|
1
|
Wehrle CJ, Tocci NX, Sun K, Jiao C, Hong H, Gross A, Allkushi E, Uysal M, Linganna MW, Stackhouse K, Hashimoto K, Schlegel A, Walsh RM, Miller C, Kwon DCH, Aucejo F. Utility of circulating tumor DNA in secondary liver malignancies: What we know and what is to come. J Surg Oncol 2025; 131:888-894. [PMID: 39155652 PMCID: PMC12120384 DOI: 10.1002/jso.27838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 07/27/2024] [Indexed: 08/20/2024]
Abstract
Secondary liver malignancies are a serious and challenging global health concern. Secondary metastasis to the liver is most commonly from colorectal cancer that has metastatically spread through splanchnic circulation. Metastatic diseases can portend poor prognosis due to the progressive nature typically found on detection. Improvements in detection of disease, monitoring therapy response, and monitoring for recurrence are crucial to the improvement in the management of secondary liver malignancies. Assessment of ctDNA in these patient populations poses an opportunity to impact the management of secondary liver malignancies. In this review, we aim to discuss ctDNA, the current literature, and future directions of this technology within secondary liver malignancies.
Collapse
Affiliation(s)
- Chase J. Wehrle
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Noah X. Tocci
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Keyue Sun
- Cleveland Clinic Foundation, Lerner Research Institute, Inflammation & ImmunityClevelandOhioUSA
| | - Chunbao Jiao
- Cleveland Clinic Foundation, Lerner Research Institute, Inflammation & ImmunityClevelandOhioUSA
| | - Hanna Hong
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Abby Gross
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Erlind Allkushi
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Melis Uysal
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Maureen Whitsett Linganna
- Department of Gastroenterology, Hepatology, and NutritionCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Katheryn Stackhouse
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Koji Hashimoto
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Andrea Schlegel
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
- Cleveland Clinic Foundation, Lerner Research Institute, Inflammation & ImmunityClevelandOhioUSA
| | - R. Matthew Walsh
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Charles Miller
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - David C. H. Kwon
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| | - Federico Aucejo
- Department of Hepato‐Pancreato‐Biliary & Liver Transplant SurgeryCleveland Clinic Foundation, Digestive Diseases and Surgery InstituteClevelandOhioUSA
| |
Collapse
|
|
2
|
Vaz da Silva DG, de Ribeiro HSDC, Dos Santos GO, Lindote MVN, Torres SM, Diniz AL, de Godoy AL, de Farias IC, Felismino TC, da Costa Junior WL, Coimbra FJF. Dense tumor-infiltrating lymphocytes (TILs) in liver metastasis from colorectal cancer are related to improved overall survival. J Surg Oncol 2024. [PMID: 38946284 DOI: 10.1002/jso.27759] [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: 04/04/2024] [Accepted: 06/02/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND AND OBJECTIVES Tumor-infiltrating lymphocytes (TILs) represent a host-tumor interaction, frequently signifying an augmented immunological response. Nonetheless, implications with survival outcomes in patients with colorectal carcinoma liver metastasis (CRLM) warrant rigorous validation. The objective was to demonstrate the association between TILs and survival in patients with CRLM. METHOD In a retrospective evaluation conducted in a single institution, we assessed all patients who underwent hepatectomy due to CRLM between 2014 and 2018. Comprehensive medical documentation reviews were executed. TILs were assessed by a liver pathologist, blinded to the clinical information, in all surgical slides. RESULTS This retrospective cohort included 112 patients. Median overall survival (OS) was 58 months and disease-free survival (DFS) was 12 months for the entire cohort. Comparison between groups showed a median OS of 81 months in the dense TILs group and 40 months in the weak/absent group (p = 0.001), and DFS was 14 months versus 9 months (p = 0.041). Multivariable analysis showed that TILs were an independent predictor of OS (HR 1.95; p = 0.031). CONCLUSIONS Dense TILs are a pivotal prognostic indicator, correlating with enhanced OS. Including TILs information in histopathological evaluations should refine the clinical decision-making process for this group of patients.
Collapse
Affiliation(s)
| | | | | | | | - Silvio Mello Torres
- Department of Abdominal Surgery, A. C. Camargo Cancer, CenterSão Paulo, Brazil
| | | | - André Luiz de Godoy
- Department of Abdominal Surgery, A. C. Camargo Cancer, CenterSão Paulo, Brazil
| | | | | | | | | |
Collapse
|
|
3
|
Storman D, Swierz MJ, Mitus JW, Pedziwiatr M, Liang N, Wolff R, Bala MM. Microwave coagulation for liver metastases. Cochrane Database Syst Rev 2024; 3:CD010163. [PMID: 38534000 PMCID: PMC10966940 DOI: 10.1002/14651858.cd010163.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
BACKGROUND Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance. OBJECTIVES To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023. SELECTION CRITERIA Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported. Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes. Microwave ablation versus conventional surgery One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL. Microwave ablation versus radiofrequency ablation One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL. One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding. We identified four ongoing trials. AUTHORS' CONCLUSIONS The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either. Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking. In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases. The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.
Collapse
Affiliation(s)
- Dawid Storman
- Chair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland
| | - Mateusz J Swierz
- Chair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland
| | - Jerzy W Mitus
- Department of Surgical Oncology, The Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch; Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland
| | - Michal Pedziwiatr
- 2nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Ning Liang
- Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | | | - Malgorzata M Bala
- Chair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland
| |
Collapse
|
|
4
|
Cheng XF, Zhao F, Chen D, Liu FL. Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis. World J Gastroenterol 2024; 30:663-672. [PMID: 38515943 PMCID: PMC10950626 DOI: 10.3748/wjg.v30.i7.663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 12/22/2023] [Accepted: 01/22/2024] [Indexed: 02/21/2024] Open
Abstract
Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.
Collapse
Affiliation(s)
- Xiao-Fei Cheng
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Feng Zhao
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| | - Fan-Long Liu
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
| |
Collapse
|
|
5
|
Qin S, Chen Y, Wang Y, Li F, Cui R, Liu G. Contrast-enhanced ultrasound with microbubbles containing sulfur hexafluoride and perfluorobutane with Kupffer phase for the detection of colorectal liver metastases. Eur Radiol 2024; 34:622-631. [PMID: 37566263 DOI: 10.1007/s00330-023-10051-1] [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: 02/13/2023] [Revised: 06/02/2023] [Accepted: 06/25/2023] [Indexed: 08/12/2023]
Abstract
OBJECTIVE To compare contrast-enhanced ultrasound (CEUS) with microbubbles containing sulfur hexafluoride (SHF) and perfluorobutane (PFB) for the detection of colorectal liver metastasis (CRLM). METHODS In this prospective study, conducted from September to November 2021, patients with colorectal cancer were consecutively recruited and underwent same-day ultrasound, SHF-CEUS, and PFB-CEUS. The reference standard was contrast-enhanced MRI and follow-up imaging. The size, depth, echogenicity, and calcification of each focal liver lesion were recorded. The number and conspicuity of CRLMs, based on washout appearance during the late phase (LP) (> 120 s)/Kupffer phase (KP), were evaluated offsite by two blinded readers. RESULTS Overall, 230 lesions (CRLMs, n = 219; benign lesions, n = 11) in 78 patients were evaluated. Lesion conspicuity (p = 0.344) and accuracy in the detection of CRLM were comparable for SHF- and PFB-CEUS (0.877 for SHF vs. 0.770 for PFB, p = 0.087). More CRLMs ≥ 10 mm were identified by LP contrast washout in SHF-CEUS than in KP PFB-CEUS (p < 0.001). More CRLMs < 10 mm were identified by KP washout in PFB-CEUS than in LP SHF-CEUS (p < 0.001). Conspicuity was better on PFB-CEUS than on SHF-CEUS (p = 0.027). In hyperechoic lesions, lesions located deeper than 80 mm, and calcified lesions, CRLM conspicuity on PFB-CEUS was inferior to that on SHF-CEUS (p < 0.05). CONCLUSIONS The overall accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF and PFB-CEUS. PFB-CEUS has the advantage of identifying washout in small CRLMs. However, larger, hyperechogenic, deep-seated, or calcified lesions were better identified using SHF-CEUS. CLINICAL RELEVANCE STATEMENT Accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF- and PFB-CEUS. PFB-CEUS has the advantage in detecting small CRLMs, whereas SHF-CEUS is better for detecting larger, hyperechogenic, deep-seated, or calcified lesions. KEY POINTS Contrast-enhanced ultrasound with sulfur hexafluoride in the late phase and perfluorobutane microbubbles in the Kupffer phase were comparable in terms of accuracy in the detection and conspicuity of colorectal liver metastases. Small colorectal liver metastases (< 10 mm) were more often identified in the Kupffer phase contrast-enhanced ultrasound imaging when using perfluorobutane microbubbles. Larger, hyperechogenic, deep-seated, or calcified lesions were better identified in the late phase contrast-enhanced ultrasound imaging (> 120 s) when using sulfur hexafluoride microbubbles.
