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Cancers
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Contemporary Treatment of Colorectal Cancer
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Contemporary Treatment of Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 10 December 2024 | Viewed by 6909

Special Issue Editor

Dr. Michel Adamina

E-Mail Website
Guest Editor
Chief of Colorectal Surgery, Department of Surgery, Cantonal Hospital Winterthur, Brauerstrasse 15, Postfach 834, 8401 Winterthur, Switzerland
Interests: colorectal cancer; IBD; machine learning; colorectal surgery; leadership; medical education; pelvic floor; health economy; peritoneal cancer; cytoreductive surgery; HIPEC; PIPAC

Special Issue Information

Dear Colleagues,

Colorectal cancer is on the rise, with younger patients affected and a higher number of patients overall. Multimodal treatment has led to significant improvements in survival and quality of life with a majority of patients now amenable to a cure, including selected patients with peritoneal or solid organ metastases. Better screening, diagnostic accuracy and refined prognosis, as well as advanced therapeutic concepts, including multimodal neoadjuvant treatment, tailored surgery and multiple lines of adjuvant therapy, all contributed to the significant progress observed in clinical care and outcomes. The present Special Issue addresses the complexity of colorectal cancer and its contemporary management, with several topics highlighted: diagnostic and prognostic markers, cutting-edge imaging, total neoadjuvant and adjuvant therapy, state-of-the-art surgical approaches, including laparoscopic, robotic and transanal surgery, cytoreductive surgery and intraperitoneal chemotherapy, adjuvant chemo- and immunotherapy and best palliative care.

Dr. Michel Adamina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • colon cancer
  • rectum cancer
  • colorectal surgery
  • neoadjuvant treatment
  • adjuvant treatment
  • radiotherapy
  • chemotherapy
  • immunotherapy
  • minimally invasive surgery
  • laparoscopic surgery
  • transanal surgery, taTME, TAMIS
  • total mesorectal excision
  • cytoreductive surgery
  • hyperthermic intraperitoneal chemotherapy, HIPEC
  • pressurized intraperitoneal chemotherapy, PIPAC

Published Papers (6 papers)

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Research

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19 pages, 939 KiB  
Article
The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer—From a Clinical Oncologic Point of View
by Balázs Pécsi and László Csaba Mangel
Cancers 2024, 16(8), 1460; https://doi.org/10.3390/cancers16081460 - 11 Apr 2024
Viewed by 324
Abstract
Aim: The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for [...] Read more.
Aim: The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. Method: We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. Results: A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36–0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33–0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18–0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18–0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58–1.26)). Conclusions: The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease’s inherent biology. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)
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13 pages, 1208 KiB  
Article
Recurrence and Survival Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Synchronous and Metachronous Peritoneal Metastases of Colorectal Origin
by Mette Fugleberg Nielsen, Sissel Ravn, Mette Møller Sørensen, Jonas Amstrup Funder and Lene Hjerrild Iversen
Cancers 2024, 16(3), 631; https://doi.org/10.3390/cancers16030631 - 01 Feb 2024
Cited by 1 | Viewed by 905
Abstract
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to [...] Read more.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved the 5-year survival for colorectal cancer (CRC) patients with peritoneal metastases (PM). Little is known about recurrence patterns and recurrence rates between synchronous (S) and metachronous (M) PM following CRS+HIPEC. We aimed to describe the recurrence patterns, overall survival (OS) and disease-free survival (DFS) in S-PM and M-PM patients after complete CRS+HIPEC. From June 2006 to December 2020, a prospective cohort study included 310 CRC patients, where 181 patients had S-PM (58.4%) and 129 patients had M-PM (41.6%). After a median 10.3-month follow-up, 247/310 (79.7%) patients experienced recurrence, and recurrence sites included isolated peritoneal (32.4%), multifocal (peritoneal and liver and/or lung(s)) (22.7%), isolated liver (17.8%), isolated lung (10.5%) and other (16.6%) sites. Recurrence patterns did not differ between S-PM and M-PM. M-PM patients had an impaired DFS compared to S-PM patients (9.4 months (95% CI: 7.3–12.1) vs. 12.5 months (95% CI: 11.2–13.9), p = 0.01). The median OS was similar for S-PM and M-PM (38.4 months (95% CI: 31.2–46.8) vs. 40.8 months (95% CI: 28.8–46.8), p = 0.86). Despite frequent recurrence at extraperitoneal locations, long-term survival was achievable after CRS+HIPEC in CRC patients with PM. The recurrence patterns and OS did not differ between groups, yet M-PM patients had a shorter DFS. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)
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16 pages, 2207 KiB  
Article
Assessment of the DNA Mismatch Repair System Is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: A Propensity Score-Matched and Win Ratio Analysis
by Eva Lieto, Francesca Cardella, Duolao Wang, Andrea Ronchi, Giovanni Del Sorbo, Iacopo Panarese, Francesca Ferraraccio, Ferdinando De Vita, Gennaro Galizia and Annamaria Auricchio
Cancers 2024, 16(1), 134; https://doi.org/10.3390/cancers16010134 - 27 Dec 2023
Viewed by 741
Abstract
A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the [...] Read more.
A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the main features of this subset. The aim of this study was to evaluate the predictive value of DNA MMR system status for its best treatment. Four hundred and three CRC patients, operated on from 2014 to 2021 and not treated with immunotherapy, entered this study. Immunohistochemistry and polymerase chain reaction, as appropriate, were used to unequivocally group specimens into microsatellite stable (MSS) and instable (MSI) tumors. The win-ratio approach was utilized to compare composite outcomes. MSI tumors accounted for 12.9% of all series. The right tumor location represented the most important factor related to MSI. The status of the DNA MMR system did not appear to correlate with outcome in early-stage CRCs not requiring adjuvant treatment; in advanced stages undergoing conventional chemotherapy, MSI tumors showed significantly poorer overall and disease-free survival rates and the highest win ratio instead. The determination of DNA MMR status is crucial to recommending correct management. There is clear evidence that instable CRCs needing adjuvant therapy should undergo appropriate treatments. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)
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17 pages, 3695 KiB  
Article
Prognostic Significance of MRE11 Overexpression in Colorectal Cancer Patients
by Vincent Ho, Liping Chung, Kate Wilkinson, Vivienne Lea, Stephanie H. Lim, Askar Abubakar, Weng Ng, Mark Lee, Tara L. Roberts, Wei Chua and Cheok Soon Lee
Cancers 2023, 15(9), 2438; https://doi.org/10.3390/cancers15092438 - 24 Apr 2023
Cited by 1 | Viewed by 1342
Abstract
Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), [...] Read more.
Meiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan–Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS; p = 0.045) and overall survival (OS; p = 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p = 0.005) and OS (p = 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034–2.785; p = 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122–3.293; p = 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p = 0.006) and LVI/PNI (p = 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)
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14 pages, 279 KiB  
Article
Surgical Outcomes, Long-Term Recurrence Rate, and Resource Utilization in a Prospective Cohort of 165 Patients Treated by Transanal Total Mesorectal Excision for Distal Rectal Cancer
by Severin Gloor, Gioia Pozza, Rebekka Troller, Markus Wehrli and Michel Adamina
Cancers 2023, 15(4), 1190; https://doi.org/10.3390/cancers15041190 - 13 Feb 2023
Cited by 3 | Viewed by 1194
Abstract
A transanal total mesorectal excision (taTME) is a smart alternative to a conventional TME. However, worrisome reports of a high recurrence and complications triggered a moratorium in a few countries. This study assessed the outcomes and resource utilization of a taTME. Consecutive patients [...] Read more.
A transanal total mesorectal excision (taTME) is a smart alternative to a conventional TME. However, worrisome reports of a high recurrence and complications triggered a moratorium in a few countries. This study assessed the outcomes and resource utilization of a taTME. Consecutive patients with distal rectal cancer treated by a taTME were prospectively included. Outcomes were reported as the median and interquartile range (IQR). One hundred sixty-five patients (67% male and 33% female) with a tumor 7 cm (IQR 5–10) from the anal verge were followed for 50 months (IQR 32–79). The resection margins were threatened in 25% of the patients, while 75% of the patients received neoadjuvant radiochemotherapy. A good mesorectal dissection and clear margins were achieved in 96% of the specimens, and 27 lymph nodes (IQR 20–38) were harvested. Ninety-day major morbidity affected 36 patients (21.8%), including 12 with anastomotic leakages (7.2%). A recurrence occurred locally in 9 patients (5.4%), and 44 patients had a distant metastasis (26.7%). The five-year disease-free survival and overall survival were 67% and 90%, respectively. A multivariate analysis found a long operation and frailty predicted an anastomotic leak, while a positive distal margin and lymph nodes predicted a local recurrence and distant metastasis. A two-team taTME saved 102 min of operative time and EUR 1385 when compared to a one-team approach. Transanal total mesorectal excision produced sound surgical quality and excellent oncologic outcomes. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)

