1245/s10434-021-11234-0. [PMID: 35254582 PMCID: PMC9174322 DOI: 10.1245/s10434-021-11234-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Colorectal cancer liver metastasis (CRLM) is a determining factor affecting the survival of colorectal cancer (CRC) patients. This study aims at developing a novel prognostic stratification tool for CRLM resection. METHODS In this retrospective study, 666 CRC patients who underwent complete CRLM resection from two Chinese medical institutions between 2001 and 2016 were classified into the training (341 patients) and validation (325 patients) cohorts. The primary endpoint was overall survival (OS). Associations between clinicopathological variables, circulating lipid and inflammation biomarkers, and OS were explored. The five most significant prognostic factors were incorporated into the Circulating Lipid- and Inflammation-based Risk (CLIR) score. The predictive ability of the CLIR score and Fong's Clinical Risk Score (CRS) was compared by time-dependent receiver operating characteristic (ROC) analysis. RESULTS Five independent predictors associated with worse OS were identified in the training cohort: number of CRLMs >4, maximum diameter of CRLM >4.4 cm, primary lymph node-positive, serum lactate dehydrogenase (LDH) level >250.5 U/L, and serum low-density lipoprotein-cholesterol (LDL-C)/high-density lipoprotein-cholesterol (HDL-C) ratio >2.9. These predictors were included in the CLIR score and each factor was assigned one point. Median OS for the low (score 0-1)-, intermediate (score 2-3)-, and high (score 4-5)-risk groups was 134.0 months, 39.9 months, and 18.7 months in the pooled cohort. The CLIR score outperformed the Fong score with superior discriminatory capacities for OS and RFS, both in the training and validation cohorts. CONCLUSIONS The CLIR score demonstrated a promising ability to predict the long-term survival of CRC patients after complete hepatic resection.
Collapse
Affiliation(s)
- Long Bai
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Xiao-Luan Yan
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Beijing, 100142, People's Republic of China
- Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China
| | - Yun-Xin Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Qi Meng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Yu-Ming Rong
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China
| | - Liu-Fang Ye
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China
| | - Zhi-Zhong Pan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China.
- Department of Colorectal Surgery, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, Guangdong, 510060, People's Republic of China.
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), Beijing, 100142, People's Republic of China.
- Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital and Institute, Beijing, 100142, People's Republic of China.
| | - De-Shen Wang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
- Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, 510060, People's Republic of China.
- Department of Medical Oncology, Sun Yat-sen University Cancer Center/Cancer Hospital, Guangzhou, People's Republic of China.
| |
Collapse
|
|
15
|
Spychalski P, Kobiela J, Wieszczy P, Bugajski M, Reguła J, Kaminski MF. Adenoma to Colorectal Cancer Estimated Transition Rates Stratified by BMI Categories—A Cross-Sectional Analysis of Asymptomatic Individuals from Screening Colonoscopy Program. Cancers (Basel) 2021; 14:cancers14010062. [PMID: 35008224 PMCID: PMC8750540 DOI: 10.3390/cancers14010062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 12/19/2021] [Accepted: 12/20/2021] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Most colorectal cancers assumedly develop from precursor lesions, i.e., colorectal adenomas (adenoma-carcinoma sequence). Epidemiological and clinical data supporting this hypothesis are limited. Therefore, the aim of the present study was to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by body mass. We have analyzed 163,129 individuals that underwent screening colonoscopy and calculated adjusted prevalences of colorectal adenomas and colorectal. Based on that data we have found that obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC. Therefore, this study provides new evidence that obesity paradox exists for colorectal cancer. Abstract Most colorectal cancers (CRC) assumedly develop from precursor lesions, i.e., colorectal adenomas (adenoma-carcinoma sequence). Epidemiological and clinical data supporting this hypothesis are limited. Therefore, the aim of the present study is to estimate relative dynamics of colorectal adenoma-carcinoma sequence for groups of screenees stratified by BMI (body mass index) based on prevalence data from Polish Colonoscopy Screening Program (PCSP). We performed a cross-sectional analysis of database records of individuals who entered the national opportunistic colonoscopy screening program for CRC in Poland. We calculated prevalence of adenomas and CRCs adjusted for sex, 5-year age group, family history of CRC, smoking, diabetes and use of aspirin, hormonal therapy and proton-pump inhibitors use. Thereafter we calculated estimated transition rate (eTR) with confidence intervals (CIs) defined as adjusted prevalence of more advanced lesion divided by adjusted prevalence of less advanced lesion. All analyzes were stratified according to the BMI categories: normal (BMI 18.0 to <25.0), overweight (BMI 25.0 to <30.0) and obese (BMI ≥ 30.0). Results are reported in the same respective order. After exclusions we performed analyses on 147,385 individuals. We found that prevalence of non-advanced adenomas is increasing with BMI category (12.19%, 13.81%, 14.70%, respectively; p < 0.001). Prevalence of advanced adenomas was increasing with BMI category (5.20%, 5.77%, 6.61%, respectively; p < 0.001). Early CRCs prevalence was the highest for obese individuals (0.55%) and the lowest for overweight individuals (0.44%) with borderline significance (p = 0.055). For advanced CRC we found that prevalence seems to be inversely related to BMI category, however no statistically significant differences were observed (0.35%, 0.31%, 0.28%; p = 0.274). eTR for non-advanced adenoma to advanced adenoma is higher for obese individuals than for overweight individuals with bordering CIs (42.65% vs. 41.81% vs. 44.95%) eTR for advanced adenoma to early CRC is highest for normal individuals, however CIs are overlapping with remaining BMI categories (9.02% vs. 7.67% vs. 8.39%). eTR for early CRC to advanced CRC is lower for obese individuals in comparison to both normal and overweight individuals with marginally overlapping CIs (73.73% vs. 69.90% vs. 50.54%). Obese individuals are more likely to develop adenomas, advanced adenomas and early CRC but less likely to progress to advanced CRC. Therefore, this study provides new evidence that obesity paradox exists for colorectal cancer.
Collapse
Affiliation(s)
- Piotr Spychalski
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, 80-210 Gdansk, Poland;
- Correspondence:
| | - Jarek Kobiela
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, 80-210 Gdansk, Poland;
| | - Paulina Wieszczy
- Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, 01-813 Warsaw, Poland; (P.W.); (M.B.); (J.R.); (M.F.K.)
- Clinical Effectiveness Research Group, Institute of Health and Society, Faculty of Medicine, University of Oslo, NO-0316 Oslo, Norway
| | - Marek Bugajski
- Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, 01-813 Warsaw, Poland; (P.W.); (M.B.); (J.R.); (M.F.K.)
- Clinical Effectiveness Research Group, Institute of Health and Society, Faculty of Medicine, University of Oslo, NO-0316 Oslo, Norway
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, 01-813 Warsaw, Poland
| | - Jaroslaw Reguła
- Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, 01-813 Warsaw, Poland; (P.W.); (M.B.); (J.R.); (M.F.K.)
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, 01-813 Warsaw, Poland
| | - Michał F. Kaminski
- Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, 01-813 Warsaw, Poland; (P.W.); (M.B.); (J.R.); (M.F.K.)
- Clinical Effectiveness Research Group, Institute of Health and Society, Faculty of Medicine, University of Oslo, NO-0316 Oslo, Norway
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, 01-813 Warsaw, Poland
- Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, 01-813 Warsaw, Poland
| |
Collapse
|
|
16
|
Venniyoor A, Al Farsi AA, Al Bahrani B. The Troubling Link Between Non-alcoholic Fatty Liver Disease (NAFLD) and Extrahepatic Cancers (EHC). Cureus 2021; 13:e17320. [PMID: 34557366 PMCID: PMC8449927 DOI: 10.7759/cureus.17320] [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] [Accepted: 08/20/2021] [Indexed: 12/12/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a fast-spreading epidemic across the globe and has serious implications far beyond that of a "benign" liver condition. It is usually an outcome of ectopic fat storage due to chronic positive energy balance leading to obesity and is associated with multiple health problems. While association with cardiovascular disease and hepatocellular cancer is well recognized, it is becoming clear the NAFLD carries with it an increased risk of cancers of extrahepatic tissues. Studies have reported a higher risk for cancers of the colon, breast, prostate, lung, and pancreas. Fatty liver is associated with increased mortality; there is an urgent need to understand that fatty liver is not always benign, and not always associated with obesity. It is, however, a reversible condition and early recognition and intervention can alter its natural history and associated complications.
