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Gharib E, Robichaud GA. From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies. Int J Mol Sci 2024; 25:9463. [PMID: 39273409 PMCID: PMC11395697 DOI: 10.3390/ijms25179463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 08/19/2024] [Accepted: 08/24/2024] [Indexed: 09/15/2024] Open
Abstract
Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma-carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications.
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Affiliation(s)
- Ehsan Gharib
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
| | - Gilles A Robichaud
- Département de Chimie et Biochimie, Université de Moncton, Moncton, NB E1A 3E9, Canada
- Atlantic Cancer Research Institute, Moncton, NB E1C 8X3, Canada
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Sönmez MR, Tuncay E, Aydin İC, Bezir N, Torun M, Uzun O, Gülmez S, Polat E, Duman M. Prognostic importance of preoperative albumin-to-alkaline phosphatase ratio in colorectal cancer patients. POLISH JOURNAL OF SURGERY 2024; 96:31-37. [PMID: 39465637 DOI: 10.5604/01.3001.0054.7078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
<b>Introduction:</b> Colorectal cancer (CRC) prognosis is typically determined based on clinical stage and histopathological findings, yet patients with the same stage and histological structure can exhibit varying survival outcomes. This highlights the need for additional prognostic biomarkers. Serum biomarkers are gaining increasing significance due to their affordability and accessibility. The albumin-alkaline phosphatase ratio (AAPR) has been associated with prognosis in hepatocellular and gastric cancers, but its role in CRC remains underexplored.<b>Aim:</b> This study aimed to evaluate the effect of the albumin-alkaline phosphatase ratio (AAPR) on the prognosis of patients with colorectal cancer (CRC).<b>Material and method:</b> Data from 358 patients who had undergone surgery for CRC were analyzed retrospectively to identify factors that could predict overall survival (OS). The Roc-Curve test was applied to determine the power of the preoperative AAPR in predicting mortality. Kaplan Meier and log-rank tests were used to examine the survival times of the patients.<b>Results:</b> Our findings revealed that an albumin-alkaline phosphatase cut-off ratio above 0.67 predicted mortality with a sensitivity of 17.54% and a specificity of 92.22%. Although patients with a lower AAPR exhibited a slightly shorter mean survival time compared to those above the cut-off value, this difference did not reach statistical significance (P = .112).<b>Conclusions:</b> The results of this study did not provide evidence to support the AAPR as a potential prognostic factor in patients with colorectal cancer.
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Affiliation(s)
- Mehmet Reşit Sönmez
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
| | - Elif Tuncay
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
| | - İsa Caner Aydin
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
| | - Nurdan Bezir
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
| | - Mehmet Torun
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
| | - Orhan Uzun
- Department of Gastrointestinal Surgery, University of Health Sciences, Kosuyolu Higher Specialty Training and Research Hospital, Istanbul, Turkey
| | - Selçuk Gülmez
- Department of Gastrointestinal Surgery, University of Health Sciences, Kosuyolu Higher Specialty Training and Research Hospital, Istanbul, Turkey
| | - Erdal Polat
- Department of Gastrointestinal Surgery, University of Health Sciences, Kosuyolu Higher Specialty Training and Research Hospital, Istanbul, Turkey
| | - Mustafa Duman
- TR University of Health Sciences, Ministry of Health Kartal Kosuyolu High Specialization Training, and Research Hospital Gastroenterological Surgery Clinic
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Topcuoglu OM, Orhan T, Gormez A, Alan N. Are survival outcomes dependent on the tumour dose threshold of 139 Gy in patients with chemorefractory metastatic colorectal cancer treated with yttrium-90 radioembolization using glass particles? A real-world single-centre study. Br J Radiol 2024; 97:1255-1260. [PMID: 38730551 PMCID: PMC11186554 DOI: 10.1093/bjr/tqae096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 04/10/2024] [Accepted: 05/05/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVES To compare the survival and objective response rate (ORR) of the patients receiving estimated tumour absorbed dose (ETAD) <140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE). METHODS Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR. RESULTS A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for group 1 (ETAD <140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (P = .181 and P = .366, respectively). ORR did not show significant difference between the groups (P = .432). CONCLUSION In real-world practice, no significant difference was found in OS, hPFS, and ORR between patients who received ETAD <140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series. ADVANCES IN KNOWLEDGE This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.
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Affiliation(s)
| | - Tolga Orhan
- Department of Radiology, Yeditepe University Hospitals, Kosuyolu 34718, Turkey
| | - Ayşegul Gormez
- Department of Radiology, Yeditepe University Hospitals, Kosuyolu 34718, Turkey
| | - Nalan Alan
- Department of Nuclear Medicine, Yeditepe University Hospitals, Kosuyolu 34718, Turkey
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Coman IS, Vital RC, Coman VE, Burleanu C, Liţescu M, Florea CG, Cristian DA, Gorecki GP, Radu PA, Pleşea IE, Erchid A, Grigorean VT. Emergency and Elective Colorectal Cancer-Relationship between Clinical Factors, Tumor Topography and Surgical Strategies: A Cohort Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:898. [PMID: 38929515 PMCID: PMC11205460 DOI: 10.3390/medicina60060898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/23/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024]
Abstract
Background and Objectives: The purpose of the study was to analyze the relationships among several clinical factors and also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that included patients admitted to our emergency surgical department and diagnosed with colorectal cancer. The study group inclusion criteria were: patients admitted during 2020-2022; patients diagnosed with colorectal cancer (including the ileocecal valve); patients who benefited from a surgical procedure, either emergency or elective. Results: In our study group, consisting of 153 patients, we accounted for 56.9% male patients and 43.1% female patients. The most common clinical manifestations were pain (73.2% of the study group), followed by abdominal distension (69.3% of the study group) and absence of intestinal transit (38.6% of the study group). A total of 69 patients had emergency surgery (45.1%), while 84 patients (54.9%) benefited from elective surgery. The most frequent topography of the tumor was the sigmoid colon, with 19.60% of the patients, followed by the colorectal junction, with 15.68% of the patients, and superior rectum and inferior rectum, with 11.11% of the patients in each subcategory. The most frequent type of procedure was right hemicolectomy (21.6% of the study group), followed by rectosigmoid resection (20.9% of the study group). The surgical procedure was finished by performing an anastomosis in 49% of the patients, and an ostomy in 43.1% of the patients, while for 7.8% of the patients, a tumoral biopsy was performed. Conclusions: Colorectal cancer remains one of the most frequent cancers in the world, with a heavy burden that involves high mortality, alterations in the quality of life of patients and their families, and also the financial costs of the medical systems.
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Affiliation(s)
- Ionuţ Simion Coman
- 10th Clinical Department—General Surgery, Discipline of General Surgery—“Bagdasar-Arseni” Clinical Emergency Hospital, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (I.S.C.); (V.E.C.); (V.T.G.)
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Raluca Cristina Vital
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Violeta Elena Coman
- 10th Clinical Department—General Surgery, Discipline of General Surgery—“Bagdasar-Arseni” Clinical Emergency Hospital, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (I.S.C.); (V.E.C.); (V.T.G.)
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Cosmin Burleanu
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Mircea Liţescu
- 2nd Department of Surgery and General Anesthesia, Discipline of Surgery and General Anesthesia—“Sf. Ioan” Clinical Emergency Hospital, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania
- General Surgery Department, “Sf. Ioan” Clinical Emergency Hospital, 13 Vitan-Bârzeşti Road, 042122 Bucharest, Romania
| | - Costin George Florea
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Daniel Alin Cristian
- 10th Clinical Department—General Surgery, Discipline of General Surgery—“Colţea” Clinical Hospital, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania;
- General Surgery Department, “Colţea” Clinical Hospital, 1 Ion C. Brătianu Boulevard, 030167 Bucharest, Romania
| | - Gabriel-Petre Gorecki
- Faculty of Medicine, “Titu Maiorescu” University, 67A Gheorghe Petraşcu Street, 031593 Bucharest, Romania;
- Department of Anesthesia and Intensive Care, CF2 Clinical Hospital, 63 Mărăşti Boulevard, 011464 Bucharest, Romania
| | - Petru Adrian Radu
- 10th Clinical Department—General Surgery, Discipline of General Surgery—“Dr. Carol Davila” Clinical Nephrology Hospital, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania;
- General Surgery Department, “Dr. Carol Davila” Clinical Nephrology Hospital, 4 Griviţei Road, 010731 Bucharest, Romania
| | - Iancu Emil Pleşea
- Pathology Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania;
| | - Anwar Erchid
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
| | - Valentin Titus Grigorean
- 10th Clinical Department—General Surgery, Discipline of General Surgery—“Bagdasar-Arseni” Clinical Emergency Hospital, Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (I.S.C.); (V.E.C.); (V.T.G.)
- General Surgery Department, “Bagdasar-Arseni” Clinical Emergency Hospital, 12 Berceni Road, 041915 Bucharest, Romania; (R.C.V.); (C.B.); (C.G.F.); (A.E.)
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Ra H, Jeong S, Lee H, Chung JW, Kim KO, Lee WS, Kim J, Kwon KA, Kim JH. Clinicopathological Differences between Right and Left Colorectal Cancer by Sex. J Clin Med 2024; 13:2810. [PMID: 38792352 PMCID: PMC11122515 DOI: 10.3390/jcm13102810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/26/2024] [Accepted: 04/30/2024] [Indexed: 05/26/2024] Open
Abstract
Background: Until now, studies on colorectal cancer (CRC) have focused on clinicopathological characteristics based on location without considering sex differences. However, as men and women have fundamentally different physiological characteristics, research results in the clinical field are limited. We aimed to elucidate the differences in the clinicopathological characteristics between right-sided CRC (RCC) and left-sided CRC (LCC) according to sex. Methods: We classified 1492 South Korean patients with no history of colon surgery between July 2005 and June 2015 based on tumor location and sex. For these patients, differences in the clinical characteristics according to sex were compared using univariate and multivariate analyses. Results: Of the 1269 patients, 951 (74.9%) had LCC, and 318 (25.1%) had RCC, making LCC approximately three times more common than RCC. When sex was not taken into account, patients with RCC had significantly higher rates of anemia and undifferentiated cancers than the rates in those with LCC. Even considering sex, anemia and undifferentiated cancer were more prevalent in RCC than in LCC in both men and women. In contrast, age over 65 years and abnormal white blood cell count differed between RCC and LCC only in women. Conclusions: The clinicopathologic characteristics of CRC vary according to the location and sex. Therefore, sex must be considered as a fundamental characteristic of personalized treatment.
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Affiliation(s)
- Hannah Ra
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
| | - Soyeon Jeong
- Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, College of Medicine, Incheon 21565, Republic of Korea;
- Gachon Medical Research Institute, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea
| | - Hannah Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
| | - Jun-Won Chung
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
| | - Kyoung Oh Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
| | - Won-Suk Lee
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea;
| | - Jisup Kim
- Department of Pathology, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea;
| | - Kwang An Kwon
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
| | - Jung Ho Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea; (H.R.); (H.L.); (J.-W.C.); (K.O.K.); (K.A.K.)
- Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, College of Medicine, Incheon 21565, Republic of Korea;
- Gachon Medical Research Institute, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon 21565, Republic of Korea
- Department of Translational-Clinical Medicine, Gachon Advanced Institute for Health Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
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Gholamalizadeh H, Zafari N, Velayati M, Fiuji H, Maftooh M, Ghorbani E, Hassanian SM, Khazaei M, Ferns GA, Nazari E, Avan A. Prognostic value of primary tumor location in colorectal cancer: an updated meta-analysis. Clin Exp Med 2023; 23:4369-4383. [PMID: 37405571 DOI: 10.1007/s10238-023-01120-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/12/2023] [Indexed: 07/06/2023]
Abstract
The clinical, histological, and molecular differences between right-sided colon cancer (RCC) and left-sided colon cancer (RCC) have received considerable attention. Over the past decade, many articles have been published concerning the association between primary tumor location (PTL) of colorectal cancer and survival outcomes. Therefore, there is a growing need for an updated meta-analysis integrating the outcomes of recent studies to determine the prognostic role of right vs left-sidedness of PTL in patients with colorectal cancer. We conducted a comprehensive database review using PubMed, SCOPUS, and Cochrane library databases from February 2016 to March 2023 for prospective or retrospective studies reporting data on overall survival (OS) and cancer-specific survival (CSS) of RCC compared with LCC. A total of 60 cohort studies comprising 1,494,445 patients were included in the meta-analysis. We demonstrated that RCC is associated with a significantly increased risk of death compared with LCC by 25% (hazard ratio (HR), 1.25; 95% confidence interval (CI), 1.19-1.31; I2 = 78.4%; Z = 43.68). Results showed that patients with RCC have a worse OS compared with LCC only in advanced stages (Stage III: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%; Stage IV: HR, 1.34; 95% CI 1.25-1.44; P < 0.0001; I2 = 69.2%) but not in primary stages (Stage I/II: HR, 1.275; 95% CI 1.16-1.4; P = 0.0002; I2 = 85.8%). Moreover, a meta-analysis of 13 studies including 812,644 patients revealed that there is no significant difference in CSS between RCC and LCC (HR, 1.121; 95% CI 0.97-1.3; P = 0.112). Findings from the present meta-analysis highlight the importance of PTL in clinical decision-making for patients with CRC, especially in advanced stages. We provide further evidence supporting the hypothesis that RCC and LCC are distinct disease entities that should be managed differently.
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Affiliation(s)
- Hanieh Gholamalizadeh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nima Zafari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Velayati
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Fiuji
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina Maftooh
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elnaz Ghorbani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mahdi Hassanian
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton and Sussex Medical School, Falmer, Brighton, Sussex, BN1 9PH, UK
| | - Elham Nazari
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- College of Medicine, University of Warith Al-Anbiyaa, Karbala, Iraq.
- School of Mechanical, Medical and Process Engineering, Science and Engineering Faculty, Queensland University of Technology, 2 George St, Brisbane, QLD, 4000, Australia.
- Faculty of Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia.
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Gökmen İ, Taştekin E, Demir N, Özcan E, Akgül F, Hacıoğlu MB, Erdoğan B, Topaloğlu S, Çiçin İ. Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer. Curr Issues Mol Biol 2023; 45:7803-7812. [PMID: 37886935 PMCID: PMC10605734 DOI: 10.3390/cimb45100491] [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: 08/24/2023] [Revised: 09/13/2023] [Accepted: 09/16/2023] [Indexed: 10/28/2023] Open
Abstract
The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients' demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAFV600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAFV600E and BRAFnon-V600E and their analysis according to specific tumor localizations showed that all four BRAFnon-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.
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Affiliation(s)
- İvo Gökmen
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - Ebru Taştekin
- Department of Pathology, Trakya University School of Medicine, Edirne 22030, Turkey;
| | - Nazan Demir
- Department of Medical Oncology, Sultan I. Murat Public Hospital, Edirne 22030, Turkey;
| | - Erkan Özcan
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - Fahri Akgül
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - Muhammed Bekir Hacıoğlu
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - Bülent Erdoğan
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - Sernaz Topaloğlu
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
| | - İrfan Çiçin
- Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, Edirne 22030, Turkey; (E.Ö.); (F.A.); (M.B.H.); (S.T.); (İ.Ç.)
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Canseco LM, Liu YW, Lu CC, Lee KC, Chen HH, Hu WH, Tsai KL, Yang YH, Wang CC, Hung CH. Survival Evidence of Local Control for Colorectal Cancer Liver Metastases by Hepatectomy and/or Radiofrequency Ablation. Cancers (Basel) 2023; 15:4434. [PMID: 37760404 PMCID: PMC10526261 DOI: 10.3390/cancers15184434] [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: 07/30/2023] [Revised: 09/03/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatectomy and/or local ablation therapy have been recommended for colorectal cancer liver metastases (CRLM). However, they still lack strong evidence for their survival benefits, in addition to systemic therapy. This study aims to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in CRLM patients from a large multi-institutional database. A total of 20,251 patients with colorectal cancer, 4521 of whom were with CRLM, were screened for eligibility. Finally, 2612 patients (637 hepatectomy, 93 RFA, 92 combined hepatectomy and RFA, and 1790 non-aggressive treatment) were enrolled. Frequency matching analysis was used to adjust for baseline differences. The 5-year overall survival (OS) was as follows: hepatectomy alone was 47.8%, combined hepatectomy plus RFA was 35.9%, RFA alone was 29.2%, and the non-aggressive treatment group was 7.4%. Kaplan-Meier curves showed that hepatectomy, RFA, and combination were significantly associated with a better OS compared to those without aggressive local therapy (p < 0.001). Multivariate Cox regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.81-0.97; p = 0.011), old age (≥60 years) (HR 1.20; 95% CI, 1.09-1.32; p < 0.001), high CEA level (>5 ng/mL) (HR 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right-sided cancer (HR 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR 0.7; 95% CI, 0.62-0.79; p < 0.001), and aggressive local therapy (hepatectomy vs. non-local therapy HR 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in a better OS than those without (p < 0.001). In conclusion, aggressive local treatment provides survival advantages over systemic therapy alone among CRLM patients.
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Affiliation(s)
- Lariza Marie Canseco
- Section of Gastroenterology, Department of Internal Medicine, De Los Santos Medical Center, Quezon City 1112, MM, Philippines;
| | - Yueh-Wei Liu
- Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (Y.-W.L.); (C.-C.W.)
| | - Chien-Chang Lu
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Ko-Chao Lee
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Hong-Hwa Chen
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Wan-Hsiang Hu
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Kai-Lung Tsai
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (C.-C.L.); (K.-C.L.); (H.-H.C.); (W.-H.H.); (K.-L.T.)
| | - Yao-Hsu Yang
- Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 61363, Taiwan;
- Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chiayi 61363, Taiwan
| | - Chih-Chi Wang
- Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan; (Y.-W.L.); (C.-C.W.)
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833401, Taiwan
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9
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Cavadas AS, Gonçalves E, Pereira CC, Rodrigues J, Pereira JC. Right colon cancer: The influence of specific location on recurrence and survival. Cancer Treat Res Commun 2023; 36:100724. [PMID: 37267659 DOI: 10.1016/j.ctarc.2023.100724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/04/2023]
Abstract
AIM This study aimed to investigate whether the site of the tumour within the right colon affects survival in patients who underwent right colectomy for colon cancer. METHODS An observational retrospective longitudinal study was performed in patients who underwent right colectomy for non-metastatic, invasive right-sided colon cancer. Patients were categorized into two groups based on tumour location: (i) caecum and ascending colon; (ii) hepatic flexure and proximal transverse colon. Demographic and clinical features were characterized, and a survival analysis was performed. RESULTS Of the 198 patients enroled in the study, 134 (67.8%) had caecal or ascending colon cancer and 64 (32.3%) had hepatic flexure or transverse colon cancer. Seventy (35.4%) were female and the mean age at the time of surgery was 71.6 (SD 11.4). The groups were comparable with respect to the number of lymph nodes sampled, the pTNM stage, the histological differentiation grade and the likelihood of patients receiving adjuvant chemotherapy. Recurrence rate was nearly twice as high in the hepatic flexure and proximal transverse colon group (12.5% vs 6.7%), but this difference was not statistically significant (p = 0.174). Kaplan-Meier analysis showed no differences in disease-free (p = 0.255) and overall survival (p = 0.258) between the groups. CONCLUSION In our population, specific location of right-sided colon cancers does not appear to have an influence on survival. Further investigation is needed to determine if tumour subsite has an impact on the recurrence rate, and whether it should be considered in defining prognosis and treatment.
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Affiliation(s)
- Ana Sofia Cavadas
- Hospital de Braga, Sete Fontes - São Victor, Braga 4710-243 Portugal.
| | - Eduarda Gonçalves
- Hospital de Braga, Sete Fontes - São Victor, Braga 4710-243 Portugal
| | | | - Jorge Rodrigues
- Hospital de Braga, Sete Fontes - São Victor, Braga 4710-243 Portugal
| | - Joaquim Costa Pereira
- Hospital de Braga, Sete Fontes - São Victor, Braga 4710-243 Portugal; Escola de Medicina da Universidade do Minho, Portugal
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10
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Pagani M, De Vincenti R, Cecchi C, Apollinari A, Pesi B, Leo F, Giannessi S, Fedi M. Hepatic Resection in Patients with Colo-Rectal Liver Metastases: Surgical Outcomes and Prognostic Factors of Single-Center Experience. J Clin Med 2023; 12:2170. [PMID: 36983170 PMCID: PMC10057410 DOI: 10.3390/jcm12062170] [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: 10/23/2022] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 03/14/2023] Open
Abstract
INTRODUCTION Surgical resection has a fundamental role in increasing the chance of survival in patients with colorectal liver metastases. The guidelines have been modified and expanded in time in order to increase the number of patients that can benefit from this treatment. The aim of this study is to analyze the main prognostic factors related to overall and disease-free survival of a series of consecutive patients undergoing liver resection for colorectal liver metastases (CRLM). MATERIALS AND METHODS A retrospective review of patients undergoing liver resection for CRLM between April 2018 and September 2021 was performed. Clinical data and laboratory parameters were evaluated using the log-rank test. OS and DFS were estimated using the Kaplan-Meier method. RESULTS A retrospective study on 75 patients who underwent liver resection for CRLM was performed. The OS and DFS at 1 and 3 years were 84.3% and 63.8% for OS, 55.6% and 30.7% for DFS, respectively. From the analysis of the data, the most significant results indicate that: patients with a lower CEA value <25 ng/mL had an OS of 93.6% and 80.1% at 1 and 3 years, with an average of 36.7 months (CI 95% 33.1-40.3); moreover, patients with a value equal to or greater than 25 ng/mL had a 1-year survival equal to 57.4%, with an average of 13.8 months (CI 95% 9.4-18.2) (p < 0.001); adjuvant chemotherapy increases by 3 years the overall survival (OS: 68.6% vs. 49.7%) (p = 0.013); localization of the primary tumor affects OS, with a better prognosis for left colon metastases (OS at 42 months: 85.4% vs. 42.2%) (p value = 0.056); patients with stage T1 or T2 cancer have a better 3 years OS (92.9-100% vs. 49.7-56.3%) (p = 0.696), while the N0 stage results in both higher 3 years OS and DFS than the N + stages (OS: 87.5% vs. 68.5% vs. 24.5%); metachronous metastases have a higher 3 years OS than synchronous ones (80% vs. 47.4%) (p = 0.066); parenchymal sparing resections have a better 3 years DFS than anatomical ones (33.7% vs. 0%) (p = 0.067); a patient with a parenchymal R1 resection has a much worse prognosis than an R0 (3 years OS: 0% vs. 68.7%) (p < 0.001). CONCLUSIONS CEA value of less than 25 ng/mL, localization of the primary tumor in the left colon, primary tumor in stage T1/2 and N0, metachronous presentation, R0 resection, fewer than four metastases, and use of adjuvant chemotherapy are all parameters that in our analysis have shown a correlation with a better prognosis; moreover, the evaluation of the series is in line with the latest evidence in the literature in defining the non-inferiority of minimally invasive and parenchymal sparing treatment compared to the classic laparotomic approach with anatomic resection.
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Affiliation(s)
| | | | | | | | | | | | | | - Massimo Fedi
- Division of General Surgery, San Jacopo Hospital, 51100 Pistoia, Italy
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11
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Abstract
Despite a steady decline in incidence and mortality rates, colorectal cancer (CRC) remains the second most common cancer diagnosis in women and the third most common in men worldwide. Notably, the liver is recognized as the most common site of CRC metastasis, and metastases to the liver remain the primary driver of disease-specific mortality for patients with CRC. Although hepatic resection is the backbone of curative-intent treatment, management of CRLM has become increasingly multimodal during the last decade and includes the use of downstaging chemotherapy, ablation techniques, and locoregional therapy, each of which are reviewed herein.
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Affiliation(s)
- Berk Aykut
- Department of Surgery, Division of Surgical Oncology, Duke University Medical Center, Box 3966, 10 Bryan Searle Drive, 466G Seeley G. Mudd Building, Durham, NC 27710, USA. https://twitter.com/BerkAykutMD
| | - Michael E Lidsky
- Department of Surgery, Division of Surgical Oncology, Duke University Medical Center, Box 3966, 10 Bryan Searle Drive, 466G Seeley G. Mudd Building, Durham, NC 27710, USA.