Collapse
Affiliation(s)
- Si Qin
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China
| | - Yao Chen
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China
| | - YiMin Wang
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China
| | - FangQian Li
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Rui Cui
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China
| | - GuangJian Liu
- Department of Medical Ultrasonics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancunerheng Rd, Guangzhou, 510655, Guangdong, China.
| |
Collapse
|
|
6
|
Werey F, Dembinski J, Michaud A, Sabbagh C, Mauvais F, Yzet T, Regimbeau JM. Right portal vein ligation is still relevant for left hemi-liver hypertrophy: results of a comparative study using a propensity score between right portal vein ligation and embolization. Langenbecks Arch Surg 2023; 409:25. [PMID: 38158401 DOI: 10.1007/s00423-023-03213-8] [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: 05/29/2023] [Accepted: 12/20/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND In two-stage hepatectomy for bilobar liver metastases from colorectal cancer, future liver remnant (FLR) growth can be achieved using several techniques, such as right portal vein ligation (RPVL) or right portal vein embolization (RPVE). A few heterogeneous studies have compared these two techniques with contradictory results concerning FLR growth. The objective of this study was to compare FLR hypertrophy of the left hemi-liver after RPVL and RPVE. STUDY DESIGN This was a retrospective comparative study using a propensity score of patients who underwent RPVL or RPVE prior to major hepatectomy between January 2010 and December 2020. The endpoints were FLR growth (%) after weighting using the propensity score, which included FLR prior to surgery and the number of chemotherapy cycles. Secondary endpoints were the percentage of patients undergoing simultaneous procedures, the morbidity and mortality, the recourse to other liver hypertrophy procedures, and the number of invasive procedures for the entire oncologic program in intention-to-treat analysis. RESULTS Fifty-four consecutive patients were retrospectively included and analyzed, 18 in the RPVL group, and 36 in the RPVE group. The demographic characteristics were similar between the groups. After weighting, there was no significant difference between the RPVL and RPVE groups for FLR growth (%), respectively 32.5% [19.3-56.0%] and 34.5% [20.5-47.3%] (p = 0.221). There was no significant difference regarding the secondary outcomes except for the lower number of invasive procedures in RPVL group (median of 2 [2.0, 3.0] in RPVL group and 3 [3.0, 3.0] in RPVE group, p = 0.001)). CONCLUSION RPVL and RPVE are both effective to provide required left hemi-liver hypertrophy before right hepatectomy. RPVL should be considered for the simultaneous treatment of liver metastases and the primary tumor.
Collapse
Affiliation(s)
- Fabien Werey
- Department of Digestive Surgery, Amiens University Medical Center and Jules Verne University of Picardie, 1 Rue du Professeur Christian Cabrol, 80054, Amiens Cedex, France
| | - Jeanne Dembinski
- Department of Digestive Surgery, Amiens University Medical Center and Jules Verne University of Picardie, 1 Rue du Professeur Christian Cabrol, 80054, Amiens Cedex, France
- SSPC UPJV 7518 (Simplifications Des Soins Patients Chirurgicaux Complexes - Simplification of Care of Complex Surgical Patients) Clinical Research Unit, Jules Verne University of Picardie, 80054, Amiens, France
| | - Audrey Michaud
- Department of Methodology, Biostatistics, Direction of Clinical Research, Amiens University Medical Center, Amiens, France
| | - Charles Sabbagh
- Department of Digestive Surgery, Amiens University Medical Center and Jules Verne University of Picardie, 1 Rue du Professeur Christian Cabrol, 80054, Amiens Cedex, France
- SSPC UPJV 7518 (Simplifications Des Soins Patients Chirurgicaux Complexes - Simplification of Care of Complex Surgical Patients) Clinical Research Unit, Jules Verne University of Picardie, 80054, Amiens, France
| | - François Mauvais
- Department of Digestive Surgery, Beauvais General Hospital, 40 Avenue Leon Blum, 60000, Beauvais Cedex, France
| | - Thierry Yzet
- Department of Radiology, Amiens University Medical Center and Jules Verne University of Picardie, 1 Rue du Professeur Christian Cabrol, 80054, Amiens Cedex, France
| | - Jean-Marc Regimbeau
- Department of Digestive Surgery, Amiens University Medical Center and Jules Verne University of Picardie, 1 Rue du Professeur Christian Cabrol, 80054, Amiens Cedex, France.
- SSPC UPJV 7518 (Simplifications Des Soins Patients Chirurgicaux Complexes - Simplification of Care of Complex Surgical Patients) Clinical Research Unit, Jules Verne University of Picardie, 80054, Amiens, France.
| |
Collapse
|
|
7
|
Wu L, Xu W, Hu Y, Chen J. Comparison of ultrasound-guided radiofrequency ablation and hepatectomy for colorectal liver metastasis: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2023; 102:e32858. [PMID: 36749245 PMCID: PMC9901950 DOI: 10.1097/md.0000000000032858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors. Surgical treatment has made great progress in CRC liver metastasis (CRLM), including radiofrequency ablation (RFA), and hepatectomy. We perform a protocol for systematic review and meta-analysis to compare the efficacy and safety of ultrasound-guided RFA and hepatectomy in treating CRLM. METHODS This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P) 2015 Statement. The protocol has been registered in PROSPERO (CRD42022371561). PubMed, EMBASE, MEDLINE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Database, ClinicalTrials.gov trials registry, and Chinese Clinical Trial Registry will be searched from January 1980 to December 2022. Only randomized controlled trials will be included. Cochrane systematic evaluation tool is used to assess the risk of bias. The RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) will be applied to conduct the meta-analyses. RESULTS The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal. CONCLUSION This study may provide more convincing evidence to help surgeons make decisions when dealing with CRLM.
Collapse
Affiliation(s)
- Lianming Wu
- Department of General Surgery, Yuhuan Second People’s Hospital, Zhejiang, China
| | - Weiwei Xu
- Department of General Surgery, Yuhuan Second People’s Hospital, Zhejiang, China
| | - Yanzi Hu
- Department of Radiology, Yuhuan Second People’s Hospital, Zhejiang, China
| | - Jing Chen
- Department of Ultrasound, Taizhou Cancer Hospital, Zhejiang, China
- *Correspondence: Jing Chen, Department of Ultrasound, Taizhou Cancer Hospital, Zhejiang 317502, China (e-mail: )
| |
Collapse
|
|
8
|
Papakonstantinou M, Fiflis S, Christodoulidis G, Giglio MC, Louri E, Mavromatidis S, Giakoustidis D, Papadopoulos VN, Giakoustidis A. Neutrophil-to-lymphocyte ratio as a prognostic factor for survival in patients with colorectal liver metastases: A systematic review. World J Clin Oncol 2022; 13:822-834. [PMID: 36337307 PMCID: PMC9630990 DOI: 10.5306/wjco.v13.i10.822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/08/2022] [Accepted: 10/11/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The inflammatory response to tumor has been proven to be closely related to the prognosis of colorectal cancer. Neutrophil to lymphocyte ratio (NLR) is a widely available inflammatory biomarker that may have prognostic value for patients with colorectal liver metastasis (CRLM). AIM To assess the role of NLR as a prognostic factor of survival and tumor recurrence in patients with CRLM. METHODS A systematic literature search of PubMed, Cochrane Library and clinicaltrials.gov was conducted by two independent researchers in order to minimize potential errors and bias. Conflicts were discussed and settled between three researchers. Studies including patients undergoing different types of medical interventions for the treatment of CRLM and evaluating the correlation between pretreatment NLR and disease-free survival (DFS) and overall survival (OS) were included in the review. Nineteen studies, involving 3283 patients matched our inclusion criteria. RESULTS In the studies included, NLR was measured before the intervention and the NLR thresholds ranged between 1.9 and 7.26. Most studies used 5 as the cut-off value. Liver metastases were treated with hepatectomy with or without chemotherapy regimens in 13 studies and with radiofrequency ablation, radioembolization, chemoembolization or solely with chemotherapy in 6 studies. High NLR was associated with decreased OS and DFS after liver resection or other medical intervention. Moreover, high NLR was associated with poor chemosensitivity. On the contrary, CRLM patients with low pretreatment NLR demonstrated improved OS and DFS. NLR could potentially be used as a predictive factor of survival and tumor recurrence in patients with CRLM treated with interventions of any modality, including surgery, chemotherapy and ablative techniques. CONCLUSION NLR is an inflammatory biomarker that demonstrates considerable prognostic value. Elevated pretreatment NLR is associated with poor OS and DFS in patients with CRLM who are submitted to different treatments.