Collapse
Affiliation(s)
- Ajit Venniyoor
- Medical Oncology, National Oncology Center, The Royal Hospital, Muscat, OMN
| | | | | |
Collapse
|
|
17
|
Monelli F, Besutti G, Djuric O, Bonvicini L, Farì R, Bonfatti S, Ligabue G, Bassi MC, Damato A, Bonelli C, Pinto C, Pattacini P, Giorgi Rossi P. The Effect of Diffuse Liver Diseases on the Occurrence of Liver Metastases in Cancer Patients: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:2246. [PMID: 34067076 PMCID: PMC8124499 DOI: 10.3390/cancers13092246] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/29/2021] [Accepted: 05/03/2021] [Indexed: 12/14/2022] Open
Abstract
This systematic review with meta-analysis aimed to assess the effect of diffuse liver diseases (DLD) on the risk of synchronous (S-) or metachronous (M-) liver metastases (LMs) in patients with solid neoplasms. Relevant databases were searched for systematic reviews and cross-sectional or cohort studies published since 1990 comparing the risk of LMs in patients with and without DLD (steatosis, viral hepatitis, cirrhosis, fibrosis) in non-liver solid cancer patients. Outcomes were prevalence of S-LMs, cumulative risk of M-LMs and LM-free survival. Risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale. We report the pooled relative risks (RR) for S-LMs and hazard ratios (HR) for M-LMs. Subgroup analyses included DLD, primary site and continent. Nineteen studies were included (n = 37,591 patients), the majority on colorectal cancer. ROB appraisal results were mixed. Patients with DLD had a lower risk of S-LMs (RR 0.50, 95% CI 0.34-0.76), with a higher effect for cirrhosis and a slightly higher risk of M-LMs (HR 1.11 95% CI, 1.03-1.19), despite a lower risk of M-LMs in patients with vs without viral hepatitis (HR 0.57, 95% CI 0.40-0.82). There may have been a publication bias in favor of studies reporting a lower risk for patients with DLD. DLD are protective against S-LMs and slightly protective against M-LMs for viral hepatitis only.
Collapse
Affiliation(s)
- Filippo Monelli
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41124 Modena, Italy;
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Giulia Besutti
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41124 Modena, Italy;
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Olivera Djuric
- Epidemiology Unit, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (O.D.); (L.B.); (P.G.R.)
- Center for Environmental, Nutritional and Genetic Epidemiology (CREAGEN), Section of Public Health, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Laura Bonvicini
- Epidemiology Unit, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (O.D.); (L.B.); (P.G.R.)
| | - Roberto Farì
- Radiology Unit, AOU Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy; (R.F.); (S.B.); (G.L.)
| | - Stefano Bonfatti
- Radiology Unit, AOU Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy; (R.F.); (S.B.); (G.L.)
| | - Guido Ligabue
- Radiology Unit, AOU Policlinico di Modena, University of Modena and Reggio Emilia, 41124 Modena, Italy; (R.F.); (S.B.); (G.L.)
| | - Maria Chiara Bassi
- Medical Library, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Angela Damato
- Oncology Department, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.D.); (C.B.); (C.P.)
| | - Candida Bonelli
- Oncology Department, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.D.); (C.B.); (C.P.)
| | - Carmine Pinto
- Oncology Department, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.D.); (C.B.); (C.P.)
| | - Pierpaolo Pattacini
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;
| | - Paolo Giorgi Rossi
- Epidemiology Unit, AUSL- IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (O.D.); (L.B.); (P.G.R.)
| |
Collapse
|
|
18
|
Chen H, Dai S, Fang Y, Chen L, Jiang K, Wei Q, Ding K. Hepatic Steatosis Predicts Higher Incidence of Recurrence in Colorectal Cancer Liver Metastasis Patients. Front Oncol 2021; 11:631943. [PMID: 33767997 PMCID: PMC7986714 DOI: 10.3389/fonc.2021.631943] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 02/08/2021] [Indexed: 12/24/2022] Open
Abstract
Purpose: Colorectal liver metastasis (CRLM) is the major cause of death due to colorectal cancer. Although great efforts have been made in treatment of CRLM, about 60–70% of patients will develop hepatic recurrence. Hepatic steatosis was reported to provide fertile soil for metastasis. However, whether hepatic steatosis predicts higher incidence of CRLM recurrence is not clear. Therefore, we aimed to determine the role of hepatic steatosis in CRLM recurrence in the present study. Methods: Consecutive CRLM patients undergoing curative treatment were retrospectively enrolled and CT liver-spleen attenuation ratio was used to detect the presence of hepatic steatosis. In patients with hepatic steatosis, we also detected the presence of fibrosis. Besides, a systematic literature search was performed to do meta-analysis to further analyze the association between hepatic steatosis and CRLM recurrence. Results: A total of 195 eligible patients were included in our center. Patients with hepatic steatosis had a significantly worse overall (P = 0.0049) and hepatic recurrence-free survival (RFS) (P = 0.0012). Univariate and multivariate analysis confirmed its essential role in prediction of RFS. Besides, hepatic fibrosis is associated with worse overall RFS (P = 0.039) and hepatic RFS (P = 0.048). In meta-analysis, we included other four studies, with a total of 1,370 patients in the case group, and 3,735 patients in the control group. The odds ratio was 1.98 (95% CI: 1.25–3.14, P = 0.004), indicating that patients with steatosis had a significantly higher incidence of CRLM recurrence. Conclusion: In summary, patients with hepatic steatosis had a significantly worse overall and hepatic RFS and it's associated with higher incidence of CRLM recurrence.
Collapse
Affiliation(s)
- Haiyan Chen
- Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang University Cancer Center, Hangzhou, China
| | - Siqi Dai
- Zhejiang University Cancer Center, Hangzhou, China.,Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yimin Fang
- Zhejiang University Cancer Center, Hangzhou, China.,Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liubo Chen
- Zhejiang University Cancer Center, Hangzhou, China.,Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Jiang
- Zhejiang University Cancer Center, Hangzhou, China.,Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qichun Wei
- Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang University Cancer Center, Hangzhou, China
| | - Kefeng Ding
- Zhejiang University Cancer Center, Hangzhou, China.,Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
19
|
Besutti G, Damato A, Venturelli F, Bonelli C, Vicentini M, Monelli F, Mancuso P, Ligabue G, Pattacini P, Pinto C, Giorgi Rossi P. Baseline liver steatosis has no impact on liver metastases and overall survival in rectal cancer patients. BMC Cancer 2021; 21:253. [PMID: 33750342 PMCID: PMC7941741 DOI: 10.1186/s12885-021-07980-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Accepted: 02/24/2021] [Indexed: 01/15/2023] Open
Abstract
Background The liver is one of the most frequent sites of metastases in rectal cancer. This study aimed to evaluate how the development of synchronous or metachronous liver metastasis and overall survival are impacted by baseline liver steatosis and chemotherapy-induced liver damage in rectal cancer patients. Methods Patients diagnosed with stage II to IV rectal cancer between 2010 and 2016 in our province with suitable baseline CT scan were included. Data on cancer diagnosis, staging, therapy, outcomes and liver function were collected. CT scans were retrospectively reviewed to assess baseline steatosis (liver density < 48 HU and/or liver-to-spleen ratio < 1.1). Among patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was defined as steatosis appearance, ≥ 10% liver volume increase, or significant increase in liver function tests. Results We included 283 stage II to IV rectal cancer patients with suitable CT scan (41% females; mean age 68 ± 14 years). Steatosis was present at baseline in 90 (31.8%) patients, synchronous liver metastasis in 42 (15%) patients and metachronous liver metastasis in 26 (11%); 152 (54%) deaths were registered. The prevalence of synchronous liver metastasis was higher in patients with steatosis (19% vs 13%), while the incidence of metachronous liver metastasis was similar. After correcting for age, sex, stage, and year of diagnosis, steatosis was not associated with metachronous liver metastasis nor with overall survival. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage was associated with higher incidence of metachronous liver metastasis and worse survival, results which need to be confirmed by larger studies. Conclusions Our data suggest that rectal cancer patients with steatosis had a similar occurrence of metastases during follow-up, even if the burden of liver metastases at diagnosis was slightly higher, compatible with chance. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-07980-9.
