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1
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Ota E, Fukunaga Y, Mukai T, Hiyoshi Y, Yamaguchi T, Nagasaki T, Akiyoshi T. Cytoreductive surgery without intra-peritoneal chemotherapy for metachronous colorectal peritoneal metastases. World J Surg Oncol 2024; 22:205. [PMID: 39085860 PMCID: PMC11290162 DOI: 10.1186/s12957-024-03471-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 07/16/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases. METHODS This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period. RESULTS The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of < 2 years after primary surgery (hazard ratio = 4.1, 95% confidence interval = 2.0-8.6, p = 0.0002) and number of metachronous peritoneal metastases ≥ 3 (hazard ratio = 9.8, 95% confidence interval = 2.3-42.3, p = 0.002) as independent factors associated with a poor prognosis. CONCLUSIONS Long intervals of more than 2 years after primary surgery and 2 or less metachronous peritoneal metastases were good selection criteria for cytoreductive surgery for metachronous peritoneal metastases from colorectal cancer.
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Affiliation(s)
- Emi Ota
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Fukunaga
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Toshiki Mukai
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yukiharu Hiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiya Nagasaki
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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2
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Karlsson S, Nyström H. The extracellular matrix in colorectal cancer and its metastatic settling – alterations and biological implications. Crit Rev Oncol Hematol 2022; 175:103712. [DOI: 10.1016/j.critrevonc.2022.103712] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 05/05/2022] [Accepted: 05/11/2022] [Indexed: 12/12/2022] Open
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3
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Lundbech M, Krag AE, Iversen LH, Hvas AM. Postoperative bleeding and venous thromboembolism in colorectal cancer patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. Int J Colorectal Dis 2022; 37:17-33. [PMID: 34626208 DOI: 10.1007/s00384-021-04021-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/25/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with peritoneal metastases from colorectal cancer. Previous studies report conflicting rates of postoperative bleeding and venous thromboembolism (VTE) after CRS + HIPEC. The aim of the present study was to systematically review the literature and to estimate the overall 30-day incidence of postoperative bleeding and the overall 90-day incidence of VTE after CRS + HIPEC. METHODS Studies were identified in PubMed, Embase, and Web of Science on 29 April 2021. Data were extracted for a qualitative synthesis and to estimate an overall mean incidence in the meta-analysis. RESULTS Fourteen studies with a total of 3268 patients were included in the systematic review. Postoperative bleeding incidence rates within 30 days ranged from 1.7 to 8.3% with an overall 30-day postoperative bleeding incidence with [95% CI] at 4.2 [2.6;6.2]%. VTE incidence rates within 90 days ranged from 0.2 to 13.6% with an overall 90-day VTE incidence with [95% CI] at 2.7 [1;5.2]% after CRS + HIPEC. CONCLUSION This systematic review and meta-analysis indicate a low risk for postoperative bleeding within 30 days and VTE within 90 days after CRS + HIPEC for peritoneal metastases from colorectal cancer.
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Affiliation(s)
- Mikkel Lundbech
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Andreas Engel Krag
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.,Department of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Lene Hjerrild Iversen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Anne-Mette Hvas
- Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. .,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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Abstract
Peritoneal surface malignancies comprise a heterogeneous group of primary tumours, including peritoneal mesothelioma, and peritoneal metastases of other tumours, including ovarian, gastric, colorectal, appendicular or pancreatic cancers. The pathophysiology of peritoneal malignancy is complex and not fully understood. The two main hypotheses are the transformation of mesothelial cells (peritoneal primary tumour) and shedding of cells from a primary tumour with implantation of cells in the peritoneal cavity (peritoneal metastasis). Diagnosis is challenging and often requires modern imaging and interventional techniques, including surgical exploration. In the past decade, new treatments and multimodal strategies helped to improve patient survival and quality of life and the premise that peritoneal malignancies are fatal diseases has been dismissed as management strategies, including complete cytoreductive surgery embedded in perioperative systemic chemotherapy, can provide cure in selected patients. Furthermore, intraperitoneal chemotherapy has become an important part of combination treatments. Improving locoregional treatment delivery to enhance penetration to tumour nodules and reduce systemic uptake is one of the most active research areas. The current main challenges involve not only offering the best treatment option and developing intraperitoneal therapies that are equivalent to current systemic therapies but also defining the optimal treatment sequence according to primary tumour, disease extent and patient preferences. New imaging modalities, less invasive surgery, nanomedicines and targeted therapies are the basis for a new era of intraperitoneal therapy and are beginning to show encouraging outcomes.
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5
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Ohira G, Miyauchi H, Hayano K, Maruyama M, Imanishi S, Tochigi T, Maruyama T, Hanaoka T, Okada K, Matsubara H. Treatment Outcome of Resection of Disseminated Peritoneal Metastases from Colorectal Cancer. In Vivo 2020; 34:1915-1920. [PMID: 32606163 DOI: 10.21873/invivo.11988] [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: 03/03/2020] [Revised: 03/30/2020] [Accepted: 04/01/2020] [Indexed: 11/10/2022]
Abstract
AIM To show the treatment outcomes of disseminated nodule resection for peritoneal metastasis of colorectal cancer and describe the details of cured cases. PATIENTS AND METHODS From January 2001 to December 2016, patients who underwent disseminated nodule resection of colorectal adenocarcinoma with no macroscopic residual tumor in our institution were retrospectively analyzed for clinicopathological factors associated with prognosis. RESULTS Forty-one cases were included in this study. The 3-year relapse-free survival was 12.5%, and the 5-year overall survival was 38.4%. In a multivariate analysis, lack of post-operative adjuvant chemotherapy and pre-operative carbohydrate antigen 19-9 over 100 IU/l were extracted as independent factors associated with short relapse-free survival, respectively. Among 41 cases, 32 were followed-up 5 years after surgery and five (15.6%) survived without relapse and were regarded as 'cured'. CONCLUSION More than a few cases of colorectal peritoneal metastasis, which is thought to be difficult to cure, were cured by resection of disseminated nodules without resorting to highly invasive treatment.
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Affiliation(s)
- Gaku Ohira
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Hideaki Miyauchi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Koichi Hayano
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Michihiro Maruyama
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shunsuke Imanishi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Toru Tochigi
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tetsuro Maruyama
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Toshiharu Hanaoka
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Koichiro Okada
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Chiba University Graduate School of Medicine, Chiba, Japan
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6
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Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy. Pharm Res 2020; 37:119. [DOI: 10.1007/s11095-020-02818-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 04/06/2020] [Indexed: 12/12/2022]
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7
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Liesenfeld LF, Hillebrecht HC, Klose J, Schmidt T, Schneider M. Impact of Perfusate Concentration on Hyperthermic Intraperitoneal Chemotherapy Efficacy and Toxicity in a Rodent Model. J Surg Res 2020; 253:262-271. [PMID: 32388389 DOI: 10.1016/j.jss.2020.03.067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 03/14/2020] [Accepted: 03/27/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be beneficial in treating limited peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Perfusate volume directly affects treatment concentration and therefore is a key parameter defining HIPEC; yet little is known about the impact of perfusate concentration on systemic toxicity and treatment morbidity. MATERIALS AND METHODS PC was induced through intraperitoneal injection of human CRC cell lines. A novel perfusion model was developed to treat athymic nude mice with continuous circulation of adequately miniaturized volumes of heated perfusate. Oxaliplatin HIPEC was performed applying different volumes of perfusate with fixed doses or fixed concentrations. Early postoperative mortality and morbidity were assessed as well as long-term survival. In addition, antiproliferative and proapoptotic effects of HIPEC were determined in vitro and in vivo. RESULTS Perfusate concentration crucially affected the toxicity of fixed-dose oxaliplatin HIPEC as indicated by postoperative weight loss and early postoperative mortality. Applying different perfusate volumes at a fixed concentration did not influence toxicity. Adequately miniaturized HIPEC with oxaliplatin did not exert relevant cytotoxic effects toward PC arising from human CRC cells in vivo. CONCLUSIONS We describe a novel murine model that adequately miniaturizes all physical parameters of HIPEC as applied in humans. HIPEC drug concentration is a crucial parameter determining excess toxicity and should be better standardized. HIPEC with oxaliplatin fails to induce relevant antitumor activity or to improve survival in this murine model of PC from CRC.