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12
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Jin X, Wu Y, Feng Y, Lin Z, Zhang N, Yu B, Mao A, Zhang T, Zhu W, Wang L. A population-based predictive model identifying optimal candidates for primary and metastasis resection in patients with colorectal cancer with liver metastatic. Front Oncol 2022; 12:899659. [PMID: 36276059 PMCID: PMC9585382 DOI: 10.3389/fonc.2022.899659] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Accepted: 09/13/2022] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND The survival benefit of primary and metastatic resection for patients with colorectal cancer with liver metastasis (CRLM) has been observed, but methods for discriminating which individuals would benefit from surgery have been poorly defined. Herein, a predictive model was developed to stratify patients into sub-population based on their response to surgery. METHODS We assessed the survival benefits for adults diagnosed with colorectal liver metastasis by comparing patients with curative surgery vs. those without surgery. CRLM patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were identified for model construction. Other data including CRLM patients from our center were obtained for external validation. Calibration plots, the area under the curve (AUC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram compared with the tumor-node-metastasis (TNM) classification. The Kaplan-Meier analysis was performed to examine whether this model would distinguish patients who could benefit from surgery. RESULTS A total of 1,220 eligible patients were identified, and 881 (72.2%) underwent colorectal and liver resection. Cancer-specific survival (CSS) for the surgery group was significantly better than that for the no-surgery group (41 vs. 14 months, p < 0.001). Five factors were found associated with CSS and adopted to build the nomograms, i.e., age, T stage, N stage, neoadjuvant chemotherapy, and primary tumor position. The AUC of the CRLM nomogram showed a better performance in identifying patients who could obtain benefits in the surgical treatment, compared with TNM classification (training set, 0.826 [95% CI, 0.786-0.866] vs. 0.649 [95% CI, 0.598-0.701]; internal validation set, 0.820 [95% CI, 0.741-0.899] vs. 0.635 [95% CI, 0.539-0.731]; external validation set, 0.763 [95% CI, 0.691-0.836] vs. 0.626 [95% CI, 0.542-0.710]). The calibration curves revealed excellent agreement between the predicted and actual survival outcomes. The DCA showed that the nomogram exhibited more clinical benefits than the TNM staging system. The beneficial and surgery group survived longer significantly than the non-beneficial and surgery group (HR = 0.21, 95% CI, 0.17-0.27, p < 0.001), but no difference was observed between the non-beneficial and surgery and non-surgery groups (HR = 0.89, 95% CI, 0.71-1.13, p = 0.344). CONCLUSIONS An accurate and easy-to-use CRLM nomogram has been developed and can be applied to identify optimal candidates for the resection of primary and metastatic lesions among CRLM patients.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Weiping Zhu
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lu Wang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
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13
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Minami Y, Kanemura S, Kusaka J, Kinouchi M, Suzuki S, Nishino Y, Miura K. Associations of cigarette smoking, alcohol drinking and body mass index with survival after colorectal cancer diagnosis by anatomic subsite: a prospective patient cohort study in Japan. Jpn J Clin Oncol 2022; 52:1375-1388. [PMID: 36007230 DOI: 10.1093/jjco/hyac140] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 08/03/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Cigarette smoking, alcohol drinking and obesity are known to be risk factors for colorectal cancer. These factors may affect survival after diagnosis, but evidence has been inconsistent. We investigated subsite-specific associations between prediagnosis smoking, alcohol drinking and body mass index and survival in colorectal cancer. METHODS Subjects were 1300 patients (colon 778; rectum 502; concurrent 20) with histologically confirmed colorectal cancer diagnosed during 1997-2013 at a single institution in Japan. Histories of smoking and alcohol drinking, height and prediagnosis weight were assessed using a self-administered questionnaire. Using Cox proportional hazards model, hazard ratios and 95% confidence intervals of mortality were estimated. RESULTS During a median follow-up period of 6.7 years, 479 deaths were documented. Ever-smoking was associated with an increased risk of all-cause death among patients with colon cancer (hazard ratio: 1.47; 95% confidence interval: 1.07-2.02 compared with never-smoking). According to colon subsite, this increased risk was clear in patients with proximal colon cancer (hazard ratio: 2.09; 95% confidence interval: 1.28-3.40). There was no association between smoking and rectal cancer survival. Alcohol drinking was not associated with survival for either colon or rectal cancer. Among patients with rectal cancer, higher body mass index was associated with a lower risk of all-cause (Ptrend = 0.0006) and disease-specific death (Ptrend = 0.02). For colon cancer, lower body mass index tended to be associated with a higher risk of all-cause death (Ptrend = 0.05). CONCLUSIONS The results indicate that lifestyles identified as risk factors for colorectal cancer may impact differently on patient survival according to anatomic subsite.
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Affiliation(s)
- Yuko Minami
- Department of Health Sciences, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.,Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan.,Center for Preventive Medicine, Osaki Citizen Hospital, Osaki, Miyagi, Japan
| | - Seiki Kanemura
- Division of Cancer Epidemiology and Prevention, Miyagi Cancer Center Research Institute, Natori, Miyagi, Japan
| | - Jun Kusaka
- Department of Gastroenterology, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
| | - Makoto Kinouchi
- Department of Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
| | - Shinichi Suzuki
- Department of Gastroenterology, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
| | - Yoshikazu Nishino
- Deapartment of Epidemiology and Public Health, Kanazawa Medical University, Kahoku, Ishikawa, Japan
| | - Koh Miura
- Department of Surgery, Miyagi Cancer Center Hospital, Natori, Miyagi, Japan
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14
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Cheng P, Chen H, Huang F, Li J, Liu H, Zheng Z, Lu Z. Nomograms predicting cancer-specific survival for stage IV colorectal cancer with synchronous lung metastases. Sci Rep 2022; 12:13952. [PMID: 35977984 PMCID: PMC9385743 DOI: 10.1038/s41598-022-18258-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 08/08/2022] [Indexed: 12/24/2022] Open
Abstract
This study aimed to establish a nomogram for the prediction of cancer-specific survival (CSS) of CRC patients with synchronous LM. The final prognostic nomogram based on prognostic factors was evaluated by concordance index (C-index), time-dependent receiver operating characteristic curves, and calibration curves. In the training and validation groups, the C-index for the nomogram was 0.648 and 0.638, and the AUC was 0.793 and 0.785, respectively. The high quality of the calibration curves in the nomogram models for CSS at 1-, 3-, and 5-year was observed. The nomogram model provided a conventional and useful tool to evaluate the 1-, 3-, and 5-year CSS of CRC patients with synchronous LM.
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Affiliation(s)
- Pu Cheng
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haipeng Chen
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fei Huang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiyun Li
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hengchang Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaoxu Zheng
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Zhao Lu
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
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15
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Valenzuela CD, Moaven O, Gawdi R, Stauffer JA, Del Piccolo NR, Cheung TT, Corvera CU, Wisneski AD, Cha C, Mangieri CW, Zarandi NP, Dourado J, Perry KC, Russell G, Shen P. Association of primary tumor laterality with surgical outcomes for colorectal liver metastases: results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC). HPB (Oxford) 2022; 24:1351-1361. [PMID: 35289279 PMCID: PMC9356971 DOI: 10.1016/j.hpb.2022.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Revised: 02/01/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary laterality of colorectal cancer is thought to be associated with differences in outcomes. Liver metastasis is the most common site of solitary colorectal cancer spread. However, how primary colorectal cancer laterality affects outcomes in colorectal liver metastasis remains unclear. METHODS The Colorectal Liver Operative Metastasis International Collaborative (COLOMIC) of operative hepatectomy cases for colorectal liver metastasis was compiled from five participating institutions. This included consecutive cases from 2000 to 2018 at all sites. A total of 884 patients were included in this study. Univariate, multivariate, and Kaplan-Meier analyses were performed. RESULTS Patients with left-sided versus right-sided cancers had significantly better overall survival: 49.4 vs. 41.8 months (p < 0.05). Patients with KRAS mutations had significantly worse median overall survival compared to KRAS wild-type (43.6 vs 56.1 months; p < 0.001). In left-sided cancers, KRAS mutations were associated with significantly worse median overall survival compared to KRAS wild-type cancers (43.6 vs 56.6 months; p < 0.01). This association was absent in patients with right-sided primary tumors. Multivariate Cox regression analysis revealed different variable sets (non-overlapping) were associated with overall survival, when comparing left-sided and right-sided cancers. CONCLUSION Understanding how primary tumor laterality and related biological aspects affect long-term outcomes can potentially inform treatment decisions for patients with colorectal liver metastases.
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Affiliation(s)
- Cristian D Valenzuela
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Omeed Moaven
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA; Department of Surgical Oncology, Mayo Clinic in Florida, Jacksonville, FL, USA
| | - Rohin Gawdi
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - John A Stauffer
- Department of Surgical Oncology, Mayo Clinic in Florida, Jacksonville, FL, USA
| | - Nico R Del Piccolo
- Department of Surgical Oncology, Mayo Clinic in Florida, Jacksonville, FL, USA
| | - Tan To Cheung
- Department of Surgery, University of Hong Kong, Hong Kong, China
| | - Carlos U Corvera
- Department of Hepatobiliary & Pancreatic Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Andrew D Wisneski
- Department of Hepatobiliary & Pancreatic Surgery, University of California San Francisco, San Francisco, CA, USA
| | - Charles Cha
- Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Christopher W Mangieri
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Nima P Zarandi
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Justin Dourado
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Kathleen C Perry
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA
| | - Gregory Russell
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Perry Shen
- Department of Surgical Oncology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
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16
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Ten Hoorn S, Waasdorp C, van Oijen MGH, Damhofer H, Trinh A, Zhao L, Smits LJH, Bootsma S, van Pelt GW, Mesker WE, Mol L, Goey KKH, Koopman M, Medema JP, Tuynman JB, Zlobec I, Punt CJA, Vermeulen L, Bijlsma MF. Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer. BMC Cancer 2022; 22:394. [PMID: 35413826 PMCID: PMC9004139 DOI: 10.1186/s12885-022-09436-0] [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: 06/22/2021] [Accepted: 03/21/2022] [Indexed: 12/03/2022] Open
Abstract
Background Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC). Methods Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20). Results ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11–1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06–3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25–3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers. Conclusions Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09436-0.
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Affiliation(s)
- Sanne Ten Hoorn
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Oncode Institute, Amsterdam, The Netherlands
| | - Cynthia Waasdorp
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Oncode Institute, Amsterdam, The Netherlands
| | - Martijn G H van Oijen
- Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Helene Damhofer
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Anne Trinh
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA
| | - Lan Zhao
- Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong
| | - Lisanne J H Smits
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, Boelelaan 1117, Amsterdam, the Netherlands
| | - Sanne Bootsma
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Oncode Institute, Amsterdam, The Netherlands
| | - Gabi W van Pelt
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wilma E Mesker
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Linda Mol
- Department of Data Management, Netherlands Comprehensive Cancer Center (IKNL), Nijmegen, The Netherlands
| | - Kaitlyn K H Goey
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Jan Paul Medema
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Oncode Institute, Amsterdam, The Netherlands
| | - Jurriaan B Tuynman
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, Boelelaan 1117, Amsterdam, the Netherlands
| | - Inti Zlobec
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Cornelis J A Punt
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht University, Utrecht, The Netherlands
| | - Louis Vermeulen
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands.,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands.,Oncode Institute, Amsterdam, The Netherlands.,Amsterdam UMC location University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Maarten F Bijlsma
- Amsterdam UMC location University of Amsterdam, Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Imaging and Biomarkers, Meibergdreef 9, Amsterdam, the Netherlands. .,Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands. .,Oncode Institute, Amsterdam, The Netherlands.
