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Paramythiotis D, Karlafti E, Tsavdaris D, Apostolidou Kiouti F, Haidich AB, Ioannidis A, Panidis S, Michalopoulos A. The Effect of Hepatic Surgical Margins of Colorectal Liver Metastases on Prognosis: A Systematic Review and Meta-Analysis. J Clin Med 2024; 13:7776. [PMID: 39768699 PMCID: PMC11727772 DOI: 10.3390/jcm13247776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/14/2024] [Accepted: 12/16/2024] [Indexed: 01/16/2025] Open
Abstract
Introduction: Colorectal cancer is the third most common malignancy, with around half of patients developing liver metastases. Hepatectomy is the preferred treatment, but its success depends on several factors, including surgical margins. Various surgical margins have been suggested to achieve optimal results. This systematic review and meta-analysis aim to explore the impact of negative surgical margins ranging from 1 to 10 mm, and >10 mm on survival, with the objective of identifying optimal surgical margins. Methods: A systematic literature search was conducted on the MEDLINE, Scopus, and Cochrane databases. The six included studies that examined the effect of surgical margins at the aforementioned distances on patient survival. Studies were assessed for risk of bias using the Quality in Prognosis Studies tool. Statistical analysis was performed using SPSS software. Results: The results of the meta-analysis revealed the superiority of wider surgical margins (>10) on overall survival compared to smaller margins (1-10 mm), as the HR was calculated to be 1.38 [1.10; 1.73]. Specifically, negative margins between 1 and 10 mm are linked to a 38% increased risk of mortality compared to margins larger than 10 mm. The low heterogeneity indicates consistent findings across studies, and the statistically significant hazard ratio underscores the importance of aiming for larger surgical margins to enhance patient outcomes. In the subgroup that included only studies in which patients received neoadjuvant therapy, the HR was 1.48 [1.06; 2.07], further emphasizing the importance of ensuring negative surgical margins in today's era. Conclusions: In summary, this systematic review and meta-analysis highlights the impact of surgical margin width on the survival of patients with colorectal liver metastases, as well as the importance of margin optimization in surgical management strategies.
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Affiliation(s)
- Daniel Paramythiotis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Eleni Karlafti
- Emergency Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Dimitrios Tsavdaris
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Fani Apostolidou Kiouti
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece (A.-B.H.)
| | - Anna-Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece (A.-B.H.)
| | - Aristeidis Ioannidis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Stavros Panidis
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
| | - Antonios Michalopoulos
- First Propaedeutic Surgery Department, University General Hospital of Thessaloniki AHEPA, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece; (D.P.); (D.T.); (A.I.); (S.P.); (A.M.)
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Miller ED, Klamer BG, Cloyd JM, Pawlik TM, Williams TM, Hitchcock KE, Romesser PB, Mamon HJ, Ng K, Gholami S, Chang GJ, Anker CJ. Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review. Clin Colorectal Cancer 2024; 23:160-173. [PMID: 38365567 DOI: 10.1016/j.clcc.2024.01.004] [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: 11/21/2023] [Revised: 01/11/2024] [Accepted: 01/20/2024] [Indexed: 02/18/2024]
Abstract
BACKGROUND A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.
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Affiliation(s)
- Eric D Miller
- Department of Radiation Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH.
| | - Brett G Klamer
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH
| | - Jordan M Cloyd
- Department of Surgery, Division of Surgical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH
| | | | | | - Paul B Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Harvey J Mamon
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Sepideh Gholami
- Department of Surgery, Division of Surgical Oncology, Northwell Health, New Hyde Park, NY
| | - George J Chang
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Christopher J Anker
- Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, VT
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Marion S, Facchino S, Cheng-Oviedo S, Collin Y. Colorectal cancer hepatic metastases resection margins outcomes: a single-centre retrospective cohort study. Ann Med Surg (Lond) 2023; 85:4694-4702. [PMID: 37811094 PMCID: PMC10553064 DOI: 10.1097/ms9.0000000000001113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 07/17/2023] [Indexed: 10/10/2023] Open
Abstract
Background Surgical resection is the most efficient treatment for isolated colorectal cancer hepatic metastases. Among the known prognostic factors of this procedure, the impact of the resection margin width is still a controversial matter in the literature. Methods A retrospective cohort study was performed including 170 patients who underwent surgical resection of colorectal cancer liver metastases (CRLMs) between 2006 and 2016 in our hepatobiliary unit. Resection margin width was determined histologically by measuring the distance from the tumour in millimetres or centimetres. Patients' clinical characteristics were also collected. Patients were then stratified in two tumour margin groups: below 5 mm (group A) and equal to or above 5 mm (group B). Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. Results Kaplan-Meier curves showed significantly better outcomes for cases having resection margins above 5 mm for both DFS with 1508.7 days (range 1151.2-1866.2) in group A, compared to 2463.9 days (range 2021.3-2906.5) in group B (P=0.049), and OS with 1557.8 days (range 1276.3-1839.3) for group A and 2303.8 days (range 1921.2--2686.4) for group B (P=0.020). This survival benefit was not significant for patients presenting with stage IV CRC at diagnosis or cases where extended (7+ segments) resections were performed. Conclusion Five-millimetre margins provide a significant survival advantage and should be aimed for in the treatment of CRLMs. Further research on the cause for this finding, including tumour biology's impact on survival, is required.
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Affiliation(s)
- Samuel Marion
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
| | - Sabrina Facchino
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Sonia Cheng-Oviedo
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Yves Collin
- Centre intégré universitaire de santé et de services sociaux de l’Estrie – Centre hospitalier universitaire de Sherbrooke (CIUSSE – CHUS)
- Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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Sakamoto K, Beppu T, Ogawa K, Tamura K, Honjo M, Funamizu N, Takada Y. Prognostic Impact of Surgical Margin Width in Hepatectomy for Colorectal Liver Metastasis. J Clin Transl Hepatol 2023; 11:705-717. [PMID: 36969881 PMCID: PMC10037520 DOI: 10.14218/jcth.2022.00383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 10/01/2022] [Accepted: 11/06/2022] [Indexed: 01/19/2023] Open
Abstract
As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20-30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.
