|
1
|
Chen CY, Huang TH, Lee LW, Lung J, Ou YC, Hung CH, Chuang HC, Chen MC, Wang TY. Prognostic factors of early recurrence after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Clin Cases 2024; 12:6057-6069. [PMID: 39328856 PMCID: PMC11326106 DOI: 10.12998/wjcc.v12.i27.6057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 06/25/2024] [Accepted: 07/15/2024] [Indexed: 07/29/2024] Open
Abstract
BACKGROUND Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) offer the potential for long-term survival in peritoneal carcinomatosis, outcomes following CRS/HIPEC vary significantly. AIM To identify the clinical factors associated with progression-free survival (PFS) after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal, ovarian, and gastric cancers. METHODS We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival (OS) in patients recruited between 2015 and 2020. Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year. Kaplan-Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS. RESULTS Of the 80 enrolled patients, 39 had an unfavorable PFS (< 1 year) and 41 had a favorable PFS (≥ 1 year). Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0 (CC-0) or length of CRS ≤ 6 h had a favorable PFS [odds ratio (OR) = 0.141, P = 0.004; and OR = 0.361, P = 0.027, respectively]. In multiple logistic regression, achieving CC-0 was the strongest prognostic factor for a favorable PFS (OR = 0.131, P = 0.005). A peritoneal cancer index score > 12 was associated with a lower rate of achieving CC-0 (P = 0.027). The favorable PFS group had a significantly longer OS (median 81.7 mo vs 17.0 mo, P < 0.001). CONCLUSION Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival. This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Chao-Yu Chen
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Early Childhood Care and Education, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan
| | - Tzu-Hao Huang
- Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Li-Wen Lee
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Jrhau Lung
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Medical Research and Development, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Yu-Che Ou
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chien-Hui Hung
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Huei-Chieh Chuang
- Department of Anatomic Pathology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| | - Min-Chi Chen
- Department of Public Health, Chang Gung University, Taoyuan 333, Taiwan
| | - Ting-Yao Wang
- Department of Early Childhood Care and Education, Shu-Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613, Taiwan
| |
Collapse
|
|
2
|
Nguyen QA, Chou WH, Hsieh MC, Chang CM, Luo WT, Tai YT, Chang WC. Genetic alterations in peritoneal metastatic tumors predicted the outcomes for hyperthermic intraperitoneal chemotherapy. Front Oncol 2023; 13:1054406. [PMID: 37182141 PMCID: PMC10170308 DOI: 10.3389/fonc.2023.1054406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 03/27/2023] [Indexed: 05/16/2023] Open
Abstract
Introduction Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered for patients with peritoneal metastasis (PM). However, patients selection that relies on conventional prognostic factors is not yet optimal. In this study, we performed whole exome sequencing (WES) to establish tumor molecular characteristics and expect to identify prognosis profiles for PM management. Methods In this study, blood and tumor samples were collected from patients with PM before HIPEC. Tumor molecular signatures were determined using WES. Patient cohort was divided into responders and non-responders according to 12-month progression-free survival (PFS). Genomic characteristics between the two cohorts were compared to study potential targets. Results In total, 15 patients with PM were enrolled in this study. Driver genes and enriched pathways were identified from WES results. AGAP5 mutation was found in all responders. This mutation was significantly associated with better OS (p = 0.00652). Conclusions We identified prognostic markers that might be useful to facilitate decision-making before CRS/HIPEC.
Collapse
Affiliation(s)
- Quynh-Anh Nguyen
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wan-Hsuan Chou
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Mao-Chih Hsieh
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Che-Mai Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Wei-Tzu Luo
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
| | - Yu-Ting Tai
- Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Wei-Chiao Chang
- Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- Master Program in Clinical Genomics and Proteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
- Department of Pharmacy, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Integrative Research Center for Critical Care, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| |
Collapse
|
|
3
|
Nizri E, Berger Y, Green E, Kyzer M, Aizic A, Nevo N, Gerstenhaber F, Klausner JM, Gutman M, Lahat G, Hoffman A, Geva R. Lymph Node Metastases from Visceral Peritoneal Colorectal Metastases are Associated with Systemic Recurrence. Ann Surg Oncol 2021; 29:2069-2075. [PMID: 34622371 DOI: 10.1245/s10434-021-10869-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 09/13/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Visceral peritoneal colorectal metastases (VPCMs) may further metastasize to lymph nodes that drain those organs. The rate of lymph node metastases (LNMs) from VPCMs and their clinical and prognostic significance are unknown. METHODS This study retrospectively analyzed the authors' institutional databases of 160 patients with peritoneal colorectal metastases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Patients with LNM-VPCM (n = 12) were identified by pathologic reports, and both their short- and long-term outcomes were compared with those of patients without LNM-VPCM. RESULTS The clinical presentation and primary tumor pathologic characteristics did not differ between the two groups. The patients with LNM-VPCM had a higher tumor burden (measured by the peritoneal carcinomatosis index [PCI]) and visible remnant disease compared with those who had no LNM-VPI (10 vs 5.5 [p = 0.03] vs 33.3% vs 6.8% [p = 0.007], respectively). The postoperative outcomes also were comparable. The patients with LNM-VPCM had a shorter overall survival (OS) than those without LNM-VPCM (median OS, 22.5 months; 95% confidence interval [CI], 15.1-29.9 months vs 40.1 months; 95% CI, 38.1-42 months; p = 0.02). However, only tumor grade and PCI were predictors of OS in the multivariate analysis (hazard ratio [HR], 2.33 [p = 0.001]; 1.77 [p = 0.03], respectively). The study showed that LNM-VPCM was associated with systemic but not peritoneal recurrence compared with non-LNM-VPCM (81.8% vs 51.6% for systemic recurrence, respectively; p = 0.05). CONCLUSION The small distinct group of patients defined by LNM-VPCM were prone to systemic recurrence. Given its correlation with systemic recurrence, LNM-VPCM may indicate the need for adjuvant treatment.
