|
1
|
Charbonneau J, Brind'Amour A, Sideris L, Piedimonte S, Soucisse M, Singbo N, Tremblay JF, Leblanc G, Fortin S, De Guerké L, Auclair MH, Gervais MK. Predictive Value of C-Reactive Protein for Infectious Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Single-Center Prospective Study. Ann Surg Oncol 2024; 31:8538-8548. [PMID: 39134911 DOI: 10.1245/s10434-024-15986-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 07/23/2024] [Indexed: 11/10/2024]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be associated with significant morbidity and prolonged hospital stay. Postoperative infections account for a high burden of these complications. This study aimed to assess the predictive value of postoperative C-reactive protein (CRP) levels for overall infectious complications and anastomotic leaks. METHODS This was a single-center prospective study of patients undergoing CRS and HIPEC for peritoneal metastases between 2018 and 2020 at Maisonneuve-Rosemont Hospital in Montreal, QC, Canada. CRP levels were measured daily for 10 days following surgery. A comparison was made between patients with infectious complications and those without. RESULTS Ninety-nine patients were included. Thirty patients had infectious complications (30.3%) and four patients presented an anastomotic leak (4%). CRP levels were significantly higher in patients with infectious complications from postoperative days (PODs) 2-10. Daily cut-off values most accurately predicted infectious complications on day 8 (94.3 mg/L; area under the curve [AUC] 0.85, sensitivity [SE] 76.2%, specificity [SP] 94.7%, positive predictive value [PPV] 88.9%, negative predictive value [NPV] 87.8%; p < 0.0001) and day 9 (72.7 mg/L; AUC 0.89, SE 95.2%, SP 81.8%, PPV 76.9%, NPV 96.4%; p < 0.0001). Patients with infectious complications had longer operative time, higher peritoneal cancer index, and a higher number of intestinal anastomoses, while their baseline characteristics were comparable. CONCLUSION Measurement of CRP helps predict infectious complications following CRS and HIPEC, particularly on PODs 8 and 9. Cut-off values are more accurate after the first postoperative week, especially in ruling out infectious complications.
Collapse
Affiliation(s)
- Janyssa Charbonneau
- Division of General Surgery, Department of Surgery, Université Laval, Quebec City, QC, Canada.
| | - Alexandre Brind'Amour
- Division of Surgical Oncology, Department of Surgery, Hotel-Dieu de Québec Hospital, Université Laval, Quebec City, QC, Canada
| | - Lucas Sideris
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Sabrina Piedimonte
- Division of Gynecology Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Mikaël Soucisse
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Narcisse Singbo
- Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC, Canada
| | - Jean-François Tremblay
- Division of Colorectal Surgery, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Guy Leblanc
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Suzanne Fortin
- Division of Gynecology Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Lara De Guerké
- Division of Gynecology Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Marie-Hélène Auclair
- Division of Gynecology Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| | - Mai-Kim Gervais
- Division of Surgical Oncology, Department of Surgery, Maisonneuve-Rosemont Hospital, Université de Montréal, Montreal, QC, Canada
| |
Collapse
|
|
2
|
Gurusamy K, Leung J, Vale C, Roberts D, Linden A, Wei Tan X, Taribagil P, Patel S, Pizzo E, Davidson B, Mould T, Saunders M, Aziz O, O'Dwyer S. Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis. Health Technol Assess 2024; 28:1-139. [PMID: 39254852 PMCID: PMC11417642 DOI: 10.3310/kwdg6338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/11/2024] Open
Abstract
Background We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work More randomised controlled trials are necessary. Study registration This study is registered as PROSPERO CRD42019130504. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
Collapse
Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Jeffrey Leung
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire Vale
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Xiao Wei Tan
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Priyal Taribagil
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Sonam Patel
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Elena Pizzo
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Tim Mould
- Department of Gynaecological Oncology, University College London NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
| |
Collapse
|
|
3
|
Gurusamy K, Leung J, Vale C, Roberts D, Linden A, Tan XW, Taribagil P, Patel S, Pizzo E, Davidson B, Saunders M, Aziz O, O’Dwyer ST. Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials. World J Surg 2024; 48:1385-1403. [PMID: 38658171 PMCID: PMC7617159 DOI: 10.1002/wjs.12186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 03/10/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION CRD42019130504.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Mark Saunders
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
| | - Omer Aziz
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
- Division of Cancer Studies, University of Manchester, London, UK
| | - Sarah T. O’Dwyer
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
- Division of Cancer Studies, University of Manchester, London, UK
| |
Collapse
|
|
4
|
Inflammatory biomarkers to predict postoperative infectious complications after cytoreductive surgery and HIPEC for peritoneal carcinomatosis. Eur J Surg Oncol 2021; 48:455-461. [PMID: 34565632 DOI: 10.1016/j.ejso.2021.09.015] [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: 04/22/2021] [Revised: 08/30/2021] [Accepted: 09/16/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Early detection of postoperative infectious complications (IC) is crucial after Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). The aim of this study was to evaluate the predictive role of early postoperative inflammatory biomarkers level for the detection of postoperative IC. METHODS a retrospective study was performed including 199 patients treated with complete CRS/HIPEC for PC from various primary origins from September 2012 to January 2021. Patients were monitored by a routine measurement of inflammatory biomarkers (CRP, leukocytes, neutrophils, lymphocytes, neutrophile-to-lymphocyte ratio and platelets-to-lymphocyte ratio). Inflammatory biomarkers were compared between patients with vs without IC. RESULTS IC occurred for 68 patients (34.2%). CRP values were significantly higher in patients with IC on POD 3, 5 and 7 (CRP = 166 mg/L [128-244], 155 mg/L [102-222] and 207 mg/L [135-259], respectively). The CRP on POD7, with a cut-off value of 100 mg/L, was an excellent predictor of postoperative IC (AUC = 90.1%). The CRP on POD 5, with a cut-off value of 90 mg/L, was a good predictor of postoperative IC (AUC = 83.2%). NLR values were significantly higher in patients with IC on POD 3, 5 and 7. NLR on POD 5 and 7 higher than 9.7 and 6.3, respectively, were fair predictors (AUC = 70.8 and 79.6, respectively). CONCLUSION CRP levels between POD3 and 7 are the best predictors of postoperative IC after CRS/HIPEC. The presence of postoperative IC should be suspected in patients with CRP higher than 140 mg/L, 90 mg/L or 100 mg/L on PODs 3, 5 or 7.