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Affiliation(s)
- Katsunori Sakamoto
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Kohei Ogawa
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Kei Tamura
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Masahiko Honjo
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Naotake Funamizu
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
| | - Yasutsugu Takada
- Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Toon Ehime, Japan
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A meta-analysis of short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer. Photodiagnosis Photodyn Ther 2023; 42:103497. [PMID: 36878336 DOI: 10.1016/j.pdpdt.2023.103497] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 02/26/2023] [Accepted: 03/02/2023] [Indexed: 03/07/2023]
Abstract
OBJECTIVES This meta-analysis aimed to compare the short-term and long-term effects of indocyanine green fluorescence imaging in hepatectomy for liver cancer. METHODS The databases PubMed, Embase, Scopus, Cochrane Library, Web of Science, ScienceDirect, and major scientific websites were screened up to January 2023. Randomized controlled trials and observational studies comparing fluorescence navigation-assisted and fluorescence-free navigation-assisted hepatectomy for liver cancer were included. Our meta-analysis comprises overall results and 2 subgroup analyses based on surgery type (laparoscopy and laparotomy). These estimates are presented as mean differences (MD) or odds ratio (OR) estimates with 95% CIs. RESULTS We analyzed 16 studies that included 1260 patients with liver cancer. Our results showed that fluorescent navigation-assisted hepatectomy were significantly more shorter than fluorescence-free navigation-assisted hepatectomy in the following parameters: operative time [MD = -16.19; 95% CI: -32.27 to -0.11; p = 0.050], blood loss [MD = -107.90; 95% CI: -160.46 to -55.35; p < 0.001], blood transfusion [OR = 0.5; 95% CI: 0.35 to 0.72; p = 0.0002], hospital stay [MD = -1.60; 95% CI: -2.33 to -0.87; p < 0.001], and postoperative complications [OR = 0.59; 95% CI: 0.42 to 0.82; p = 0.002], The one-year disease-free survival rate [OR = 2.87; 95% CI: 1.64 to 5.02; p = 0.0002] was higher in the fluorescent navigation-assisted hepatectomy group. CONCLUSIONS Indocyanine green fluorescence imaging has good clinical value and can improve the short-term and long-term results of hepatectomy for liver cancer.
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Zhu HQ, Wang DY, Xu LS, Chen JL, Chu EW, Zhou CJ. Diagnostic value of an enhanced MRI combined with serum CEA, CA19-9, CA125 and CA72-4 in the liver metastasis of colorectal cancer. World J Surg Oncol 2022; 20:401. [PMID: 36529741 PMCID: PMC9762109 DOI: 10.1186/s12957-022-02874-x] [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: 07/14/2022] [Accepted: 12/09/2022] [Indexed: 12/23/2022] Open
Abstract
OBJECTIVE This paper aims to explore the diagnostic value of enhanced magnetic resonance imaging (MRI) combined with a carcinoembryonic antigen (CEA) and carbohydrate antigen in terms of the liver metastasis of colorectal cancer. METHODS A total of 167 colorectal cancer patients with liver metastasis and 167 colorectal cancer patients without liver metastasis were selected as the subjects. An automatic electrochemiluminescence analyser was then used to detect the tumour markers CEA, CA19-9, CA125 and CA72-4. The consistency between the MRI examination and clinical pathological examination was also analysed, and the sensitivity, specificity and positive and negative predictive values of various combined detection methods were compared. RESULTS The abnormal rates of CEA, CA19-9, CA125 and CA72-4 in the two groups were statistically significant (P < 0.05), while the results of the enhanced MRI and clinicopathological examination for liver metastasis in patients with colon cancer were largely consistent (Kappa coefficient = 0.788, P < 0.000). However, the two methods were inconsistent. The false positive rate of the enhanced MRI examination was 15.3%, while the false negative rate was 6.0%. The specificity (94.61%), positive predictive value (92.68%) and positive likelihood ratio (12.67%) were the highest for the MRI combined with serial CEA, while the sensitivity (98.80%) and negative predictive value (97.22%) were the highest with the MRI combined with parallel CEA, and this combination returned the lowest negative likelihood ratio (0.03). CONCLUSION The combination of MRI and CEA excludes non-metastatic patients and identifies colorectal liver metastasis cancer patients. Overall, it has a higher diagnostic value.
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Affiliation(s)
- Hua-Qiang Zhu
- Department of Medical Imaging, University of Chinese Academy of Sciences Shenzhen Hospital (Guangming), No. 4253 of Pine White Rd, Guangming District, Shenzhen, 518106, Guangdong Province, China.
| | - Dong-Ye Wang
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, China
| | - Lin-Shen Xu
- Department of Medical Imaging, University of Chinese Academy of Sciences Shenzhen Hospital (Guangming), No. 4253 of Pine White Rd, Guangming District, Shenzhen, 518106, Guangdong Province, China
| | - Jian-le Chen
- Department of Medical Imaging, University of Chinese Academy of Sciences Shenzhen Hospital (Guangming), No. 4253 of Pine White Rd, Guangming District, Shenzhen, 518106, Guangdong Province, China
| | - Er-Wei Chu
- Department of Medical Imaging, University of Chinese Academy of Sciences Shenzhen Hospital (Guangming), No. 4253 of Pine White Rd, Guangming District, Shenzhen, 518106, Guangdong Province, China
| | - Cai-Jin Zhou
- Department of Medical Imaging, University of Chinese Academy of Sciences Shenzhen Hospital (Guangming), No. 4253 of Pine White Rd, Guangming District, Shenzhen, 518106, Guangdong Province, China
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Silveira Júnior S, Tustumi F, Magalhães DDP, Jeismann VB, Fonseca GM, Kruger JAP, Coelho FF, Herman P. The impact of multivisceral liver resection on short- and long-term outcomes of patients with colorectal liver metastasis: A systematic review and meta-analysis. Clinics (Sao Paulo) 2022; 77:100099. [PMID: 36122500 PMCID: PMC9489954 DOI: 10.1016/j.clinsp.2022.100099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 06/27/2022] [Accepted: 08/16/2022] [Indexed: 11/24/2022] Open
Abstract
The impact of Multivisceral Liver Resection (MLR) on the outcome of patients with Colorectal Liver Metastasis (CRLM) is unclear. The present systematic review aimed to compare patients with CRLM who underwent MLR versus standard hepatectomy regarding short- and long-term outcomes. MLR is a feasible procedure but has a higher risk of major complications. MLR did not negatively affect long-term survival, suggesting that an extended resection is an option for potentially curative treatment for selected patients with CRLM.