Collapse
Affiliation(s)
- Eran Nizri
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. .,The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
| | - Yaniv Berger
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Surgery B, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Eraan Green
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Matan Kyzer
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Surgery B, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Asaf Aizic
- Institute of Pathology, Tel- Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Nadav Nevo
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Fabian Gerstenhaber
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| | - Joseph M Klausner
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Mordechai Gutman
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Department of Surgery B, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Guy Lahat
- Peritoneal Surface Malignancy and Melanoma Unit, Department of Surgery A, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.,The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Aviad Hoffman
- Department of General Surgery, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ravit Geva
- The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.,Oncology Division, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
| |
Collapse
|
|
4
|
García-Fadrique A, Estevan Estevan R, Sabater Ortí L. Quality Standards for Surgery of Colorectal Peritoneal Metastasis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol 2021; 29:188-202. [PMID: 34435297 DOI: 10.1245/s10434-021-10642-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 07/27/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND The standardization of surgical outcomes throughout surgical procedures is mandatory. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) should provide proficient oncological and surgical outcomes. STUDY DESIGN The aim of this study was to identify clinically relevant quality indicators and their quality standard, and to determine their acceptable quality limit. A systematic review on cytoreductive results from 2000 to 2018 was performed focusing on clinical guidelines, consensus conferences, and publications. After the selection of quality indicators, a systematic review of indexed references was performed in order to calculate the quality standard for each indicator. STUDY SELECTION Unicentric/multicentric series, comparative studies, and clinical trials. Studies were to include outcomes after cytoreduction of colorectal origin and series with more than 50 patients. Quality indicators with at least 10 series were mandatory and objective measurements were also mandatory for inclusion. MAIN OUTCOME MEASUREMENTS Quality indicators selected were 1- to 5-year survival, overall disease-free survival, 1- to 5-year disease-free survival, complete surgical resection, duration of surgery, length of stay, overall morbimortality, major morbidity, re-intervention, postoperative hemorrhage, intestinal fistula, anastomotic leakage, wound infection, postoperative medical complications, overall recurrence, and failure to rescue. RESULTS The most relevant quality indicators and critical quality limits were overall disease-free survival and 5-year overall disease-free survival (14 months and <10 months, and 14% and <4%, respectively), completeness of surgical resection (89% and <80%, respectively), overall mortality (3% and >8%, respectively), overall morbidity (47% and >63%, respectively), failure to rescue (12% and <30%, respectively), reintervention (13 and <22%, respectively), anastomotic leakage (6% and <13%, respectively), and overall recurrence (60% and <74%, respectively). CONCLUSION This is the first study to assess quality standards in CRS + HIPEC for colorectal peritoneal metastases. The current data are of particular relevance for future studies to control the variability of this surgery.
Collapse
Affiliation(s)
| | | | - Luis Sabater Ortí
- Hospital Clínico Universitario, Department of Surgery, Biomedical Research Institute INCLIVA, University of Valencia, Valencia, Spain
| |
Collapse
|
|
5
|
Sutton PA, O'Dwyer ST, Barriuso J, Aziz O, Selvasekar CR, Renehan AG, Wilson MS. Indications and outcomes for repeat cytoreductive surgery and heated intra-peritoneal chemotherapy in peritoneal surface malignancy. Surg Oncol 2021; 38:101572. [PMID: 33915487 DOI: 10.1016/j.suronc.2021.101572] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/16/2020] [Accepted: 03/29/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).
Collapse
Affiliation(s)
- P A Sutton
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK.
| | - S T O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - J Barriuso
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK
| | - O Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK
| | - C R Selvasekar
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK
| | - A G Renehan
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Manchester Cancer Research Centre and NIHR Manchester Biomedical Research Centre, Manchester, UK
| | - M S Wilson
- Colorectal and Peritoneal Oncology Centre, The Christie Hospital, UK
| |
Collapse
|
|
6
|
Hulshof EC, Lim L, de Hingh IHJT, Gelderblom H, Guchelaar HJ, Deenen MJ. Genetic Variants in DNA Repair Pathways as Potential Biomarkers in Predicting Treatment Outcome of Intraperitoneal Chemotherapy in Patients With Colorectal Peritoneal Metastasis: A Systematic Review. Front Pharmacol 2020; 11:577968. [PMID: 33117169 PMCID: PMC7575928 DOI: 10.3389/fphar.2020.577968] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/27/2020] [Indexed: 12/18/2022] Open
Abstract
Background The introduction of cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with either oxaliplatin or mitomycin C for patients with colorectal peritoneal metastasis (CPM) has resulted in a major increase in overall survival. Nonetheless, despite critical patient selection, the majority of patients will develop recurrent disease within one year following CRS + HIPEC. Therefore, improvement of patient and treatment selection is needed and may be achieved by the incorporation of genetic biomarkers. This systematic review aims to provide an overview of genetic biomarkers in the DNA repair pathway that are potentially predictive for treatment outcome of patients with colorectal peritoneal metastases treated with CRS + HIPEC with oxaliplatin or mitomycin C. Methods A systematic review was conducted according to the PRISMA guidelines. Given the limited number of genetic association studies of intraperitoneal mitomycin C and oxaliplatin in patients with CPM, we expanded the review and extrapolated the data from biomarker studies conducted in colorectal cancer patients treated with systemic mitomycin C– and oxaliplatin-based chemotherapy. Results In total, 43 papers were included in this review. No study reported potential pharmacogenomic biomarkers in patients with colorectal cancer undergoing mitomycin C–based chemotherapy. For oxaliplatin-based chemotherapy, a total of 26 genetic biomarkers within 14 genes were identified that were significantly associated with treatment outcome. The most promising genetic biomarkers were ERCC1 rs11615, XPC rs1043953, XPD rs13181, XPG rs17655, MNAT rs3783819/rs973063/rs4151330, MMR status, ATM protein expression, HIC1 tandem repeat D17S5, and PIN1 rs2233678. Conclusion Several genetic biomarkers have proven predictive value for the treatment outcome of systemically administered oxaliplatin. By extrapolation, these genetic biomarkers may also be predictive for the efficacy of intraperitoneal oxaliplatin. This should be the subject of further investigation.