Collapse
Affiliation(s)
- Menelaos Papakonstantinou
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Stylianos Fiflis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | | | - Mariano Cesare Giglio
- Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples 80138, Italy
| | - Eleni Louri
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Savvas Mavromatidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Dimitrios Giakoustidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Vasileios N Papadopoulos
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| | - Alexandros Giakoustidis
- Department of Surgery, General Hospital Papageorgiou, Aristotle University of Thessaloniki, Thessaloniki 56429, Greece
| |
Collapse
|
|
9
|
Reid JL, Ting YY, Salih S, Trochsler MI, Mazzarolo D, Bonnici A, Maddern GJ. Is four years enough? An audit of post-hepatectomy surveillance for liver metastases. HPB (Oxford) 2022; 24:1697-1702. [PMID: 35491338 DOI: 10.1016/j.hpb.2022.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/03/2022] [Accepted: 04/07/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Optimal timing and modality of surveillance post hepatectomy for colorectal cancer liver metastases (CLM) has not been established. Recommendations vary between countries and surgical units. Individual clinicians do not always adhere to guidelines. METHODS Using a prospectively collected database of consecutive hepatectomy patients at The Queen Elizabeth Hospital in Adelaide, Australia, CLM patients were reviewed for evidence of recurrent disease (20 February 1996-30 June 2018). Timing and modality of disease detection was analysed. Follow up was until 30 June 2020 or death. RESULTS 244 patients underwent hepatectomy for CLM during the study period. 139 patients (57%) experienced recurrence post initial hepatectomy (mean time 13.2 months; range 0.6-84.7). For all hepatic recurrences (n = 172), majority of disease was detected in the first seven months post hepatectomy (55%) and by four years, 97.7% of recurrent disease was detected. 51 patients underwent curative repeat hepatectomy after recurrence was detected. Nearly all disease was detected via surveillance CT (160/172; 93%); 12 patients presented with clinical symptoms. CONCLUSION Hepatectomy patients are likely to experience recurrent disease and clinicians must ensure a robust surveillance plan is in place. We recommend a triple-phase CT at 6, 12, 18, 24, 36 and 48 months.
Collapse
Affiliation(s)
- Jessica L Reid
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Ying Yang Ting
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Salma Salih
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Markus I Trochsler
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Deanna Mazzarolo
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Aliyah Bonnici
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia
| | - Guy J Maddern
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, 28 Woodville Road Woodville South, South Australia 5011, Australia.
| |
Collapse
|
|
10
|
Liu F, Chen S, Yu Y, Huang C, Chen H, Wang L, Zhang W, Wu J, Ye Y. Inhibitor of DNA binding 2 knockdown inhibits the growth and liver metastasis of colorectal cancer. Gene 2022; 819:146240. [PMID: 35114275 DOI: 10.1016/j.gene.2022.146240] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 12/22/2021] [Accepted: 01/18/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Liver metastasis of colorectal cancer (CRC) remains high mortality and the mechanism is still unknown. Here we investigated the effects of inhibitor of DNA binding 2 (Id2) on growth and liver metastasis of CRC. METHODS qPCR and western blotting were used to demonstrate mRNA and protein expressions in Id2-knockdown HCT116 cells. Cell growth was observed by cell proliferation assay, colony formation assay and flow cytometry. Cell migration and invasion were observed with wound healing assay and transwell migration and invasion assay. The effects of Id2 knockdown on tumor growth and liver metastasis in vivo were evaluated respectively with subcutaneous tumor model and colorectal liver metastasis model by injecting HCT116 cells into the mesentery triangle of cecum in mice. RESULTS Id2 overexpression was found in CRC cell lines. Id2 knockdown resulted in a reduction in the proliferation, colony formation, migration and invasion of HCT116 cells. The suppression of cell proliferation was accompanied by the cell cycle arrest in the G0/G1 phase with down-regulation of Cyclin D1, Cyclin E, p-Cdk2/3, Cdk6, p-p27 and up-regulation of p21 and p27. Id2 knockdown reversed epithelial-mesenchymal transition (EMT) through increasing E-Cadherin and inhibiting N-Cadherin, Vimentin, β-catenin, Snail and Slug. Id2 was also found to inhibit CRC metastasis via MMP2, MMP9 and TIMP-1. Furthermore, Id2 knockdown suppressed CRC liver metastasis in vivo. CONCLUSION Id2 promotes CRC growth through activation of the PI3K/AKT signaling pathway, and triggers EMT to enhance CRC migration and invasion.
Collapse
Affiliation(s)
- Fang Liu
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
| | - Shuping Chen
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
| | - Yue Yu
- The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
| | - Chuanzhong Huang
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
| | - Huijing Chen
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
| | - Ling Wang
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China
| | - Wanping Zhang
- The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
| | - Junxin Wu
- Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
| | - Yunbin Ye
- Laboratory of Immuno-Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou 350014, China.
| |
Collapse
|
|
11
|
Efficacy of Drug-Eluting Bead Transarterial Chemoembolization in the Treatment of Colorectal Cancer Liver Metastasis. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:4930047. [PMID: 35463654 PMCID: PMC9020930 DOI: 10.1155/2022/4930047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 03/28/2022] [Accepted: 04/02/2022] [Indexed: 12/02/2022]
Abstract
We aimed to investigate the efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of colorectal cancer liver metastasis. A total of 120 patients with colorectal cancer liver metastasis were divided into the TACE group (receiving TACE treatment, n = 60) and the DEB-TACE group (receiving DEB-TACE treatment, n = 60). At 1 month after treatment, the objective response rate (ORR) in the TACE group and DEB-TACE group were 65.0% (39/60) and 78.3% (47/60), respectively, and the disease control rate (DCR) was 78.3% (47/60) and 85.0% (51/60), respectively. Three months later, the ORRs in TACE and DEB-TACE groups were 63.3% (38/60) and 75.0% (45/60), and the DCRs were 76.7% (46/60) and 81.7% (49/60). We showed that the 1-year overall survival (OS) in TACE and DEB-TACE groups were 100% (60/60) and 88.3% (53/60), respectively, and the 2-year OS were 78.3% (47/60) and 61.7% (37/60). Further analysis indicated that the OS in the DEB-TACE group was significantly longer than that in the TACE group (P = 0.045). DEB-TACE is effective, safe, and feasible in the treatment of colorectal cancer liver metastasis, which can effectively improve the survival of patients.
Collapse
|
|
12
|
Qin S, Hu H, Cui R, Lin J, Liu Y, Wang Y, Chen Y, Liu G. A prognostic nomogram for intrahepatic progression-free survival in patients with colorectal liver metastases after ultrasound-guided percutaneous microwave ablation. Int J Hyperthermia 2022; 39:144-154. [PMID: 35012413 DOI: 10.1080/02656736.2021.2023226] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
PURPOSE The present study identified predictors of intrahepatic progression-free survival (ihPFS) after ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastases (CRLMs) and developed a nomogram to predict ihPFS. METHODS From January 2013 to December 2018, a total of 314 patients (224 men and 90 women; mean age, 57.1 ± 11.8 years; range, 23-86 years) with 645 CRLMs (mean diameter, 16.6 ± 6.5 mm; range, 6.0-45.0 mm) treated with US-guided percutaneous MWA were included and analyzed. The average number of CRLMs per patient treated was 2 (range, 1-8). A nomogram to predict ihPFS was developed based on a multivariable Cox model. Validation of the nomogram was performed using the concordance index (C-index), calibration curves, and decision curve analyses. RESULTS The 1-, 2-, and 3-year cumulative ihPFS rates were 59.0%, 38.9%, and 30.8%, respectively. Maximal CRLM size, number of CRLMs, ablative margin, primary tumor lymph node status, and chemotherapy were five independent prognostic factors for ihPFS. The C-index of the nomogram was 0.702 (CI: 0.681-0.723). A risk classification system that perfectly classified the patients into three risk groups was constructed. The median ihPFS of patients in the low-, intermediate-, and high-risk groups was 36.3 months (95% CI: 21.4-51.1), 13.4 months (95% CI: 12.1-14.6), and 3.8 months (95% CI: 2.3-5.3), respectively. CONCLUSION The nomogram and risk classification system will facilitate the personalized assessment of ihPFS for patients receiving US-guided percutaneous MWA for CRLMs.
Collapse
Affiliation(s)
- Si Qin
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Huabin Hu
- Department of Medical Oncology, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Rui Cui
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jing Lin
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yiming Liu
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yimin Wang
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yao Chen
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Guangjian Liu
- Department of Medical Ultrasonics, Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| |
Collapse
|
|
13
|
Hewitt DB, Brown ZJ, Pawlik TM. Surgical management of intrahepatic cholangiocarcinoma. Expert Rev Anticancer Ther 2021; 22:27-38. [PMID: 34730474 DOI: 10.1080/14737140.2022.1999809] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Intrahepatic cholangiocarcinoma (ICC) incidence continues to rise worldwide, and overall survival remains poor. Complete surgical resection remains the only opportunity for cure in patients with ICC yet only one-third of patients present with resectable disease. AREAS COVERED While the low incidence rate of ICC hinders accrual of patients to large, randomized control trials, larger database and long-term institutional studies provide evidence to guide surgical management of ICC. These studies demonstrate feasibility, safety, and efficacy of aggressive surgical management in appropriately selected patients with ICC. Recent advances in the management of ICC, with a focus on surgical considerations, are reviewed. EXPERT OPINION Historically, little progress has been made in the management of ICC with stagnant mortality rates and poor long-term outcomes. However, regionalization of care to centers with experienced multidisciplinary teams, advances in minimally invasive surgical techniques, discovery and development of targeted and immunotherapy agents, and combination locoregional and systemic therapies offer signs of progress in the management of ICC.