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17
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The impact of tumor location on long-term survival outcomes in patients with right-sided colon cancer. Tech Coloproctol 2022; 26:127-133. [PMID: 34993688 DOI: 10.1007/s10151-021-02554-0] [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: 03/19/2021] [Accepted: 11/23/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The oncologic outcomes of right-sided cancers are generally grouped in studies. We hypothesized that tumor location (cecal vs. ascending vs. hepatic flexure) may influence cancer-specific outcomes. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients over 18 with non-metastatic, invasive (American Joint Committee on Cancer stage I-III) right-sided adenocarcinoma of the colon from 1988 to 2014 who underwent partial colectomy. Patients were categorized into groups: (1) cecum (2) ascending colon (3) hepatic flexure. Demographic, clinical and pathologic factors were compared between groups. Disease-specific and overall survival were described using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis determined the independent association of primary tumor location. RESULTS We identified 167,450 patients. Mean age was 72.2 ± 12.3 years and 54.9% were female. Of these, 81,611, 66,857, and 18,982 had cecal, ascending colon, and hepatic flexure cancers, respectively. Cecal cancers were associated with a lower number of examined nodes but a higher likelihood of nodal positivity. Cecal cancer patients were significantly older, had larger tumors, and higher tumor stage. On univariate analysis, cecal cancers were associated with poorer disease-specific and overall survival (all p values < 0.001). On multivariate analysis controlling for sex, age, tumor size, number of examined nodes and stage, hepatic flexure cancers were associated with worse disease-specific (HR 1.05) and overall survival (HR 1.03). CONCLUSION Hepatic flexure cancers are associated with worse survival compared to more proximal colon cancers. The cause is likely multifactorial, including biological and technical factors. More aggressive surgical and multimodal therapy may be considered for hepatic flexure colon cancers.
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18
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Turhan VB, Ünsal A, Gök HF, Öztürk B, Öztürk D, Simsek GG, Buluş H. Predictive Value of Preoperative Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio in Determining the Stage of Colon Tumors. Cureus 2021; 13:e18381. [PMID: 34725625 PMCID: PMC8555626 DOI: 10.7759/cureus.18381] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2021] [Indexed: 11/07/2022] Open
Abstract
Introduction Biomarkers such as the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are associated with the colon tumor stage and prognosis. Therefore, in our study, we investigated whether these biomarkers are important in determining the colon cancer stage. Materials and methods The outcomes in 268 patients operated on with the diagnosis of colon cancer between January 2011 and March 2019 were retrospectively analyzed. The relationship of the stage of the patients with the NLR or PLR was evaluated. In addition, according to the stage of colorectal tumors, stage I and other stages (stages II, III, and IV) were compared in terms of NLR and PLR. Groups that had lymph node (LN) metastasis were compared with those that did not. Finally, groups with and without metastasis were also compared. Results In our cohort, 144 patients (57.6%) were male, and 84 (42.4%) were female. The mean age was found to be 68.28 ±12.71 years. The patients were evaluated according to their stages: 26 patients were stage I, 78 patients were stage II, 75 patients were stage III, and 19 patients were stage IV. There was a significant difference in NLR values between the groups (p: 0.05). Also, 104 patients were LN-negative (stages I-II), and 94 patients were LN-positive (stages III-IV). When PLR was compared between the two groups, no significant difference was found between tumor stages and these values (p: 0.099). However, there was a significant difference in NLR values (p: 0.034). Conclusion Based on our findings, it has been concluded that increased PLR may not be associated with the colon cancer stage. However, the increase in NLR was found to be correlated with tumor stage and LN metastasis.
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Affiliation(s)
- Veysel Barış Turhan
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
| | - Abdulkadir Ünsal
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
| | - Halil Fatih Gök
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
| | - Bülent Öztürk
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
| | - Doğan Öztürk
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
| | - Gulcin Guler Simsek
- Pathology, University of Medical Sciences, Gülhane Training and Research Hospital, Ankara, TUR
| | - Hakan Buluş
- General Surgery, Health Sciences University Keçiören Training and Research Hospital, Ankara, TUR
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19
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Di Giorgio A, Santullo F, Attalla El Halabieh M, Lodoli C, Abatini C, Calegari MA, Martini M, Rotolo S, Pacelli F. Clinical and Molecular Features in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinosis from Colorectal Cancer. J Gastrointest Surg 2021; 25:2649-2659. [PMID: 34244953 DOI: 10.1007/s11605-021-05073-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 06/04/2021] [Indexed: 01/31/2023]
Abstract
PURPOSE Careful patient selection plays a crucial role in avoiding overtreatment and further increases survival rates in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC) with peritoneal metastases (PM). METHODS The clinical and molecular factors influencing survival in patients who had undergone CRS with HIPEC between January 2015 and December 2018 were analyzed. RESULTS Sixty-six patients underwent CRS with HIPEC during the study period. The median overall survival (OS) was 36 months, with a 3-year OS of 43%. Multivariate analysis revealed increased PCI (HR: 1.21; 95% CI: 1.02-1.41; p = 0.020), right-sided primary tumor (HR: 3.01; 95% CI: 1.27-7.13; p = 0.017), and BRAF V600E mutation (HR: 4.55; 95% CI: 1.21-17.21; p = 0.025) as independent predictors for worse OS. CONCLUSION In addition to confirming the prognostic role of PCI, our study extends the role of BRAF mutation and right primary tumor location as markers for worse prognosis.
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Affiliation(s)
- Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Francesco Santullo
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.
| | - Miriam Attalla El Halabieh
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Claudio Lodoli
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Carlo Abatini
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | | | - Maurizio Martini
- Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Stefano Rotolo
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.,Surgery, Oncology, and Stomatology Unit, University of Palermo, Palermo, Italy
| | - Fabio Pacelli
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy
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20
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BIANCHI PP, GIULIANI G, SALAJ A, FERRARO L, OPOCHER E, TOTI F, FORMISANO G. Bottom-up suprapubic approach for robotic right colectomy: technical aspects and preliminary outcomes. Minerva Surg 2021; 76:129-137. [DOI: 10.23736/s2724-5691.20.08664-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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21
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Guo JN, Li MQ, Deng SH, Chen C, Ni Y, Cui BB, Liu YL. Prognostic Immune-Related Analysis Based on Differentially Expressed Genes in Left- and Right-Sided Colon Adenocarcinoma. Front Oncol 2021; 11:640196. [PMID: 33763372 PMCID: PMC7982460 DOI: 10.3389/fonc.2021.640196] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/27/2021] [Indexed: 02/05/2023] Open
Abstract
Background Colon adenocarcinoma (COAD) can be divided into left-sided and right-sided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, particularly immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, therefore the prognostic key IRGs could be identified. Methods The gene sets and clinical information of COAD patients were derived from TCGA and GEO databases. The comparison of differentially expressed genes (DEGs) of LCCs and RCCs were conducted with appliance of “Limma” analysis. The establishment about co-expression modules of DEGs related with immune score was conducted by weighted gene co-expression network analysis (WGCNA). Furthermore, we screened the module genes and completed construction of gene pairs. The analysis of the prognosis and the establishment of PRSM were performed with univariate- and lasso-Cox regression. We employed the PRSM in the model group and verification group for the purpose of risk group assignment and PRSM accuracy verification. Finally, the identification of the prognostic key IRGs was guaranteed by the adoption of functional enrichment, “DisNor” and protein-protein interaction (PPI). Results A total of 215 genes were screened out by differential expression analysis and WGCNA. A PRSM with 16 immune-related gene pairs (IRGPs) was established upon the genes pairing. Furthermore, we confirmed that the risk score was an independent factor for survival by univariate- and multivariate-Cox regression. The prognosis of high-risk group in model group (P < 0.001) and validation group (P = 0.014) was significantly worse than that in low-risk group. Treg cells (P < 0.001) and macrophage M0 (P = 0.015) were highly expressed in the high-risk group. The functional analysis indicated that there was significant up-regulation with regard of lymphocyte and cytokine related terms in low-risk group. Finally, we identified five prognostic key IRGs associated with better prognosis through PPI and prognostic analysis, including IL2RB, TRIM22, CIITA, CXCL13, and CXCR6. Conclusion Through the analysis and screening of the DEGs between LCCs and RCCs, we constructed a PRSM which could predicate prognosis of LCCs and RCCs, and five prognostic key IRGs were identified as well. Therefore, the basis for identifying the benefits of immunotherapy and immunomodulatory was built.
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Affiliation(s)
- Jun-Nan Guo
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Ming-Qi Li
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shen-Hui Deng
- Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chen Chen
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yin Ni
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Bin-Bin Cui
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yan-Long Liu
- Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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22
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Feasibility of robotic right colectomy with complete mesocolic excision and intracorporeal anastomosis: short-term outcomes of 161 consecutive patients. Updates Surg 2021; 73:1065-1072. [PMID: 33666853 DOI: 10.1007/s13304-021-01001-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 02/09/2021] [Indexed: 01/19/2023]
Abstract
Technical and oncological aspects are still debated when dealing with minimally-invasive right colectomy. Main controversial issues still remain about whether the anastomosis should be performed intra- or extracorporeally and if a complete mesocolic excision (CME) should be carried out. We report the feasibility of robotic right colectomy with CME and intracorporeal anastomosis (IA) for right sided colon cancer. Data from patients who underwent robotic right colectomy with IA and CME from January 2015 to April 2020 were prospectively collected and retrospectively analyzed. Intraoperative outcomes and complications (minor I-II and major III-IV according to Clavien-Dindo classification), conversion rate, 30-day postoperative outcomes and pathological outcomes were the variables assessed. A total of 161 patients undergoing robotic right colectomy for cancer met the inclusion criteria. Mean operative time was 185 min, no intraoperative complications were observed, and the conversion rate was 3.7% (6 patients requiring elective conversions). Overall, mean postoperative stay was 4.9 days and the overall 30-day complication rate was 16.1%. 20 patients (12.4%) had minor complications, while major postoperative complications occurred in six patients (3.7%). Anastomotic leak was recorded in one patient (0.6%) and the 30-day re-admission rate was 0.6%. Mean number of harvested lymph nodes was 21.9. Patients requiring conversion experienced two minor complications, with a mean length of stay of 7 days. Robotic right colectomy with CME and IA is feasible and it is associated with good intraoperative and short-term postoperative clinical outcomes.
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23
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Liu C, Hu C, Huang J, Xiang K, Li Z, Qu J, Chen Y, Yang B, Qu X, Liu Y, Zhang G, Wen T. A Prognostic Nomogram of Colon Cancer With Liver Metastasis: A Study of the US SEER Database and a Chinese Cohort. Front Oncol 2021; 11:591009. [PMID: 33738248 PMCID: PMC7962604 DOI: 10.3389/fonc.2021.591009] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/25/2021] [Indexed: 12/12/2022] Open
Abstract
Background Among colon cancer patients, liver metastasis is a commonly deadly phenomenon, but there are few prognostic models for these patients. Methods The clinicopathologic data of colon cancer with liver metastasis (CCLM) patients were downloaded from the Surveillance, Epidemiology and End Results (SEER) database. All patients were randomly divided into training and internal validation sets based on the ratio of 7:3. A prognostic nomogram was established with Cox analysis in the training set, which was validated by two independent validation sets. Results A total of 5,700 CCLM patients were included. Age, race, tumor size, tumor site, histological type, grade, AJCC N status, carcinoembryonic antigen (CEA), lung metastasis, bone metastasis, surgery, and chemotherapy were independently associated with the overall survival (OS) of CCLM in the training set, which were used to establish a nomogram. The AUCs of 1-, 2- and 3-year were higher than or equal to 0.700 in the training, internal validation, and external validation sets, indicating the favorable effects of our nomogram. Besides, whether in overall or subgroup analysis, the risk score calculated by this nomogram can divide CCLM patients into high-, middle- and low-risk groups, which suggested that the nomogram can significantly determine patients with different prognosis and is suitable for different patients. Conclusion Higher age, the race of black, larger tumor size, higher grade, histological type of mucinous adenocarcinoma and signet ring cell carcinoma, higher N stage, RCC, lung metastasis, bone metastasis, without surgery, without chemotherapy, and elevated CEA were independently associated with poor prognosis of CCLM patients. A nomogram incorporating the above variables could accurately predict the prognosis of CCLM.