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MESH Headings
- Animals
- Cell Line, Tumor
- Chemotherapy, Adjuvant/adverse effects
- Chemotherapy, Adjuvant/methods
- Chemotherapy, Cancer, Regional Perfusion/adverse effects
- Chemotherapy, Cancer, Regional Perfusion/methods
- Colorectal Neoplasms/mortality
- Colorectal Neoplasms/pathology
- Colorectal Neoplasms/therapy
- Cytoreduction Surgical Procedures
- Dose-Response Relationship, Drug
- Female
- Humans
- Hyperthermia, Induced/adverse effects
- Hyperthermia, Induced/methods
- Mice
- Oxaliplatin/administration & dosage
- Oxaliplatin/toxicity
- Peritoneal Neoplasms/mortality
- Peritoneal Neoplasms/secondary
- Peritoneal Neoplasms/therapy
- Peritoneum/drug effects
- Peritoneum/pathology
- Treatment Failure
- Xenograft Model Antitumor Assays
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Affiliation(s)
- Lukas F Liesenfeld
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - H Christian Hillebrecht
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Johannes Klose
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Martin Schneider
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
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8
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Imaizumi K, Nishizawa Y, Ikeda K, Tsukada Y, Sasaki T, Ito M. Prognostic Impact of Curative Resection for Peritoneal Recurrence of Colorectal Cancer. Ann Surg Oncol 2020; 27:2487-2497. [PMID: 32052301 DOI: 10.1245/s10434-020-08242-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Indexed: 12/26/2022]
Abstract
BACKGROUND Peritoneal recurrence (PR) of colorectal cancer is a poor prognostic factor but may be treatable by curative resection. We investigated the efficacy of this treatment and identified risk factors for postoperative recurrence. METHODS The subjects were patients who underwent radical surgery for colorectal cancer between January 2006 and March 2014. Those with PR were retrospectively reviewed. Prognostic factors for overall survival (OS) and risk factors for postoperative recurrence were identified. RESULTS Among 2256 patients, 66 had PR (2.9%). Surgical resection of PR was performed in 41 patients. Curative resection was achieved macroscopically in 38 cases without diffuse metastases in the peritoneum distant from the primary tumor and with a peritoneal cancer index < 10. In multivariate analysis, curative resection was a significant prognostic factor [hazard ratio (HR) 0.198] for better 5-year OS compared with cases without curative resection (68.7% vs. 6.3%, P < 0.001). In 28 cases with concurrent metastasis, curative resection significantly improved 5-year OS compared with no curative resection (78.7% vs. 0%, P = 0.008). In the 38 patients with curative resection, the 3-year recurrence-free survival rate was 21.4%. In multivariate analysis, concurrent metastasis was a significant risk factor [HR 3.394] for postoperative recurrence, and cases with concurrent metastasis more frequently had recurrence within 2 years after curative resection. CONCLUSIONS Curative resection improved the prognosis in patients with limited and resectable PR of colorectal cancer with or without concurrent metastasis. However, recurrence after curative resection was common and concurrent metastasis was a risk factor for this recurrence.
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Affiliation(s)
- Ken Imaizumi
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Yuji Nishizawa
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
| | - Koji Ikeda
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Yuichiro Tsukada
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Takeshi Sasaki
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Masaaki Ito
- Department of Colorectal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
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9
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Thaysen HV, Lomborg K, Seibaek L. Patient involvement in comprehensive, complex cancer surgery: Perspectives of patients, relatives and health professionals. Eur J Cancer Care (Engl) 2019; 28:e13071. [PMID: 31050065 DOI: 10.1111/ecc.13071] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 03/14/2019] [Accepted: 04/08/2019] [Indexed: 11/30/2022]
Abstract
We investigated the perspectives of patients, relatives and health professionals on the drivers and barriers to patient involvement (PI) in the treatment of peritoneal carcinomatosis with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). During 2016-2017, individual and focus group interviews were conducted with purposively selected participants during CRS and HIPEC, supplemented by field observations. This material was analysed using meaning condensation (Kvale). Fifteen patients, eight relatives and nine health professionals participated in 31 individual and two focus group interviews, supplemented by 37 observations. The findings were structured into themes concerning treatment decisions, organisation of pathways, knowledge of the patient and life during treatment. Deciding to treat was determined not only by preoperative biomedical information, personal preferences but also findings during surgery. This circumstance put the patients under mental pressure and affected their ability to process the offered information. They furthermore perceived the pathway as complex and occasionally unclear, leading them to attempt to coordinate transitions themselves. The study has highlighted barriers to, rather than drivers of, PI. To promote PI during comprehensive complex cancer surgery, we suggest that patients and relatives are offered patient-centred care, such as support in posing questions, overview of their treatment pathway and coherent transitions.
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Affiliation(s)
- Henriette Vind Thaysen
- Department of Surgery, Section of Coloprotology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,The Research Programme in Patient Involvement, Aarhus University Hospital, Aarhus, Denmark
| | - Kirsten Lomborg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,The Research Programme in Patient Involvement, Aarhus University Hospital, Aarhus, Denmark
| | - Lene Seibaek
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,The Research Programme in Patient Involvement, Aarhus University Hospital, Aarhus, Denmark.,Department of Gynaecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
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10
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Thadi A, Khalili M, Morano WF, Richard SD, Katz SC, Bowne WB. Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for Peritoneal Metastasis. Vaccines (Basel) 2018; 6:E54. [PMID: 30103457 PMCID: PMC6160982 DOI: 10.3390/vaccines6030054] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 08/06/2018] [Accepted: 08/06/2018] [Indexed: 12/23/2022] Open
Abstract
Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors expressing carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate receptor α expressing tumors improved T-cell tumor localization and survival when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial cell adhesion molecule (EpCAM) and has shown considerable promise with control of malignant ascites. Herein, we discuss immunologic approaches under investigation for treatment of PM.