Collapse
Affiliation(s)
- D Brock Hewitt
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Zachary J Brown
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| |
Collapse
|
|
14
|
Serifis N, Tsilimigras DI, Cloonan DJ, Pawlik TM. Challenges and Opportunities for Treating Intrahepatic Cholangiocarcinoma. Hepat Med 2021; 13:93-104. [PMID: 34754247 PMCID: PMC8572023 DOI: 10.2147/hmer.s278136] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/22/2021] [Indexed: 12/29/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is one of the rarest and most aggressive types of cancer. The symptoms of ICC patients can be vague, leading to late diagnosis and dismal prognosis. In this review, we investigated the treatment options for ICC, as well as ways to overcome challenges in identifying and treating this disease. Imaging remains the gold standard to diagnose ICC. Patients are staged based on the tumor, nodes and metastases (TNM) staging system. Patients eligible for surgical resection should undergo surgery with curative intent with the goal of microscopically disease-free margins (R0 resection) along with lymphadenectomy. Minimal invasive surgery (MIS) and liver transplantation have recently been offered as possible ways to improve disease outcomes. ICC recurrence is relatively common and, thus, most patients will need to be treated with systemic therapy. Several clinical trials have recently investigated the use of neoadjuvant (NT) and adjuvant therapies for ICC. NT may offer an opportunity to downsize larger tumors and provide patients, initially ineligible for surgery, with an opportunity for resection. NT may also treat occult micro-metastatic disease, as well as define tumor biology prior to surgical resection, thereby decreasing the risk for early postoperative recurrence. Adjuvant systemic therapy may improve outcomes of patients with ICC following surgery. Ongoing clinical trials are investigating new targeted therapies that hold the hope of improving long-term outcomes of patients with ICC.
Collapse
Affiliation(s)
- Nikolaos Serifis
- Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA
| | | | - Daniel J Cloonan
- Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| |
Collapse
|
|
15
|
Kang ST, Moran R, Hussain L, Guend H, Dunki-Jacobs EM, Lee DY. Metastasectomy for Stage IVA Colon Cancer: Does the Type of Treating Institution Make a Difference? Am Surg 2021; 88:1976-1982. [PMID: 34077694 DOI: 10.1177/00031348211023389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Treatment of metastatic colon cancer has evolved over time. More evidence has been emerging in recent years supporting metastasectomy in selected patients. We sought to elucidate whether the type of institution-community, comprehensive community, academic/research, and integrated cancer network-would have an effect on patient outcome, specifically those colon cancer patients with isolated liver metastasis. This retrospective cohort study queried the National Cancer Database (NCDB) from 2010 to 2014 for patients who were 18 years of age or older with stage IVA colon cancer with isolated liver metastasis. We then performed uni- and multivariate analyses comparing patients based on such factors as age, tumor characteristics, primary tumor location, rate of chemotherapy, and type of treating institution. Patients who came from regions of higher income, receiving chemotherapy, and presenting to an academic/research hospital were more likely to undergo metastasectomy. Median survival was longest at academic/community hospitals at 22.4 months, 6 to 7 months longer than the other three types of institutions. Factors positively affecting survival included receiving chemotherapy, presenting to an academic/research institution, and undergoing metastasectomy, all at P < .05. In our study, the rate of metastasectomy was more than double at academic/research institutions for those with stage IVA colon cancer with isolated liver metastasis. Prior studies have quoted a mere 4.1% synchronous colon resection and metastasectomy. Our findings suggest that we should maintain multidisciplinary approach to this complex disease process and that perhaps it is time for us to consider regionalization of care in treating metastatic colon cancer.
Collapse
Affiliation(s)
- Shinho T Kang
- Good Samaritan Hospital General Surgery Residency Program, TriHealth, Cincinnati, OH, USA
| | - Ryan Moran
- 12303University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Lala Hussain
- Department of Biostatistics, TriHealth Hatton Research Institute, Cincinnati, OH, USA
| | - Hamza Guend
- Division of Colorectal Surgery, TriHealth Surgical Institute, Cincinnati, OH, USA
| | - Erik M Dunki-Jacobs
- Division of Surgical Oncology, TriHealth Cancer Institute, Cincinnati, OH, USA
| | - David Y Lee
- Division of Surgical Oncology, Schar Cancer Institute, Inova Health System, Fairfax, VA, USA
| |
Collapse
|
|
16
|
Michel M, Kaps L, Maderer A, Galle PR, Moehler M. The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy. Cancers (Basel) 2021; 13:2296. [PMID: 34064974 PMCID: PMC8150459 DOI: 10.3390/cancers13102296] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/28/2021] [Accepted: 05/03/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.
Collapse
Affiliation(s)
- Maurice Michel
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Leonard Kaps
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
- Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center Mainz, 55131 Mainz, Germany
| | - Annett Maderer
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Peter R. Galle
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Markus Moehler
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| |
Collapse
|
|
17
|
Okubo S, Shindoh J, Kobayashi Y, Hashimoto M. Safety of bioabsorbable membrane (Seprafilim®) in hepatectomy in the era of aggressive liver surgery. HPB (Oxford) 2021; 23:528-532. [PMID: 32859492 DOI: 10.1016/j.hpb.2020.08.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 08/07/2020] [Accepted: 08/11/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Repeat hepatectomy has been recognized as an effective treatment for hepatic malignancies, and a sheet type adhesion barrier, Seprafilm® has increasingly been used during hepatectomy to ease future relaparotomy. However, there is not yet sufficient evidence to support the safety of use of Seprafilm in liver surgery. METHODS Data of 151 patients who had undergone open hepatectomy were retrospectively reviewed and the incidence of major abdominal morbidity was compared between patients in whom Seprafilm had and had not been used. RESULTS Seprafilm was used in 108 patients (Seprafilm group) and no adhesion barrier was used in 43 patients (comparison group). There was no significant difference in the rate of major abdominal morbidities between the two groups (Seprafilm vs. comparison: 10% vs. 16%, P = 0.403). Although the Seprafilm group showed a tendency toward increased incidence of bile leakage (7% vs. 2%), and placement of Seprafilm on the hepatoduodenal ligament or on the visceral surface of the liver seemed to be associated with an increased incidence of major morbidity, multivariate analysis showed no significant correlation between the use of Seprafilm and postoperative major abdominal morbidity. CONCLUSION Use of Seprafilm may not increase the risk of major abdominal morbidity in liver surgery.
Collapse
Affiliation(s)
- Satoshi Okubo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan; Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | - Yuta Kobayashi
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| | - Masaji Hashimoto
- Hepato-Biliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Japan
| |
Collapse
|
|
18
|
Ren W, Sell NM, Ferrone CR, Tanabe KK, Lillemoe KD, Qadan M. Size of the Largest Colorectal Liver Metastasis Is an Independent Prognostic Factor in the Neoadjuvant Setting. J Surg Res 2020; 259:253-260. [PMID: 33160635 DOI: 10.1016/j.jss.2020.09.039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 07/31/2020] [Accepted: 09/22/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Up to 50% of patients diagnosed with colorectal cancer develop metastases during the course of their disease. Surgical resection remains the only curative treatment option for colorectal liver metastases (CRLM), frequently in conjunction with neoadjuvant chemotherapy. This study sought to determine if the pathologic size of the largest CRLM impacted disease-free survival (DFS) and disease-specific survival (DSS) in the setting of neoadjuvant chemotherapy. METHODS All patients diagnosed with CRLM who underwent neoadjuvant chemotherapy for liver resection at the Massachusetts General Hospital between 2004 and 2016 were reviewed. The median size of the largest liver lesion was used as the cutoff for grouped evaluation. RESULTS A total of 214 patients were included. Median follow-up was 100.0 mo (interquartile range 68.9-133.8 mo). The median size of the largest lesion was 21 mm. Patients with lesions ≥21 mm exhibited significantly worse median DFS (12.5 mo versus 16.6 mo; P = 0.033) and median DSS (71.3 mo versus 103.5 mo; P = 0.038). CRLM lesions ≥21 mm were associated with poorer DFS on univariate analysis (hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.03-1.95 P = 0.033) and multivariable analysis (HR = 1.58, 95% CI 1.07-2.35, P = 0.023). CRLM lesions ≥21 mm were also independently associated with poorer DSS after liver resection on univariate analysis (HR = 1.51, 95% CI 1.02-2.24; P = 0.037) and multivariable analysis (HR = 1.98, 95% CI: 1.27-3.07; P = 0.002). CONCLUSIONS The size of the largest CRLM is an important prognostic factor for both DFS and DSS after neoadjuvant therapy and serves as a useful indicator of tumor biology.