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Affiliation(s)
- Chuan Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Chuan Hu
- Medical College, Qingdao University, Qingdao, China
| | - Jiale Huang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Kanghui Xiang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Zhi Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Jinglei Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Ying Chen
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Bowen Yang
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Xiujuan Qu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Yunpeng Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
| | - Guangwei Zhang
- Smart Hospital Management Department, The First Hospital of China Medical University, Shenyang, China
| | - Ti Wen
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, China
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Metwally IH, Shetiwy M, Elalfy AF, Abouzid A, Saleh SS, Hamdy M. Epidemiology and survival of colon cancer among Egyptians: a retrospective study. JOURNAL OF COLOPROCTOLOGY 2021. [DOI: 10.1016/j.jcol.2017.09.418] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Abstract
Introduction Colorectal cancer is the 4th commonest cancer in the world. Studies had shown different tumor behavior depending on the site, pathology and stage. However the characters of Egyptian colon cancer patients are not well addressed.
Method Computerized registry of a tertiary cancer hospital in Egypt was searched for colon cancer cases. Demographic, pathologic and treatment data were collected and analyzed using SPSS program.
Results About 360 colon cancer patients attended our center in the last 12 years. Tumor characters showed great diverse from that of developed countries, with especially different prognosis and survival.
Conclusion Egyptians have unique tumor characters and behavior, and different compliance with treatment regimens. Multicenter prospective studies, as well as evolving Egyptian treatment guidelines are needed to address this.
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Affiliation(s)
- Islam H. Metwally
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
| | - Mosab Shetiwy
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
| | - Amr F. Elalfy
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
| | - Amr Abouzid
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
| | - Saleh S. Saleh
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
| | - Mohamed Hamdy
- Oncology Center Mansoura University (OCMU), Surgical Oncology Unit, Mansoura, Egypt
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25
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Abstract
IMPORTANCE Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide with more than 1.85 million cases and 850 000 deaths annually. Of new colorectal cancer diagnoses, 20% of patients have metastatic disease at presentation and another 25% who present with localized disease will later develop metastases. OBSERVATIONS Colorectal cancer is the third most common cause of cancer mortality for men and women in the United States, with 53 200 deaths projected in 2020. Among people diagnosed with metastatic colorectal cancer, approximately 70% to 75% of patients survive beyond 1 year, 30% to 35% beyond 3 years, and fewer than 20% beyond 5 years from diagnosis. The primary treatment for unresectable metastatic CRC is systemic therapy (cytotoxic chemotherapy, biologic therapy such as antibodies to cellular growth factors, immunotherapy, and their combinations.) Clinical trials completed in the past 5 years have demonstrated that tailoring treatment to the molecular and pathologic features of the tumor improves overall survival. Genomic profiling to detect somatic variants is important because it identifies the treatments that may be effective. For the 50% of patients with metastatic CRC with KRAS/NRAS/BRAF wild-type tumors, cetuximab and panitumumab (monoclonal antibodies to the epithelial growth factor receptor [EGFR]), in combination with chemotherapy, can extend median survival by 2 to 4 months compared with chemotherapy alone. However, for the 35% to 40% of patients with KRAS or NRAS sequence variations (formerly termed mutations), effective targeted therapies are not yet available. For the 5% to 10% with BRAF V600E sequence variations, targeted combination therapy with BRAF and EGFR inhibitors extended overall survival to 9.3 months, compared to 5.9 months for those receiving standard chemotherapy. For the 5% with microsatellite instability (the presence of numerous insertions or deletions at repetitive DNA units) or mismatch repair deficiency, immunotherapy may be used in the first or subsequent line and has improved treatment outcomes with a median overall survival of 31.4 months in previously treated patients. CONCLUSIONS AND RELEVANCE Advances in molecular profiling of metastatic CRC facilitate the ability to direct treatments to the biologic features of the tumor for specific patient subsets. Although cures remain uncommon, more patients can anticipate extended survival. Genomic profiling allows treatment selection so that more patients derive benefit and fewer are exposed to toxicity from ineffective therapies.
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Affiliation(s)
- Leah H Biller
- Division of Gastrointestinal Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
- Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts
| | - Deborah Schrag
- Division of Gastrointestinal Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
- Department of Medical Oncology, Harvard Medical School, Boston, Massachusetts
- Division of Population Sciences, Dana Farber Cancer Institute, Boston, Massachusetts
- Associate Editor, JAMA
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Neumann PA, Berlet MW, Friess H. Surgical oncology in the age of multimodality therapy for cancer of the upper and lower gastrointestinal tract. Expert Rev Anticancer Ther 2021; 21:511-522. [PMID: 33355020 DOI: 10.1080/14737140.2021.1868991] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION To date, all efforts to fight gastrointestinal cancer, regardless of its origin and entity, have resulted in complex therapeutic regimens involving a combination of systemic therapy, radiation therapy and surgery. It is generally accepted across all disciplines that not one, but the combination and the proper timing of all modalities result in the best oncologic outcome. AREAS COVERED Here, we provide insight into the current and future value of multimodal therapeutic approaches for upper and lower gastrointestinal cancer. Various aspects of treatment as well as open questions regarding indication and timing of multimodal strategies are addressed in this review. EXPERT OPINION In order to further improve the survival and quality of life of patients with gastrointestinal tumors in the future, scientifically proven multimodal therapy concepts are needed first and foremost. In addition, markers are pivotal to assign individual patients to a specific concept and to monitor the success of therapy. The main question is in which situation a neoadjuvant, perioperative or adjuvant radio-, chemo- or immunotherapy is superior. In fact, almost every curatively intended concept still contains surgical resection. Thus, improvement in surgical technique is also critical for multimodality concepts.
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Affiliation(s)
| | | | - Helmut Friess
- Department of Surgery, School of Medicine, Technical University of Munich, Germany
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27
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Gholami S, Stewart S, Kemeny N, Gönen M, Groot Koerkamp B, Cercek A, Kingham P, Balachandran V, Allen P, DeMatteo R, Wei A, Connell L, Drebin J, Jarnagin W, D'Angelica M. Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients. Ann Surg Oncol 2020; 28:3685-3694. [PMID: 33230748 DOI: 10.1245/s10434-020-09369-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 10/26/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population. METHODS Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor. RESULTS From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67]. CONCLUSIONS Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.
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Affiliation(s)
- Sepideh Gholami
- Department of Surgery, UC Davis Cancer Center, Sacramento, CA, USA
| | - Susan Stewart
- Division of Biostatistics, UC Davis Cancer Center, Sacramento, CA, USA
| | - Nancy Kemeny
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mithat Gönen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Andrea Cercek
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vinod Balachandran
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ronald DeMatteo
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alice Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Louise Connell
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeffrey Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - William Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Song J, Yang J, Lin R, Cai X, Zheng L, Chen Y. Molecular heterogeneity of guanine nucleotide binding-protein γ subunit 4 in left- and right-sided colon cancer. Oncol Lett 2020; 20:334. [PMID: 33123245 PMCID: PMC7584031 DOI: 10.3892/ol.2020.12197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 09/07/2020] [Indexed: 12/20/2022] Open
Abstract
Molecular heterogeneity determines the differences in the pathological features, prognosis and survival after relapse when comparing left-sided colon cancer (LCC) and right-sided colon cancer (RCC). At present, the discrepancy in the underlying molecular events between the two types of colon cancer has not been thoroughly investigated. The present study aimed to explore novel targets to predict the disease stage and prognosis of LCC and RCC. Expression analysis of guanine nucleotide binding-protein γ subunit 4 (GNG4) was performed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine databases. Survival and association analyses were performed using GEPIA and the colon adenocarcinoma dataset from The Cancer Genome Atlas database. GNG4-positive cells in a tissue microarray were examined using immunohistochemistry. According to the GNG4 expression data from Caucasian patients included in the TCGA dataset, GNG4 was highly expressed and positively associated with pathological stage and overall survival (OS) rates in colon cancer. GNG4 expression was higher in LCC than in RCC. Patients with LCC with high GNG4 expression exhibited higher pathological stage and lower survival rates, whereas this was not observed in patients with RCC. In addition, the clinical tissues used in the microarray showed that GNG4 expression was increased in Chinese patients with LCC compared with that in patients with RCC. Consistently, GNG4 expression was negatively associated with OS in patients with LCC, but not in patients with RCC. However, no association was observed between GNG4 expression and the disease stage of colon cancer in both patients with LCC and RCC. Overall, the molecular heterogeneity of GNG4 in LCC and RCC suggests that GNG4 may be used as a diagnostic and prognostic biomarker in patients with LCC.
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Affiliation(s)
- Jintian Song
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
| | - Jianwei Yang
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
| | - Rongbo Lin
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
| | - Xiongchao Cai
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
| | - Liang Zheng
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
| | - Yigui Chen
- Department of Abdominal Oncology, The Affiliated Cancer Hospital of Fujian Medical University, Fuzhou, Fujian 350014, P.R. China
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Targeting Gut Microbial Biofilms-A Key to Hinder Colon Carcinogenesis? Cancers (Basel) 2020; 12:cancers12082272. [PMID: 32823729 PMCID: PMC7465663 DOI: 10.3390/cancers12082272] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/06/2020] [Accepted: 08/10/2020] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
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Nitsche U, Weber C, Kaufmann B, von Figura G, Assfalg V, Miller G, Friess H, Hüser N, Hartmann D. Simultaneous Versus Staged Resection of Colorectal Cancer Liver Metastasis: A Retrospective Single-Center Study. J Surg Res 2020; 255:346-354. [PMID: 32599454 DOI: 10.1016/j.jss.2020.05.076] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/08/2020] [Accepted: 05/24/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND For patients with colorectal cancer and synchronous liver metastasis, either a simultaneous, or a two-staged resection of the primary tumor and the liver metastases is possible. There are currently no guidelines preferring one approach to the other. MATERIAL AND METHODS Consecutive patients who underwent hepatic resection at our university hospital from 2007-2016 were included. Clinical, histopathologic, serologic, and survival data were analyzed. The primary end point was tumor-specific survival for patients with simultaneous versus staged resections. RESULTS Of all 140 patients, 68 underwent simultaneous resection and 72 underwent staged resection. The characteristics of both groups were comparable. Patients with simultaneous resections had a shorter duration of cumulative operation time (299 versus 460 min; P = 0.003) and a shorter cumulative length of hospital stay (23 versus 43 d; P = 0.002). Perioperative mortality (P = 0.257) did not differ significantly; however, patients with simultaneous resections had higher rates of grade 2 complications according to Clavien-Dindo (P < 0.001). Tumor-specific 1-y survival was 85 ± 5% for simultaneous and 83 ± 5% for staged resection (P = 0.631). On multivariable analysis, pT4 (P = 0.038), pN3 (P = 0.003), and G3/4 (P = 0.041) of the primary tumor and postoperative complications (Clavien-Dindo 3/4/5, P = 0.003) were poor prognostic factors regarding tumor-specific survival. CONCLUSIONS This is one of the largest and most thoroughly documented retrospective single-center studies of consecutive patients with synchronous hepatic metastases. Simultaneous resection of colorectal cancer together with hepatic metastases is a safe procedure in selected patients and does not have a significant influence on long-term survival.
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Affiliation(s)
- Ulrich Nitsche
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
| | - Constance Weber
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Benedikt Kaufmann
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Guido von Figura
- Department of Medicine II, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Volker Assfalg
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Gregor Miller
- Department of Mathematics, Technical University of Munich, Munich, Germany
| | - Helmut Friess
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Norbert Hüser
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Daniel Hartmann
- Department of Surgery, TUM School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
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Del Rio P, Rossini M, Giuffrida M, Cozzani F, Guarnieri E, Dell'abate P. Rightward shift in colorectal cancer: experience in 1101 patients. MINERVA CHIR 2020; 75:225-233. [PMID: 32456392 DOI: 10.23736/s0026-4733.20.08263-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND In the past decades the right colon cancer showed a higher incidence rate than left colon cancer. This trend is known as "proximal shift" or "rightwards shift." We evaluated rightward shift phenomenon in our region. METHODS We collected data from 1101 colorectal cancer patients who underwent curative surgery at Parma University Hospital from 01 January 2004 through 01 January 2018. We divided patients into seven subgroups according to the time of surgery to evaluate epidemiological changes through the years of colon cancer. RESULTS We found a non-linear rightward shift trend of CRC. The incidence of RCC was the 40% between 2004-2005 and 51% in the biennium 2016-2017 (60% in 2012-2013 and 57% in 2014-2015). The patients with RCC were significantly older than patients with LCC. RCCs have poor differentiated tumors. Metastatic disease showed a similar distribution both in left and right CRCs. Peritoneum was the most common metastasis location from right-sided colon cancer. CONCLUSIONS Data suggest the existence of two different tumor entities in CRC between right-sided colon cancer and left-sided colon cancer. The proximal shift may be a reflection of improved screening programs, diagnostic accuracy and population aging. Ethnicity, gender, diet, environment, and socioeconomic status contribute to CRC incidence and prevalence in different regions.