Collapse
Affiliation(s)
- Giulia Besutti
- Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, Modena, Italy.,Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Angela Damato
- Medical Oncology Unit, AUSL-IRCCS of Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia, Italy.,Department of Medical Biotechnologies, University of Siena, Strada delle Scotte 4, 53100, Siena, Italy
| | - Francesco Venturelli
- Epidemiology Unit, AUSL-IRCCS of Reggio Emilia, Via Amendola 2, 42122, Reggio Emilia, Italy
| | - Candida Bonelli
- Medical Oncology Unit, AUSL-IRCCS of Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia, Italy
| | - Massimo Vicentini
- Epidemiology Unit, AUSL-IRCCS of Reggio Emilia, Via Amendola 2, 42122, Reggio Emilia, Italy
| | - Filippo Monelli
- Clinical and Experimental Medicine PhD program, University of Modena and Reggio Emilia, Modena, Italy. .,Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
| | - Pamela Mancuso
- Epidemiology Unit, AUSL-IRCCS of Reggio Emilia, Via Amendola 2, 42122, Reggio Emilia, Italy
| | - Guido Ligabue
- Department of Radiology, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio Emilia, 41124, Modena, Italy
| | - Pierpaolo Pattacini
- Radiology Unit, Department of Diagnostic Imaging and Laboratory Medicine, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Carmine Pinto
- Medical Oncology Unit, AUSL-IRCCS of Reggio Emilia, Viale Risorgimento 80, 42123, Reggio Emilia, Italy
| | - Paolo Giorgi Rossi
- Epidemiology Unit, AUSL-IRCCS of Reggio Emilia, Via Amendola 2, 42122, Reggio Emilia, Italy
| |
Collapse
|
|
20
|
Juszczyk K, Kang S, Putnis S, Winn R, Chen J, Aghmesheh M, Fylyk G, Brungs D. High body mass index is associated with an increased overall survival in rectal cancer. J Gastrointest Oncol 2020; 11:626-632. [PMID: 32953146 DOI: 10.21037/jgo-20-48] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Background The impact of increased body mass index (BMI) on clinical outcomes in locoregional rectal cancer is unknown. Methods This is a retrospective cohort study which included 453 consecutive rectal cancer patients undergoing definitive treatment, with confirmed stage I, II or III rectal adenocarcinoma. The association of BMI at diagnosis with overall survival (OS), cancer specific survival (CSS) and disease-free survival (DFS) was explored, controlling for key covariates using multivariable analyses. BMI as defined by the World Health Organization (WHO) is as follows: BMI <18.5-underweight; 18.5-24.9-normal; 25.0-29.9-pre-obesity; >30-obese. Results Overweight and obese patients had significantly better OS than underweight/normal weight patients (5-year OS 80% for overweight, 77% for obese, and 65% for underweight/normal weight patients, P=0.02). High BMI (>25) was significantly associated with improved OS in univariate [0.62 (0.4-0.8) P=0.007] and multivariable [0.65 (0.4-0.9) P=0.023] analyses. When stratified by stage, high BMI was associated with improved OS in stage III patients (P=0.0009), but not stage II (P=0.21) or stage I (0.54). High BMI was also significantly associated with improved CSS in univariate (HR 0.62, P=0.048) and multivariable analyses (HR 0.58, P=0.03). Conclusions In our study a BMI greater than 25 is significantly associated with a longer OS and CSS in patients with locoregional rectal cancer. These findings may be due to the reduced metabolic capacity for non-obese patients to deal with rectal cancer treatment as well as the burden of disease, however further research is needed to evaluate this.
Collapse
Affiliation(s)
- Karolina Juszczyk
- Division of Surgery, Colorectal Unit, Wollongong Hospital, NSW, Australia
| | - Sharlyn Kang
- Department of Radiation Oncology, Illawarra Cancer Care Centre, Wollongong Hospital, NSW, Australia.,Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
| | - Soni Putnis
- Division of Surgery, Colorectal Unit, Wollongong Hospital, NSW, Australia
| | - Robert Winn
- Division of Surgery, Colorectal Unit, Wollongong Hospital, NSW, Australia
| | - James Chen
- Department of Radiation Oncology, Illawarra Cancer Care Centre, Wollongong Hospital, NSW, Australia
| | - Morteza Aghmesheh
- Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia.,Department of Medical Oncology, Illawarra Cancer Care Centre, Wollongong Hospital, NSW, Australia
| | - Glaucia Fylyk
- Department of Radiation Oncology, Shoalhaven Cancer Care Centre, Shoalhaven Hospital, NSW, Australia
| | - Daniel Brungs
- Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia.,Department of Medical Oncology, Illawarra Cancer Care Centre, Wollongong Hospital, NSW, Australia
| |
Collapse
|
|
21
|
Kus T, Cinkir HY, Aktas G, Abali H. Recurrence pattern in the presence of hepatosteatosis in breast cancer: does it facilitate liver metastasis? Future Oncol 2020; 16:1257-1267. [PMID: 32356676 DOI: 10.2217/fon-2019-0634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: We aimed to investigate the impact of hepatosteatosis (HS) severity on the recurrence pattern of breast cancer and to clarify whether HS causes affinity to recurrence with liver metastasis. Materials & methods: The median follow-up was 80.0 (4-217) months and the mean age was 47.9 ± 11.3 years. Among all, 181 (39.9%) patients were diagnosed with grades 2 and 3 HS. Of total, 158 (34.8%) patients have experienced recurrence. Results: While higher degree of HS was more common in patients presented with liver recurrence (odds ratio; 95% CI: 2.50; 1.27-4.92; p = 0.007), it was lesser in those with other metastatic sites (all were >0.05). Liver-recurrence-free survival was significantly worse in the group with higher degree of HS (hazard ratio; 95% CI: 2.46; 1.4-4.3; p = 0.002) together with younger age (hazard ratio; 95% CI: 2.44; 1.4-4.3; p = 0.002) in multivariate analysis. Conclusion: HS might have produced an affinity for liver metastasis in common types of breast cancer patients in remission independent from metabolic disorders or clinicopathologic features.