Collapse
|
|
5
|
Kitai T. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan. Surg Today 2021; 51:1085-1098. [PMID: 33185798 DOI: 10.1007/s00595-020-02180-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 09/29/2020] [Indexed: 02/07/2023]
Abstract
The prognosis of peritoneal carcinomatosis is poor. However, the emergence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) as a treatment option has prolonged survival and it can even potentially cure patients with peritoneal carcinomatosis. Randomized controlled studies and other observational studies indicated that this combined therapy potentially improved the prognosis of patients with colon, gastric, and ovarian cancers with acceptable morbidity and mortality rates. Even in rarer diseases, such as pseudomyxoma peritonei and malignant peritoneal mesothelioma, CRS + HIPEC markedly improved the prognoses over those with conventional treatment. Based on the accumulated evidence, clinical guidelines recommend CRS + HIPEC for selected patients with peritoneal carcinomatosis. However, several issues still need to be overcome. A standard method for HIPEC has not yet been established. Furthermore, the criteria employed for patient selection need to be clarified to achieve real benefits. The peritoneal cancer index, chemo-sensitivity and several biological markers are considered to be key factors.
Collapse
Affiliation(s)
- Toshiyuki Kitai
- Department of Surgery, Kishiwada City Hospital, 1001 Gakuharacho, Kishiwada, Osaka, 5968501, Japan.
| |
Collapse
|
|
6
|
Mulens-Arias V, Nicolás-Boluda A, Pinto A, Balfourier A, Carn F, Silva AKA, Pocard M, Gazeau F. Tumor-Selective Immune-Active Mild Hyperthermia Associated with Chemotherapy in Colon Peritoneal Metastasis by Photoactivation of Fluorouracil-Gold Nanoparticle Complexes. ACS NANO 2021; 15:3330-3348. [PMID: 33528985 DOI: 10.1021/acsnano.0c10276] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Peritoneal metastasis (PM) is considered as the terminal stage of metastatic colon cancer, with still poor median survival rate even with the best recent chemotherapy treatment. The current PM treatment combines cytoreductive surgery, which consists of resecting all macroscopic tumors, with hyperthermic intraperitoneal chemotherapy (HIPEC), which uses mild hyperthermia to boost the diffusion and cytotoxic effect of chemotherapeutic drugs. As HIPEC is performed via a closed circulation of a hot liquid containing chemotherapy, it induces uncontrolled heating and drug distribution in the whole peritoneal cavity with important off-site toxicity and a high level of morbidity. Here, we propose a safer precision strategy using near-infrared (NIR) photoactivated gold nanoparticles (AuNPs) coupled to the chemotherapeutic drug 5-fluorouracil (5-FU) to enable a spatial and temporal control of mild chemo-hyperthermia targeted to the tumor nodules within the peritoneal cavity. Both the 16 nm AuNPs and the corresponding complex with 5-FU (AuNP-5-FU) were shown as efficient NIR photothermal agents in the microenvironment of subcutaneous colon tumors as well as PM in syngeneic mice. Noteworthy, NIR photothermia provided additional antitumor effects to 5-FU treatment. A single intraperitoneal administration of AuNP-5-FU resulted in their preferential accumulation in tumor nodules and peritoneal macrophages, allowing light-induced selective hyperthermia, extended tumor necrosis, and activation of a pro-inflammatory immune response while leaving healthy tissues without any damage. From a translational standpoint, the combined and tumor-targeted photothermal and chemotherapy mediated by the AuNP-drug complex has the potential to overcome the current off-target toxicity of HIPEC in clinical practice.
Collapse
Affiliation(s)
- Vladimir Mulens-Arias
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
- Department of Immunology and Oncology, National Center for Biotechnology/CSIC, Darwin 3, Cantoblanco Campus, 28049 Madrid, Spain
| | - Alba Nicolás-Boluda
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
| | - Amandine Pinto
- Université de Paris, UMR 1275 CAP Paris-Tech, F-75010 Paris, France
- Service de chirurgie digestive et cancérologique, Hôpital Lariboisière, 2 rue Ambroise Paré, F-75010 Paris, France
| | - Alice Balfourier
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
| | - Florent Carn
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
| | - Amanda K A Silva
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
| | - Marc Pocard
- Université de Paris, UMR 1275 CAP Paris-Tech, F-75010 Paris, France
- Service de chirurgie digestive et cancérologique, Hôpital Lariboisière, 2 rue Ambroise Paré, F-75010 Paris, France
| | - Florence Gazeau
- Université de Paris, Laboratoire MSC Matière et Systèmes Complexes, CNRS UMR 7057, 10 Rue Alice Domon et Léonie Duquet, 75205 Cedex 13 Paris, France
| |
Collapse
|
|
7
|
Gurusamy K, Vale CL, Pizzo E, Bhanot R, Davidson BR, Mould T, Mughal M, Saunders M, Aziz O, O'Dwyer S. Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness. BMJ Open 2020; 10:e039314. [PMID: 32404398 PMCID: PMC7228534 DOI: 10.1136/bmjopen-2020-039314] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 04/17/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019130504.
Collapse
Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire L Vale
- Meta-analysis Group, MRC Clinical Trials Unit at UCL, London, UK
| | - Elena Pizzo
- Department of Applied Health Research, University College London, London, UK
| | - R Bhanot
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of HPB Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - Tim Mould
- Gynaecological Oncology, University College London Hospitals NHS Trust, London, UK
| | - Muntzer Mughal
- Surgery, University College London Hospital NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| |
Collapse
|
|
8
|
Abdel-Rahman O. Impact of cytoreductive surgery on outcomes of metastatic appendiceal carcinoma: a real-world, population-based study. J Comp Eff Res 2020; 9:431-439. [PMID: 32253936 DOI: 10.2217/cer-2019-0179] [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: 11/21/2022] Open
Abstract
Aim: To evaluate the impact of cytoreductive surgery on the outcomes of patients with metastatic appendiceal carcinoma. Methods: Surveillance, Epidemiology and End Results (SEER) database was accessed and patients with metastatic appendiceal carcinoma diagnosed (2010-2015) were reviewed. Kaplan-Meier survival estimates/log-rank testing were then used to assess overall survival outcomes according to cytoreductive surgery. Multivariable Cox regression analysis was then used to evaluate factors affecting cancer-specific survival. Factors included in this model were age, race, sex, stage and histology and cytoreductive surgery. Results: A total of 1339 patients with metastatic appendiceal carcinoma were included in the current study. Using Kaplan-Meier survival estimates to evaluate overall survival, patients with surgery for metastatic disease have better overall survival compared with patients without surgery for metastatic disease (p < 0.001). Stratifying survival analysis according to histology, the overall survival benefit from surgery for the metastases seems to be limited to patients with mucinous adenocarcinoma (p = 0.002) rather than patients with nonmucinous adenocarcinoma (p = 0.401). Multivariable Cox regression analysis was then conducted to evaluate factors predicting cancer-specific survival. The following factors were associated with worse cancer-specific survival: African-American race (hazard ratio [HR]: 1.356; 95% CI: 1.036-1.774; p = 0.026), more advanced stage (HR: 3.910; 95% CI: 2.735-5.588; p < 0.001), nonmucinous adenocarcinoma (HR for signet ring carcinoma vs mucinous adenocarcinoma: 2.119; 95% CI: 1.674-2.683; p < 0.001) and no surgical resection of metastatic disease (HR: 1.273; 95% CI: 1.067-1.519; p < 0.001). Conclusion: The current study suggests that among patients with metastatic appendiceal carcinoma, surgical cytoreduction of metastatic disease is associated with improved outcomes for patients with mucinous adenocarcinoma but not in patients with nonmucinous adenocarcinoma.