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Affiliation(s)
- Paolo Del Rio
- Unit of General Surgery, Parma University Hospital, Parma, Italy
| | - Matteo Rossini
- Unit of General Surgery, Parma University Hospital, Parma, Italy -
| | - Mario Giuffrida
- Unit of General Surgery, Parma University Hospital, Parma, Italy
| | - Federico Cozzani
- Unit of General Surgery, Parma University Hospital, Parma, Italy
| | - Elena Guarnieri
- Unit of General Surgery, Parma University Hospital, Parma, Italy
| | - Paolo Dell'abate
- Unit of General Surgery, Parma University Hospital, Parma, Italy
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Bingham G, Shetye A, Suresh R, Mirnezami R. Impact of primary tumour location on colorectal liver metastases: A systematic review. World J Clin Oncol 2020; 11:294-307. [PMID: 32728532 PMCID: PMC7360521 DOI: 10.5306/wjco.v11.i5.294] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/09/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date.
AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM).
METHODS MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria.
RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC.
CONCLUSION Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.
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Affiliation(s)
- George Bingham
- Department of General Surgery, St. Thomas’s Hospital, Lambeth, London SE1 7EH, United Kingdom
| | - Alysha Shetye
- Department of Colorectal Surgery, Royal Free Hospital, Hampstead, London NW3 2QG, United Kingdom
| | - Reena Suresh
- Department of General Surgery, St. Thomas’s Hospital, Lambeth, London SE1 7EH, United Kingdom
| | - Reza Mirnezami
- Department of Colorectal Surgery, Royal Free Hospital, Hampstead, London NW3 2QG, United Kingdom
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Post JB, Roodhart JML, Snippert HJG. Colorectal Cancer Modeling with Organoids: Discriminating between Oncogenic RAS and BRAF Variants. Trends Cancer 2020; 6:111-129. [PMID: 32061302 DOI: 10.1016/j.trecan.2019.12.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 11/27/2019] [Accepted: 12/06/2019] [Indexed: 12/12/2022]
Abstract
RAS and BRAF proteins are frequently mutated in colorectal cancer (CRC) and have been associated with therapy resistance in metastatic CRC patients. RAS isoforms are considered to act as redundant entities in physiological and pathological settings. However, there is compelling evidence that mutant variants of RAS and BRAF have different oncogenic potentials and therapeutic outcomes. In this review we describe similarities and differences between various RAS and BRAF oncogenes in CRC development, histology, and therapy resistance. In addition, we discuss the potential of patient-derived tumor organoids for personalized therapy, as well as CRC modeling using genome editing in preclinical model systems to study similarities and discrepancies between the effects of oncogenic MAPK pathway mutations on tumor growth and drug response.
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Affiliation(s)
- Jasmin B Post
- Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, CX Utrecht, The Netherlands; Oncode Institute Netherlands, Office Jaarbeurs Innovation Mile, Utrecht, The Netherlands
| | - Jeanine M L Roodhart
- Department of Medical Oncology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Oncode Institute Netherlands, Office Jaarbeurs Innovation Mile, Utrecht, The Netherlands
| | - Hugo J G Snippert
- Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, CX Utrecht, The Netherlands; Oncode Institute Netherlands, Office Jaarbeurs Innovation Mile, Utrecht, The Netherlands.
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Bylsma LC, Gillezeau C, Garawin TA, Kelsh MA, Fryzek JP, Sangaré L, Lowe KA. Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta-analysis. Cancer Med 2019; 9:1044-1057. [PMID: 31856410 PMCID: PMC6997095 DOI: 10.1002/cam4.2747] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 09/23/2019] [Accepted: 10/29/2019] [Indexed: 12/12/2022] Open
Abstract
Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti‐epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta‐analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty‐four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta‐analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left‐sided tumors, 41.3% among right‐sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left‐sided tumors, 46.3% among right‐sided tumors; P < .0001) and BRAF mutations (4.3% among left‐sided tumors, 16.3% among right‐sided tumors; P < .0001). Among right‐sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left‐sided tumors and the prevalence of BRAF mutations in right‐sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression‐free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.
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Wang SM, Jiang B, Deng Y, Huang SL, Fang MZ, Wang Y. Clinical significance of MLH1/ MSH2 for stage II/III sporadic colorectal cancer. World J Gastrointest Oncol 2019; 11:1065-1080. [PMID: 31798786 PMCID: PMC6883179 DOI: 10.4251/wjgo.v11.i11.1065] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Revised: 08/10/2019] [Accepted: 09/10/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The development of colorectal cancer (CRC) is a complicated multistep process that involves an accumulation of mutations in tumor suppressor genes and oncogenes. In the process of DNA replication, base mismatch often occurs due to various factors leading to abnormal expression of mismatch repair genes (MMR), among which MLH1 and MSH2 are the most important. Recently, numerous studies indicated that MLH1/MSH2 phenotype is associated with CRC. We wanted to elucidate the role of MLH1/MSH2 in the prediction and prognosis of CRC through long-term clinical observation.
AIM To evaluate the prognostic and predictive significance of MLH1/MSH2 in patients with stage II-III CRC using immunohistochemical analysis and GeneScan.
METHODS Specimens from 681 patients with CRC (395 stage II and 286 stage III, 387 males and 294 females) who underwent curative surgical resection from 2013 to 2016 were tested. Immunohistochemistry was used to analyze MMR status and the microsatellite status of 133 patients was determined by GeneScan analysis.
RESULTS Five hundred and fifty (80.76%) patients were MLH1/MSH2 positive and 131 (19.24%) were negative by immunohistochemistry. MLH1/MSH2-positive tumors were significantly more frequent in the colon than in the rectum, and had poor differentiation and less mucin production (P < 0.05). Patients of different groups did not differ in terms of age, gender, tumor size, tumor stage, lymphocytic infiltration, or circumscribed margin. MLH1/MSH2-negative patients had a more favorable OS than MLH1/MSH2-positive patients (P < 0.001). Univariate and multivariate analyses demonstrated MLH1/MSH2 expression as an independent prognostic and predictive factor for stage II/III CRC. MLH1/MSH2 expression was a strong prognostic factor in all patients [P < 0.001, hazard ratio (HR) = 4.064, 95%CI: 2.241–7.369]. Adjuvant chemotherapy had a greater correlation with survival advantage in MLH1/MSH2-negative patients with stage III disease (P < 0.001, HR = 7.660, 95%CI: 2.974–15.883). However, patients with stage II disease or MLH1/MSH2-positive patients with stage III disease did not benefit from adjuvant chemotherapy. GeneScan analysis demonstrated that among 133 patients, 105 (78.95%) were microsatellite stable, and 28 (21.05%) had microsatellite instability (MSI), including 18 (13.53%) with high MSI and 10 (7.52%) with low MSI. This is consistent with the immunohistochemical results.
CONCLUSION MLH1/MSH2 phenotype constitutes a pathologically and clinically distinct subtype of sporadic CRC. MLH1/MSH2 is an independent prognostic and predictive factor for outcome of stage II-III CRC.
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Affiliation(s)
- Shui-Ming Wang
- National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Bin Jiang
- National Center of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Youping Deng
- Bioinformatics Core, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI 96813, United States
| | - Shu-Liang Huang
- Department of Pathology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Ming-Zhi Fang
- Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
| | - Yu Wang
- Bioinformatics Core, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI 96813, United States
- Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, Jiangsu Province, China
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Su C, Zhao J, Hong X, Yang S, Jiang Y, Hou J. Microarray‑based analysis of COL11A1 and TWIST1 as important differentially‑expressed pathogenic genes between left and right‑sided colon cancer. Mol Med Rep 2019; 20:4202-4214. [PMID: 31545476 PMCID: PMC6797952 DOI: 10.3892/mmr.2019.10667] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023] Open
Abstract
Colonic cancer has become a main reason of mortality associated with cancer; however, left and right-sided colonic cancer have diverse outcomes in terms of epidemiological, histological, clinical parameters and prognosis. We aimed to examine the discrepancies between these two types of colon cancers to identify potential therapeutic targets. In the present study, three gene expression profiles (GSE44076, GSE31595, GSE26906) from Gene Expression Omnibus (GEO) database were downloaded and further analyzed. A PPI (protein-protein interaction) network of the differentially-expressed genes (DEGs) of GSE44076 between tumor and normal was established with the Search Tool for the Retrieval of Interacting Genes database. Then, the DEGs of these two colon cancers (left, right) samples were identified. Subsequently, the intersection of DEGs of left and right-sided colon cancer samples obtained from three databases, and DEGs of tumor and normal samples were analyzed. Collagen type XI α1 chain (COL11A1), Twist family bHLH transcription factor 1 (TWIST1), insulin-like 5 and chromogranin A were upregulated proteins, while 3β-hydroxysteroid dehydrogenase was downregulated protein in right colon cancer than in left-sided tumor samples. Through further experimental verification, we revealed that COL11A1 and TWIST1 were significantly upregulated at the mRNA and protein levels within right-sided colon cancer compared with in left-sided colon cancer samples (P<0.05), consistent with bioinformatical analysis. Furthermore, a positive correlation between COL11A1 and TWIST1 protein expression was observed (P<0.0276). Collectively, our data showed that COL11A1 and TWIST1 may be potential prognostic indicators and molecular targets for the treatment of right-sided colon cancer.
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Affiliation(s)
- Chen Su
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China
| | - Jiabao Zhao
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China
| | - Xinya Hong
- Department of Medical Imaging and Ultrasound, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China
| | - Sijiu Yang
- Department of Critical Care Medicine, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China
| | - Ying Jiang
- Department of Clinical Medicine, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Jingjing Hou
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, P.R. China
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McVey JC, Sasaki K, Margonis GA, Nowacki AS, Firl DJ, He J, Berber E, Wolfgang C, Miller CC, Weiss M, Aucejo FN. The impact of resection margin on overall survival for patients with colon cancer liver metastasis varied according to the primary cancer location. HPB (Oxford) 2019; 21:702-710. [PMID: 30501989 DOI: 10.1016/j.hpb.2018.11.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 10/25/2018] [Accepted: 11/01/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Investigation into right and left-sided primary colon liver metastasis (CLM) has revealed differences in the tumor biology and prognosis. This indicates that preoperative and operative factors may affect outcomes of right-sided primary CLM differently than left. This retrospective analysis investigated the effects of resection margin stratified by left and right-sided primary CLM on overall survival (OS) for patients undergoing hepatectomy. METHODS A total of 732 patients undergoing hepatic resection for CLM at the Cleveland Clinic and Johns Hopkins were identified between 2002 and 2016. Clinically significant variables were analyzed using Cox proportional hazard regression. The cohort was then divided into patients with right and left-sided CLM and analyzed separately using Kaplan Meier analysis and Cox proportional hazard regression. RESULTS Cox proportional hazard regression showed that left-sided CLM with an R0 margin was a statistically significant predictor of OS even after controlling for other important factors (HR = 0.629, P = 0.024) but right-sided CLM with R0 margin was not (HR = 0.788, P = 0.245). Kaplan-Meier analysis demonstrated that patients with a left-sided CLM and R0 margin had the best prognosis (P = 0.037). CONCLUSION Surgical margin is an important prognostic factor for left-sided primary CLM but tumor biology may override surgical technique for right-sided CLM.