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Affiliation(s)
- Anusha Thadi
- Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
| | - Marian Khalili
- Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
| | - William F Morano
- Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
| | - Scott D Richard
- Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
| | - Steven C Katz
- Department of Surgery, Boston University School of Medicine, Boston, MA 02118, USA.
| | - Wilbur B Bowne
- Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
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11
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Sluiter NR, Rovers KP, Salhi Y, Vlek SL, Coupé VMH, Verheul HMW, Kazemier G, de Hingh IHJT, Tuynman JB. Metachronous Peritoneal Metastases After Adjuvant Chemotherapy are Associated with Poor Outcome After Cytoreduction and HIPEC. Ann Surg Oncol 2018; 25:2347-2356. [PMID: 29855834 PMCID: PMC6028868 DOI: 10.1245/s10434-018-6539-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of colorectal cancer (CRC) patients with peritoneal metastases. Patient selection is key since this treatment is associated with high morbidity. Patients with peritoneal recurrence within 1 year after previous adjuvant chemotherapy are thought to benefit less from HIPEC treatment; however, no published data are available to assist in clinical decision making. This study assessed whether peritoneal recurrence within 1 year after adjuvant chemotherapy was associated with survival after HIPEC treatment. METHODS Peritoneal recurrence within 1 year after adjuvant chemotherapy, as well as other potentially prognostic clinical and pathological variables, were tested in univariate and multivariate analysis for correlation with primary outcomes, i.e. overall survival (OS) and disease-free survival (DFS). Two prospectively collected databases from the VU University Medical Center Amsterdam and Catherina Hospital Eindhoven containing 345 CRC patients treated with the intent of HIPEC were utilized. RESULTS High Peritoneal Cancer Index (PCI) scores were associated with worse DFS [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00-1.08, p = 0.040] and OS (HR 1.11, 95% CI 1.07-1.15, p < 0.001) in multivariate analysis. Furthermore, patients with peritoneal recurrence within 1 year following adjuvant chemotherapy had worse DFS (HR 2.13, 95% CI 1.26-3.61, p = 0.005) and OS (HR 2.76, 95% CI 1.45-5.27, p = 0.002) than patients who did not receive adjuvant chemotherapy or patients with peritoneal recurrence after 1 year. CONCLUSION Peritoneal recurrence within 1 year after previous adjuvant chemotherapy, as well as high PCI scores, are associated with poor survival after cytoreduction and HIPEC. These factors should be considered in order to avoid high-morbidity treatment in patients who might not benefit from such treatment.
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Affiliation(s)
- Nina R Sluiter
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
| | - Koen P Rovers
- Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands
| | - Youssra Salhi
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
| | - Stijn L Vlek
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
| | - Veerle M H Coupé
- Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
| | - Henk M W Verheul
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
| | - Geert Kazemier
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
| | | | - Jurriaan B Tuynman
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
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12
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Cesna V, Sukovas A, Jasukaitiene A, Naginiene R, Barauskas G, Dambrauskas Z, Paskauskas S, Gulbinas A. Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells. World J Gastroenterol 2018; 24:1072-1083. [PMID: 29563752 PMCID: PMC5850127 DOI: 10.3748/wjg.v24.i10.1072] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 01/02/2018] [Accepted: 01/16/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells. METHODS AGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin. RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively. CONCLUSION In addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.
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Affiliation(s)
- Vaidotas Cesna
- Department of Surgery, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Arturas Sukovas
- Department of Obstetrics and Gynecology, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Aldona Jasukaitiene
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Rima Naginiene
- Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Giedrius Barauskas
- Department of Surgery, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Zilvinas Dambrauskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Saulius Paskauskas
- Department of Obstetrics and Gynecology, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
| | - Antanas Gulbinas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas LT-50161, Lithuania
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13
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Morano WF, Khalili M, Chi DS, Bowne WB, Esquivel J. Clinical studies in CRS and HIPEC: Trials, tribulations, and future directions-A systematic review. J Surg Oncol 2017; 117:245-259. [PMID: 29120491 DOI: 10.1002/jso.24813] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2017] [Accepted: 07/24/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The field of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has suffered from a lack of clinical trials to validate its expanding use. OBJECTIVE To evaluate published and ongoing clinical trials seeking to better define role of CRS/HIPEC in the treatment of peritoneal surface malignancies. METHODS Systematic review by PubMed search was performed using terms "Clinical trial," "intraperitoneal chemotherapy," and "HIPEC." ClinicalTrials.gov and EudraCT registries were searched for active clinical trials. Eligibility included CRS/HIPEC trials investigating adult patient populations from published clinical reports and/or trials currently accruing or at completion. RESULTS Thirteen published trials and 57 active clinical trials were included for review. CONCLUSIONS Published and ongoing U.S. and international clinical trials for CRS and HIPEC are defining important parameters that include improving patient selection, strategic sequences of treatment, cytoreductive strategies, chemotherapeutics, optimal hyperthermic temperature and timing, and toxicity profiles. Main barriers or limitations to trial development remain patient enrollment, trial design, and oncologic community collaboration. Overall progress is positive with increasing number of clinical trials throughout the world. Collaboration between surgeons and the wider oncologic community will be crucial to validate this important treatment strategy.
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Affiliation(s)
- William F Morano
- Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Marian Khalili
- Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Dennis S Chi
- Section of Ovarian Cancer Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Wilbur B Bowne
- Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania
| | - Jesus Esquivel
- Department of Surgery, Frederick Memorial Hospital, Frederick, Maryland
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Organoids as preclinical models to improve intraperitoneal chemotherapy effectiveness for colorectal cancer patients with peritoneal metastases: Preclinical models to improve HIPEC. Int J Pharm 2017; 531:143-152. [DOI: 10.1016/j.ijpharm.2017.07.084] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 07/31/2017] [Indexed: 02/06/2023]
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15
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Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hübner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg 2017; 104:669-678. [PMID: 28407227 DOI: 10.1002/bjs.10521] [Citation(s) in RCA: 126] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Revised: 12/15/2016] [Accepted: 02/01/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a minimally invasive approach under investigation as a novel treatment for patients with peritoneal carcinomatosis of various origins. The aim was to review the available evidence on mechanisms, clinical effects and risks. METHODS This was a systematic review of the literature on pressurized intraperitoneal chemotherapy published between January 2000 and October 2016. All types of scientific report were included. RESULTS Twenty-nine relevant papers were identified; 16 were preclinical studies and 13 were clinical reports. The overall quality of the clinical studies was modest; five studies were prospective and there was no randomized trial. Preclinical data suggested better distribution and higher tissue concentrations of chemotherapy agents in PIPAC compared with conventional intraperitoneal chemotherapy by lavage. Regarding technical feasibility, laparoscopic access and repeatability rates were 83-100 and 38-82 per cent. Surgery-related complications occurred in up to 12 per cent. Postoperative morbidity was low (Common Terminology Criteria for Adverse Events grade 3-5 events reported in 0-37 per cent), and hospital stay was about 3 days. No negative impact on quality of life was reported. Histological response rates for therapy-resistant carcinomatosis of ovarian, colorectal and gastric origin were 62-88, 71-86 and 70-100 per cent respectively. CONCLUSION PIPAC is feasible, safe and well tolerated. Preliminary good response rates call for prospective analysis of oncological efficacy.
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Affiliation(s)
- F Grass
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - A Vuagniaux
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - H Teixeira-Farinha
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - K Lehmann
- Department of Visceral Surgery, University Hospital Zurich, Zurich, Switzerland
| | - N Demartines
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
| | - M Hübner
- Department of Visceral Surgery, University Hospital of Lausanne (CHUV), Lausanne, Switzerland
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Nagata H, Ishihara S, Hata K, Murono K, Kaneko M, Yasuda K, Otani K, Nishikawa T, Tanaka T, Kiyomatsu T, Kawai K, Nozawa H, Watanabe T. Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer. Ann Surg Oncol 2016; 24:1269-1280. [PMID: 27995451 DOI: 10.1245/s10434-016-5732-z] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. METHODS Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. RESULTS Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of <1 year (HR 2.02, 95% CI 1.04-3.87; p = 0.040), Peritoneal Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p < 0.001), and peritoneal nodule resection (HR 0.31, 95% CI 0.13-0.65; p = 0.002). CONCLUSIONS A proportion of colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.