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Affiliation(s)
- Sérgio Silveira Júnior
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Francisco Tustumi
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Daniel de Paiva Magalhães
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil.
| | - Vagner Birk Jeismann
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Gilton Marques Fonseca
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Jaime Arthur Pirola Kruger
- Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Fabricio Ferreira Coelho
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
| | - Paulo Herman
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil
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Hu X, Chen Q, Guo H, Li K, Fu B, Chen Y, Zhao H, Wei M, Li Y, Wu H. Identification of Target PTEN-Based miR-425 and miR-576 as Potential Diagnostic and Immunotherapeutic Biomarkers of Colorectal Cancer With Liver Metastasis. Front Oncol 2021; 11:657984. [PMID: 34490081 PMCID: PMC8418231 DOI: 10.3389/fonc.2021.657984] [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: 01/24/2021] [Accepted: 07/28/2021] [Indexed: 12/19/2022] Open
Abstract
A major complication of colorectal cancer (CRC), one of the most common and fatal types of cancers, is secondary liver metastasis. For patients with this fate, there are very few biomarkers available in clinical application, and the disease remains incurable. Recently, increasing studies demonstrated that tumorigenesis and development are closely related to immune escape, indicating that the roles of immune-related indicators might have been neglected in the past in colorectal cancer liver metastases (CRLM). Here, we unveil that elevated miR-425 and miR-576 promote CRLM through inhibiting PTEN-mediated cellular immune function. Specifically, miR-425 and miR-576 were identified for their significant upregulation in CRLM compared with the primary CRC tissues based on GSE81581 (n = 8) and GSE44121 (n = 18) datasets. Besides, we determined that the two microRNAs (miRNAs) coparticipated in restraining P53 and transforming growth factor beta (TGF-β) signaling pathways associated with tumor metastasis, and both shortened the overall survival of the patients with metastatic susceptibility. Notably, in situ hybridization on relatively large samples of paired CRC tissues (n = 157) not only substantiated that the expression of miR-425 and miR-576 was dramatically upregulated in CRLM but also revealed that they were closely related to tumor deterioration, especially liver metastases. Moreover, we further confirmed that the combination of miR-425 and miR-576 was an effective predictive model for liver metastases and poor clinical outcomes. Mechanically, downregulated PTEN (GSE81558, n = 6) was verified to be a shared target of miR-425 and miR-576 acting as metastasis-related oncogenes, on account of the presence of binding sites (+2928-+2934 and +4371-+4378, respectively) and the collaborative suppression of P53/TGF-β signaling in CRLM, which was further confirmed in CRC cells (HCT116 and SW480) based on systematic molecular biology experiments. Importantly, the target PTEN was strongly associated with microsatellite instability, tumor microenvironment, and immune cell infiltration. Thus, we speculate that miR-425 and miR-576 are novel biomarkers for CRLM prevention and immunotherapy and upstream inhibitors of the PTEN-P53/TGF-β function axis.
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Affiliation(s)
- Xiaoyun Hu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Qiuchen Chen
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Hao Guo
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Kuo Li
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Boshi Fu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Yu Chen
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Haishan Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Yalun Li
- Department of Anorectal Surgery, First Hospital of China Medical University, Shenyang, China
| | - Huizhe Wu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
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Zhang Y, Ge L, Weng J, Tuo WY, Liu B, Ma SX, Yang KH, Cai H. Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis. World J Clin Cases 2021; 9:6357-6379. [PMID: 34435001 PMCID: PMC8362587 DOI: 10.12998/wjcc.v9.i22.6357] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 04/14/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In recent years, neoadjuvant chemotherapy (NAC) has been increasingly used in patients with resectable colorectal liver metastases. However, the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases (CRLM) are still controversial.
AIM To assess the efficacy and application value of NAC in patients with resectable CRLM.
METHODS We searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC. Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.
RESULTS In total, 32 studies involving 11236 patients were included in this analysis. We divided the patients into two groups, the NAC group (that received neoadjuvant chemotherapy) and the non-NAC group (that received no neoadjuvant chemotherapy). The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) were HR = 0.49, 95%CI: 0.39-0.61, P = 0.000 and HR = 0.48 95%CI: 0.36-0.63, P = 0.000. The duration of surgery in the NAC group was longer than that of the non-NAC group [standardized mean difference (SMD) = 0.41, 95%CI: 0.01-0.82, P = 0.044)]. The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group (SMD = 0.73, 95%CI: 0.02-1.43, P = 0.043). The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group (SMD = 1.24, 95%CI: 1.07-1.43, P = 0.004).
CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM. At the same time, the NAC group did not increase the risk of any adverse event compared to the non-NAC group.
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Affiliation(s)
- Yue Zhang
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Long Ge
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jun Weng
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Wen-Yu Tuo
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Bin Liu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Shi-Xun Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Ke-Hu Yang
- Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
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Wang HW, Wang LJ, Jin KM, Bao Q, Li J, Wang K, Xing BC. The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis. J Surg Oncol 2021; 124:619-626. [PMID: 34081792 DOI: 10.1002/jso.26557] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 04/20/2021] [Accepted: 05/16/2021] [Indexed: 11/11/2022]
Abstract
BACKGROUND Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score. METHODS R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0-3) and high-risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence-free survival rate (RFS) were examined. RESULTS In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection. CONCLUSION The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.
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Affiliation(s)
- Hong-Wei Wang
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Li-Jun Wang
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Ke-Min Jin
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Quan Bao
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Juan Li
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Kun Wang
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
| | - Bao-Cai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, Beijing Cancer Hospital and Institute, Ministry of Education, Peking University School of Oncology, Beijing, China
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11
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Protic M, Krsmanovic O, Solajic N, Kukic B, Nikolic I, Bogdanovic B, Radovanovic Z, Kresoja M, Mannion C, Man YG, Stojadinovic A. Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases. J Cancer 2021; 12:3701-3714. [PMID: 33995645 PMCID: PMC8120181 DOI: 10.7150/jca.58580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 04/19/2021] [Indexed: 01/10/2023] Open
Abstract
Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a “gold standard”. RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the “gold standard”, it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.
