Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Filip, Stanislav; Vymetalková, Veronika; Petera, Jiřı́; Vodičková, Ľudmila; Kubeček, Ondřej; John, Stanislav; Čečka, Filip; Krupova, Marketa; Manethova, Monika; Červená, Klára; Vodička, Pavel

doi:10.3390/ijms21155255

Cited by 51 publications

(45 citation statements)

References 206 publications

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“…Even though initially carrying identical mutations, further mutations result in genetic heterogeneity between the primary tumor and metastases (intertumor heterogeneity). Thus, primary tumor and distant metastases must be considered genetically heterogeneous 15 …”

Section: Methodsmentioning

confidence: 99%

Biomarkers in colorectal liver metastases: Rising complexity and unknown clinical significance?

Fichtner‐Feigl

2021

Annals of Gastroent Surgery

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Colorectal cancer (CRC) has 1.8 million cases globally and is the third most common cancer and ranks second by mortality. The incidence is rising due to socioeconomic developments, exposome changes, and the rise in age. 1 In all, 65% of CRC patients will develop metastases and 40% of those occur in the liver. Currently, the majority of CRC patients are assigned to curative surgery followed by adjuvant chemotherapy, which is predominantly determined by clinicopathologic features like primary tumor stage, carcinoembryonic antigen (CEA) level, nodal status, number and size of liver metastases, resection margin status, and the interval between primary tumor diagnosis and liver metastasis. 2,3 Notably, centers offering multidisciplinary treatment approaches including pathologists, radiologists, oncologists, and colorectal as well as liver surgeons show better survival rates than general hospitals or nonspecialized centers. 4 Over 50% of CRC patients will develop colorectal liver metastasis (CLM) and complete surgical removal still offers the best chance for long-term survival. 5 Nonetheless, one-third of CLM patients still succumb because of recurrent disease in the liver, which affects two-thirds of patients after resection. 6,7 Even modern multidisciplinary approaches that entail, e.g., two-stage hepatectomies after portal vein embolization, radiation, multiple ablation techniques for CLM (radiofrequency and microwave ablation), and expanding surgical techniques did not change this situation significantly until now. Currently, perioperative systematic therapy is suggested; however, a large randomized controlled trial by Nordlinger et al involving 364 patients showed no improvement in 5-year overall survival (OS) (51% vs 48%; P = .34) in

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Section: Methodsmentioning

confidence: 99%

Biomarkers in colorectal liver metastases: Rising complexity and unknown clinical significance?

Fichtner‐Feigl

2021

Annals of Gastroent Surgery

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“… 26 , 27 The indications for liver metastasis site resection and interventional therapy need to be carefully evaluated in colon adenocarcinoma. 28 Recently, some reports suggested that liver metastasis site resection could also benefit co-NEC patients. 29 – 31 More attempts to improve co-NEC patient survival and quality of life were encouraged.…”

Section: Discussionmentioning

confidence: 99%

Primary tumor location (right versus left side of the colon) and resection affect the survival of patients with liver metastases from colonic neuroendocrine carcinoma: a population-based study

Cui

Zhang

et al. 2021

Therap Adv Gastroenterol

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Background: Colonic neuroendocrine carcinomas (co-NECs) are heterogeneous and aggressive, especially with regard to metastasis. Whether co-NECs on the right and left sides of the colon have different characteristics from colon adenocarcinoma is unknown. Methods: The co-NEC patients were selected from the 2010–2017 Surveillance, Epidemiology, and End Results Program (SEER) database. The right and left sides of the colon were separated by the splenic flexure. Coarsened exact matching (CEM) was performed to adjust for relevant factors before regression models were constructed. Results: A total of 669 pathologically diagnosed co-NEC patients with sufficient baseline data were identified from the SEER database. A total of 80.72% of the patients had co-NEC that originated from the right side of the colon, and their mean overall survival (mOS) was similar to that of the patients with left-sided co-NECs (right versus left: 22.30 m versus 22.55 m). A total of 44.84% of the patients were diagnosed with liver metastasis (46.68% right side versus 37.98% left side). In patients with liver metastasis, those with right-sided co-NECs had better survival than those with left-sided co-NECs (mOS right versus left: 15.37 m versus 9.62 m; adjusted hazard ratio (HR) = 0.69, 95% confidence interval (CI): 0.49–0.98, p = 0.035). To further investigate the survival benefits of primary site resection, we separated the patients who had liver metastasis according to the primary site and performed CEM to balance the groups (no patients underwent liver metastasis resection or intervention). The results suggested that primary surgery could benefit patients with both left- and right-sided co-NECs (adjusted HR = 0.50, 95% CI: 0.33–0.77, p = 0.001 on the right side; HR = 0.38, 95% CI: 0.16–0.89, p = 0.026 on the left side). Conclusions: Co-NECs frequently originate on the right side and commonly develop liver metastasis. Right-sided co-NECs are associated with better survival than left-sided co-NECs after liver metastasis has occurred. Primary site resection is associated with prolonged survival in co-NEC patients with liver metastasis, regardless of the side from which the co-NEC has originated.

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“…During the slow development phases of polyp, different mutations start to accumulate and transform some of the polyps into malignant carcinoma [ 3 ]. Early stages of CRC are curable by surgery, however, when cancer metastasizes to lymph nodes or other distant organs, the prognosis of CRC becomes poor [ 4 ]. Furthermore, about 20% of CRC patients have already progressed into a metastatic state at the time of presentation and more than 30% of patients with early CRC have been reported to develop metastatic disease eventually [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis

Khan

Chowdhury

Billah

et al. 2021

IJMS

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Neutrophils form sticky web-like structures known as neutrophil extracellular traps (NETs) as part of innate immune response. NETs are decondensed extracellular chromatin filaments comprising nuclear and cytoplasmic proteins. NETs have been implicated in many gastrointestinal diseases including colorectal cancer (CRC). However, the regulatory mechanisms of NET formation and potential pharmacological inhibitors in the context of CRC have not been thoroughly discussed. In this review, we intend to highlight roles of NETs in CRC progression and metastasis as well as the potential of targeting NETs during colon cancer therapy.

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Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

Cited by 51 publications

References 206 publications

Biomarkers in colorectal liver metastases: Rising complexity and unknown clinical significance?

Biomarkers in colorectal liver metastases: Rising complexity and unknown clinical significance?

Primary tumor location (right versus left side of the colon) and resection affect the survival of patients with liver metastases from colonic neuroendocrine carcinoma: a population-based study

Neutrophil Extracellular Traps in Colorectal Cancer Progression and Metastasis

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