Collapse
Affiliation(s)
- Omar Abdel-Rahman
- Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, T6G 1Z2, Canada
| |
Collapse
|
|
9
|
Baaten ICPA, West NP, Quyn AJ, Seymour MT, Seligmann JF. Colorectal cancer peritoneal metastases: Biology, treatment and next steps. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:675-683. [PMID: 31806517 DOI: 10.1016/j.ejso.2019.10.035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/18/2019] [Accepted: 10/28/2019] [Indexed: 01/22/2023]
Abstract
The presence of peritoneal metastases in patients with advanced colorectal cancer is associated with poor prognosis but the mechanisms for this are unclear. This review summarises the current knowledge of the pathophysiology, clinical features, prevalence, prognosis, and molecular biology of peritoneal metastases and the risk factors for the development of peritoneal metastases following resection of a primary colorectal tumour. Furthermore, the evidence for treatment strategies are described including cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, early post-operative intraperitoneal chemotherapy, sequential post-operative intraperitoneal chemotherapy and emerging novel strategies. Active areas of research should include the identification of individuals at high risk of peritoneal metastases after curative resection of primary tumour, development of a surveillance program for high-risk patients, optimisation of systematic therapies and further investigation of the use of intraperitoneal chemotherapy.
Collapse
Affiliation(s)
- Ilona C P A Baaten
- Leeds Institute of Clinical Trial Research, University of Leeds, Leeds, United Kingdom.
| | - Nicholas P West
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Aaron J Quyn
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Matthew T Seymour
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| | - Jenny F Seligmann
- Leeds Institute of Medical Research at St. James's, University of Leeds, St James's University Hospital, Beckett Street, Leeds, United Kingdom.
| |
Collapse
|
|
10
|
Fields AC, Lu PW, Li GZ, Welten V, Jolissaint JS, Vierra BM, Saadat LV, Larson AC, Atkinson RB, Melnitchouk N. Current practices and future steps for hyperthermic intraperitoneal chemotherapy. Curr Probl Surg 2020; 57:100727. [PMID: 32151327 DOI: 10.1016/j.cpsurg.2019.100727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 12/23/2019] [Indexed: 11/20/2022]
Affiliation(s)
- Adam C Fields
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| | - Pamela W Lu
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - George Z Li
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Vanessa Welten
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Joshua S Jolissaint
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | | | - Lily V Saadat
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Abby C Larson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Rachel B Atkinson
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Nelya Melnitchouk
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
| |
Collapse
|
|
11
|
Gamboa AC, Zaidi MY, Lee RM, Speegle S, Switchenko JM, Lipscomb J, Cloyd JM, Ahmed A, Grotz T, Leiting J, Fournier K, Lee AJ, Dineen S, Powers BD, Lowy AM, Kotha NV, Clarke C, Gamblin TC, Patel SH, Lee TC, Lambert L, Hendrix RJ, Abbott DE, Vande Walle K, Lafaro K, Lee B, Johnston FM, Greer J, Russell MC, Staley CA, Maithel SK. Optimal Surveillance Frequency After CRS/HIPEC for Appendiceal and Colorectal Neoplasms: A Multi-institutional Analysis of the US HIPEC Collaborative. Ann Surg Oncol 2020; 27:134-146. [PMID: 31243668 PMCID: PMC6925634 DOI: 10.1245/s10434-019-07526-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Indexed: 01/19/2023]
Abstract
BACKGROUND No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.
Collapse
Affiliation(s)
- Adriana C Gamboa
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Rachel M Lee
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shelby Speegle
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Jeffrey M Switchenko
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Joseph Lipscomb
- Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ahmed Ahmed
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Andrew J Lee
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sean Dineen
- Department of Surgery, H. Lee Moffitt Cancer Center, Tampa, FL, USA
| | | | - Andrew M Lowy
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA
| | - Nikhil V Kotha
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Tiffany C Lee
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Laura Lambert
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Ryan J Hendrix
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Daniel E Abbott
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Kara Vande Walle
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Kelly Lafaro
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Byrne Lee
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | | | - Jonathan Greer
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Maria C Russell
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Charles A Staley
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
| |
Collapse
|
|
12
|
Elizabeth McCracken EK, Samsa GP, Fisher DA, Farrow NE, Landa K, Shah KN, Blazer DG, Zani S. Prognostic significance of primary tumor sidedness in patients undergoing liver resection for metastatic colorectal cancer. HPB (Oxford) 2019; 21:1667-1675. [PMID: 31155452 PMCID: PMC7243173 DOI: 10.1016/j.hpb.2019.03.365] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Revised: 01/25/2019] [Accepted: 03/14/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Approximately 38% of patients with colorectal cancer will develop isolated liver metastases. Sidedness of colon tumor is identified in non-metastatic and unresected metastatic cancers as predictive of survival, yet its dedicated analysis in resected liver metastases is minimal. Our primary aim was to assess whether left-sided primary tumors improve prognosis in stage IV cancer patients undergoing curative-intent liver metastasectomy; it was hypothesized that it would. METHODS This is a retrospective, observational cohort study from 1996 to 2016 in a single tertiary-care facility. Survival from diagnosis was calculated via Kaplan-Meier method and compared between the right and left sides via log-rank analysis. RESULTS Median survival differs significantly between colorectal tumors of the right and left origins after hepatic metastasectomy in 612 patients. In patients with right-sided tumors, median survival from diagnosis was 4.5 years (IQR 4.1-5.3), and 6.3 years (IQR 5.6-6.9) in those with left tumors (HR 1.5, 95% CI 1.38-1.60, p < 0.001). CONCLUSION As in studies on earlier-stage or unresected metastatic disease, tumor sidedness is an important prognostic factor in patient survival with liver metastasectomy. Clinical risk scores should include side of primary tumor. Further work is needed to determine the molecular basis for this difference.