Collapse
Affiliation(s)
- Weizheng Ren
- Department of Hepatopancreatobiliary Surgery, PLA General Hospital, First Medical Center, Beijing, PR China; Harvard Medical School, Boston, Massachusetts
| | - Naomi M Sell
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Cristina R Ferrone
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Kenneth K Tanabe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Keith D Lillemoe
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Motaz Qadan
- Harvard Medical School, Boston, Massachusetts; Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
| |
Collapse
|
|
19
|
Sneidere M, Schrem HH, Mahlmann JC, Beetz O, Cammann S, Oldhafer F, Kleine M, Klempnauer J, Kaltenborn A, Zwirner U, Kulik U. Proposal of a Multivariable Prediction Model for Graded Morbidity after Liver Resection for Colorectal Metastases. Zentralbl Chir 2020; 148:147-155. [PMID: 33091938 DOI: 10.1055/a-1243-0746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Prognostic models to predict individual early postoperative morbidity after liver resection for colorectal liver metastases (CLM) are not available but could enable optimized preoperative patient selection and postoperative surveillance for patients at greater risk of complications. The aim of this study was to establish a prognostic model for the prediction of morbidity after liver resection graded according to Dindo. METHODS N = 679 cases of primary liver resection for CLM were retrospectively analyzed using univariable and multivariable ordinal regression analyses. Receiver operating characteristics curve (ROC) analysis was utilised to assess the sensitivity and specificity of predictions and their potential usefulness as prognostic models. Internal validation of the score was performed using data derived from 129 patients. RESULTS The final multivariable regression model revealed lower preoperative levels, a greater number of units of intraoperatively transfused packed red blood cells (pRBCs), longer duration of surgery, and larger metastases to independently influence postoperatively graded morbidity. ROC curve analysis demonstrated that the multivariable regression model is able to predict each individual grade of postoperative morbidity with high sensitivity and specificity. The areas under the receiver operating curves (AUROC) for all of these predictions of individual grades of morbidity were > 0.700, indicating potential usefulness as a predictive model. Moreover, a consistent concordance in Grades I, II, IV, and V according to the classification proposed by Dindo et al. was observed in the internal validation. CONCLUSION This study proposes a prognostic model for the prediction of each grade of postoperative morbidity after liver resection for CLM with high sensitivity and specificity using pre- and intraoperatively available variables.
Collapse
Affiliation(s)
- Mara Sneidere
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | | | | | - Oliver Beetz
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | - Sebastian Cammann
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | - Felix Oldhafer
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | - Moritz Kleine
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | - Juergen Klempnauer
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | | | - Ulrich Zwirner
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| | - Ulf Kulik
- General, Visceral and Transplantation Surgery, Hannover Medical School, Germany
| |
Collapse
|
|
20
|
Mahlmann JC, Wirth TC, Hartleben B, Schrem H, Mahlmann JF, Kaltenborn A, Klempnauer J, Kulik U. Chemotherapy and Hepatic Steatosis: Impact on Postoperative Morbidity and Survival after Liver Resection for Colorectal Liver Metastases. Visc Med 2020; 37:198-205. [PMID: 34250077 DOI: 10.1159/000510661] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Accepted: 08/03/2020] [Indexed: 01/22/2023] Open
Abstract
Background Hepatic steatosis and chemotherapy in the treatment of colorectal liver metastases (CLM) are often linked to increased mortality and morbidity after liver resection. This study evaluates the influence of macrovesicular hepatic steatosis and chemotherapeutic regimes on graded morbidity and mortality after liver resection for CLM. Methods A total of 323 cases of liver resection for CLM were retrospectively analysed using univariable and multivariable linear, ordinal and Cox regression analyses. The resected liver tissue was re-evaluated by a single observer to determine the grade and type of hepatic steatosis. Results Macrovesicular steatosis did not influence postoperative morbidity and survival, as evidenced by risk-adjusted multivariable Cox regression analysis (p = 0.521). Conversion chemotherapy containing oxaliplatin was an independent and significant risk factor for mortality in risk-adjusted multivariable Cox regression analysis (p = 0.005). Identified independently, significant risk factors for postoperative morbidity were neoadjuvant treatment of metastases of the primary tumour with irinotecan (p = 0.003), the duration of surgery in minutes (p = 0.001) and the number of intraoperatively transfused packed red blood cells (p ≤ 0.001). Surprisingly, macrovesicular hepatic steatosis was not a risk factor for postoperative morbidity and was even associated with lower rates of complications (p = 0.006). Conclusion The results emphasize the multifactorial influence of preoperative liver damage and chemotherapy on the severity of postoperative morbidity, as well as the significant impact of conversion chemotherapy containing oxaliplatin on survival.
Collapse
Affiliation(s)
- Jan C Mahlmann
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Thomas C Wirth
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | | | - Harald Schrem
- Division of Transplant Surgery, Department of Surgery, Medical University of Graz, Graz, Austria
| | - Jens F Mahlmann
- Departament d'Astronomia i Astrofísica, Universitat de València, Valencia, Spain
| | - Alexander Kaltenborn
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Jürgen Klempnauer
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Ulf Kulik
- General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| |
Collapse
|
|
21
|
Li P, Kong L, Wang Y, Lv X, Wang J, Gao H. Comparative analysis of radiofrequency ablation and resection for colorectal liver metastases in caudate lobe: a retrospective study. Acta Chir Belg 2020; 120:321-328. [PMID: 31187689 DOI: 10.1080/00015458.2019.1631614] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective: To assess the therapeutic efficiency of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) in the caudate lobe compared with that of surgical resection.Methods: After approved by institutional review board, we retrospectively reviewed 20 patients with caudate CRLM treated by RFA or resection between 2006 and 2017. Comparative analysis was performed based on the different therapies, including patient characteristics, therapeutic outcomes, recurrences, and survivals.Results: During the median follow-up of 7 years (range, 2 -11 years), no differences in complications and recurrences were found between RFA and surgery groups (p > .05). The median overall survival (OS) of patients after RFA and resection were 41 months (95% confidence interval (CI) 23.5-70.5) and 54 months (95% CI 31.1-77.7), respectively (p = .627, hazard radio (HR) 0.7, 95% CI 0.2-2.6). However, OS of resection group was better than that of RFA group for large caudate CRLMs (>3 cm) (p = .042, HR 4.4, 95% CI 0.6-32.6).Conclusions: RFA is a feasible, safe, and effective treatment for CRLM in the caudate. Surgical resection revealed superior outcomes in the treatment of caudate CRLMs, particularly in cases with a hepatic tumor size >3 cm.
Collapse
Affiliation(s)
- Peizhe Li
- Department of Gastrointestinal Surgery, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| | - Lingjia Kong
- Department of Digestive System, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| | - Yitong Wang
- Department of Ultrasound, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| | - Xukun Lv
- Department of Gastrointestinal Surgery, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| | - Jinkai Wang
- Department of Gastrointestinal Surgery, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| | - Hengling Gao
- Department of Gastrointestinal Surgery, The Second People’s Hospital of Liaocheng, Liaocheng, PR China
| |
Collapse
|
|
22
|
Quantified MRI and 25OH-VitD3 can be used as effective biomarkers for patients with neoadjuvant chemotherapy-induced liver injury in CRCLM? BMC Cancer 2020; 20:767. [PMID: 32799832 PMCID: PMC7429712 DOI: 10.1186/s12885-020-07282-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Accepted: 08/09/2020] [Indexed: 12/26/2022] Open
Abstract
Background To evaluate proton-density fat-fraction (PDFF) and intravoxel incoherent motion (IVIM) techniques, and human 25-hydroxyvitamin D3 (25OH-VitD3) levels, as potential biomarkers in patients with colorectal cancer with liver metastasis (CRCLM). Changes were compared with those related to chemotherapy-associated steatohepatitis (CASH) and sinusoidal obstruction syndrome (SOS). Methods 63 patients with pathologically confirmed colorectal adenocarcinoma received 4–6 courses of NC before liver resection and underwent magnetic resonance imaging (MRI) with iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantification and IVIM sequences. Blood samples were analyzed using CTCAE. Pathological changes of liver tissues outside the metastases were assessed as the gold standard, and receiver operating characteristic (ROC) curves were analyzed. Results 16 cases had CASH liver injury, 14 cases had SOS changes, and 4 cases had CASH and SOS, and 7 showed no significant changes. Consistency between biochemical indices and pathological findings was poor (kappa = 0.246, p = 0.005). The areas under the ROC curve (AUCs) of ALT, AST, ALP, GGT, and TBIL were 0.571–0.691. AUCs of D, FF, and 25OH-VitD3 exceeded 0.8; when considering these markers together, sensitivity was 85.29% and specificity was 93.13%. ANOVA showed statistically significant differences among D, FF, and 25OH-VitD3 for different grades of liver injury (F = 4.64–26.5, p = 0.000–0.016). Conclusions D, FF, and 25OH-VitD3 are biomarkers for accurate prediction of NC-induced liver injury in patients with CRCLM, while FF and 25OH-VitD3 might be beneficial to distinguish liver injury grades. Trial registration Current Trials was retrospectively registered as ChiCTR1800015242 at Chinese Clinical Trial Registry on March 16, 2018.