Collapse
Affiliation(s)
- Emma C Hulshof
- Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, Netherlands.,Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands
| | - Lifani Lim
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands
| | - Ignace H J T de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, Netherlands.,GROW, School for Oncology and Development Biology, Maastricht University, Maastricht, Netherlands
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands
| | - Henk-Jan Guchelaar
- Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.,Leiden Network for Personalized Therapeutics, Leiden, Netherlands
| | - Maarten J Deenen
- Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, Netherlands.,Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands
| |
Collapse
|
|
7
|
Spiegelberg J, Neeff H, Holzner P, Runkel M, Fichtner-Feigl S, Glatz T. Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer. World J Gastrointest Oncol 2020; 12:903-917. [PMID: 32879667 PMCID: PMC7443840 DOI: 10.4251/wjgo.v12.i8.903] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 05/29/2020] [Accepted: 06/14/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents include mitomycin C (MMC) and oxaliplatin. Studies have reported varying results, and the evidence for the choice of the HIPEC agent and uniform procedure protocols is limited.
AIM To evaluate therapeutic benefits and complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors.
METHODS One hundred and two consecutive patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient’s demographics and tumour characteristics, operative details, postoperative complications and survival were noted. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival.
RESULTS The two groups did not differ significantly regarding baseline characteristics. We found no difference in median overall survival between MMC and oxaliplatin HIPEC. Regarding postoperative complications, patients treated with oxaliplatin HIPEC suffered increased complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infection, and had a prolonged intensive care unit stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as peritoneal cancer index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise peritoneal cancer index-scoring regarding peritoneal carcinomatosis.
CONCLUSION In this single-institution retrospective review of patients undergoing CRS with either oxaliplatin or MMC HIPEC, overall survival was not different, though oxaliplatin was associated with a higher postoperative complication rate, indicating treatment favourably with MMC. Further studies comparing HIPEC regimens would improve evidence-based decision-making.
Collapse
Affiliation(s)
- Julia Spiegelberg
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Hannes Neeff
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Philipp Holzner
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Mira Runkel
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
| | - Torben Glatz
- Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
- Department of Surgery, Marien Hospital Herne, Ruhr-University Bochum, Herne 44625, Germany
| |
Collapse
|
|
8
|
Rezaeian M, Sedaghatkish A, Soltani M. Numerical modeling of high-intensity focused ultrasound-mediated intraperitoneal delivery of thermosensitive liposomal doxorubicin for cancer chemotherapy. Drug Deliv 2020; 26:898-917. [PMID: 31526065 PMCID: PMC6758722 DOI: 10.1080/10717544.2019.1660435] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU). A computational model is developed to evaluate the proposed drug delivery system. Results show an order of magnitude increase in drug penetration depth into the tumor compared to the conventional IP delivery. Furthermore, the effects of thermal conditions applied to the tumor, TSL size, tumor vessel permeability, and tumor size are investigated. Results indicate an improved efficiency of the drug delivery by expanding the heated region, yet, it increases the risk of unintentional TSL drug load release in the peritoneal cavity. Results also indicate that smaller TSLs have better treatment outcome. However, there is a significant reduction in treatment efficacy for TSLs with sizes smaller than the vessel wall pore size. Thus, tuning the size of TSL should be based on the tumor microvascular permeability. The simulation results suggest that the TSL-Dox delivery system in smaller tumors is far advantageous than larger ones. Results of our model can be used as guidelines for future preclinical studies.
Collapse
Affiliation(s)
- Mohsen Rezaeian
- Department of Mechanical Engineering, K. N. Toosi University of Technology , Tehran , Iran
| | - Amir Sedaghatkish
- Department of Mechanical Engineering, Isfahan University of Technology , Isfahan , Iran
| | - M Soltani
- Department of Mechanical Engineering, K. N. Toosi University of Technology , Tehran , Iran.,Advanced Bioengineering Initiative Center, Computational Medicine Center, K. N. Toosi University of Technology , Tehran , Iran.,Department of Electrical and Computer Engineering, University of Waterloo , Waterloo , Canada.,Centre for Biotechnology and Bioengineering (CBB), University of Waterloo , Waterloo , Canada.,Cancer Biology Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences , Tehran , Iran
| |
Collapse
|
|
9
|
Analysis of Bacterial and Fungal Infections after Cytoreduction Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Observational Single-Centre Study. Int J Microbiol 2019; 2019:6351874. [PMID: 31467552 PMCID: PMC6701354 DOI: 10.1155/2019/6351874] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 06/19/2019] [Indexed: 12/18/2022] Open
Abstract
Introduction While hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreduction surgery (CRS) has been shown to improve patient survival and disease-free progression in peritoneal carcinoma (PC) patients, the procedure relates to a high postoperative infection rate. Herein, we report the bacterial and fungal infections after CRS and HIPEC from a single institution in Saudi Arabia. Patients and Methods A prospective observational study was conducted on 38 patients with PC selected for CRS/HIPEC procedure between 2012 and 2015 in our centre. Results Postoperative bacterial and fungal infection within 100 days was 42.2%, bacterial infection was reported always, and fungal infection was reported in 5 (13.2%) cases. Infections from the surgical site were considered the most common infection site. Multidrug-resistant extended-spectrum beta-lactamase (ESBL) Escherichia coli was the most frequent isolate, followed by multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Lower preoperative albumin and a prolonged preoperative activated partial thromboplastin time (APTT) are associated with postoperative infections, while a prolonged preoperative hospital stay (hazard ratio (HR) = 1.064; confidence interval (CI) = 1.002–1.112; P=0.042) and more intraoperative blood loss (>10%) (HR = 3.919; 95% CI = 1.024–14.995; P=0.046) were independent risk factors for postoperative infections. Three cases died during the follow-up period; all were due to infection. Discussion The infection rate in our centre compared to previous studies of comparable patients was matching. Effective management of postoperative infections should be considered, and identified risk factors in this study can help to focus on effective prevention and treatment strategies.
Collapse
|
|
10
|
Ni Y, Xue L, Zhu G, Chen Y. Serum Homocysteine, VEGF and TGF-β1 dynamic change in colorectal cancer patients prior and post-operation. Pteridines 2019. [DOI: 10.1515/pteridines-2019-0014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Abstract
Background: The aim of the study was to evaluate the serum homocysteine (Hcy), vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) dynamic change in colorectal cancer patients pre- and post-operation.