Review

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21 pages, 3446 KiB  
Review
Alternative Splicing Events and Their Clinical Significance in Colorectal Cancer: Targeted Therapeutic Opportunities
by Mosebo Armstrong Manabile, Rodney Hull, Richard Khanyile, Thulo Molefi, Botle Precious Damane, Nigel Patrick Mongan, David Owen Bates and Zodwa Dlamini
Cancers 2023, 15(15), 3999; https://doi.org/10.3390/cancers15153999 - 07 Aug 2023
Cited by 1 | Viewed by 1668
Abstract
Colorectal cancer (CRC) ranks as one of the top causes of cancer mortality worldwide and its incidence is on the rise, particularly in low-middle-income countries (LMICs). There are several factors that contribute to the development and progression of CRC. Alternative splicing (AS) was [...] Read more.
Colorectal cancer (CRC) ranks as one of the top causes of cancer mortality worldwide and its incidence is on the rise, particularly in low-middle-income countries (LMICs). There are several factors that contribute to the development and progression of CRC. Alternative splicing (AS) was found to be one of the molecular mechanisms underlying the development and progression of CRC. With the advent of genome/transcriptome sequencing and large patient databases, the broad role of aberrant AS in cancer development and progression has become clear. AS affects cancer initiation, proliferation, invasion, and migration. These splicing changes activate oncogenes or deactivate tumor suppressor genes by producing altered amounts of normally functional or new proteins with different, even opposing, functions. Thus, identifying and characterizing CRC-specific alternative splicing events and variants might help in designing new therapeutic splicing disrupter drugs. CRC-specific splicing events can be used as diagnostic and prognostic biomarkers. In this review, alternatively spliced events and their role in CRC development will be discussed. The paper also reviews recent research on alternatively spliced events that might be exploited as prognostic, diagnostic, and targeted therapeutic indicators. Of particular interest is the targeting of protein arginine methyltransferase (PMRT) isoforms for the development of new treatments and diagnostic tools. The potential challenges and limitations in translating these discoveries into clinical practice will also be addressed. Full article
(This article belongs to the Special Issue Contemporary Treatment of Colorectal Cancer)
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