Colorectal Liver Metastasis (Volume II)

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

Deadline for manuscript submissions: closed (20 October 2023) | Viewed by 8062

Special Issue Editors


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Guest Editor
Director of Department of Surgery, Division of Hepatobiliary Surgery & General Surgery, Humanitas Research Hospital, 20089 Rozzano, Italy
Interests: liver; laparoscopic surgery; intraoperative US of liver
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Department of Biomedical Science, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy
2. Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 Rozzano, Italy
Interests: liver cancer; hepatocellular carcinoma; colangiocellular carcinoma; colorectal liver metastases; liver surgery

Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one, “Colorectal Liver Metastasis” (https://www.mdpi.com/journal/cancers/special_issues/CLM_Cancers).

Colorectal cancer is one of the leading causes of cancer-related deaths, presenting an advanced stage at diagnosis in more than 20% of patients, with the liver being the most common metastatic site. Surgery is considered the only curative treatment but cannot be carried out in up to 80% of cases. For patients with unresectable liver metastases, image-guided thermal ablations and radiation therapy have been proposed as effective and safe therapeutic options with curative intent. Several improvements have also been achieved in the systemic therapy for patients with unresectable disease, aimed at disease control and survival improvement. Other treatment strategies, such as transarterial chemoembolization or radioembolization, have been applied and represent promising treatment options for patients.

In this Special Issue, the state of the art and most recent innovations in the treatment of colorectal liver metastases will be presented and discussed.

Prof. Dr. Guido Torzilli
Dr. Guido Costa
Guest Editors

Manuscript Submission Information

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Keywords

  • liver surgery
  • hepatectomy
  • hepatic resection
  • colorectal liver metastases
  • treatment strategies

Published Papers (6 papers)