Material and methods: One hundred and eighteen CRC patients treated with surgery (CRC group) and 56 healthy controls (Control group) were included in this work. The serum Hcy, VEGF TGF-β1 were examined by enzymatic cycle and enzyme-linked immunosorbent assay (ELISA) of the two groups. We followed patients for 12 months and out of the 118 CRC patients, 14 patients had recurrent disease. Serum Hcy, VEGF and TGF-β1 were measured before and after surgery and repeated every 2 months.
Results Serum Hcy, VEGF and TGF-β1 were 16.20 ± 4.79 μmol/L, 492.36 ± 97.32 pg/ml, 29.23 ± 7.47 pg/ml for the CRC group and 8.98 ± 3.02 μmol/L, 315.21 ± 56.28 pg/ml, 7.69 ± 2.31 pg/ml for the control groups. Serum Hcy, VEGF and TGF-β1 was significantly (p<0.05) lower after surgery in both recurrent and nonrecurrent CRC patients (p<0.05). Interestingly, serum Hcy, VEGF and TGF-β1 gradually increased with time.
Conclusion Serum Hcy, VEGF and TGF-β1 levels are elevated in CRC patients and may correlated with the post-operative disease recurrence.
Collapse
Affiliation(s)
- Yayi Ni
- Department of Hepatobiliary Surgery , Zhuji People‘s Hospital of Zhejiang Province 311800 PR China Zhuji
| | - Lihua Xue
- Department of Hepatobiliary Surgery , Zhuji People‘s Hospital of Zhejiang Province 311800 PR China Zhuji
| | - Guangbo Zhu
- Department of Hepatobiliary Surgery , Zhuji People‘s Hospital of Zhejiang Province 311800 PR China Zhuji
| | - Yangrong Chen
- Department of Clinical laboratory , Tianjin Union Medical Center (Tianjin People’s Hospital) 300121 PR China Tianjin
| |
Collapse
|
|
11
|
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
|
|
12
|
Hentzen JEKR, Rovers KP, Kuipers H, van der Plas WY, Been LB, Hoogwater FJH, van Ginkel RJ, Hemmer PHJ, van Dam GM, de Hingh IHJT, Kruijff S. Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study. Ann Surg Oncol 2019; 26:2210-2221. [PMID: 30877495 PMCID: PMC6545176 DOI: 10.1245/s10434-019-07294-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Indexed: 12/21/2022]
Abstract
Background Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. Methods Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien–Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan–Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. Results The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18–2.26). Conclusions Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure. Electronic supplementary material The online version of this article (10.1245/s10434-019-07294-y) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Judith E K R Hentzen
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Koen P Rovers
- Department of Surgery, Division of Surgical Oncology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands
| | - Hendrien Kuipers
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Willemijn Y van der Plas
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Lukas B Been
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Frederik J H Hoogwater
- Department of Surgery, Division of Hepatopancreatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Robert J van Ginkel
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Patrick H J Hemmer
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Gooitzen M van Dam
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,Department of Nuclear Medicine and Molecular Imaging and Intensive Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Ignace H J T de Hingh
- Department of Surgery, Division of Surgical Oncology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands.,GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands
| | - Schelto Kruijff
- Department of Surgery, Division of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| |
Collapse
|
|
13
|
Alzahrani NA, Valle SJ, Fisher OM, Sugarbaker PH, Yonemura Y, Glehen O, Goere D, Honore C, Brigand C, de Hingh I, Verwaal VJ, Deraco M, Baratti D, Kusamura S, Pocard M, Piso P, Maerz L, Marchal F, Moran B, Levine EA, Dumont F, Pezet D, Abboud K, Kozman MA, Liauw W, Morris DL. Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience. J Surg Oncol 2019; 119:336-346. [PMID: 30554404 DOI: 10.1002/jso.25277] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 09/24/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.
Collapse
Affiliation(s)
- Nayef A Alzahrani
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
- College of Medicine, Al-Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Sarah J Valle
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
| | - Oliver M Fisher
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
| | - Paul H Sugarbaker
- MedStar Washington Hospital Center, Peritoneal Surface Oncology Unit, Washington, DC
| | - Yutaka Yonemura
- Peritoneal Metastasis Center, Kishiwada Tokushukai Hospital, Osaka, Japan
| | - Olivier Glehen
- Surgical Oncology Department, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Dianne Goere
- Institute Gustave Roussy Cancer Campus, Department of Digestive and Oncology Surgery, Paris, France
| | - Charles Honore
- Institute Gustave Roussy Cancer Campus, Department of Digestive and Oncology Surgery, Paris, France
| | - Cecile Brigand
- General & Digestive Surgery, CHRU Hautepierre, Strasbourg, France
| | - Ignace de Hingh
- Catharina Hospital, Department of Surgery, Eindhoven, Netherlands
| | - Vic J Verwaal
- Catharina Hospital, Department of Surgery, Eindhoven, Netherlands
- Department of Surgical Oncology, Aarhus University Hospital, Denmark
| | - Marcello Deraco
- Fondazione IRCCS Istituto Nazionale dei Tumori, Peritoneal Surface Malignancies Program, Milan, Italy
| | - Dario Baratti
- Fondazione IRCCS Istituto Nazionale dei Tumori, Peritoneal Surface Malignancies Program, Milan, Italy
| | - Shigeki Kusamura
- Fondazione IRCCS Istituto Nazionale dei Tumori, Peritoneal Surface Malignancies Program, Milan, Italy
| | - Mark Pocard
- Surgical Oncology Department, St. Louis Hospital Lariboisiere, Paris, France