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Affiliation(s)
- Mladjan Protic
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Olivera Krsmanovic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Armed Forces of Bosnia and Herzegovina, Logistics Command, Doboj, Bosnia and Herzegovina
| | - Nenad Solajic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Department of Pathoanatomical and Laboratory Diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Biljana Kukic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Ivan Nikolic
- Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.,Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Bogdan Bogdanovic
- Clinic for Internal Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Zoran Radovanovic
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Milana Kresoja
- Clinic for Surgical Oncology, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia.,Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
| | - Ciaran Mannion
- Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA.,Department of Pathology, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA
| | - Yan-Gao Man
- Department of Pathology, Hackensack University Medical Center, Hackensack, New Jersey, USA
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12
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Casadei R, Ricci C, Selva S, Minni F. Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches. World J Gastroenterol 2020; 26:6529-6555. [PMID: 33268945 PMCID: PMC7673966 DOI: 10.3748/wjg.v26.i42.6529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.
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Affiliation(s)
- Emilio De Raffele
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Mariateresa Mirarchi
- Dipartimento Strutturale Chirurgico, Ospedale SS Antonio e Margherita, 15057 Tortona (AL), Italy
| | - Dajana Cuicchi
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Ferdinando Lecce
- Surgery of the Alimentary Tract, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Riccardo Casadei
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Claudio Ricci
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
| | - Saverio Selva
- Division of Pancreatic Surgery, Department of Digestive Diseases, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, 40138 Bologna, Italy
| | - Francesco Minni
- Division of Pancreatic Surgery, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, 40138 Bologna, Italy
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13
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Indocyanine green fluorescence navigation in laparoscopic hepatectomy: a retrospective single-center study of 120 cases. Surg Today 2020; 51:695-702. [PMID: 33128594 PMCID: PMC8055570 DOI: 10.1007/s00595-020-02163-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/18/2020] [Indexed: 02/07/2023]
Abstract
Purpose To explore the role of indocyanine green (ICG) fluorescence navigation in laparoscopic hepatectomy and investigate if the timing of its administration influences the intraoperative observation. Methods The subjects of this retrospective study were 120 patients who underwent laparoscopic hepatectomy; divided into an ICG-FN group (n = 57) and a non-ICG-FN group (n = 63). We analyzed the baseline data and operative data. Results There were no remarkable differences in baseline data such as demographic characteristics, lesion-related characteristics, and liver function parameters between the groups. Operative time and intraoperative blood loss were significantly lower in the ICG-FN group. The rate of R0 resection of malignant tumors was comparable in the ICG-FN and non-ICG-FN groups, but the wide surgical margin rate was significantly higher in the ICG-FN group. The administration of ICG 0–3 or 4–7 days preoperatively did not affect the intraoperative fluorescence imaging. Operative time, intraoperative blood loss, and a wide surgical margin correlated with ICG fluorescence navigation. ICG fluorescence navigation helped to minimize intraoperative blood loss and achieve a wide surgical margin. Conclusion ICG fluorescence navigation is safe and efficient in laparoscopic hepatectomy. It helps to achieve a wide surgical margin, which could result in a better prognosis. The administration of ICG 0–3 days preoperatively is acceptable. Electronic supplementary material The online version of this article (10.1007/s00595-020-02163-8) contains supplementary material, which is available to authorized users.
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14
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Matteo B, Gaetano P, Delfina T, Riccardo M, Roberto S, Guglielmo P, Claudia C, Carmelo L, Carla C, Daris F, Maria IA, Gaetano B, Carrafiello G, Enrico O. Immunohistochemical evaluation of microsatellite instability in resected colorectal liver metastases: a preliminary experience. Med Oncol 2020; 37:63. [PMID: 32556620 DOI: 10.1007/s12032-020-01388-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 06/06/2020] [Indexed: 12/30/2022]
Abstract
In this retrospective study, we evaluated the predictive role of different immunohistochemical expression (IHC) of the mismatch repair proteins (MMR) in patients with colorectal liver metastasis (CRLM) submitted to liver resection. A total of 108 patients were retrieved, and 15 patients were excluded from the study because of the impossibility to obtain adequate formalin-fixed tissue blocks. The final analysis included 93 patients. Twenty-eight cases (30%) presented a no loss of expression or microsatellite stability (MSS) status, 59 cases (63%) showed a hybrid loss of expression, while 6 cases (7%) presented a complete loss of expression or microsatellite instability status (MSI). Patients with complete or hybrid loss of expression of MMR developed a high intra-hepatic recurrence rate compared to other ones (54% vs 21% OR of 4.278, 95% CI 1.53-11.93) (p = 0.004). The same difference in terms of liver recurrence has been found among patients with R0 resection (50% vs 17% OR of 0.2, 95% CI 0.06-0.65) (p = 0.005). However, there was no difference in terms of disease-free survival and overall survival. Complete or hybrid loss of expression of MMR could be considered a risk factor for intra-hepatic recurrences after liver resections for CRLM.
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Affiliation(s)
- Barabino Matteo
- Hepatobiliary Surgery Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
| | - Piccolo Gaetano
- Hepatobiliary Surgery Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Tosi Delfina
- Pathology Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Masserano Riccardo
- Hepatobiliary Surgery Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | | | - Piozzi Guglielmo
- Hepatobiliary Surgery Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Cigala Claudia
- Pathology Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Luigiano Carmelo
- Digestive Endoscopy Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Codecà Carla
- Division of Oncology, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Ferrari Daris
- Division of Oncology, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Ierardi Anna Maria
- Radiology Unit, IRCCS Ca' Granda Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Bulfamante Gaetano
- Pathology Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
| | - Gianpaolo Carrafiello
- Radiology Unit, IRCCS Ca' Granda Foundation, Policlinico Hospital, University of Milan, Milan, Italy
| | - Opocher Enrico
- Hepatobiliary Surgery Unit, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy
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15
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Greenbaum LE, Ukomadu C, Tchorz JS. Clinical translation of liver regeneration therapies: A conceptual road map. Biochem Pharmacol 2020; 175:113847. [PMID: 32035080 DOI: 10.1016/j.bcp.2020.113847] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 02/04/2020] [Indexed: 02/07/2023]
Abstract
The increasing incidence of severe liver diseases worldwide has resulted in a high demand for curative liver transplantation. Unfortunately, the need for transplants by far eclipses the availability of suitable grafts leaving many waitlisted patients to face liver failure and often death. Routine use of smaller grafts (for example left lobes, split livers) from living or deceased donors could increase the number of life-saving transplants but is often limited by the graft versus recipient weight ratio defining the safety margins that minimize the risk of small for size syndrome (SFSS). SFSS is a severe complication characterized by failure of a small liver graft to regenerate and occurs when a donor graft is insufficient to meet the metabolic demand of the recipient, leading to liver failure as a result of insufficient liver mass. SFSS is not limited to transplantation but can also occur in the setting of hepatic surgical resections, where life-saving large resections of tumors may be limited by concerns of post-surgical liver failure. There are, as yet no available pro-regenerative therapies to enable liver regrowth and thus prevent SFSS. However, there is optimism around targeting factors and pathways that have been identified as regulators of liver regeneration to induce regrowth in vivo and ex vivo for clinical use. In this commentary, we propose a roadmap for developing such pro-regenerative therapy and for bringing it into the clinic. We summarize the clinical indications, preclinical models, pro-regenerative pathways and safety considerations necessary for developing such a drug.