Collapse
Affiliation(s)
- Emily K. Elizabeth McCracken
- Department of Surgery, Duke University Medical Center, Department of Surgery, Geisinger Medical Center, United States
| | - Gregory P. Samsa
- Department of Biostatistics & Bioinformatics, Duke University Medical Center, United States
| | - Deborah A. Fisher
- Division of Gastroenterology, Department of Medicine, Duke University Medical Center, United States
| | - Norma E. Farrow
- Department of Surgery, Duke University Medical Center, United States
| | - Karenia Landa
- Department of Surgery, Duke University Medical Center, United States
| | - Kevin N. Shah
- Division of Advanced Oncologic and Gastrointestinal Surgery, Department of Surgery, Duke University Medical Center, United States
| | - Dan G. Blazer
- Division of Advanced Oncologic and Gastrointestinal Surgery, Department of Surgery, Duke University Medical Center, United States
| | - Sabino Zani
- Division of Advanced Oncologic and Gastrointestinal Surgery, Department of Surgery, Duke University Medical Center, United States
| |
Collapse
|
|
13
|
Steffen T, Putora PM, Hübner M, Gloor B, Lehmann K, Kettelhack C, Adamina M, Peterli R, Schmidt J, Ris F, Glatzer M. Diagnostic Nodes of Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Among Colorectal Cancer Patients: A Swiss National Multicenter Survey. Clin Colorectal Cancer 2019; 18:e335-e342. [PMID: 31371166 DOI: 10.1016/j.clcc.2019.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 06/03/2019] [Accepted: 06/17/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The management of patients with colorectal cancer (CRC) with peritoneal metastases is challenging, and the roles of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are unclear and debated among experts. MATERIALS AND METHODS The experts of the Swiss Peritoneal Cancer Group were contacted and agreed to participate in this analysis. Experts from 9 centers in Switzerland provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Their responses were converted into decision trees on the basis of objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. RESULTS The final treatment algorithms included a total of 5 decision criteria (age, Peritoneal Cancer Index [PCI], extraperitoneal metastases, Peritoneal Surface Disease Severity Score, and various risk factors [RF]) and 2 treatment options (HIPEC, yes or no). HIPEC was never recommended for patients without peritoneal metastases in the absence of RF for peritoneal metastases. For patients with a PCI ≤15 without organ metastases, all centers recommended CRS/HIPEC. There was also a consensus not to perform CRS/HIPEC in elderly patients (80 years and older), those with a PCI >20, and those with unresectable metastases. For patients with a PCI = 16 to 20, there was no consensus. CONCLUSION Multiple decision criteria relevant to all participating centers were identified. Because patient selection for CRS/HIPEC remains difficult, uniform criteria for the term "high risk" for peritoneal metastases and systemic metastases are helpful. Future trials and guidelines should take these criteria into account.
Collapse
Affiliation(s)
- Thomas Steffen
- Department of Surgery, Kantonsspital St Gallen, St Gallen, Switzerland.
| | - Paul Martin Putora
- Department of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland; Department of Radiation Oncology, University of Bern, Bern, Switzerland
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Beat Gloor
- Department of Surgery, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Kuno Lehmann
- Department of Surgery and Transplantation, University Hospital of Zürich, Zürich, Switzerland
| | | | - Michel Adamina
- Department of Surgery, Kantonsspital Winterthur, Winterthur, Switzerland
| | - Ralph Peterli
- Department of Surgery, St Claraspital, Basel, Switzerland
| | - Jan Schmidt
- Department of Surgery, Klinik Hirslanden, Zürich, Switzerland
| | - Frédéric Ris
- Department of Surgery, University Hospital of Geneva, Geneva, Switzerland
| | - Markus Glatzer
- Department of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland
| |
Collapse
|
|
14
|
Ito K, Takemura N, Inagaki F, Mihara F, Kurokawa T, Gohda Y, Kiyomatsu T, Yano H, Kokudo N. Hepatectomy for metachronous colorectal liver metastases following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases: a report of three cases. World J Surg Oncol 2019; 17:99. [PMID: 31196097 PMCID: PMC6567639 DOI: 10.1186/s12957-019-1646-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 06/05/2019] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis (PM) from colorectal cancer (CRC) has been reported to substantially improve the prognosis and the quality of life of patients in comparison to systemic chemotherapy or palliative approaches. This study aimed to demonstrate the safety and feasibility of hepatectomy for metachronous liver metastases from CRC following CRS and HIPEC for PM on the basis of three case reports. CASE PRESENTATION We describe three cases involving patients who underwent hepatectomy for metachronous liver metastases from CRC after CRS and HIPEC for PM. All patients underwent CRS and HIPEC after primary tumor resection, and hepatectomy was performed for the metachronous liver metastases after CRS and HIPEC. The hepatectomy procedures for cases 1, 2, and 3 were left hemihepatectomy and partial resection of S5, posterior sectionectomy, and left-lateral sectionectomy and partial resection of S5 and S8, respectively. Although adhesion of surrounding organs to the liver surface was observed on a broad level, dissections and hepatectomy could be performed safely. No recurrence was detected in cases 1 and 2 after hepatectomy. In case 3, liver metastases were detected from the time of the initial diagnosis of the primary tumor, and complete remission was achieved once with systemic chemotherapy. Although we performed hepatectomy for the recurrence of liver metastases after complete remission, early re-recurrence was observed after hepatectomy. CONCLUSIONS Hepatectomy for metachronous liver metastases after CRS and HIPEC for PM could be a multi-modality treatment option for CRC recurrence.
Collapse
Affiliation(s)
- Kyoji Ito
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Fuyuki Inagaki
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Fuminori Mihara
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Toshiaki Kurokawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Yoshimasa Gohda
- Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Hideaki Yano
- Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
| |
Collapse
|
|
15
|
Frøysnes IS, Andersson Y, Larsen SG, Davidson B, Øien JMT, Julsrud L, Fodstad Ø, Dueland S, Flatmark K. ImmunoPeCa trial: Long-term outcome following intraperitoneal MOC31PE immunotoxin treatment in colorectal peritoneal metastasis. Eur J Surg Oncol 2019; 47:134-138. [PMID: 31036394 DOI: 10.1016/j.ejso.2019.04.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 04/09/2019] [Accepted: 04/19/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The ImmunoPeCa trial investigated the use of intraperitoneal MOC31PE immunotoxin as a novel therapeutic principle for the treatment of peritoneal metastasis from colorectal cancer (PM-CRC). We here report long-term outcome from the trial. METHODS This was a dose-finding trial aiming to evaluate safety and toxicity (primary endpoint) upon a single dose of intraperitoneal MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with mitomycin C. Overall survival (OS) and disease-free survival (DFS) were secondary endpoints. Twenty-one patients received the study drug at four dose levels on the first postoperative day, including six patients constituting an expansion cohort. RESULTS With a 34-month follow-up, the median OS was not reached and the estimated 3-year OS was 78%. Median DFS for all patients was 21 months and the 3-year DFS was 33%, with a median follow-up of 31 months. When excluding patients with potential favorable characteristics from the analysis (n = 4), the median DFS was 13 months and the 3-year OS 72%. CONCLUSIONS The promising long-term outcome combined with low systemic absorbance, high drug concentration and cytotoxic activity in peritoneal fluid support further investigations of clinical efficacy.