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Affiliation(s)
- Hiroshi Nagata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan.
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Keisuke Hata
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Murono
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Manabu Kaneko
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Koji Yasuda
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kensuke Otani
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Tanaka
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Kazushige Kawai
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Hiroaki Nozawa
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, The University of Tokyo, Bunkyo, Tokyo, Japan
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Tamhankar AS, Ingle P, Engineer R, Bal M, Ostwal V, Saklani A. Signet ring colorectal carcinoma: Do we need to improve the treatment algorithm? World J Gastrointest Oncol 2016; 8:819-825. [PMID: 28035252 PMCID: PMC5156848 DOI: 10.4251/wjgo.v8.i12.819] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 07/11/2016] [Accepted: 09/13/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To elaborate about this peculiar variant from a tertiary cancer center from India. METHODS It's a retrospective study (2011-2014) of all patients diagnosed with signet ring colo-rectal cancer (SRCC). Various clinico-pathological variables were studied. RESULTS One hundred and seventy consecutive patients with SRCC were diagnosed (11.4% of all colorectal cancers). Median Age of the cohort was 41 years. Most common location was recto-sigmoid area (54.7%). Majority patients presented in stage III and IV (91.2%). Most of the stage IV patients had isolated peritoneal metastases (86.5%). Colonic tumors had higher incidence of peritoneal metastases (91.8% vs 83.3%) as well as isolated peritoneal recurrences (37.5% vs 16.7%) than rectal primaries. Thirty-seven point five percent of patients recurred after curative surgery. Amongst them 63.63% patients had isolated peritoneal recurrences. Circumferential resection margin (CRM) was involved in 17.9% patients. Median relapse free survival (RFS) and overall survival (OS) of the cohort were 14.9 and 18.13 mo respectively. CRM involvement, colonic primary were associated with poorer RFS and OS. CONCLUSION SRCC has predilection for peritoneal dissemination. More aggressive and/or extended chemotherapy schedules as well as prophylactic hyperthermic intra-peritoneal chemotherapy at the time of primary surgery may be attempted in these patients.
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Huang Y, Alzahrani NA, Chua TC, Liauw W, Morris DL. Impacts of peritoneal cancer index on the survival outcomes of patients with colorectal peritoneal carcinomatosis. Int J Surg 2016; 32:65-70. [PMID: 27353848 DOI: 10.1016/j.ijsu.2016.06.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 06/11/2016] [Accepted: 06/15/2016] [Indexed: 01/31/2023]
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Fan R, Li X, Deng J, Gao X, Zhou L, Zheng Y, Tong A, Zhang X, You C, Guo G. Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity. Sci Rep 2016; 6:28373. [PMID: 27324595 PMCID: PMC4914940 DOI: 10.1038/srep28373] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 06/03/2016] [Indexed: 02/05/2023] Open
Abstract
One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.
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Affiliation(s)
- Rangrang Fan
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Xiaoling Li
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Jiaojiao Deng
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Xiang Gao
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Liangxue Zhou
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Yu Zheng
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Aiping Tong
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Xiaoning Zhang
- Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, and Collaborative Innovation Center for Biotherapy, Beijing 100084, P. R. China
| | - Chao You
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
| | - Gang Guo
- State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, P. R. China
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20
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Huang Y, Alzahrani NA, Chua TC, Liauw W, Morris DL. Impacts of low peritoneal cancer index on the survival outcomes of patient with peritoneal carcinomatosis of colorectal origin. Int J Surg 2015; 23:181-185. [PMID: 26361862 DOI: 10.1016/j.ijsu.2015.08.078] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 08/08/2015] [Accepted: 08/15/2015] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The combination of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) have been proposed as an innovative technique for peritoneal carcinomatosis and is currently considered as a standard treatment for colorectal peritoneal carcinomatosis (CRPC) in selected patients. Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes of patients with CRPC. In this paper, we have studied patients with CRPC and a very low PCI of 5 or less and their survival outcomes. METHODS This is a retrospective study of prospectively collected data of 60 consecutive patients with CRPC and PCI ≤ 5, who underwent CRS and PIC by the same surgical team at St George hospital in Sydney, Australia between January 1996 and April 2015. Clinical outcomes of these patients were analysed. RESULTS Hospital mortality was 0%. 14 patients (23.4%) had grade III/IV morbidity. The median follow-up was 22.2 months (range = 0.1-104.2). The median survival was 80.6 months (95% confidence interval (CI) = 35.1-126.1), with an overall 1-year, 3-year, and 5-year survival rate of 96.1%, 72.6% and 54.7% respectively. Among 60 patients, 31 patients experienced the recurrence of the disease (51.7%). The median disease-free survival was 10.8 months (95% CI = 7.2-14.4). CONCLUSION This innovative approach combining CRS and PIC has shown encouraging outcomes and offers hope for patients with CRPC. Our results suggest that CRS and PIC can be performed safely to provide significant survival benefits for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes.
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Affiliation(s)
- Yeqian Huang
- St George Clinical School, University of New South Wales, New South Wales, Australia
| | - Nayef A Alzahrani
- Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia; College of Medicine, Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Terence C Chua
- Department of Surgery, Ryde Hospital, North Shore Ryde Health Service, New South Wales, Australia
| | - Winston Liauw
- Department of Medical Oncology, University of New South Wales, St George Hospital, Sydney, New South Wales, Australia
| | - David L Morris
- Department of Surgery, University of New South Wales, St George Hospital, New South Wales, Australia.
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Schaaf L, van der Kuip H, Zopf W, Winter S, Münch M, Mürdter TE, Thon KP, Steurer W, Aulitzky WE, Ulmer C. A Temperature of 40 °C Appears to be a Critical Threshold for Potentiating Cytotoxic Chemotherapy In Vitro and in Peritoneal Carcinomatosis Patients Undergoing HIPEC. Ann Surg Oncol 2015; 22 Suppl 3:S758-65. [PMID: 26350370 DOI: 10.1245/s10434-015-4853-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Indexed: 01/25/2023]
Abstract
BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery is a radical but effective treatment option for patients with peritoneal carcinomatosis (PC). Unfortunately, a standardized HIPEC protocol is missing impeding systematic comparisons with regard to minimal effective temperatures. OBJECTIVE The purpose of the present study was to systematically analyse the precise minimal temperature needed for potentiation of chemotherapy effects in vitro and for patient survival. METHODS We established a cell line-based model to mimic HIPEC conditions used in clinical practice, and evaluated intracellular drug concentrations and long-term survival using different temperatures ranging from 38 to 42 °C combined with cisplatin or doxorubicin. In parallel, we evaluated the temperature reached in the clinical setting by measuring inflow and outflow, as well as in two locations in the peritoneal cavity in 34 patients. Finally, we determined the influence of different HIPEC temperatures on survival. RESULTS Long-term survival of cells treated with either cisplatin or doxorubicin was further improved only at temperatures above 40 °C. In patients, during HIPEC, constant temperatures were reached after 10 min in the peritoneal cavity. A temperature above 40 °C for at least 40 min was achieved in 68 % of patients over the 60 min duration of HIPEC. Importantly, we observed a significantly enhanced overall survival (OS) and progression-free survival (PFS) in those patients reaching temperatures above 40 °C. CONCLUSIONS Hyperthermia significantly potentiated the chemotherapy effects only at temperatures above 40 °C in vitro. Importantly, this temperature threshold was also critical for OS and PFS of PC patients.