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Affiliation(s)
- Linda E Greenbaum
- Novartis Institutes for Biomedical Research, Novartis Pharma AG, East Hanover, NJ, United States.
| | - Chinweike Ukomadu
- Novartis Institutes for BioMedical Research, Novartis Pharma AG, Cambridge, MA, United States.
| | - Jan S Tchorz
- Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland.
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16
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Zhang H, Wang R, Wang M. miR-331-3p suppresses cell invasion and migration in colorectal carcinoma by directly targeting NRP2. Oncol Lett 2019; 18:6501-6508. [PMID: 31807170 PMCID: PMC6876315 DOI: 10.3892/ol.2019.11029] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 07/30/2019] [Indexed: 12/21/2022] Open
Abstract
Colorectal carcinoma (CRC) is a common tumor of the digestive system with poor prognosis. Studies have shown that aberrant microRNA (miRNA) expression can affect CRC progression by regulating target genes. In the present study, we investigated the functional roles and potential mechanisms of miR-331-3p in CRC. The expression of miR-331-3p and neuropilin-2 (NRP2) in CRC was detected by RT-qPCR. Then, Transwell assays were conducted to investigate the influence of miR-331-3p on CRC cell invasion and migration abilities. Luciferase reporter assays were performed to determine the target gene of miR-331-3p. It was found that miR-331-3p expression was notably declined in CRC and inversely correlated with the NRP2 expression. miR-331-3p upregulation significantly inhibited CRC cell invasion and migration. Additionally, western blot analysis demonstrated that miR-331-3p restoration evidently suppressed CRC cell EMT. Moreover, NRP2 was conformed to be a novel target of miR-331-3p and knockdown of NRP2 partially inversed the effects of the miR-331-3p inhibitor on cell invasion and migration. These results suggested that miR-331-3p exerted tumor suppressive roles in CRC by targeting NRP2 and miR-331-3p/NRP2 may serve as a potential therapy for CRC.
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Affiliation(s)
- Hongye Zhang
- Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| | - Ruiyu Wang
- Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
| | - Mingxia Wang
- Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
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17
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Pencovich N, Houli R, Lubezky N, Goykhman Y, Nakache R, Klausner JM, Nachmany I. R1 resection of colorectal liver metastasis - What is the cost of marginal resection? J Surg Oncol 2018; 119:347-354. [PMID: 30548552 DOI: 10.1002/jso.25321] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/13/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection. METHODS Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed. RESULTS In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P < 0.001), increased use of preoperative volume manipulation (14.6% vs 5.5%, P = 0.001), and inferior vena-cava involvement (21.9% vs 8.7%, P < 0.001). These patients had higher rates of major postoperative complications (19.5% vs 6.8%, P < 0.001) and reoperations (7.3% vs 2.4%, P < 0.001). Multivariate analysis demonstrated that R1 resections were not associated with decreased recurrence-free survival or overall survival. CONCLUSIONS Although R1 resection is associated with worse disease behavior and postoperative complications, the long-term outcome of patients following an R1 resection is non-inferior to those who underwent an R0 resection.
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Affiliation(s)
- Niv Pencovich
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Rotem Houli
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Nir Lubezky
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Yaacov Goykhman
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Richard Nakache
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Joseph M Klausner
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Ido Nachmany
- Department of General Surgery B, Division of Surgery, Tel-Aviv Sourasky Medical Center, The Nikolas & Elizabeth Shlezak Fund for Experimental Surgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Margonis GA, Buettner S, Andreatos N, Wagner D, Sasaki K, Galjart B, Kamphues C, Pawlik TM, Poultsides G, Kaczirek K, Lønning PE, Verhoef C, Kreis ME, Wolfgang CL, Weiss MJ. The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis. J Surg Oncol 2018; 118:1074-1080. [PMID: 30261094 DOI: 10.1002/jso.25251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/01/2018] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVES In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)-related CRLM have not been studied to date. METHODS Patients who underwent resection for IBD-related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic variables. Overall survival (OS) and recurrence-free survival (RFS) were subsequently assessed. RESULTS Twenty-eight patients had IBD-related CRLM. Synchronous extrahepatic disease was more common in IBD-related CRLM patients than patients with sporadic CRLM (28.6% vs 8.3%; P < 0.001), most commonly located in the lungs. In multivariable analysis, IBD did not have a significant influence on OS ( P = 0.835), and had a hazard ratio (HR) close to 1 (HR, 0.95; 95% confidence interval [CI], 0.57-1.57). IBD was also not associated with inferior RFS (HR, 1.07; 95%CI, 0.68-1.68; P = 0.780). Among patients with IBD-related CRLM, 9(50%) had isolated intrahepatic recurrence and 8(44.4%) isolated extrahepatic recurrence, while only 1(5.6%) developed combined recurrence. Of those who experienced recurrence after resection of IBD-related CRLM, 10 had their recurrence treated with curative intent. CONCLUSIONS Patients with IBD-related CRLM had similar survival compared with patients with sporadic CRLM, even though they more often present with extrahepatic disease. In addition, patients with IBD-related CRLM may experience patterns of recurrence different from patients with sporadic CRLM.