Collapse
Affiliation(s)
- Ida S Frøysnes
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Yvonne Andersson
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Stein G Larsen
- Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Ben Davidson
- Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | | | - Lars Julsrud
- Department of Radiology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Øystein Fodstad
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Kjersti Flatmark
- Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
| |
Collapse
|
|
16
|
Progressive Oncological Surgery Is Associated with Increased Curative Resection Rates and Improved Survival in Metastatic Colorectal Cancer. Cancers (Basel) 2019; 11:cancers11020218. [PMID: 30769860 PMCID: PMC6406820 DOI: 10.3390/cancers11020218] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 02/07/2019] [Accepted: 02/12/2019] [Indexed: 02/07/2023] Open
Abstract
Background: Secondary resection rates in first-line chemotherapy trials for metastatic colorectal cancer (mCRC) remain below 15%, representing a clear contrast to reports by specialised surgical centres, where progressive liver, peritoneal-surface, and pulmonary surgery increased access to curative-intent treatment. We present a long-term evaluation of oncosurgical management in a single-centre, analysing the aggregate effect of gradual implementation of surgical subspecialties and systemic treatments on mCRC patients’ resection rates and prognosis. Methods: Patients with newly diagnosed mCRC from 2003 to 2014 were retrospectively categorised into palliative treatment (PAT) and curative intent surgery (CIS) and three time periods were analysed for treatment changes and factors associated with survival. Results: Four hundred-twenty patients were treated (PAT:250/CIS:170). Over time periods, the number of presenting patients remained consistent, whereas curative resection rates increased from 29% to 55%, facilitated by an increment of patients undergoing hepatectomy (21 to 35%), pulmonary surgery (6 to 17%), and peritonectomy/intraoperative chemotherapy (0 to 8%). Also, recently, significantly more multi-line systemic treatments were applied. The median survival markedly improved from 21.9 months (2003–2006; 95% confidence interval (CI) 17.3–26.5) to 36.5 months (2011–2014; 95% CI 26.6–46.4; p = 0.018). PAT was a significant factor of poor survival and diagnosis of mCRC in the latest time period was independently associated with a distinctly lower risk for palliative treatment (odds ratio 0.15). Conclusions: In modern eras of medical oncology, achieving appropriate resection rates through utilization of state-of-the-art oncological surgery by dedicated experts represents a cornerstone for long-term survival in mCRC.
Collapse
|
|
17
|
Pinto A, Pocard M. Photodynamic therapy and photothermal therapy for the treatment of peritoneal metastasis: a systematic review. Pleura Peritoneum 2018; 3:20180124. [PMID: 30911668 PMCID: PMC6404999 DOI: 10.1515/pp-2018-0124] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/29/2018] [Indexed: 12/13/2022] Open
Abstract
Background The aim of this review was to analyze preclinical studies and clinical trials evaluating photodynamic therapy (PDT), and photothermal therapy (PTT) in peritoneal metastasis (PM) treatment. Content Systematic review according PRISMA guidelines. Electronic searches using PubMed and Clinical Trials. Summary A total of 19 preclinical studies analyzing PDT in PM treatment were included. Each new generations of photosensitizers (PS) permitted to improve tumoral targeting. Phase III preclinical studies showed an important tumoral biodistribution (ratio 9.6 vs normal tissue) and significant survival advantage (35.5 vs 52.5 days for cytoreductive surgery vs cytoreductive surgery+PDT, p<0.005). Height clinical trials showed important side effects (capillary leak syndrome and bowel perforation), mainly explained by low tumor-selectivity of the PS used (first generation mainly). Peritoneal mesothelioma apparition with carbon nanotubes first limited the development of PTT. But gold nanoparticles, with a good tolerance, permitted a limitation of tumoral growth (reduction of bioluminescence to 37 % 20 days after PTT), and survival benefit (35, 32, and 26 days for PTT with cisplatine, PTT alone and laser alone, respectively). Outlook Recent improvement in tumor-selectivity and light delivery systems is promising but further development would be necessary before PDT and PTT routinely applied for peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Amandine Pinto
- Paris Diderot University, Sorbonne Paris Cité, CART, INSERM U965, Paris, France
| | - Marc Pocard
- Paris Diderot University, Sorbonne Paris Cité, CART, INSERM U965, Paris, France.,Surgical Oncologic & Digestive Unit, Lariboisière Hospital, AP-HP, 2 rue Ambroise Paré, 75475 Paris Cedex 10, France
| |
Collapse
|
|
18
|
Teo MCC, Tan GHC. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastrointestinal cancers: fad or standard of care? Singapore Med J 2018; 59:116-120. [PMID: 29568842 DOI: 10.11622/smedj.2018025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Peritoneal metastases (PM) are the common endpoint for patients with advanced gastrointestinal cancers. PM from these cancers are often managed in a similar fashion to other sites of systemic metastases, but the following must be taken into consideration. (a) PM do not respond to systemic chemotherapy in the same fashion as liver and lung metastases. (b) PM cause local problems, resulting in disruption of chemotherapy. (c) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) actually work for PM. (d) PM are not easily detected on imaging modalities. There has been mounting evidence of the effectiveness of CRS-HIPEC at prolonging survival in selected patients with colorectal and gastric PM, but there remains a reluctance to explore this treatment modality. This is likely because of the perceived morbidity and mortality. An effective management strategy employing CRS-HIPEC for selected patients with gastrointestinal PM can only be achieved if a concerted effort is made to understand this disease and address the concerns regarding this treatment.