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Affiliation(s)
- Lea Schaaf
- Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany.
| | - Heiko van der Kuip
- Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany
| | - Waltraud Zopf
- Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany
| | - Stefan Winter
- Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany
| | - Marina Münch
- Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany
| | - Thomas E Mürdter
- Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany
| | - Klaus-Peter Thon
- Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany
| | - Wolfgang Steurer
- Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany
| | | | - Christoph Ulmer
- Department of Surgery, Robert Bosch Hospital, Stuttgart, Germany.
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22
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Gu Z, Shan K, Chen H, Chen YQ. n-3 Polyunsaturated Fatty Acids and their Role in Cancer Chemoprevention. ACTA ACUST UNITED AC 2015; 1:283-294. [PMID: 26457243 DOI: 10.1007/s40495-015-0043-9] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Polyunsaturated fatty acids (PUFAs), including omega-3 (n-3) and omega-6 (n-6) PUFAs, are essential for human health. Recent research shows n-3 PUFAs and their mediators can inhibit inflammation, angiogenesis and cancer via multiple mechanisms, including reduced release of n-6 fatty acid arachidonic acid from cell membranes, inhibition of enzymatic activities, and direct competition with arachidonic acid for enzymatic conversions. In this review, we discuss inflammation-related cancer, anti-inflammatory effects of n-3 PUFA lipid mediators, antineoplastic activities of n-3 PUFA in vitro and in vivo, and present an update on recent human trials.
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Affiliation(s)
- Zhennan Gu
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P.R. China ; The Synergistic Innovation Center for Food Safety and Nutrition, Wuxi 214122, P.R. China ; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Kai Shan
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P.R. China ; The Synergistic Innovation Center for Food Safety and Nutrition, Wuxi 214122, P.R. China
| | - Haiqin Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P.R. China ; The Synergistic Innovation Center for Food Safety and Nutrition, Wuxi 214122, P.R. China
| | - Yong Q Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, P.R. China ; The Synergistic Innovation Center for Food Safety and Nutrition, Wuxi 214122, P.R. China ; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
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Dubé P, Sideris L, Law C, Mack L, Haase E, Giacomantonio C, Govindarajan A, Krzyzanowska MK, Major P, McConnell Y, Temple W, Younan R, McCart JA. Guidelines on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy arising from colorectal or appendiceal neoplasms. ACTA ACUST UNITED AC 2015; 22:e100-12. [PMID: 25908915 DOI: 10.3747/co.22.2058] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
To meet the needs of patients, Canadian surgical and medical oncology leaders in the treatment of peritoneal surface malignancies (psms), together with patient representatives, formed the Canadian HIPEC Collaborative Group (chicg). The group is dedicated to standardizing and improving the treatment of psm in Canada so that access to treatment and, ultimately, the prognosis of Canadian patients with psm are improved. Patients with resectable psm arising from colorectal or appendiceal neoplasms should be reviewed by a multidisciplinary team including surgeons and medical oncologists with experience in treating patients with psm. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy should be offered to appropriately selected patients and performed at experienced centres. The aim of this publication is to present guidelines that we recommend be applied across the country for the treatment of psm.
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Affiliation(s)
- P Dubé
- Department of Surgery, University of Montreal, Montreal, QC. ; Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC
| | - L Sideris
- Department of Surgery, University of Montreal, Montreal, QC. ; Department of Surgery, Hôpital Maisonneuve-Rosemont, Montreal, QC
| | - C Law
- Department of Surgery, University of Toronto, Toronto, ON. ; Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON
| | - L Mack
- Department of Surgery, University of Calgary, Calgary, AB
| | - E Haase
- Department of Surgery, University of Alberta, Edmonton, AB
| | | | - A Govindarajan
- Department of Surgery, University of Toronto, Toronto, ON. ; Department of Surgery, Mount Sinai Hospital, Toronto, ON
| | - M K Krzyzanowska
- Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON
| | - P Major
- Department of Medical Oncology and Hematology, Juravinski Cancer Centre, Hamilton, ON
| | - Y McConnell
- Department of Surgery, University of British Columbia, Vancouver, BC
| | - W Temple
- Department of Surgery, University of Calgary, Calgary, AB
| | - R Younan
- Department of Surgery, University of Montreal, Montreal, QC. ; Department of Surgery, Centre Hospitalier de l'Université de Montréal, Montreal, QC
| | - J A McCart
- Department of Surgery, University of Toronto, Toronto, ON. ; Department of Surgery, Mount Sinai Hospital, Toronto, ON
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Razenberg LGEM, van Gestel YRBM, Creemers GJ, Verwaal VJ, Lemmens VEPP, de Hingh IHJT. Trends in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of synchronous peritoneal carcinomatosis of colorectal origin in the Netherlands. Eur J Surg Oncol 2015; 41:466-71. [PMID: 25680955 DOI: 10.1016/j.ejso.2015.01.018] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 01/14/2015] [Accepted: 01/22/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Population-based data on the percentage of colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis (PC) being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently lacking. The current population-based study describes trends in the use of CRS-HIPEC in the Netherlands, one of the first countries where CRS and HIPEC was introduced. METHODS All patients diagnosed with synchronous PC of CRC between 2005 and 2012 were extracted from the Netherlands Cancer Registry (n = 4623). Patients with primary appendiceal cancer were excluded resulting in a study population of 4430 patients. Trends in the use of CRS-HIPEC over time were analyzed by means of a Cochrane-Armitage trend test. Survival proportions were calculated as the time between diagnosis and date of death or last follow-up (January 2014). RESULTS Of the total 4430 patients with synchronous PC, 297 (6.4%) underwent treatment with CRS-HIPEC. The proportion of colorectal PC patients receiving CRS-HIPEC increased significantly over time from 3.6% in 2005-2006 to 9.7% in 2011-2012 (p < 0.0001). Overall median survival (MS) for patients treated with CRS-HIPEC was 32.3 months, whereas MS rates were respectively 12.6, 6.1 and 1.5 for months palliative chemotherapy with/without surgery, palliative surgery and best supportive care. CONCLUSION The proportion of patients diagnosed with synchronous PC from CRC treated with CRS-HIPEC has increased significantly over time and currently almost 10% of PC patients are treated with CRS-HIPEC. Median survival in this population based group is 32.3 months.
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Affiliation(s)
- L G E M Razenberg
- Department of Oncology, Catharina Hospital, Eindhoven, The Netherlands; Eindhoven Cancer Registry/Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, The Netherlands
| | - Y R B M van Gestel
- Eindhoven Cancer Registry/Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, The Netherlands
| | - G-J Creemers
- Department of Oncology, Catharina Hospital, Eindhoven, The Netherlands
| | - V J Verwaal
- Department of Surgical Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - V E P P Lemmens
- Eindhoven Cancer Registry/Netherlands Comprehensive Cancer Organisation (IKNL), Eindhoven, The Netherlands; Department of Public Health, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
| | - I H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
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Li X, Fan R, Wang Y, Wu M, Tong A, Shi J, Xiang M, Zhou L, Guo G. In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis. RSC Adv 2015. [DOI: 10.1039/c5ra21067d] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
A novel local drug delivery system composed of docetaxel loaded micelles and an oxaliplatin loaded hydrogel was fabricated and proved to be potentially useful in the treatment of colorectal peritoneal carcinomatosis.