Collapse
|
|
23
|
Wisneski AD, Jin C, Huang CY, Warren R, Hirose K, Nakakura EK, Corvera CU. Synchronous Versus Metachronous Colorectal Liver Metastasis Yields Similar Survival in Modern Era. J Surg Res 2020; 256:476-485. [PMID: 32798995 DOI: 10.1016/j.jss.2020.06.038] [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: 02/27/2020] [Revised: 06/07/2020] [Accepted: 06/16/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Synchronous colorectal cancer liver metastasis (CRLM) has been viewed as being more aggressive and having shorter survival than metachronous disease. Advances in CRLM management led us to examine differences in treatment characteristics of synchronous versus metachronous CRLM patients along with survival and recurrence. MATERIALS AND METHODS A retrospective review of hepatic resection for CRLM at a tertiary academic medical center was performed for two periods: a historic cohort from 1992 to 2010 (n = 121), and a modern cohort (n = 179) from 2012 to 2018. Clinical variables were compared between the patient groups, and survival outcomes were characterized. RESULTS Five-year disease-specific survival for the modern synchronous group compared to the historic synchronous group was 71.7% versus 44.3% (P = 0.02). Modern metachronous versus modern synchronous 5-y disease-specific survival rates were 49.8% versus 71.7% (P = 0.31). Compared to the historic cohort, the modern one had significantly different timing of hepatic resection (P < 0.01) with increased use of liver-first (30.1% versus 7.5%) and simultaneous liver-colon resections (24.1% versus 10.4%), along with greater use of neoadjuvant chemotherapy (96.4% versus 65.6%; P < 0.01). Significantly more patients in the modern synchronous cohort had disease-free or alive-with-disease status at last follow-up, compared to the historic group (P < 0.01), and experienced less disease recurrence (62.7% versus 77.6%; P < 0.05). CONCLUSIONS Modern synchronous CRLM patients who underwent hepatic resection experienced significantly improved survival compared to a historic cohort. We postulate that increased use of neoadjuvant chemotherapy and liver-first/simultaneous liver-colon resections in the modern synchronous cohort contributed to improved survival.
Collapse
Affiliation(s)
- Andrew D Wisneski
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Chengshi Jin
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California
| | - Robert Warren
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Kenzo Hirose
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Eric K Nakakura
- Department of Surgery, University of California San Francisco, San Francisco, California
| | - Carlos U Corvera
- Department of Surgery, University of California San Francisco, San Francisco, California.
| |
Collapse
|
|
24
|
Filip S, Vymetalkova V, Petera J, Vodickova L, Kubecek O, John S, Cecka F, Krupova M, Manethova M, Cervena K, Vodicka P. Distant Metastasis in Colorectal Cancer Patients-Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review. Int J Mol Sci 2020; 21:E5255. [PMID: 32722130 PMCID: PMC7432613 DOI: 10.3390/ijms21155255] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/21/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.
Collapse
Affiliation(s)
- Stanislav Filip
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Veronika Vymetalkova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Jiri Petera
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Ondrej Kubecek
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Stanislav John
- Department of Oncology and Radiotherapy, Charles University, Faculty of Medicine in Hradec Kralove, Šimkova 870, 50001 Hradec Králové, Czech Republic; (J.P.); (O.K.); (S.J.)
| | - Filip Cecka
- Department of Surgery, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic;
| | - Marketa Krupova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Monika Manethova
- The Fingerland Department of Pathology, University Hospital in Hradec Kralove, Sokolská 581, 50005 Hradec Králové, Czech Republic; (M.K.); (M.M.)
| | - Klara Cervena
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, Czech Republic; (V.V.); (L.V.); (K.C.)
- Biomedical Centre, Faculty of Medicine in Pilsen, Charles University, Alej Svobody 1655, 32300 Pilsen, Czech Republic
- Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Albertov 4, 12800 Prague, Czech Republic
| |
Collapse
|
|
25
|
Abstract
BACKGROUND Transarterial radioembolization (TARE) is a locoregional minimally invasive therapeutic strategy to treat primary and secondary hepatic neoplasia. AIM The objective was to assess TARE-induced immuno-oncological effects and its perspective for potential therapy improvement by using a combinatory strategy with immune checkpoint inhibitors (ICI). RESULTS Yttrium-90 (90Y) TARE is used in patients with persisting liver function as the first- and second-line treatment for cholangiocarcinoma and hepatocellular carcinoma and chemotherapy refractory liver metastasis of different primaries. Combination therapy with 90Y TARE and ICI may synergistically improve antitumoral immunity and patient outcome. Currently, there are no clinical studies with published data regarding this combination therapy and the subsequently induced immunological effects. Clinical data on other isotopes, e.g., holmium-166 (166Ho), are also lacking. CONCLUSION The clinical evidence of combined treatment with TARE and ICI must be considerably improved. This innovative therapy concept must be studied in new trials assessing the immunological data, including cellular phenotypes, activation, functions, and biomarkers. This may provide valid, sensitive, and specific models in order to evaluate the optimal therapy concept and/or the therapy combination for the best patient outcome.
Collapse
Affiliation(s)
- Borna Relja
- Experimentelle Radiologie, Otto-von-Guericke Universität, Leipziger Straße 44, 39120, Magdeburg, Deutschland.
| | - Maciej Pech
- Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität, Leipziger Straße 44, 39120, Magdeburg, Deutschland.
| |
Collapse
|
|
26
|
Lv Y, Feng QY, Wei Y, Ren L, Ye Q, Wang X, Cui Y, Liu T, Zhou B, Wang M, Rao S, Wang J, Ding J, He GD, Xu JM. Benefits of multi-disciplinary treatment strategy on survival of patients with colorectal cancer liver metastasis. Clin Transl Med 2020; 10:e121. [PMID: 32627392 DOI: 10.1002/ctm2.121] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 12/13/2022] Open
Affiliation(s)
- Yang Lv
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Qing-Yang Feng
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Ye Wei
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Li Ren
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - QingHai Ye
- Department of Liver Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - XiaoYing Wang
- Department of Liver Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - YueHong Cui
- Department of Oncology, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - TianShu Liu
- Department of Oncology, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Bo Zhou
- Department of Intervention treatment, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - MingLiang Wang
- Department of Radiology, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - ShengXiang Rao
- Department of Radiology, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Jian Wang
- Department of Radiotherapy, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - JianYong Ding
- Department of Thoracic Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Guo-Dong He
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| | - Jian-Min Xu
- Department of General Surgery, ZhongShan Hospital, Fudan University, Shanghai, Shanghai, China
| |
Collapse
|
|
27
|
Swierz MJ, Storman D, Riemsma RP, Wolff R, Mitus JW, Pedziwiatr M, Kleijnen J, Bala MM, Cochrane Hepato‐Biliary Group. Transarterial (chemo)embolisation versus no intervention or placebo for liver metastases. Cochrane Database Syst Rev 2020; 3:CD009498. [PMID: 32163181 PMCID: PMC7066934 DOI: 10.1002/14651858.cd009498.pub4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of people; therefore, other treatments have to be considered. One possible option is based on the concept that the blood supply to hepatic tumours originates predominantly from the hepatic artery. Transarterial chemoembolisation (TACE) of the hepatic artery can be achieved by administering a chemotherapeutic drug followed by vascular occlusive agents, and can lead to selective necrosis of the liver tumour while it may leave normal parenchyma virtually unaffected. This can also be performed without chemotherapy, which is called bland transarterial embolisation (TAE). OBJECTIVES To assess the beneficial and harmful effects of TAE or TACE compared with no intervention or placebo in people with liver metastases. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and four more databases (December 2019). We also searched two trials registers and the US Food and Drug Administration database (September 2019). SELECTION CRITERIA Randomised clinical trials assessing beneficial and harmful effects of TAE or TACE compared with no intervention or placebo for liver metastases. DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodological procedures. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of evidence with GRADE. We resolved disagreements by discussion. MAIN RESULTS We included one randomised clinical trial with 61 participants (43 male and 18 female) with colorectal cancer with liver metastases: 22 received transarterial embolisation (TAE; hepatic artery embolisation), 19 received transarterial chemoembolisation (TACE; 5-fluorouracil hepatic artery infusion chemotherapy with degradable microspheres), and 20 received 'no active therapeutic intervention' as a control. Most tumours were synchronous, unresectable metastases involving up to 75% of the liver. Participants were followed for a minimum of seven months. The trial was at high risk of bias. Very-low-certainty evidence found inconclusive results for mortality at 44 months between the TAE and TACE versus no intervention groups (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.06; 61 participants). Local recurrence was reported in 10 participants without any details about the group allocation. Very-low-certainty evidence found little or no difference in mortality between the TAE and no intervention groups (RR 0.91, 95% CI 0.75 to 1.10; 42 participants). Median survival was 7 months from trial entry (range 2 to 44 months) in the TAE group and 7.9 months (range 1 to 26 months) in the control group, and 8.7 months after diagnosis (range 2 to 49 months) in the TAE group and 9.6 months (range 1 to 27 months) in the control group. The trial authors reported the differences were not statistically significant. There were no reported side effects in the control group. In the TAE group, 18 participants experienced short-term symptoms of 'post-embolisation syndrome', which were relieved with symptomatic treatment; one participant also had a local puncture site haematoma. Very-low-certainty evidence found little or no difference in mortality between the TACE and no intervention groups (RR 0.83, 95% CI 0.65 to 1.07; 39 participants). Median survival in the TACE group was 10.7 months (range 3 to 38 months) from trial entry, and 13.0 months (range 3 to 38 months) after diagnosis. The trial authors reported that differences between groups were not statistically significant. All participants experienced short-term nausea, with or without vomiting, immediately after treatment; one participant developed a wound infection, and one developed deep vein thrombosis. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Cancer Research Campaign, a non-profit organisation, provided a grant for the trial; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. We identified one ongoing trial comparing TACE plus chemotherapy versus chemotherapy alone in people with unresectable colorectal liver metastases who failed with first-line chemotherapy (NCT03783559). AUTHORS' CONCLUSIONS Based on one, small randomised trial at high risk of bias, the evidence is very uncertain about the effect of TAE or TACE versus no active therapeutic intervention on mortality for people with liver metastases as the true effect may be substantially different. The trial did not measure failure to clear liver metastases, time to progression of liver metastases, tumour response measures, or health-related quality of life. Short-term, minor adverse events were recorded in the intervention groups only. Large trials, following current standards of conduct and reporting, are required to explore the benefits and harms of TAE or TACE compared with no intervention or placebo in people with resectable and unresectable liver metastasis.