Collapse
|
|
19
|
Metastatic Colorectal Cancer to the Peritoneum: Current Treatment Options. Curr Treat Options Oncol 2018; 19:49. [DOI: 10.1007/s11864-018-0563-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
20
|
Laparoscopic gastrectomy and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) using a closed system with turbulent-flow circuit: technical aspects and preliminary results of a pilot study. Eur Surg 2018. [DOI: 10.1007/s10353-018-0538-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
|
|
21
|
Montori G, Coccolini F, Fugazzola P, Ceresoli M, Tomasoni M, Rubicondo C, Raimondo S, Pinelli D, Colledan M, Frigerio L, Ansaloni L. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian and gastrointestinal peritoneal carcinomatosis: results from a 7-year experience. J Gastrointest Oncol 2018; 9:241-253. [PMID: 29755762 DOI: 10.21037/jgo.2017.12.04] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Background An increasing promising evidence and increasing long-term oncologic outcomes support the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as locoregional treatment for peritoneal carcinosis (PC) especially from ovarian and gastrointestinal tumors, but also for others cancers. Methods A prospective monocentric study was performed in Papa Giovanni XXIII Hospital, Bergamo (Italy). Patients and tumor characteristics were analyzed. Overall survival (OS), disease free survival (DFS) and morbidity were analyzed with Kaplan-Meier curves and log-rank testing. Results A total of 150 patients undergone CRS + HIPEC were analyzed from January 2011 to June 2017. The principal origins of PC were: gastric cancer (GC) (n=40), colon cancer (n=31), appendiceal cancer (AC) (n=18), ovarian cancer (OC) (n=49), others (n=12). Major morbidity [≥3 Common Terminology Criteria for Adverse Events (CTCAE)] and perioperative mortality rates were 38% and 2.7% respectively. Re-operation rate was 15.3%. Median OS is 9, 35, 47, 51, 82 months (29% 3-year OS; 27% 5-year OS; 48% 5-year OS; 40% 5-year OS; 67% 5-year OS respectively) in GC, colorectal cancer (CRC), OC, others tumors and AC respectively. Median DFS is 4, 14, 17, 19, 82 months (32% 3-year DFS; 22% 5-year DFS; 29% 5-year DFS; 11% 5-year DFS; 67% 5-year DFS respectively) in GC, CRC, others tumors, OC and AC respectively. Conclusions A therapeutic approach that combined CRS + HIPEC could achieve long-term survival in selected groups of patients with PC from gastrointestinal, gynecological and others tumors with acceptable morbidity and mortality. A good expertise and a high volume of patients are necessary to manage PC and to further improve results.
Collapse
Affiliation(s)
- Giulia Montori
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Federico Coccolini
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Paola Fugazzola
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Marco Ceresoli
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Matteo Tomasoni
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Carolina Rubicondo
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Stefano Raimondo
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Domenico Pinelli
- Unit of Hepato-biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Michele Colledan
- Unit of Hepato-biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Luigi Frigerio
- Unit of Gynecology and Obstetrics, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Luca Ansaloni
- Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy
| |
Collapse
|
|
22
|
Lawler M, Alsina D, Adams RA, Anderson AS, Brown G, Fearnhead NS, Fenwick SW, Halloran SP, Hochhauser D, Hull MA, Koelzer VH, McNair AGK, Monahan KJ, Näthke I, Norton C, Novelli MR, Steele RJC, Thomas AL, Wilde LM, Wilson RH, Tomlinson I. Critical research gaps and recommendations to inform research prioritisation for more effective prevention and improved outcomes in colorectal cancer. Gut 2018; 67:179-193. [PMID: 29233930 PMCID: PMC5754857 DOI: 10.1136/gutjnl-2017-315333] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 10/24/2017] [Accepted: 10/25/2017] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes. DESIGN RG analysis was conducted by a multidisciplinary panel of patients, clinicians and researchers (n=71). Eight working groups (WG) were constituted: discovery science; risk; prevention; early diagnosis and screening; pathology; curative treatment; stage IV disease; and living with and beyond CRC. A series of discussions led to development of draft papers by each WG, which were evaluated by a 20-strong patient panel. A final list of RGs and research recommendations (RR) was endorsed by all participants. RESULTS Fifteen critical RGs are summarised below: RG1: Lack of realistic models that recapitulate tumour/tumour micro/macroenvironment; RG2: Insufficient evidence on precise contributions of genetic/environmental/lifestyle factors to CRC risk; RG3: Pressing need for prevention trials; RG4: Lack of integration of different prevention approaches; RG5: Lack of optimal strategies for CRC screening; RG6: Lack of effective triage systems for invasive investigations; RG7: Imprecise pathological assessment of CRC; RG8: Lack of qualified personnel in genomics, data sciences and digital pathology; RG9: Inadequate assessment/communication of risk, benefit and uncertainty of treatment choices; RG10: Need for novel technologies/interventions to improve curative outcomes; RG11: Lack of approaches that recognise molecular interplay between metastasising tumours and their microenvironment; RG12: Lack of reliable biomarkers to guide stage IV treatment; RG13: Need to increase understanding of health related quality of life (HRQOL) and promote residual symptom resolution; RG14: Lack of coordination of CRC research/funding; RG15: Lack of effective communication between relevant stakeholders. CONCLUSION Prioritising research activity and funding could have a significant impact on reducing CRC disease burden over the next 5 years.
Collapse
Affiliation(s)
- Mark Lawler
- Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
| | | | | | - Annie S Anderson
- Research into Cancer Prevention and Screening, University of Dundee, Dundee, UK
| | - Gina Brown
- Department of Radiology, Royal Marsden Hospital, Sutton, UK
| | | | - Stephen W Fenwick
- Hepatobiliary Surgery Unit, Aintree University Hospital, Liverpool, UK
| | - Stephen P Halloran
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Daniel Hochhauser
- Department of Oncology, University College London Cancer Institute, London, UK
| | - Mark A Hull
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - Viktor H Koelzer
- Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK
| | - Angus G K McNair
- Centre for Surgical Research, University of Bristol, Bristol, UK
| | - Kevin J Monahan
- Family History of Bowel Cancer Clinic, Imperial College London, London, UK
| | - Inke Näthke
- School of Life Sciences, University of Dundee, Dundee, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing and Midwifery, King’s College London, London, UK
| | - Marco R Novelli
- Research Department of Pathology, University College London Medical School, London, UK
| | - Robert J C Steele
- Research into Cancer Prevention and Screening, University of Dundee, Dundee, UK
| | - Anne L Thomas
- Leicester Cancer Research Centre, University of Leicester, Leicester, UK
| | - Lisa M Wilde
- Bowel Cancer UK, London, UK
- Atticus Consultants Ltd, Croydon, UK
| | - Richard H Wilson
- Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
| | - Ian Tomlinson
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| |
Collapse
|
|
23
|
Morris DL. Reply: "Adjuvant" Hyperthermic Intraperitoneal Chemotherapy: A Call to Action. Ann Surg Oncol 2017; 24:616. [PMID: 29159737 DOI: 10.1245/s10434-017-6171-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Indexed: 11/18/2022]
Affiliation(s)
- David L Morris
- Department of Surgery, St George Hospital and University of New South Wales, Sydney, NSW, Australia.
| |
Collapse
|
|
24
|
Pouliquen DL, Nawrocki-Raby B, Nader J, Blandin S, Robard M, Birembaut P, Grégoire M. Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma. Oncotarget 2017; 8:57552-57573. [PMID: 28915695 PMCID: PMC5593667 DOI: 10.18632/oncotarget.15744] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2016] [Accepted: 02/06/2017] [Indexed: 12/15/2022] Open
Abstract
A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives.