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Affiliation(s)
- John C McVey
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
| | - Kazunari Sasaki
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Georgios A Margonis
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy S Nowacki
- Department of Quantitative Health Sciences, Cleveland Clinic, OH
| | - Daniel J Firl
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Eren Berber
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Christopher Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Charles C Miller
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Federico N Aucejo
- Department of General Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
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Gasser E, Braunwarth E, Riedmann M, Cardini B, Fadinger N, Presl J, Klieser E, Ellmerer P, Dupré A, Imai K, Malik H, Baba H, Ulmer H, Schneeberger S, Öfner D, Dinnewitzer A, Stättner S, Primavesi F. Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score. PLoS One 2019; 14:e0217411. [PMID: 31150437 PMCID: PMC6544347 DOI: 10.1371/journal.pone.0217411] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 05/10/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) represents a major cause for cancer death and every third patient develops liver metastases (CRLM). Several factors including number and size of metastases and primary tumour lymph-node status have been linked to survival. The primary tumour location along the colo-rectum continuum (sidedness) was analysed in first-line chemotherapy trials, where right-sided CRCs showed decreased survival. This association has not yet been clearly established in patients undergoing resection for CRLM. METHODS Clinicopathological differences in CRLM resections according to sidedness in two Austrian centres (2003-2016) are described and survival is compared through Kaplan-Meier and multivariable analysis. A risk-score is presented with time-dependent receiver operating curve analysis and international validation in two major hepatobiliary centres. Furthermore, a systematic meta-analysis of studies on primary tumour location and survival after CRLM resection was performed. RESULTS 259 patients underwent hepatectomy. Right-sided CRC patients (n = 59) more often had positive primary tumour lymph-nodes (76.3%/61.3%;p = 0.043) and RAS-mutations (60%/34.9%;p = 0.036). The median overall and disease-free survival was 33.5 and 9.1 months in right-sided versus 55.5 (p = 0.051) and 12.1 months (p = 0.078) in left-sided patients. In multivariable analysis nodal-status (HR 1.52), right-sidedness (HR 1.53), extrahepatic disease (HR 1.71) and bilobar hepatic involvement (HR 1.41) were significantly associated with overall survival. Sidedness was not independently associated with disease-free survival (HR 1.33; p = 0.099). A clinical risk score including right-sidedness, nodal-positivity and extrahepatic involvement significantly predicted overall (p = 0.005) and disease-free survival (p = 0.027), which was confirmed by international validation in 527 patients (p = 0.001 and p = 0.011). Meta-analysis including 10 studies (n = 4312) showed a significant association of right-sidedness with overall survival after resection (HR 1.55;p<0.001). There was no significant association with disease-free survival (HR 1.22;p = 0.077), except when rectal-cancers were excluded (HR 1.39;p = 0.006). CONCLUSIONS Patients with liver metastases from right-sided CRC experience worse survival after hepatic resection. Sidedness is a simple yet effective factor to predict outcome.
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Affiliation(s)
- Elisabeth Gasser
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eva Braunwarth
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Marina Riedmann
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Benno Cardini
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Nikolaus Fadinger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Jaroslav Presl
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Eckhard Klieser
- Institute of Pathology, Paracelsus Medical University, Salzburg, Austria
| | - Philipp Ellmerer
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Aurélien Dupré
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Liverpool, United Kingdom
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan
| | - Hassan Malik
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Liverpool, United Kingdom
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan
| | - Hanno Ulmer
- Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Dietmar Öfner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Adam Dinnewitzer
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
| | - Florian Primavesi
- Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
- Department of Surgery, Paracelsus Medical University, Salzburg, Austria
- * E-mail:
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Lee JM, Han YD, Cho MS, Hur H, Min BS, Lee KY, Kim NK. Impact of tumor sidedness on survival and recurrence patterns in colon cancer patients. Ann Surg Treat Res 2019; 96:296-304. [PMID: 31183334 PMCID: PMC6543053 DOI: 10.4174/astr.2019.96.6.296] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 02/15/2019] [Accepted: 04/01/2019] [Indexed: 02/07/2023] Open
Abstract
Purpose Previous studies have reported conflicting results regarding the prognostic value of tumor sidedness in colon cancer. We investigated the oncologic impact of tumor location and examined whether recurrence patterns were related to tumor sidedness in colon cancer patients. Methods We identified stage I-III colon adenocarcinoma patients from a prospective colorectal cancer registry at Severance Hospital, Seoul, Korea, who underwent complete mesocolic excision between 2005 and 2012. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for predictors of cancer-specific survival (CSS), recurrence-free survival (RFS), and cumulative recurrence at specific anatomic sites were examined using Cox proportional hazard regression analysis. Results Overall, 1,912 patients, 1,077 (56.3%) with left-sided colon cancer (LCC), and 835 (43.7%) with right-sided colon cancer (RCC), at a median follow-up of 59 months, were eligible and included in the study. In univariate analysis, similar 5-year CSS and RFS were observed for LCC and RCC in the total patient population, and when stratified by stage for stage I and II patients. For stage III patients, an adjusted Cox regression analysis indicated that RCC patients had a higher risk of cancer-specific mortality (HR, 1.75; 95% CI, 1.07-2.86; P = 0.024) and recurrence (HR, 1.78; 95% CI, 1.22-2.60; P = 0.003). Furthermore, RCC was an independent predictor of peritoneal recurrence (HR, 1.86; 95% CI, 1.05-3.29; P = 0.031) in stage III patients. Conclusion RCC correlated with worse CSS and RFS than LCC. In stage III patients, RCC correlated with increased risk of peritoneal recurrence. The reasons for these differences remain to be investigated.
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Affiliation(s)
- Jong Min Lee
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Dae Han
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Min Soo Cho
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Hyuk Hur
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Soh Min
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Kang Young Lee
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Nam Kyu Kim
- Division of Colorectal Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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Kotha NV, Baumgartner JM, Veerapong J, Cloyd JM, Ahmed A, Grotz TE, Leiting JL, Fournier K, Lee AJ, Dineen SP, Dessureault S, Clarke C, Mogal H, Zaidi MY, Russell MC, Patel SH, Sussman JJ, Dhar V, Lambert LA, Hendrix RJ, Abbott DE, Pokrzywa C, Lafaro K, Lee B, Greer JB, Fackche N, Lowy AM, Kelly KJ. Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study. Ann Surg Oncol 2019; 26:2234-2240. [PMID: 31016486 DOI: 10.1245/s10434-019-07373-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Indexed: 01/05/2023]
Abstract
INTRODUCTION The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. RESULTS Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6-15.3) versus 13.1 months (95% CI 9.5-16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5-36.6) versus 45.4 months (95% CI 35.9-54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19-2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09-2.73; p = 0.020). CONCLUSION Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.
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Affiliation(s)
- Nikhil V Kotha
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Joel M Baumgartner
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Jula Veerapong
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Jordan M Cloyd
- Department of Surgery, Ohio State University, Columbus, OH, USA
| | - Ahmed Ahmed
- Department of Surgery, Ohio State University, Columbus, OH, USA
| | | | | | - Keith Fournier
- Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Andrew J Lee
- Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA
| | - Sean P Dineen
- Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | | | - Callisia Clarke
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Harveshp Mogal
- Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | | | - Sameer H Patel
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Jeffrey J Sussman
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Vikrom Dhar
- Department of Surgery, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - Laura A Lambert
- Department of Surgery, Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Ryan J Hendrix
- Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Daniel E Abbott
- Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Courtney Pokrzywa
- Department of Surgery, University of Wisconsin Hospital and Clinics, Madison, WI, USA
| | - Kelly Lafaro
- Department of Surgery, City of Hope Cancer Center, Duarte, CA, USA
| | - Byrne Lee
- Department of Surgery, City of Hope Cancer Center, Duarte, CA, USA
| | - Jonathan B Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Andrew M Lowy
- Department of Surgery, University of California, San Diego, San Diego, CA, USA
| | - Kaitlyn J Kelly
- Department of Surgery, University of California, San Diego, San Diego, CA, USA.
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Campo-Sánchez S, Camargo-Trillos J, Calle-Ramírez J, Gómez-Wolff L, Sánchez-Patiño L, García-García H. Colorectal cancer survival at an oncologic center in Colombia. A historic cohort study. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2018.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Wang G, Yu Y, Wang YZ, Wang JJ, Guan R, Sun Y, Shi F, Gao J, Fu XL. Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy. J Cell Physiol 2019; 234:17023-17049. [PMID: 30888065 DOI: 10.1002/jcp.28436] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 02/02/2019] [Accepted: 02/14/2019] [Indexed: 12/19/2022]
Abstract
Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
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Affiliation(s)
- Gang Wang
- Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai, China
| | - Yang Yu
- Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Yu-Zhu Wang
- Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Jun-Jie Wang
- Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai, China
| | - Rui Guan
- Information Resources Department, Hubei University of Medicine, Shiyan, Hubei, China
| | - Yan Sun
- Information Resources Department, Hubei University of Medicine, Shiyan, Hubei, China
| | - Feng Shi
- Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Jing Gao
- Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xing-Li Fu
- Department of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
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Kelly KJ, Alsayadnasser M, Vaida F, Veerapong J, Baumgartner JM, Patel S, Ahmad S, Barone R, Lowy AM. Does Primary Tumor Side Matter in Patients with Metastatic Colon Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy? Ann Surg Oncol 2019; 26:1421-1427. [PMID: 30815802 DOI: 10.1245/s10434-019-07255-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Indexed: 01/11/2023]
Abstract
BACKGROUND Primary tumor location has been shown to be prognostic of overall survival (OS) in patients with both locally advanced and metastatic colorectal cancer. The impact of sidedness on prognosis has not been evaluated in the setting of peritoneal-only metastases treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS A retrospective review of prospectively maintained databases of patients with peritoneal surface malignancy undergoing CRS/HIPEC from three high-volume centers was performed. RESULTS A total of 115 patients with metastatic colon cancer to the peritoneum who underwent CRS/HIPEC with mitomycin C were identified. Fifty-one patients (45%) had left-sided primary tumors, and 64 (55%) had right-sided primary tumors. Patients with right-sided tumors were more likely to be older (median age 56 vs. 49 years, p = 0.007) and to have signet ring cell histology (17% vs. 4%, p = 0.026). Patients with right-sided tumors had median disease-free survival (DFS) and OS of 14 months (95% confidence interval [CI] 10.5-17.5) and 36 months (95% CI 27.4-44.6), respectively, versus 16 months (95% CI 11.0-21.0) and 69 months (95% CI 24.3-113.7) for those patients with left-sided tumors. On multivariate analysis, primary tumor side was an independent predictor of both DFS and OS. CONCLUSIONS In this study, there was a dramatic, clinically significant difference in OS between patients with right- and left-sided tumors, and primary tumor side was an independent predictor of DFS and OS. Primary tumor side should be considered in patient selection for CRS with or without HIPEC.
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Affiliation(s)
- Kaitlyn J Kelly
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
| | - Masumah Alsayadnasser
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Florin Vaida
- Department of Family Medicine and Public Health, Division of Biostatistics and Bioinformatics, University of California, San Diego, San Diego, CA, USA
| | - Jula Veerapong
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Joel M Baumgartner
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
| | - Sameer Patel
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Syed Ahmad
- Department of Surgery, Division of Surgical Oncology, University of Cincinnati, Cincinnati, OH, USA
| | - Robert Barone
- Department of Surgery, Sharp Memorial Hospital, San Diego, CA, USA
| | - Andrew M Lowy
- Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
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Wang Z, Wang X, Zhang Z, Wang X, Chen M, Lu L, Zhu W, Zhang J, Jia H, Chen J. Association between Primary Tumor Location and Prognostic Survival in Synchronous Colorectal Liver Metastases after Surgical Treatment: A Retrospective Analysis of SEER Data. J Cancer 2019; 10:1593-1600. [PMID: 31205514 PMCID: PMC6547995 DOI: 10.7150/jca.29294] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 01/20/2019] [Indexed: 12/20/2022] Open
Abstract
The prognostic and predictive role of primary tumor location (PTL) in localized and metastatic colorectal cancer (CRC) is a hotspot issue in recent years. However, its prognostic role is still unclear in synchronous colorectal liver metastases (sCRLM), especially in those receiving surgical treatment of primary tumor and liver metastases. Here, a retrospective survival analysis was performed using the Surveillance, Epidemiology, and End Results Program (SEER) database between 2010 and 2014, on patients who were pathologically confirmed sCRLM, and received surgical treatment of both primary tumor and liver metastases. After stringent exclusive procedure, a total of 1508 patients with sCRLM (872 men [57.8%] and 636 women [42.2%]; mean age, 60.9 years) were eligible for the final study. Compared with sCRLM with left-sided PTL, cases with right-sided PTL were more likely to be T4 (31.3% vs. 20.1%, p<0.001), N2 (42.5% vs. 31.8%, p<0.001) and poorly differentiated (30.5% vs. 15.1%, p<0.001). Furthermore, right-sided sCRLM showed significantly shorter cancer specific survival (CSS) than those from left-side (p<0.001). After Cox hazard regression analysis, right-sided PTL still remained to be a strong independent predictor for poor prognosis in this cohort of sCRLM patients (OS, HR=1.75, 95% CI 1.34-2.29; CSS, HR=1.76, 95% CI 1.33-2.35). In conclusion, according to this population-based cohort from the SEER database, PTL was a critical prognostic factor that affect long-term OS and CSS in patients with sCRLM after surgical treatment of primary tumor and liver metastases.