Collapse
Affiliation(s)
- Mateusz J Swierz
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics; Systematic Reviews UnitKrakowPoland
| | - Dawid Storman
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics; Systematic Reviews UnitKrakowPoland
| | - Robert P Riemsma
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Robert Wolff
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Jerzy W Mitus
- The Maria Sklodowska‐Curie Institute, Oncology Center, Krakow Branch; Department of Anatomy, Jagiellonian University Medical CollegeDepartment of Surgical Oncologyul. Garncarska 11KrakowPoland31‐115
| | - Michal Pedziwiatr
- Jagiellonian University Medical College2nd Department of General SurgeryJakubowskiego Street 2KrakowMalopolskaPoland30‐688
| | - Jos Kleijnen
- School for Public Health and Primary Care (CAPHRI), Maastricht UniversityMaastrichtNetherlands6200 MD
| | - Malgorzata M Bala
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics; Systematic Reviews UnitKrakowPoland
| | | |
Collapse
|
|
28
|
Swierz MJ, Storman D, Riemsma RP, Wolff R, Mitus JW, Pedziwiatr M, Kleijnen J, Bala MM, Cochrane Hepato‐Biliary Group. Percutaneous ethanol injection for liver metastases. Cochrane Database Syst Rev 2020; 2:CD008717. [PMID: 32017845 PMCID: PMC7000212 DOI: 10.1002/14651858.cd008717.pub3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour. OBJECTIVES To assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS We searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index - Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019). SELECTION CRITERIA Randomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases. DATA COLLECTION AND ANALYSIS We followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion. MAIN RESULTS We identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm. Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases. The single included trial did not provide information on funding nor on conflict of interest. AUTHORS' CONCLUSIONS Evidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.
Collapse
Affiliation(s)
- Mateusz J Swierz
- Jagiellonian University Medical CollegeDepartment of Hygiene and Dietetics, Systematic Reviews UnitKrakowPoland
| | - Dawid Storman
- University HospitalDepartment of Hygiene and Dietetics, Systematic Reviews Unit, Jagiellonian University Medical College, Department of Adult PsychiatryKrakowPoland
| | - Robert P Riemsma
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Robert Wolff
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Jerzy W Mitus
- The Maria Sklodowska‐Curie Institute, Oncology Center, Krakow Branch; Department of Anatomy, Jagiellonian University Medical CollegeDepartment of Surgical Oncologyul. Garncarska 11KrakowPoland31‐115
| | - Michal Pedziwiatr
- Jagiellonian University Medical College2nd Department of General SurgeryJakubowskiego Street 2KrakowMalopolskaPoland30‐688
| | - Jos Kleijnen
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
- School for Public Health and Primary Care (CAPHRI), Maastricht UniversityMaastrichtNetherlands6200 MD
| | - Malgorzata M Bala
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine, Department of Hygiene and Dietetics; Systematic Reviews UnitKopernika 7KrakowPoland31‐034
| | | |
Collapse
|
|
29
|
Škrbić V, Simatović M, Janjić G, Šaran D. Surgical treatment of colorectal cancer metastases. SCRIPTA MEDICA 2020. [DOI: 10.5937/scriptamed51-26579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
|
|
30
|
Ruzzenente A, Bagante F, Ratti F, Beal EW, Alexandrescu S, Merath K, Makris EA, Poultsides GA, Margonis GA, Weiss MJ, Popescu I, Aldrighetti L, Guglielmi A, Pawlik TM. Response to preoperative chemotherapy: impact of change in total burden score and mutational tumor status on prognosis of patients undergoing resection for colorectal liver metastases. HPB (Oxford) 2019; 21:1230-1239. [PMID: 30792047 DOI: 10.1016/j.hpb.2019.01.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/29/2018] [Accepted: 01/18/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size. METHODS Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS). RESULTS Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS<6 at diagnosis, genetic status was the most important prognostic variable. Patients with a TBS<6, 5-year OS was 55%, 35%, and 0% for patients with KRAS/NRAS/BRAF wild-type, KRAS/NRAS, and BRAF mutations, respectively. Among patients who presented with CRLM with a TBS≥6, only Δ-TBS was prognostically important and patients with a Δ-TBS ≥ -10% had a 5-year OS of 27% compared with 49% for patients with a Δ-TBS < -10%. CONCLUSIONS Prognostic stratification of patients with CRLM receiving preoperative chemotherapy should be multi-faceted and include consideration of initial tumor burden, change in tumor burden due to chemotherapy, and tumor genetic status.
Collapse
Affiliation(s)
| | - Fabio Bagante
- Department of Surgery, University of Verona, Verona, Italy; Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | - Eliza W Beal
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | - Katiuscha Merath
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | | | | | - Georgios A Margonis
- Department of Surgery, The Johns Hopkins University Hospital, Baltimore, MD, USA
| | - Matthew J Weiss
- Department of Surgery, The Johns Hopkins University Hospital, Baltimore, MD, USA
| | - Irinel Popescu
- Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania
| | | | | | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
| |
Collapse
|
|
31
|
Bala MM, Riemsma RP, Wolff R, Pedziwiatr M, Mitus JW, Storman D, Swierz MJ, Kleijnen J, Cochrane Hepato‐Biliary Group. Cryotherapy for liver metastases. Cochrane Database Syst Rev 2019; 7:CD009058. [PMID: 31291464 PMCID: PMC6620095 DOI: 10.1002/14651858.cd009058.pub3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma. Liver metastases are significantly more common than primary liver cancer and long-term survival rates reported for patients after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients. Cryotherapy is performed with the use of an image-guided cryoprobe which delivers liquid nitrogen or argon gas to the tumour tissue. The subsequent process of freezing is associated with formation of ice crystals, which directly damage exposed tissue, including cancer cells. OBJECTIVES To assess the beneficial and harmful effects of cryotherapy compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases. SEARCH METHODS We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and six other databases up to June 2018. SELECTION CRITERIA Randomised clinical trials assessing beneficial and harmful effects of cryotherapy and its comparators for liver metastases, irrespective of the location of the primary tumour. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, and data on the outcomes important for our review, as well as information on the design and methodology of the trials. Two review authors independently assessed risk of bias in each study. One review author performed data extraction and a second review author checked entries. MAIN RESULTS We found no randomised clinical trials comparing cryotherapy versus no intervention or versus systemic treatments; however, we identified one randomised clinical trial comparing cryotherapy with conventional surgery. The trial was conducted in Ukraine. The trial included 123 participants with solitary, or multiple unilobar or bilobar liver metastases; 63 participants received cryotherapy and 60 received conventional surgery. There were 36 women and 87 men. The primary sites for the metastases were colon and rectum (66.6%), stomach (7.3%), breast (6.5%), skin (4.9%), ovaries (4.1%), uterus (3.3%), kidney (3.3%), intestines (1.6%), pancreas (1.6%), and unknown (0.8%). The trial was not reported sufficiently enough to assess the risk of bias of the randomisation process, allocation concealment, or presence of blinding. It was also not possible to assess incomplete outcome data and selective outcome reporting bias. The certainty of evidence was low because of risk of bias and imprecision.The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. The calculated by us relative risk (RR) with 95% Confidence Interval (CI) was: RR 0.88, 95% CI 0.77 to 1.02. We judged the evidence as low-certainty evidence. Regarding adverse events and complications, separately and in total, our calculation showed no evidence of a difference in recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (RR 0.90, 95% CI 0.80 to 1.01; low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, the authors did not report whether there was any evidence of a difference. There were no intervention-related mortality or bile leakages.We identified no evidence for health-related quality of life, cancer mortality, or time to progression of liver metastases. The study reported tumour response in terms of the carcinoembryonic antigen level in 69% of participants, and reported results in the form of a graph for 30% of participants. The carcinoembryonic antigen level was lower in the cryotherapy group, and decreased to normal values faster in comparison with the control group (P < 0.05). FUNDING the trial did not provide information on funding. AUTHORS' CONCLUSIONS The evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.