Collapse
Affiliation(s)
- Daniel L Pouliquen
- INSERM, UMR 1232, Nantes, France.,Université de Nantes, Nantes, France.,CNRS ERL, Nantes, France
| | - Béatrice Nawrocki-Raby
- INSERM, UMR-S 903, Reims, France.,Université de Reims Champagne-Ardenne, Reims, France.,SFR CAP-Santé, Reims, France
| | - Joëlle Nader
- INSERM, UMR 1232, Nantes, France.,Université de Nantes, Nantes, France.,CNRS ERL, Nantes, France
| | - Stéphanie Blandin
- Université de Nantes, Nantes, France.,Plate-forme MicroPICell, SFR François Bonamy, Nantes, France
| | - Myriam Robard
- Université de Nantes, Nantes, France.,Plate-forme MicroPICell, SFR François Bonamy, Nantes, France
| | - Philippe Birembaut
- INSERM, UMR-S 903, Reims, France.,Université de Reims Champagne-Ardenne, Reims, France.,SFR CAP-Santé, Reims, France.,Laboratory of Biopathology, CHU Reims, Reims, France
| | - Marc Grégoire
- INSERM, UMR 1232, Nantes, France.,Université de Nantes, Nantes, France.,CNRS ERL, Nantes, France
| |
Collapse
|
|
25
|
Frøysnes IS, Andersson Y, Larsen SG, Davidson B, Øien JMT, Olsen KH, Giercksky KE, Julsrud L, Fodstad Ø, Dueland S, Flatmark K. Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial. Ann Surg Oncol 2017; 24:1916-1922. [PMID: 28224367 DOI: 10.1245/s10434-017-5814-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Indexed: 01/20/2023]
Abstract
BACKGROUND MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC. METHODS This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC. RESULTS No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies. CONCLUSIONS Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.
Collapse
Affiliation(s)
- Ida S Frøysnes
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Yvonne Andersson
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Stein G Larsen
- Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Ben Davidson
- Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | | | - Kari Hauge Olsen
- Department of Medical Biochemistry, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Karl-Erik Giercksky
- Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Lars Julsrud
- Department of Radiology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Øystein Fodstad
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Kjersti Flatmark
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. .,Faculty of Medicine, University of Oslo, Oslo, Norway. .,Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
| |
Collapse
|
|
26
|
Jeong SJ, Yoon YS, Lee JB, Lee JL, Kim CW, Park IJ, Lim SB, Yu CS, Kim JC. Palliative surgery for colorectal cancer with peritoneal metastasis: a propensity-score matching analysis. Surg Today 2017; 47:159-165. [PMID: 27549772 DOI: 10.1007/s00595-016-1402-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 04/19/2016] [Indexed: 01/23/2023]
Abstract
PURPOSE Peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with poor prognosis. We conducted this study to assess whether palliative resection (PR) of the primary tumor improved the overall survival (OS) of patients with PM-CRC. METHODS We analyzed retrospectively, data collected prospectively from patients with CRC. PM was categorized into three subgroups according to the Japanese classification of PM. A propensity-score model was used to compare the outcomes of patients who underwent PR (PR group) and those who did not [non-resection (NR) group]. RESULTS Among 1909 patients with metastatic CRC, 309 (16 %) had only peritoneal metastases and 255 of these patients who underwent palliative surgery (R2) were the subjects of our analysis: 161 in the PR group and 94 in the NR group. Median OS was significantly longer in the PR group than in the NR group (23 vs. 11 months, P < 0.001). Patients in the PR group had less extensive PM and a higher rate of receiving palliative chemotherapy than those in the NR group (P < 0.001). In a Cox multivariate analysis of 69 propensity-score matched pairs, PR resulted in significantly longer OS than NR (hazard ratio 0.496, 95 % confidence interval 0.268-0.919, P = 0.025). CONCLUSIONS Our results show that PR resulted in better OS than NR for patients with PM-CRC, when their overall condition permitted a more aggressive approach.
Collapse
Affiliation(s)
- Seon Jeong Jeong
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - Yong Sik Yoon
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
| | - Jung Bok Lee
- Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
| | - Jong Lyul Lee
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - Chan Wook Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - In Ja Park
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - Seok Byung Lim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - Chang Sik Yu
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea
| | - Jin Cheon Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea.
| |
Collapse
|
|
27
|
Sánchez-Velázquez P, Moosmann N, Töpel I, Piso P. “ En bloc” caudate lobe and inferior vena cava resection following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal and liver metastasis of colorectal cancer. World J Gastroenterol 2016; 22:10249-10253. [PMID: 28028374 PMCID: PMC5155185 DOI: 10.3748/wjg.v22.i46.10249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Revised: 09/10/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
There are diverse protocols to manage patients with recurrent disease after primary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis. We describe a case of metachronous liver metastasis after CRS and HIPEC for colorectal cancer, successfully treated with a selective metastectomy and partial graft of the inferior vena cava. A 35-year-old female presented with a large tumour in the cecum and consequent colonic stenosis. After an emergency right colectomy, the patient received adjuvant chemotherapy. One year later she was diagnosed with peritoneal carcinomatosis, and it was decided to carry out a CRS/HIPEC. After 2 years of total remission, an isolated metachronous liver metastasis was detected by magnetic resonance imaging surveillance. The patient underwent a third procedure including a caudate lobe and partial inferior vena cava resection with a prosthetic graft interposition, achieving an R0 situation. The postoperative course was uneventful and the patient was discharged on postoperative day 17 after the liver resection. At 18-mo follow-up after the liver resection the patient remained free of recurrence. In selected patients, the option of re-operation due to recurrent disease should be discussed. Even liver resection of a metachronous metastasis and an extended vascular resection are acceptable after CRS/HIPEC and can be considered as a potential treatment option to remove all macroscopic lesions.