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Affiliation(s)
- Georgios Antonios Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Stefan Buettner
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Doris Wagner
- Department of General Surgery, Medical University of Graz, Graz, Austria
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Boris Galjart
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Carsten Kamphues
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - George Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Klaus Kaczirek
- Department of General Surgery, Medical University of Vienna, Vienna, Austria
| | - Per Eystein Lønning
- Department of Clinical Science, University of Bergen, Bergen, Norway
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - Cornelis Verhoef
- Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - Martin E Kreis
- Department of General, Visceral and Vascular Surgery, Charite Campus Benjamin Franklin, Berlin, Germany
| | | | - Matthew J Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Oshi M, Margonis GA, Sawada Y, Andreatos N, He J, Kumamoto T, Morioka D, Wolfgang CL, Tanaka K, Weiss MJ, Endo I. Higher Tumor Burden Neutralizes Negative Margin Status in Hepatectomy for Colorectal Cancer Liver Metastasis. Ann Surg Oncol 2018; 26:593-603. [PMID: 30483976 DOI: 10.1245/s10434-018-6830-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection is difficult. METHODS Clinicopathological variables in an exploration cohort of 290 patients receiving hepatectomy in Japan for CRLM were investigated. R0 resection was defined as a margin width > 0 mm. Tumor burden was assessed using the recently introduced Tumor Burden Score (TBS), which was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. The principal findings were validated using a cohort from the United States. RESULTS R1 resection rates significantly increased as TBS increased: 4/86 (4.7%) in patients with TBS < 3, 29/171 (17.0%) in patients with TBS ≥ 3 and < 9, and 9/33 (27.3%) in patients with TBS ≥ 9 (p < 0.001). R0 resection was significantly superior to R1 resection in patients with TBS ≥ 5; however, this was not the case for TBS ≥ 6, as confirmed by both univariate and multivariate analyses. Furthermore, prehepatectomy chemotherapy was associated with significantly improved survival for patients with TBS ≥ 8. Analysis of the validation cohort yielded similar results. CONCLUSIONS R0 resection appeared to have a positive impact on prognosis among patients with low tumor burden; however, this was not the case for patients with high tumor burden. As such, systemic treatment, in addition to surgery, may be central to achieving satisfactory outcomes in the latter patient population.
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Affiliation(s)
- Masanori Oshi
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Yu Sawada
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nikolaos Andreatos
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Takafumi Kumamoto
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Daisuke Morioka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | | | - Kuniya Tanaka
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Matthew John Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
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Association Between Surgical Margin Status and Local Recurrence in Iranian Patients Suffering from Colorectal Cancer. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2018. [DOI: 10.5812/ijcm.83029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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De Raffele E, Mirarchi M, Cuicchi D, Lecce F, Ricci C, Casadei R, Cola B, Minni F. Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases. World J Gastrointest Oncol 2018; 10:293-316. [PMID: 30364774 PMCID: PMC6198303 DOI: 10.4251/wjgo.v10.i10.293] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Revised: 07/28/2018] [Accepted: 08/21/2018] [Indexed: 02/05/2023] Open
Abstract
Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.
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Affiliation(s)
- Emilio De Raffele
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Mariateresa Mirarchi
- U.O. di Chirurgia Generale, Dipartimento Strutturale Chirurgico, Ospedale “Antonio e Margherita, ” Tortona (AL) 15057, Italy
| | - Dajana Cuicchi
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Ferdinando Lecce
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Claudio Ricci
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Riccardo Casadei
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
| | - Bruno Cola
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), Alma Mater Studiorum, Policlinico S.Orsola-Malpighi, University of Bologna, Bologna 40138, Italy
| | - Francesco Minni
- Unità Operativa di Chirurgia Generale, Dipartimento dell’Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna 40138, Italy
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The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases. J Gastrointest Surg 2018; 22:1350-1357. [PMID: 29633114 DOI: 10.1007/s11605-018-3748-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Accepted: 03/15/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width = 0 mm) or a margin width < 1 mm. Consequently, patients with a margin width of 0-1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins. METHODS Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin. RESULTS Five hundred thirty-nine (85.2%) patients had a margin width ≥ 1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥ 1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P = 0.03) or an involved margin (65 vs. 33 months; P < 0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P = 0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04-2.67; P = 0.04, and HR 2.14, 1.46-3.16; P < 0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41-2.65; P < 0.001). CONCLUSIONS Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width > 1 mm. Consequently, a uniform definition of R1 as a margin width < 1 mm should perhaps be employed by future studies.
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Berardi G, De Man M, Laurent S, Smeets P, Tomassini F, Ariotti R, Hoorens A, van Dorpe J, Varin O, Geboes K, Troisi RI. Radiologic and pathologic response to neoadjuvant chemotherapy predicts survival in patients undergoing the liver-first approach for synchronous colorectal liver metastases. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2018; 44:1069-1077. [PMID: 29615295 DOI: 10.1016/j.ejso.2018.03.008] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/26/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate the short- and long-term outcomes of liver first approach (LFA) in patients with synchronous colorectal liver metastases (CRLM), evaluating the predictive factors of survival. METHODS Sixty-two out of 301 patients presenting with synchronous CRLM underwent LFA between 2007 and 2016. All patients underwent neoadjuvant chemotherapy. After neoadjuvant treatment patients were re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). Liver resection was scheduled after 4-6 weeks. Changes in non-tumoral parenchyma and the tumor response according to the Tumor Regression Grade score (TRG) were assessed on surgical specimens. Primary tumor resection was scheduled 4-8 weeks following hepatectomy. RESULTS Five patients out of 62 (8.1%) showed "Progressive Disease" at re-evaluation after neoadjuvant chemotherapy, 22 (35.5%) showed "Stable Disease" and 35 (56.5%) "Partial Response"; of these latter, 29 (82%) showed histopathologic downstaging. The 5-year survival (OS) rate was 55%, while the 5-year disease-free survival (DFS) rate was 16%. RECIST criteria, T-stage, N-stage and TRG were independently associated with OS. Bilobar presentation of disease, RECIST criteria, R1 margin and TRG were independently associated with DFS. Patients with response to neoadjuvant chemotherapy had better survival than those with stable or progressive disease (radiological response 5-y OS: 65% vs. 50%; 5-y DFS: 20% vs. 10%; pathological response 5-y OS: 75% vs. 56%; 5-y DFS: 45% vs. 11%). CONCLUSIONS LFA is an oncologically safe strategy. Selection is a critical point, and the best results in terms of OS and DFS are observed in patients having radiological and pathological response to neoadjuvant chemotherapy.