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Research

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13 pages, 1478 KiB  
Article
Resection of Colorectal Liver Metastases with Major Vessel Involvement
by Janine Baumgart, Sebastian Hiller, Kristina Stroh, Michael Kloth and Hauke Lang
Cancers 2024, 16(3), 571; https://doi.org/10.3390/cancers16030571 - 29 Jan 2024
Viewed by 490
Abstract
Background: Treatment of CRLM with major vessel involvement is still challenging and valid data on outcomes are still rare. We analyzed our experience of hepatectomies with resection and reconstruction of major hepatic vessels with regard to operative and perioperative details, histopathological findings and [...] Read more.
Background: Treatment of CRLM with major vessel involvement is still challenging and valid data on outcomes are still rare. We analyzed our experience of hepatectomies with resection and reconstruction of major hepatic vessels with regard to operative and perioperative details, histopathological findings and oncological outcome. Methods: Data of 32 hepatectomies with major hepatic vessel resections and reconstructions were included. Results were correlated with perioperative and oncological outcome. Results: Out of 1236 surgical resections due to CRLM, we performed 35 major hepatic vessel resections and reconstructions in 32 cases (2.6%) during the study period from January 2008 to March 2023. The vena cava inferior (VCI) was resected and reconstructed in 19, the portal vein (PV) in 6 and a hepatic vein (HV) in 10 cases. Histopathological examination confirmed a vascular infiltration in 6/32 patients (VCI 3/17, HV 2/10 and PV 1/6). There were 27 R0 and 5 R1 resections. All R1 situations affected the parenchymal margin. Vascular wall margins were R0. Ninety-day mortality was 0. The median overall survival (OS) for the patient group with vascular infiltration (V1) was 21 months and for the V0 group 33.3 months. Conclusion: Liver resections with vascular resection and reconstruction are rare and histological vessel infiltration occurs seldom. In cases with presumed vascular wall infiltration, liver resection combined with major vessel resection and reconstruction can be performed with low morbidity and mortality. We prefer a parenchymal sparing liver resection with vascular resection and reconstruction to achieve negative resection margins, but in technically difficult cases with higher risk for postoperative complications, tumor detachment from vessels without resection is a most reasonable surgical alternative. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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12 pages, 1277 KiB  
Article
Clinical Outcomes of Upfront Primary Tumor Resection in Synchronous Unresectable Metastatic Colorectal Cancer
by Ji Eun Shin, Ho Jung An, Byoung Yong Shim, Hyunho Kim, Hyung Soon Park, Hyeon-Min Cho, Bong-Hyeon Kye, Ri Na Yoo, Ji-Yeon Moon, Sung Hwan Kim, Jonghoon Lee, Hyo Chun Lee, Ji-Han Jung, Kang-Moon Lee and Ji Min Lee
Cancers 2023, 15(20), 5057; https://doi.org/10.3390/cancers15205057 - 19 Oct 2023
Viewed by 751
Abstract
The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group [...] Read more.
The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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28 pages, 10767 KiB  
Article
Vessel-Guided Mesohepatectomy for Liver Partition and Staged Major Parenchyma-Sparing Hepatectomies with Super-Selective Portal Vein Embolization or Enhanced ALPPS to Achieve R0 Resection for Colorectal Liver Metastases at the Hepatocaval Confluence
by Lucio Urbani, Nicolò Roffi, Roberto Moretto, Stefano Signori, Riccardo Balestri, Elisabetta Rossi, Piero Colombatto, Gabriella Licitra, Chiara Leoni, Rita Martinelli, Daniele Anacleto Meiattini, Emidio Bonistalli, Beatrice Borelli, Carlotta Antoniotti, Gianluca Masi, Daniele Rossini, Piero Boraschi, Francescamaria Donati, Maria Clotilde Della Pina, Alessandro Lunardi, Francesco Daviddi, Laura Crocetti, Michele Tonerini, Roberto Gigoni, Francesca Quilici, Raffaele Gaeta, Francesca Turco, Adriana Paolicchi, Duccio Volterrani, Vincenzo Nardini, Piero Buccianti, Francesco Forfori, Marco Puccini and Chiara Cremoliniadd Show full author list remove Hide full author list
Cancers 2023, 15(19), 4683; https://doi.org/10.3390/cancers15194683 - 22 Sep 2023
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Abstract
Background. R0 minor parenchyma-sparing hepatectomy (PSH) is feasible for colorectal liver metastases (CRLM) in contact with hepatic veins (HV) at hepatocaval confluence since HV can be reconstructed, but in the case of contact with the first-order glissonean pedicle (GP), major hepatectomy is [...] Read more.
Background. R0 minor parenchyma-sparing hepatectomy (PSH) is feasible for colorectal liver metastases (CRLM) in contact with hepatic veins (HV) at hepatocaval confluence since HV can be reconstructed, but in the case of contact with the first-order glissonean pedicle (GP), major hepatectomy is mandatory. To pursue an R0 parenchyma-sparing policy, we proposed vessel-guided mesohepatectomy for liver partition (MLP) and eventually combination with liver augmentation techniques for staged major PSH. Methods. We analyzed 15 consecutive vessel-guided MLPs for CRLM at the hepatocaval confluence. Patients had a median of 11 (range: 0–67) lesions with a median diameter of 3.5 cm (range: 0.0–8.0), bilateral in 73% of cases. Results. Grade IIIb or more complications occurred in 13%, median hospital stay was 14 (range: 6–62) days, 90-day mortality was 0%. After a median follow-up of 17.5 months, 1-year OS and RFS were 92% and 62%. In nine (64%) patients, MLP was combined with portal vein embolization (PVE) or ALPPS to perform staged R0 major PSH. Future liver remnant (FLR) volume increased from a median of 15% (range: 7–20%) up to 41% (range: 37–69%). Super-selective PVE was performed in three (33%) patients and enhanced ALPPS (e-ALPPS) in six (66%). In two e-ALPPS an intermediate stage of deportalized liver PSH was necessary to achieve adequate FLR volume. Conclusions. Vessel-guided MLP may transform the liver in a paired organ. In selected cases of multiple bilobar CRLM, to guarantee oncological radicality (R0), major PSH is feasible combining advanced surgical parenchyma sparing with liver augmentation techniques when FLR volume is insufficient. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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15 pages, 2127 KiB  
Article
Tas-102 for Refractory Metastatic Colorectal Cancer: A Multicenter Retrospective Cohort Study
by Matteo Conti, Elena Bolzacchini, Giovanna Luchena, Lorenza Bertu’, Paola Tagliabue, Stefania Aglione, Antonio Ardizzoia, Jessica Arnoffi, Francesco Maria Guida, Alessandro Bertolini, Alessandro Pastorini, Maria Duro, Donato Bettega, Giovambattista Roda’, Salvatore Artale, Alessandro Squizzato and Monica Giordano
Cancers 2023, 15(13), 3465; https://doi.org/10.3390/cancers15133465 - 02 Jul 2023
Cited by 2 | Viewed by 1361
Abstract
Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. [...] Read more.
Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. We conducted a retrospective multicenter study to assess the effectiveness and safety of TAS-102 in consecutive patients with pretreated mCRC. In particular, we estimated the effectiveness and safety of TAS-102 in elderly patients (aged ≥70, ≥75 and ≥80 years) and in special subgroups, e.g., patients with concomitant heart disease. One hundred and sixty patients were enrolled. In particular, 71 patients (44%) were 70 years of age or older, 50 (31%) were 75 years of age or older, and 23 (14%) were 80 years of age or older. 19 patients (12%) had a concomitant chronic heart disease, three (2%) patients were HIV positive, and one (<1%) patient had a DPYD gene polymorphism. In 115 (72%) cases TAS-102 was administered as a third-line treatment. The median overall survival (OS) in the overall population was 8 months (95% confidence interval [CI], 6–9), while the median progression-free survival (PFS) was 3 months (95% CI, 3–4). No significant age-related reduction in effectiveness was observed in the subpopulations of elderly patients included. The toxicity profile was acceptable in both the whole and subgroups’ population. Our study confirms the effectiveness and safety of TAS-102 in patients with pretreated mCRC, suggesting a similar risk-benefit profile in the elderly. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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14 pages, 2446 KiB  
Article
Individualized Selection Criteria Based on Tumor Burden in Future Remnant Liver for Staged Hepatectomy of Advanced CRLM: Conventional TSH or ALPPS
by Kun-Ming Chan, Hao-Chien Hung, Jin-Chiao Lee, Tsung-Han Wu, Yu-Chao Wang, Chih-Hsien Cheng, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou and Wei-Chen Lee
Cancers 2022, 14(14), 3553; https://doi.org/10.3390/cancers14143553 - 21 Jul 2022
Viewed by 1433
Abstract
Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) [...] Read more.
Staged hepatectomy is a promising strategy for curative resection of advanced colorectal liver metastasis (CRLM) to prevent inadequate future remnant liver (FRL). However, the selection criteria for conventional two-stage hepatectomy (cTSH) and associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) remain unclear. This study aimed to propose a selection criterion for determining the optimal staged hepatectomy for patients with advanced CRLM. A selection criterion based on the degree of metastatic tumors within the FRL was established to determine staged hepatectomy approaches. Generally, ALPPS is recommended for patients with ≤3 metastatic nodules and whose nodules do not measure >3 cm in the FRL. cTSH is performed for patients whose tumor burden in FRL beyond the selection criteria. Data of 37 patients who underwent staged hepatectomy and curative intent of CRLM were analyzed. The clinical characteristics and outcomes of the two approaches were compared. Overall, cTSH and ALPPS were performed for 27 (73.0%) and 10 (27.0%) patients, respectively. Of those, 20 patients in the cTSH group and all patients in the ALPPS group had completed staged hepatectomy. The 1-, 3-, and 5-year survival rates were 91.6%, 62.4%, and 45.4% for all patients, respectively. The outcomes of patients who had successfully completed the staged hepatectomy were significantly better than those of other patients who failed to achieve staged hepatectomy. However, no significant difference was observed in the overall survival of patients who underwent staged hepatectomy between the two groups, but those in the ALPPS group had 100% survival at the end of this study. The individualized selection criteria based on tumor burden in the FRL that could balance the operative risk and oncologic outcome appear to be a promising strategy for achieving complete staged hepatectomy in patients with advanced CRLM. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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Review