Collapse
Affiliation(s)
- Tulay Kus
- Department of Medical Oncology, Adıyaman University, Training & Research Hospital, TR 02040, Adıyaman, Turkey
| | - Havva Yesil Cinkir
- Department of Medical Oncology, School of Medicine, Gaziantep University, TR 27310, Gaziantep, Turkey
| | - Gokmen Aktas
- Department of Medical Oncology, School of Medicine, Kahramanmaras Sütçü İmam University, TR 46100, Kahramanmaraş, Turkey
| | - Huseyin Abali
- Department of Medical Oncology, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Adana, Turkey
| |
Collapse
|
|
22
|
Lv Y, Zhang HJ. Effect of Non-alcoholic Fatty Liver Disease on the Risk of Synchronous Liver Metastasis: Analysis of 451 Consecutive Patients of Newly Diagnosed Colorectal Cancer. Front Oncol 2020; 10:251. [PMID: 32181157 PMCID: PMC7059642 DOI: 10.3389/fonc.2020.00251] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 02/13/2020] [Indexed: 12/24/2022] Open
Abstract
Background: The purpose of this study was to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on the risk of synchronous colorectal liver metastasis (synCRLM). Methods: A retrospective analysis was performed on 451 consecutive patients with newly diagnosed colorectal cancer (CRC) from January 2014 to January 2019. According to the presence of NAFLD, the CRC patients were divided into two groups, NAFLD group (60 cases) and the control group (391 cases). The clinicopathological features and the prevalence of synCRLM between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of synCRLM. Different non-invasive liver fibrosis scoring models were used to evaluate the effect of advanced fibrosis and cirrhosis stage in NAFLD on the prevalence of synCRLM. Results: The prevalence of synCRLM was significantly higher in patients with NAFLD than that in patients without NAFLD (18.33 vs. 7.42%; χ2 = 7.669, P = 0.006). A logistic regression analysis indicated that NAFLD, CEA, CA19-9, and lymph node status were risk factors for synCRLM, and NAFLD showed the highest hazard ratio (3.930 [95% confidence interval: 1.616 ~ 9.560]). In NAFLD patients, both fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were significantly lower in those with synCRLM compared to those without synCRLM [FIB-4: 1.246 (0.833 ~ 1.276) vs. 1.436 (1.016 ~ 2.699), Z = −2.130, P = 0.033; NFS: −1.282 (−2.407 ~ −0.262) vs. −0.255 (−1.582 ~ 0.755), Z = −2.302, P = 0.021; Mann-Whitney test]. Conclusion: NAFLD may be associated with increased liver metastasis, and for NAFLD-related advanced liver fibrosis and cirrhosis may be associated with reduced synchronous liver metastasis in CRC patients. However, the correlation between simple steatosis and steatohepatitis remains to be further determined. Certain factors such as NAFLD, lymph node metastasis, elevated levels of preoperative CEA and CA19-9 are suggesting a high risk of synCRLM.
Collapse
Affiliation(s)
- Yan Lv
- Department of Oncology, The Affiliated Zhongda Hospital of Southeast University, Medical School of Southeast University, Nanjing, China
| | - Hai-Jun Zhang
- Department of Oncology, The Affiliated Zhongda Hospital of Southeast University, Medical School of Southeast University, Nanjing, China
| |
Collapse
|
|
23
|
Hu X, Marietta A, Dai WX, Li YQ, Ma XJ, Zhang L, Cai SJ, Peng JJ. Prediction of hepatic metastasis and relapse in colorectal cancers based on concordance analyses with liver fibrosis scores. Clin Transl Med 2020; 9:13. [PMID: 32025991 PMCID: PMC7002812 DOI: 10.1186/s40169-020-0264-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 01/20/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Liver fibrosis, resulted from several liver diseases, are increasing up to 25% in population in global. It remains undetermined how much impact liver fibrosis have on the development of hepatic metastasis and relapse in colorectal cancer (CRC). Hence the aim of this study was to clarify the role of liver fibrosis on hepatic metastasis and relapse in CRC undergoing curative therapy. METHODS We enrolled consecutive 1652 patients with radical colorectal surgery as the discovery cohort, and the validation set enrolled 432 CRC patients with hepatic metastasis. To determine liver fibrosis, the NFS, FIB4 and APRI scores were applied. The influence of liver fibrosis on hepatic metastasis and relapse was assessed by survival analyses. Nomograms with fibrosis score incorporated were established to identify the incremental value for individualized relapse estimation, which was then assessed with respect to calibration, discrimination, and clinical usefulness. RESULTS The high liver fibrosis score patients had significantly worse outcomes than low score in 5-year hepatic metastasis (22.6 vs. 8.7%) in discovery cohort, and relapse (58.2 vs. 44.1%) in validation cohort. Multivariate analysis also revealed liver fibrosis as an independent prognostic factor. The distribution analysis also demonstrated higher liver fibrosis score a powerful prognostic factor for hepatic metastasis and relapse. The nomogram incorporated with liver fibrosis score resulted in better performance than TNM staging system and clinicopathologic nomograms. Importantly, the discriminatory capacity of the fibrosis score was superior to that of the CRS score in predicting hepatic specific disease-free survival (DFS) and relapse-free survival (RFS), as demonstrated by the C-index and AUC. The concordance study showed well agreement among NFS, FIB4 and APRI in predicting DFS and RFS. Among these three noninvasive liver fibrosis scores, NFS score performed the best in predicting hepatic specific DFS and RFS. CONCLUSION The liver fibrosis was a powerful predictor of hepatic specific DFS and RFS in CRC. Fibrosis niche may be a favorable microenvironment for metastatic formation in the liver.
Collapse
Affiliation(s)
- Xiang Hu
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Audrey Marietta
- Universitas Sriwijaya/RSUP Dr. Mohammad Hoesin, Palembang, Indonesia
| | - Wei-Xing Dai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Ya-Qi Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xiao-Ji Ma
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Long Zhang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - San-Jun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Jun-Jie Peng
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 20032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
| |
Collapse
|
|
24
|
Lv Y, Patel N, Zhang HJ. The progress of non-alcoholic fatty liver disease as the risk of liver metastasis in colorectal cancer. Expert Rev Gastroenterol Hepatol 2019; 13:1169-1180. [PMID: 31774328 DOI: 10.1080/17474124.2019.1697231] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: The liver is the most common metastatic site of colorectal cancer (CRC), and the long-term survival rate of CRC patients who cannot resect liver metastatic lesions radically is extremely low. Early identification of risk factors for liver metastasis from CRC may be an effective strategy to reduce the incidence of liver metastasis. The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in parallel with an increasing prevalence of obesity and metabolic syndrome (MS), which has become one of the main causes of chronic liver disease worldwide.Areas covered: An overview of the related research progress of the association between NAFLD and colorectal liver metastasis (CRLM).Expert opinion: Certain research proves that there is a close relationship between NAFLD and CRC, and the presence of NAFLD can promote the formation and development of CRC. Although the effect of liver diseases on the incidence of liver metastasis in CRC has been noted in recent years, the results are inconsistent and haven't reached a unified conclusion. Therefore, the association between liver metastasis and NAFLD remains the main focal point in the evolution of CRC.
Collapse
Affiliation(s)
- Yan Lv
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China
| | - Nishant Patel
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China
| | - Hai-Jun Zhang
- Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China.,Precision Medicine Center, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China
| |
Collapse
|
|
25
|
Ohashi K, Wang Z, Yang YM, Billet S, Tu W, Pimienta M, Cassel SL, Pandol SJ, Lu SC, Sutterwala FS, Bhowmick N, Seki E. NOD-like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD. Hepatology 2019; 70:1582-1599. [PMID: 31044438 PMCID: PMC6819206 DOI: 10.1002/hep.30693] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Accepted: 04/23/2019] [Indexed: 12/16/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) enhances the growth and recurrence of colorectal cancer (CRC) liver metastasis. With the rising prevalence of NAFLD, a better understanding of the molecular mechanism underlying NAFLD-associated liver metastasis is crucial. Tumor-associated macrophages (TAMs) constitute a large portion of the tumor microenvironment that promotes tumor growth. NOD-like receptor C4 (NLRC4), a component of an inflammasome complex, plays a role in macrophage activation and interleukin (IL)-1β processing. We aimed to investigate whether NLRC4-mediated TAM polarization contributes to metastatic liver tumor growth in NAFLD. Wild-type and NLRC4-/- mice were fed low-fat or high-fat diet for 6 weeks followed by splenic injection of mouse CRC MC38 cells. The tumors were analyzed 2 weeks after CRC cell injection. High-fat diet-induced NAFLD significantly increased the number and size of CRC liver metastasis. TAMs and CD206-expressing M2 macrophages accumulated markedly in tumors in the presence of NAFLD. NAFLD up-regulated the expression of IL-1β, NLRC4, and M2 markers in tumors. In NAFLD, but not normal livers, deletion of NLRC4 decreased liver tumor growth accompanied by decreased M2 TAMs and IL-1β expression in tumors. Wild-type mice showed increased vascularity and vascular endothelial growth factor (VEGF) expression in tumors with NAFLD, but these were reduced in NLRC4-/- mice. When IL-1 signaling was blocked by recombinant IL-1 receptor antagonist, liver tumor formation and M2-type macrophages were reduced, suggesting that IL-1 signaling contributes to M2 polarization and tumor growth in NAFLD. Finally, we found that TAMs, but not liver macrophages, produced more IL-1β and VEGF following palmitate challenge. Conclusion: In NAFLD, NLRC4 contributes to M2 polarization, IL-1β, and VEGF production in TAMs, which promote metastatic liver tumor growth.