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Affiliation(s)
- Giammauro Berardi
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Marc De Man
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Stéphanie Laurent
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Peter Smeets
- Dept. of Radiology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Federico Tomassini
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Riccardo Ariotti
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium
| | - Anne Hoorens
- Dept. of Pathology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Jo van Dorpe
- Dept. of Pathology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Oswald Varin
- Dept. of Gastroenterology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Karen Geboes
- Dept. of Oncology, Ghent University Hospital and Medical School, Ghent, Belgium
| | - Roberto I Troisi
- Dept. of General Hepatobiliary and Liver Transplantation Surgery, Ghent University Hospital and Medical School, C. Heymanslaan 10, Ghent 9000, Belgium; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
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Prominent Information of jN3 Positive in Stage III Colorectal Cancer Removed by D3 Dissection: Retrospective Analysis of 6866 Patients From a Multi-institutional Database in Japan. Dis Colon Rectum 2018. [PMID: 29521826 DOI: 10.1097/dcr.0000000000001009] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND The presence of main or lateral lymph node metastasis in colorectal cancer is classified as jN3 by the Japanese Society for Cancer of the Colon and Rectum. Whether information on jN3 status adds value to the TNM classification remains unclear. OBJECTIVE We aimed to assess the prognostic relevance of colorectal cancer nodal staging through the Japanese jN3 categorization compared with that through TNM. DESIGN This was a retrospective study. SETTING The study used the multi-institutional database of the Japanese Society for Cancer of the Colon and Rectum. PATIENTS Clinical and pathological data of 6866 patients with histologically proven stage III colorectal cancer who underwent curative surgery (R0) with D3 dissection between 1995 and 2006 were derived from the database. MAIN OUTCOME MEASURES We investigated the prognostic significance of jN3 status in each TNM N class (N1/N2a/N2b) and stage (IIIA/IIIB/IIIC) based on cancer-specific survival. RESULTS Comparison of cancer-specific survival rates revealed significant differences between jN3+ and jN3- colorectal cancer patient groups according to the TNM N status (5-year cancer-specific survival; N1, 70.4% (jN3+) vs 85.5% (jN3-), p < 0.001; N2a, 59.2% vs 77.0%, p < 0.001; N2b, 39.2% vs 68.7%, p < 0.001) and the TNM stage (stage IIIA, 72.5% vs 94.9%, p < 0.001; stage IIIB, 67.9% vs 84.0%, p < 0.001; stage IIIC, 42.4% vs 70.6%, p < 0.001). LIMITATIONS This study was limited by its retrospective nature. CONCLUSIONS Assessment and inclusion of jN3 status are of clinical importance for patients with stage III colorectal cancer with D3 dissection, because it contributes to improved understanding of recurrence risk and subsequent decision-making for follow-up procedures and adjuvant therapy. See Video Abstract at http://links.lww.com/DCR/A506.
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Memeo R, de Blasi V, Adam R, Goéré D, Piardi T, Lermite E, Turrini O, Navarro F, de'Angelis N, Cunha AS, Pessaux P. Margin Status is Still an Important Prognostic Factor in Hepatectomies for Colorectal Liver Metastases: A Propensity Score Matching Analysis. World J Surg 2018; 42:892-901. [PMID: 28929341 DOI: 10.1007/s00268-017-4229-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The width of resection margin is still a matter of debate in case of colorectal liver metastasis resection. The aim of this study was to determine the risk factors for R1 resection. Once risk factors had been identified, patients were matched according to Fong's prognostic criteria, in order to evaluate whether R1 resection still remained a negative prognostic factor impacting overall and disease-free survival. METHODS A total of 1784 hepatectomies were analyzed from a multicentric retrospective cohort of hepatectomies. Patients were compared before and after a 1:1 propensity score analysis in order to compare R0 versus R1 resections according to Fong criteria. RESULTS Primary tumor nodes found positive after colorectal resection (RR = 1.20, p = 0.02), operative time (> 240 min) (RR = 1.26, p = 0.05), synchronous liver metastasis (RR = 1.27, p = 0.02), pedicle clamping (> 40 min) (RR = 1.52, p = 0.001), lesion size larger than 50 mm (RR = 1.54, p = 0.001), rehepatectomy (RR = 1.68, p = 0.001), more than 3 lesions (RR = 1.69, p = 0.0001), and bilateral lesions (RR = 1.74, p = 0.0001) were identified as risk factors in multivariate analysis. After a 1:1 PSM according to Fong criteria, R1 resection still remained a negative prognostic factor impacting overall and disease-free survival, with 1-, 3-, 5-year OS at 94, 81, and 70% in R0 and 92, 75, and 58% in R1, respectively, (p = 0.008), and disease-free survival (DFS) with 1-, 3-, 5-year survival at 64, 41, and 28% in R0 versus 51, 28, and 18% in R1 (p = 0.0002), respectively. CONCLUSION Even after using PSM as an oncological prognostic criterion, R1 resection still impacts overall and disease-free survival negatively.
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Affiliation(s)
- Riccardo Memeo
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Vito de Blasi
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France
| | - Rene Adam
- Department of Surgery, Hôpital Paul Brousse, Villejuif, France
| | - Diane Goéré
- Department of Surgery, Institut Gustave Roussy, Villejuif, France
| | - Tullio Piardi
- Department of Surgery, Hôpital Robert Debré, Reims, France
| | | | - Olivier Turrini
- Department of Surgery, Institut Paoli-Calmettes, Marseilles, France
| | - Francis Navarro
- Department of Digestive Surgery, Université de Montpellier, Hôpital Saint-Eloi, Montpellier, France
| | | | | | - Patrick Pessaux
- Institut Hospitalo-Universitaire (IHU), Institute for Minimally Invasive Hybrid Image-Guided Surgery, Université de Strasbourg, Strasbourg, France.
- Institut de Recherche Contre les Cancers de l'Appareil Digestif (IRCAD), Strasbourg, France.
- General, Digestive, and Endocrine Surgery, Nouvel Hôpital Civil, Strasbourg, France.
- HepatoBiliary and Pancreatic Surgery Department, 1, place de l'Hôpital, 67091, Strasbourg, France.