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Affiliation(s)
- Xiaoling Li
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Rangrang Fan
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Yuelong Wang
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Min Wu
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Aiping Tong
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Juan Shi
- National Laboratory of Medical Molecular Biology
- Institute of Basic Medical, Sciences
- Chinese Academy of Medical Sciences and Peking Union Medical College
- Beijing 100005
- PR China
| | - Mingli Xiang
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Liangxue Zhou
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
| | - Gang Guo
- State Key Laboratory of Biotherapy and Cancer Center
- Department of Neurosurgery
- West China Hospital
- Sichuan University
- Collaborative Innovation Center for Biotherapy
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Aoyagi T, Terracina KP, Raza A, Takabe K. Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol 2014; 20:12493-12500. [PMID: 25253949 PMCID: PMC4168082 DOI: 10.3748/wjg.v20.i35.12493] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/10/2014] [Accepted: 06/05/2014] [Indexed: 02/06/2023] Open
Abstract
Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC.
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van Oudheusden TR, Braam HJ, Nienhuijs SW, Wiezer MJ, van Ramshorst B, Luyer MD, Lemmens VE, de Hingh IH. Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis. Ann Surg Oncol 2014; 21:2621-2626. [PMID: 24671638 DOI: 10.1245/s10434-014-3655-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2014] [Indexed: 01/26/2023]
Abstract
BACKGROUND When peritoneal carcinomatosis (PC) is diagnosed during emergency surgery for colorectal cancer (CRC), further treatment with curative intent may seem futile given the known poor prognosis of both PC and emergency surgery. The aim of the current study was to investigate the feasibility and effectiveness of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC patients who previously underwent emergency surgery in the presence of PC. METHODS All patients with synchronous PC of CRC referred to two tertiary centers between April 2005 and November 2013 were included in this study. Operative, postoperative and survival details were compared between patients presenting in an emergency or elective setting. RESULTS In total, 149 patients with synchronous PC underwent CRS and HIPEC. Amongst these patients, 36 (24.2 %) initially presented with acute symptoms requiring emergency surgery. Acute presentation did not result in a longer interval between the initial operation and HIPEC (2.2 vs. 2.1 months; P = 0.09). When comparing operative outcomes, no significant differences were found in blood loss (P = 0.47), operation time (P = 0.39), or completeness of cytoreduction (P = 0.97). In addition, complication rates, degree and types of complication did not differ between the groups. Median survival was 36.1 months for emergency presentation compared with 32.1 in the elective group (P = 0.73). CONCLUSION CRS + HIPEC may be performed safely in patients with PC of colorectal origin presenting with acute symptoms requiring emergency surgery. More importantly, the 5-year survival rate in these patients was equal to elective cases. This should be regarded as promising and therefore considered for these patients.
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Hompes D, Aalbers A, Boot H, van Velthuysen ML, Vogel W, Prevoo W, van Tinteren H, Verwaal V. A prospective pilot study to assess neoadjuvant chemotherapy for unresectable peritoneal carcinomatosis from colorectal cancer. Colorectal Dis 2014; 16:O264-72. [PMID: 24433532 DOI: 10.1111/codi.12560] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2013] [Accepted: 12/13/2013] [Indexed: 12/30/2022]
Abstract
AIM Twelve to 13% of patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PC), the majority of whom present with unresectable disease. This study aimed to document the actual response rate to and response characteristics of preoperative modern systemic chemotherapy in this patient group. METHOD Patients underwent a positron emission tomography (PET)/CT scan, laparoscopy and peritoneal biopsy to document unresectable PC. After four courses of preoperative chemotherapy (capecitabine/oxaliplatin ± bevacizumab), the extent of PC was re-evaluated by PET/CT(or CT), laparoscopy and peritoneal biopsy (if considered safe). RESULTS Ten patients (seven men, three women) with good performance status of median age 60.3 (45.6-72.8) years were studied. The first laparoscopy documented unresectable PC. One patient was excluded because of systemic metastases on PET/CT. Nine proceeded to follow the trial protocol. Of these, one developed early progressive disease, two had macroscopically stable disease and five had progressive disease at second laparoscopy. One patient developed a small bowel perforation at first laparoscopy and received palliative chemotherapy outside the protocol, after which progressive disease was found at an explorative laparotomy. Thus, 7 (78%) patients with unresectable PC from CRC developed progressive disease under neoadjuvant chemotherapy and 2 (22%) patients remained stable. No clear macroscopic response to chemotherapy could be demonstrated. CONCLUSION Unresectable PC from CRC does not respond well to systemic chemotherapy.
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Affiliation(s)
- D Hompes
- Department of Surgical Oncology, Antoni van Leeuwenhoek-Hospital/the Netherlands Cancer Institute, Amsterdam, the Netherlands
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Thomassen I, van Gestel Y, Aalbers A, van Oudheusden T, Wegdam J, Lemmens V, de Hingh I. Peritoneal carcinomatosis is less frequently diagnosed during laparoscopic surgery compared to open surgery in patients with colorectal cancer. Eur J Surg Oncol 2014; 40:511-514. [DOI: 10.1016/j.ejso.2014.01.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2013] [Revised: 12/23/2013] [Accepted: 01/21/2014] [Indexed: 01/14/2023] Open
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Cai W, Dong F, Wang Z, Yang X, Zheng M, Che X. Heated and humidified CO2pneumoperitoneum inhibits tumour cell proliferation, migration and invasion in colon cancer. Int J Hyperthermia 2014; 30:201-9. [DOI: 10.3109/02656736.2014.898339] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
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Rodt AP, Svarrer RO, Iversen LH. Clinical course for patients with peritoneal carcinomatosis excluded from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. World J Surg Oncol 2013; 11:232. [PMID: 24040889 PMCID: PMC3850876 DOI: 10.1186/1477-7819-11-232] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 08/28/2013] [Indexed: 12/16/2022] Open
Abstract
Background Cytoreductive surgery combined with 'Hyperthermic IntraPEritoneal Chemotherapy’ (HIPEC) represents the only potentially curative treatment available for carcinomatosis secondary to colorectal cancer (CRC), pseudomyxoma peritonei (PMP), malignant peritoneal mesothelioma (MM) and goblet cell carcinoma (GCC). Despite preoperative investigation some patients are excluded perioperatively because of unacceptably massive tumor extent. The data available on the clinical course of these patients are sparse. The aim of this study was to investigate mortality, morbidity and clinical course for patients who were excluded. Methods This was a retrospective observational study based on records from 35 patients (21 men, 14 women) treated in a national center (Surgical Department P, Aarhus University Hospital) from June 2006 to August 2011 and excluded from the cytoreductive surgery perioperatively. The study population included patients aged 18 to 70 years with CRC (n = 19), PMP (n = 11), MM (n = 3) or GCC (n = 2). Vital status was obtained by 29 November 2012. Three patients were lost to follow-up. Results The 30-day mortality rate was 0%. Postoperative complications within 30 days occurred in three patients (9.4%). In all, 19 patients (54%) had palliative surgery during exploratory laparotomy. In total, 28 patients (88%) received postoperative palliative chemotherapy. The median survival for CRC and PMP patients was 12.7 (95% CI 4.0 to 21.4) and 26.9 (95% CI 25.7 to 28.1) months, respectively. Conclusions Exploratory laparotomy for intended curative treatment of peritoneal carcinomatosis did not imply major morbidity or mortality for patients excluded from treatment due to advanced stage of disease.
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Affiliation(s)
- Anne Peen Rodt
- Department of Surgery P, Aarhus University Hospital, Tage Hansens Gade 2, Aarhus DK-8000, Denmark.