Collapse
Affiliation(s)
- Koichiro Ohashi
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | - Zhijun Wang
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Yoon Mee Yang
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea
| | - Sandrine Billet
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | - Wei Tu
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Michael Pimienta
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | - Suzanne L. Cassel
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | - Stephen J. Pandol
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California 90048, USA
| | - Shelly C. Lu
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California 90048, USA
| | - Fayyaz S. Sutterwala
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA
| | - Neil Bhowmick
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California 90048, USA
| | - Ekihiro Seki
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA,Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California 90048, USA
| |
Collapse
|
|
26
|
Narayan RR, Harris JW, Chou JF, Gönen M, Bao F, Shia J, Allen PJ, Balachandran VP, Drebin JA, Jarnagin WR, Kemeny NE, Kingham TP, D'Angelica MI. Prediction of Recurrence Patterns from Hepatic Parenchymal Disease After Resection of Colorectal Liver Metastases. Ann Surg Oncol 2019; 27:188-195. [PMID: 31617122 DOI: 10.1245/s10434-019-07934-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Obesity and metabolic syndrome are associated with inflammatory hepatic parenchymal disease (HPD) and increased risk for recurrence after resection of colorectal liver metastases (CRLM). The independent impact of HPD on recurrence patterns has not been well defined. METHODS The nonalcoholic fatty liver disease activity score (NAS) was used to quantify HPD including steatosis and fibrosis for all patients with completely resected CRLM between April 2003 and March 2007. Clinicopathologic factors, perioperative history, and outcomes were compared with the NAS. Fisher's exact test was used to examine the association between severe HPD (NAS ≥ 3) with clinical and perioperative characteristics. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS). The cumulative incidences of recurrence [any intrahepatic recurrence (IHR), extrahepatic recurrence only (EHR), and death without recurrence (DWR)] were estimated using competing risks methods. RESULTS Among the 357 patients included in this study, microsteatosis was noted in 124 (35%) patients, severe HPD in 31 (9%), steatohepatitis in 14 (4%), and sinusoidal injury in 36 (10%). After median follow-up of 127 months (range 4-175 months), 10-year RFS was 22% [95% confidence interval (CI) 17-27%]. Ten-year cumulative incidence for IHR, EHR, and DWR was 37%, 30%, and 12%, respectively. After controlling for confounders, NAS ≥ 3 was independently associated with higher risk of IHR [hazard ratio (HR) 1.76, 95% CI 1.07-2.90, p = 0.027] and lower risk of EHR (HR 0.18, 95% CI 0.04-0.75, p = 0.019) on multivariable analysis. CONCLUSIONS Severe HPD was associated with increased IHR risk and decreased EHR risk. Future investigation into whether improving HPD from reversible etiologies can reduce the risk for IHR is warranted.
Collapse
Affiliation(s)
- Raja R Narayan
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.,Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Jennifer W Harris
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joanne F Chou
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gönen
- Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Fei Bao
- Department of Pathology, Scripps Clinic, La Jolla, CA, USA
| | - Jinru Shia
- Department of Pathology, Gastrointestinal Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey A Drebin
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nancy E Kemeny
- Department of Medicine, Gastrointestinal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| |
Collapse
|
|
27
|
Jian M, Chang W, Ren L, Liu T, Chen Y, Wei Y, Lin Q, Xu J, Qin X. Predictive And Prognostic Value Of Hepatic Steatosis In Conversion Therapy For Colorectal Liver-limited Metastases: A Propensity Score Matching Analysis. Cancer Manag Res 2019; 11:8315-8326. [PMID: 31571989 PMCID: PMC6750205 DOI: 10.2147/cmar.s210185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 09/01/2019] [Indexed: 01/07/2023] Open
Abstract
Purpose To evaluate the role of hepatic steatosis (HS) in patients with synchronous colorectal liver-limited metastases (CLLMs) undergoing conversion therapy. Patients and methods From March 2013 to March 2017, a total of 406 patients with initially unresectable CLLMs accepted conversion therapy in multidisciplinary team (MDT). Before the implementation of conversion therapy, all patients underwent CT scan to assess the presence of hepatic steatosis and divided into the HS group (n = 124) and the non-HS group (n = 282). After using propensity score matching (PSM) to eliminate the potential confounding bias of the two groups, the conversion hepatectomy rate and long-term oncological survival in two groups were compared. Results After 1:1 PSM, no significant difference was observed at baseline between patients in the HS group (n = 119) and the non-HS group (n = 119). Patients in the HS group had higher conversion hepatectomy rate from MDT evaluation (31.1% vs 18.5%, P = 0.029) and actual hepatectomy rate (30.2% vs 18.5%, P = 0.030), when compared with patients in the non-HS group, respectively. In addition, the HS group achieved better progression-free survival (PFS, P = 0.047) and overall survival (OS, P = 0.035) than that of the non-HS group. Multivariate logistic analysis confirmed that pretreatment HS was an independent predictor for conversion hepatectomy rate (OR, 2.393; 95% CI, 1.463–4.315, P = 0.001), and multivariate Cox analysis revealed that HS was an independent prognostic factor for PFS (HR, 0.493, 95% CI 0.281–0.866, P = 0.014) and OS (HR, 0.559, 95% CI 0.398–0.785, P = 0.001). Conclusion For CLLM patients who underwent conversion therapy, hepatic steatosis could be an effective predictor for conversion hepatectomy rate and an independent prognostic factor for PFS and OS.
Collapse
Affiliation(s)
- Mi Jian
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Wenju Chang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Li Ren
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Tianyu Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Yijiao Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Ye Wei
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Qi Lin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Jianmin Xu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| | - Xinyu Qin
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China.,Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive, Zhongshan Hospital, Fudan University, Shanghai 200030, People's Republic of China
| |
Collapse
|
|
28
|
Spychalski P, Kobiela J, Wieszczy P, Kamiński MF, Reguła J. Clinical stages of colorectal cancer diagnosed in obese and overweight individuals in the Polish Colonoscopy Screening Program. United European Gastroenterol J 2019; 7:790-797. [PMID: 31316783 DOI: 10.1177/2050640619840451] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 03/07/2019] [Indexed: 12/14/2022] Open
Abstract
Background Obesity is a known risk factor of colorectal cancer (CRC). However, precise interconnections between excessive body fat and CRC are still vague. Therefore, the aim of this study was to assess whether stage of CRC detected in overweight and obese individuals differs from individuals with normal body mass index (BMI). A secondary aim of this study was to elucidate whether overweight and obesity influence the overall survival in CRC. Methods This study was a cross-sectional analysis of 163,129 individuals who underwent screening colonoscopy performed on data from a prospectively maintained database of the Polish Colonoscopy Screening Program. Results Overweight and obese individuals present with a less advanced CRC in screening setting (p = 0.014). This trend is the most pronounced in males (p = 0.001). Univariable and multivariable analyses revealed that obesity was a negative predictor of detection of advanced CRC with odds ratio 0.72 (95% confidence interval 0.52-1.00; p = 0.047). Furthermore, overweight and obesity were not statistically significant predictors of risk of death (p = 0.614 and p = 0.446, respectively). Conclusions Obese screenees present with a less advanced disease in comparison to non-obese. Moreover, survival stratified by clinical stage seems to not be influenced by BMI category. Therefore, a higher proportion of early diagnosed cancers can potentially create a survival benefit in this group.