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18 pages, 1787 KiB  
Review
Colorectal Liver Metastasis: Can Cytokines Make the Difference?
by Costanza Ballarò, Valeria Quaranta and Gianluigi Giannelli
Cancers 2023, 15(22), 5359; https://doi.org/10.3390/cancers15225359 - 10 Nov 2023
Viewed by 1164
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Metastasis is the prime driver of CRC-related mortality, and the liver is the organ most frequently involved. Despite the overall success of current treatments, colorectal liver metastasis (CRLM) is associated with [...] Read more.
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Metastasis is the prime driver of CRC-related mortality, and the liver is the organ most frequently involved. Despite the overall success of current treatments, colorectal liver metastasis (CRLM) is associated with poor prognoses and a survival rate of only 14%. Recent studies have highlighted the importance of the tumor microenvironment (TME) and the crosstalk within it in determining the invasion of distant organs by circulating cancer cells. In the TME, cellular communication is mediated via soluble molecules, among which cytokines have recently emerged as key regulators, involved in every aspect of tumor progression and the metastatic cascade. Indeed, in the serum of CRC patients elevated levels of several cytokines are associated with cancer development and progression. The current review evaluates the role of different cytokines during CRLM development. Additionally, considering the increasing amount of data concerning the importance of cytokine complex networks, we outline the potential of combination treatments using targeted cytokines together with other well-established therapies, such as immune checkpoint blockades, chemotherapy, or gene therapy, to improve therapeutic outcomes. Full article
(This article belongs to the Special Issue Colorectal Liver Metastasis (Volume II))
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