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Kuijpers AMJ, Mirck B, Aalbers AGJ, Nienhuijs SW, de Hingh IHJT, Wiezer MJ, van Ramshorst B, van Ginkel RJ, Havenga K, Bremers AJ, de Wilt JHW, Te Velde EA, Verwaal VJ. Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol. Ann Surg Oncol 2013; 20:4224-30. [PMID: 23897008 PMCID: PMC3827901 DOI: 10.1245/s10434-013-3145-9] [Citation(s) in RCA: 178] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Indexed: 12/27/2022]
Abstract
PURPOSE This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol. METHODS In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival. RESULTS Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III-V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0-166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36-46 months). Median progression-free survival was 15 months (95 % CI 13-17 months) for CRC patients and 53 months (95 % CI 40-66 months) for PMP patients. Overall median survival was 33 (95 % CI 28-38 months) months for CRC patients and 130 months (95 % CI 98-162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients. CONCLUSIONS The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.
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Affiliation(s)
- Anke M J Kuijpers
- Department of Surgical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands,
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Klaver YLB, Lemmens VEPP, de Hingh IHJT. Outcome of surgery for colorectal cancer in the presence of peritoneal carcinomatosis. Eur J Surg Oncol 2013; 39:734-41. [PMID: 23523316 DOI: 10.1016/j.ejso.2013.03.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2012] [Revised: 02/18/2013] [Accepted: 03/04/2013] [Indexed: 12/15/2022] Open
Abstract
AIM The detection of peritoneal carcinomatosis (PC) in colorectal cancer patients frequently results in a dilemma with regard to the optimal treatment strategy, especially when PC is encountered unexpectedly during surgery. The aim of this study was to evaluate outcomes of patients undergoing surgery for colorectal carcinoma in the presence of synchronous PC. METHODS Patients diagnosed with primary colorectal cancer and synchronous PC in three community hospitals were selected from the Eindhoven Cancer Registry database. Outcomes of postoperative complications, in-hospital mortality and overall survival were collected and analyzed according to the type of intervention performed. RESULTS Between 1995 and 2009, 169 colorectal cancer patients were diagnosed with synchronous PC, most of them unexpectedly during surgery (n = 130). 142 patients underwent surgery: primary tumor resection (n = 91), palliative procedure (n = 46) or exploration only (n = 5). In-hospital mortality was 41% after palliative surgery and 14% after primary tumor resection. Median survival was 12 weeks after palliative surgery or exploration as opposed to 55 weeks after primary tumor resection. CONCLUSION PC is most often encountered unexpectedly during surgery for colorectal cancer. Results of palliative procedures are very poor with a high in-hospital mortality rate and short survival. Resection of the primary tumor can be performed safely with relatively good outcomes but some patients could have benefited from an even more radical approach when the presence of PC would have been diagnosed at an earlier stage. Improvement of imaging techniques to detect PC prior to surgery is therefore urgently needed. Until this is the case, a high index of suspicion is required when subtle signs of PC are encountered.
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Affiliation(s)
- Y L B Klaver
- Department of Medical Oncology, Catharina Hospital, Post Box 1350, 5602 ZA Eindhoven, The Netherlands
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Klaver YLB, Lemmens VEPP, Nienhuijs SW, Luyer MDP, de Hingh IHJT. Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options. World J Gastroenterol 2012; 18:5489-5494. [PMID: 23112540 PMCID: PMC3482634 DOI: 10.3748/wjg.v18.i39.5489] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2012] [Revised: 05/31/2012] [Accepted: 06/08/2012] [Indexed: 02/06/2023] Open
Abstract
Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.
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Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for colorectal and appendiceal carcinomatosis. Dis Colon Rectum 2012; 55:1044-52. [PMID: 22965403 DOI: 10.1097/dcr.0b013e318265ad42] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Delayed repeated intraperitoneal chemotherapy after cytoreductive surgery for carcinomatosis may be an alternative to intraoperative hyperthermic infusion. OBJECTIVE The aim of this study was to evaluate the safety and feasibility of delayed repeated intraperitoneal chemotherapy after cytoreduction of colorectal and appendiceal carcinomatosis and pseudomyxoma peritonei. DESIGN This study constitutes a retrospective case series. SETTING This study was conducted at a single institution. PATIENTS A total of 31 patients with peritoneal carcinomatosis (23) and pseudomyxoma peritonei (8) were included. INTERVENTIONS Cytoreduction was followed by placement of an adhesion barrier and intraperitoneal catheters. Peritoneal scintigraphy preceded biweekly intraperitoneal 5-fluorouracil and systemic combination chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX). MAIN OUTCOME MEASURES The primary outcomes measured are safety, feasibility, and short-term survival. RESULTS Cytoreduction to a score of 0 to 1 was possible in 25 patients (80%). Complications occurred in 16 patients (51.6%) and were confined to grades I to III. There were no deaths, and no digestive fistulae occurred. Port malfunction or complication resulted in removal in 5 patients (16.1%). Intraperitoneal chemotherapy was possible in 83.8% of patients; 55% completed the full course. Peritoneal scintigraphy demonstrated free diffusion of tracer in 18 patients (58%), 4 (12.9%) had diffusion in each gutter with limited communication, 5 (16.1%) had limited diffusion around each catheter without communication, and 2 (6.5%) had no diffusion on scintigraphy. Overall survival for peritoneal carcinomatosis was 44.5% at 3 years (95% CI = 23%-65%). LIMITATIONS The nonrandomized nature of this study and the early experience are limitations. CONCLUSIONS Delayed repeated intraperitoneal and systemic chemotherapy after cytoreduction is feasible and has acceptable morbidity rates. Delayed intraperitoneal chemotherapy is possible in 83% of patients.
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Chua TC, Esquivel J, Pelz JOW, Morris DL. Summary of current therapeutic options for peritoneal metastases from colorectal cancer. J Surg Oncol 2012; 107:566-73. [PMID: 22688776 DOI: 10.1002/jso.23189] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2012] [Accepted: 05/15/2012] [Indexed: 12/23/2022]
Abstract
BACKGROUND Peritoneal metastases remain an under addressed problem for which this review serves to investigate the efficacy of systemic chemotherapy and radical surgical treatments in this disease entity. METHODS The literature between 1995 and June 2009 was surveyed systematically through a review of published studies on the treatment outcomes of metastatic colorectal cancer to the peritoneum on the Medline and PubMed databases. RESULTS A total of 2,492 patients from 19 studies were reviewed. One thousand and eighty-four patients treated with complete cytoreductive surgery (CCS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and 1,408 patients were treated with palliative surgery and/or systemic chemotherapy. For CCS HIPEC, the overall survival ranged between 20 and 63 (median 33) months, and 5-year survival ranged between 17% and 51% (median 40%). For palliative surgery and/or systemic chemotherapy, the overall survival ranged between 5 and 24 (median 12.5) months, and 5-year survival ranged between 13% and 22% (median 13%). CONCLUSION Systemic therapies have not proved effective and randomised clinical trials have not sufficiently addressed patient subpopulations with metastatic disease of this entity. Current evidence have demonstrated the efficacy associated with CCS HIPEC for which should now be embraced as the standard of care.
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Affiliation(s)
- Terence C Chua
- Hepatobiliary and Surgical Oncology Unit, Department of Surgery, University of New South Wales, St George Hospital, Sydney, Australia
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Cyto-reductive Surgery combined with Hyperthermic Intra-peritoneal Chemotherapy for Peritoneal Surface Malignancies: current treatment and results. Cancer Treat Rev 2011; 38:258-68. [PMID: 21807464 DOI: 10.1016/j.ctrv.2011.07.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2011] [Revised: 07/03/2011] [Accepted: 07/06/2011] [Indexed: 02/06/2023]
Abstract
Cyto-reductive Surgery (CS) combined with Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) as loco-regional treatment of Peritoneal Surface Malignancies (PSM) has increasingly gained acceptance in clinical practice. This review summarizes the more relevant studies on this topic. Indications, pre-operative work-up, technical aspects, outcome and future directions of this combined approach in the treatment of Peritoneal Surface Malignancies are discussed here and proposed in an informative and didactic manner.