Collapse
Affiliation(s)
- Piotr Spychalski
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland
| | - Jarek Kobiela
- Department of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Gdansk, Poland.,Department of Cancer Prevention, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Paulina Wieszczy
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Cancer Prevention, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Michał F Kamiński
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Oncological Gastroenterology, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.,Institute of Health and Society, University of Oslo, Oslo, Norway.,Department of Cancer Prevention, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Jarosław Reguła
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.,Department of Cancer Prevention, the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| |
Collapse
|
|
29
|
Chen J, Bian D, Zang S, Yang Z, Tian G, Luo Y, Yang J, Xu B, Shi J. The association between nonalcoholic fatty liver disease and risk of colorectal adenoma and cancer incident and recurrence: a meta-analysis of observational studies. Expert Rev Gastroenterol Hepatol 2019; 13:385-395. [PMID: 30791768 DOI: 10.1080/17474124.2019.1580143] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIM Lifestyle modification plays a key role in nonalcoholic fatty liver disease (NAFLD) and colorectal adenoma and/or cancer (CRA/CRC) development. However, the association between NAFLD and the risk of CRA/CRC has not been carefully evaluated. METHODS In this meta-analysis, we assessed 21 eligible studies including 124,206 participants to determine the association between NAFLD and the risk of incident and recurrent CRA/CRC. RESULTS NAFLD presence was associated with an increased risk of any incident CRA (aOR: 1.30, 95% CI: 1.19-1.43) and advanced incident CRA/CRC (aOR: 1.57, 95% CI: 1.21-2.04). The severity of NAFLD affected this correlation: compared to mild and/or moderate NAFLD, severe NAFLD was associated with an increased risk of incident CRA/CRC (aOR: 2.19, 95% CI: 1.33-3.60). Although pooled cOR revealed that NAFLD was associated with an increased risk of recurrent CRA/CRC (cOR = 1.73; 95% CI: 1.12-2.68), after adjustment for confounding factors, NAFLD had less correlation with the risk of recurrent CRA/CRC (aOR: 1.81, 95% CI: 0.70-4.65). CONCLUSIONS The presence and severity of NAFLD are associated with an increased risk of incident CRA/CRC. However, there is insufficient evidence to indicate that NAFLD is associated with an increased risk of recurrent CRA/CRC.
Collapse
Affiliation(s)
- Jin Chen
- a Department of Postgraduates , Zhejiang Chinese Medical University , Hangzhou , Zhejiang , China
| | - Dongxue Bian
- b Department of Digestive Disease , Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine , Yancheng , Jiangsu , China
| | - Shufei Zang
- c Department of Endocrinology , The Fifth Affiliated Hospital of Fudan University , Shanghai , China
| | - Zongxing Yang
- d Department of Infectious Disease , Hangzhou Xixi hospital , Hangzhou , Zhejiang , China
| | - Guoyan Tian
- e Department of Transformation Medical platform , Hangzhou Normal University Affiliated Hospital , Hangzhou , Zhejiang , China
| | - Yan Luo
- e Department of Transformation Medical platform , Hangzhou Normal University Affiliated Hospital , Hangzhou , Zhejiang , China
| | - Jing Yang
- e Department of Transformation Medical platform , Hangzhou Normal University Affiliated Hospital , Hangzhou , Zhejiang , China
| | - Beibei Xu
- f Department of Postgraduates , China Medical University , Shenyang , Liaoning , China
| | - Junping Shi
- g Department of Liver Diseases , Hangzhou Normal University Affiliated Hospital , Hangzhou , Zhejiang , China
| |
Collapse
|
|
30
|
Wu W, Liao H, Ye W, Li X, Zhang J, Bu J. Fatty liver is a risk factor for liver metastasis in Chinese patients with non-small cell lung cancer. PeerJ 2019; 7:e6612. [PMID: 30886784 PMCID: PMC6421062 DOI: 10.7717/peerj.6612] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 02/13/2019] [Indexed: 12/24/2022] Open
Abstract
Background The hepatic microenvironment, which may include chronic inflammation and fibrosis, is considered to contribute to the development of liver metastases. Hepatic steatosis (HS) might cause liver inflammation and fibrosis. However, to date, no studies have investigated the impact of HS on liver metastasis in patients with non-small cell lung cancer (NSCLC). Methods A retrospective cohort study was performed on patients who received NSCLC treatment at two hospitals affiliated with the Southern Medical University from January 2005 to December 2015. The patients were grouped according to the presence of HS. The clinicopathological features of patients between the two groups were compared. The effect of HS on liver metastasis and overall metastasis was evaluated, adjusting for other confounders using Cox regression analyses. Results In total, 1,873 patients with NSCLC with no distant metastases were included in this study, and 408 (21.8%) patients were diagnosed with HS (at the time of diagnosis or before diagnosis). Liver metastases occurred in 166 (8.9%) patients. Liver metastasis-free survival was significantly worse in the study (HS) group (hazard ratio (HR) 1.42; (95% CI [1.03–1.96]); P = 0.031). Multivariate regression analysis demonstrated that HS was an independent risk factor for liver metastasis (HR 1.43; 95% CI [1.02–2.01]; P = 0.039). However, HS was not associated with overall metastasis of NSCLC (HR 0.99; 95% CI [0.84–1.17]; P = 0.895). Conclusion Hepatic steatosis was an independent predictor of liver metastasis from in patients with NSCLC.
Collapse
Affiliation(s)
- Wenyu Wu
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.,Target and Interventional Therapy Department of Oncology, First People's Hospital of Foshan, Foshan, China
| | - Haiyan Liao
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Weilin Ye
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xi Li
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jian Zhang
- Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Junguo Bu
- Department of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| |
Collapse
|
|
31
|
Wu K, Zhai MZ, Weltzien EK, Cespedes Feliciano EM, Meyerhardt JA, Giovannucci E, Caan BJ. Non-alcoholic fatty liver disease and colorectal cancer survival. Cancer Causes Control 2018; 30:165-168. [PMID: 30443695 DOI: 10.1007/s10552-018-1095-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 11/08/2018] [Indexed: 01/20/2023]
Abstract
PURPOSE Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between NAFLD and mortality in colorectal cancer patients. METHODS Colorectal Cancer-Sarcopenia and Near-term Survival (C-SCANS) is a retrospective cohort study which included 3,262 stage I-III patients, aged 18-80 years, and diagnosed between 2006 and 2011 at Kaiser Permanente Northern California. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS After up to 10 years of follow-up, 879 deaths, including 451 from CRC were identified. Cases diagnosed with NAFLD before and within 1 month after CRC diagnosis (pre-existing NAFLD; n = 83) had a HR of 1.64 (95% CI 1.06-2.54) for overall and a HR of 1.85 (95% CI 1.03-3.30) for CRC-specific mortality compared to those without NAFLD. Findings did not differ significantly by sex, stage, tumor location, and smoking status, and were also similar when restricted to obese patients only. CONCLUSIONS Independent of body mass index and prognostic indicators, CRC patients with pre-existing NAFLD had a worse prognosis than those without NAFLD.
Collapse
Affiliation(s)
- Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | | | - Erin K Weltzien
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | | | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Edward Giovannucci
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Bette J Caan
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| |
Collapse
|
|
32
|
Lino-Silva LS, Aguilar-Cruz E, Salcedo-Hernández RA, Zepeda-Najar C. Overweight but not obesity is associated with decreased survival in rectal cancer. Contemp Oncol (Pozn) 2018; 22:158-164. [PMID: 30455587 PMCID: PMC6238088 DOI: 10.5114/wo.2018.78937] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 05/15/2018] [Indexed: 12/15/2022] Open
Abstract
AIM OF THE STUDY To analyse the influence of overweight and obesity in disease-specific survival (DSS) in rectal cancers at stages I-III in a population with high prevalence of overweight/obesity. MATERIAL AND METHODS The population (N = 304) consisted of Mexican patients with stage I-III rectal cancer during the period between 2009 and 2015. Patients were divided based on their body mass index (BMI) into normal weight 18-25 kg/m2, overweight 25-29 kg/m2, and obesity BMI > 30 kg/m2 groups. Comparison of clinicopathologic features and survival analysis were performed. RESULTS The median age was 58 years (interquartile range [IQR] 50-65) and the mean BMI was 26.03 ±4.06 kg/m2. Patients in the obesity and overweight groups received a lower proportion of preoperative treatment and had a higher proportion of patients in stage II. Overweight patients had a lower baseline neutrophil/lymphocyte ratio and lower survival rate than patients with normal weight and with obesity (mean survival of 69.5 months vs. 81.15 months and 86.4 months, respectively). The estimated five-year DSS was 51% for the overweight group, 81% for the normal group, and 82% for the obesity group (p = 0.026). CONCLUSIONS Patients with stage I-III rectal cancer in the overweight group showed a lower DSS compared to groups with normal weight and with obesity, with the last two being similar.