| | - Pompiliu Piso
- Department of Surgical Oncology, Hospital Barmherzige Brueder Regensburg, Germany
| | - Loreen Maerz
- Department of Surgical Oncology, Hospital Barmherzige Brueder Regensburg, Germany
| | - Frederic Marchal
- Department of Surgical Oncology, Institute of Cancer, Vandoeeuvre Les Nancy, France
| | - Brendan Moran
- Peritoneal Malignancy Department, Basingstoke North Hampshire Hospital, Basingstoke, UK
| | - Edward A Levine
- Wake Forest Baptist Health, Surgical Oncology, Winston-Salem, North Carolina
| | - Frédéric Dumont
- Surgical Oncology, René Gauducheau Cancer Center, Nantes, France
| | - Denis Pezet
- Department of Digestive Surgery, CHU Estaing, Clermont Ferrand, France
| | - Karine Abboud
- Department of General Surgery, CHU Nord, Saint Etienne, France
| | - Mathew A Kozman
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
| | - Winston Liauw
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
- Cancer Care Centre, St. George Hospital, Sydney, NSW, Australia
| | - David L Morris
- St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia
| |
Collapse
|
|
14
|
Feferman Y, Solomon D, Bhagwandin S, Kim J, Aycart SN, Feingold D, Sarpel U, Labow DM. Sites of Recurrence After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis from Colorectal and Appendiceal Adenocarcinoma: A Tertiary Center Experience. Ann Surg Oncol 2018; 26:482-489. [PMID: 30539491 DOI: 10.1245/s10434-018-6860-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND This report describes patterns of disease recurrence after optimal cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of colorectal (CRC) and appendiceal adenocarcinoma (AC) origin. METHODS Patients undergoing optimal CRS/HIPEC (2007-2016) at the authors' institution were retrospectively reviewed from a prospectively maintained database. Data regarding disease recurrence were analyzed. RESULTS Of 74 patients who underwent CRS/HIPEC for PC from CRC (n = 46) or AC (n = 28), 49 (66%) had recurrence during a median follow-up period of 39.5 months. The sites of recurrence were peritoneal-only (n = 34, 69%), hematogenous-only (n = 6, 12%), and combined peritoneal and hematogenous (n = 9, 19%) sites. No patients with AC had hematogenous-only recurrence. The median disease-free survival (DFS) time for all the patients was 15 months (95% confidence interval [CI] 12.5-17.5 months). The recurrence rate after CRS/HIPEC was 41% at 1 year, 73% at 3 years, and 76% at 5 years. All the patients with hematogenous-only metastases experienced recurrence within 12 months after CRS/HIPEC. Mucinous or signet ring features predicted peritoneal recurrence (p = 0.041), whereas a complete cytoreduction of 1 was a predictor of early recurrence (p = 0.040). Patients who underwent repeat cytoreduction survived longer than those who received systemic chemotherapy alone. The median survival time after peritoneal-only recurrence was 33 months (95% CI 27.8-38.9 months). CONCLUSION Recurrence for patients with PC is common, even after optimal CRS/HIPEC. Hematogenous-only recurrence occurs early after CRS/HIPEC, suggesting occult disease at the time of treatment and highlighting the need for methods to identify micro-metastases and improve patient selection. Patients experiencing peritoneal-only recurrence had long survival period after CRS/HIPEC, suggesting its effectiveness at controlling peritoneal disease for a time.
Collapse
Affiliation(s)
- Yael Feferman
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Daniel Solomon
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shanel Bhagwandin
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joseph Kim
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Samantha N Aycart
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Daniela Feingold
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Umut Sarpel
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Daniel M Labow
- Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| |
Collapse
|
|
15
|
Wonder E, Simón-Gracia L, Scodeller P, Majzoub RN, Kotamraju VR, Ewert KK, Teesalu T, Safinya CR. Competition of charge-mediated and specific binding by peptide-tagged cationic liposome-DNA nanoparticles in vitro and in vivo. Biomaterials 2018; 166:52-63. [PMID: 29544111 PMCID: PMC5944340 DOI: 10.1016/j.biomaterials.2018.02.052] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 02/14/2018] [Accepted: 02/27/2018] [Indexed: 12/31/2022]
Abstract
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells. Such guidelines are desirable to accelerate the optimization of formulations with novel peptides. Using PEG-lipids functionalized with a library of prototypical tumor-homing peptides, we varied the peptide density and other parameters (binding motif, peptide charge, CL/DNA charge ratio) to study their effect on the binding and uptake of the corresponding NPs. We used flow cytometry to quantitatively assess binding as well as internalization of NPs by cultured cancer cells. Surprisingly, full peptide coverage resulted in less binding and internalization than intermediate coverage, with the optimum coverage varying between cell lines. In, addition, our data revealed that great care must be taken to prevent nonspecific electrostatic interactions from interfering with the desired specific binding and internalization. Importantly, such considerations must take into account the charge of the peptide ligand as well as the membrane charge density and the CL/DNA charge ratio. To test our guidelines, we evaluated the in vivo tumor selectivity of selected NP formulations in a mouse model of peritoneally disseminated human gastric cancer. Intraperitoneally administered peptide-tagged CL-DNA NPs showed tumor binding, minimal accumulation in healthy control tissues, and preferential penetration of smaller tumor nodules, a highly clinically relevant target known to drive recurrence of the peritoneal cancer.