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Affiliation(s)
- Zheng Wang
- Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiangyu Wang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Ze Zhang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Xuan Wang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Mo Chen
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Lu Lu
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Wenwei Zhu
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Jubo Zhang
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Huliang Jia
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
| | - Jinhong Chen
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China
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Tapia Rico G, Price T, Tebbutt N, Hardingham J, Lee C, Buizen L, Wilson K, Gebski V, Townsend A. Right or Left Primary Site of Colorectal Cancer: Outcomes From the Molecular Analysis of the AGITG MAX Trial. Clin Colorectal Cancer 2019; 18:141-148. [PMID: 30713134 DOI: 10.1016/j.clcc.2018.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 12/02/2018] [Accepted: 12/11/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND For metastatic colorectal cancer, previous reports have described differences in biology and outcome, including response to biologic agents, based on whether the primary tumor is right- or left-sided. We explored the molecular markers from the AGITG MAX trial. PATIENTS AND METHODS The AGITG MAX trial was a randomized study comparing capecitabine versus capecitabine + bevacizumab versus capecitabine + bevacizumab + mitomycin C as first-line therapy in advanced colorectal cancer. Patients were classified as having right-sided (caecum to transverse colon) or left-sided (descending colon to rectum) disease according to anatomic location. Baseline characteristics and previously described molecular profiles were compared by side of primary tumor. Survival outcomes were analyzed by the Kaplan-Meier approach and proportional hazards regression modeling. RESULTS Among the 471 patients, the location of primary tumor was known in 440 patients (93%). Molecular profile was known in 298 patients (63%). Twenty-eight percent had right-sided primary tumors. Major differences between right and left are as follows: female 49% versus 33% (P < .01), BRAF mutant 16% versus 3.5% (P ≤ .001), and phosphatase and tensin homolog (PTEN) loss 27.6% versus 53% (P = .01). There were no differences in RAS mutation, PIK3CA mutation, or high versus low expression of assessed angiogenic markers. Right-sided primary lesion predicted a poor outcome for median overall survival: right-sided disease 13.2 months versus left-sided disease 20 months (P = .001; hazard ratio [HR] = 0.67; 95% confidence interval [CI], 0.53-0.85), but not for progression-free survival (HR 0.96; 95% CI, 0.78-1.20). The relative treatment effect did not differ significantly according to location of primary tumor: right primary tumor HR (bevacizumab containing arm vs. capecitabine monotherapy arm) was 0.82 (95% CI, 0.54-1.22), and left primary HR (bevacizumab containing arm vs. capecitabine monotherapy arm) was 0.51 (95% CI, 0.4-0.63) (interaction P = .10). CONCLUSION There are more negative prognostic factors in patients with right-sided primary tumors, in particular high BRAF mutations, and these patients have inferior overall survival compared to those with a left-sided primary tumor. There was no suggestion that side of primary site had any impact on bevacizumab effect on progression-free survival.
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Affiliation(s)
- Gonzalo Tapia Rico
- Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia.
| | - Timothy Price
- Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia; Basil Hetzel Institute, Woodville, Australia; University of Sydney, Sydney, Australia
| | - Niall Tebbutt
- University of Sydney, Sydney, Australia; Department of Medical Oncology, Austin Health, Melbourne, Australia
| | - Jennifer Hardingham
- Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia; Basil Hetzel Institute, Woodville, Australia
| | - Chee Lee
- NHMRC Clinical Trials Centre, Sydney, Australia
| | - Luke Buizen
- NHMRC Clinical Trials Centre, Sydney, Australia
| | - Kate Wilson
- NHMRC Clinical Trials Centre, Sydney, Australia
| | - Val Gebski
- NHMRC Clinical Trials Centre, Sydney, Australia
| | - Amanda Townsend
- Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Australia; University of Adelaide, Adelaide, Australia; Basil Hetzel Institute, Woodville, Australia
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Abstract
Colorectal cancer (CRC) is a heterogeneous disease, and the search for clinical and molecular prognostic and predictive factors is thus necessary to better tailor each individual patient's management. Primary tumor location (PTL) seems to act as a master prognostic factor pooling different clinical, pathological, and molecular poor prognostic factors. In fact, right-sided (RS) CRC patients are more frequently female and elderly with microsatellite unstable, BRAF mutated, CpG island methylator phenotype (CIMP)-high, poorly differentiated tumors, compared to left-sided (LS) CRC patients. PTL does not seem to clearly influence disease-free survival (DFS) in localised colon cancer even though the opposite prognostic value of RS tumors on DFS depending on RAS/BRAF mutational status has been recently suggested in these patients. In metastatic CRC (mCRC), the poor prognosis associated with RS tumors is confirmed in the most recent publications in the era of double and triple chemotherapeutic regimens and targeted agents. Concerning the predictive value of PTL, in patients with RAS wild-type mCRC in the first-line setting, anti-epidermal growth factor receptor (EGFR) therapy combined with chemotherapy appears to be more effective than bevacizumab in LS CRC, while patients with RS CRC benefit less from anti-EGFR therapy, and intensive chemotherapy plus bevacizumab may be more appropriate but EGFR antibodies remain an option if objective response is needed. Due to the limitation of the current data (unplanned and retrospective analyses), these conclusions must be interpreted with caution. Clinical trials in RS CRC may be of interest to clarify what is the best treatment strategy in these patients.
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Liao CK, Chiang JM, Tsai WS, You JF, Hsieh PS, Hung HY, Chen HH, Tang RP, Chen JS, Yeh CY. Primary tumor location in stage III colon cancer has prognostic impact on subsequent liver metastasis. J Surg Oncol 2018; 118:1301-1310. [PMID: 30408183 DOI: 10.1002/jso.25270] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 09/16/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND OBJECTIVES We aim to investigate whether a difference exists between right-sided and left-sided colon cancer at the same disease stage and subsequent liver metastasis and identify whether tumor location can independently influence survival. METHODS Right-sided colon cancer was defined as malignancy arising from the cecum to the transverse colon; left-sided colon cancer was defined as malignancy arising from the splenic flexure to the sigmoid colon. Clinicopathological features and survival data were collected for analysis. RESULTS Overall, 1442 patients were included for analysis. The median follow-up time was 58.2 months. Patients with left-sided colon cancer had better 5-year overall survival (75.2% vs 61.7%, P = 0.005), 5-year cancer-specific survival (81.6% vs 73.4%, P = 0.001), and 5-year recurrence-free survival (70.9% vs 66.5%, P = 0.033) compared with patients having right-sided colon cancer. After the presentation of subsequent liver metastasis, patients with primary left-sided colon cancer had better 3-year cancer-specific survival ( P < 0.001). In the multivariate analysis, cancer location was an independent prognostic factor for cancer-specific survival (right vs left, HR: 1.276, 95% CI: 1.002-1.625). CONCLUSIONS The primary tumor location can serve as a prognostic factor for treatment outcomes either in primary stage III colon cancer or subsequent liver metastasis.
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Affiliation(s)
- Chun-Kai Liao
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Jy-Ming Chiang
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Wen-Sy Tsai
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Jeng-Fu You
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Pao-Shiu Hsieh
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Hsin-Yuan Hung
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Hong-Hwa Chen
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Rei-Ping Tang
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Jinn-Shiun Chen
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Yuh Yeh
- Department of Surgery, Colorectal Section, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan
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Jacobs D, Zhu R, Luo J, Grisotti G, Heller DR, Kurbatov V, Johnson CH, Zhang Y, Khan SA. Defining Early-Onset Colon and Rectal Cancers. Front Oncol 2018; 8:504. [PMID: 30460196 PMCID: PMC6232522 DOI: 10.3389/fonc.2018.00504] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2018] [Accepted: 10/15/2018] [Indexed: 12/14/2022] Open
Abstract
Background: Colorectal cancer (CRC) incidence is rising in the young, yet the age of those affected is not clearly defined. In this study, we identify such cohorts and define clinicopathological features of early-onset colon and rectal cancers. Methods: The Surveillance, Epidemiology and End Results Program (SEER) database was queried to compare clinicopathological characteristics of colon and rectal cancers diagnosed during 1973–1995 with those diagnosed during 1995–2014. Results: We identified 430,886 patients with colon and rectal cancers. From 1973–1995 to 1995–2014, colon cancer incidence increased in patients aged 20–44 years, while rectal cancer incidence increased in patients aged ≤54 years. The percent change of cancer incidence was greatest for rectal cancer with a 41.5% (95% confidence interval (CI): 37.4–45.8%) increase compared to a 9.8% (CI: 6.2–13.6%) increase in colon cancer. Colon cancer has increased in tumors located in ascending, sigmoid, and rectosigmoid locations. Adenocarcinoma histology has increased in both colon and rectal cancers (P < 0.01), but mucinous and signet ring cell subtypes have not increased (P = 0.13 and 0.08, respectively). Incidence increases were race-specific, with rectal cancer seeing similar rises in white (38.4%, CI: 33.8–43.1%) and black populations (38.0%, CI: 26.2–51.2%), while colon cancer as a whole saw a rise in white (11.5%, CI: 7.2–15.9%) but not black populations (−6.8%, CI: −14.6–1.9%). Conclusions: Our study underscores the existence of key differences between early-onset colon (20–44 years) and rectal cancers (≤54 years) and provides evidence-based inclusion criteria for future investigations. We recommend that future research of CRC in the young should avoid investigating these cases as a single entity.
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Affiliation(s)
- Daniel Jacobs
- Yale University School of Medicine, New Haven, CT, United States
| | - Rebecca Zhu
- Yale University School of Medicine, New Haven, CT, United States
| | - Jiajun Luo
- Department of Surgery, Yale University School of Medicine, New Haven, CT, United States
| | - Gabriella Grisotti
- Department of Surgery, Yale University School of Medicine, New Haven, CT, United States
| | - Danielle R Heller
- Department of Surgery, Yale University School of Medicine, New Haven, CT, United States
| | - Vadim Kurbatov
- Department of Surgery, Yale University School of Medicine, New Haven, CT, United States
| | - Caroline H Johnson
- Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, United States.,Yale Cancer Center New Haven, CT, United States
| | - Yawei Zhang
- Department of Surgery, Yale University School of Medicine, New Haven, CT, United States.,Department of Environmental Health Sciences, Yale University School of Public Health, New Haven, CT, United States
| | - Sajid A Khan
- Section of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT, United States
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Arora SP, Ketchum NS, Michalek J, Gelfond J, Mahalingam D. Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials? J Gastrointest Cancer 2018; 49:283-287. [PMID: 28432610 PMCID: PMC11801167 DOI: 10.1007/s12029-017-9948-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test. RESULTS One hundred thirty-nine patients with a median age 59 (33-81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. LOCATION right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03). CONCLUSIONS In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.
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Affiliation(s)
- Sukeshi Patel Arora
- Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Norma S Ketchum
- Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Joel Michalek
- Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Jonathon Gelfond
- Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Devalingam Mahalingam
- Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA.
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