Collapse
|
|
33
|
Cheng L, Geng L, Dai B, Zheng T, Fu J, Qiao L, Cai W, Wang Y, Yang J. Repression of let-7a cluster prevents adhesion of colorectal cancer cells by enforcing a mesenchymal phenotype in presence of liver inflammation. Cell Death Dis 2018; 9:489. [PMID: 29695839 PMCID: PMC5916926 DOI: 10.1038/s41419-018-0477-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Revised: 02/06/2018] [Accepted: 02/14/2018] [Indexed: 01/10/2023]
Abstract
The liver is the most common site of metastasis in patients with colorectal cancer, and colorectal cancer liver metastasis (CRLM) is associated with poor rates of survival. However, CRLM occurs infrequently in livers exhibiting signs of hepatitis or cirrhosis, suggesting a role for inflammation in attenuating CRLM. The molecular mechanisms driving this phenomenon remain unclear. The aim of this study was to confirm the mechanism by which liver inflammation inhibits CRLM. We used BALB/c animal models of inflammatory liver diseases to confirm that liver inflammation inhibits CRLM, and then elucidated the molecular mechanisms governing that process. Out data showed that liver inflammation induces IFN-γ expression, which then downregulates expression of the let-7a cluster through IRF-1 in colorectal cancer cells. Finally, we showed that modulation of let-7a expression regulated the epithelial–mesenchymal transition in colorectal cancer cell lines, and inhibited their capacity to metastasize in vivo. Cumulatively, we clarified the critical role played by the IFN-γ/IRF-1/let-7a cluster/EMT pathway in regulating the spread of circulating colorectal cancer cells to the liver, and highlighted the critical role that the hepatitis microenvironment plays in modulating that process.
Collapse
Affiliation(s)
- Lipeng Cheng
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Li Geng
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Binghua Dai
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Tao Zheng
- Department of General Surgery, People's Liberation Army Nanjing General Hospital, Nanjing, 210002, China
| | - Jun Fu
- Department of Hepatobiliary Pancreatic and Spleen Surgery, Xuzhou Central Hospital, Xuzhou, 221000, China
| | - Liang Qiao
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Wenchang Cai
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
| | - Yue Wang
- Research Center of Developmental Biology, Second Military Medical University, Shanghai, 200433, China.
| | - Jiamei Yang
- Department of Special Treatment and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
| |
Collapse
|
|
34
|
Lin Y, Wang Y, Wu Q, Jin H, Ma G, Liu H, Wang M, Zhang Z, Chu H. Association between obesity and bladder cancer recurrence: A meta-analysis. Clin Chim Acta 2018; 480:41-46. [DOI: 10.1016/j.cca.2018.01.039] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 01/18/2018] [Accepted: 01/21/2018] [Indexed: 10/18/2022]
|
|
35
|
Specific features of colorectal cancer in patients with metabolic syndrome: a matched case-control analysis of 772 patients. Langenbecks Arch Surg 2018; 403:443-450. [PMID: 29704123 DOI: 10.1007/s00423-018-1677-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Accepted: 04/18/2018] [Indexed: 12/18/2022]
Abstract
PURPOSE Although association between colorectal cancer (CRC) and metabolic syndrome (MetS) is established, specific features of CRC arising in patients presenting with MetS have not been clearly identified. METHOD All patients who underwent colectomy for CRC from January 2005 to December 2014 at Institut Mutualiste Montsouris were identified from a prospectively collected database and characteristics were compared in the entire population and in a 1:2 matched case-control analysis [variables on which matching was performed were CRC localization (right- or left-sided) and AJCC stage (0 to IV)]. RESULTS Out of the 772 identified patients, 98 (12.7%) presented with MetS. Entire population analysis revealed that CRC associated with MetS was more frequent in men (71.4 vs. 47.8%, p < 0.001), more often right-sided (71.4 vs. 50.4%, p < 0.001) and presented with less synchronous liver metastasis (4.1 vs. 8.7%, p = 0.002). Case-control analysis confirmed the gender association (p < 0.001) and showed HNPCC (p < 0.001) and history family of CRC (p = 0.010) to be significantly more frequent in Non-MetS patients. CONCLUSIONS CRC associated with MetS is more frequent in men, more often right-sided, and presents with fewer synchronous metastasis. Further investigations should be designed in order to confirm these results and to enhance our knowledge of carcinogenesis related to MetS.
Collapse
|
|
36
|
|
|
37
|
Fatty liver decreases the risk of liver metastasis in patients with breast cancer: a two-center cohort study. Breast Cancer Res Treat 2017; 166:289-297. [PMID: 28741275 DOI: 10.1007/s10549-017-4411-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 07/20/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND The influence of hepatic steatosis (HS) on liver metastasis in patients with non-metastatic breast cancer (BC) remains unclear. The aim of this study was to clarify the relationship between HS and liver metastasis in non-metastatic BC patients. METHODS Patients who underwent treatment for BC at two affiliated hospitals of Southern Medical University, between January 1, 2005 and December 31, 2015, were retrospectively reviewed. BC patients were divided into the study and control groups based on the presence of HS. The association between HS and liver metastasis was analyzed, adjusting for the confounding factors using Cox regression and propensity score case-match analysis. RESULTS In total, 1230 female BC patients were included, and 372 (30.2%) patients were diagnosed with HS (at the time of diagnosis BC or before). The cumulative liver metastasis-free survival (MFS) rate was significantly higher in the study group than in the control group (hazard ratio 0.61; 95% confidence interval 0.40-0.94; P = 0.024). On multivariate analysis, HS was an independent protective factor for local liver metastasis (HR 0.55; 0.35-0.86; P = 0.008). After one-to-one matching of the study group (344) with the control group (344), liver MFS remained significantly better in the study group (HR 0.42; 0.26-0.69; P = 0.001). CONCLUSION This study indicated that HS may serve as an independent factor to decrease liver metastasis in patients with BC. Additional prospective studies are necessary to validate this finding.
Collapse
|
|
38
|
Molla NW, Hassanain MM, Fadel Z, Boucher LM, Madkhali A, Altahan RM, Alrijraji EA, Simoneau EB, Alamri H, Salman A, Gao Z, Metrakos PP. Effect of non-alcoholic liver disease on recurrence rate and liver regeneration after liver resection for colorectal liver metastases. ACTA ACUST UNITED AC 2017; 24:e233-e243. [PMID: 28680292 DOI: 10.3747/co.24.3133] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Resection of metastases is the only potential cure for patients with liver metastasis from colorectal cancer (crc-lm). But despite an improved overall 5-year survival, the recurrence rate is still as high as 60%. Non-alcoholic fatty liver disease (nafld) can decrease the liver's capacity to regenerate after resection and might also affect cancer recurrence, potentially by elevating transforming growth factor β, levels of specific metalloproteinases, and oxidative stress. The objective of the present work was to determine the effect of the histologic features of nafld on cancer recurrence and liver regeneration. METHODS This retrospective analysis considered 60 patients who underwent an R0 hepatectomy for crc-lm. Volumetric analysis of the liver was calculated using axial view, portovenous phase, 2.5 mm thickness, multiphasic computed tomography images taken before and after surgery. The histologic features of nafld (steatosis, inflammation, and ballooning) were scored using the nafld activity score, and the degree of fibrosis was determined. RESULTS The hepatic recurrence rate was 38.33%. Median overall survival duration was 56 months. Median disease-free survival duration was 14 months, and median hepatic disease-free survival duration was 56 months. Multivariate analysis revealed significant correlations of hepatic disease-free survival with hepatocyte ballooning (p = 0.0009), lesion diameter (p = 0.014), and synchronous disease (p = 0.006). Univariate and multivariate analyses did not reveal any correlation with degree of steatosis or recurrence rate. CONCLUSIONS This study reveals an important potential negative effect of hepatocyte ballooning on hepatic disease-free survival.