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Long-term follow-up in the treatment of peritoneal carcinomatosis. Am J Surg 2011; 201:650-4. [PMID: 21545916 DOI: 10.1016/j.amjsurg.2011.01.013] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2010] [Revised: 01/06/2011] [Accepted: 01/06/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND The objective of this study was to report a long-term survival analysis of a phase II protocol of cytoreductive surgery (CS) and heated intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis (PCs). METHODS Between 2000 and 2008, 101 consecutive patients were treated with CS, HIPEC and early postoperative intraperitoneal chemotherapy using a standardized protocol. Disease recurrence and mortality data were collected prospectively. Primary outcomes were median, 3-year, and 5-year disease-free survival (DFS) and overall survival (OS). RESULTS The median age was 49 years (range, 18-77 years), and the majority (82%) had complete CS with no gross residual cancer. Tumor types included appendiceal (n = 58), colorectal (n = 31), and other (n = 12). Median follow-up was 28 months (range, 0-119 months), with minimum of 24 months among survivors. For appendiceal tumors, median DFS was 34 months (range, 0-119 months) and OS has not yet been defined. Three-year and 5-year DFS was 48% and 42%, respectively, and 3-year and 5-year OS was 76% and 62%, respectively. For colorectal carcinomatosis, median disease-free and OS was 9 months (range, 0-87 months) and 27 months (range, 0-87 months), respectively. Three-year and 5-year DFS was 34% and 26%, respectively, and 3-year and 5-year OS was 38% and 34%, respectively. CONCLUSIONS Long-term survival with regional treatment of PC from appendiceal or colorectal primary tumors with CS and HIPEC is achievable.
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Hompes D, Boot H, van Tinteren H, Verwaal V. Unresectable peritoneal carcinomatosis from colorectal cancer: a single center experience. J Surg Oncol 2011; 104:269-73. [PMID: 21465492 DOI: 10.1002/jso.21937] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Accepted: 03/15/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES For unresectable peritoneal carcinomatosis (PC) median overall survival (OS) is 5-6 months. This article analyzes patients with PC from colorectal cancer (CRC) uneligible for debulking and hyperthermic intra-peritoneal chemotherapy, describing patient- and tumor-related factors possibly affecting survival. PATIENTS AND METHODS From 2005 to 2009, 43 patients presented with unresectable PC from CRC: male/female ratio was 29/14, median age was 57.1 years (range 34.8-76.8). "Unresectability" was defined as: six to seven abdominal regions affected by PC, involvement of mesentery or small bowel in the PC, presence of liver metastases, retroperitoneal lymph nodes, vascular invasion, and/or neural invasion. RESULTS Median time interval between diagnosis of the primary tumor and diagnosis of PC was 7.2 months (range 0.0-102.3). Primary tumors were right-sided in >50% and had been previously resected in >58%, 74.4% of PC occurred synchronously. Ascites was present at primary diagnosis in 37.2%. In 70% of cases, six to seven abdominal regions were affected and in 58.1% PC involved small bowel/mesentery. Systemic disease was present in 16.3%. In 18.6% of patients, a palliative diversion or ostomy was constructed. Median OS was 6.3 months (range 0.4-33.1). Thirty-one patients (72.1%) received palliative chemotherapy. Median OS was 9.3 months (range 0.9-33.1) with versus 3.1 months (range 0.4-6.5) without chemotherapy (P = 0.000), with less favorable patient and tumor characteristics in the latter group. No other factors clearly influenced OS. CONCLUSION Palliative chemotherapy results in better OS, but this is probably attributable to factors influencing the patient's general condition.
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Affiliation(s)
- Daphne Hompes
- Department of Gastro-intestinal Surgery, Antoni van Leeuwenhoek Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
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Klaver YL, de Hingh IH, Boot H, Verwaal VJ. Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after early failure of adjuvant systemic chemotherapy. J Surg Oncol 2010; 103:431-4. [DOI: 10.1002/jso.21836] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2010] [Accepted: 11/24/2010] [Indexed: 11/08/2022]
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Klaver YLB, Hendriks T, Lomme RMLM, Rutten HJT, Bleichrodt RP, de Hingh IHJT. Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery for peritoneal carcinomatosis in an experimental model. Br J Surg 2010; 97:1874-80. [PMID: 20806291 DOI: 10.1002/bjs.7249] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2010] [Indexed: 12/22/2022]
Abstract
BACKGROUND The combination of cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment of choice for selected patients with peritoneal carcinomatosis (PC) of colorectal origin. However, it remains to be proven whether the addition of HIPEC to CS is essential for the reported survival benefit. METHODS Sixty WAG/Rij rats were inoculated intraperitoneally with the rat colonic carcinoma cell line CC-531. Animals were randomized into three treatment groups: CS alone, CS followed by HIPEC (mitomycin 15 mg/m(2) ) and CS followed by HIPEC (mitomycin 35 mg/m(2) ). Survival was the primary outcome parameter. RESULTS The median survival of rats treated with CS alone was 43 days. Rats receiving HIPEC 15 mg/m(2) and HIPEC 35 mg/m(2) both had a significantly longer median survival of 75 days (P = 0·003) and 97 days (P < 0·001) respectively. Rats receiving HIPEC showed a significantly lower tumour load at autopsy compared with rats treated with CS alone. CONCLUSION A combination of CS and HIPEC results in longer survival than CS alone in rats with PC of colorectal origin.
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Affiliation(s)
- Y L B Klaver
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands.
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Verzijden JCM, Klaver YLB, de Hingh IHJT, Bleichrodt RP. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis in patients with colorectal cancer. Hippokratia 2010. [DOI: 10.1002/14651858.cd008479] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- JCM Verzijden
- Radboud University Medical Centre; Surgery; Geert Grooteplein Zuid 10 Nijmegen Netherlands 6525 GA
| | - YLB Klaver
- Catharine Ziekenhuis Eindhoven; Surgery; Michelangelolaan 2 Eindhoven Netherlands 5623 EJ
| | | | - RP Bleichrodt
- Radboud University Medical Centre; Surgery; Geert Grooteplein Zuid 10 Nijmegen Netherlands 6525 GA
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Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-Year Follow-up of Randomized Trial: Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy in Patients with Peritoneal Carcinomatosis of Colorectal Cancer. Ann Surg Oncol 2008; 15:2426-32. [DOI: 10.1245/s10434-008-9966-2] [Citation(s) in RCA: 765] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2008] [Revised: 04/25/2008] [Accepted: 04/25/2008] [Indexed: 02/06/2023]
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Yan TD, Chu F, Links M, Kam PC, Glenn D, Morris DL. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival. Eur J Surg Oncol 2006; 32:1119-24. [PMID: 16887321 DOI: 10.1016/j.ejso.2006.06.007] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2006] [Accepted: 06/21/2006] [Indexed: 02/01/2023] Open
Abstract
AIMS Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.
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Affiliation(s)
- T D Yan
- Peritoneal Surface Malignancy Program, Department of Surgery, University of New South Wales, the St. George Hospital, Sydney, NSW 2217, Australia
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