Collapse
Affiliation(s)
- Emily Wonder
- Materials, Physics, and Molecular, Cellular, & Developmental Biology Departments, University of California at Santa Barbara, Santa Barbara, CA 93106, USA
| | - Lorena Simón-Gracia
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 14b, 50411 Tartu, Estonia
| | - Pablo Scodeller
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 14b, 50411 Tartu, Estonia; Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
| | - Ramsey N Majzoub
- Materials, Physics, and Molecular, Cellular, & Developmental Biology Departments, University of California at Santa Barbara, Santa Barbara, CA 93106, USA
| | - Venkata Ramana Kotamraju
- Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
| | - Kai K Ewert
- Materials, Physics, and Molecular, Cellular, & Developmental Biology Departments, University of California at Santa Barbara, Santa Barbara, CA 93106, USA
| | - Tambet Teesalu
- Materials, Physics, and Molecular, Cellular, & Developmental Biology Departments, University of California at Santa Barbara, Santa Barbara, CA 93106, USA; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 14b, 50411 Tartu, Estonia; Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
| | - Cyrus R Safinya
- Materials, Physics, and Molecular, Cellular, & Developmental Biology Departments, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
| |
Collapse
|
|
16
|
Tu Y, Tian Y, Wu Y, Cui S. Clinical significance of heat shock proteins in gastric cancer following hyperthermia stress: Indications for hyperthermic intraperitoneal chemoperfusion therapy. Oncol Lett 2018; 15:9385-9391. [PMID: 29946371 DOI: 10.3892/ol.2018.8508] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 08/01/2017] [Indexed: 12/24/2022] Open
Abstract
Heat shock proteins (HSPs) are important factors in the response of cancer cells to thermo- and chemotherapy. Transient hyperthermic intraperitoneal chemoperfusion (HIPEC) therapy results in the upregulation of HSP expression, which may compromise the efficacy of additional anticancer treatments. The aim of the present study was to monitor the kinetics of HSP expression in tumor cells and patients with gastric cancer following HIPEC. Thus, in vitro and in vivo experiments were conducted to investigate the expression of two HSP family members, HSP70 and HSP90. Cells from two gastric tumor strains were subjected to HIPEC-mimicking treatment, and HSPs expression was analyzed at specific time points up to 48 h. Serum HSP concentrations were analyzed in patients with gastric cancer who had previously received cytoreductive surgery plus HIPEC treatment. The in vitro experiments indicated a significant elevation of HSP90 expression in gastric adenocarcinoma cells following hyperthermic treatment. However, HSP70 expression increased from 4 h up to 20 h post-exposure and decreased to normal levels 36 h post-exposure. Analysis of HSPs in serum samples collected from 22 patients with gastric cancer confirmed that serum HSP90 and HSP70 levels increased following HIPEC therapy, peaking at 18 h and returning to normal 24 h post-exposure. It is therefore advisable to apply the second round of HIPEC or chemotherapy at least 24 h following the first treatment to minimize any potential thermoresistance and chemoresistance of tumor cells.
Collapse
Affiliation(s)
- Yinuo Tu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Yunhong Tian
- Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Yinbing Wu
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| | - Shuzhong Cui
- Intracelom Hyperthermic Perfusion Therapy Center, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China
| |
Collapse
|
|
17
|
Bin Traiki T, Fisher O, Valle S, Parikh R, Kozman M, Glenn D, Power M, Liauw W, Alzahrani N, Morris D. Percutaneous lung ablation of pulmonary recurrence may improve survival in selected patients undergoing cytoreductive surgery for colorectal cancer with peritoneal carcinomatosis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2017; 43:1939-1948. [PMID: 28888800 DOI: 10.1016/j.ejso.2017.08.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Revised: 06/16/2017] [Accepted: 08/04/2017] [Indexed: 12/20/2022]
|
|
18
|
Fang Z, Wang Y, Li H, Yu S, Liu Z, Fan Z, Chen X, Wu Y, Pan X, Li X, Wang C. Combination Treatment of Citral Potentiates the Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with Pirarubicin for Colorectal Cancer. Mol Pharm 2017; 14:3588-3597. [DOI: 10.1021/acs.molpharmaceut.7b00652] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Zhiyuan Fang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
- Key
Laboratory of Regenerative Biology, South China Institute for Stem
Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine
and Health, Chinese Academy of Sciences, Guangzhou 510530, China
| | - Yu Wang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Hao Li
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Shuaishuai Yu
- Department
of Biology, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Ziying Liu
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Zhichao Fan
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xiaomin Chen
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Yuying Wu
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xuebo Pan
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Xiaokun Li
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| | - Cong Wang
- School
of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325030, China
| |
Collapse
|
|
19
|
Kwakman R, Schrama AM, van Olmen JP, Otten RH, de Lange-de Klerk ES, de Cuba EM, Kazemier G, Te Velde EA. Clinicopathological Parameters in Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Metastases: A Meta-analysis. Ann Surg 2017; 263:1102-11. [PMID: 26756756 DOI: 10.1097/sla.0000000000001593] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC. SUMMARY BACKGROUND DATA Peritoneal metastases (PMs) originating from colorectal cancer are treated with CRS and HIPEC. Despite increasing survival, high morbidity and mortality warrant selection of patients with optimal benefit from this treatment. Many studies report a number of variables to be associated with survival after CRS and HIPEC, but no definitive analysis has been made to validate various markers. METHODS In concordance with PRISMA guidelines, we performed a literature search encompassing 4110 articles to select 50 articles that reported the influence of 1 or more clinicopathological variables on overall survival after CRS and HIPEC. In absence of RCTs, 25 cohort studies could be used to perform a meta-analysis on 10 prognostic variables. RESULTS We determined that concurrent liver metastasis, lymph node metastasis, Eastern Cooperative Oncology Group score, tumor differentiation, and signet ring cell histology are all negative prognostic variables on overall survival after CRS and HIPEC. Conversely, sex and location of primary could not be validated as prognostic markers. More research is required to make definitive conclusions about neoadjuvant chemotherapy, onset of PMs, and mucinous histology. CONCLUSIONS Current clinical practice, which selects patients based on extraperitoneal metastasis, lymph node stage, performance status, and tumor histology, is validated by our pooled analysis. Our data merit further research into neoadjuvant chemotherapy in the setting of CRS and HIPEC for PMs.
Collapse
Affiliation(s)
- Riom Kwakman
- *Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands†Medical Library, VU University, Amsterdam, The Netherlands‡Department of Biomedical Statistics, VU University Medical Center, Amsterdam, The Netherlands§Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
| | | | | | | | | | | | | | | |
Collapse
|
|
20
|
Horvath P, Beckert S, Struller F, Königsrainer A, Königsrainer I. Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei. World J Gastrointest Pharmacol Ther 2016; 7:434-439. [PMID: 27602245 PMCID: PMC4986400 DOI: 10.4292/wjgpt.v7.i3.434] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 03/18/2016] [Accepted: 05/11/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy (HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.
METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort (n = 32) received Mitomycin C (MMC)-based HIPEC intraperitoneally (35 mg/m² for 90 min) and the second cohort (n = 10) received a bi-directional therapy consisting of oxaliplatin (OX) (300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil (5-FU) 400 mg/m² plus folinic acid 20 mg/m² intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC (completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery (CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m³.
RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group (10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients (33%) required medical treatment. Patients affected by leukopenia were predominantly female (7/10 patients) and older than 50 years (8/10 patients). The length of hospital stay tended to be higher in the MMC-group without reaching statistical significance (22.5 ± 11 vs 16.5 ± 3.5 d). Length of operation (08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger post-HIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies.
CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMC-based HIPEC protocols primarily affecting females and older patients.
Collapse
|
|
21
|
Simón-Gracia L, Hunt H, Scodeller P, Gaitzsch J, Kotamraju VR, Sugahara KN, Tammik O, Ruoslahti E, Battaglia G, Teesalu T. iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes. Biomaterials 2016; 104:247-57. [PMID: 27472162 DOI: 10.1016/j.biomaterials.2016.07.023] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Revised: 07/14/2016] [Accepted: 07/16/2016] [Indexed: 12/11/2022]
Abstract
Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models. Here we studied whether intraperitoneally administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the treatment of peritoneal carcinomatosis. First, we demonstrated that the pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR peptide) or iRGD internalize in the cells that express NRP-1, and that internalized polymersomes release their cargo inside the cytosol. CendR-targeted polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric (MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and iRGD-polymersomes showed higher tumor-selective accumulation and penetration than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel showed improved efficacy in peritoneal tumor growth inhibition and in suppression of local dissemination compared to the pristine paclitaxel-polymersomes or Abraxane. Our study demonstrates that iRGD-functionalization improves efficacy of paclitaxel-polymersomes for intraperitoneal treatment of peritoneal carcinomatosis.
Collapse
Affiliation(s)
- Lorena Simón-Gracia
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50411, Tartu, Estonia.
| | - Hedi Hunt
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50411, Tartu, Estonia
| | - Pablo Scodeller
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50411, Tartu, Estonia; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA
| | - Jens Gaitzsch
- Department of Chemistry, University College London, 20 Gordon Street, WC1H OAJ, London, UK; Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056, Basel, Switzerland
| | - Venkata Ramana Kotamraju
- Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA
| | - Kazuki N Sugahara
- Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA; Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Olav Tammik
- Department of Surgical Oncology, Tartu University Hospital, Puusepa 8, 50411, Tartu, Estonia
| | - Erkki Ruoslahti
- Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA; Center for Nanomedicine, Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, 93106, CA, USA
| | - Giuseppe Battaglia
- Department of Chemistry, University College London, 20 Gordon Street, WC1H OAJ, London, UK
| | - Tambet Teesalu
- Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 14b, 50411, Tartu, Estonia; Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA; Center for Nanomedicine, Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, 93106, CA, USA.
| |
Collapse
|
|
22
|
Mogal H, Chouliaras K, Levine EA, Shen P, Votanopoulos KI. Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: review of indications and outcomes. J Gastrointest Oncol 2016; 7:129-42. [PMID: 26941991 DOI: 10.3978/j.issn.2078-6891.2015.131] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment option in selected patients with peritoneal dissemination from a variety of epithelial primaries. Even though a small proportion will be alive and potentially cured at 10 years, the majority will eventually develop recurrent disease. Repeat CRS/HIPEC is a valid consideration in a selected subpopulation of patients with isolated peritoneal recurrence. This review summarizes the data on patient selection, feasibility, limitations and outcomes of repeat CRS/HIPEC.
Collapse
Affiliation(s)
- Harveshp Mogal
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Konstantinos Chouliaras
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Edward A Levine
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Perry Shen
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Konstantinos I Votanopoulos
- Division of Surgical Oncology, Department of General Surgery, Wake Forest University, Winston-Salem, NC, USA
| |
Collapse
|
|
23
|
Simkens GA, van Oudheusden TR, Braam HJ, Wiezer MJ, Nienhuijs SW, Rutten HJ, van Ramshorst B, de Hingh IH. Cytoreductive surgery and HIPEC offers similar outcomes in patients with rectal peritoneal metastases compared to colon cancer patients: a matched case control study. J Surg Oncol 2016; 113:548-53. [PMID: 27110701 DOI: 10.1002/jso.24169] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 12/28/2015] [Indexed: 12/22/2022]
Abstract
BACKGROUND & OBJECTIVES The effect of cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with rectal peritoneal metastases (PM) is unclear. This case-control study aims to assess the results of cytoreduction and HIPEC in patients with rectal PM compared to colon PM patients. METHODS Colorectal PM patients treated with complete macroscopic cytoreduction and HIPEC were included. Two colon cancer patients were case-matched for each rectal cancer patient, based on prognostic factors (T stage, N stage, histology type, and extent of PM). Short- and long-term outcomes were compared between both groups. RESULTS From 317 patients treated with complete macroscopic cytoreduction and HIPEC, 29 patients (9.1%) had rectal PM. Fifty-eight colon cases were selected as control patients. Baseline characteristics were similar between groups. Major morbidity was 27.6% and 34.5% in the rectal and colon group, respectively (P = 0.516). Median disease-free survival was 13.5 months in the rectal group and 13.6 months in the colon group (P = 0.621). Two- and five-year overall survival rates were 54%/32% in rectal cancer patients, and 61%/24% in colon cancer patients (P = 0.987). CONCLUSIONS Cytoreduction and HIPEC in selected patients with rectal PM is feasible and provides similar outcomes as in colon cancer patients. Rectal PM should not be regarded a contra-indication for cytoreduction and HIPEC in selected patients. J. Surg. Oncol. 2016;113:548-553. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Geert A Simkens
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | | | - Hidde J Braam
- Department of Surgical Oncology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Marinus J Wiezer
- Department of Surgical Oncology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Simon W Nienhuijs
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Harm J Rutten
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| | - Bert van Ramshorst
- Department of Surgical Oncology, St. Antonius Hospital, Nieuwegein, the Netherlands
| | - Ignace H de Hingh
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, the Netherlands
| |
Collapse
|
|
24
|
van Oudheusden TR, Nienhuijs SW, Luyer MD, Nieuwenhuijzen GA, Lemmens VE, Rutten HJ, de Hingh IH. Incidence and treatment of recurrent disease after cytoreductive surgery and intraperitoneal chemotherapy for peritoneally metastasized colorectal cancer: A systematic review. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2015; 41:1269-1277. [PMID: 26175345 DOI: 10.1016/j.ejso.2015.05.018] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 05/24/2015] [Accepted: 05/27/2015] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The optimal treatment for peritoneal carcinomatosis (PC) of colorectal origin is a combination of cytoreductive surgery and intraperitoneal chemotherapy (CRS + IPC). Although 5-year survival rates of up to 40% have been reported, recurrent disease remains common and is estimated to be a strong negative prognostic factor for survival. This systematic review elaborates on the incidence of recurrent disease and the possibilities to prevent and treat recurrence. METHODS Two searches were performed. To identify the magnitude of recurrent the disease, a search was performed in Pubmed and EMBASE until September 2014. A second search was performed in Pubmed to identify treatment of recurrent disease with secondary CRS + IPC. RESULTS The first search resulted in 139 and 94 articles in Pubmed and EMBASE respectively. Among those, 28 were included. Overall recurrence rates ranged from 22.5 to 82%. Local, systemic and combined local-systemic recurrence ranged from 6 to 42.5%, 10.4-43% and 5.8-21.5%. Median time to recurrence varied from 9 to 23 months, three-year disease free survival ranged from 14 to 41.5%. The second search resulted in 140 articles among which 17 met the inclusion criteria. A total of 190 patients underwent secondary CRS. Median survival after the second procedure ranged from 18 to 55.7 months. One, two and three-year survival ranged between 66 and 94, 44-50 and 0-66%. CONCLUSION Recurrence is very common after cytoreductive surgery and intraperitoneal chemotherapy for PC of colorectal origin. Repeat cytoreductive surgery suggests a potential survival benefit for a highly selected group. Therefore, strategies to prevent recurrence are of the utmost importance.