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Prognostic Significance of Surgical Margin Size After Neoadjuvant FOLFOX and/or FOLFIRI for Colorectal Liver Metastases. J Gastrointest Surg 2017; 21:1831-1840. [PMID: 28884391 DOI: 10.1007/s11605-017-3557-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 08/18/2017] [Indexed: 02/08/2023]
Abstract
PURPOSE Optimal margin size when resecting colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin size in patients who received neoadjuvant FOLFOX and/or FOLFIRI prior to resection of CRLM. METHODS Clinicopathologic factors were collected for patients who underwent curative liver resections for CRLM between 4/2004-1/2016 and received neoadjuvant oxaliplatin and/or irinotecan and 5-FU (FOLFOX, FOLFIRI). Margins were categorized as < 1, ≥ 1-< 5, ≥ 5-< 10, or ≥ 10 mm and evaluated for association with overall survival (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (< 1 mm) or negative (≥ 1 mm) and similarly evaluated. RESULTS Of 227 patients, the median age was 58 years and most had synchronous (80%) lesions. The majority had colon cancers (75%). Margin sizes were 13% < 1 mm, 27% ≥ 1-< 5 mm, 23% ≥ 5-< 10 mm, 36% ≥ 10 mm. Most (63%) received chemotherapy post-liver resection. Five-year OS and DFS were 54% (95% CI 46-62%) and 22% (95% CI 16-28%), respectively. Positive margins significantly increased the risk of death without post-liver resection chemotherapy (HR = 3.32, p = 0.0077), but not with post-liver resection chemotherapy (HR = 1.00, p = 0.99). Negative margin sizes of ≥ 1-< 5, ≥ 5-< 10, and ≥ 10 mm were not significant predictors of OS (p > 0.05). CONCLUSION Patients undergoing liver resection for CRLM should receive post-resection chemotherapy if negative margins (≥ 1 mm) cannot be achieved. For patients receiving FOLFOX and/or FOLFIRI chemotherapy, wider margins did not improve OS.
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Strowitzki MJ, Schmidt T, Keppler U, Ritter AS, Mahmoud S, Klose J, Mihaljevic AL, Schneider M, Büchler MW, Ulrich AB. Influence of neoadjuvant chemotherapy on resection of primary colorectal liver metastases: A propensity score analysis. J Surg Oncol 2017; 116:149-158. [PMID: 28409832 DOI: 10.1002/jso.24631] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 03/07/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND OBJECTIVES There is ongoing debate about whether patients planned for liver resection of colorectal liver metastases (CRLM) benefit from neoadjuvant chemotherapy (NC). Therefore, we performed a retrospective survival analysis of patients with and without NC prior to surgery. METHODS Data prospectively collected from 468 consecutive patients were analyzed in a retrospective design. We performed a survival analysis and added propensity score matching (PSM). Univariate and multivariate analysis was performed to determine independent prognostic risk factors. RESULTS NC was performed in 145/468 patients. NC did not have a significant influence on overall survival (OS) either before or after PSM. Patients receiving NC showed increased complication rates, especially concerning non-surgical complications after primary resection (P = 0.025) of CRLM. Multivariate analysis before and after PSM revealed that the Memorial Sloan Kettering Cancer Center (MSKCC) score and CEA values are strong predictors for OS in patients with CRLM. CONCLUSIONS NC was not associated with increased OS in patients suffering from CRLM. Additionally, potentially harmful chemotherapy prior to surgery increases the risk of postoperative complications in these patients.
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Affiliation(s)
- Moritz J Strowitzki
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Ulrich Keppler
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Alina S Ritter
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Sarah Mahmoud
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Johannes Klose
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - André L Mihaljevic
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
| | - Alexis B Ulrich
- Department of General, Visceral, and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
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Lee-Ying R, Bernard B, Gresham G, Chen L, Speers C, Kennecke HF, Lim HJ, Cheung WY, Renouf DJ. A Comparison of Survival by Site of Metastatic Resection in Metastatic Colorectal Cancer. Clin Colorectal Cancer 2016; 16:e23-e28. [PMID: 27637559 DOI: 10.1016/j.clcc.2016.07.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 07/19/2016] [Accepted: 07/28/2016] [Indexed: 12/24/2022]
Abstract
BACKGROUND Metastatic resection (MR) of liver-limited disease is an effective therapy for selected patients with metastatic colorectal cancer (mCRC). Despite limited data, this approach has been expanded to include MR of other sites, such as the lung, locoregional, and other distant disease (ODD). We performed a population-based study of patients with mCRC who had undergone MR and compared survival between MR of the liver and MR of other sites. METHODS Patients with mCRC who were referred to the British Columbia Cancer Agency between 1995 and 2010 were reviewed. Patients were included if they had an R0 MR with a negative margin and no residual disease. The site of MR was classified according to collaborative staging criteria as liver, lung, locoregional, or ODD. Median overall survival (mOS) was assessed with Kaplan-Meier methods and compared using the log-rank test. A Cox proportional-hazards model was used to compare mOS, while adjusting for known prognostic factors. RESULTS A total of 2082 patients with mCRC were identified, of whom 257 underwent R0 MR. Sites of MR included liver (65%), lung (16%), locoregional (5%), and ODD (14%). The mOS of liver, lung, locoregional, and ODD were 48.0, 42.8, 37.2, and 26.2 months, respectively (P = .087). On multivariate analysis, only MR of ODD had a significantly different survival estimate than MR of the liver (hazard ratio, 1.78; 95% confidence interval, 1.13-2.80; P = .012). CONCLUSIONS Patients with limited lung and locoregional disease seem to have a comparable survival advantage from MR as patients with liver-limited metastases.
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Affiliation(s)
- Richard Lee-Ying
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Brandon Bernard
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Gillian Gresham
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Leo Chen
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Caroline Speers
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Hagen F Kennecke
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Howard John Lim
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Winson Y Cheung
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada
| | - Daniel John Renouf
- Division of Medical Oncology, University of British Columbia, British Columbia Cancer Agency, Vancouver, Canada.
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29
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Li MX, Bi XY, Li ZY, Huang Z, Han Y, Zhao JJ, Zhao H, Cai JQ. Impaction of surgical margin status on the survival outcome after surgical resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Surg Res 2016; 203:163-73. [PMID: 27338547 DOI: 10.1016/j.jss.2016.02.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 02/03/2016] [Accepted: 02/11/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. MATERIALS AND METHODS We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. RESULTS A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542-2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030-4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. CONCLUSIONS Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized.
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Affiliation(s)
- Mu-Xing Li
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Xin-Yu Bi
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Zhi-Yu Li
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Zhen Huang
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Yue Han
- Department of Radiofrequency Ablation, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Jian-Jun Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China
| | - Hong Zhao
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China.
| | - Jian-Qiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, P. R. China.
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