Collapse
Affiliation(s)
- N W Molla
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Radiology, McGill University Health Centre, Montreal, QC.,Department of Radiology and
| | - M M Hassanain
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - Z Fadel
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - L M Boucher
- Department of Radiology, McGill University Health Centre, Montreal, QC
| | - A Madkhali
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - R M Altahan
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - E A Alrijraji
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - E B Simoneau
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - H Alamri
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Surgery, King Saud University, Riyadh, Saudi Arabia
| | - A Salman
- Department of Surgery, Section of Hepatopancreatobiliary, and
| | - Z Gao
- Department of Pathology, McGill University Health Centre, Montreal, QC
| | - P P Metrakos
- Department of Surgery, Section of Hepatopancreatobiliary, and.,Department of Pathology, McGill University Health Centre, Montreal, QC
| |
Collapse
|
|
39
|
Coimbra FJF, Ribeiro HSDC, Marques MC, Herman P, Chojniak R, Kalil AN, Wiermann EG, Cavallero SRDA, Coelho FF, Fernandes PHDS, Silvestrini AA, Almeida MFA, de Araújo ALE, Pitombo M, Teixeira HM, Waechter FL, Ferreira FG, Diniz AL, D'Ippolito G, D'Ippolito G, Begnami MDFDS, Prolla G, Balzan SMP, de Oliveira TB, Szultan LA, Lendoire J, Torres OJM. FIRST BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 1: PRE-TREATMENT EVALUATION. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2016; 28:222-30. [PMID: 26734788 PMCID: PMC4755170 DOI: 10.1590/s0102-6720201500040002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 08/11/2015] [Indexed: 02/07/2023]
Abstract
Background : Liver metastases of colorectal cancer are frequent and potentially fatal event
in the evolution of patients with these tumors. Aim : In this module, was contextualized the clinical situations and parameterized
epidemiological data and results of the various treatment modalities established.
Method: Was realized deep discussion on detecting and staging metastatic colorectal
cancer, as well as employment of imaging methods in the evaluation of response to
instituted systemic therapy. Results : The next step was based on the definition of which patients would have their
metastases considered resectable and how to expand the amount of patients elegible
for modalities with curative intent. Conclusion : Were presented clinical, pathological and molecular prognostic factors,
validated to be taken into account in clinical practice.
Collapse
Affiliation(s)
| | | | | | - Paulo Herman
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | - Rubens Chojniak
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | - Marcos Pitombo
- American Hepato-Pancreato-Biliary Association, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Kondo T, Okabayashi K, Hasegawa H, Tsuruta M, Shigeta K, Kitagawa Y. The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer. Br J Cancer 2016; 115:34-9. [PMID: 27280634 PMCID: PMC4931372 DOI: 10.1038/bjc.2016.155] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 04/26/2016] [Accepted: 05/04/2016] [Indexed: 12/19/2022] Open
Abstract
Background: The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC. Methods: Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses. Results: A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4–94.7 vs NL 96.0%, 95% CI 94.3–97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23–7.21; P=0.02). Conclusion: HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC.
Collapse
Affiliation(s)
- Takayuki Kondo
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| | - Hirotoshi Hasegawa
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| | - Masashi Tsuruta
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| | - Kohei Shigeta
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 1608582, Japan
| |
Collapse
|
|
41
|
Schulz PO, Ferreira FG, Nascimento MDFA, Vieira A, Ribeiro MA, David AI, Szutan LA. Association of nonalcoholic fatty liver disease and liver cancer. World J Gastroenterol 2015; 21:913-918. [PMID: 25624725 PMCID: PMC4299344 DOI: 10.3748/wjg.v21.i3.913] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 07/18/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors.
METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade.
RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the relationship between the presence of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis, and their risk factors, showed no significant statistical association for any of the tumors studied.
CONCLUSION: NAFLD is more common in patients with liver metastases caused by colorectal cancer.
Collapse
|
|
42
|
Cai B, Liao K, Song XQ, Wei WY, Zhuang Y, Zhang S. Patients with chronically diseased livers have lower incidence of colorectal liver metastases: a meta-analysis. PLoS One 2014; 9:e108618. [PMID: 25265536 PMCID: PMC4181318 DOI: 10.1371/journal.pone.0108618] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 08/23/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND 70 years ago, it was put forward that the diseased liver was not a favorable soil for metastatic tumor cells. In addition, a few studies have demonstrated that rare occurrence of colorectal liver metastases among patients with fatty liver, cirrhosis or chronic hepatitis B and C virus infection. We performed a meta-analysis to verify the association between the incidences of colorectal liver metastases with chronically diseased livers. METHODS Relevant studies were identified by a search of electronic database PubMed, Cochrane Library, OVID, Web of Science and CNKI (up to February 24, 2014). Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using random- or fixed-effect models when appropriate. Meta-analysis and publication bias (Bgger's test) was evaluated with STATA 12.0. RESULTS A total of 10,349 colorectal cancer patients from 10 studies were included. The meta-analysis result showed there was a significant difference in the incidences of colorectal liver metastases between patients with normal and chronically diseased livers (OR = 0.32; 95% CI 95%: 0.26-0.38, P = 0.000 fixed-effects model). The result of Begg's test (Pr>|z| = 0.089; P>0.05) revealed no publication bias. CONCLUSIONS The results of this meta-analysis demonstrated that patients with chronically diseased livers had significantly lower incidences of colorectal liver metastases than those with normal livers.
Collapse
Affiliation(s)
- Bin Cai
- Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Kai Liao
- Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Xian-qing Song
- Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Wei-yuan Wei
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Yuan Zhuang
- School of preclinical Medicine, Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| | - Sen Zhang
- Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China
| |
Collapse
|
|
43
|
Seishima R, Okabayashi K, Hasegawa H, Sugiyama D, Ishii Y, Tsuruta M, Takebayashi T, Kitagawa Y. Obesity was associated with a decreased postoperative recurrence of rectal cancer in a Japanese population. Surg Today 2014; 44:2324-31. [PMID: 24840399 DOI: 10.1007/s00595-014-0899-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 01/23/2014] [Indexed: 12/25/2022]
Abstract
PURPOSE Obesity contributes to the technical difficulty of rectal surgery and is considered to be a risk factor for postoperative complications. The impact of obesity on the long-term outcomes of rectal cancer surgery remains unclear. METHODS A total of 263 consecutive rectal cancer patients who underwent surgery were categorized into two groups according to the body mass index (BMI) based on the Asian BMI classification: non-obese (BMI <25 kg/m(2)) and obese (BMI ≥25 kg/m(2)). The postoperative survival and recurrence rates and oncological surgical quality indicators were compared between groups using the univariate and multivariate analyses. The differences in recurrence patterns were assessed by a competing risk regression analysis. RESULTS 64 (24%) patients were included in the obese group. The number of retrieved lymph nodes was significantly greater in the non-obese group than in the obese group (22.4 vs. 16.0, P < 0.01). The 5-year disease-free survival (DFS) rates were 86.5 and 68.8% in the obese and non-obese groups, respectively (P = 0.01). The multivariate analysis demonstrated that obesity significantly decreased the postoperative recurrence rate (P = 0.04). Moreover, the BMI was significantly associated with distant metastasis (P = 0.04). CONCLUSIONS Obese rectal cancer patients have high DFS rates and a decreased incidence of distant metastases compared to non-obese patients. The BMI may be a key factor for predicting the postoperative prognosis and determination of an appropriate strategy for the treatment of rectal cancer patients.
Collapse
Affiliation(s)
- Ryo Seishima
- Department of Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 1608582, Japan
| | | | | | | | | | | | | | | |
Collapse
|