Collapse
|
|
28
|
Maciver AH, Al-Sukhni E, Esquivel J, Skitzki JJ, Kane JM, Francescutti VA. Current Delivery of Hyperthermic Intraperitoneal Chemotherapy with Cytoreductive Surgery (CS/HIPEC) and Perioperative Practices: An International Survey of High-Volume Surgeons. Ann Surg Oncol 2016; 24:923-930. [DOI: 10.1245/s10434-016-5692-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Indexed: 12/19/2022]
|
|
29
|
Electromagnetic-Guided Bedside Placement of Nasoenteral Feeding Tubes by Nurses Is Non-Inferior to Endoscopic Placement by Gastroenterologists: A Multicenter Randomized Controlled Trial. Am J Gastroenterol 2016; 111:1123-32. [PMID: 27272012 DOI: 10.1038/ajg.2016.224] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2016] [Accepted: 05/02/2016] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement. METHODS We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals. Patients were randomly assigned (1:1) to undergo EM-guided or endoscopic nasoenteral feeding tube placement. The primary end point was the need for reinsertion of the feeding tube (e.g., after failed initial placement or owing to tube-related complications) with a prespecified non-inferiority margin of 10%. RESULTS Reinsertion was required in 29 (36%) of the 80 patients in the EM-guided group and 31 (42%) of the 74 patients in the endoscopy group (absolute risk difference -6%, upper limit of one-sided 95% confidence interval 7%; P for non-inferiority=0.022). No differences were noted in success and complication rates. In the EM-guided group, there was a reduced time to start of feeding (424 vs. 535 min, P=0.001). Although the level of discomfort was higher in the EM-guided group (Visual Analog Scale (VAS) 3.9 vs. 2.0, P=0.009), EM-guided placement received higher recommendation scores (VAS 8.2 vs. 5.5, P=0.008). CONCLUSIONS EM-guided bedside placement of nasoenteral feeding tubes by nurses was non-inferior to endoscopic placement by gastroenterologists in surgical patients and may be considered the preferred technique for nasoenteral feeding tube placement.
Collapse
|
|
30
|
Frøysnes IS, Larsen SG, Spasojevic M, Dueland S, Flatmark K. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis in Norway: Prognostic factors and oncologic outcome in a national patient cohort. J Surg Oncol 2016; 114:222-7. [PMID: 27173150 DOI: 10.1002/jso.24290] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 04/29/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can offer long-term survival to patients with resectable peritoneal metastasis (PM) from colorectal cancer (CRC), a condition with otherwise dismal prognosis. This study describes short- and long-term outcome in a national patient cohort and aims to identify prognostic factors. METHODS All patients treated with CRS-HIPEC for non-appendiceal PM-CRC in Norway 2004-2013 were included (n = 119), and outcome and potential prognostic factors were examined using survival- and ROC-curve analysis. RESULTS Five-year overall survival (OS) and disease-free survival (DFS) were 36% and 14%, respectively, with 45 months median follow-up. The only factor associated with OS in multivariable analysis was peritoneal cancer index (PCI), with HR 1.05 (1.01-1.09) for every increase in PCI-score (P = 0.015). Peritoneal relapse was associated with shorter OS than distant metastasis (P = 0.002). ROC-curves identified PCI > 12 as a marker with 100% specificity for prediction of disease relapse. Severe postoperative complications (Clavien-Dindo ≥ 3) occurred in 15% of patients and there was no 100-day mortality. CONCLUSIONS Long-term outcome was in line with published results, morbidity was acceptable and there was no 100-day mortality. The results reemphasize CRS-HIPEC as an important treatment option in PM-CRC, with particularly good results in patients with PCI < 12. J. Surg. Oncol. 2016;114:222-227. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Ida S Frøysnes
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Stein G Larsen
- Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Milan Spasojevic
- Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Kjersti Flatmark
- Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| |
Collapse
|
|
31
|
Heaney RM, Shields C, Mulsow J. Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases. World J Gastrointest Oncol 2015; 7:445-454. [PMID: 26688707 PMCID: PMC4678391 DOI: 10.4251/wjgo.v7.i12.445] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 06/20/2015] [Accepted: 10/09/2015] [Indexed: 02/05/2023] Open
Abstract
Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectable disease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, PubMed and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732 (62%) underwent a complete cytoreduction while 986 (35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.
Collapse
|
|
32
|
Khan MAS, Hakeem AR, Scott N, Saunders RN. Significance of R1 resection margin in colon cancer resections in the modern era. Colorectal Dis 2015; 17:943-53. [PMID: 25808496 DOI: 10.1111/codi.12960] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 02/23/2015] [Indexed: 02/08/2023]
Abstract
AIM Circumferential resection margin involvement (R1) in rectal cancer is a predictive factor for poor prognosis. The aim of this study was to confirm the prognostic significance of R1 in colon cancer resection and to establish whether the introduction of laparoscopic colorectal surgery influenced this. METHOD Prospectively collected data on a patient pathway data manager for sequential patients with colon cancer treated at our specialist unit from January 2005 to December 2010 were analysed. There were 1110 colonic resections (elective 865; emergency 245). A circumferential resection margin involvement of < 1 mm was considered positive. RESULTS The total R1 rate was 13.3% (elective 10.4%; emergency 23.6%; P < 0.001). Other statistically significant risk factors for an R1 resection included tumour perforation (P < 0.001), poorly differentiated carcinoma (P < 0.001), T4 tumour (P < 0.001), vascular invasion (P < 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and palliative resection (P < 0.001). Over half of the elective resections were undertaken laparoscopically (486/865; 56.2%). When compared with elective open resection (379/865; 43.8%), the R1 rate was similar (P = 0.491) with similar disease-free survival (DFS) and overall survival (OS). The overall relapse rate was 18.9% in R0 and 55.5% in R1 resections (P < 0.001). Kaplan-Meier survival analysis showed significant improvements in DFS and OS in R0 over R1 patients. CONCLUSION The R1 margin in colon cancer resection is an important marker for advanced disease and a prognostic factor for DFS and OS. The introduction of laparoscopic surgery has not influenced the outcome in our unit despite a complex case mix.
Collapse
Affiliation(s)
- M A S Khan
- John Goligher Unit of Coloproctology, Leeds, UK
| | - A R Hakeem
- John Goligher Unit of Coloproctology, Leeds, UK
| | - N Scott
- Department of Pathology, St James's Hospital, Leeds, UK
| | | |
Collapse
|
|
33
|
März L, Piso P. Treatment of peritoneal metastases from colorectal cancer. Gastroenterol Rep (Oxf) 2015; 3:298-302. [PMID: 26424828 PMCID: PMC4650975 DOI: 10.1093/gastro/gov044] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2015] [Accepted: 08/07/2015] [Indexed: 02/07/2023] Open
Abstract
Peritoneal seedings of a colorectal tumor represent the second most frequent site of metastasis (after the liver). In the era of 5-fluorouracil (5-FU)-only chemotherapy, the prognosis was poor for colorectal cancer with peritoneal metastases. Within the last few years, new chemotherapeutic and targeted agents have improved the prognosis; however, the response to these treatments seems to be lower than that for liver metastases. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have further improved both disease-free survival and overall survival. Keeping this in mind, every patient presenting with peritoneal metastases from colorectal cancer should be evaluated and receive adequate treatment, if possible in the above-mentioned combination. This paper reviews recent advancements in the therapy of peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Loreen März
- Department of Surgery, St. John of God Hospital Regensburg, Regensburg, Germany
| | - Pompiliu Piso
- Department of Surgery, St. John of God Hospital Regensburg, Regensburg, Germany
| |
Collapse
|