Collapse
Affiliation(s)
- Malgorzata M Bala
- Jagiellonian University Medical CollegeChair of Epidemiology and Preventive Medicine; Department of Hygiene and Dietetics; Systematic Reviews UnitKopernika 7KrakowPoland31‐034
| | - Robert P Riemsma
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Robert Wolff
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
| | - Michal Pedziwiatr
- Jagiellonian University Medical College2nd Department of General SurgeryKopernika Street 21KrakówMalopolskaPoland31‐501
| | - Jerzy W Mitus
- Centre of Oncology, Maria Skłodowska – Curie Memorial Institute, Krakow Branch. Department of Anatomy, Jagiellonian University Medical College Krakow, PolandDepartment of Surgical Oncologyul. Garncarska 11KrakowPoland31‐115
| | - Dawid Storman
- University HospitalDepartment of Hygiene and Dietetics, Systematic Reviews Unit, Jagiellonian University Medical College, Department of Adult PsychiatryKrakowPoland
| | - Mateusz J Swierz
- Jagiellonian University Medical CollegeDepartment of Hygiene and Dietetics, Systematic Reviews UnitKrakowPoland
| | - Jos Kleijnen
- Kleijnen Systematic Reviews LtdUnit 6, Escrick Business ParkRiccall Road, EscrickYorkUKYO19 6FD
- School for Public Health and Primary Care (CAPHRI), Maastricht UniversityMaastrichtNetherlands6200 MD
| | | |
Collapse
|
|
32
|
Lee RM, Cardona K, Russell MC. Historical perspective: Two decades of progress in treating metastatic colorectal cancer. J Surg Oncol 2019; 119:549-563. [PMID: 30806493 DOI: 10.1002/jso.25431] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 12/11/2022]
Abstract
Colorectal cancer is the third most commonly diagnosed cancer in the United States. While screening methods strive to improve rates of early stage detection, 25% of patients have metastatic disease at the time of diagnosis, with the most common sites being the liver, lung, and peritoneum. While once perceived as hopeless, the last two decades have seen substantial strides in the medical, surgical, and regional therapies to treat metastatic disease offering significant improvements in survival.
Collapse
Affiliation(s)
- Rachel M Lee
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Maria C Russell
- Department of Surgery, Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia
| |
Collapse
|
|
33
|
Xu F, Tang B, Jin TQ, Dai CL. Current status of surgical treatment of colorectal liver metastases. World J Clin Cases 2018; 6:716-734. [PMID: 30510936 PMCID: PMC6264988 DOI: 10.12998/wjcc.v6.i14.716] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Revised: 09/14/2018] [Accepted: 10/22/2018] [Indexed: 02/05/2023] Open
Abstract
Liver metastasis (LM) is one of the major causes of death in patients with colorectal cancer (CRC). Approximately 60% of CRC patients develop LM during the course of their illness. About 85% of these patients have unresectable disease at the time of presentation. Surgical resection is currently the only curative treatment for patients with colorectal LM (CRLM). In recent years, with the help of modern multimodality therapy including systemic chemotherapy, radiation therapy, and surgery, the outcomes of CRLM treatment have significantly improved. This article summarizes the current status of surgical treatment of CRLM including evaluation of resectability, treatment for resectable LM, conversion therapy and liver transplantation for unresectable cases, liver resection for recurrent CRLM and elderly patients, and surgery for concomitant hepatic and extra-hepatic metastatic disease (EHMD). We believe that with the help of modern multimodality therapy, an aggressive oncosurgical approach should be implemented as it has the possibility of achieving a cure, even when EHMD is present in patients with CRLM.
Collapse
Affiliation(s)
- Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Bin Tang
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Tian-Qiang Jin
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Chao-Liu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, Liaoning Province, China
| |
Collapse
|
|
34
|
Squires MH, Cloyd JM, Dillhoff M, Schmidt C, Pawlik TM. Challenges of surgical management of intrahepatic cholangiocarcinoma. Expert Rev Gastroenterol Hepatol 2018; 12:671-681. [PMID: 29911912 DOI: 10.1080/17474124.2018.1489229] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy arising from biliary tract epithelium within bile ducts proximal to the secondary biliary radicles. The majority of patients are diagnosed with locally advanced or metastatic disease at presentation. Surgical resection remains the only potentially curative option, but poses unique challenges due to the large size and aggressive behavior of these tumors. Areas covered: The goal of surgical management of iCCA is margin negative (R0) hepatic resection with preservation of adequate size liver remnant and function. Data regarding role of staging laparoscopy, margin status, portal lymphadenectomy, and vascular resection for iCCA are reviewed. Perioperative systemic therapy may have value, although prospective data have been lacking. Recurrence rates remain high even after R0 resection; among patients with recurrent disease limited to the liver, re-resection or locoregional therapies may play a role. Liver transplantation may be an option for select patients with very early-stage iCCA, although this should be done on a protocol-only basis. Expert commentary: Appropriate preoperative patient selection and surgical technique are paramount to ensure optimal oncologic outcomes for patients with resectable iCCA. Improving systemic and locoregional therapy options may help decrease recurrence rates and improve long-term survival for this aggressive malignancy.
Collapse
Affiliation(s)
- Malcolm H Squires
- a Division of Surgical Oncology, Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Jordan M Cloyd
- a Division of Surgical Oncology, Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Mary Dillhoff
- a Division of Surgical Oncology, Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Carl Schmidt
- a Division of Surgical Oncology, Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| | - Timothy M Pawlik
- a Division of Surgical Oncology, Department of Surgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA
| |
Collapse
|
|
35
|
Tsilimigras DI, Ntanasis-Stathopoulos I, Bagante F, Moris D, Cloyd J, Spartalis E, Pawlik TM. Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence. Surg Oncol 2018; 27:280-288. [PMID: 29937183 DOI: 10.1016/j.suronc.2018.05.012] [Citation(s) in RCA: 142] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Revised: 04/27/2018] [Accepted: 05/03/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatic resection is considered the optimal potentially curative treatment for colorectal liver metastases (CRLM). Following resection, up to two-thirds of patients will develop recurrence within 5-years. Genetic mutation analysis of CRLM, especially KRAS status, has been proposed as a means to guide treatment, as well as identifying patients who can derive the most survival benefit from hepatic resection. METHODS A systematic review of the literature was conducted the PubMed, Embase and Cochrane library through February 8th, 2018. The following algorithm was applied: "(colorectal OR rectal OR colon OR colonic) AND (liver OR hepatic) AND (metastasis OR metastases) AND (gene OR mutation OR KRAS OR BRAF OR SMAD4 OR RAS OR TP53 OR P53 OR APC OR PI3K OR MSI OR EGFR OR MACC1 OR microsatellite)." RESULTS From the 2404 records retrieved, 78 studies were finally deemed eligible; 47 studies reported mutational data on patients with resectable CRLM, whereas 31 studies reported on patients with unresectable CRLM. Mutational analyses were mostly performed on the CRLM specimen rather than the primary CRC. The vast majority of studies reported on the KRAS mutational status (88.5%, n = 69/78). Prevalence of KRAS mutations ranged from 25% to 52%. Most studies reported that RAS mutation was a negative prognostic factor for overall (OS) (n = 24) and recurrence-free (RFS) (n = 9) survival; a few reports noted no effect of RAS mutational status on OS (n = 4) or RFS (n = 6). Twelve studies reported on BRAF mutations with a prevalence of BRAF mutation ranging from 0 to 9.1% in resected CRLM specimens. BRAF mutation was strongly associated with a worse prognosis. TP53 and PIK3CA gene mutations did not affect long-term outcomes. CONCLUSIONS The biological status of each tumor provides the basis for individualized cancer therapeutics. Data on the mutational status on CRLM should be a part of multidisciplinary discussions to help inform the therapeutic approach, type of chemotherapy, as well as timing and approach of surgical resection.
Collapse
Affiliation(s)
- Diamantis I Tsilimigras
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Fabio Bagante
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Demetrios Moris
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Jordan Cloyd
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
| | - Eleftherios Spartalis
- Laboratory of Experimental Surgery and Surgical Research, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
| |
Collapse
|