Collapse
Affiliation(s)
- T R van Oudheusden
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | - S W Nienhuijs
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | - M D Luyer
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | - G A Nieuwenhuijzen
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | - V E Lemmens
- Department of Research, Eindhoven Cancer Registry/Comprehensive Cancer Centre the Netherlands (IKNL), PO Box 213, 5600 AE Eindhoven, The Netherlands
| | - H J Rutten
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | - I H de Hingh
- Department of Surgical Oncology, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands.
| |
Collapse
|
|
25
|
Simkens GA, van Oudheusden TR, Luyer MD, Nienhuijs SW, Nieuwenhuijzen GA, Rutten HJ, de Hingh IH. Serious Postoperative Complications Affect Early Recurrence After Cytoreductive Surgery and HIPEC for Colorectal Peritoneal Carcinomatosis. Ann Surg Oncol 2015; 22:2656-2662. [PMID: 25515200 DOI: 10.1245/s10434-014-4297-y] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND The prognosis of patients with peritoneally metastasized colorectal cancer has improved significantly with the introduction of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Although a macroscopically complete resection is achieved in nearly every patient, recurrence rates are high. This study aims to identify risk factors for early recurrence, thereby offering ways to reduce its occurrence. METHODS All patients with colorectal peritoneal carcinomatosis treated with CRS + HIPEC and a minimum follow-up of 12 months, in April 2014, were analyzed. Patient data were compared between patients with or without recurrence within 12 months after CRS + HIPEC. Risk factors were determined using logistic regression analysis. Postoperative complications were graded according to the serious adverse events (SAEs) score, with grade 3 or higher indicating complications requiring intervention. RESULTS A complete macroscopic cytoreduction was achieved in 96 % of all patients treated with CRS + HIPEC. Forty-six of 133 patients (35 %) developed recurrence within 12 months. An SAE ≥3 after CRS + HIPEC was the only significant risk factor found for early recurrence (odds ratio 2.3; p = 0.046). Median survival in the early recurrence group was 19.3 months compared with 43.2 months in the group without early recurrence (p < 0.001). Patients with an SAE ≥3 showed a reduced survival compared with patients without such complications (22.1 vs. 31.0 months, respectively; p = 0.02). CONCLUSIONS Early recurrence after CRS + HIPEC is associated with a significant reduction in overall survival. This study identifies postoperative complications requiring intervention as the only significant risk factor for early recurrence, independent of the extent of peritoneal disease, highlighting the importance of minimizing the risk of postoperative complications.
Collapse
Affiliation(s)
- Geert A Simkens
- Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Ceelen W, Van Nieuwenhove Y, Putte DV, Pattyn P. Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis. Ann Surg Oncol 2014; 21:3023-8. [PMID: 24756812 DOI: 10.1245/s10434-014-3713-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population. METHODS Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200-460 mg/m(2)) or mitomycin C (35 mg/m(2)). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis. RESULTS Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8-33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019). CONCLUSIONS Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.
Collapse
Affiliation(s)
- Wim Ceelen
- Department of Surgery, Ghent University Hospital, Ghent, Belgium,
| | | | | | | |
Collapse
|
|
27
|
Braam HJ, van Oudheusden TR, de Hingh IHJT, Nienhuijs SW, Boerma D, Wiezer MJ, van Ramshorst B. Patterns of recurrence following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. J Surg Oncol 2014; 109:841-7. [PMID: 24619813 DOI: 10.1002/jso.23597] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 02/17/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVES CytoReductive Surgery (CRS) combined with Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has an established role in the treatment of peritoneally metastasized colorectal cancer. The aim of the study was to describe the recurrence patterns and to evaluate treatment options and related survival. METHODS Patients treated with CRS + HIPEC in two tertiary referral centers between April 2005 and March 2013 were analyzed retrospectively. The prognostic value of several parameters was calculated using Cox Regression. RESULTS One hundred thirty two of 287 patients (46%) with peritoneal carcinomatosis treated with complete CRS and HIPEC were diagnosed with recurrent disease, after a median disease-free interval of 11.4 months. Recurrence were locoregional (43%), distant metastases (26%) or both (31%). Thirty-two of the 132 patients with recurrences (24%) were treated surgically with curative intent, which extended the median survival from 12 months to 43 months, compared to palliative treatment (best supportive care or chemotherapy; P < 0.001). Initial nodal status (P = 0.01) and the number of affected regions at initial CRS (P = 0.02) were significantly correlated to survival after disease recurrence. CONCLUSION Disease recurrence after CRS and HIPEC is common; in selected patients, an aggressive surgical approach may be beneficial and extend survival.
Collapse
Affiliation(s)
- Hidde J Braam
- Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands
| | | | | | | | | | | | | |
Collapse
|